Appendix

The following letter from the Secretary of the Council was sent to Parke, Davis & Company, March 20, 1917. No reply to it has been received:

The referee of the Council who is conducting an investigation of silver preparations asked me to inquire if you are willing to submit your evidence for the following claims which are made in your circulars for Silvol:

1. How it is possible for the solution to be astringent, and at the same time nonirritant and noncoagulant?

2. That intestinal irrigation with a Silvol solution containing 10 to 15 grains to the pint is sufficiently bactericidal to “be used in the abortive treatment of such infectious processes as dysentery, cholera infantum, and colitis.”

3. What evidence have you as to the degree of antiseptic and germicidal power of Silvol solutions?

4. What evidence have you as to the degree of antiseptic and germicidal power of 5 per cent. Silvol Ointment?

A reply to the above questions and any other information in regard to Silvol will receive careful consideration.--(From The Journal A. M. A., July 13, 1918.)

KATHARMON

Report of the Council on Pharmacy and Chemistry

Following inquiries, the Council took up “Katharmon” for consideration and authorized publication of the following report.

W. A. Puckner, Secretary.

The Katharmon Chemical Company of St. Louis in advertising its Katharmon appeals especially to a profession whose members, should they live up to their ethical code, could not prescribe it.[124] In 1893 (when the publication of “a formula” for proprietary preparations was thought to satisfy the requirements of scientific medicine) an advertisement in The Journal of the American Medical Association gave the following “formula” for Katharmon:

[124] “... it is equally unethical to prescribe or dispense secret medicines or other secret remedial agents,...” Sec. 6, Art. I, Chapter II, Principles of Medical Ethics.

“Hydrastis Canadensis, Phytolacca Decandra, Acid Salicylous C. P. (from Oil of Wintergreen), Acid Boric C. P., Mentha Arvensis, Thymus Vulgaris, Dist. Ext. Hamamelis Virg. Conc.”

In 1907 an advertisement in the Kansas City Medical Index-Lancet declared that:

“Katharmon represents in chemical combination the active principles of Hydrastis Canadensis, Gaultheria Procumbens, Hamamelis Virginica, Phytolacca Decandra, Mentha Arvensis, Thymus Vulgaris, with two grains C. P. Boric Acid to each fluid drachm.”

Now the advertisements which appear in some medical journals state:

“KATHARMON represents in combination Hydrastis Canadensis, Thymus Vulgaris, Mentha Arvensis, Phytolacca Decandra, 10-1/2 grains Acid Borosalicylic, 24 grains Sodium Pyroborate to each fluid ounce of Pure Distilled Extract of Witch Hazel.”

A comparison of these so-called formulas shows that they have not only varied from time to time, but that in no instance was a quantitative statement with regard to all the asserted ingredients given.

The Chemical Laboratory of the A. M. A. reports: Katharmon has an alkaline reaction and therefore cannot contain boric acid, salicylic acid or “borosalicylic acid” (the latter is unknown to medical literature except as loosely applied to a simple mixture of boric and salicylic acids). The solution gives tests for sodium, borate, and salicylate and therefore probably contains sodium borate and sodium salicylate. Examined by the methods used for the determination of hydrastin in goldenseal preparations, a residue giving only a faint test for alkaloid was obtained; if present at all, hydrastis canadensis (goldenseal) is there only in very small amounts.

A circular wrapped with the trade package of Katharmon contained the following, palpably unwarranted, claims:

“INTERNALLY it is very useful in acute indigestion, Gastric Catarrh, Diarrhoea and Cholera Infantum.”

“... it has demonstrated its remarkable curative effects, not only in preventing unhealthy conditions of fresh wounds, but also in correcting the decaying of putrefactive processes peculiar to the body under certain circumstances. It has, further, a remarkable efficacy in surface inflammations, whether produced by accident or disease, and is an indispensable remedy in the affections of the mucous membranes of the nose, mouth, stomach, bowels, vagina, uterus, urethra, bladder and rectum.”

Katharmon is in conflict with Rules 1 and 4 of the Council on Pharmacy and Chemistry because of its indefinite and secret composition and the method of advertising it indirectly to the public; it is in conflict with Rules 10, 6 and 8, in that it is an irrational shotgun mixture sold under unwarranted therapeutic claims and under a name nondescriptive of its composition.--(From The Journal A. M. A., Aug. 10, 1918.)

IODINIZED EMULSION (SCOTT) AND CREOSOTONIC (SCOTT)

Report of the Council on Pharmacy and Chemistry

“Iodinized Emulsion (Scott)” and “Creosotonic (Scott)” are proprietary preparations of the Dawson Pharmacal Company, Dawson Springs, Ky. The latter preparation used to be known as “Iodinized Emulsion (Scott) with Hypophosphites, Guaiacol and Creosote.” In 1907 these preparations were considered by the Council and found inadmissible to New and Nonofficial Remedies. Examination of the preparations having been again requested, the Council considered them anew because the composition and claims had been changed somewhat and because at the previous consideration no report was published.

The reports which appear below were sent to the Dawson Pharmacal Company for comment before publication. In reply the company offered to revise its claims for the preparations. The Council replied that the report sent explained that both preparations are irrational mixtures, and hence a revision of the claims would not make them eligible for New and Nonofficial Remedies. It advised that publication of the report would be withheld sixty days and that it would be revised if new information or evidence was submitted permitting such revision. After expiration of the stipulated postponement, the Dawson Pharmacal Company wrote that no new advertising matter had been prepared, but that the old circulars were not being sent out.

As these irrational preparations were still sold and advertised to the medical profession and presumably used by some physicians, the Council directed publication of its report with this explanation.

W. A. Puckner, Secretary.

Iodinized Emulsion (Scott)

The label for Iodinized Emulsion (Scott) declares:

“Each fluidram contains: Alcohol, m. 4-3/4; Rectified Ol. of Turpentine, m. 3-1/2; Iodin, gr. 1/8; Phenol, gr. 1/2; Glycerine and Elixir Lactated Pepsin with Aromatic Oils in the form of a perfect emulsion.”

A circular which gives what is asserted to be the composition of Iodinized Emulsion, declares that, among other ingredients, each fluidram contains “one and three quarters m. Tincture of Iodine.” Both the statement on the label that the preparation contains “iodin” and the one in the circular that tincture of iodin is present in the product are incorrect, for the A. M. A. Chemical Laboratory reports that no free iodin could be detected in the preparation, and that it responded to tests for iodid instead.

An advertising circular for Iodinized Emulsion (Scott) makes unwarranted claims for the therapeutic properties of the constituents. For example:

“... the great usefulness of Turpentine in diseases, especially of the Intestinal Infection, such as the Meteorism and Tympanites of Typhoid.”

And this absurdity:

“... where Turpentine, Carbolic Acid or Iodine or even Pepsin is indicated, that it will give satisfaction in each and every case.”

Iodinized Emulsion (Scott) is not a “pharmaceutical triumph”; it is an irrational mixture--a reminder of a decadent polypharmacy--sold under misleading and unwarranted claims. It is inadmissible to New and Nonofficial Remedies for conflict with Rules 1, 6, 8 and 10.

Creosotonic (Scott)

Creosotonic (Scott), advertised as a “reconstructive tonic” for the tuberculous, according to the label, contains in each fluidram:

“Alcohol, m. 2-1/2; Creosote and Guaiacol sulphonates of each, gr. 1; Compound Hypophosphites, gr. 1 (including Quinine Hypophosphites, gr. 1/36 and Strychnine Hypophosphites, gr. 1/256), with Iodinized Emulsion (Scott) m. 30.”

As in the case of Iodinized Emulsion (Scott), the advertising makes exaggerated therapeutic claims for the individual constituents of the preparation and for the heterogeneous mixture of guaiacol and creosote sulphonates, hypophosphites, quinin, strychnin, turpentine, phenol, iodin, “lactated pepsin,” etc. Thus, while it is well established that in guaiacol sulphonate and creosote sulphonate the phenolic constituent is bound so firmly that, when administered, but very little is split off in the organism, yet the advertising claims “that the system can be saturated in a shorter time and with smaller doses of creosote and guaiacol sulphonates than with any other form of these drugs” and that (on the false premise that the guaiacol and creosote from these drugs will permeate the tissues of the lungs) “they help to clear up the local infection and thus aid in returning to normal the diseased mucous membrane.”

In the advertising pamphlet, following a discussion of the effect of climate and food in the treatment of the tuberculous, we read:

“While admitting the great importance of the foregoing points, we are firmly of the opinion that proper medication is a great aid in the treatment of pulmonary tuberculosis, and, with this in view, we offer to the profession Creosotonic (Scott) believing that in it we have a superior preparation for this purpose.”

This is unwarranted. Of course suitable medication to meet special conditions is proper in the treatment of tuberculosis, but the routine administration of a complex and irrational mixture such as Creosotonic (Scott) is bound to cause inattention to the prime requisites for the proper treatment of the tuberculous--hygienic surroundings and good food.

Creosotonic (Scott) is an irrational mixture, sold under misleading and unwarranted claims. It is inadmissible to New and Nonofficial Remedies for conflict with Rules 1, 6, 8 and 10.--(From The Journal A. M. A., Aug. 24, 1918.)

CAMPETRODIN AND CAMPETRODIN NO. 2

Report of the Council on Pharmacy and Chemistry

The following report on Campetrodin and Campetrodin No. 2 has been adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

The following report of the A. M. A. Chemical Laboratory on “Campetrodin” and “Campetrodin No. 2,” sold by the A. H. Robins Company, Richmond, Va., was submitted to the Council by a referee of the Committee on Pharmacology:

Campetrodin and Campetrodin No. 2, Double Strength, are called “ethical medicinal specialties” by the A. H. Robins Company, Richmond, Va., which sells them. An advertisement in the Maryland Medical Journal (December, 1917) contains the following claim for composition:

“CAMPETRODIN (Made in Two Strengths of Iodine). This preparation is an Oleaginous Solution of Iodine in Camphor.”

A booklet describing the “specialties” of the Robins Company contains the following in reference to Campetrodin: “Composition: Camphor, Iodine Element, Oleaginous Solvent.” From this it appears that the preparations are claimed to contain elementary (free) iodine in an “oleaginous solvent.” Since free iodin, as is well known, readily combines with fats, it was decided to determine the form in which the iodin was present in these preparations. The examination demonstrated that both preparations contained but a trace of free iodin. On steam distillation there was obtained from both preparations a distillate amounting to about 35 per cent. by volume which had an odor strongly suggestive of turpentine, while the residue contained the iodin and had the characteristics of an iodized fatty oil.

Quantitative determinations indicated that Campetrodin contained approximately 0.03 per cent. of free iodin and 1.3 per cent. of iodin in combination with the fatty oil. Campetrodin No. 2, Double Strength, contained approximately 0.03 per cent. free iodin and 2 per cent. of iodin in combination with the fatty oil.

Thus, contrary to the published statements, Campetrodin is not a preparation of free (elementary) iodin and Campetrodin No. 2, Double Strength, does not contain twice as much iodin as Campetrodin.

The report of the Chemical Laboratory shows that the statements made in regard to the composition of Campetrodin and Campetrodin No. 2 are incomplete in some respects and false in others. In view of the Laboratory’s findings it appears superfluous to inquire into the therapeutic claims made for the preparations: It is evident, however, that a solution containing practically no free iodin is not, as claimed by the Robins Company, “adapted for use wherever ... iodin is indicated externally....”

It is recommended that Campetrodin and Campetrodin No. 2 be declared inadmissible to New and Nonofficial Remedies because of false statements as to chemical composition and therapeutic action, constituting conflicts with Rules 1 and 6.

The Council adopted the recommendation of the referee and authorized publication of this report.--(From The Journal A. M. A., Sept. 21, 1918.)

CARMINZYM

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following which explains why Carminzym was not accepted for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Carminzym is a tablet sold by Fairchild Bros. and Foster, New York. Each tablet contains, according to claims made, approximately 32 mg. of an extract of pancreas, 50 mg. sodium bicarbonate, 172 mg. prepared chalk, 1.5 mg. powdered ipecac and “aromatics q. s.” Without considering other possible conflicts with its rules, the Council held the preparation inadmissible to New and Nonofficial Remedies for conflict with Rule 10 which holds that unscientific or useless articles are not acceptable products.

The Council holds that complex mixtures of remedial agents are, from every point of view, inimical to therapeutic progress and therefore to the public welfare. Such mixtures are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions; because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of individual patients without which there can be no rational drug therapy. On the contrary, with the use of such mixture therapeutic treatment becomes haphazard and mere guesswork.

The Council, appreciating that long established customs cannot be changed at once, has applied Rule 10 concerning the recognition of mixtures with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture it has frequently directed that Rule 10 should not apply pending further clinical trial of such mixture. In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer warrant for the admission of complex mixtures to New and Nonofficial Remedies or for the retention of any that have been admitted unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision several mixtures now described in New and Nonofficial Remedies will be omitted at the expiration of the three year period for which articles are accepted.

Reverting to the Carminzym tablet: When it is desired to obtain the effects of pancreatic extract by oral administration it must be administered with a view of preventing its destruction by the gastric fluid. With this end in view an antacid should be administered to decrease the acidity of the gastric juice. The amount of alkali may be supplied in the form of any of the official preparations, but the amount must be adjusted to the individual patient for the reason that no two successive patients are likely to have the same degree of gastric acidity.

Ipecac has a well defined though limited field of usefulness. When it is used, it should be given with a due regard to the amount needed by the patient and the frequency of the repetition of the dose. There is no reason to suppose that any two successive patients will require ipecac and extract of pancreas in a fixed proportion and with equal frequency. As a matter of fact, the amount of ipecac in Carminzym is so small that no definite therapeutic action can be assigned to it and its use in this combination is purely empirical.

In a word, the employment of mixtures of pancreatic extract, alkalis, ipecac and carminatives in fixed proportion leads to slipshod treatment and irrational therapeutics. Carminzym is an irrational mixture the use of which is detrimental to therapy.

The preceding report was sent to Fairchild Bros. and Foster for comment in accordance with the Council’s usual procedure. The following reply was received:

The long established custom of the use of mixtures of remedial agents rests upon considerations well known and generally accepted. This is equally true of combinations of drugs of similar and dissimilar properties. The drugs of these combinations, especially those of marked therapeutic action, are well known and used by themselves when indicated.

In fact, dissimilarity of action is a cause of combination, an essential of synergism.

Drugs classed as similar are by no means alike in action; laxatives, tonics, carminatives, diuretics are combined with distinct advantage, economy of dose, enhanced effect, potency not obtainable with the single drug.

Your sweeping arbitrary conclusions that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress is not, it seems to us, sustained by fact and experience. There is therapeutic progress in the considerate use and observation of combinations as well as in the use of a single drug. Indeed, in the production of a synthetic chemical substance as a therapeutic agent, the combination of potent and dissimilar elements is worked out to mitigate and correct an objectionable side effect, and promote desirable action.

As for ourselves, at the very outset in our line of work we quite voluntarily declared our principles and our intentions as opposed to incompatible and therefore unstable or inert combinations of the enzymes; and against the “unnecessary multiplication of preparations”--see Fairchild’s Hand-Book of the Digestive Ferments.

Is not this after all the crux of the whole matter--does a combination contain the ingredients stated, does it possess the demonstrable properties which are to be attributed to it in consequence of this composition; and if for a certain purpose, is it well designed therefor?

Carminzym presents certain agents of well known properties, not in the least of incompatible or antagonistic action, but indeed especially suitable for the particular purpose designed; its efficacy not to be measured and judged by theory or opinion as to the efficiency of a certain dosage of a particular drug by itself. That the doses as contained are minimal and effective is distinctly advantageous.

The alkaline carbonates are in Carminzym in stated quantities; the physician adjusts the dosage to the individual patient and with obvious evidence of the efficiency of the adjustment. As we understand it, the employment of alkaline carbonates is not based on purely chemic considerations--a definite known quantity of acid of the gastric juice is to be neutralized; the whole literature and practice dealing with the alkaline carbonates show them to be accredited with a much wider field of use and repute in gastro-intestinal disorders.

The pancreatic extract in Carminzym is designed to be diffusible in the stomach, the tablet is preferable to be crushed in the mouth before swallowing, and we believe the pancreatic extract to be an effective constituent as administered in Carminzym.

You comment as follows:

“Ipecac has a well defined though limited field of usefulness. When it is used it should be given with due regard to the amount needed by the patient and the frequency of the repetition of the dose.”

This in a sense may be said of any of the most useful drugs, but not in the least special degree does it apply to ipecac, which is, on the contrary, of quite characteristic, peculiar range of therapeutic properties, useful in varying combinations and in widely varying proportions and doses according to the purpose for which it is employed.

Ipecac in well known official alkaline, carminative, laxative preparations occurs in the “average dose” in the varying quantities of 1/14, 1/10, 1/8, and 3/16 of a grain.

The ipecac in combination with the other ingredients in Carminzym is designed for a tablet which shall carry a minimal quantity whilst capable of adequate remedial action, thus admitting of increase of dosage or repetition as occasion requires. The quantity of ipecac was not taken at random, but chosen after long trial and consideration.

We believe that Carminzym possesses carminative properties in a superior degree and that, furthermore, in consequence of its composition it directly stimulates the gland secretions and thus exerts a beneficial action upon the whole digestive functions.

Carminzym is for use as occasion requires, and this is to be especially noted. Thus it is not only of direct benefit, but helpful in promoting systematic therapeutic measures and regimen.

The Council takes the ground that complex mixtures of remedial agents are so wrong that there is no longer warrant for their admission into New and Nonofficial Remedies; and that Carminzym is an irrational mixture.

We hold that certain desirable therapeutic properties may rationally be attributable to Carminzym; and that these are manifested in practice.

During the time since the description was sent and the receipt of the statement of the action of the Council, some ten months, Carminzym has proved of constantly increasing service.

The statement in the letter of Fairchild Bros. and Foster “The long established custom of the use of mixtures of remedial agents rests on considerations well known and generally accepted” might well be paraphrased to read: The one-time prevalent custom of using ill-considered combinations of remedial agents has been thoroughly discredited and is generally abandoned by progressive practitioners. Such arguments as that “laxatives, tonics, carminatives, diuretics are combined with distinct advantage” have led to the use of irrational mixtures such as the compound syrup of hypophosphites and the electuary of theriaca. The Council is confident that no one who has studied the causes and treatment of digestive disorders will find occasion to prescribe at one time all the ingredients stated to be contained in Carminzym, and certainly not in the fixed proportions present therein.

The comments in the Council’s report concerning ipecac certainly does apply to all active therapeutic agents. Ipecac was mentioned in the report because the several constituents of Carminzym were under discussion and hence it was necessary to point out the futility of the small dosage of ipecac in this mixture.

The announcement that “Carminzym has proved of constantly increasing service” is not convincing. The Council does not know of a single clinical study of the action of Carminzym under conditions which would have afforded satisfactory evidence of its therapeutic value.--(From The Journal A. M. A., Sept. 28, 1918.)

PHILLIPS’ PHOSPHO-MURIATE OF QUININE COMP.

Report of the Council on Pharmacy and Chemistry

The following report on Phillips’ Phospho-Muriate of Quinine Comp. has been adopted by the Council and authorized for publication.

W. A. Puckner, Secretary.

Phillips’ Phospho-Muriate of Quinine Comp.[125] is sold by the Charles H. Phillips Chemical Co., New York. According to the published formula, each fluidram contains:

Phosphoric Acid 2 minims Potassium Phosphate } Magnesium Phosphate } Calcium Phosphate } 2-1/4 grains Ferric Phosphate } Quinin Muriate (equal to nearly 1/2 gr. Bi-Sulph.) 1/4 grain Strychnin 1/120 grain Flavoring, Glycerin and Syrup, q. s.

[125] The evolution of “Phillips’ Phospho-Muriate of Quinine Comp.” from “Phillips’ Wheat Phosphates” may be interesting. Every one knows that therapeutics tends to fashions, and “Phillips’ Wheat Phosphates” appears to have had its inception as the result of the observation that super-refined white flour contains less phosphates than the corresponding amount of wheat. It was assumed that such flour must be deficient in an essential constituent, and the Wheat Phosphates preparation was apparently designed to fill the want. It was exploited for the relief of numerous conditions that were supposed, without satisfactory evidence, to result from this deficiency. When iron, quinin and strychnin mixtures became the vogue a quarter of a century ago, it was only natural to ride on the wave of popularity and the already widely advertised “Wheat Phosphates” was further enhanced--commercially--by the addition of the iron, quinin and strychnin, the amount of alkaloid added being practically negligible. Those who are not familiar with the various phases of the phosphorus, phosphoric acid, lactophosphate, lecithin, nuclein and glycerophosphate propaganda are referred to a report of the Council on Pharmacy and Chemistry in The Journal A. M. A., Sept. 30, 1916, p. 1033.

Some typical claims made for the preparation are:

“With marked beneficial action upon the nervous system. To be relied on where a deficiency of the phosphates is evident.”

“... brace those tired nerves and aid that worn stomach with Phillips’ Phospho-Muriate of Quinine.”

“The maintenance of a satisfactory blood pressure level free from intervals of depression may be accomplished by the use of Phillips’ Phospho-Muriate of Quinine Compound in appropriate doses.”

“The quantities of quinin and strychnin in this preparation are so well balanced that they relieve the depression and fatigue from mental or physical exertion, without the necessity of recourse to alcoholic stimulation.”

“The other ingredients of Phillips’ Phospho-Muriate of Quinine--phosphoric acid, and the phosphates of potash, magnesia, lime, and iron--are the most rational as well as convenient means of administering these tissue remedies, and of introducing phosphorus--the vitalizing constituent of the nervous system--into the organism.”

The action of such a mixture as a whole is practically that of the sum of the actions of its constituents. The therapeutic action of strychnin and quinin are described in every text-book of therapeutics, but it is necessary to distinguish carefully between the various conditions in which these alkaloids have been used without discrimination, and those conditions in which they have been proved to be of value. While both have been widely used in a great variety of conditions, neither is of proved value in more than a distinctly limited range of diseases. The manufacturers of Phillips’ Phospho-Muriate of Quinine Comp. seem to appeal to the less discriminating who use these alkaloids without any definite conception of exactly what they seek to accomplish with them. Quinin, although used by the uncritical in a host of diseases, has a definite field of usefulness in the treatment of malaria, both prophylactic and curative, but the required dose in the treatment of malaria is many times larger than that recommended in the Phillips’ preparation. The claim that the “strychnin and quinin in this preparation are so well balanced that they produce a mild, buoyant effect, so advantageous, instead of alcoholic stimulation, to relieve depression and fatigue from mental or physical exertion” is nonsensical, if, indeed, it is not mendacious balderdash.

Calcium and potassium have important functions in the body, but any deficiency that may arise is usually attributable to an inability of the body to utilize that which is supplied, for there is seldom any deficiency of these salts in the food, and when they are needed they are best supplied as simple solutions of the salts in appropriate doses without all of the other constituents of Phillips’ Phospho-Muriate of Quinine Comp.

Phosphoric acid exerts practically the same actions as other mineral acids, hydrochloric being usually preferred for internal administration in certain forms of indigestion, aside from which they are seldom used as such.

In the more recent literature for Phillips’ Phospho-Muriate of Quinine Comp., we find the attempt to utilize the well known craze about phosphorus, which has been through so many phases, every one of which has had its day and has been discarded.

The phosphoric acid and phosphates present in Phillips’ Phospho-Muriate of Quinine are of no more value in nervous diseases than is simple sodium phosphate which does not require the addition of a host of other ingredients for its action. As a matter of fact, the phosphates of calcium and potassium present in a dose of Phillips’ Phospho-Muriate of Quinine are probably devoid of appreciable effect in practically all conditions.

To pretend that one who suffers from physical and nervous exhaustion can be materially benefited by this mixture is sheer nonsense and is unworthy of a moment’s consideration by a clinician who is called on to treat such patients.

Iron is useful in anemia, as every one knows. Iron has practically no other field of usefulness in therapeutics. When it is indicated it should be administered in a simple form, such as the pill of ferrous carbonate, for example, and not in a “shotgun” mixture that is quite as likely to do harm as good.

The claim that a satisfactory level of blood pressure can be maintained by Phillips’ Phospho-Muriate of Quinine is mentioned only to condemn as the limit of impudent therapeutic claims. It is an insult to the intelligence of any practitioner to pretend that any known agent or combination of remedial agents can maintain a uniform blood pressure in any one of innumerable conditions.

In short, Phillips’ Phospho-Muriate of Quinine Comp. is a complex and irrational mixture exploited by means of unwarranted claims. It is a survival of the old days of therapeutic chaos when impossible and fantastic chemical formulas were gravely published and as solemnly accepted without question, and also without the slightest understanding on the part of many; when the most eminent of practitioners did not hesitate to give glowing testimonials for lithia waters that contained no more lithium than ordinary river water; when no therapeutic claim was too preposterous to receive acceptance, no theory too nonsensical to justify the use of all manner of claptrap mixtures for all manner of conditions.--(From The Journal A. M. A., Oct. 19, 1918.)

B. IODINE AND B. OLEUM IODINE

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on “B. Iodine” and “B. Oleum Iodine,” together with the reply submitted by the manufacturer and a discussion thereon by the referee in charge of the preparations.

W. A. Puckner, Secretary.

Specimens of B. Iodine and B. Oleum Iodine (B. Iodine Chemical Company) and an advertising pamphlet were sent to the Council by John Bohlander, A.M., M.D., with the declaration:

“Well knowing the value of Iodin in surgical operations and dressings, prompted me for the benefit of my fellow physicians as well as myself, and for Humanity’s sake, to make Iodin my master-piece in chemistry.

“After several years of diligent work in my private laboratory I succeeded in discovering a new product of Iodin--Nitrogen, hydrate of Iodin.”

While “B. Iodine” is said to be nitrogen hydrate of iodin and “B. Oleum Iodine” a 5 per cent. solution thereof, the examination made by Prof. A. H. Clark of the University of Illinois, School of Pharmacy (working in the A. M. A. Chemical Laboratory), indicates that the first is a simple mixture of iodin and ammonium iodid, and the second a solution of iodin in liquid petrolatum. The Council adopted the report of the A. M. A. Chemical Laboratory (which appears below) and declared B. Iodine and B. Oleum Iodine inadmissible to New and Nonofficial Remedies because:

1. The composition is incorrectly declared. B. Iodine is not a newly discovered iodin compound, “Nitrogen Hydrate of Iodine,” but a mixture of iodin and ammonium iodid. B. Oleum Iodine is not a 5 per cent. solution of B. Iodine as suggested by the statement on the label and in the advertising, but a solution of iodin in liquid petrolatum containing about 0.85 per cent. of iodin.

2. Since B. Iodine is a mixture of Iodin and ammonium iodid, its solution in water will have the properties of other solutions of iodin made by the aid of iodid, such as a dilution of tincture of iodin or of compound solution of iodin (Lugol’s solution). Hence, the therapeutic claim that B. Iodine “being of a colloidal nature has the advantage of being more readily absorbed and taken up by all cellular structure, thus getting a perfect cellular medication of Iodine,” is unwarranted.

3. The names “B. Iodine” and “B. Oleum Iodine” are not descriptive of the pharmaceutical mixtures to which they are applied.

4. B. Iodine and B. Oleum Iodine are unessential modifications of established articles. B. Iodine has no advantage over tincture of iodin or compound solution of iodin. (As more convenient of transportation, the Medical Department of the U. S. Army supplies its field hospitals with a mixture of iodin and iodid ready for solution in water, either in tablet form or in powdered form in tubes.) Solutions of iodin in liquid petrolatum may be readily prepared (Reports Council Pharm. and Chem., 1917, p. 88).

[Contribution from the A. M. A. Chemical Laboratory]

B. IODINE PRODUCTS

A. H. Clark, Ph.G., B.S.

“B. Iodine” products are marketed by the B. Iodine Chemical Company, Cincinnati, Ohio; John Bohlander, A.M., M.D., is said to be the discoverer. They consist of “B. Iodine,” “B. Oleum Iodine,” and “B. Aqua Iodine.” B. Iodine and B. Oleum Iodine were submitted to the Council.

In a circular submitted by the B. Iodine Chemical Company, B. Iodine is said to be “Nitrogen Hydrate of Iodin.” It is claimed that “coming in contact with water, H₂O, a chemical change takes place forming Hydro Oxid of Iodin, the Nitrogen of the Nitrogen Hydrate of Iodin escaping, the balance taking up one of oxygen of the water. Its companion, the H₂, escaping at the same time with the Nitrogen then combining with the remainder of the water to form the solution of Hydrogen Oxid of Iodin; so you can readily see that you really have a pure water of Iodin, nothing but the H, the O and the I.”--(From the Journal A. M. A., Feb. 1, 1919.)

B. IODINE

According to the circular, B. Iodine is soluble in alcohol, chloroform, and ether. Also it:

“Has odor, taste, melting and boiling point, same as regular Iodin, has a great affinity for water and will respond to all the tests of Iodin. Appears in a Bluish Black Granulated mass or Powder. When heated in vaporating dish will throw off large purple volumes of Iodin leaving a slight white crystalline precipitate, which on continuous heating will entirely disappear. With careful manipulation you can get prismatic needle point like crystals, looking like spores of glass, these dissolving in water will yield pure Iodin coloring the water Iodin.

“PHARMACOLOGIC, THERAPEUTICAL AND PHYSIOLOGICAL ACTION: Same as Iodin, being of a colloidal nature has the advantage of being more readily absorbed and taken up by all cellular structure, thus getting a perfect cellular medication of Iodin.”

A sample of B. Iodine, marked “Nitrogen Hydrate of Iodin” was submitted by the manufacturers and this sample was examined.

B. Iodine was found to be a granular powder, almost black with a purple cast. It has an odor of iodin and dissolves in water readily. It is also quite soluble in alcohol, but not entirely soluble in chloroform and ether. Ether quickly dissolves iodin from B. Iodine, leaving a residue of a white granular substance. Chloroform acts the same as ether except that the iodin is dissolved out with some difficulty. On heating B. Iodine, vapors of iodin escape. If the heating is done on a water bath, a residue of a white granular substance, subsequently identified as ammonium iodid, remains. If heated in a bunsen flame, no residue remains. These tests all indicate that iodin is held in the form of a simple mixture.

Ammonia: B. Iodine when mixed with an excess of sodium hydroxid and warmed, evolves ammonia.

Iodine: 0.1567 gm. B. Iodine dissolved in water required 5.88 c.c. tenth-normal sodium thiosulphate solution indicating 48.28 per cent. iodin. 0.3721 gm. B. Iodine required 14.18 c.c. tenth-normal sodium thiosulphate solution indicating 48.37 per cent. iodin. The average is 48.33 per cent. iodin.

Ammonium Iodide: 0.3453 gm. of the residue after heating B. Iodine on a water bath until all iodin had volatilized was dissolved in water, acidulated with phosphoric acid, and hydrogen dioxid solution added. The liberated iodin was extracted with chloroform and titrated with tenth-normal sodium thiosulphate. 23.78 c.c. were required indicating 0.3447 gm., or 99.83 per cent., ammonium iodid.

A mixture of 5 gm. iodin and 5 gm. ammonium iodid has the properties of B. Iodine mentioned above.

The conclusion is that B. Iodine is essentially a mixture of iodin and ammonium iodid in equal parts, the two substances being finely powdered and intimately mixed.

B. OLEUM IODINE

The following regarding B. Oleum Iodine is quoted from the circular submitted:

“B. OLEUM IODINE: Iodine soluble in mineral oil 5 and 10% for Nasal, Pharyngeal, Laryngeal, Bronchial, Rectal, etc., and all meucoid affections and abnormal conditions of the mucous membrane.”

A sample of B. Oleum Iodine was submitted by the manufacturer and examined. The label on the bottle states that it is 5 per cent. B. Oleum Iodine in mineral oil. This sample has the characteristics of a solution of iodin in liquid petrolatum. It is oily and has the characteristic violet color.

Ammonia: B. Oleum Iodine, since it is presumed to be a solution of B. Iodine, was examined for ammonium compounds. A small quantity was mixed with an equal volume of strong sodium hydroxid solution and heated. No ammonia was evolved. A few crystals of ammonium chlorid were added to a little of B. Oleum Iodine and treated as above. Ammonia was readily detected.

Iodine: 5.255 gm. B. Oleum Iodine was dissolved in chloroform and placed in a separator. A solution of potassium iodid was added and the iodin titrated with a tenth-normal sodium thiosulphate solution. It required 3.5 c.c. indicating 0.85 per cent. iodin.

The conclusion is that B. Oleum Iodine is a simple solution of iodin in liquid petrolatum to the extent of 0.85 per cent. and not 5 per cent. as claimed. Furthermore, it is not a solution of B. Iodine since no ammonium compound is present.

The preceding report was sent to the B. Iodine Chemical Company. The following reply was received:

Your letter of the 21st inst., received and contents noted and cannot quite agree with your report.

Reasons why: NH₄I, a Nitro Hydrate Iodide; NH₄I₂, a Nitro Hydrate Iodate; and NH₄I₂I₂, Per Iodide, a molecular compound, which I claim, they all being of a NH group, so what can be the objection of Nitrogen Hydrate of Iodine? Of course when your chemist, with the aid of heat, drove off all the Iodine, he naturally brought it back to a NH₄I. There’s where he gets the A.M.. I claim a molecular compound.

The Oil of Iodine I sent you by mistake was a 1 per cent. and not a 5 per cent. as marked. I claim it is made from the resublimed Iodine in mineral oil and not the B. Iodine. I claim a 5 per cent. has heretofore never been accomplished, so I therefore can claim something new.

Tr. Iodine contains Alcohol and Potash as a base, the alcohol a dehydrater and Potash an escharotic, and all other soluble Iodines like the tincture have a metallic base. Mine has not. My iodine is compatible almost with all the salts, alkaloids, tannates, and even the metals. You can’t say that for the tincture or the others. Now why should mine not be superior to others?

Preparations as yet are not on the market and a few pamphlets were printed to meet with the requirements of your rulings and approval and shall be corrected if we only can agree on a proper name as you may suggest.

Yours very truly, THE B. IODINE CHEMICAL CO. By John Bohlander, A.M, M.D.

P.S. We are sending you under separate cover another sample of the Oil of Iodine which is a 5 per cent. solution, and allowing for deterioration will test at least four per cent.

The referee in charge of the preparations submitted the above letter to the Council with the following comments:

The principal statements in the letter are essentially erroneous or misleading: Mixtures or double salts of ammonium iodid and iodin were not discovered by Dr. Bohlander, and are nothing new. Watery solutions of iodin by means of an iodid have long been known and used in the form of Lugol’s solution.

There is no evidence that ammonium iodid is less irritating than potassium iodid. On the contrary, ammonium salts are generally more irritating than the corresponding potassium salts. B. Iodine is not compatible with alkaloids, but behaves essentially like Lugol’s solution. The A. M. A. Chemical Laboratory reports that the new sample of B. Oleum Iodine contains only 1.2 per cent. of free iodin, instead of the claimed amount. It is therefore somewhat weaker than the iodin petrolatum prepared by the A. M. A. Chemical Laboratory (Reports Council Pharm. and Chem., 1917, p. 88).

However good Dr. Bohlander’s intentions may be, the statements that he makes about his products are misleading or erroneous, and the products are ineligible for N. N. R.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 44.)

ANTITHYROID PREPARATIONS (ANTITHYROIDIN-MOEBIUS AND THYREOIDECTIN) OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of antithyroid preparations (Antithyroidin-Moebius and Thyreoidectin) has been authorized for publication.

W. A. Puckner, Secretary.

New and Nonofficial Remedies, 1918, contains a discussion of “antithyroid” preparation and describes two of these: Antithyroidin-Moebius (E. Merck, Darmstadt, Germany) and Thyreoidectin (Parke, Davis & Company, Detroit, Mich.).

The referee reported that these “antithyroid preparations” evidently have not realized the expectations of their promoters, and are viewed with skepticism by practically all critical clinicians.

Consequently, notwithstanding the cautiously worded statements of claims made by the manufacturers of Thyreoidectin, the Council approved the recommendation that this preparation (Thyreoidectin) be omitted from New and Nonofficial Remedies for conflict with Rule 6 (unwarranted therapeutic claims) and Rule 10 (unscientific and useless articles) (Antithyroidin-Moebius had already been omitted because it was off the market). The Council further directed that the general article “antithyroid preparations” be also omitted.

The Council having adopted the recommendation of the referee, Thyreoidectin is omitted from N. N. R., while the general article appears below, as a matter of record:

Antithyroid preparations are obtained from the blood or milk of animals, after the removal of the thyroid glands.

The use of these preparations is based on the theory that the thyroid gland secretes products which are toxic, but which neutralize and are neutralized by, other toxic substances produced elsewhere in the body. Removal of the thyroid glands would then lead to the accumulation of these second toxic substances as evidenced by the phenomena of cachexia strumipriva and myxedema. On the other hand, the blood or milk of such animals is claimed to be capable of preventing the effects of hypersecretion of thyroid substance, such as is supposed to occur in hyperthyroidism (Basedow’s or Graves’ disease--generally called exophthalmic goiter).

These views are largely hypothetical; attempts to give to them a rational experimental basis have failed, but some clinical observers report distinctly beneficial results in the milder forms of the diseases, and in obscure nervous disorders which are supposedly connected with thyroid hypersecretion from the administration of the milk from thyroidectomized goats and also from the use of the proprietary blood preparations listed below. The value of these preparations is very doubtful. The reported improvements may only be psychical or due to associated measures, as is often seen in this disease. Other measures of treatment should not be neglected.

Improvement is said to occur in two or three weeks and to be indicated by an amelioration of the nervous symptoms, tremor, palpitation, insomnia and excitability.

The administration must be long continued. Oral and hypodermic administration are said to be equally effective, but the former is usually preferred. These preparations are not known to be toxic, even when very large doses are used.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 50.)

CEPHAELIN AND SYRUP CEPHAELIN-LILLY OMITTED FROM N. N. R. AND SYRUP EMETIC-LILLY NOT ACCEPTED

Report of Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, which explains the omission of cephaelin and Syrup Cephaelin-Lilly from New and Nonofficial Remedies and the non-acceptance of Syrup Emetic-Lilly.

W. A. Puckner, Secretary.

New and Nonofficial Remedies, 1918, describes cephaelin (an alkaloid obtained from ipecacuanha root) and lists Syrup Cephaelin-Lilly (containing 0.088 Gm. cephaelin hydrochlorid per 100 Cc.) as a pharmaceutical preparation of it.

The period of acceptance for Syrup Cephaelin-Lilly having expired, Eli Lilly & Company were asked to send the current advertising and labels so that the Council might determine if the acceptance of this preparation might be continued. In reply the firm wrote:

“We have changed the name Syrup Cephaeline to Syrup Emetic but the product remains the same as before. We have no circulars describing Syrup Emetic and can only send copies of the label.”

The new name “Syrup Emetic” conflicts with the rules of the Council in that it does not indicate the potent ingredient of this simple pharmaceutical preparation and in that it is therapeutically suggestive. Emetics are powerful agents, and physicians should be given every opportunity of knowing what they prescribe for the purpose.

The name being in conflict with Rule 8, the Council voted to omit Syrup Cephaelin-Lilly and not to accept Syrup Emetic-Lilly.

As the cephaelin syrup was the only preparation of cephaelin admitted to New and Nonofficial Remedies, and as the alkaloid appears to have no important therapeutic field, the Council directed that the description of cephaelin also be omitted.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 52.)

COLALIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Colalin has been authorized for publication.

W. A. Puckner, Secretary.

Colalin is a bile salt preparation claimed to consist essentially of hyoglycocholic and hyotaurocholic acids. It is manufactured by Rufus Crowell and Company, Somerville, Mass., and marketed by Schieffelin and Company, New York.

An examination of the current advertising by the referee of the Council in charge of bile salt preparations having revealed that claims were made for Colalin which were not in harmony with the known action of bile preparations, Schieffelin and Company were informed that in the opinion of the referee the Colalin circular matter required radical revision. In this communication the referee’s objections to the claims were set forth in detail.

No reply to this letter was received, and hence a copy of the letter was sent to Schieffelin and Company and also to Rufus Crowell and Company with the explanation that unless the statements in the Colalin advertising which the referee had questioned were substantiated by satisfactory evidence, were suitably revised, or else the advertising matter withdrawn pending revision, the referee would be obliged to recommend to the Council that Colalin be omitted from New and Nonofficial Remedies.

In reply, Schieffelin and Company wrote that they were not “engaged actively in the introduction of Colalin,” and agreed to the omission of Colalin from N. N. R.

In view of the failure to substantiate the claims objected to or an agreement to discontinue them, the Council directed that Colalin and Colalin Tablets be omitted from New and Nonofficial Remedies for conflict with Rule 6 (unwarranted therapeutic claims).

The following are the claims which the referee questioned:

“Colalin embodies the physiological function of the bile in the intestinal canal and also possesses properties of its own which are intimately connected with the function of the liver.”

The quotation implies that Colalin has properties essentially different from those of bile salts, a claim which requires substantiation.

“In the liver its action seems to be that of a general stimulant of all the hepatic functions.”

This is a claim which requires substantiation.

“By the introduction of Colalin it has therefore become possible to actually utilize the bile for therapeutic purposes.”

This is an unwarranted claim, for bile was used therapeutically before Colalin was introduced.

“As gall-stones are chiefly composed of cholesterin, experiments were made to determine whether Colalin would dissolve these concretions outside of the body. These were completely successful and were then followed by an extensive series of clinical investigations on persons suffering with cholelithiasis, which demonstrated that by the administration of Colalin in many instances gall-stones were evacuated by the natural passages and their further formation prevented without resort to surgical intervention.”

This is misleading in that the context shows that “without surgical intervention” is meant to imply a connection between the experiments showing the solvent power of Colalin and the passage of concretions.

“... Colalin not only acts as a solvent of cholesterin calculi, but prevents their further formation by removing the causes upon which their development depends.”

This conveys the impression that such solvent action is exerted in the body, that is, that such concretions in the gallbladder may be dissolved and evacuated by the use of Colalin. For this claim there is no evidence.

“To understand the value of Colalin in intestinal disorders it is necessary to bear in mind the important functions of the bile in the intestinal canal, namely, its participation in the digestion of fats, its antitoxic action, and its influence upon the peristalsis.”

“... through its antiseptic influence inhibits the production of toxins in the intestines.”

The referee believes that there is no satisfactory evidence that bile or bile salts can inhibit the production of toxins in that part of the intestine--the colon--in which they are commonly produced.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 52.)

FORAL

Report of the Council on Pharmacy and Chemistry

The following report on Foral, a depilatory preparation, has been authorized for publication by the Council.

W. A. Puckner, Secretary.

Foral is sold by the Foral Products Company, Pittsburgh, Pa., as an “antiseptic depilatory” with the special claim for its use for the removal of hair prior to surgical operation or the dressing of wounds. In addition to claims made for its hair dissolving action, it is asserted that, in removing the hair from an open wound, Foral acts as “an antiseptic, which guarantees against any infection.” It is also claimed that, though hair will return after its use, “by proper use it will diminish the growth of hair and cause the hair to grow much slower, and unlike the razor, the hair will not return coarser and thicker.”

We are informed by the Foral Products Company that their preparation is used in many hospitals and that “... one and all are well pleased and a great satisfaction to do away with the old style razor ...”

Foral is stated to be made according to the following formula:

To manufacture seventy-five pounds of FORAL

Starch 35 pounds Barium-Sulphide 20 pounds Zinc-Oxide 10 pounds Calcium-Carbonated-Precip. 10 pounds Potassium-Permanganate 10 grams Menthol-Crystallized 10 grams Carbolic-Acid 1/2 ounce Lilac or Citronel oil 3 ounces

The four above chemicals are going to a heating process before mixing or sifting.

In consideration of the preceding, the Council declared Foral inadmissible to New and Nonofficial Remedies for conflict with its rules, thus:

1. Foral is an unessential and irrational modification of an established article.

While its manufacturer states that Foral has been on the market for eighteen years, the following depilatory formula appears in a book published thirty-five years ago (A practical Treatise on Diseases of the Skin, Louis A. Duhring, Ed. 3, 1883) and is to be found in most books on dermatology:

Barium Sulphid 2 drams Zinc oxid 3 drams Starch 3 drams

Permanganates and sulphids mutually destroy each other, and therefore the addition of the small amount of potassium permanganate cannot serve any useful purpose. The amounts of phenol, menthol and “Lilac or Citronel oil” are too small to exercise any effect (other than that of a flavor) and must be considered unessential additions.

2. Foral is a pharmaceutical mixture marketed under a non-informing name.

Whereas it is in the interest of rational medicine that physicians should know the composition of the preparations which they use, the name of this pharmaceutical mixture fails to indicate that it contains the well-known and by no means always harmless barium sulphid.

3. Foral is sold under exaggerated and unwarranted claims.

In view of the small amount of phenol present and the method of using the preparation, the claim that the use of Foral which, when operating on open wounds, “guarantees against any infection,” is evidently unwarranted.

There is no evidence for the claim that the use of depilatories such as Foral retards the growth of hair or renders hair less coarse. On the contrary, the commonly prevailing opinion is that depilation, like shaving, makes the hair coarser.

To determine if “one and all” of those who had used Foral were still using the preparation, four of the testimonials, appearing in an advertising pamphlet, were investigated. The pharmacist of the hospital from which the first of these testimonials was stated to have emanated replied that the person whose name appeared in connection with it had left the hospital about ten years ago and that no depilatory preparation has been used in this hospital for some time. So far as he knew, depilatories were not now in use in the surgical wards of the hospital. In regard to the second testimonial, the pharmacist of this hospital wrote that the hospital had not bought the preparation, but that some of it had been obtained for an elderly deaconness, who had personal use for a depilatory. The physician signing the third testimonial replied that the preparation was effectual for the removal of hair from the scalp, but that “... we have gotten out of the habit of using it.” In the case of the fourth testimonial, its asserted author wrote “... if it is applied in too large a quantity or too concentrated, or permitted to remain on too long, it will vesicate. It was for this reason chiefly that I discontinued its use. It is a very bad smelling mixture and patients complain of it very bitterly.”--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 55.)

GRANULAR EFFERVESCENT BROMIDE AND ACETANILID COMPOUND-MULFORD

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Granular Effervescent Bromide and Acetanilid Compound-Mulford has been authorized for publication.

W. A. Puckner, Secretary.

The Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of the individual patients without which there can be no drug therapy. On the contrary, with the use of such mixtures, therapeutic treatment becomes haphazard and mere guesswork.

The Council, appreciating that long established customs cannot be changed at once, has applied Rule 10, concerning the recognition of mixtures, with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture, it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer warrant for the admission of complex mixtures to New and Nonofficial Remedies, or for the retention of any that have been admitted, unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision, several mixtures now described in New and Nonofficial Remedies will be omitted at the expiration of the three year period for which articles are accepted.

Granular Effervescent Bromide and Acetanilid Compound-Mulford is listed in the Appendix to New and Nonofficial Remedies. Each 100 Gm. of the mixture contains sodium bromide, 5 Gm., and acetanilid, 1.5 Gm. According to the label, an amount containing acetanilid, 6.5 grains, and sodium bromide, 22 grains, is to be taken at a dose, to be repeated in half an hour if necessary. For “children,” half this dose is advised.

The Council has considered the available evidence for mixtures of this sort, and has reached the conclusion that they are inimical to rational medicine and the public, and therefore in conflict with Rule 10. It holds that the use of mixtures of acetanilid and sodium bromide in fixed proportion is irrational and prone to induce their indiscriminate use by the public. Despite the perfectly frank declaration of the composition of this mixture that is made by the Mulford Company, the “directions” will be followed blindly and the preparation will be given to “children” and “repeated in half an hour, if necessary” in cases in which it would be held unwarranted to administer a dose of 3 grains of acetanilid to a child.

The period of acceptance having expired for Granular Effervescent Bromide and Acetanilid Compound-Mulford, the Council directed its omission from New and Nonofficial Remedies for conflict with Rule 10.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 58.)

HOLADIN AND BILE SALT MIXTURES

Holadin and Bile Salts-Fairchild; Capsules of Bile Salts, Succinate of Soda and Phenolphthalein-Fairchild; Capsules of Holadin, Bile Salts and Phenolphthalein-Fairchild; Capsules of Holadin, Succinate of Soda and Bile Salts-Fairchild.

Report of the Council on Pharmacy and Chemistry

To explain the omission from New and Nonofficial Remedies of certain mixtures, the Council has authorized publication of the matter which appears below.

W. A. Puckner, Secretary.

The Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of individual patients without which there can be no rational drug therapy. On the contrary, with the use of such mixtures, therapeutic treatment becomes haphazard and mere guesswork.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer any warrant for the admission of complex mixtures to New and Nonofficial Remedies or for the retention of any that have been admitted unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision, several mixtures now described in New and Nonofficial Remedies will be omitted as soon as the three year period for which articles are accepted has expired.

The following preparations are included in New and Nonofficial Remedies, 1918:

Holadin and Bile Salts-Fairchild.--A mixture of holadin, 5 parts, with bile salts-Fairchild, 1 part, put up in 3 grain capsules.

Capsules of Bile Salts, Succinate of Soda and Phenolphthalein.--Each capsule contains bile salts-Fairchild, 0.065 Gm. (1 grain); sodium succinate exsiccated, 0.2 Gm. (3 grains), and phenolphthalein, 0.03 Gm. (1/2 grain).

Capsules of Holadin, Bile Salts and Phenolphthalein.--Each capsule contains holadin, 0.13 Gm. (2 grains); bile salts-Fairchild, 0.03 Gm. (1/2 grain), and phenolphthalein, 0.065 Gm. (1 grain).

Capsules of Holadin, Succinate of Soda and Bile Salts.--Each capsule contains holadin, 0.20 Gm. (3 grains); sodium succinate exsiccated, 0.20 Gm. (3 grains), and bile salts-Fairchild, 0.03 Gm. (1/2 grain).

Oxbile has long been credited with a cholagogue action, which, however, has probably been greatly overestimated. When pure bile salts were placed on the market some years ago, they and their compounds were admitted to N. N. R.

Holadin is said to represent all the constituents of the pancreas and to possess great potency in respect to the several enzymes, trypsin, amylopsin, lipase, and the milk-curdling ferment.

It is not clear when such a substance is indicated therapeutically. While it may be useful when there is a deficiency of pancreatin and gastric secretion, it should be used alone.

It is also quite possible that bile salts may have a distinct, though limited, field of usefulness when there is a deficiency of biliary secretion; but the bile salts are best administered alone, or in combination with such laxatives as may be deemed necessary by the physician while keeping in mind the fact that different patients show the widest difference in their reaction to laxatives, making combinations of these agents in fixed proportion irrational.

Phenolphthalein was popularized by nostrum makers; and while it has some therapeutic value, this has been greatly overestimated, and it should be used only in amounts deemed necessary for each patient, preferably alone.

Succinate of sodium was introduced as a saline cathartic, with the claim that it exerts an antiseptic action on the biliary passages and gallbladder. There is no satisfactory evidence to substantiate this claim.

The Council maintains a liberal attitude toward new preparations, but it feels that it is impossible to determine the value of the several constituents of such complex mixtures when used as such; it holds that these mixtures are superfluous and that the several substances of which they are composed should be used singly or at most with greater attention to the individual requirements of the patient than is possible when these fixed mixtures are prescribed.

Despite the fact that these mixtures have been in use for more than nine years, there is no satisfactory evidence that they possess any advantage over the simple laxatives or the preparations of bile or pancreatic extract. They are therefore held to be in conflict with Rule 10, and the Council has directed that they be not included in N. N. R. after Dec. 31, 1918.

Having adopted the preceding report, the Council, in accordance with its regular procedure, submitted this to Fairchild Bros. and Foster for comment.

The following reply was received:

We are entirely at variance with you in the arbitrary conclusion expressed concerning the inimical influence of mixtures on therapeutic progress, the practice of medicine and the public welfare.

If the combinations of Holadin and Bile Salts, etc., in capsules, were ever properly within the scope of New and Nonofficial Remedies, they should be retained. If, however, complex mixtures are to be held as, a priori, unworthy of consideration, the rejection of all would naturally be a logical proceeding.

We believe that the particular combination of Holadin and Bile Salts etc., have been clearly in the line of therapeutic progress--a natural evolution, improvement and development.

For many years combinations of pancreatic extract and ox gall had naturally suggested themselves.

When we realized the fact that the bile salts were quite clearly the active principles of the bile, and that they must necessarily exist in greatly varying percentages in the official inspissated or ox gall, and also because these ox gall products of pharmacy were of extremely varying density, even from that of treacle to resin--and of other objectionable character, we undertook to prepare bile salts.

These combinations are now further justified in view of physiological considerations, the simultaneous secretion of the pancreas and bile, and the state of our knowledge of the function of bile salts, and as co-ferments, promoting and supplementing the pancreas enzymes.

The question suggested as to whether the cholagogic action of ox gall (and bile salts) has been overestimated seems to us no clear purport. The bile salts are obviously employed as the means of administering and thus realizing whatever properties this secretion may have in medicine, of which the cholagogic action is by no means the only consideration.

As for phenolphthalein, which is credited with purely laxative properties, we are at a loss to see any bearing in the remark that phenolphthalein was popularized by nostrum makers. We cannot see that the physician’s or chemist’s estimate of phenolphthalein, its properties and uses, can be in the least degree influenced one way or the other by the statement that “phenolphthalein has been popularized by nostrum makers.”

The phenolphthalein and succinate of soda combinations were originally both prescribed, and we have simply placed them at the service of the physician without other exploitation of them than that designed to call attention to their use in the conditions indicated.

These combinations are offered in a form which may be administered by the mouth with the best promise of introducing the substance more directly in the intestinal tract during the digestion period or at such interval after or prior to, the digestion period, as would best, in the judgment of the physician, meet the indications.

These particular combinations are especially desirable in these “fixed forms” since they are stable and reliable resources at the command of the physicians, the enzymes retaining their stability and potency without material deterioration for many years, and they naturally possess the advantages which are obviously due to the character of the particular pancreas and bile products used in the combinations.

Furthermore, the hygroscopic and soluble organic substances in admixture cannot extemporaneously be so prepared in sealed capsules as to be readily available under the practical requirements of prescribing and dispensing. And we do not believe that those who practice medicine will be in accord with your view that the pancreas substance should necessarily be administered alone, or the bile substance alone.

It now appears that these combinations are to be dropped from New and Nonofficial Remedies in consequence of the view, so stated, that in clinical experience “for more than nine years there is no satisfactory evidence that they possess any advantage over the simple laxatives or preparations of bile or pancreatic extract.”

In reply to this we would simply make the following comment:

During these “nine years” these combinations have inevitably been put to an informing clinical trial, because of the fact that they have been employed with success in disorders of the pancreas and bile functions and often in chronic and serious cases where the clinical conditions were obvious and unmistakable.

The reports of these cases come to us from physicians widely separated and each of his own independent initiative. It would seem gratuitous, to say the least, to state that the observers are “disinterested,” since it is quite clear that there is no other interest than that of the practitioner and his patient.

It is not a case of a new drug or combinations of new remedies, but simply resources which, upon well grounded reasons, both from a theoretical and material standpoint, justify clinical trial, and with results which would seem from any ordinary human standpoint to be satisfactory clinical evidence.

As to the interpretation of competent clinical evidence by the Council, we would, in view of the circumstances and without comment, ask to embody in this text this rule:

“Clinical Evidence.”--“To be acceptable, the clinical evidence must offer objective data with such citation of authority as will enable the Council to confirm the facts and establish the scientific value of the conclusions drawn. Clinical data are worthless when the author is not cited. The facts on which claims with regard to the value of a remedy are based must have been rendered accessible for investigation and confirmation by disinterested observers, either through publication or through the records of a hospital or other institution.”

To discredit these combinations would seem to us not only unjustified, but sterile of any real advancement in medicine, or of anything in the way of helpfulness to the patient in the class of cases in which these products have been resorted to with benefit; this on no other ground really than the opinion “that they have no advantage over the simple preparations themselves.”

Naturally we shall continue to prepare these products and shall continue to take such action as we deem best to bring them to the attention of the physician, for the conduct of our business must remain in the hands of those who are personally responsible for it.

And it is now forty years since we took up this line of work and with the declared intention of devoting ourselves to the applied science of the digestive ferments and “to their development and practical application in every useful purpose in medicine.”

We have been consistently in sympathy with the fundamental purpose of the Council, which must first rest upon fact as to the character of the products offered as medicinal agents. The weight of evidence justifies the position that these particular products rationally should be, and as a matter of fact are, of important special service in the utilization of these organic secretions in medicine.

As explained in the preceding report, the Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible to determine accurately the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because such a practice tends strongly to discourage careful consideration of the special needs of individual patients without which there can be no therapeutic progress. On the contrary, with their use, therapeutic treatment becomes haphazard and mere guesswork.

The dismissal of the holadin and bile salts mixtures does not involve the question of the usefulness of holadin or of bile salts alone; on the contrary, the possible usefulness of these preparations is admitted in the report. It is the combination of holadin, bile salts, sodium succinate and phenolphthalein to which objection is made.

The statement of Fairchild Bros. and Foster that “these combinations are now further justified in view of physiological considerations” is somewhat misleading. It is true that bile and the pancreatic secretion cooperate in intestinal digestion, but there is no evidence that in every case in which there is a deficiency of one of these secretions there is also a deficiency of the other, and it is an axiom of scientific therapeutics that no drug or remedial agent should be administered except to fill a definite want. Otherwise the practice of therapeutics becomes mere empiricism.

The properties of phenolphthalein are not in the least influenced by the manner of its introduction, as Messrs. Fairchild Bros. and Foster emphasize; but the important fact in this connection is that the popular conception of their actions is greatly influenced by the mode of introduction, and phenolphthalein has been widely advertised in a variety of conditions, so that the popular notion concerning it is not that of scientific therapeutics.

In short, the entire argument of Messrs. Fairchild Bros. and Foster concerning the exploitation of these preparations may be summed up by saying that they have been used by clinicians who believe that good results have followed their use, and that the firm will therefore continue to supply the demand. The tendency of some to use anything brought to their notice, and the readiness of manufacturers to market anything that physicians will use, presents the greatest obstacle to therapeutic progress. There was never a nostrum so irrational or worthless that honest but undiscriminating clinicians could not be found who reported wonderful results from its use.

According to Fairchild Bros. and Foster, these holadin and bile salts mixtures have been in use for some nine years. Yet the Council is not aware of any investigation of their merits that meets the requirements of scientific research.

The Council is not acquainted with a single clinical investigation of their action under conditions which afford satisfactory evidence of their therapeutic value.

It is obviously wholly insufficient for a clinician to report that the use of a mixture was followed by good results. The fallacy of such arguments was demonstrated long ago. He must make a comparison of the results obtained with the remedial agent with those obtained in as nearly similar conditions as possible except for the use of the agent. We are not aware that any such study of the mixtures in question has been made. It is in the last degree irrational to hold that because bile salts are the active constituents of bile, therefore such complex mixtures as these are necessary.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 59)

LIQUOR SANTAIVA, S. & D., OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Liquor Santaiva, S. & D., has been authorized for publication.

W. A. Puckner, Secretary.

So far the Council has applied Rule 10 concerning the recognition of mixtures with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture, it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

The Council being engaged in the annual revision of New and Nonofficial Remedies, the referee in charge of santal preparations reported that the three year period of acceptance had expired for Liquor Santaiva (Sharp & Dohme).

The referee held that Liquor Santaiva, S. & D., declared to be a solution of santal oil and copaiba with aromatic oils, in a mixture of alcohol and water, is plainly in conflict with the current interpretation of Rule 10, because there was no sound evidence to indicate that any useful end is gained by the simultaneous administration of santal oil and copaiba in any proportion, and that so, of course, there is no evidence of the special advantage in the fixed proportions represented by the mixture. He pointed out that the formula is essentially a survival of the discredited shotgun gonorrhea mixtures and therefore recommended that its acceptance be not continued.

The Council agreed to the recommendation of the referee and directed that Liquor Santaiva, S. & D., be omitted from New and Nonofficial Remedies.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 66)

MALTZYME, MALTZYME WITH CASCARA SAGRADA, MALTZYME WITH COD LIVER OIL, MALTZYME FERRATED AND MALTZYME WITH YERBA SANTA OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of the Maltzyme preparations has been authorized for publication.

W. A. Puckner, Secretary.

In 1916, the Council voted to omit Maltzyme with Hypophosphites, and Maltzyme with Phosphate of Iron, Quinine and Strychnine. At that time the labels used on the Maltzyme preparations still in New and Nonofficial Remedies contained a list of Maltzyme combinations which included those which had been dismissed. As the Council does not permit an accepted article to be used as a means of advertising an article not accepted, it voted to continue the following preparations for a period of three years on condition that reference to the deleted articles be omitted from the labels when those then in stock had been used up: Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver Oil, Maltzyme Ferrated and Maltzyme with Yerba Santa. While the Maltzyme Company made no definite agreement to revise its advertising propaganda in accordance with the Council’s requirements, the Maltzyme preparations were retained in the belief that in due time the required revision of the labels would be made.

The Council being engaged in preparing the 1919 edition of New and Nonofficial Remedies, the referee in charge of malt extracts reported that the Maltzyme Company had not revised its labels in accordance with the stipulation of the Council. The referee further reported he had become convinced that the claim that Maltzyme is “rich in malt enzymes” is unwarranted and that the term “Maltzyme” (malt plus enzyme) is misleading; this because of the recognized instability of malt extracts (Jour. A. M. A., March 30, 1912, p. 954) and because the Maltzyme Company makes no definite statement with regard to the diastase (malt enzyme) content of its preparations.[126] For this reason it had been the referee’s intention to propose the deletion of all Maltzyme preparations when their period of acceptance expired in 1919. As, however, the present Maltzyme preparations are in contravention with the Council’s requirements, he recommended that the acceptance of these preparations be canceled now.

[126] Manufacturers are warned by the Department of Agriculture, through the Bureau of Chemistry, that combinations claiming to contain digestive enzymes must be active when sold. If preparations tend to deteriorate in a short time, each lot should be dated and not sold after the period when they become inactive. While every manufacturer must be considered innocent until proved guilty, and ignorant until proved knowing, it is a matter of knowledge that manufacturers have marketed their various digestive mixtures with full appreciation of their worthlessness.--(Jour. A. M. A., Dec. 19, 1914, p. 2234.)

The Council agreed to the recommendation of the referee and directed that Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver Oil, Maltzyme Ferrated, and Maltzyme with Yerba Santa be omitted from N. N. R.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 67)

METHAFORM OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Methaform has been authorized for publication.

W. A. Puckner, Secretary.

Methaform is the proprietary name applied by F. Stearns & Co. to chlorbutanol.

Being engaged in the annual revision of New and Nonofficial Remedies, and the term of acceptance for Methaform having expired, a trade package was purchased to determine if the product was marketed in compliance with the rules of the Council. It was then found that a circular was wrapped with the trade package which advertised Methaform Inhalant, a preparation not accepted for New and Nonofficial Remedies.

For obvious reasons, the Council does not countenance the use of an accepted article as a means of advertising an article not accepted. Accordingly F. Stearns & Co. was advised that the Council would be obliged to withdraw the acceptance of Methaform unless the objectionable circular was omitted from the Methaform packages. Stearns & Co. did not give the requested assurance, and therefore the Council directed that Methaform be omitted from New and Nonofficial Remedies.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 68)

PINEAL GLAND, RED BONE-MARROW AND THYMUS GLAND AND THEIR PREPARATIONS OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of pineal gland, red bone-marrow and thymus gland and their preparations has been authorized for publication.

W. A. Puckner, Secretary.

Pineal gland, red bone-marrow and thymus gland were admitted to New and Nonofficial Remedies when these products gave promise of having therapeutic value.

The term of acceptance for the preparations of pineal gland, red bone-marrow and thymus gland having expired, the referee in charge of animal organ preparations recommended in his report for the annual revision of N. N. R. that these products and the general articles describing them be omitted from New and Nonofficial Remedies. He held that the experimental and clinical experience with them leads to the conclusion that they are without value.

In accordance with the recommendation of the referee, the Council voted that the following preparations be omitted from New and Nonofficial Remedies: Desiccated Pineal Gland-Armour; Pineal Gland Tablets-Armour; Extract of Red Bone-Marrow-Armour; Desiccated Thymus-Armour; Thymus Tablets-Armour.

As a matter of record, the descriptive articles for pineal gland, red bone-marrow and thymus gland, which appeared in New and Nonofficial Remedies, 1918, are given below.

Pineal Gland

The functions of this gland have not yet been established but there is some pathological and some experimental evidence that there is a relation between the gland and some processes of development and growth; the nature of this relation is unknown. Adiposis is a frequent sign of disturbed pineal function, but observers are not agreed whether to interpret this as indicating hypofunction or hyperfunction, or possibly a concurrent disturbance of the pituitary. In some instances intravenous injections of pineal extract have seemed to cause a distinct fall in blood pressure. It has been inferred from observations in cases of pineal tumors in the young that the gland in young individuals furnishes a secretion which inhibits growth, particularly the development of the reproductive glands, but the results of experimental administration of pineal substance orally have led other observers to infer that the pineal secretion favors physical and possibly mental and sexual development. It has been suggested that, as all evidence points to the fact that the function of the pineal gland is one of early life, extract of adult pineal glands might be expected to be inert. Experiment has also indicated greater activity in glands obtained from young animals than in those obtained from older ones. The Council has decided to admit preparations of pineal gland to New and Nonofficial Remedies simply for experimental purposes.

Red Bone-Marrow

Red bone-marrow consists largely (more than 90 per cent.) of fat. In new-born animals a third or more of this fat consists of lecithin. The marrow of the bones of new-born animals contains iron (up to 1 per cent. or more) in various forms of organic combination. Both lecithin and iron decrease rapidly in the first weeks after birth. The commercial preparations contain very variable amounts of these constituents.

Actions and Uses.--Red bone-marrow is supposed to stimulate the formation of red blood corpuscles; whatever action it may have in this direction is probably due largely to the iron and lecithin which it contains.

It is said to be useful in simple and pernicious anemias.

Thymus Gland

Little is known as to the functions of the thymus, but it is believed to have an important relation to growth. There also seems to be some relation between the thymus and thyroid, for the former is frequently abnormal in diseases involving the latter (hyperthyroidism).

The use of thymus is purely empirical. It has been employed in the treatment of hyperthyroidism, rickets, tuberculosis, hemophilia, and infantile marasmus and atrophy; its use in the latter conditions is said to be the most promising. It is claimed on very doubtful grounds to exert a somewhat favorable effect in certain cases of cancer.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 69)

PIPERAZINE AND LYCETOL OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Piperazine and Lycetol has been authorized for publication.

W. A. Puckner, Secretary.

Piperazine (diethylenediamene) and Lycetol (a methyl derivative of diethylenediamene) were accepted for New and Nonofficial Remedies in 1906. Both Piperazine and Lycetol were asserted to be efficient uric acid solvents and efficacious remedies in the treatment of gout and rheumatism. These products have been retained until now because there was no investigation which definitely showed their uselessness as uric acid solvents, though their use is generally admitted to have been disappointing.

From an exhaustive and critical study of the available evidence, Hanzlik (Jour. Lab. & Clin. Med., February, 1917) concluded that scientific evidence, though limited, and clinical opinion indicate that Piperazine is valueless in gout and that there is sufficient scientific evidence to indicate the worthlessness of Lycetol.

The referee in charge of Piperazine and Lycetol recommended that these products be omitted from New and Nonofficial Remedies for the reason that they have been sufficiently tried to justify the conclusion that they are not of value. The period of acceptance having expired, the Council directed that Piperazine and Piperazine Tablets (The Bayer Company, Inc.) and Lycetol (The Bayer Company, Inc.) be omitted from New and Nonofficial Remedies.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 70.)

STANOLIND LIQUID PARAFFIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

As explained in the report which follows, “Stanolind Liquid Paraffin” was omitted from New and Nonofficial Remedies at the request of the proprietors. Announcement of this omission was made in the preface to New and Nonofficial Remedies, 1918, but publication of the Council’s report was postponed pending actual conflict with the rules. The Council now authorizes publication of the report because a circular indirectly advertising the product to the public was found enclosed with the trade package of Stanolind Liquid Paraffin.

W. A. Puckner, Secretary.

Stanolind Liquid Paraffin was admitted to New and Nonofficial Remedies in 1916, when its method of marketing conformed to the rules of the Council. This brand of liquid petrolatum, by action of the Council, has been omitted from New and Nonofficial Remedies on request of the Standard Oil Company of Indiana, its manufacturer, who wrote to the Secretary of the Council stating that:

“In order that our facilities for the manufacture of this oil shall be constantly engaged, it will be necessary for us to find sales on a larger scale than in the past. To do this under our present advertising and marketing arrangement we feel will be impossible.”

This letter, in addition, suggested “that physicians are not prescribing Stanolind Liquid Paraffin in any considerable proportion of their orders” and “that the situation which now confronts us would not be materially helped if Stanolind was specified in all such prescriptions.” Further, the Council is asked to consider whether it “might be willing to declare this preparation as not a Council product,” on the alleged grounds that “liquid paraffin is not medicinal in its action and passes through the digestive tract in practically unaltered condition.”

The Council holds that Stanolind Liquid Paraffin is a drug, and that, therefore, its direct advertising to the public is in contravention of the Council’s rules. Constipation should be treated by dietary and hygienic means. Evacuants are only temporary measures. Liquid petrolatum is medicinal; it greatly modifies the intestinal flora; it acts as a lubricant and emollient; it modifies the absorptive powers of the intestinal mucous membrane; it is capable of influencing the digestion of fats. In short, liquid petrolatum, being a drug, its indiscriminate and excessive use should not be encouraged.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 72)

WESTERFIELD’S DIGITALIS TABLETS

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Westerfield’s Digitalis Tablets (The Westerfield Pharmacal Co., Dayton, Ohio) are claimed to represent a fat free tincture of digitalis and to be “enteric coated.” It is claimed that because of this coating these tablets pass the stomach unchanged and dissolve in the intestine, and that this obviates any possibility of gastric disturbance.

The circular which sets forth the asserted advantages of the tablets states that digitalis contains a fat which is an irritant to the gastric membrane. It also contains the following:

“We feel no hesitation in saying that if this remedy is given a fair trial where it is properly indicated, the result obtained will be a gratifying surprise.

“It is a common expression from physicians who have tried this remedy to say, ‘Surely I have never used Digitalis before.’”

If these quotations mean anything, they imply that these tablets present a distinct advance in digitalis therapy. There is no warrant for such a claim. The statement with reference to the occurrence of an oil in digitalis is partly false and partly misleading. Tincture of digitalis, which the tablets are claimed to represent, is fat free; the fixed oil that is present in the drug is not soluble in 70 per cent. alcohol, the menstruum used for the preparation of the official tincture of digitalis. Furthermore, a fairly large amount of this oil (such as is present in 100 therapeutic doses of the drug) is incapable of causing gastric disturbance. Gastric disturbance is a side action that is inseparable from slight overdosage with all true digitalis bodies and is not in any way due to local gastric action. The claim that such action is prevented by the use of enteric pills or tablets is obviously false and misleading.

The alleged “common expression from physicians who have tried this remedy” does not constitute acceptable evidence of the value of the preparation.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Nonofficial Remedies because unwarranted therapeutic claims are made for this product.

When the preceding report was submitted to the Westerfield Pharmacal Co., a reply was received indicating that the firm did not know that progressive manufacturers had discontinued the claim that “fat free” digitalis preparations were devoid of gastric effects. It also submitted a revised circular, which, however, reiterated the claim that the tablet presented a distinct advance in digitalis therapy in that it was “fat free,” and coated to prevent disintegration in the stomach.

Since tincture of digitalis and extract of digitalis are practically devoid of fatty material, and since it is now well known that the fat does not cause gastric disturbance and that therapeutic doses of digitalis do not exert a local irritant action on the stomach, the manufacturer’s product and the claims made for it merely tend to perpetuate old errors.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Nonofficial Remedies on the ground that this presents an unessential modification of pills of an official substance. It directed publication of its report with this explanation.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 75)

XEROFORM-HEYDEN AND BISMUTH TRIBROMPHENATE-MERCK OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Bismuth Tribromphenate-Merck and Xeroform-Heyden. These two products were found not to comply with the standards for bismuth tribromphenate adopted for New and Nonofficial Remedies, and hence could not be retained. As the manufacturers of both products announce that efforts toward the production of a satisfactory product are continued, the omission of the two brands is without prejudice to their reacceptance when a satisfactory product becomes available.

W. A. Puckner, Secretary.

The referee in charge of bismuth preparations submitted the following report of the A. M. A. Chemical Laboratory which shows that Xeroform-Heyden and Bismuth Tribromphenate-Merck do not comply with the adopted standards for bismuth tribromphenate.

Some time ago a request was received from the Medical Section of the National Council of Defense for a report on a brand of bismuth tribromphenate. In accordance with this request the firm’s product was examined, and at the same time and for comparison, an examination was also made of a specimen of bismuth tribromphenate received from Merck and Company, October, 1915, and of another specimen of bismuth tribromphenate “Xeroform-Heyden” obtained from the Chicago branch of the Heyden Chemical Works in April, 1918.

The examination brought out that the bismuth tribromphenate submitted to the national Council of Defense contained a large amount of uncombined tribromphenol, while the specimen of Xeroform-Heyden contained an excessive quantity of bismuth.

When the latter finding was submitted to the Heyden Chemical Works, the firm stated: “The product had to be made in this country after importations from Europe became impossible and the first lots were not fully up to the standard ...” The firm stated that it could now furnish a product which it considered fully equal to that which was previously imported, and offered to submit “samples of the new material.”

Having been requested to do so, a specimen of Xeroform-Heyden was received from the Heyden Chemical Works, New York. This and a second specimen, purchased from a Chicago wholesale drug house, were examined. Whereas the standards for bismuth tribromphenate which had been formulated by the Laboratory and accepted by the Heyden Chemical Works required that the product should contain from 40 to 49 per cent. of bismuth and contain not more than 3.3 per cent. of uncombined tribromphenol, the specimen purchased in Chicago contained 67.7 per cent. of bismuth, while the specimen received direct from the Heyden Chemical Works contained 24 per cent. of uncombined tribromphenol. When this result was reported to the Heyden Chemical Works, the firm replied:

“It seems that we are not yet in a position to supply a product that answers a uniform standard and that we have to continue our efforts in this direction.

“We will take this matter up with you again as soon as we have been successful ...”

At the time when the preceding examination was being made, bismuth tribromphenate-Merck could not be obtained from the Chicago wholesale houses. A request sent to Merck and Company for a specimen of the market supply brought the information that the product was temporarily unavailable. Though unable to supply the product, the firm gave valuable advice for a revision of the somewhat loosely drawn tests for bismuth tribromphenate in New and Nonofficial Remedies, 1918.

Recently (November, 1918) Merck and Company sent a specimen of its product labeled “Bismuth Tribromphenate-Merck” “Merck and Company, New York, Distributors and Guarantors,” and wrote “... You will notice this sample conforms in nearly all details to the tests we submitted with our letter of June 4th. We have been able to produce better goods, but just at present unsatisfactory starting material confronts us. The sample conforms to N. N. R., 1918, but will not meet the test for uncombined tribromphenol submitted by you in your letter of September 4th ...”

Examination of the specimen demonstrated that it was soluble to a considerable extent in alcohol (the N. N. R., 1918, description provides that it should be only slightly soluble in alcohol) and according to the standards adopted for New and Nonofficial Remedies, 1919, contains 18 per cent. uncombined tribromphenol (more than five times the permitted amount).

In view of the Laboratory’s report, the referee recommended that the acceptance of Xeroform-Heyden and Bismuth Tribromphenate-Merck be withdrawn, without prejudice to their reinstatement when satisfactory products are again offered for sale. The Council adopted the recommendation of the referee, and accordingly Xeroform-Heyden and Bismuth Tribromphenate-Merck are omitted from New and Nonofficial Remedies, 1919.

When the Laboratory’s findings with regard to Xeroform-Heyden and the action of the Council deleting the article from New and Nonofficial Remedies was reported to the Heyden Chemical Works, the firm expressed regret that efforts to produce a product equal to that formerly obtained from Germany had so far not been successful and announced that it had decided to withdraw Xeroform-Heyden from the market for the present.

When Merck and Company was advised in regard to the report of the Laboratory and the Council’s action, this firm questioned the feasibility of producing a product meeting the Council’s standards and suggested that the test for free tribromphenol be revised to permit as much as 15 per cent. of this constituent. When Merck and Company was reminded that its product, submitted in 1915, essentially complied with the adopted standards and that the estimate of the therapeutic value of bismuth tribromphenate is based on a product essentially free from alcohol-soluble material, the firm replied:

“As stated in our letter of the 12th inst. we do not wish to market the chemical unless it meets all legitimate requirements of the physicians that use it. If, therefore, your standard proves to be good and it is commercially possible to make supplies conforming to it, we shall do so. We shall discontinue the article unless it is of suitable quality.”

--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 76.)

CREAM OF MUSTARD REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

Cream of Mustard, The Cream of Mustard Co., South Norwalk, Conn., is said to be made by mixing 2 drachms of oil of mustard and 2 drachms of oil of turpentine with one pound of white petrolatum. According to the label it is “for Tonsillitis, Rheumatism, Sore Muscles, Croup, Pleurisy, Frosted Feet, Sore Throat, Neuralgia, Sprains, Bronchitis, Headache, Chilblains, Stiff Neck, Congestion, Bruises, Asthma, Lumbago, Pains and Aches, Colds in Chest.”

The Council refused recognition to Cream of Mustard:

Because it is a simple pharmaceutical mixture of well-known ingredients and has no advantage over established rubefacients which every physician knows how to prescribe and every pharmacist to compound. Incidentally, the name “Cream of Mustard” is misleading and not descriptive of the composition of this pharmaceutical of oils of mustard and turpentine.--(From Reports of Council on Pharmacy and Chemistry, 1918, p. 79)

“PLURIGLANDULAR” MIXTURES

Caps. Adreno-Spermin Comp., Caps. Antero-Pituitary Comp., Caps. Placento-Mammary Comp., Caps. Thyro-Ovarian Comp., Caps. Hepato-Splenic Comp., Caps. Pancreas Comp., and Caps. Thyroid Comp., Not Admitted to N. N. R.

Report of the Council on Pharmacy and Chemistry

After considering the evidence for the several “pluriglandular” mixtures described below, the Council declared them inadmissible to New and Nonofficial Remedies. The Council’s action was communicated to the manufacturer, Henry R. Harrower, in accordance with the usual procedure. After giving due consideration to the manufacturer’s reply the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

With the offer “to supply you with as much literature as may be necessary and as little of the actual remedies as may be desired” if “the prospects for the inclusion of these formulas in N. N. R. are good,” Henry R. Harrower sent the Council a booklet descriptive of his preparations and labels for the following mixtures:

Caps. Adreno-Spermin Comp., each said to contain “Adrenal Gland (total) gr. 1/4, Thyroid Gland (U. S. P.) gr. 1/12, Spermin Extr. (from Gonads), Brain and Spinal Cord aa gr. 1, Calc. Glycerophosphate q. s. ad gr. 5.”

Caps. Antero-Pituitary Comp., each said to contain “Anterior Pituitary Body gr. 2, Thymus Gland gr. 1, Thyroid Gland (U. S. P.) gr. 1/12, Calcium-phosphorus Comp. q. s. ad gr. 5.”

Caps. Placento-Mammary Co., each said to contain “Desiccated Placenta gr. 2, Mammary Substance gr. 1-1/2, Pituitary Body (total) gr. 1/3, Calcium-phosphorus Comp. q. s. ad. gr. 5.”

Caps. Thyro-Ovarian Comp., each said to contain “Desic. Corpora Lutea Ovarian Substance gr. 2-1/2, Thyroid Gland (U. S. P.) gr. 1/12, Pituitary Gland (total) gr. 1/8, Calcium-phosphorus Comp. q. s. ad gr. 5.”

Caps. Hepato-Splenic Comp., each said to contain “Liver Parenchyma, Spleen Substance aa gr. 2, Powd. Bile Salts gr. 1/2, Adreno-Spermin Co. (No. 1) gr. 1.”

Caps. Pancreas Comp., each said to contain “Adrenal Gland, Pituitary Gland (total) aa gr. 1/2, Ovarian Substance gr. 1, Pancreas Substance q. s. ad gr. 5.”

Caps. Thyroid Comp., each said to contain “Desic. Thyroid Gland (U. S. P.) gr. 1/8, Calcium-phosphorus Comp. q. s. ad gr. 5.”

The Council declared these preparations inadmissible to New and Nonofficial Remedies, for reasons which follow:

1. Each of the mixtures contains one ingredient or more, which is neither recognized in the U. S. Pharmacopeia nor admitted to New and Nonofficial Remedies, namely: “Spermin Extract,” “Brain,” “Spinal Cord,” “Desiccated Placenta,” “Liver Parenchyma,” “Spleen Substance,” “Pancreas Substance” and “Calcium Phosphorus Comp. (Each 100 gm. represents Magnes. Phos. 1; Calc. glycerophos. 4; Potas. bicarb. 15; Sod. bicarb. 22 and Sod. chlor. q. s.).” For obvious reasons the Council does not accept a mixture containing an indefinite ingredient and hence it would be necessary as a preliminary for the consideration of any one of the mixtures that their unofficial ingredients be made eligible for New and Nonofficial Remedies by the submission of evidence that such ingredient is of uniform composition and that it is therapeutically valuable when given by mouth. There is no evidence that many of these organs have any value whatever when administered by the mouth or in any other way.

2. In the light of our knowledge the administration of gland mixtures in the host of conditions enumerated in the advertising circular is irrational and on a par with the use of the shotgun mixtures once in vogue.

Be it a pharmaceutical mixture, a “mixed” vaccine, or a “pluriglandular” product, the combination of two medicinal ingredients in a mixture must be considered contrary to rational therapy unless a good reason exists for such combination. Such mixtures are held in conflict with Rule 10 unless the manufacturer presents acceptable evidence for the value of his combination. A physician may prescribe any mixture which he considers indicated in a given case, but the marketing of mixtures of drugs in fixed proportions is in most instances irrational and a detriment to sound therapy.--(From The Journal A. M. A., Jan. 18, 1919)

CERELENE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report declaring Cerelene inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Cerelene, a paraffin preparation for the treatment of burns, was submitted to the Council by the Holliday Laboratories, with the statement that it was composed of 84 per cent. paraffin, 15 per cent. myricyl palmitate, and 1 per cent. purified elemi gum to which is added oil of eucalyptus 2 per cent. and betanaphthol 0.25 per cent. It was explained:

“Myricyl Palmitate is a purified form of Beeswax, free from all impurities, acids, etc., which is solely manufactured by this Company....”

It was also stated that on “special order” Cerelene has been made containing oil of eucalyptus and resorcin, oil of eucalyptus and picric acid, and picric acid alone. The following report on the preparation was presented to the Council by the referee to whom Cerelene had been assigned:

Cerelene is another compound wax for the treatment of burns. According to the work of Sollmann (J. A. M. A., 68:1799, 1917) it is highly improbable that compound mixtures have any advantage over simple paraffin of low melting point. Cerelene must therefore be considered as an unessential modification of paraffin, and as in conflict with Rule 10; unless definite evidence of superiority is submitted. Cerelene mixtures containing medicinal ingredients also appear unscientific since the evidence that the ingredients do not leave the wax has not been successfully contradicted. Finally, the claims made for Cerelene are rather extreme, and would need some revision before they could be accepted.

The A. M. A. Chemical Laboratory reports:

The physical properties of Cerelene are as follows:

Melting point 50.0 C. by U. S. P. method. Ductility limit 30.5 C. Plasticity limit 26.4 C. Not strong at 38 C.

Adheres moderately well; detaches with “pulling.” On heating, readily loses eucalyptol, and a small amount of resinous substance forms in the bottom of the beaker. If Cerelene is heated to 145 C. and cooled, the resulting product no longer has the properties of the original Cerelene.

It is recommended that the preceding report be sent to the Holliday Laboratories, and that unless its superiority over simple paraffins is demonstrated and the unwarranted claims abandoned, Cerelene be declared inadmissible to New and Nonofficial Remedies for conflict with Rules 6 and 10.

This report was submitted to the Holliday Laboratories with the information that it had been adopted, Oct. 3, 1917. It was also explained that before Cerelene could be accepted, the unofficial and unstandardized constituent “myricyl palmitate” would have to be considered and accepted for New and Nonofficial Remedies since, for obvious reasons, the Council does not accept a preparation which contains an unofficial and unstandardized substance not in N. N. R.

The Holliday Laboratories acknowledged receipt of the Council’s report and asked that the matter be held in abeyance until the requested evidence had been obtained. Later the Council was advised that the advertising circulars for Cerelene had been withdrawn with the exception of one giving directions for its use. Five months later, the firm stated that experiments were being made “to determine the actual strength of Cerelene in comparison with other paraffin waxes....” Nothing further has been heard from the Holliday Laboratories and no reply has been received to an inquiry made Oct. 12, 1918. The Council therefore authorizes publication of its report declaring Cerelene inadmissible to New and Nonofficial Remedies.--(From the Journal A. M. A., Feb. 15, 1919).

COLLOSOL COCAINE NOT ADMITTED TO N. N. R

Report of the Council on Pharmacy and Chemistry

The report which appears below was adopted by the Council and sent to the Anglo-French Drug Co., Ltd., New York, for comment in December, 1918. No explanation has been received from the manufacturer. For the information of the profession the Council has now authorized publication of the report.

W. A. Puckner, Secretary.

“Collosol Cocaine” was submitted to the Council in October, 1918, by the Anglo-French Drug Co., Ltd., New York, under the claim that it was an “absolute colloid” and that it contained “1 per cent. cocain.” The label on the submitted specimen declares:

“Collosol Cocaine 1-100”

“... the Cocaine exists as the pure alkaloid in the Colloidal state--the condition in which it is isomorphic with the protein of the body fluids. The effect is more prolonged than that of a molecular Cocaine Solution and being non-toxic absorption presents no practical danger.”

The product was assigned to the Committee on Pharmacology for consideration. The following report was submitted and its adoption by the Council recommended by the committee:

“Collosol Cocaine” is said to be a colloidal form of cocain and is alleged to possess a remarkably low toxicity. The subjoined report of the A. M. A. Chemical Laboratory, however, shows that the preparation does not have the composition claimed for it and it is, in effect, misbranded. In fact, the English manufacturers concede that it is not an “absolute colloid” and that the declaration with regard to the percentage of cocain is incorrect.

It is recommended that, without considering other conflicts with the rules of the Council at this time, “Collosol Cocaine” be declared inadmissible to New and Nonofficial Remedies for conflict with Rule 1 which requires that the composition of an article must be correctly declared. The report of the A. M. A. Chemical Laboratory is appended.

REPORT OF THE A. M. A. CHEMICAL LABORATORY

Simpson, Hewlett and Eyre (Lancet, April 28, 1917, p. 660) reported “Collosol Cocaine” to be much less toxic than cocain. These writers, however, did not verify the statements as to the composition and in the light of subsequent chemical examination it is not to be wondered at that “Collosol Cocaine 1.0 per cent.” was much less toxic than a solution containing 1.0 per cent. of cocain hydrochlorid.

Barger, Dale and Durham report from the Department of Biochemistry and Pharmacology, Medical Research Committee (Lancet, Dec. 1, 1917, p. 825), that they examined “Collosol Cocaine” and found it to contain but 0.25 per cent. of cocain. They also found that the cocain was not present in a colloidal form. Discussing the low toxicity claimed by the manufacturers, these investigators state:

“In the samples which we examined the toxicity was, indeed, much lower than that of an ordinary 1 per cent. solution of a cocain salt; but the local anesthetic action was low to a corresponding degree, and both actions corresponded satisfactorily with the proportion of cocain chemically recoverable from the solution.”

Stroud, of the Crookes Laboratory (which manufactures the preparation), who apparently had been informed of this work in advance of publication, admits the correctness of it, and states (British Medical Journal, Nov. 24, 1918, p. 710) that “whilst the colloidal protective apparently absorbs a portion of the cocain, the remainder is found not to exhibit the attributes of a colloid,...”

The specimen of “Collosol Cocaine” submitted to the Council and labeled “Collosol Cocaine 1-100” was found to contain at most 0.4 per cent. cocain. The examination was made in accordance with the method used by Barger, Dale and Durham and calculated as cocain. This method, however, probably would not distinguish between cocain and basic decomposition products, but would include all as cocain in the amount found. The specimen of “Collosol Cocaine” examined was neutral or slightly acid, a fact which tends to confirm the conclusion of the British investigators that “Collosol Cocaine” contains cocain in noncolloidal form and precludes an increased physiologic effect due to alkalinity.

The Council adopted both the report submitted by the committee and that of the A. M. A. Laboratory and declared “Collosol Cocaine” inadmissible to New and Nonofficial Remedies.--(From The Journal A. M. A., April 12, 1919.)

CUPRASE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Cuprase, sold by the Anglo-French Drug Co., Ltd. The Council’s criticisms of the advertising claims were sent to the firm, December, 1918. The firm made no reply and essentially the same claims are contained in recent advertisements.

W. A. Puckner, Secretary.

“Cuprase” is now being advertised and sold in the United States by the Anglo-French Drug Co., Ltd., the firm which also markets it in England. It is said to be “prepared in the Laboratories of F. Ducatte, 8 Place de la Medeleine, Paris.” According to an advertising circular entitled “The Medical Treatment of Cancer” “Cuprase” is “chemical colloidal copper”; in another place it is “a colloidal copper hydroxid,” which is said to be obtained chemically by the reduction of salts of copper in the presence of albumosic acid.

A box (price $8.50 less 10 per cent. discount) of “Cuprase-Doctor Gaube du Gers” was purchased recently from the Anglo-French Drug Co., Ltd. It contained eight ampules each containing approximately $1 $2$3 of a brownish fluorescent liquid. No information of composition was given on the box, except the line: “Chaque ampoule contient: $1 $2$3 .00121 de Cuivre pur” (Each ampule contains O.00121 gr. of pure copper). The A. M. A. Chemical Laboratory reports that the preparation does contain a small amount of copper, with some protein material and about 1 per cent. sodium chlorid.

The therapeutic claims in the advertising circular are those commonly made for cancer “cures” and are about equally convincing. The publication of such statements and quotations as the following, which appear in a pamphlet “The Medical Treatment in Cancer,” cannot be too strongly condemned in a medicament that at best has only an experimental status:

“A special preparation, Cuprase, has been introduced into therapeutics which has been remarkably successful. In the history of the therapeutics of cancer, nothing has been found which can compare with the effects produced by means of Cuprase. Clinical facts carry greater weight than theoretical deductions. It follows, from the clinical observations which I have collected, that in the large majority of cases Cuprase effects the diminution or disappearance of the pains, an improvement in the general condition, a diminution or arrest of the neoplasms, and finally in certain cases, a cure has been effected. It should be remarked that all or nearly all the observations refer to inoperable cases in which the prognosis was unfavorable at an early date. It is needless to emphasize the practical importance of a preparation capable of yielding such results, even relative, in the worst stages of a disease which has always been regarded as absolutely resisting the action of all internal remedies.”

“To sum up, Cuprase has given positive results in about 94 per cent. of the cases in which it has been employed for a sufficiently long period, and some brilliant results in about 20 per cent. of these cases. Therefore, it may be affirmed, that among the internal remedies for cancer, Cuprase is the one which has produced the most successful results, and can, under certain circumstances, compete with surgical methods, even, so far as the rapidity of their results are concerned.”

“It is indicated:

(a) apart from all operation, and as a specific and curative remedy;

(b) before an operation, in order to give tone to the patient, mobilise the tumor, destroy its toxins;

Essentially the same statements are made in the more recent advertisements (f. i. Urological and Cutaneous Review, Feb., 1919). Opposed to these loose statements are the results of Richard Weil (The Journal A. M. A., 1913, Sept. 27, p. 1034; ibid, 1915, April 17, p. 1283). Weil avoided pitfalls of subjective impressions and used as the essential criterion of efficiency “the demonstrable reduction in size of a tumor, of a kind not to be attributed to the natural processes of evolution of that tumor or of its associated lesions” (l. c. 1915, p. 1289).

The available evidence for Cuprase is far from meeting this criterion. That published by the manufacturers and agents presents only vague generalities, and no definite data. The evidence gathered by Weil himself permits an estimate of the value of Cuprase and it is entirely unfavorable. He states (l.c. 1915, p. 1288):

“Colloidal copper has been used in recent time for the same purpose by Gaube du Gers and by others. I have recently examined the effects of colloidal copper on malignant tumors in man, and have been unable to find that it has any therapeutic value. Furthermore, a study of the distribution of the copper in tumors obtained at operation or by necropsy from individuals so treated failed to show that the copper had been deposited therein.”

In view of the extravagant and cruelly misleading therapeutic claims, and the indefinite statements of composition, the Council voted Cuprase ineligible to N. N. R., and authorized the publication of this report.--(From The Journal A. M. A., April 12, 1919.)

COLLOSOL PREPARATIONS

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below declaring “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur” inadmissible to New and Nonofficial Remedies, because their composition is uncertain (conflict with Rule 1). In the few cases in which the therapeutic claims for these preparations were examined, the claims were found to be so improbable or exaggerated (conflict with Rules 6 and 10) as to have necessitated the rejection of these products.

W. A. Puckner, Secretary

The Anglo-French Drug Co., Ltd., London and New York, in November, 1918, requested the Council to consider the products “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur.” The term “Collosol” appears to be a group designation for what are claimed to be permanent colloidal solutions, marketed by the Anglo-French Drug Co., Ltd. Were this claim correct, “Collosols” should contain their active constituents in the form of microscopic or ultramicroscopic suspensions, protected against spontaneous precipitation by the presence of proteins or some similar “stabilizers.”

According to the original patent specifications for Collosols, the metals are precipitated or treated with “peptone,” which acts as the suspending or stabilizing agent. The method of using the peptone makes it doubtful, in the first place, whether the major part of the metals is present in colloidal form, or merely in the form of peptonates, i. e., as ordinary salts. Moreover, the later patents indicate that the products have been unsatisfactory; “experience having shown that some metal colloids under certain conditions not yet fully understood have the tendency to break down after a certain period” (U. S. patent No. 1,116,247). Phenol, it is claimed has a tendency to counteract this decomposition, and the patent covers the use of phenol for this purpose.

It is difficult to see how phenol could possibly have such action. In fact, it obviously does not, for a number of the samples of Collosols submitted to the Council had separated. For instance, “Collosol Hydrargyrum” was not a colloidal solution at all, but a suspension of a coarse powder. The ampules of “Collosol Ferrum” contained a considerable quantity of flocculent precipitate. If either of these preparations were injected intravenously as directed, death might result, making the physician morally if not legally liable.

The recklessness of the claims is further illustrated by the advice that these indefinite mixtures of poisonous metals can be injected in unlimited quantities. Thus, Henry Crookes stated (Chemical News, May 7, 1914, p. 218) that Collosols “contain so small a proportion of metal, viz., 1 in 2000, that even a poisonous body like arsenic can be used with impunity.” He stated that they may be applied as a lotion, intramuscular or intravenous injection, and that “one pint or more can be injected intravenously.”

In the case of “Collosol Cocain,” as was brought out in the Council’s report published in The Journal, April 12, 1919, the manufacturers have admitted that the product is not what they have claimed--and still claim--for it. The report of the A. M. A. Chemical Laboratory showed that “Collosol Cocain,” instead of containing 1 per cent. cocain as claimed, contained, in fact, at most not more than 0.4 per cent. cocain.

The report of the A. M. A. Chemical Laboratory on the Collosol products was sent by the Council to the New York office of the Anglo-French Drug Co., Ltd., in duplicate in order to facilitate reference to the London office. This was some months ago. The information which the Council requested has not yet been received, nor has the Anglo-French Drug Co., Ltd., indicated its intention of supplying such information. On the other hand, claims to which specific objection have been made, continue to appear in current advertising. Accordingly, the Council authorizes publication of this report, and declares the Collosol preparations previously named ineligible to New and Nonofficial Remedies.

Additional Notes on Collosol Evidence

In addition to the preceding the following notes of the referee on the evidence so far submitted were sent to the Anglo-French Drug Company, Ltd., for consideration:

Collosol Iodine: The leaflet which describes Collosol Iodine contains claims that are improbable, not in accord with accepted facts nor substantiated by evidence; for instance:

“This preparation contains Iodine in its most active form ...”

“The disadvantages of ‘iodism’ and nausea frequently associated with iodides never occur with Collosol Iodine.”

“In the case of Colloidal Iodine the whole of the Iodine is absorbed and enters into molecular combination with protein to form an iodo-amino acid and ... exerts a reducing action on the lipoids producing a different condition of the blood--hence the use of Iodine as an ‘alterative’.”

“Intravenously the action of Collosol Iodine is more rapid ... in cases of pyemia ... thus showing its absolute non-toxicity.”

“‘Per se’ Colloidal Iodine is only slightly parasitotropic and bacteriotropic but micro-organisms are very greatly influenced by its action, and not only is the effect of a subsequently administered remedy greatly increased but also the insoluble colloidal protein of serum itself is reduced to smaller particles, thus increasing its surface and adsorptive capacity and consequent germicidal power. In some cases the serum, thus aided, is enabled to throw off a milk microbial invasion. The above action can be readily demonstrated ‘in vitro’ by means of the ultramicroscope.”

“In Cancer, the intravenous injection of Collosol Iodine relieves pain, even where large dosage of morphine is ineffective.”

“In Rheumatism the ionic method of treatment with Collosol Iodine is strongly advised.”

“In Recovery from Alcoholism the internal administration of Collosol Iodine restores the normal condition of cell activity, ensuring rapid recovery.”

Collosol Hydrargyrum: This is said to be a preparation of colloidal mercury and would therefore be similar to Electromercurol (New and Nonofficial Remedies, 1919, p. 167). Colloidal mercury preparations have been used to some extent; they appear to have no decided advantage over other, noncolloidal, mercury compounds. They differ sufficiently from them, however, to justify acceptance for New and Nonofficial Remedies, providing that reasonable claims are made for them. The leaflet advertising Collosol Hydrargyrum contains statements that cannot be accepted and require thorough revision to make them acceptable. The following are instances:

“Although--especially locally--the action of mercurials is markedly antiseptic, when taken internally or injected, it has been stated by some of the best known authorities, that their action is rather to increase the natural resisting power of the body to disease, probably because of stimulation of the oxidases.”

With the soluble mercurials “considerable upset of the normal cell conditions of the tissues ensues whilst these soluble salts are being converted to a condition in which the body can make use of them.”

“The colloidal state ... is stated by some authorities in the case of mercury to be invariably precedent to absorption.... With the usual forms of mercury the danger of too great a dose per cell is considerable, but in the case of colloidal mercury, the diffusion is extremely rapid and chemical affinity low. Hence the danger to the individual leucocyte is minimized and the maximum effect obtained.”

“... absence of pain is usual in the administration of colloidal preparations and is due to their isomorphism with the colloidal lipoid and protein of the tissues and body fluids.”

“According to McDonagh,... mercury acts as an oxidizing agent and that the process of oxidation is more effective in the early stages of syphilis in producing the death of the causal organism....”

Collosol Manganese: The circular submitted to the referee is a reprint of a paper by Sir Malcolm Morris on “The Treatment of Furunculosis and Other Deep-Seated Coccogenic Infections by Collosol Manganese.” It reports four cases of furunculosis, each of which cleared up after the intramuscular injection of a few doses of Collosol Manganese. The author seems to attribute the cure to the manganese but the evidence is not convincing. Even the author admits that, in the treatment of furunculosis in general “when at last the dismal procession ends, this often appears to be less the result of treatment than because the disease has run its natural course.” Unless much better evidence is in existence, the preparation must be considered to conflict with Rule 6, which requires therapeutic claims to be substantiated.

Collosol Argentum: The evidence submitted as to actions consists of a single reprint by Roe, which is not convincing, and this fantastic statement by Boys:

“A young girl, aged 18, came to my house with acute inflammation of one eye with an ulcer on the cornea. Two drops of Collosol Argentum were dropped in the eye at 7 p. m., and a pad placed over the eye. When she came next morning the eye was quite well; the ulcer had disappeared, and there was no inflammation.”

There is no evidence that this preparation acts as catalyzer and assists the natural resisting bodies of the tissues; or that these are “oxygen carriers.” Unless the claims are supported by better evidence, they, in the opinion of the referee, could not be accepted.

There have been submitted to the Council samples of the following metallic Collosols:

COLLOSOL ARGENTUM COLLOSOL FERRUM COLLOSOL ARSENICUM COLLOSOL HYDRARGYRUM COLLOSOL CUPRUM COLLOSOL MANGANESE

Also Collosols of Iodine and Sulphur, and finally Collosols of Cocain and Quinin. Of all the above, except sulphur, only three small ampules have been submitted. This does not admit of any chemical examination but a statement of the physical appearance may be of interest.

Collosol Arsenicum, 0.2 per cent.: Very turbid with large quantities of a lemon yellow flocculent precipitate. On shaking does not become homogeneous and rapidly separates again.

Collosol Argentum, 1-2000: The liquid has a slight opalescence. There is considerable deposit of a heavy black precipitate. Does not become homogeneous on shaking and the black substance quickly separates again.

Collosol Cuprum, 0.5 per cent.: Dark red somewhat opalescent liquid. No precipitate. May be colloidal.

Collosol Ferrum, 1-2000: Liquid clear. Large quantities of dark brown flocculent precipitate. The precipitate is not distributed evenly when the mixture is shaken and settles out quickly on standing.

Collosol Hydrargyrum, 5 per cent.: Milky liquid. Large quantities of white deposit mixed with considerable black. The deposit mixes fairly well but the greater part settles out after standing an hour or two.

Collosol Manganese, 2.5-1000: Clear reddish-brown liquid without deposit of any kind. Is not opalescent or fluorescent.

Collosol Iodin, 1-500: Very pale straw colored liquid without deposit. Has a slight opalescence.

Collosol Sulphur, 1-100: Liquid is opalescent. There is some deposit of yellow particles. A four ounce bottle was also submitted. The liquid in this bottle is milky with considerable deposit of yellow crystals like ordinary crystalline sulphur.

Collosol Cocain, 1-100: Transparent, colorless liquid with no deposit. Chemical examination showed 0.4 per cent. of what may have been cocain. This residue gave alkaloidal tests.

Collosol Quinin, 1-100: Slightly opalescent, colorless liquid, with no deposit. Gives alkaloidal reactions.--(From The Journal A. M. A., June 7, 1919.)

PULVOIDS CALCYLATES COMPOUND

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, not so much because the preparation with which it deals is of any great importance, but as a protest against the large number of similar irrational complex mixtures which are still offered to physicians.

W. A. Puckner, Secretary.

Pulvoids Calcylates Compound (The Drug Products Co., Inc.) are tablets each of which is claimed to contain:

“Calcium and Strontium Disalicylate, 5 grs.; Resin Guaiac, 1/2 gr.; Digitalis, 1/4 gr.; Cochium [colchicum?] Seed, 1/4 gr.; Squill, 1/4 gr.; Cascarin, 1/16 gr. with aromatics.”

“Pulvoids Calcylates Compound (Sugar coated orange color)” is advertised (Medical Times, January, 1919) as being “Analgesic-Antipyretic and Diuretic,” and is included in the preparations designated by the advertiser as “Approved Remedies for LaGrippe and ‘Flu.’” The claim that “Their tolerance is remarkable” refers not to the physicians who tolerate such products, but to the alleged fact that Pulvoids Calcylates are tolerated remarkably well. The advertisement continues:

“May be given persistently and continuously without gastric disturbances.”

“They are uniformly efficient. More certain in effect than the ordinary Salicylates.”

It would be difficult to find an advertisement of equal length containing a greater number of misleading or directly false statements than are found in this one. The Journal (April 22, 1916, p. 1307) has called attention to the lack of justification for this absurd mixture of drugs and has discussed the preparation with especial reference to its use in acute rheumatism, in which the salicylates occupy a special field. The advertisement just quoted mentions La Grippe and “Flu” (or Influenza) as special fields of usefulness for this preparation. This, apparently, is merely an attempt to spread the sail for any breeze. Salicylates have a field of usefulness in influenza in that they often afford relief from pain. There is no reason to suppose that a mixture containing calcium and strontium salicylates--the “Calcium and Strontium Disalicylate” of Pulvoids Calcylates is probably a mixture of calcium and strontium salicylate[127]--has any greater salicylic effect than an equal amount of sodium salicylate. On the other hand, it is worse than useless to give colchicum, squill and digitalis for the relief of such pains.

[127] See report, The Journal, Sept. 9, 1916, p. 827.

Should cardiac dilatation develop, and digitalis medication be required it would be impossible to adjust the dose of such a mixture with special reference to the digitalis action, which alone would be indicated for that condition. No educated physician at present would think of giving resin of guaiac merely because his patient required digitalis, nor would he administer “cascarin,” whatever that may be, in fixed doses, every time he gave a dose of salicylate.

It is impossible to recognize the several effects induced by this therapeutic omneity, and the medical profession should consider it an insult to be offered mixtures such as Pulvoids Calcylates Compound.

Pulvoids Calcylates Compound is, per se, of no great importance; it is one of a type. It has been selected as one of the utterly irrational and therefore potentially dangerous mixtures, that may be found by the score or the hundred in the catalogues of practically every pharmaceutical manufacturing firm in the United States.--(From The Journal A. M. A., June 14, 1919.)

PROTEOGENS OF THE WM. S. MERRELL COMPANY

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the statement which appears below, declaring Proteogen No. 1 (Plantex) for Cancer, Proteogen No. 2 for Rheumatism, Proteogen No. 3 for Tuberculosis, Proteogen No. 4 for Hay Fever and Bronchial Asthma, Proteogen No. 5 for Dermatoses, Proteogen No. 6 for Chlorosis, Proteogen No. 7 for Secondary Anemia, Proteogen No. 8 for Pernicious Anemia, Proteogen No. 9 for Goitre, Proteogen No. 10 for Syphilis, Proteogen No. 11 for Gonorrhea, and Proteogen No. 12 for Influenza and Pneumonia inadmissible to New and Nonofficial Remedies because their composition is secret; because the therapeutic claims made for them are unwarranted; and because the secrecy and complexity of their composition makes the use of these preparations irrational.

The Council took up the consideration of the Merrell Proteogens because of inquiries received, and on January 27 invited the Merrell Company to aid in the proposed investigation by submitting information in regard to the composition of the preparations, submitting the current advertising, and presenting evidence for the claims that were made for the preparations. While the Merrell Company agreed to submit the requested information, this had not been received at the time the report of the referee to whom the products had been assigned (Referee 1), was adopted. This report was sent to the company on April 4. In reply the Merrell Company protested against the conclusions of the report and submitted considerable material in an attempt to support the claims made for the products. This material was examined by the first referee and then transmitted to a second referee (Referee 2) for consideration. The second referee concluded that the matter submitted offered no evidence that would justify the Council in modifying the report first adopted, and hence recommended that its publication be authorized.

In accordance with this recommendation (report of Referee 2) the Council authorized the publication of the reports of both the first and second referees.

W. A. Puckner, Secretary.

Report of First Referee on Proteogens

“Proteogens,” according to the William S. Merrell Co., are “Polyvalent Proteins of Non-Toxic Plant Origin.” The subject of Proteogens can best be approached by recalling the history of “Autolysin,” an alleged remedy for cancer, originated by A. S. Horowitz, Ph.D. This was exploited some years ago, and was finally shown to be worthless. Proteogens are said to be prepared “under the personal supervision of the originator, Dr. A. S. Horowitz.” The composition of the different Proteogens is essentially secret. The assertion was made at one time, but is not found in the present advertising matter, that Plantex--now called “Proteogen No. 1”--is similar to Autolysin. Now the Proteogens are said to be “prepared by a special process employing various combinations of plants.” Further:

The biologic principles present are chlorophyll, chromoplast, lipoids and vitamines; these are ferments or enzymes. The vegetable acids, metalloids and metals present in all plants in colloid form act biochemically. Among the metalloids are hydrogen, carbon, manganese, oxygen, sulphur, phosphorus and chlorine; the heavy metals are iron, potassium, sodium, magnesium and copper. These biochemic principles are always present in plants as colloids.”

It is claimed by the Merrell Company that:

“Proteogens stimulate the cytogenic mechanism to higher activity; therefore, indirectly cleave the invading microorganism and eliminate their special toxins. Proteogens swing the disturbed metabolism back to normal and, by natural processes, build up effective defenses against recurrent bacterial attacks.”

Proteogen No. 1 was first introduced as “Plantex,” and at that time the Merrell Company referred to a preparation that was the result of “a series of studies” carried out by a “noted biologist” with a view of “evolving a Cancer remedy” that was “to be autolytic in character,” and announced:

“The House of Merrell always interested in the progress of plant therapy, began pharmacological experimentations to reproduce this same substance. The qualitative and quantitative analysis of the substance as used in New York having been published simplified matters. A somewhat similar remedy has now been prepared. It consists of the following substances--Menyanthes trifoliata [Buckbean], Melilotus officinalis [Yellow sweet clover], Mentha crispa [Curled mint], Brassica alba [White mustard], Anemone hepatica [Liver leaf], Viola tricolor [Pansy], Anthemis [Roman chamomile], Fructus colocynthidis [Colocynth], Lignum quassiæ [Quassia], Urtica dioica [Nettle], Radix rhei [Rhubarb root], Hedge hyssop. These substances are in approximately equal proportions with the exception of the mustard which forms 20 per cent. of the mixture, and the colocynth fruit which is 5 per cent.”

With respect also to the other Proteogens listed above, study of medical literature revealed no evidence establishing their therapeutic value; in fact, no evidence was found other than that appearing in the advertising matter of the manufacturer. The range of diseases in which Proteogens are recommended is so wide as to make obvious the lack of scientific judgment which characterizes their exploitation. A circular letter, received January, 1919, reminded the physician that about a year ago his attention had been directed to Proteogen No. 1 for cancer, that later developments enabled the firm to recommend for his consideration “a series of Proteogens (Nos. 2 to 9),” and that now “In response to an insistent demand, Dr. A. S. Horowitz has prepared two new Proteogens--No. 10 for Syphilis and No. 11 for Gonorrhea.” A postscript to this circular letter announced another preparation, “Proteogen No. 12 for Influenza and Pneumonia,” a “development out of the present influenza epidemic,” and admitted that “It has not had the clinical experimentation that precedes our introduction of a new product.”

The introduction of No. 12 was effected by means of a special bulletin which consists exclusively of clinical reports from seven physicians, all from Chicago save one, and all purporting to show most favorable results from No. 12. They describe cases which any physician with experience with influenza can duplicate without any special treatment.

It is difficult to give serious consideration to a set of alleged remedies when the only evidence is that furnished by the proponents of the alleged remedies. This is particularly true when the alleged remedy does not make a sufficient appeal to one’s sense of the rational in therapeutics to lead one to feel justified in asking a trial at the hands of careful clinical observers. Considering the grave nature of the diseases for which Proteogens are recommended, particularly cancer, tuberculosis, and pernicious anemia, the want of a rational basis for the method of treatment and the general tenor of the advertising matter, it appears safe to conclude that these agents do not represent any definite advance in therapeutics.

As the use of preparations, secret in composition, and of no established value, is contrary to rational therapy, it is recommended that the Proteogen preparations be declared in conflict with Rules 1, 6 and 10.

Report of Second Referee Reviewing Manufacturers’ Reply

The report declaring the Proteogens of the William S. Merrell Company inadmissible to New and Nonofficial Remedies was adopted by the Council, but before publication it was sent to the Merrell Company for such comments as it might desire to make. In due time the reply of the firm was received. It consisted of two volumes bound in limp morocco, each stamped in gold: “Report Proteogen Therapy Requested by the American Medical Association, 1919; The Wm. S. Merrell Company.” The first volume contained 79 pages of typewritten material; the second volume contained 76 pages of typewritten material and a number of advertising booklets put out by the Wm. S. Merrell Company, exploiting the Proteogens.

Among the typewritten material was a 14-page report on “Proteogen Therapy” by its originator, A. S. Horowitz. Following this there are several pages devoted to what is termed “a short qualitative description of the ingredients of major importance in Proteogens.” Then follows a page describing the advertising of Proteogens, and the remainder of the two books is devoted to testimonials, lauding the benefit of Proteogens in diseases such as cancer, tuberculosis, rheumatism, asthma, influenza, enlarged prostate, rheumatic endocarditis, syphilis, eczema, psoriasis, diabetes, secondary anemia, gonococcic infections, etc. Finally, there are attached samples of advertising pamphlets.

The dissertation by A. S. Horowitz contains little actual information concerning these substances, but is concerned principally with discussion of foreign proteins, “antiferments,” “non-specific proteins,” “anti-virolins” and speculations on their hypothetical actions and interactions on each other and on the organs of the body and on bacteria. The report contains many questionable statements.

One finds in this report but few definite statements of facts which are known to be accurate or which could be accepted without question. The qualitative description of the proteins and their components is as vague as the previous discussion. The differentiation between the various Proteogens is extremely indefinite; that for Tuberculosis, No. 3 is described as “polyvalent, non-specific protein which rapidly attacks the acid-fast, encapsulated tubercle bacilli”; Proteogen No. 10 for syphilis is said to be a combination of “non-specific plant proteins and different chemicals which has the power to paralyze and destroy living spirochete.” It is stated that Proteogens are scientific preparations based on standard ingredients and that the standardization is more accurate than in serums, vaccines or toxins, etc. The report gives no proof of such statements.

The testimonials that are submitted are typical of “reports” that manufacturers are able to obtain from some physicians, to prove the efficacy of almost any preparation in any disease. Each consists, practically, of the opinion of the individual who has employed the Proteogens or the opinion of the patient who has been treated. Few data are given in these reports from which an impartial conclusion might be drawn. A few of the testimonials presented by the William S. Merrell Company follow. The valuelessness of such material as scientific evidence is obvious:

RHEUMATISM:--Proteogen No. 2.--The Doctor has one case being treated with No. 2. She has improved so rapidly she cannot express her pleasure, and will continue for some time on the treatments. She is a patient who was confined during the time she suffered from a rheumatic illness, and it seemed to affect her mental condition. This condition is clearing up also, very much to the pleasure of both patient and doctor.--November 27, 1918.

INFLUENZA:--Proteogen No. 12.--First day, temperature 102, gave 1 c.c. Proteogen No. 12; second day, temperature 100, gave 1 c.c. Proteogen No. 12; third day, temperature 98.8, gave 1 c.c. Proteogen No. 12, and then discharged the case as recovered.--October 31, 1918.

ASTHMA:--Proteogen No. 4.--Splendid results obtained from a sample of Proteogen No. 4. Three ampoules affected [effected?] complete recovery.--October 9, 1918.

CANCER:--Proteogen No. 1.--Mrs. B. pronounced recovered from Cancer by Dr. O. W. A., of Catlin, after having injections of Proteogen No. 1 for some time.--October 4, 1918.

ECZEMA:--Proteogen No. 5.--Tried No. 5 on a patient with eczema, and with happy results. Have not done anything for him for about five months--and he is now at his business. Proteogen No. 5 also RELIEVED HIM OF CONSTIPATION AND WHAT HE CLAIMED A TRAUMATIC STRICTURE OF THE LOWER PORTION OF SIGMOID FLEXURE. He is sure pleased and recommending them to his friends. (Proteogens).--February 17, 1919.

SYPHILIS:--Proteogen No. 10.--I am getting such excellent results with the No. 10 Proteogen for Syphilis that I am badly in need of more, as I am treating so many cases. Please send me four dozen C. O. D.--October 9, 1918.

ENLARGED PROSTATE:--Proteogen No. 1.--Have used Plantex in four cases, with good results in each case. One of them his father, an elderly man.--April 25, 1918.

LOBAR PNEUMONIA:--Proteogen No. 12.--The only case I have used Proteogen No. 12, was a man who had Lobar Pneumonia of left lung following Influenza. After crisis came, patient continued to have slight rise in temperature, cough, and after using 10 doses of your Proteogen No. 12, temperature was normal, cough very much better, patient began to take on flesh and is still improving.--December 26, 1918.

TUBERCULOSIS:--Proteogen No. 3.--The Doctor writes: The Proteogen No. 3 sent me worked wonders in my patient. The case came under my care when he was too far gone for anything to benefit him a great deal, but the Proteogen did for him more than anyone could have expected, yet he died leaving me with a few ampoules to try on the next patient.--September 20, 1918.

GONORRHEAL CYSTITIS:--Proteogen No. 11.--My patient has taken two boxes of your Proteogen No. 11 given for gonorrheal cystitis of probably two years’ standing and at this writing I consider her almost, if not entirely, cured which I think speaks very highly of your remedy. I expect to use more of your preparations in the future.--April 12, 1919. [This testimonial, either by clerical error, or because the results were considered remarkable, was repeated elsewhere in the material submitted by the Merrell Company.]

ACUTE GONORRHEA:--Proteogen No. 11.--Mr. A. E. R., age 65, weight 140 pounds. First attack. Had had no previous treatment. Came to me January 2, 1919. Had discharge, all acute symptoms, burning, etc. Gave seventeen injections of Proteogen No. 11, also mild antiseptic urethral wash. Discharged on February 15, 1919, clinically cured.--April 11, 1919.

EPITHELIOMA OF BUTTOCK.--Proteogen No. 1.--I used Proteogen No. 1 on an epithelioma of buttock some six months ago with favorable results and no return of symptoms as yet.--April 13, 1919.

It is obvious that the Proteogen preparations are in conflict with Rules 1, 6 and 10, and should not be admitted to “New and Nonofficial Remedies.” It is recommended that the previous action of the Council be allowed to stand and that publication of both reports be authorized.--(From The Journal A. M. A., July 12, 1919)

“ARSENOVEN S. S.” AND “ARSENO-METH-HYD”

Report of the Council on Pharmacy and Chemistry

The Council authorizes publication of the following report. This report declares Arsenoven S. S. of the S. S. Products Company and Solution of Arsenic and Mercury (formerly called Arseno-Meth-Hyd) of the New York Intravenous Laboratory, inadmissible to New and Nonofficial Remedies. The Council takes this opportunity to repeat its warning against the abuses--often dangerous--to which patients are frequently subjected when “intravenous therapy” is employed.

W. A. Puckner, Secretary.

Because of inquiries received, the Council took up the consideration of Arsenoven S. S. and Arseno-Meth-Hyd (now sold as Solution of Arsenic and Mercury). The preparations having been referred to a committee for consideration, this committee reported:

ARSENOVEN S. S.

“Arsenoven S. S.” is a preparation put out by the S. S. Products Company, Philadelphia. The claims are made that it is “a simplified office treatment for syphilis” and is “a combination of arsenic and mercury for office use, offering maximum efficiency, safety and convenience.” According to the company, “Arsenoven S. S.” contains Dimethylarsenin 15.4 grains, Mercury biniodid 1/10 grain, Sodium iodid 1/2 grain. With regard to the identity of “dimethylarsenin” the company claims: “This product is a compound of cacodylic acid similar to sodium cacodylate but with a more pronounced therapeutic action.” The committee recommends to the Council that “Arsenoven S. S.” be declared inadmissible to New and Nonofficial Remedies because of unwarranted therapeutic claims.

ARSENO-METH-HYD

“Arseno-Meth-Hyd,” is sold by the New York Intravenous Laboratory, New York City, for the treatment of syphilis. It comes in three dosages, 2 gm., 1.5 gm., and 0.7 gm., respectively. The claim is made that “Arseno-Meth-Hyd 2 gm.” contains “2 gm. (31 grains) of Sodium Dimethylarsenate (Cacodylate), U. S. P.. and Mercury Iodid 5 mg. (1/12 grain)” in 5 c.c. of solution. Physicians are told:

“In primary and early secondary case administer Arseno-Meth-Hyd 2 gm. every sixth day and Mercury Oxycyanide .008 (1/8 grain) intravenously between each injection.”

“In Tertiary cases and those of long standing alternate with intravenous injection of Sodium Iodid 2 gm.”

The following claims are made for the alleged effectiveness and safety of the cacodylate:

“This methyl compound of arsenic has come into almost universal use for syphilis. On account of lack of toxicity an aggressive routine can be carried on. The simple technic and absence of reactions make it most desirable for the regular practitioner. This large dose gives more uniform results both as healing manifestations and negative Wassermann’s.”

“Much discussion has surrounded the use of Methyl Compounds of Arsenic and it has been demonstrated beyond doubt that Cacodylate of Soda proves an effective remedy for syphilis provided that it is properly administered.” [sic]

“The low toxicity of this Methyl compound of arsenic is remarkable. It is contraindicated only where a decided idiosyncrasy for even small doses of arsenic exists.”

These statements are essentially false and misleading. Cacodylate has not come into universal use in the treatment of syphilis, nor has its usefulness been “demonstrated beyond doubt.” On the contrary, H. N. Cole (The Journal, Dec. 30, 1916, p. 2012) has shown that doses so large as to produce renal injury were almost totally ineffective against syphilis. Obviously, “effective doses” if such exist, are not harmless. The dosage advised for Arseno-Meth-Hyd may not produce acute toxic symptoms; nevertheless smaller doses have produced nephritic phenomena. The “Arseno-Meth-Hyd” treatment includes the intravenous injection of about 1/4 grain of a mercury salt. Although this is less than the usual dose (about 1 grain per week), the mercury is probably more effective than the cacodylate.

The committee recommends to the Council that, because of the unwarranted therapeutic claims, “Arseno-Meth-Hyd” be held inadmissible to New and Nonofficial Remedies.

The Council adopted both reports of the committee and declared “Arsenoven S. S.” and “Solution of Arsenic and Mercury” (“Arseno-Meth-Hyd”) inadmissible to New and Nonofficial Remedies. The committee’s reports on these two products impel the Council again to call attention to the undesirable and dangerous abuses to which “Intravenous Therapy” lends itself. There is a distinct field for the intravenous administration of drugs in those cases in which immediate drug action is necessary, or when the medicament is likely to be changed if absorbed through the ordinary channels. Unless such indications exist, however, intravenous administration involves not only inconvenience and expense to the patient, but what is more important, unnecessary danger. The fact that indiscriminate intravenous administration is peculiarly profitable to certain manufacturing houses makes it all the more necessary for the medical profession to be on its guard in this matter.

In this connection it is well worth while to quote the closing paragraph from an editorial on “Intravenous Therapy” that appeared in The Journal, Nov. 11, 1916. It is as true today as when it appeared:

“Intravenous therapy will be most securely advanced if its employment is restricted to such well defined fields. [As those mentioned above.] These fields can be satisfactorily determined only by a scientific pharmacologic study of the action of these drugs when so administered in animals, as well as in man, under conditions in which the results are carefully controlled. The intravenous method is an impressive one, approaching in preparation almost to that which goes with a surgical operation. The patient is usually interested and impressed by this new, and, to him, mysterious method. There is a psychic element in his reaction to the injection which is not a factor in his reaction to the same drug when given by mouth. The intravenous injection of a complex mixture would appear to be particularly reprehensible. Little is known, as has been stated, of the results to be expected from intravenous therapy, even with simple substances. The use of complex mixtures will without doubt react against the proper use of the method.”

After the report on Arseno-Meth-Hyd had been presented to the Council, a letter was received from the New York Intravenous Laboratory announcing that the preparation “Arseno-Meth-Hyd” was now called “Solution of Arsenic and Mercury” and expressing a desire to have its products accepted for inclusion in New and Nonofficial Remedies. In view of this letter, the committee’s report on “Arseno-Meth-Hyd” and the Council’s protest against promiscuous intravenous therapy were sent the New York Intravenous Laboratory for consideration.

The reply of the New York Intravenous Laboratory contained nothing which permitted a revision of the preceding report. The change of the name of “Arseno-Meth-Hyd” to “Solution of Arsenic and Mercury” means little as the name still does not disclose the important fact that the arsenic is present as sodium cacodylate, nor does it tell the character of the mercury compound. The Council voted that “Solution of Arsenic and Mercury” and “Arsenoven S. S.” be declared inadmissible to New and Nonofficial Remedies because the therapeutic claims advanced for them are unwarranted (Rule 6) and because the names of these pharmaceutical preparations are not descriptive of their composition (Rule 8).

In filing its reply with the Council, the New York Intravenous Laboratory announced that that document would be circulated to the medical profession. This is of course the firm’s privilege. The Council notes, however, with interest, that the reply is devoted almost entirely to points which were not raised by the Council and that it fails to discuss the objections which were actually made.

The reply constantly confuses the efficiency of cacodylate in anemia and in syphilis. The Council’s report on “Arseno-Meth-Hyd” does not discuss or even touch on the question of cacodylates in anemia. It is confined to a discussion of the disappointing results obtained with cacodylates as such (i. e., without mercury) in the treatment of syphilis. This attempt on the part of the New York Intravenous Laboratory to confuse the issue and to attribute to the Council an opinion that it has never stated or held is an inexcusable misrepresentation. The company in its reply said:

“We believe that you have previously stated that a solution cacodylate of soda possesses no more action than so much water. In other words, it was inert. Now you try to show that it produces renal injury.”

The Council has never declared that cacodylates are inert. In the report it is merely stated “that doses so large as to produce renal injury were almost totally ineffective against syphilis.” Neither has the Council stated that cacodylate is “peculiarly dangerous.” In fact the absolute toxicity of cacodylates is low but Cole’s results were quoted as a caution that “effective” doses are not harmless. A great portion of the remainder of the reply is devoted to disparaging arsphenamin--a product that is not involved in this action of the Council, and one about which the physician is amply informed.

Amongst other wholly extraneous matters, the firm’s “reply” tried to resurrect the pepsin pancreatin controversy. This also has nothing to do with the efficiency or harmlessness of sodium cacodylate. In order to dispose of the matter, however, it may be pointed out that the implications are entirely misleading. The work which is quoted against the Council was undertaken by the Council itself, to clarify obscurities in the older data. The outcome of these new investigations showed the essential correctness of the deductions from the older work, namely, that pancreatin is destroyed by pepsin-hydrochloric acid. Dr. Long’s work to which the firm’s reply evidently refers, showed that under favorable conditions, namely, when protected by an excess of protein, some trypsin may escape destruction in the stomach; but it fully confirmed the original conclusion that pepsin and pancreatin mixtures as ordinarily administered are practically worthless (J. H. Long, Jour. Amer. Pharmaco. Assoc., Sept. 19, 1917).

As regards the editorial on intravenous therapy, a concession may be made the New York Intravenous Laboratory: intravenous injections are no longer quite as “impressive” as in 1916, but that does not alter the fact that they should be used only when a distinct advantage is to be gained.--(From The Journal A. M. A., Aug. 2, 1919)

HORMOTONE AND HORMOTONE WITHOUT POST-PITUITARY

Report of the Council on Pharmacy and Chemistry.

“Hormotone,” of the G. W. Carnrick Company, is advertised as “A pluriglandular tonic for asthenic conditions.” “Hormotone Without Post-Pituitary” is recommended for use “in neurasthenic conditions associated with high blood pressure.” These preparations are sold in the form of tablets for oral administration. The Council declares these preparations inadmissible to New and Nonofficial Remedies because: (1) Their composition is semisecret (Rule 1); (2) the therapeutic claims are unwarranted (Rule 6); (3) they are sold under names not descriptive of their composition but suggestive of indiscriminate use as “tonics” (Rule 8); (4) in the light of our present knowledge the routine administration of polyglandular mixtures is irrational (Rule 10). In explanation of this action, the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Each tablet of “Hormotone” (G. W. Carnrick Co., New York City) is said to contain 1/10 grain of desiccated thyroid and 1/20 grain of entire pituitary, together with the hormones of the ovary and testes--the amounts and the form in which the latter are supposed to be present are not given. From this it will be seen that the only definite information given to the medical profession regarding the composition of Hormotone is that it is a weak thyroid and a still weaker pituitary preparation.

What results can be anticipated from one or two tablets three times daily (the recommended dose of Hormotone) each containing 1/10 grain of thyroid and 1/20 grain entire pituitary? Such doses of thyroid may, of course, have a beneficial action in a limited number of cases of myxedema and cretinism. An extract of the posterior lobe of the pituitary (Liquor Hypophysis, U. S. P., for example) will, when injected subcutaneously or intramuscularly, have a pronounced effect on the parturient uterus; its action on certain other forms of smooth muscle will be much less certain. But the oral administration (for which Hormotone is recommended) of the posterior lobe of the pituitary has not been shown to have any such effect. The use of the anterior lobe in doses of 1 to 4 grains (doses very many times larger than those recommended for the entire gland in Hormotone) is in the experimental stage and its only probable value seems to be in those cases of known gland deficiency.

As to the other alleged ingredients of Hormotone--hormones of the ovary and testes, amounts not stated: all physicians know the uncertainties attending the use of ovarian preparations and the serious question as to whether testicular extracts have any therapeutic value. Whatever may be the physicians views as to the probable therapeutic value of these organs, the first thing he desires to know is how much of the substance he is giving and from what part of the gland it is obtained.

So much for the facts; yet the physician is asked to jump from this region of solid fact into a sea of hypothesis; to believe that small amounts of the well-known drugs thyroid and pituitary, plus an unknown amount of unknown hormones of the testes and ovary are of great value in conditions that in themselves are often purely hypothetical. He is asked to believe that this combination has virtues in such conditions as “hypofunction of the adrenal system,” neurasthenia, the “fatigue syndrome,” amenorrhea, dysmenorrhea, “natural and artificial menopause,” sexual neuroses, cold extremities, cardiac asthenia, low blood pressure, infantilism, sterility, melancholic conditions, obesity, anorexia, anemia, slow metabolism, constipation, psychasthenia, lowered virility and the sexual neuroses of the unmarried, hysteria following functional exhaustion of the nerve centers, frigidity, etc., etc., especially if he guesses that the trouble is due to a “pluriglandular disturbance,” “glandular hypofunction,” an “adreno-pituitary deficiency,” suboxidation, etc.

The physician is invited to use Hormotone because, among other reasons, each alleged constituent is said to be “in physiologic sympathy and therapeutic harmony with the others,” and further, because:

“Pluriglandular therapy has the endorsement of high authorities, is both logical and effective and Hormotone is a splendid example of it. It will be seen at its best where the patient lacks snap and vim and vigor. Asthenic conditions necessarily indicate hypofunction of the adrenal system ...” etc.

“The use of gland extracts in the treatment of aplasias of the pluriglandular system has become an established therapeutic measure of miraculous potency (Bayard Holmes: The Internal Secretory Glands, Lancet-Clinic, Sept. 19, 1914).”

The G. W. Carnrick Company also advertises a “Hormotone Without Post-Pituitary,” each tablet of which is said to contain 1/10 grain desiccated thyroid, and to “present” “hormone bearing extracts of thyroid, anterior pituitary, ovary, and testes.” This product is just as irrational as “Hormotone.”--(From The Journal A. M. A., Aug. 16, 1919)

FORMALDEHYDE LOZENGES

Report of the Council on Pharmacy and Chemistry

The Council has voted Hex-Iodin (Daggett and Miller Co., Inc., Providence, R. I.), Formitol Tablets (E. L. Patch Co., Boston), and Cin-U-Form Lozenges (McKesson and Robbins, New York City) inadmissible to New and Nonofficial Remedies, and authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Some years ago, the Council published (The Journal A. M. A., Aug. 28, 1915, p. 816) a report on Formamint, a proprietary medicine widely exploited as a peculiar chemical compound of sugar of milk and formaldehyde. The formaldehyde was said to be liberated slowly by the action of the saliva, and because of this liberation of formaldehyde, Formamint was claimed to be a powerful germicide. Extravagant claims were made for its curative and prophylactic effects. The Council found that the therapeutic claims were grossly unwarranted and that its exploitation to the public was a public danger.

During the recent epidemic of influenza, a variety of tablets or lozenges were advertised, and are still being advertised, having formaldehyde, in some form or other, as the nucleus around which revolve the therapeutic claims. In some cases, the advertising clearly indicates the character of the formaldehyde compound that is claimed to be present; in others the statements are vague and indefinite or misleading.

It is hardly necessary to remind physicians that the use of tablets containing hexamethylenamin or other formaldehyde compounds can neither cure respiratory infections, nor even confer protection against such infections. To be effective, formaldehyde would need to be supplied to the entire respiratory tract continuously for some time or else in concentrations that would be distinctly irritant and damaging to the tissues. Saliva-dissolved tablets, obviously cannot reach the nasal or tracheal mucosae directly; and the application of quickly acting concentrations of formaldehyde is out of the question. This altogether aside from the fact that hexamethylenamin, the basis of some of these tablets, does not liberate formaldehyde in the mouth, and for this reason alone would be quite useless for this purpose! (See Hanzlik and Collins, Archives of Internal Medicine, November, 1913.)

An inefficient antiseptic is more than merely useless; it is a menace to public safety, in that it tends to lead to the neglect of rational and effective protective measures. It therefore seems advisable for the Council again to call the attention of physicians to the subject. Accordingly, three specimens of these products were purchased and examined in the Association’s Chemical Laboratory.

Hex-Iodin

Hex-Iodin (Hexamethylenetetramine and Iodum) Lozenges are manufactured by Daggett and Miller Company, Inc., Providence, R. I. They weigh 15-1/2 grs. each, are sweetened and are flavored with mint or menthol. The package and circulars do not contain a definite statement of composition. The rather indefinite synonyms “Hexameth. and Iodine Comp.” and “Hexamethylenetetramine and Iodum” suggest that the lozenges contain hexamethylenamin and free iodin. The further statement that they “contain the combined medicinal antiseptic and prophylactic properties of Hexamethylenetetramine and Iodum” is also rather indefinite. The therapeutic action claimed for the lozenges, however, could only be produced by free iodin and by liberated formaldehyde.

It is unnecessary to discuss in detail the extravagant claims made for these lozenges. The inefficiency of hexamethylenamin has already been referred to; the limitations of iodin, free or combined, in lozenge form, need not be discussed because the examination made in the A. M. A. Chemical Laboratory showed that Hex-Iodin lozenges contained no free iodin, and only traces of combined iodin. Neither formaldehyde nor paraformaldehyde was present; hexamethylenamin was present but, the lozenges being neutral no formaldehyde is generated in contact with water or with the alkaline saliva.

Thus Hex-Iodin is shown to be worthless for the purpose for which it is advertised. Of the two important ingredients said to be present, iodin and hexamethylenamin, only traces could be found of the former while the latter, as has been shown, is incapable of exerting any effect when used as the manufacturers direct.

Formitol Tablets

These tablets are prepared by the E. L. Patch Co., Boston. Each tablet weighs 13-1/2 grs. They have the odor of thymol or menthol and an acid taste and reaction. They are, according to the label:

“For the throat and mouth. Soothing, Astringent, Antiseptic. Rapidly destroys germs of infection, preventing and relieving sore throat and mouth.”

In a circular, it is stated, that one of the qualities of Formitol:

“... is the generation of formaldehyde when in contact with water or the saliva.”

“Besides generating formaldehyde, Formitol, Patch contains astringent, demulcent and soothing ingredients which render the combination unusually effective.”

A bacteriologic report is given in this circular in which it is stated that, in 2-1/2 minutes one Formitol Tablet rendered sterile a plate culture of a “characteristic throat micrococci.” The instructions are to dissolve a tablet in the mouth, slowly, once an hour or a half-tablet every half hour.

The A. M. A. Chemical Laboratory reported that Formitol Tablets contained formaldehyde (or paraformaldehyde), and ammonium compound, and some hexamethylenamin. It is probable that the formaldehyde (or paraformaldehyde) was produced by the decomposition of hexamethylenamin originally present in the tablets but decomposed by long contact with the acid.[128]

[128] The E. L. Patch Company declares that “no hexamethylenamine has ever been used in the manufacture of Formitol tablets,” and that ammonium chloride and paraformaldehyde are among the ingredients used in the manufacture of these tablets. The hexamethylenamine present in the tablets, therefore, must have been produced by interaction of the paraformaldehyde and ammonium chloride. This does not alter the laboratory findings regarding the composition of the tablets, namely, that they “contain formaldehyde (or paraformaldehyde), an ammonium compound and some hexamethylenamine.”

These tablets differ from Hex-Iodin in that they really contain active formaldehyde and, therefore, possibly produce antiseptic effect in test-tube cultures. The conditions in the mouth, however, are very different from those in the test-tube, since in the mouth the formaldehyde would be immediately “bound” or absorbed. The claimed absence of irritation indicates sufficiently the absence of efficient quantities of formaldehyde under clinical conditions.

Cin-U-Form Lozenges

Cin-U-Form Lozenges, manufactured by McKesson and Robbins, New York City, are marketed in bottles of 24 for 25 cents. They have a strong odor of cinnamon, weigh 15-1/2 grs. each, and are acid in taste and reaction. The label states that they contain:

“Cinnamon, Eucalyptus, Formaldehyde and Menthol--all powerful germicides against Influenzal bacilli, but not injurious to the system in this palatable form.”

A circular contains the same statement as to composition and claims further that they:

“... help to prevent the infection of Spanish Influenza, Pneumonia, Grip Colds and to guard against Sore Throat, Tonsillitis, Pharyngitis, etc.”

The A. M. A. Chemical Laboratory reported that Cin-U-Form Lozenges contained some formaldehyde (or paraformaldehyde) and no hexamethylenamin. It is obvious that the mouth and throat cannot be “disinfected” by these lozenges. They would be totally ineffective against bacteria that enter through the nose; they cannot prevent influenza, pneumonia, etc.--(From The Journal A. M. A., Oct. 4, 1919)

LAVORIS

Report of the Council on Pharmacy and Chemistry

Lavoris was considered by the Council in 1913, and its proprietors--the Lavoris Chemical Company--were advised that the preparation was inadmissible to New and Nonofficial Remedies because of conflict with Rules 1, 4, 6, 8 and 10. No report was published at that time. As the preparation is still widely advertised to physicians, the Council has again examined Lavoris and authorized publication of the following report.

W. A. Puckner, Secretary.

In recent years Lavoris has been widely advertised as “THE IDEAL ORAL ANTISEPTIC,” particularly to the dental profession. A printed card sent out by the Lavoris Chemical Company in 1913 read: “LAVORIS, the Pyorrhea Remedy. The Original ZINC CHLORIDE Mouth Wash. One grain zinc to each ounce.” The card also gave a “formula” to the effect that each pint of Lavoris contained:

Zinc Chloride 1.040 Resorcin 0.520 Menthol 0.400 Saccharin 0.195 Formalin 0.195 Ol. Cassia Zeyl 0.780 Ol. Caryophyl 0.195

Advertisements now appearing in medical journals repeat the older “formula” except that resorcin is omitted. The formula while seemingly frank and open is in reality indefinite and misleading in that no denomination of weight is given for the various constituents. It is uncertain, for example, if the figures in the formula are intended to represent grains, grams or percentages of the several constituents. In view of the indefinite statement of composition, a chemical examination of Lavoris was undertaken in the A. M. A. Chemical Laboratory. The report of the laboratory follows:

Zinc.--This was determined electrolytically. Fifty c.c. gave 0.026 gm. zinc and 100 c.c. gave 0.0531 gm. zinc. The average is 0.0526 gm. zinc in 100 c.c. This is equivalent to 0.1102 gm. anhydrous zinc chlorid in 100 c.c.

Chlorid.--After decolorizing some of Lavoris with chlorid-free animal charcoal, the chlorid was determined by the Volhard method. Twenty-five c.c. Lavoris required 4.328 c.c. tenth-normal silver nitrate solution equivalent to 0.01535 gm. chlorid (chloridion) or 0.0614 gm. in 100 c.c. A second 25 c.c. of Lavoris required 4.112 gm. tenth-normal silver nitrate solution equivalent to 0.01458 gm. chlorid (chloridion) or 0.05832 gm. in 100 c.c. Average is 0.05985 gm. This is equivalent to 0.1150 gm. zinc chlorid in 100 c.c. This agrees closely with the foregoing zinc determination.

Resorcin.--The method of the U. S. Pharmacopeia was used. The total bromin absorption of 25 c.c. Lavoris was 3.68 c.c. tenth-normal bromin solution. This would be equivalent to 0.00675 gm. resorcin in 25 c.c. or 0.02700 gm. in 100 c.c. In a duplicate test, 25 c.c. Lavoris required 3.8 c.c. tenth-normal bromin solution equivalent to 0.00697 gm. resorcin or 0.02788 gm. in 100 c.c. Since oil of cinnamon absorbs bromin, 50 c.c. of Lavoris was boiled until very little or no odor of the oil was noted, keeping the volume nearly constant by adding a little water from time to time, and the bromin absorption then taken. In one experiment, 0.36 c.c. of tenth-normal bromin solution was consumed, and in a duplicate no bromin was absorbed. This shows the absence of resorcin.

Residue.--On evaporating 25 c.c. Lavoris on a steam bath and subsequent drying of the residue at 100 C., 0.0455 gm. of residue was obtained. This is equivalent to 0.1820 gm. in 100 c.c.

Saccharin.--Saccharin was detected in the residue and ether-extract of the residue by its intense sweet taste when a little sodium bicarbonate was added to it.

Formaldehyd.--This could be detected by the Jarrison test. The color was not very pronounced and the quantity of formaldehyd was small.

Oil of Cinnamon.--The odor and taste of Lavoris is characteristic of cinnamon.

Menthol and Oil of Cloves.--The odor of menthol and of oil of cloves could not be detected, but no tests were made to demonstrate their presence.

The analysis thus indicates that the Lavoris of today contains no resorcin but does contain a small amount of formaldehyd, a little saccharin, and oil of cinnamon (menthol and oil of cloves could not be detected by the odor, but were not tested for). The analysis showed that the principal constituent of Lavoris is zinc chlorid, of which there is about 0.1 gm. per 100 c.c. (about 1/2 grain to the ounce).

The amount of zinc chlorid given in the published formula, i. e., 1.04, is meaningless because the unit of weight or measure is not given; furthermore, the analysis shows that it is inaccurate for any unit of weight that might be assumed from the published figures. Since the amount of the most active medicinal ingredient is both indefinite and inaccurate, the composition of the preparation is essentially secret. Lavoris is indirectly advertised to the public by having included in the package a circular giving a list of diseases for which the preparation was recommended. The combination of zinc chlorid, formaldehyd and oil of cinnamon (assuming the menthol and oil of cloves to be present as flavors) in a mixture is irrational and likely to lead its users to ascribe a false and exaggerated value to the preparation. The name is objectionable in that it does not indicate the composition of the potent ingredients of the mixture, but instead suggests its use as a mouth wash.

From a standpoint of public safety, the most serious objection to Lavoris, however, lies in the many unwarranted therapeutic claims and suggestions. It is generally held that zinc chlorid solutions which possess a strength of from 1 to 200 up to 1 to 500 exercise a weak antiseptic action. The strength of zinc chlorid in Lavoris is approximately 1 to 1,000. The directions for its use recommend that Lavoris should be diluted. A dilution of 1 to 4 is recommended for a variety of mouth conditions while for cystitis irrigations and as a vaginal douche, it is recommended that one tablespoonful be added to a quart of warm water or salt solution. The strength of zinc chlorid in the last suggested dilution would approximate 1 to 64,000. It is evident that no antiseptic action could be expected from such dilutions.

The recommendation that diluted Lavoris be used for the treatment of coryza, nasal catarrh, hay fever, inflamed eyes, hemorrhoids and leucorrhea is objectionable and irrational. Especially dangerous is the recommendation that members of a family exposed to diphtheria or scarlet fever should use Lavoris freely as a preventive. Such recommendations can but give a false sense of security and lead to the neglect of proved methods for preventing the spread of these diseases. Equally unwarranted is the recommendation that in gonorrhea one teaspoonful of Lavoris to eight of warm water be used with a blunt end syringe.

The use of Lavoris as recommended would not only prove valueless in many instances but might lead to serious consequences because really valuable methods of prevention or treatment might be neglected. For these reasons the preparation is in conflict with Rule 6.

The Council declared Lavoris ineligible for New and Nonofficial Remedies.--(From The Journal A. M. A., Nov. 1, 1919)

MEDINAL

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Medinal (Schering and Glatz, Inc.).

W. A. Puckner, Secretary.

Medinal is a proprietary name applied to barbital sodium (sodium diethylbarbiturate) the sodium salt of barbital (diethylbarbituric acid). The latter was first introduced as Veronal.

Medinal was deleted from New and Nonofficial Remedies in 1916 because the advertising issued by Schering and Glatz (who then acted as agents for Chemische Fabrik auf Actien vorm. E. Schering, the German manufacturer) contained misleading and unwarranted therapeutic claims. The Council did not publish its report because by the time the report was ready for publication the product was practically off the American market, and it was hoped that when Medinal again became available, Schering and Glatz would revise the claims and thus permit its reacceptance.

Medinal, said to be manufactured in the United States, is now marketed by Schering and Glatz, Inc. In October, 1918, the firm sent to the Council a typewritten copy of a proposed circular for Medinal. The firm was informed that this leaflet was subject to the objections that had been raised when Medinal was deleted from New and Nonofficial Remedies. In April, 1919, the firm submitted a printed circular which it was sending out. This contained numerous misleading statements, among them, these:

“MEDINAL removes its [Diethylbarbituric acid] one objectionable feature--insufficient solubility--and thus fulfills the three prerequisites of a truly rational hypnotic: Quick absorption, insuring prompt action, rapid and complete excretion, affording protection from cumulative toxic after effects, and the choice of rectal and subcutaneous administration.”

There is no justification for the claim that diethylbarbituric acid (barbital) has only one objectionable feature and that a minor matter of “insufficient solubility.” The Council has called the attention of Schering and Glatz, Inc., to the fact that the difference in the time of absorption between Medinal (barbital sodium) and barbital is, at the most, but one of minutes and that there is no evidence that Medinal is excreted more rapidly than barbital. Hence the claims that the danger of toxic side-actions and that cumulative after-effects are avoided in this product, are wholly unwarranted.

It is also claimed, and the claim is unsupported by satisfactory evidence, that Medinal is useful in the insomnia of tuberculosis in which condition it is said to have a double advantage owing to its favorable effects on the night-sweats. It is claimed that Medinal is used in the withdrawal treatment of morphin addiction with great success; there is no evidence that Medinal has any special usefulness in this treatment of the morphin habit. It is claimed further that success has been reported with Medinal in the treatment of whooping cough. The Council knows of no satisfactory evidence to show that Medinal is of special value in whooping cough; on the contrary, it is capable of doing a great deal of harm. The recommendations that Medinal be used for the control of labor pains and in acute neuralgic pains that resist other forms of treatment are wholly unwarranted as the value of the drug in such conditions is inherently improbable and until satisfactory evidence in support of them is forthcoming, must be deemed misleading.--(From The Journal A. M. A., Nov. 15, 1919)

OMISSION OF COTARNIN SALTS (STYPTICIN AND STYPTOL) FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Salts of the base cotarnin have been used as local and systemic hemostatics. The hydrochlorid was first introduced as “Stypticin,” and is now in the pharmacopeia as cotarnin hydrochlorid (Cotarninae Hydrochloridum, U. S. P.). The phthallic acid salt of cotarnin--cotarnin phthallate--was introduced as “Styptol.” Both Stypticin and Styptol were admitted to New and Nonofficial Remedies. In 1918 the Council voted to omit Stypticin because the former American agents were no longer offering it for sale. Styptol was retained and is described in N. N. R., 1919.

As was pointed out in the description (N. N. R., 1918), the evidence for the usefulness of the cotarnin salts has been contradictory and unsatisfactory; but since the available data against the efficiency were at least equally unreliable, the Council deemed it best to retain them in N. N. R. pending a thorough investigation of the subject. This was undertaken by P. J. Hanzlik, at the suggestion of the Therapeutic Research Committee of the Council.

A reliable judgment of hemostatic efficiency can be formed only on a basis of strictly controlled conditions, which can best be furnished in the laboratory. Hanzlik repeated the principal experiments published by previous investigators, and applied a number of new or improved methods. The results (published in the Journal of Pharmacology and Experimental Therapeutics =10=:523, 1918; =12=:71, 1919) show the following:

Direct Application to Wounds.--The widely quoted results of the gynecologist K. Abel, on the footpad of cats, were found to be quite unreliable. When the experiment is properly controlled, the results are either negative or the bleeding may be increased. Quantitative experiments on wounds of the footpad of dogs showed that cotarnin invariably increased the bleeding. Equally negative or unfavorable results were obtained with wounds to the comb of roosters, and to the liver and spleen.

Direct Action on Vessels.--The results of perfusion experiments were variable, but, in general, showed a vasodilation action instead of constriction. This holds true also of the uterine vessels. The vessels in the living animal (rabbit’s ear) were also unaffected.

Systemic Administration.--The bleeding from an irrigated wound was not modified directly by intravenous injection of cotarnin salts, but varied merely with the state of the blood pressure.

The evidence for the inefficiency of cotarnin salts as hemostatics seemed so conclusive as to warrant the Council in rescinding the acceptance of Styptol, and directing the omission of the general article on cotarnin salts and the description of Styptol from New and Nonofficial Remedies.--(From The Journal A. M. A., Nov. 22, 1919)

MICAJAH’S WAFERS AND MICAJAH’S SUPPOSITORIES

Report of the Council on Pharmacy and Chemistry

“Micajah’s Medicated Wafers” and “Micajah’s Suppositories,” sold by Micajah & Co., Warren, Pa., are declared inadmissible to “New and Nonofficial Remedies” because (1) their composition is essentially secret (Rule 1); (2) name of neither of these mixtures is indicative of its composition (Rule 8); (3) of exaggerated and unwarranted therapeutic claims (Rule 6), and (4) the therapeutic advice which accompanies the trade packages constitutes an indirect advertisement to the public (Rule 4).

W. A. Puckner, Secretary.

Micajah’s Medicated Wafers (formerly called “Micajah’s Medicated Uterine Wafers”) were analyzed in the A. M. A. Chemical Laboratory in 1910. They were found to consist essentially of dried (“burnt”) alum, boric acid and borax, in approximately the following proportions:

Alum, dried 59.86 per cent. Borax, dried 15.62 per cent. Boric acid 5.67 per cent. Water of hydration 18.85 per cent.

There are a number of drugs that are more or less effective in the treatment of local lesions of mucous membranes and the skin. They are classed as astringents. Among these are included alum, borax and boric acid. Every physician has used them. To say that a wafer consists of alum, borax and boric acid inspires but little awe. But there is something much more mysterious and impressive in declaring that a wafer “consists of an astringent and antiseptic base, in which are incorporated certain medicaments which both locally and after absorption, contribute to the astringent, antiphlogistic, depletive, soothing and healing action of the product.” This gives the impression that some powerful and almost incomprehensible factors are at work. Yet, after all is said and done, the substances contained in Micajah’s Medicated Wafers are just the homely old alum, boric acid and borax.

In addition to “Micajah’s Medicated Wafers,” Micajah & Co. also put out “Micajah’s Suppositories for Hemorrhoids.” These have been examined in the A. M. A. Chemical Laboratory and, like the “Medicated Wafers” have been found to contain alum, boric acid and borax--and these substances practically alone--incorporated in cocoa butter. The company claims that “to these have been added Ammonii Ichthyosulphonate, Balsam of Peru, Ext. Belladonae.” The A. M. A. chemists report, however, that if extract of belladonna is present at all it is in amounts too small to be detected by the method commonly employed in the chemical examination of alkaloidal drugs. The chemists report further that while ammonium ichthyosulphonate and balsam of Peru both have a decided odor and are dark in color, the suppositories have but little color and the odor of the cocoa butter that forms their base is not covered by these drugs; obviously, therefore, if ammonium ichthyosulphonate and balsam of Peru are present at all it is in amounts utterly insufficient to exert any therapeutic effect.

It would be hard to find better examples of mischievous proprietary medicines than these two products of the Micajah Company. “Twins of Efficiency,” they are called in an advertising pamphlet. The composition is not stated. A physician using the “twins” does so absolutely in the dark. To him they are secret preparations. He is encouraged to use them in a great variety of conditions in which other drugs are much more useful. Inevitably, physicians using them will be likely to overlook, or pass over, new growths, specific infections and diseases that require radical remedial measures.

In addition to misleading and exaggerated claims, there is a reference to a report from the usual “well-known and reliable bacteriological laboratory.” The excerpts published from this report of an unnamed laboratory are sufficiently vague to incriminate no one.

From time to time it is worth while to emphasize facts regarding proprietary medicines that while obvious are sometimes forgotten. For this reason attention is directed to Micajah’s Uterine Wafers and Micajah’s Suppositories.--(From The Journal A. M. A., Nov. 29, 1919)

ALKALITHIA

Report of the Council on Pharmacy and Chemistry

Alkalithia was introduced at a time when it was believed that the administration of lithium salts served to remove uric acid from the system. The product was considered by the Council in 1906, and found ineligible for New and Nonofficial Remedies. No report, however, was published at that time.

Because of inquiries received, the Council examined the current claims for Alkalithia, and authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Keasbey and Mattison Company’s Effervescent Alkalithia is sold with the following statement of composition:

“Each dose or heaping teaspoonful contains 1 grain of Caffeine, 10 grains each of Bi-carbonates of soda and potash, and 5 grains of Carbonate of Lithia.”

The A. M. A. Chemical Laboratory reports that Alkalithia is an effervescent mixture which contains alkaline carbonates and bicarbonates together with caffein, free tartaric acid and free citric acid. The major portion of the alkali carbonates and bicarbonates is converted into citrates and tartrates when the preparation is dissolved in water--as is done before it is taken. An excess of alkali is present, however, as the solution has an alkaline reaction. Each “heaping teaspoonful” (which was found to be about 4.85 Gm.) contains about 0.044 Gm. of caffein (the manufacturers claim 0.0648 Gm. per heaping teaspoonful). As taken, Alkalithia, therefore, represents caffein in a solution of alkali tartrate, citrate and bicarbonate containing free carbonic acid. If it is assumed that all of the tartrate and citrate in Alkalithia is converted into carbonate in the organism, a “heaping teaspoonful” of Alkalithia would represent about 2.9 Gm. of sodium bicarbonate. This assumption is, however, not correct, for it is known that tartrates are not completely converted into carbonates in the organism.

According to the label on the bottle, this mixture of caffein and alkali salts is “a common sense remedy for the relief and treatment of conditions dependent upon perverted metabolism as manifested by neuralgic, rheumatic, cardiac and renal symptoms.” Wrapped with a trade package is a circular in which is discussed the “uric acid diathesis” as “a cause of Rheumatism in its various forms, Calculus, Gravel and Inflammation of the Bladder and Kidneys, Asthma, Hay Fever, Catarrh, Quinsy and Bronchitis, Eczema, Hives, Itching and Burning of the Skin, Palpitation of the Heart and Cold Hands and Feet, Dizziness, Mental Depression, Melancholia, Neuralgia, Chorea, Hysteria, Numbness and a great variety of purely nervous symptoms.” The arguments for the use of Alkalithia as “a safe and scientific treatment for the uric acid diathesis” found in the circular constitute an indirect appeal to the laity (conflict with Rule 4).

In the circular matter sent direct to the physicians, Keasbey and Mattison claim that in rheumatism, Alkalithia is prescribed by the medical profession more often than any other remedy. The claim is made that, “In five minutes the urine will be discolorized and analysis will show it to be loaded with urates.” The manufacturers further assert:

“You can change the character of the urinary secretion in a few minutes completely” by Alkalithia, and “In nine cases out of ten, when the doctor prescribes ‘Alkalithia’ his patient greatly improves, or gets well.”

The firm advises that “Renal Insufficiency” be determined by the old method of multiplying the ounces of urine in twenty-four hours by the last two numbers of the specific gravity, adding 10, which gives the number of grains of solids excreted in the twenty-four hours. If this is low, no matter what the cause, they advise Alkalithia, “that ideal eliminant.”

The Council declared Alkalithia inadmissible to New and Nonofficial Remedies because the claims made on the label and the circular accompanying the trade package lead the public to its detriment to depend on this preparation (Rule 4); and because the therapeutic claims are unwarranted (Rule 6).--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 65)

ARHOVIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Arhovin is a solution of dephenylamine, thymol benzoate and ethyl benzoate, marketed by Schering and Glatz, Inc. It was omitted from New and Nonofficial Remedies because the therapeutic claims made for the preparation were unwarranted and because the firm had refused to discontinue the distribution of the advertising which contained the objectionable claims prior to Jan. 1, 1919. When the report which appears below explaining the dismissal was submitted to Schering and Glatz, Inc., the firm again promised a revision of its advertising, but refused discontinuance of the objectionable circular before Jan. 1, 1920. Since Arhovin is still marketed with unwarranted therapeutic claims, the Council has authorized publication of this report.

W. A. Puckner, Secretary.

The attention of the firm Schering and Glatz, Inc., was called to misleading statements in its booklet for Arhovin in 1915, and in 1918 the firm was informed that unless the misleading statements were withdrawn before Jan. 1, 1919, Arhovin would be omitted from New and Nonofficial Remedies.

The following quotations are taken from the circular in question, and illustrate the character of the claims to which objection was made:

“Striking also is the antiphlogistic and anesthetic effect of Arhovin on the inflamed mucosae, an effect which, as all authorities agree, is far greater than that of all other internal anti-gonorrheaics.”

“Under its influence vesical and prostatic complications, gonorrheal arthritis, endocarditis, etc., are rarely incurred.”

References to the indexes of leading textbooks, including those of Meyer and Gottlieb, Cushny, Sollman and Bastedo, fails to show that Arhovin is so much as mentioned by those authors; hence, it is obviously false to state, as is done in the first of the quotations above, that all authors agree concerning the striking effects of Arhovin.

Many of the statements are objectionable by reason of the actions implied, rather than stated directly. The following are examples:

“Arhovin in Gonorrheal Infections of the Male Genito-Urinary Organs. Anterior Urethritis. This is the class of cases in which the most favorable results from Arhovin have been reported.”

“Posterior Urethritis.

“Here also the striking effects from Arhovin medication, both in acute and chronic cases, are rapid decrease of discharge, disappearance of gonococci from the secretion, and cessation of subjective difficulties, such as strangury.”

While the firm did not agree to withdraw the objectionable advertising before Jan. 1, 1919, which made necessary the omission of Arhovin from New and Nonofficial Remedies, 1919, it did submit a proposed folder in which the most objectionable of the claims are still made.

The following statement, which was in the proposed “folder” and is included in an advertising pamphlet sent out during 1919, serves to illustrate those points:

“Its action is three-fold:

“Strong antiseptic and bactericidal effect upon the urethral and vesical mucosae, highly conducive to shortening and palliation of the acute disease course.”

No evidence has been presented that Arhovin is capable of destroying the gonococcus in the urethra, and consequently, the Council declared the recommendation for the use of Arhovin in the treatment of gonorrhea, by means of claims such as those just cited, is both misleading and dangerous.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 66)

CHLORON, CHLORAX AND NUMBER “3”

Report of the Council on Pharmacy and Chemistry

The report which appears below was sent to the Chlorine Products Company, Inc., May 14, 1919. In reply to an inquiry sent the Chlorine Products Company, July 8, the company wrote that it could send no reply because the medical director was still in France. However, Chloron and Chlorax are being advertised in medical journals; also essentially the same advertising as that discussed in the report was recently received by a physician from the Chlorine Products Company.

The preceding facts having been reported to the Council, publication of the report was authorized.

W. A. Puckner, Secretary.

Chloron, Chlorax and Number “3” are preparations of essentially similar composition put out by the Chlorine Products Company, Inc., New York.

Chloron

Chloron, according to the label, is “A stable CHLORINE remedy for the reduction of inflammation, relief of pain and for all wounds, burns, scalds and every description of sores except cancer and lupus.” Its composition is given as:

“Free chlorine, 0.200 per cent.; calcium chloride, 0.190 per cent.; mercurous chloride, 0.030 per cent.; lithium chloride, 0.035 per cent.; calcium hydrate, 0.010 per cent.; water to 100 parts.”

The Council asked the manufacturers for further information in regard to the composition or preparation of Chloron and received this reply:

“Chlorine gas is prepared in the usual way and purified and passed into water until a saturated solution is made.

“Water to the extent of three times the volume of the chlorine solution is used to dissolve the necessary amount of calcium chloride, and the two solutions are mixed.

“The necessary amounts of Lithium and Mercurous Chloride are then intimately mixed and made into solution. This solution is then added to the above and the whole is agitated for some minutes.”

A specimen of Chloron was examined in the A. M. A. Chemical laboratory and the chemists reported:

Qualitatively the presence of the following constituents was confirmed: calcium, mercury, lithium, chlorid, free chlorin. The solution was alkaline. Of course, the declaration that Chloron contains mercurous chlorid (calomel) is obviously incorrect, as mercurous chlorid cannot exist in a solution containing active (free) chlorin, but is oxidized to mercuric chlorid (corrosive sublimate). As the solution was alkaline in reaction, it seemed unlikely that all the active chlorin was present in the free state, as declared on the label. Quantitative determination of free chlorin and of total active (“available”) chlorin gave: free chlorin, 0.036 gm. per hundred c.c.; total “available” chlorin, 0.330 gm. per hundred c.c., or 165 per cent. of the claimed amount.

A comparison of the information sent to the Council with the analytic findings leads to the conclusion that Chloron is not of reliable composition.

As evidence of the therapeutic value of Chloron, the following “case reports” were submitted:

“In a case of second degree burn involving the most of one leg from the middle of the calf down, CHLORON was the only dressing used. The burn was a bad one and the patient in a rundown anaemic condition, at no time was there any appearance of pus, the surface looked clean and bright and the healing was accomplished with practically no scar whatever. The burn was kept wet with the solution by hourly applications day and night. The skin which has grown on the wound is clear, healthy and firm.

In another case of Varicose veins of long standing, the result was surprising. The patient told of two years vibrating from Hospital to Hospital and getting no real relief. Each leg had large open running sores, the only dressing used was wet compresses of this solution. The pus disappeared at once, the wound began to cicatrise from the edges and in two weeks the man was discharged from the hospital practically cured.”

“CHLORON was recently tried at the ---- and ---- Hospital on cases presenting ulcers and other sores which did not readily yield to other methods, with good results, in fact were of an indolent type. In these cases CHLORON proved very valuable.”

“I have used CHLORON on a series of cases (surgical) presenting pus foci and I have found the application very beneficial and healing, the pus early disappearing. In cases of Osteomyelitis, Suppurating Arthritis, Cellulitis and Chronic Ulcers, CHLORON is particularly valuable, its good effects quickly observed and the time of restoration to health shortened.”

In the first case report, there is no evidence that Chloron is more efficient in the treatment of burns than any other commonly used procedure might have been. In the case of the varicose ulcers, while there was some apparent benefit from Chloron, no credit is given to rest and the general treatment which is known to be important in the treatment of such conditions. The evidence in the other case reports is quite inconclusive. Consideration of the “case reports” leads to the conclusion that clinical evidence for the value of Chloron is lacking.

Attention should be called to the fact that the amount of active chlorin, claimed to be present in Chloron as well as the amount found by the association laboratory, is less than that considered effective by Dakin, Dunham and others; seemingly in preparing Chloron no attention has been paid to the degree of alkalinity, yet the importance of this factor is now generally recognized.

Chloron fails to comply with the requirements for surgical solution of chlorinated soda (N. N. R., 1919, p. 133), yet the manufacturers make free use of the text of Dakin and Dunham’s Handbook of Antiseptics in their advertising pamphlet. Thus:

From the Chloron pamphlet:

“This ideal antiseptic effects complete sterilization within its sphere of action without causing any damage to the cells or tissues. An important method of judging the injurious action of antiseptics is to investigate their effects on the leucocytes. From experiments in vitro by Parry Morgan and in vivo by Col. C. J. Bond with the strength of antiseptics commonly used in surgery, it has been found that Chlorine antiseptics and mercury salts have little effect on phagocytosis in comparison with other germicides.

The activity of the leucocytes from wounds which have recently been treated with CHLORON may be demonstrated experimentally.”

“In addition to its antiseptic action CHLORON is a strong oxidizing agent and deodorant and possesses to a marked degree the property of decomposing toxins. In this connection it is interesting and pertinent to note that Dean, by the regulated action of hypochlorous acid, has prepared a nontoxic dysentery vaccine and it is now a common observation that the free use of CHLORON may reduce the constitutional symptoms arising from septic processes and that they reappear on discontinuing the antiseptic treatment.”

Dakin and Dunham Handbook of Antiseptics:

“The ideal surgical antiseptic should effect complete sterilization within its sphere of action without causing any damage to animal cells. At the moment such a substance does not appear likely to be found, but on the other hand it is surprising to see how little damage may be done to animal tissues by some active antiseptics. An important method of judging of the injurious action of antiseptics is to investigate the condition of the leucocytes in wounds recently treated with the substance under consideration. In general it appears from experiments in vitro that, with the strength of antiseptics commonly used in surgery, mercury salts and hypochlorites have relatively little effect on phagocytosis as compared with phenol (Parry Morgan). It is a regular phenomenon to observe activity of the leucocytes obtained from wounds which have been recently treated with hypochlorites.

Ingenious methods for determining the influence in vivo of antiseptics on the activities of leucocytes have been worked out by Col. C. J. Bond.

“In addition to their disinfecting action, the Chlorine antiseptics are strong oxidizing agents and deodorants and moreover possess in high degree the property of decomposing toxins. By the regulated action of hypochlorous acid, Dean has prepared a nontoxic dysentery vaccine and it is a common observation that the free use of hypochlorites may reduce the constitutional symptoms arising from septic processes and that they reappear on discontinuing the antiseptic treatment.”

Chlorax

Chlorax is said to be “A stable CHLORINE solution for internal use,” in “Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood Dicrasias,” “Lithemias and Rheumatism,” and “Nervous Conditions.” It is claimed to have the same composition as that of Chloron with the addition of 0.016 per cent. of tincture of opium.

The A. M. A. Chemical Laboratory reported that the free chlorin in Chlorax was 0.01 gm. per hundred c.c. and the total amount of active (“available”) chlorin was 0.25 gm. per hundred c.c., or 125 per cent. of the amount claimed. The laboratory notes that though the chlorin content of Chloron and Chlorax is claimed to be the same, that of Chlorax actually is less. This is not surprising when the presence in Chlorax of reducing substances such as alcohol is borne in mind. The laboratory concludes that Chlorax is not of reliable composition.

The following is typical of the “case reports” submitted to show the value of Chlorax:

“In January last I used Chlorax on a case of Diabetes Mellitus and with excellent results.

“The patient had been suffering for about nine years and when first brought to my care Toxemia had set in, he was drowsy, irritable and unable to leave the house. I prescribed Chlorax in teaspoonful doses four times a day and am pleased to say that in one week he showed marked improvement. Soon after he was able to leave the house and attend to his business and after two months’ treatment resumed a normal diet and habits apparently without injurious effects.

“I believe that in this case Chlorax undoubtedly prolonged life.”

No mention is made of the dietary or other measures used. The wide variation in diabetes and its response to proper diet is so well known that the noncommittal statement concerning the beneficial effects of Chlorax amounts to no evidence at all in favor of the preparation.

The other “case reports” furnished by the Chlorine Products Company, Inc., which concern the treatment of gastric ulcers, acute alcoholic gastritis, tonsillitis, etc., are equally unconvincing. In fact, no satisfactory evidence for the clinical value of Chlorax has been presented.

The following from the advertising for Chlorax is unwarranted and absurd:

“Mercurous chloride (calomel) is perhaps the most widely used internal antiseptic and alterative and has established itself in the therapy of constipation, cholera, dysentery, cardiac dropsy, pleurisy, malignant fever, malaria, syphilis, worms, infectious diseases, gout and rheumatism; lithium chloride is particularly efficacious in acute and chronic parenchymatous nephritis and in various lithemic conditions; while Opium has no rival as an anodyne and can be used to stabilize and conserve the alkaline reserve of the body against the acidosing influence of infections.”

Further, on page 14 we find:

“In chills and fever malaria and other blood dicrasias, CHLORAX is indicated as an internal antiseptic and it exerts a beneficial effect on the course of these diseases.”

The claims made for Chlorax are exaggerated and misleading.

Number “3”

According to the label, Number “3” is “A STABLE CHLORINE remedy for the purification of the blood,” with the composition:

“Free Chlorine, 0.35 per cent.; Calcium Chloride, 0.30 per cent.; Mercurous Chloride, 0.03 per cent.; Lithium Chloride, 0.04 per cent.; Calcium Hydrate, 0.01 per cent.; Opium, 0.02 per cent.; Ethyl Alcohol, 0.10 per cent.; water to 100 parts.”

It will be noticed that the composition claimed for Number “3” is essentially similar to that claimed for Chloron. It differs from Chloron in that the amounts of some of the constituents are somewhat greater, and in that, like Chlorax, it contains some tincture of opium.

The A. M. A. Chemical Laboratory reports that the free chlorin in a specimen of Number “3” was 0.024 gm. in 100 c.c. and the total active (“available”) chlorin 0.173 gm. per hundred c.c., or about 50 per cent. of the claimed amount. The examination indicates that Number “3” is of unreliable composition. The Chlorine Products Company, Inc., submitted no clinical evidence for Number “3” to which it refers as “our Syphilis remedy.” It stated that two physicians had used the preparation “with good results,” and admitted that “the company requires further evidence before pushing it.”

The Council declared “Chloron,” “Chlorax” and “Number ‘3’” in conflict with the rules governing admission to New and Nonofficial Remedies. All are of unreliable composition (conflict with Rule 1). The therapeutic claims made for the preparations are not substantiated by acceptable evidence and are unwarranted and misleading. Chloron is inferior as an antiseptic to the well-known surgical solution of chlorinated soda on account of its low chlorin content and uncontrolled reaction. There is no warrant for the claim that Chlorax is useful in the treatment of “Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood Dicrasias,” “Lithemias and Rheumatism,” and “Nervous Conditions,” nor is there warrant for the claim that “Number ‘3’” is a remedy for the purification of the blood or a “Syphilis remedy” (conflict with Rule 6).

The names of these pharmaceutical mixtures are not descriptive of their composition (conflict with Rule 8).

All three preparations are irrational. No evidence has been furnished that the lithium salt is of value in the mixtures. It is not rational to combine an active chlorin preparation and a mercury salt in one mixture, nor is there evidence that the addition of opium to the preparations proposed for internal use is of value or rational. Experimentation with Number “3” as a “Syphilis remedy” is to be severely condemned in that those on whom it is used will in the meantime be deprived of efficient medication (conflict with Rule 10).--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 70)

ELARSON OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report announcing the omission of Elarson from New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Elarson, now sold by the Winthrop Chemical Company, Inc., was formerly sold in the United States by the Bayer Co., Inc. It was admitted to New and Nonofficial Remedies in 1914.

The circular issued by the Winthrop Chemical Co. contains several statements markedly at variance with the results of an investigation made, at the request of Fischer, by Joachimoglu (Arch. f. exper. Path. u. Pharmakol. 78:1914). The circular states that Elarson contains about 13 per cent. arsenic. Joachimoglu found from 10.8 to 11.1 per cent. to be present. The circular states further:

“The fact that Elarson represents a lipoid-like chemical combination of arsenic has an important bearing upon its absorption and utilization in the system ... there is good reason to believe that when arsenic is administered in a stable, lipoid-like combination, as in Elarson, it is more readily taken up by the cells and more completely utilized than when given in the customary manner.”

“As regards the behavior of Elarson in the system, it has been shown that its active constituent, chlorarseno-behenol, is almost completely absorbed in this form, probably as a chlor-behenolate of sodium or potassium.”

As a matter of fact, Joachimoglu found that very little arsenic was absorbed when Elarson was given to dogs and rabbits; most of it was recovered from the feces; only traces were found in the liver and kidneys and none in the blood and brain. The absence from the latter organs shows that the lipoid solubility does not obtain in the body. It is claimed in the circular that Elarson has the advantage over Fowler’s solution “in that it is free from any irritating action upon the gastro-intestinal tract”; it is stated that as many as sixty tablets have been given to dogs daily without any toxic effects. Joachimoglu, on the other hand, found powdered Elarson to be very irritating to the gastro-intestinal tract; also that the dog could not stand sixty tablets at all (gar nicht vertragen), such doses causing vomiting, diarrhea and intestinal hemorrhages; on repeated administration the symptoms became progressively more severe. Joachimoglu also found that, compared on the basis of arsenic content, Elarson, given intravenously, is from ten to twelve times as poisonous as arsenic trioxid. Elarson is recommended for the class of cases in which Fowler’s solution is used.

To sum up: None of the special claims made for Elarson--the arsenic content, ready absorbability, freedom from irritating action on the gastro-intestinal tract and its alleged better adaptation for continued administration--have been substantiated; on the contrary, they have been disproved as well as the theory of its mode of absorption proposed by Fischer and Klemperer. Furthermore, Joachimoglu found that when it actually got into the circulation (intravenous injection) in the form in which Fischer and Klemperer supposed it to be absorbed, it was from ten to twelve times as toxic as arsenic trioxid.

The Council voted to omit Elarson from New and Nonofficial Remedies because it is sold under unproved and consequently unwarranted claims and because it is an unscientific and relatively useless article. Elarson has not been shown to have advantages over Fowler’s solution; on the contrary, in some respects at least, it is inferior.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 75.)

IODIPHOS

Report of the Council on Pharmacy and Chemistry

A report which appears below was sent Charles L. Heffner for consideration. No reply having been received, the Council authorized its publication.

W. A. Puckner, Secretary.

Iodiphos, marketed by Charles L. Heffner, Brooklyn, N. Y., is declared to contain ferric citro-iodine, 6 grains; calcium glycerophosphate, 8 grains; sodium glycerophosphate, 8 grains, and hypophosphorous acid, 2 minims in each fluidounce, and to present “the Metallic and Non-Metallic elements: Iron, Iodine, Phosphorous, Calcium and Sodium (each in separate Basic combination).”

According to the label, Iodiphos is “ALTERATIVE, TONIC, NERVINE and ANTI-TUBERCULAR” and is “For Treatment of BLOOD, NERVES and PULMONARY ORGANS.” An advertising circular[129] asserts that “Iodiphos exerts its Physiological action rapidly in hardening of the Arteries, High Blood Pressure, Anaemia, Glandular Swelling, Neurasthenia, Hypochondria, Phthisis, Bronchitis, Asthma, Pneumonia and as an Intestinal Antiseptic and Appetizer,” and declares it to be “Indispensable as a Tonic and Restorative.”

[129] After publication of the foregoing report had been authorized by the Council, a letter was received from Charles L. Heffner, advising that the distribution of the circulars has been discontinued.

In the advertising circular it is averred that in the production of Iodiphos “Chemistry Again Aids the Modern Physician.” Iodiphos is another instance when a decadent polypharmacy proposes haphazard medication and so obstructs the efforts of modern medicine to establish the use of single drugs to meet definite indications.

Iodiphos is inadmissible to New and Nonofficial Remedies because it is an irrational mixture of drugs sold with therapeutic claims that are unwarranted, and under a name which is not descriptive of its composition.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 81.)

MERVENOL AND ARMERVENOL NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the report which appears below declaring Mervenol and Armervenol, marketed by the Hille Laboratories, inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Mervenol is stated by the proprietors--The Hille Laboratories, Chicago--to be a hydrosol (colloidal suspension) of the sulphides of mercury and copper, containing sufficient sodium chloride to make it isotonic with blood serum, and “inert proteid” and “carbohydrate” to stabilize the colloidal suspension: each cubic centimeter is stated to contain 0.005 gm. mercury, 0.0016 gm. copper, and 0.0016 gm. sulphur.

It is claimed that this preparation is of value in pneumonia, influenza, and other conditions and diseases requiring increased leukocytosis.

It is further claimed that the properties and therapeutic effects of this preparation are as follows: “Practically non-irritant; practically non-toxic; lower temperature, often crisis like; lower pulse, with better elimination; greatly accelerated recovery from Influenza; fewer Pneumonia complications; lower mortality rate in Influenza and Pneumonia; remarkable Leucocyte stimulation.” Administration by mouth and by intramuscular and intravenous injection are advocated.

In the recent influenza epidemic, it is reported that therapeutic results of some value were obtained at the Great Lakes Training Station and at Fort Sheridan. The reports of certain medical officers indicate that this preparation seemed to have some effect on the course of pneumonia and influenza, on the temperature, and on the leukocyte count. But those conducting the experiments state that it was “absolutely impossible” to fulfil ideal conditions as to controls and other observations at the time the experiments were conducted.

So far as the Council knows, no effort has been made to determine the potent constituent, or constituents, of this preparation; whether the mercury, the copper, or the protein in the mixture was responsible for the claimed benefits is an open question.

These reports were given careful consideration, but it was decided not to accept this preparation because of (1) exaggerated therapeutic claims, conflicting with Rule 6 (aside from the report of its use in influenza and pneumonia at the Great Lakes Training Station and the Post Hospital at Fort Sheridan, which reports are of work done and observations made under conditions which did not permit careful controls, no evidence has been presented to the Council supporting the therapeutic claims) and (2) being an irrational mixture, conflicting with Rule 10--a mixture containing colloidal mercury, copper and sulphur with proteins and carbohydrates in addition, it is difficult to predict the changes which occur in such mixtures on standing.

Samples of Mervenol (two 1-ounce bottles) submitted by the manufacturer, June 5, 1919, were found when opened, Aug. 18, 1919, to have undergone decomposition. A very disagreeable odor had developed, the liquid was turbid, and a large amount of precipitate had formed.

Armervenol is stated by the proprietors--The Hille Laboratories, Chicago--to be a hydrosol (colloidal suspension) of “mercury-copper-sulpharsenite” containing sufficient sodium chlorid to make it isotonic with blood serum and “inert proteid” and “carbohydrate” to stabilize the solution: each cubic centimeter is declared to contain 0.0025 gm. arsenic, 0.005 gm. mercury, 0.0016 gm. copper, and 0.0032 gm. sulphur.

The use of Armervenol as advised by the Hille Laboratories is the same as that of Mervenol, and in addition its use in syphilis is emphasized. The criticisms of this mixture are similar in every respect to those directed against Mervenol--the addition of arsenic introduces still another factor of uncertainty.

After investigating these claims, it was decided not to accept this preparation on the ground (1) that the therapeutic claims are unproved and unwarranted, conflicting with Rule 6, and (2) that the mixture is an irrational one, conflicting with Rule 10.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 82.)

NORMAL PHENOL SERUM (CANO) AND METHYL-PHENOL SERUM (CANO) NOT ACCEPTED FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following statement declaring Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) ineligible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

No statement of the composition of these preparations was submitted to the Council and none appears on the labels of the trade packages. However, the advertising circular contains statements such as:

“... normal phenol serum--phenol with methyl blue dissolved in anaphylactic serum ...”

“... a combination of human or horse serum with Phenol and Methylene-blue, thereby forming a new chemico-biologic product which he termed Methyl-phenol Serum or, chemically, Chloride of Phenol Thionin Tetramethylene-Seric.”

“Methyl-phenol Serum is a chemico-biological product in which Phenol is the chief factor. Each ampule of 10 c.c. contains the therapeutic equivalent of 0.5 gm. (7.5 grains) of Phenol.”

From the foregoing it appears that both preparations contain phenol and methylthionine chloride (methylene blue) and that the second does not contain methyl phenol (cresol) as the name would indicate.

No definite evidence for the value of these preparations is brought forward and even the manufacturer is constrained to caution, “We assume no responsibility for the therapeutic action of the serum....” On the other hand there are a great many statements in the papers of Cano and his colleagues to which exception must be taken. Of these, from among many similar, the following statements are to be cited and commented on:

“Accepting that the gonorrheal infection gives systemic toxemia from absorption of the toxins ...”

It is the general opinion that in the majority of instances there is no systemic toxemia.

“The technique of intraprostatic injection, while less simple than that of the intravenous, is by no means so difficult or complicated as to place it exclusively in the category of the urologist.”

This obviously is an attempt to encourage the general use of these preparations and to minimize the necessity for careful study and special skill in their employment. It is most unwise for one to attempt intraprostatic injections unless he is specially trained in the technique of this procedure.

“This injection to be performed after the 5th or 6th intravenous injection of Methyl-phenol Serum....”

Intravenous injections have a place in sane therapy only when the medicament to be so administered is of known composition and when evidence is available which gives assurance that definite results shall follow its use. In the absence of these conditions it is manifestly unwise and even unexcusable to employ any medicament in this manner, and its repeated use is reprehensible.

“Intravenous injection of Methyl-phenol Serum alternating with intravenous injections of mercury should be given every 48 hours until infection is under control.”

This quotation further emphasizes that the treatment, as advised, carries with it a certain element of danger.

“Methylene blue prevents the phenol from exerting its usual action upon the red blood corpuscles, and ensures rapid elimination through healthy kidneys. It preserves the antiseptic power of the phenol and prevents the phenol from interfering with the chemico-biological function of the white and red blood cells. The serum component favors chemotaxis, it strengthens bodily defense, it prevents anaphylaxis even in debilitated patients, and it replaces the resistance which has been impaired by the demands that have already been made upon it.”

No evidence is submitted to substantiate these claims. It seems strange that phenol should lose its power and that this should be restored by the methylene blue.

“It has a refractory chemico-biological action, and exercises no vicious effect on the red blood corpuscles in the circulation, but, on the contrary, by its inoffensive presence, it wholly preserves all of the physiological properties of the blood.”

What “a refractory chemico-biologic action” is, is not clear, but there is no evidence that this preparation has any action which might be defined as “refractory chemico-biological,” that its presence is inoffensive or that it wholly preserves all the physiologic properties of the blood.

“The treatment of gonorrhea by Cano’s theory ... is firmly based upon chemico-biological facts and accepted authoritative theories and bears the same relation to gonorrhea that intravenous injections of arsenicals bear to syphilis.”

Quite an exaggerated and unwarranted statement. In the same way, objection is taken to the following quotations:

“Phenol administered intravenously in combination with methylene blue, to protect the red-blood globule, undergoes no change, and preserves all of its actual antiseptic effect on the gonococcus and its toxins as though employed in the test tube.”

“When thus introduced into the human body its elimination is unique, effective, antiseptic, germicidal, being completely and exclusively thrown off through the kidneys in a period varying from one-half to twelve hours without local injury or disturbance to the general economy.”

“Combinations of phenol are unstable, but they do have the advantage of mitigating direct action on the cells and globules. It is also known that ordinary phenol has a coagulant action on the albumins and an oxidizing power on the tissues, which power, if permanent, produces gangrene. By virtue of this dual action it therefore acts as a modifier; by its oxidizing power on the germ it is germicidal, and prevents the growth of the gonococcus; and by its coagulant power on the toxins it relieves paragonococcal lesions (mono- and poly-arthritides) and affections of the serous organs (endo- and pericarditis, meningitis), and some definite systemic disturbances, the pathology of which is often confused with that of other infections.”

“Lymphocytosis is often persistent in some individuals in whom the internal secretions and the processes of assimilation and disassimilation are deficient; and because of the lack of these the organic physiological ferments are insufficient for the mechanism of nutrition and the phenomena of hematopoiesis.”

Until proof is available showing that phenol, administered intravenously in the quantities employed in Cano’s Normal Phenol Serum and Cano’s Methyl-Phenol Serum, acts as a germicide and methylthionine chloride (“methylene blue”) prevents the deleterious effects of phenol on the red blood corpuscles; that repeated intravenous injections of phenol and mercury are without danger; that there is no danger of anaphylaxis; that the physiologic properties of the blood are preserved by these medicaments; and, finally, that these preparations have an effect on gonorrhea and its complications, these substances Normal Phenol Serum (Cano) and Methyl-Phenol (Cano), are inadmissible to New and Nonofficial Remedies.

The following quotations taken from the circular are admissions that these preparations are not innocuous:

“That the economy will tolerate to a surprising degree substances directly introduced through the blood stream is now well known. By the intravenous injection of 10 c.c. of methyl-phenol serum we throw into the human body a massive dose of an alien substance. The immediate effect of this injection is upon the central nervous system. The recipient usually becomes either pale or suffused, he has a ringing in his ears, has a sensation of great altitude, and occasionally has a dryness of the fauces and a metallic or a garlic taste.”

“In some patients secondary reactions occur in from one to four hours after injection. The phenomena we have observed in these secondary reactions are pronounced chill and rigor ...”

There is no doubt that considerable harm may be done by the intravenous and by the intraprostatic administration of these preparations and until there is good evidence showing the therapeutic value of the treatment, the routine use of these preparations, except perhaps at hospitals in selected and well controlled and carefully guarded cases, is to be strongly discouraged.

When the foregoing statement was sent to the Mulford Company for comment, the firm submitted a letter from Dr. Perry Townsend to the Mulford Company in which he declared that the results obtained with the Cano preparations had been satisfactory and without untoward results. In this letter, Dr. Townsend proposed that a series of injections with these preparations be carried out under the observation of members of the Council and the supervision of Dr. Cano or himself.

The report of the Council, the letter from the Mulford Company and that of Dr. Townsend were sent to a number of urologists for their opinion concerning this whole matter. It was explained that the referee held that no reason had been presented which would warrant the Council to depart from its customary procedure, namely, to require that clinical evidence be submitted in the form of published reports which permit investigation and verification by independent observers but that, before making further recommendation to the Council, he desired the opinion of urologists of recognized standing concerning the report submitted to the Mulford Company. All replies received approved the Council’s position.

The following is one of the replies received:

Your letter in regard to Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) received. I wish to state that I have read the correspondence between the Council and H. K. Mulford Co. and in my opinion the referee and the Council are quite correct in their attitude in the matter. In my opinion I would emphasize the following:

(1) There is absolutely nothing about the remedies directed specifically against the gonococcus and no evidence to show that any action against them is obtained. As we know there are certain states of normal serum which are highly toxic and any normal serum from another animal will produce disturbances in man when injected intravenously--particularly if repeated. The addition of substances to serum normal or otherwise is apt to and frequently does render that serum highly toxic! The substances added in the instances referred to--phenol and methylene blue are not in any way calculated to lessen the toxicity of serum. The element of danger existing in the indiscriminate use of serums intravenously is, in my opinion, increased by the addition of the substances mentioned, and it would be unwise to encourage the general use of any such remedies. Furthermore the products are condemned by the very evidence of the originators and their admissions are quite sufficient to deter anyone from using the products as they suggest.

As to the intraprostatic injections with the serums it does not at all meet my views; although the introduction of serums by this route have been frequently advocated and I have personally carried this mode out I cannot allow the impression to go out that it could be done in a routine manner--nor that no ill results could follow--for I have seen otherwise. Furthermore from theoretical standpoint serums need not be given in this way.

In consideration of the opinion expressed by the Council’s consultants the referee recommended that Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) be declared ineligible for New and Nonofficial Remedies because of conflict with Rule 6 (unwarranted therapeutic claims) without considering possible conflicts with other rules, and that publication of the report be authorized.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 85.)

SOAMIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Soamin is the name under which the firm of Burroughs Wellcome and Company sells its brand of sodium arsanilate. The Council directed the omission of Soamin from New and Nonofficial Remedies and authorized publication of the report which appears below after the proprietors of the product had declined to withdraw or suitably revise the unwarranted therapeutic claims which it made.

W. A. Puckner, Secretary.

The proprietary brand “Soamin” of sodium arsanilate was admitted to New and Nonofficial Remedies several years ago at a time when the therapeutic value of arsanilic acid had not been definitely determined. Experience with this drug has shown that it is far more dangerous and also has a more limited field of usefulness than was at first recognized. The proprietors of the Soamin brand have continued to include in the list of conditions in which it “would seem” to be a “very effective agent” cerebrospinal meningitis and pellagra; in fact, meningitis is the first in the list of conditions mentioned, syphilis the second and pellagra third. In support of their belief in the efficacy of the remedy in meningitis, three reports, published from six to nine years ago, are quoted. In one of these it is stated that two patients “were cured”; in another report, seven of eight patients in whom the clinical, but not the microscopic, diagnosis of meningitis had been made were reported as having recovered; in the third report, fifty-six of ninety cases were reported cured; in this larger series of cases the author neglects to state the method of administration. The firm quotes but one paper (which is a very uncritical report) in regard to pellagra.

It seems to the Council that the evidence of value of sodium arsanilate in these conditions (which are now treated by more rational methods) is too slight to justify the emphasis laid on it by the firm, especially as sodium arsanilate is admittedly a dangerous agent, several cases of blindness having been reported from its use.

For these reasons it was voted to omit Soamin from New and Nonofficial Remedies.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 89.)

SOME MIXED VACCINES NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

The consideration of the following “mixed” vaccines was requested by F. I. Lackenbach, San Francisco:

Special Bacterial Vaccine No. 2 (Staph-Strep. Bacterin) containing killed Staphylococcus albus, Staphylococcus aureus and streptococcus.

Special Bacterial Vaccine No. 3 (Pneumo-Staph-Strep. Bacterin) containing killed Staphylococcus albus, Staphylococcus aureus, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 4 (Pneumo-Staph-Strep-Coli Bacterin) containing killed Staphylococcus albus, Staphylococcus aureus, Staphylococcus citreus, Bacillus coli, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 5 (Influenza Combined Bacterin) containing killed Staphylococcus albus, Staphylococcus aureus, Bacillus Friedländer, Bacillus influenzae, Micrococcus catarrhalis, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 11 (Pneumo-Strep. Bacterin) containing killed streptococcus and pneumococcus.

Special Bacterial Vaccine No. 15 (Combined Whooping Cough Bacterin) containing killed Bacillus pertussis, Staphylococcus albus, Staphylococcus aureus, Micrococcus catarrhalis, Bacillus influenzae, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 16 (Mixed Gonococcus Bacterin) containing killed gonococcus, Staphylococcus albus, Staphylococcus aureus, Bacillus coli, diphtheroid bacillus, streptococcus and pneumococcus.

Mr. Lackenbach states that these bacterial mixtures were prepared for him by E. R. Squibb & Sons. Their sale in interstate commerce is permitted under the license granted to the latter firm by the U. S. Treasury Department. However, no evidence of any kind was presented to the Council proving the therapeutic efficacy of the several mixed vaccines. As a mixture of two or more kinds of organisms is accepted for New and Nonofficial Remedies only if there is satisfactory evidence that its therapeutic use is rational, the Council declared the several vaccine mixtures ineligible for New and Nonofficial Remedies (Rule 10).--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 90.)

SOMNOFORM

Report of the Council on Pharmacy and Chemistry

The Council examined the available evidence for Somnoform, sold by Stratford-Cookson Company, successors to E. de Trey and Sons, and found the preparation inadmissible to New and Nonofficial Remedies. The Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Somnoform is sold in the United States by Stratford-Cookson Company, successors to E. de Trey and Sons. According to the label on a package of Somnoform sent the Council.

“This mixture contains Chloride of Ethyl, 83 per cent.; Chloride of Methyl, 16 per cent.; Bromide of Ethyl, 1 per cent.”

Although Somnoform has been on the market for a long time, the published reports present no proof that it is superior to ethyl chlorid used alone. Moreover, the published reports and statistics do not necessarily apply to the Somnoform now sold for the reason that mixtures of varying composition have been sold as Somnoform in the past. Thus, when Somnoform was considered by the Council in 1909, it was claimed to be composed of chloride of ethyl, 60 per cent.; chloride of methyl, 35 per cent., and bromide of ethyl, 5 per cent. Federal chemists found, however, that it contained no bromide of ethyl (Notice of Judgment No. 571). It is a question, therefore, whether a given report applies to a mixture containing 5 per cent. bromide of ethyl, 1 per cent. of this substance, or none at all.

The present advertising booklet for Somnoform does not present acceptable evidence of the therapeutic value of the preparation. An ignorance concerning the elementary facts of physiology and pharmacology is evident in the second sentence: when having stated that “Somnoform is the result of several years of study and investigation by Dr. George Rolland, Dean of the Bordeau Dental School,” the pamphlet continues: “He sought an anesthetic which would enter, dwell in, and leave the body in the same manner that oxygen does....”

The claim as to the value of the 1 per cent. of ethyl bromide in the mixture is highly improbable; certainly no evidence in support of the claimed value of this constituent is available to the referee.

No evidence is submitted which proves the claim of superiority of Somnoform over similar preparations, asserted in the following:

“The peculiar manner in which the elements are combined is what makes Somnoform at once so efficient and so safe.”

The Council declared Somnoform inadmissible to New and Nonofficial Remedies because, in the absence of acceptable evidence showing its exceptional safety and value, the claims are unwarranted (Rule 6), and because the name of the mixture is not descriptive of its composition (Rule 8).--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 90.)

TABLETS FORMOTHALATES

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report which declares Tablets Formothalates (Tailby-Nason Company, Boston, Mass.) ineligible for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Tablets Formothalates are sold by Tailby-Nason Company, Boston, Mass. On the label a formula is given: “Constituents: Acetanilid 2 gr.; phenolphthalein 1/2 gr. In a balanced combination with Hexamene [a name sometimes applied to hexamethylenamin] and Oil of Cinnamon. Indications: Influenza, Colds, Grippe, Headache, Neuralgia, Rheumatism.” The same formula is given in advertisements and in this advertisement it is claimed that they are “For Influenza and Grip” and if “given in the acute stage may avert a serious attack” (_Boston M. & S. J._, Oct. 3, 1918). The dose is given as one to two tablets at 6 p. m. and repeat at bedtimes.

The A. M. A. Chemical Laboratory reported that the tablets weigh an average of 0.4882 Gm., or 7-1/2 grains; that they have the odor and taste of cinnamon; and that they contain hexamethylenamin, are neutral and therefore give up no formaldehyde in the presence of water alone. The Laboratory further reported that they contain phenolphthalein and acetanilid. These tablets were directed to be taken internally and therefore their effect was not intended to be local.

The amount of hexamethylenamin was not determined, but in any case could not exceed 5 grains per tablet. It is evident that 4 grains of acetanilid and 10 grains of hexamethylenamin and 1 grain of phenolphthalein (in two tablets) “if given in the acute stage” of influenza would not “avert a serious attack,” as claimed in the advertisements.

The Council declared Tablets Formothalates inadmissible to New and Nonofficial Remedies.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 92.)

TRIPLE ARSENATES WITH NUCLEIN

Report of the Council on Pharmacy and Chemistry

The Council has declared Triple Arsenates with Nuclein No. 1 and Triple Arsenates with Nuclein No. 2, tablets marketed by the Abbott Laboratories, inadmissible to New and Nonofficial Remedies because unwarranted therapeutic claims (Rule 6) are made for them and because they present an illogical combination of drugs (Rule 10). The publication of the following report has been authorized by the Council.

W. A. Puckner, Secretary.

The following claims are made for Triple Arsenates with Nuclein:

“Puts ‘pep’ and strength back into that patient recovering from Spanish Influenza, pneumonia, typhoid, or surgical operation. An extremely powerful reconstructive tonic. Try it for that ‘run down’ feeling.”

Triple Arsenates with Nuclein is said to contain “Strychnin Arsenate gr. 1/128, Quinin Arsenate gr. 1/64, Iron Arsenate gr. 1/64, Nuclein Solution mins. 4.” A second preparation, of double strength--Triple Arsenates with Nuclein No. 2--is also advertised. The Council voted not to accept these preparations for New and Nonofficial Remedies on the following grounds:

The quantities of quinin, iron and nuclein in the doses represented in these mixtures are negligible; thus, one tablet of Triple Arsenates with Nuclein containing 1/64 grain of quinin arsenate contains only about 1/90 grain of anhydrous quinin; the tablet containing 1/64 grain of iron arsenate contains 1/210 grain of iron; 4 minims of the nuclein solution (assuming it to be the “Nuclein Solution-Abbott”) would contain but 2/5 of a grain of nuclein--a substance which even in large doses is of questionable therapeutic value. The amounts of iron and nuclein contained in doses of this preparation are insignificant in comparison with the amounts present in ordinary foods. The only substances present in even small therapeutic doses are strychnin and arsenic. The effects of arsenic and strychnin are very different and there are comparatively few conditions in which they should be prescribed at the same time. Hence a preparation containing these two in fixed proportions is illogical.--(From Reports of Council on Pharmacy and Chemistry, 1919, p. 92.)

“ANTI-PNEUMOCOCCIC OIL” AND THE USE OF CAMPHOR IN PNEUMONIA

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below. This report declares “Anti-Pneumococcic Oil” (a solution of camphor in oil sold by Eimer and Amend, New York) ineligible for New and Nonofficial Remedies because (1) the recommendations for its use in pneumonia are not warranted by the evidence, (2) the name is not descriptive of its composition but is therapeutically suggestive, and (3) the sale of a solution of camphor in oil under a name nondescriptive of its composition is unscientific and a hindrance to therapeutic progress.

W. A. Puckner, Secretary.

The Council having decided to consider Anti-Pneumococcic Oil (Eimer and Amend, New York), the preparation was assigned to the Committee on Therapeutics for report. The report that follows was made by a member of this committee:

According to the advertising, Anti-Pneumococcic Oil is a “twenty-five per cent. solution of camphor in a thin oil” which was “originated” by August Seibert, M.D. The following directions are given for its use:

“10 c.c. (150 minims) to every 100 pounds of body weight, to be injected hypodermically every eight to twelve hours in pneumococcic pneumonia, as soon after the initial chill as possible.”

It is claimed that the prescribed dose one hour before general anesthesia begins, “safeguards against postoperative pneumonia,” and, that “animals can so be immunized against later and otherwise fatal intravenous pneumococcic infection (Boehnke, Institute for Experimental Therapy, Frankfort).” The advice is given:

“In pneumococcic meningitis, endocarditis and pleuritis, 3% of salicylic acid should be added to this oil.”

In an article by Seibert, “Camphor and Pneumococci” (Medical Record, April 20, 1912), a reprint of which is used to advertise Anti-Pneumococcic Oil, previous work (München, med. Wchnschr., No. 36, 1909) is mentioned as the starting point for the use of camphor in pneumonia. In this article, the author reports his first case, that of a young woman who entered St. Francis’ Hospital on the third day after the initial chill “with the symptoms of severe toxemia (unconscious, temperature 105.5 F., pulse 130, and respiration 40) and involvement of both lower lobes.” “Large doses of camphor,” 12 c.c. of a 20 per cent. solution, were injected hypodermically “every twelve hours, resulting in gradual improvement and recovery by the fourth day, without a crisis.” Seibert reports success in its use in twenty-one cases, but gives no case histories or protocols. He admits, however, that in four out of sixteen cases, following the first twenty-one so reported certain “limitations of this treatment were observed,” and a “sudden rise of temperature in two patients on the second and third days of treatment, respectively, proved to be due to pneumococcic nephritis, promptly subdued by appropriate doses of urotropin, while the camphor injections were continued and resulting in speedy recovery.” He further admits that empyema occurs, and states: “This proves that the camphor brought into the blood cannot prevent the as yet living organisms, constantly entering the blood current from the affected alveoli, from colonizing in the renal and pleural tissue.”

He reports, among thirty-seven patients treated in this manner, one death, that of a man 68 years old, weighing 200 pounds, with a fatty heart. Heart failure was the real cause of death. Seibert also reports some very incomplete experimental work; Dr. Hensel, assistant and pathologist of the German Hospital, found that “1/10,000 part of camphor added to the usual culture media inhibited the growth of pneumococci, while the controls all thrived”; Dr. J. C. Welch, pathologist of the Lying-in Hospital, found that rabbits infected with lethal doses of pneumococcus cultures intravenously were saved by large doses of camphorated oil; fragmentary protocols are given. The assistant pathologist of St. Francis’ Hospital carried on the experimental work, adding salicylic acid to the camphor. No blood cultures are reported. The conclusion reached by Dr. Seibert is that salicylic acid up to 3 per cent., added to the camphorated oil, is effective in preventing pleural infection. In the article by Dr. Seibert, there appear most sketchy reports of cases, recovery being reported without crisis in from three to nine days.

The referee has made a careful search of the literature, with the following results: Boehnke (Berl. klin. Wchnschr. 50:818, 1913), using white mice, failed to confirm the experiments reported in Seibert’s paper, unless camphorated oil were given before the pneumococci, and even then, he felt that the results were too irregular to be of great significance. When given with anti-pneumococcic serum, however, he felt that there was some benefit to be seen by the administration of camphor; his protocols, however, are not detailed. There is no report of blood cultures, etc.

Another worker, H. Leo (Deutsch. med. Wchnschr. 39:690, 1913), reported that camphor water given intravenously prolonged the lives of thirty-eight rabbits inoculated with pneumococci. Here again there were no adequate protocols and very little evidence of careful experimental work appears.

In the literature of the past ten years, there appear sketchy clinical articles on the value of huge doses of camphor in pneumonia. Markevitch (Russk. Vrach, June 27, 1914; abstr., The Journal, Dec. 5, 1914, p. 2081) treated 226 cases of pneumonia with 5 c.c. of camphorated oil hypodermically four times daily, at the same time giving digitalis (amount not stated), with a mortality of 6.6 per cent., whereas, in 322 cases untreated, there was a mortality of 13.3 per cent. He reports 133 grave cases; sixty-six received no camphor; 48 per cent. died. Of sixty-seven treated with camphor, only 22 per cent. died. He reports temperature falling by lysis when camphor is used, and comments on the symptomatic improvement following its use. With the great variation in the clinical course of pneumonia, the above figures, though suggestive, certainly need further support before the routine use of camphor as recommended by Seibert can be sanctioned.

Later articles found on the subject refer to it in a very cursory way, giving no protocols and no cases, and giving the referee the feeling that the conclusions were very impressionistic.

RÉSUMÉ

After a careful search of the literature, the referee concludes that: Huge doses of camphor, to 250 grains in twenty-four hours, may be given to man without serious results. No satisfactory evidence, however, appears that camphor has a specific germicidal action on pneumococci (similar to that of ethylhydrocuprein). The clinical evidence, as found in the literature, is certainly of very little value. It appears that the sale of a simple solution of camphor in oil under the guise of “Anti-Pneumococcic Oil” is to be deplored (a 20 per cent. solution of camphor in cottonseed oil is official in the U. S. Pharmacopeia as camphor liniment). It is recommended that the preparation be held inadmissible to New and Nonofficial Remedies because exaggerated therapeutic claims are advanced for it, and because the name is not descriptive of the composition, but is, instead, therapeutically suggestive.--(From The Journal A. M. A., Jan. 3, 1920.)

DIAL “CIBA”

Report of the Council on Pharmacy and Chemistry

Dial “Ciba” has not been accepted for “New and Nonofficial Remedies” because, as the report which follows shows, unwarranted claims are made for the product. It is a definite new chemical compound which might be made eligible for N. N. R. if misleading therapeutic claims were eliminated. The Council directed that Dial “Ciba” be included with Articles Described but Not Accepted, so that physicians might be informed with regard to its character and properties.

W. A. Puckner, Secretary.

Dial “Ciba” is a hypnotic manufactured by the Society of Chemical Industry of Basle, Switzerland, and is sold in the United States by A. Klipstein and Company, Inc., New York. Chemically, Dial “Ciba” is diallylbarbituric acid and is, therefore, closely related to diethylbarbituric acid or barbital (“veronal”).

The claims made for Dial “Ciba” are (1), that the “allyl” group in its molecule makes it more readily decomposed by oxidizing agents than barbital, which contains the “ethyl” group; (2) that because of this ease of oxidation, it is more readily decomposed in the body and more rapidly and completely eliminated, and (3) that because of its alleged rapid elimination, it is devoid of the after effects of barbital and other hypnotics.

The Council took up the substance in February, 1918, and referred the matter to the referee in charge of barbital preparations. The referee considered unwarranted the claim that Dial “Ciba” did not have the after-effects of other hypnotics due to its alleged total decomposition in the body. The American agents, A. Klipstein and Company, were informed of the referee’s objections. Their attention was also called to the fact that, notwithstanding the claimed absence of after-effects in one part of the advertising, other parts of the same advertising admitted certain post-hypnotic effects of the product. It was pointed out also that while it was claimed in one of the advertising circulars that lowering of the blood pressure is never observed after administration of Dial “Ciba,” yet two of the authors quoted in the same circular definitely stated that a lowering of the blood pressure followed even small doses of the drug and these authors warn against this very danger in certain conditions.

A year later, a circular letter sent out by A. Klipstein and Company reiterated the claim that the asserted decomposition of Dial “Ciba” in the body prevents after-effects, the drug being still contrasted with barbital (“veronal”). In view of the reiteration of this highly improbable claim, the referee undertook to study the comparative action of Dial “Ciba” as compared with other hypnotics. It was found that the actions of Dial “Ciba” are not distinguishable, qualitatively, from those of barbital, there being no perceptible difference in the after-effects or in the nature of the side actions. In toxic doses, both caused profound depression with the temperature falling to that of the room (or about one degree above), the respiration being extraordinarily slow and shallow as one would expect with lowering of the temperature. There were also the same evidences of nausea that are so frequently seen after toxic doses of the various hypnotics of this group. In view of these results, the Council declared that it is unwarranted to claim freedom from after-effects for Dial “Ciba.”

The Council held that the following statement is unwarranted:

“The therapeutic field for Dial ‘Ciba,’ as shown by tests on rabbits, is just as broad as the field for Diethylbarbituric Acid.”

Tests on rabbits do not and cannot show the breadth of the therapeutic field for a hypnotic. The Council also declared the following statement improbable, and contrary to the evidence obtained by the referee:

“In dogs, the increase of dosage beyond the therapeutic dose to the point of death is decidedly in favor of Dial ‘Ciba,’ which required a larger dose [than diethylbarbituric acid] to produce death.”

The referee’s experiments on cats show that Dial “Ciba” is several times as toxic as hydrated chloral, and more than twice as toxic as diethylbarbituric acid (barbital).

Since the circular to which objection was made in 1918 was still being sent out in December, 1919, the Council held Dial “Ciba” inadmissible to N. N. R. and voted that report of its action in the matter be authorized for publication. The Council further directed that Dial “Ciba” be included with Articles Described but Not Accepted.--(From The Journal A. M. A., Jan. 24, 1920.)

APOTHESINE

Report of the Council on Pharmacy and Chemistry

Apothesine is a synthetic drug for producing local anesthesia, made by Parke, Davis & Company. In the fall of 1917 the Council wrote to Parke, Davis & Company offering its aid in establishing the identity, purity and therapeutic efficiency of this synthetic local anesthetic with the ultimate object of accepting the product for inclusion in New and Nonofficial Remedies should the facts warrant such acceptance. The Council’s letter was never acknowledged. After Apothesine was put on the market the Council desired to accept it for inclusion in New and Nonofficial Remedies but, unfortunately, was unable to do so because some of the claims made for the product were not justified by acceptable evidence. The manufacturers were notified of the Council’s desire to admit this product to N. N. R. and the wish was expressed that the company would either so modify its claims as to make the product acceptable under the Council’s rules or else would submit evidence to the Council in proof of the claims made and thus permit the Council to revise its conclusions. Parke, Davis & Company were, apparently, either unwilling or unable to submit evidence that would sustain their claims; neither did they offer to modify the claims themselves. The product, therefore, is ineligible to inclusion in New and Nonofficial Remedies; it will, however, be listed in the “Described But Not Accepted” department of New and Nonofficial Remedies. The report on Apothesine that follows has been authorized for publication.

W. A. Puckner, Secretary.

Apothesine, “the hydrochlorid of diethyl-amino-propyl-cinnamate,” is an efficient local anesthetic. It belongs to the procain rather than to the cocain type, that is, it belongs to that type which, while effective for injection anesthesia (especially when combined with epinephrin) is relatively inefficient when applied to mucous membranes. Apothesine may also be used for spinal anesthesia. Its absolute toxicity is less than that of cocain (as 20 is to 15, see table below) but about twice that of procain (as 20 is to 40, see table below). It is non-irritant, is easily soluble and makes a stable solution so that it may readily be sterilized.

The Council took exception to certain claims made by Parke, Davis & Company for their product on the ground that these claims were not supported by acceptable scientific evidence. One of the claims was that Apothesine is applicable in any case in which any other local anesthetic is used. This statement, made in many advertisements, is distinctly misleading as used. When applied to mucous membranes Apothesine is far inferior to cocain and to some other local anesthetics, yet the claim obviously suggests that Apothesine is an efficient substitute for any local anesthetic.

The manufacturers claimed, too, that Apothesine is as potent as cocain. The claim would lead the physician to think that Apothesine had the same anesthetic potency as cocain in solution of equal strength. This statement, so far as it refers to the drug when applied to mucous membranes, is not in accord with the facts and is true for injection anesthesia only when stronger solutions are used. The only support for the claim of equal efficiency appears to be the experiments with intracutaneous injections made by H. C. Hamilton[130] in Parke, Davis & Company’s laboratory. These differed considerably from the results of Sollmann.[131] A further series of experiments were made by Sollmann to compare still further the diverse results previously reported by him and Hamilton. The latest series, while showing considerable variations in the susceptibility of different skin areas, especially toward Apothesine, demonstrated in every case that the efficiency of Apothesine is unmistakably lower than that of cocain, being at best one half. The series also showed that the potency of Apothesine was never greater than procain and averaged considerably below it.

[130] The Comparative Values of Some Local Anesthetics by H. C. Hamilton, Detroit, Mich., from the Research Laboratory of Parke, Davis & Co., J. Lab. & Clin. M. =4=:60 (Nov.) 1918.

[131] Comparative Efficiency of Local Anesthetics, V, by T. Sollmann, from the Pharmacological Laboratory of the School of Medicine, Western Reserve University, J. Pharmacol. & Exper. Therap. =11=:69 (Feb.) 1918.

Another claim made for Apothesine which the Council holds is not supported by evidence is that of superior safety. This claim is made on the basis of hypodermic injections in guinea-pigs carried out in the laboratory of Parke, Davis & Company. Such experiments prove little because of the fact--well known to laboratory workers--that the use of rodents in toxicity tests made by injecting a drug into the subcutaneous tissues does not give a reliable index of the relative toxicity of such a drug for man. This is due partly to the peculiar resistance of rodents to poisons and partly to the great importance of the rate of absorption. The organism destroys most local anesthetics so rapidly that the rate of absorption is more important than the absolute dose. The absorption from hypodermic injections into guinea-pigs differs, of course, from that in clinical accidents, especially where the drug has been applied to mucous membranes. One cannot, therefore, reliably estimate the degree of clinical danger on animals.

It has been shown that when toxicity tests of local anesthetics are made on cats these animals seem to respond to the drugs in a manner more closely approximating humans and it is a suggestive fact that the more toxic of local anesthetics, as shown by tests on cats, have been found the most dangerous in clinical use. The absolute toxicity of Apothesine has been measured by Eggleston and Hatcher[132] by the intravenous injection in cats. The fatal doses, in terms of milligrams per kilogram ranged as follows:

Alypin, Holocain 10 Beta Eucain 12.5 Cocain 15 Apothesine 20 Tropacocain 20-25 Stovain 25-30 Nirvanin 30-35 Procain 40-45

[132] A Further Contribution to the Pharmacology of the Local Anesthetics by Eggleston and Hatcher, from the Department of Pharmacology, Cornell University Medical College, New York City, J. Pharmacol. & Exper. Therap. =13=:433 (Aug.) 1919.

The absolute toxicity of Apothesine is, therefore, only a little lower than that of cocain, and is twice as great as that of procain. The clinical dangers cannot be predicted by either method, since clinical accidents depend, in most instances, on idiosyncrasies, or the technic of application.--(From The Journal A. M. A., Jan. 24, 1920.)

EUMICTINE

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below. This report declares “Eumictine” ineligible for New and Nonofficial Remedies because (1) it conflicts with Rule 10 in that it is unscientific, (2) it conflicts with Rule 6 in that it is sold under unwarranted therapeutic claims, (3) it conflicts with Rule 4 against indirect advertising to the public in that the name “Eumictine” is blown in the bottle for the obvious purpose of bringing the product to the attention of the public when it is prescribed in the original package, and (4) because the name is therapeutically suggestive and not in any way descriptive of its composition.

W. A. Puckner, Secretary.

Eumictine is a preparation from the laboratory of Maurice Le Prince, Paris, France, and is marketed in this country by George J. Wallau, Inc., New York. It is claimed that the product is “a balsamo-antiseptic preparation composed of Santalol, Salol, and Hexamethylene-Tetramine, in the form of gluten-coated capsules.” Nowhere in the advertising are the amounts of the ingredients given. According to the American agent, however, “each capsule is supposed to contain 20 centigrams of Santalol, 5 centigrams of Salol, 5 centigrams of Hexamethylene-Tetramine.”

Eumictine is advised “in treating genito-urinary diseases (urethritis, cystitis, prostatitis, pyelitis, etc.).” It is claimed to be “both an antiphlogistic modifying agent, a well-tolerated diuretic” which “may be administered for long periods without ill effects.”

The Council declares Eumictine ineligible for New and Nonofficial Remedies because it is exploited in conflict with the following rules:

It is unscientific (Rule 10). Eumictine is composed of hexamethylenamin, salol and sanalol in fixed proportions. Hexamethylenamin may serve a useful purpose in some forms of infection of the urinary tract, but neither it nor salol is of any considerable value in gonorrhea. It is now known that the balsamic preparations, formerly so widely used, do not have the curative effects in gonorrhea and associated conditions that used to be ascribed to them. To combine three substances, none of which has any distinct therapeutic value in the conditions for which Eumictine is proposed, does not enhance their value. There is nothing original in the combination used in Eumictine, or in the manner of dispensing it.

It is sold under unwarranted therapeutic claims (Rule 6). These claims are made not only for the components of Eumictine but for the combination itself. Though santalol has certain advantages over the somewhat variable oil of santal and other balsamic resins, it is not true that santalol “does not cause congestion of the renal epithelium” or that it does not “produce exanthema as do copaiba, cubebs, and the ordinary santal oil.” It is not true that salol is “devoid of toxicity.” Neither is it correct to say that salol “asepticizes and disinfects the bladder, the prostate and the urethra.” The claim that hexamethylenamin “is of value when any acute symptoms or tendency to inflammation subsist” is not justified. The claim that hexamethylenamin “renders soluble the uric acid and urates” is also without foundation. The following paragraph is characteristic of the claims made for Eumictine:

“Anti-gonorrhoic by its Santalol, diuretic, urolytic and analgetic by its hexamethylenetetramin (Urotropin) antiseptic and antipyretic by its Salol, Eumictine represents a real therapeutic advance in the scientific treatment of diseases of the urinary passages.”

Instead of being “a real therapeutic advance” in the treatment of diseases of the urinary passages, Eumictine presents one of the complex combinations that have long retarded the scientific treatment of these diseases. Eumictine also conflicts with Rules 4 and 8 of the Council.--(From The Journal A. M. A. Feb. 21, 1920.)

PLATT’S CHLORIDES

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on “Platt’s Chlorides.” It also declares the preparation inadmissible to New and Nonofficial Remedies because its composition is uncertain and indefinite and because the claims made for it are exaggerated and misleading.

W. A. Puckner, Secretary

“Platt’s Chlorides,” marketed by Henry B. Platt, New York, is sold as a disinfectant and germicide. Only incomplete and contradictory statements have been made in regard to its composition. Many years ago (about 1899) the composition of Platt’s Chlorides was given as “The Chlorids of Zn 40 per cent., Pb 20, Ca 15, Al 15, Mg 5, K 5.” The statement that the preparation contained 20 per cent. of lead chlorid is interesting, in view of the fact that lead chlorid is soluble in water at ordinary temperatures to the extent of less than 1 per cent. In a booklet, also issued a number of years ago, the following “Formula of Platt’s Chlorides” was given:

“A saturated solution of Metallic Chlorids combined in the following proportions:

“Sol. Zinc Chlorid 40 per cent. “Sol. Aluminum Chlorid 15 per cent. “Sol. Lead Chlorid 20 per cent. “Sol. Calcium Chlorid 15 per cent. “Sol. Magnesium Chlorid 5 per cent. “Sol. Potassium Chlorid 5 per cent.”

The label on a bottle purchased in 1911, describes Platt’s Chlorides as:

“A Highly Concentrated Solution of the Chlorids of Aluminum, Calcium, Lead, Zinc, etc.”

The label of a bottle purchased in 1919 reads:

“Contains Inert Material: Water 84.0%. Sodium Chlorid 4.8%. Calcium Chlorid 0.3%.”

This statement is obviously made to meet the requirements of the federal Insecticide Act. This law requires either that the identity and the amounts of potent ingredients in disinfecting preparations be declared or else that the percentage of the inert ingredients of such preparations be given. The omission from the label of all statements with regard to the potent ingredients of the preparation and the absence of such a statement in recent advertising matter suggests either that the older statements about its composition were false or else that the composition has been changed.

Tscheppe published (Pharmaceutische Rundschau =8=:109, 1890) an analysis of Platt’s Chlorides which has been quoted in other publications as indicating the composition of the preparation. He reported that he found each quart of the preparation to contain aluminum sulphate 6 ounces, zinc chlorid 1-1/3 ounces, sodium chlorid 2 ounces, calcium chlorid 3 ounces.

Some years ago (about 1911) the company made the following statement relative to the germicidal power (phenol co-efficient) of Platt’s Chlorides:

“... for some time the carbolic acid co-efficiency of our output has been from 2.5 to 4.3, the average being about 3; namely about three times stronger than pure carbolic acid.”

In 1912, the U. S. Public Health and Marine Hospital Service reported (Bulletin 82, Public Health and Marine Hospital Service, p. 69) that the phenol coefficient of a sample of Platt’s Chlorides was so low that it could not be determined and also that the sample was found to contain some mercuric chlorid. In 1913, the North Dakota Agricultural Experiment Station reported (Bulletin, July, 1913, p. 292), that Platt’s Chlorides contained principally zinc chlorid, also some aluminum chlorid, calcium chlorid, and traces of mercuric chlorid. The phenol coefficient, determined by the Hygienic Laboratory method, was found to be 0.05.

The preceding suggests that the composition of Platt’s Chlorides had been changed (without notice to the consumer) and that it had been fortified by the addition of mercuric chlorid. Years ago part of the advertising of this product was a testimonial from a health official which declared that, for disinfection, “bichlorid of mercury is useless in disinfecting sputum or discharges from the bowels, being rendered inert by the albumin present” and it lauded Platt’s Chlorides as devoid of such drawbacks.

RECENT ANALYSES OF PLATT’S CHLORIDES

To determine the present composition of Platt’s Chlorides and to compare it with that sold formerly, the A. M. A. Chemical Laboratory has made an analysis of a specimen purchased in 1919 and also of one purchased in 1911 and since kept unopened in the files of the Council on Pharmacy and Chemistry. The following table contains the results of these analyses (all quantities given are Gm. per 100 c.c.):

1911 SPECIMEN 1919 SPECIMEN

Color Colorless Straw Color Odor None None Specific Gravity at 25 Cc. 1.1229 1.1313 Total Solids (residue at 100 Cc.) 16.49 18.33 Chlorid (Cl-) 7.60 10.74 Sulphate (SO₄--) 1.11 .16 Aluminum (Al+++) .22 .90 Calcium (Ca++) .19 .13 Zinc (Zn++) 5.11 3.93 Lead (Pb++) .046 Traces Mercury (Hg++) .. .0086 Sodium (Na+) 1.01 1.39

These quantities transposed to hypothetical combinations would indicate that Platt’s Chlorides has the following composition:

1911 Specimen 1919 Specimen

Aluminum Sulphate 1.32 .18 Aluminum Chlorid .07 4.29 Calcium Chlorid .54 .37 Zinc Chlorid 10.66 8.19 Lead Chlorid .06 Traces Mercury Chlorid .. .0116 Sodium Chlorid 2.57 4.81 Hydrogen Chlorid .43 None

In the past, the advertising has suggested, more or less directly, that, as chlorinated lime (bleaching powder) may be made to give off chlorin gas which disinfects, so the air in a room may be disinfected by evaporating Platt’s Chlorides. Thus the label of the 1911 specimen contains the following:

“FOR STORE ROOMS, Refrigerators, and Closets, keep a sponge saturated with the pure liquid in a saucer on an upper shelf.”

On the label of the 1919 specimen, the statement reads:

“REFRIGERATORS AND STOREROOMS--As a disinfectant wash regularly with one part Chlorides to eight of water. As a deodorant, keep in an open vessel a sponge or cloth saturated with the Chlorides full strength.”

That the owner of Platt’s Chlorides really believes that the vapors of the preparation have disinfecting properties is seen from a letter over the name of Henry B. Platt printed in the New York Tribune in 1916. This read, in part:

“... by keeping in a dish or saucer on radiators Platt’s Chlorides diluted one-half, the hot solution will evaporate and purify the air, thus destroying the grip germ which is the cause of all the trouble.”

From the analysis of Platt’s Chlorides, it is evident that when the preparation is evaporated, water vapor only escapes.[133] Whatever disinfecting or germicidal action the preparation may possess is exercised only when the solution is brought in direct contact with the substance to be disinfected.

[133] It is well known that when a solution of mercuric chlorid in water is evaporated, mercuric chlorid passes off with the water vapors, but under any condition the amount is but a fraction of the whole. As in Platt’s Chlorides other metallic chlorids are present, the formation of complex mercuric compounds which is bound to have occurred, should retard or prevent the volatilization of mercuric chlorid. That this actually occurs was confirmed by the following experiment: When 1 gm. mercuric chlorid was dissolved in 1 liter of water and the solution distilled, the distillate contained a very small amount of mercury. Then the experiment was repeated after adding sodium chlorid to the solution to simulate the conditions in Platt’s Chlorides. In this case no mercury was found in the distillate. Even were all the mercury in a bottle of Platt’s Chlorides volatilized in a room 10 by 12 by 9 feet, this would be equivalent to only about 1/500 grain mercuric chlorid per cubic foot.

The aluminum and zinc salts present may be useful as deodorants but they are not effective as germicides. The presence of mercuric chlorid in a concentration of 1 to 10,000 is hardly to be considered as materially increasing the efficiency. The directions recommend the use of a mixture of 1 part of Platt’s Chlorides to 10 parts of water for rinsing the hands, and a mixture of 1 part to 4 parts of water for the disinfection of discharges. It is further stated that 1 quart makes 2 gallons sufficiently strong for general use. It is evident that such dilutions decrease considerably the feeble germicidal action of the original fluid.--(From The Journal A. M. A., March 27, 1920.)

ANTI-TUBERCULOUS LYMPH COMPOUND (SWEENY) AND ANTI-SYPHILITIC COMPOUND (SWEENY)

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the reports which appear below, declaring Anti-Tuberculous Lymph Compound (Sweeny) and Anti-Syphilitic Compound (Sweeny) ineligible for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Anti-Tuberculous Lymph Compound (Sweeny)

“Anti-Tuberculous Lymph Compound (Sweeny)” is put out by the National Laboratories of Pittsburgh, Dr. Gilliford B. Sweeny, “Medical Director.” Sweeny has claimed at different times that he became interested in the subject of von Behring’s efforts to immunize cattle to tuberculosis at a time when he was an assistant in von Behring’s laboratory. He claims to have conceived the idea while there of transferring bovine immunity to tuberculosis to the human subject and later to have evolved his “treatment” at the Pasteur Institute in Paris.

Just how Anti-Tuberculous Lymph Compound is made today is not stated--at least so far as one is able to learn from recent advertising. Some years ago Sweeny declared that his “Anti-Tubercular Lymph” (as it was then called) was derived from a bullock which had been immunized to tuberculosis. Then:

“The immunized animal having been slaughtered, the contents of the lymph reservoirs are carefully collected and an aqueous extract is made from the grey cerebral substance, spinal cord and the lymph glands. It is then filtered under high pressure and de-albuminized by succussion. To this, the lymph, together with a definite proportion (50 per cent.), of the naturally phosphorized brain fats is added, with a small amount of chloride of gold (about 1-60 gr. to the dose), the latter as a preservative.”

It is a fair assumption that however the preparation may have been made originally, it is not now made in such a manner as to bring it under the federal laws governing the preparation of serums and similar preparations. The claims made for Anti-Tuberculous Lymph Compound are of the usual uncritical and unscientific type. Mainly, of course, they are of the testimonial class. The physician is told that the preparation has been carefully tested by men whose judgment is worthy of consideration; that the verdict has been altogether favorable to the “Compound.” Thus:

“... the remedy was submitted to a selected body of skilled physicians, recognized for their skill and care in making therapeutic observations. These men represented widely varying conditions, climatic and otherwise. Those who said ten years ago that Anti-Tuberculous Lymph Compound has a specific immunizing influence upon the tuberculosis patient, find the same to be true today.”

Careful reading of the matter just quoted will reveal its ambiguity and inherent lack of frankness. The inference conveyed is that the “selected body of skilled physicians” have unqualifiedly endorsed Anti-Tuberculous Lymph Compound (Sweeny)--but it does not say so!

It is the history of all such preparations, introduced to the medical profession with the usual blare of trumpets, that a certain number of favorable testimonials can be obtained. It is also the history of such products that one has but to wait a few years and the physicians who had written most enthusiastically regarding the preparation--in the first flush of their optimism following its use and the perusal of the manufacturers’ literature--will acknowledge that they were mistaken in their original estimate and are no longer using the agent. In this connection an investigation of some of the old testimonials for Anti-Tuberculous Lymph Compound by the Propaganda department of The Journal is instructive.

In a somewhat elaborate booklet published in 1907 by Sweeny, an Indiana physician was said to have reported favorable results following the administration of the “lymph.” A letter written to this physician in October, 1919, asking for his present opinion on the product brought this reply, in part:

“... it being twelve years since using the serum and no reference or repeated orders since should surely suffice as evidence of my lack of faith in the serum....”

An Illinois physician was reported in the same booklet to have described a case of a young man with an active tuberculosis, who was given injections of the “lymph” in February, 1907. The patient, it was claimed, showed immediate improvement and the Sweeny booklet (published in August, 1907) stated that “improvement in this case continued and terminated in complete recovery.” A letter written to the physician in October, 1919, brought out the fact that the young man in question, after receiving “Anti-Tuberculous Lymph Compound” and other treatment was removed “on a stretcher” “to New Mexico, where he remained for three or four years” and recovered. The doctor adds:

“I do not think that the Anti-Tuberculous Lymph had anything to do with the man’s recovery, although I realize the difficulty of definitely analyzing just what did effect the cure. I did since that time use that preparation in several other cases without beneficial results so that I gave it up a good many years ago adding it to that large heap of pharmaceutical material ‘weighed and found wanting.’”

A physician in Texas also reported in the 1907 booklet as having had very satisfactory results with the Anti-Tuberculous Lymph Compound in one case of pulmonary tuberculosis was written to in October, 1919. He replied:

“I will state that subsequent use of this compound did not bear out the apparent good results from its use in the first case or two.”

In a “Bulletin” issued by the Sweeny concern in 1912, a Pennsylvania physician was quoted as having treated three cases with Anti-Tuberculin Lymph Compound with resultant cures. This physician was written to in October, 1919, and he replied:

“I have no knowledge of the use of my name by any Pittsburgh concern and know nothing of a lymph of the name of Sweeny; neither do I recollect ever curing three cases of tuberculosis with any lymph.”

The same “Bulletin” quoted the alleged statement by a Delaware physician to the effect that he believed Anti-Tuberculous Lymph Compound to be the most successful treatment of tuberculosis extant. This in 1912. To an inquiry sent in October, 1919, this physician briefly replied:

“Am not using it now.”

The result of the Propaganda department’s questionnaire was what might have been expected. Every physician who answered the inquiry regarding his previous and present opinions of Anti-Tuberculous Lymph Compound (Sweeny) declared, in effect, that he had long since ceased to have faith in its value or efficacy.

According to claims made in Sweeny literature, “Anti-Tuberculous Lymph Compound exercises its immunizing power through a specific action upon the blood cells.” The statement that “it destroys the tuberculosis germ when this is present in the system of the patient” is untrue. The facts are, no serum or lymph has thus far been proved to have any value in the treatment of tuberculosis even when fortified by “a small proportion of chloride of gold and soda” as one circular tells us the “lymph” is. In spite of research by competent investigators, we are still without any aid in the form of a serum in the treatment of tuberculosis.

Anti-Tuberculous Lymph Compound (Sweeny) is one of those preparations that need no elaborate laboratory tests, nor even exact therapeutic research, to convince any clear-thinking person that it is patently and obviously worthless. One would hesitate before asking any reputable clinician to test a preparation of this sort. It is a constant source of surprise that some physicians allow themselves to be persuaded by advertising literature that is obviously uncritical and unscientific, to use preparations which have no more reasonable foundation than this one.

The Council declares Anti-Tuberculous Lymph Compound (Sweeny) not acceptable for New and Nonofficial Remedies.

Anti-Syphilitic Compound (Sweeny)

This preparation also is made by or under the direction of the same Dr. Gilliford B. Sweeny whose researches (?) led to the production and evolution of the Anti-Tuberculous Lymph Compound (Sweeny). According to the data at hand, this preparation is made by suspending benzoate of mercury in lymph from the bullock. Case reports are given of alleged cures of syphilis after two months of treatment; indeed, the circular exploiting the agent makes the statement that it is seldom necessary to continue the treatment beyond two months, which, if one chose to be credulous, would indicate extraordinary power for the mercury.

Mercury of course has a proper place in the treatment of syphilis, but that any physician could be induced to place his trust in this preparation is almost unthinkable though testimonials--which the “National Laboratories” claim to have received from physicians--are published. They all stamp the writers as not only gullible but also incompetent. The tenor of the claims is on a par with those made for the Anti-Tuberculous Lymph Compound; they do not justify the time required for detailed consideration.

The Council declares Anti-Syphilitic Lymph Compound (Sweeny) not acceptable for N. N. R.--(From The Journal A. M. A., April 3, 1920.)

SYRUP LEPTINOL (FORMERLY SYRUP BALSAMEA)

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on “Syrup Leptinol” (formerly “Syrup Balsamea”). The product is inadmissible to “New and Nonofficial Remedies,” first, because the manufacturers fail to give the profession information regarding either the amount of the potent ingredient or the method of determining its identity and uniformity; second, because of the unwarranted recommendation for its use in such infectious diseases as pneumonia and epidemic influenza and for lack of satisfactory supporting evidence of its alleged therapeutic efficacy in other diseases and, third, because the recommendations for its use appearing on and in the trade package constitute an indirect advertisement to the public.

W. A. Puckner, Secretary.

Syrup Leptinol is sold by the Balsamea Co. of San Francisco. It was first introduced as Syrup Balsamea. In recent advertising, Syrup Leptinol is also referred to simply as “Leptinol.”

According to the statements of the Balsamea Co., Syrup Leptinol is prepared from the root of a species of Leptotaenia (a plant belonging to the parsnip family) which grows in Nevada and which has heretofore not been used in medicine. The manufacturer states that the botanists who have been consulted have been unable to agree on the botanical classification of the plant. The dried root of this unclassified species of Leptotaenia is extracted with alcohol and from the extract so obtained the syrup is made, but no information has been furnished to show how the alcohol-soluble material is incorporated in the syrup. Further, the manufacturer has not announced tests whereby the identity and uniformity of the finished preparation may be determined.

A booklet contains the following:

“The species of Leptotaenia from which LEPTINOL is produced was first used in medicine by Dr. E. T. Krebs, who, after thorough laboratory investigation and clinical application over a period of several months, which resulted in the perfecting of LEPTINOL, prescribed the preparation for Influenza during the epidemic of that disease in 1918 with remarkably good results. Since this first use, LEPTINOL has been exhaustively tested by clinicians in private practice and in hospitals in the treatment of Pneumonia, Influenza Bronchitis, etc., and has been universally endorsed.”

In a circular letter it is asserted that the use of “Leptinol” during the “influenza epidemic” of 1918-1919 “demonstrated its almost specific action in respiratory affections”; that “during this epidemic it proved to be five times as efficacious as any other treatment in pneumonia ...”; and that “it is now as firmly fixed in the mind of many doctors for respiratory diseases as quinine is for malaria and the salicylates for rheumatism.”

In the booklet it is further stated that the therapeutic action of the preparation is primarily that of a “stimulating expectorant” and secondarily as a “sedative expectorant”; that “its antiseptic action in the respiratory tract is prompt”; that it “is an effectual cardiac tonic where the tone of the heart muscle is impaired by fever”; that “in acute pulmonary conditions it effectively improves the respiratory action and allays cerebral irritation due to fever and toxins”; that it acts “as a vital stimulant and nerve sedative”; that “it stimulates the excretion of acid by the skin and in fever it has a strongly diaphoretic and antipyretic action without depressing the circulation or the central nervous system”; that it is “mildly diuretic” and “slightly augments the biliary flow” and that “it increases the gastric and intestinal secretions and allays intestinal fermentation.”

No evidence has been presented to the Council which shows that Syrup Leptinol has the actions ascribed to it. The reports of clinical trial are little more than chance observations and lack all control. This applies also to the following, stated to be a quotation from the report of the Tonopah Mines Hospital Association:

“In the spring of 1919 a recurrence of the Influenza epidemic of the previous winter was experienced. During the first period of this second epidemic, prior to April 15th, there were treated one hundred sixteen cases of Influenza, fourteen of which developed Influenzal Pneumonia, with six deaths. The Pneumonia was of the very virulent type which prevails in this high altitude.... After April 15th, when the clinical use of Leptinol was inaugurated, three hundred and sixty-eight cases of Influenza were treated and not a single case developed Pneumonia. Twenty-two cases of Influenzal Pneumonia were received and treated with LEPTINOL, with a consequent one hundred per cent. recovery....

“In the cases where LEPTINOL was used the treatment was the same as had been previously followed, as to diet, fresh air, etc., but the medication was confined to LEPTINOL. Syrup LEPTINOL was started immediately in one-dram doses at one-hour intervals, in cases with high temperatures, and this was continued until temperature and pulse subsided. It was then used in one-dram doses at three-hour intervals as recovery progressed. On admission to the hospital, calomel in 1/4 grain doses, was given at fifteen minute intervals for eight doses. The last calomel was followed in six hours by 1/2 ounce Magnesium Sulphate in saturated solution. The second day 1/10 grain of calomel was given at one-hour intervals for ten doses....”

Medical journals are replete with reports of remarkable results obtained with the most varied forms of treatment instituted at the time that the “influenza epidemic” had been reached. In these cases it is more than probable that the lessened virulence of the causative factor of the disease, the gradually established resistance of those stricken with it in the latter period and the improved management resulting from experience deserve the credit for the successful outcome of the treatment, rather than the particular form of medication employed.

The report of the Tonopah Mines Hospital Association directly implies that Syrup Leptinol prevents the development of pneumonia in practically all cases of influenza in which it would develop and that it entirely abolishes the mortality of that disease. However, it is well known that innumerable remedies have been recommended as specifics in the treatment of pneumonia on the basis of the treatment of a limited number of cases which recovered, and that eventually these asserted specifics have been discarded as of little value. In the present instance, the recovery of twenty-two cases in succession afford prima facie evidence that those cases were not the virulent type of pneumonia in which the death rate is very high under any methods of treatment. While no effort appears to have been made to determine the nature of the infecting organism, the records show fairly conclusively that they belonged to those causing the milder type of pneumonia.

The Council finds Syrup Leptinol (formerly Syrup Balsamea) inadmissible to New and Nonofficial Remedies because: (1) the information in regard to composition does not state the amount of potent ingredient, nor permit the determination of its identity and uniformity; (2) the recommendation for its use in such infectious diseases as pneumonia and epidemic influenza is unwarranted and its claimed therapeutic efficacy in other diseases is without satisfactory supporting evidence; and (3) the recommendations for its use which appear on the label and the circular wrapped with the trade package constitute an indirect advertisement to the public.

The Council accepts the explanation of the manufacturer that he has been unable to obtain a satisfactory classification of the plant from which Syrup Leptinol is made. It would be undesirable to exclude from therapeutic use a valuable drug simply because its botanical character has not been determined or because an exhaustive chemical examination had so far not been made. However, in the absence of such information the manufacturer should give full information with regard to the preparation or standardization of his remedy and the therapeutic claims made for it should be accompanied by indisputable, thoroughly controlled clinical evidence. In the case of Syrup Leptinol, there is no satisfactory evidence available showing that the preparation has any value in the treatment of epidemic influenza, pneumonia, whooping cough, etc. While it is probable that a balsamic syrup, such as Syrup Leptinol, has palliative properties in coughs, such action does not at all justify the claim that it is useful in the contagious diseases for which it is proposed. The Council cannot recognize a syrup presenting an unknown plant in uncertain proportions which is recommended in a variety of dangerous contagious diseases in which it ultimately may be harmful, even though in early stages of these diseases it may serve to allay some of the milder symptoms.

Concerning the composition of the plant from which Syrup Leptinol is prepared, the Balsamea Company states that it contains “Alkaloids, acids, glucosides, volatile and fixed oils, gums and resins.” This information is valueless, since no information is given concerning the character, amounts or pharmacologic action of the ingredients. Further, it is unreliable as far as the presence of alkaloids is concerned since the A. M. A. Chemical Laboratory has been unable to find any alkaloids in the specimen of the crude drug furnished by the manufacturers.

In accordance with its regular procedure, the Council submitted the preceding statement to the manufacturer.

In reply the Balsamea Company stated that it is more than ever of the belief that Syrup Leptinol is deserving of recognition by the Council, basing this opinion on further clinical experience with it in the treatment of influenza.

The manufacturer stated that the use of the words “Leptinol” and “Syrup Leptinol” interchangeably was due to an oversight and promised to limit the use of the word “Leptinol” to an alcoholic extract of the plant.

Concerning the method of preparation of this alcoholic extract and the amount used in the preparation of Syrup Leptinol the Balsamea Company replied as follows:

“The alcoholic extract of the Leptotaenia, which we have termed ‘Leptinol’ is a preparation of definite and uniform strength, as determined by two methods: (a) the gravity test using the U. S. Hydrometer Scale for spirits, by which Leptinol registers 52 degrees at 60 degrees F., and (b) by gentle evaporation of the alcohol content and the measuring of the active constituents, which measures twenty-five per cent. by weight.

“The alcoholic extract ‘Leptinol’ is glycerinated in a machine, using one part of the alcoholic concentration to four parts of glycerin. This is then added to eleven parts of a heavy syrup, containing 7-1/2 pounds of sugar to the gallon of syrup, and thoroughly mixed in an agitating machine. Leptinol is the sole active ingredient of Syrup Leptinol. Syrup Leptinol is a preparation of uniform strength. It is far more uniform in strength than most of the syrups of the U. S. P. made from fluid extracts which are made from crude drugs which are not uniform in strength.”

This claim cannot be allowed as meeting the conflict with Rule 1. It is well known that plants vary in their composition at different times of the year; under different conditions of cultivation and growth; and under other conditions; hence the claim that alcoholic extracts of equal specific gravity insure uniformity of composition in active principles must be considered entirely illogical, especially since the exact nature of the active principles, if any be present, is unknown. If these are known their nature should be stated and tests for their identity be given. If they are unknown it is manifestly misleading to state that the preparation is of uniform strength.

It is evident that the Council cannot approve of the use of a preparation of unknown composition without satisfactory evidence of its value, especially when it is recommended in a variety of serious infectious diseases such as influenza and pneumonia. The mere fact that a small number of patients who have received the drug recover is no evidence of its curative value, and until carefully controlled clinical tests of the preparation are made, it is not entitled to the consideration of physicians.--(From The Journal A. M. A., June 5, 1920.)

FORMITOL TABLETS, II

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following supplementary report on Formitol Tablets.

W. A. Puckner, Secretary.

In the Council report (The Journal A. M. A., Oct. 4, 1919, p. 1077) on the ineffectiveness of lozenges claimed either to contain formaldehyd or to liberate formaldehyd in the mouth, the composition of Formitol Tablets of the E. L. Patch Co. was briefly discussed in the following terms:

“The A. M. A. Chemical Laboratory reported that Formitol Tablets contained formaldehyd (or paraformaldehyd), an ammonium compound, and some hexamethylenamin. It is probable that the formaldehyd (or paraformaldehyd) was produced by the decomposition of hexamethylenamin originally present in the tablets but decomposed by long contact with the acid.”

At the time this report was published, the label and the advertising matter contained but vague and indefinite statements with regard to the composition of Formitol Tablets. In the October, 1919, issue of Patchwork, the house organ of the E. L. Patch Co., it was denied that these tablets contain hexamethylenamin since none had ever been used in their manufacture. It was also claimed that the company had a “printed sheet giving the formula of these tablets.”

The Council advised the E. L. Patch Co. that it desires to publish only facts about the products which it examines and that if the report on Formitol Tablets was inaccurate in any way the Council would want to correct any error it might have unintentionally made. As the Formitol advertising in the files of the Council contained no information as to the composition of the tablets, the firm was also requested to send the printed sheet giving the “formula.”

When this printed “formula” came it was found to be a sheet used by the E. L. Patch Co. for the purpose of giving its salesmen information regarding Formitol tablets, to be passed on to the physician. This printed sheet conveyed the information that Formitol Tablets contain ammonium chlorid, benzoic acid, citric acid, guaiac, hyoscyamus, menthol, paraformaldehyd and tannic acid, but it gave no information in regard to the amount of any of the ingredients except that it declared that each tablet represents the equivalent of 10 minims of a 1 per cent. formaldehyd solution.

Because of the nonquantitative, and, therefore meaningless printed “formula” and because, also, of its complexity, it was thought desirable to make a more complete analysis of Formitol Tablets. Experience has shown that frequently the real formula of a thing is quite different from the alleged formula published by the manufacturer. The details of the laboratory’s later analysis will appear in the Annual Reports of the Chemical Laboratory or may be had on request.

The result of the laboratory’s additional experimental work, especially when taken in connection with investigations made elsewhere on the interaction of formaldehyd and ammonium chlorid justifies the conclusion that Formitol Tablets do contain some hexamethylenamin, even though the amount may be very small. As the E. L. Patch Co. declare that no hexamethylenamin is put into Formitol Tablets the conclusion drawn in the Council’s original report to the effect that the formaldehyd probably was formed by the decomposition of hexamethylenamin was evidently an error. The hexamethylenamin present is doubtless produced by the action of the paraformaldehyd on the ammonium chlorid present.

The analysis also showed that more than 78 per cent. of the weight of Formitol Tablets was made up of sugars and about 16.5 per cent. was starch and other material, some of which was talcum or similar material. This means that about 94 per cent. of the total weight of the tablets is sugar and starch, neither of which is mentioned in the printed “formula.” The significance of this is apparent when it is considered that there are eight ingredients listed in the “formula” for which therapeutic effects are claimed. Since a tablet weighs about 13.5 grains, the combined weight of all the claimed active ingredients is less than 1 grain per tablet!

The amount of ammonium chlorid found, as indicated by the total nitrogen, was not more than 1.0 per cent. or about 1/8 grain per tablet. The amount of benzoic acid found was 0.34 per cent. or 1/25 grain per tablet. Yet these two drugs are said to exert their peculiar expectorant action. (The U. S. P. lozenge of ammonium chlorid contains 1-1/2 grains ammonium chlorid or twelve times the amount of this drug in a Formitol Tablet.)

The tannic acid contained in the tablets could not be determined with accuracy but it was much less than 1 per cent. (or 1/8 grain per tablet) yet it is said to add valuable astringent qualities to Formitol Tablets! (The U. S. P. lozenge of tannic acid contains 1 grain of tannic acid.)

The quantity of guaiac (as resin) is but a fraction of 1 per cent. Yet it is said to impart to Formitol Tablets “stimulant resolvent” properties and it is intimated that there is sufficient to be of value in “cases of abscess of the throat and inflammation of the tissues.”

The total acidity indicates the presence of about 2 per cent. of citric acid or 1/4 grain per tablet. Yet this amount is said to be “antiseptic” and “aids in the general results.”

While the presence of the drug hyoscyamus (henbane) was not positively identified by microscopic examination, alkaloids were present.

The manufacturers claim that the tablets contain menthol yet only a suggestion of menthol could be obtained from the odor. However, the odor of methyl salicylate--a constituent not declared in the “formula”--predominated throughout the operations of analysis.

Formitol Tablets furnish a good illustration of some well established but often ignored truths:

1. “Formulas” that are nonquantitative are valueless or worse than valueless.

2. The fact that a manufacturer puts certain drugs in a mixture, is no proof that these drugs are there when the mixture reaches the patient. The physician must be assured that they are there when he prescribes them.

3. Complex mixtures should be avoided. It is absurd to expect, as is claimed in the case of Formitol Tablets, anodyne, antiseptic, astringent, expectorant, and resolvent action all at the same time.--(From The Journal A. M. A., June 19, 1920.)

SUKRO-SERUM AND APHLEGMATOL

Report of the Council on Pharmacy and Chemistry

Two years ago, American newspapers contained accounts of an alleged cure for pulmonary tuberculosis “discovered” by Prof. Domenico Lo Monaco of Rome, Italy. At that time no reference to the “cure” could be found in medical journals which had come from Italy and other European countries (The Journal A. M. A., July 13, 1918, p. 142). Later, reports were published of experiments carried out in Italy, according to which the intramuscular injection of solutions of sugar (saccharose--cane sugar) diminished pulmonary secretion and was of considerable value in the treatment of tuberculosis (The Journal A. M. A., Sept. 28, 1918, p. 1083). On the whole the reports of the trial of what has been called the Italian Sugar Cure for Consumption have been unfavorable. At a meeting in Paris in October, 1918, Drs. Louis Rénon and Mignot reported that they had found that the disease in guinea-pigs was not modified by the treatment and with humans the results were also negative (Paris Letter, The Journal A. M. A., Nov. 23, 1918, p. 1760).

In view of the exploitation of this treatment in the United States by the Anglo-French Drug Co., which offers “Sukro-Serum,” and by G. Giambalvo & Co., which sells “Aphlegmatol,” and because of inquiries received, the Council has authorized publication of the statement which follows.

W. A. Puckner, Secretary.

A circular issued by the Anglo-French Drug Co., describes “Sukro-Serum” as a “Sterilized Solution of lacto-gluco-saccharose.” By reading the circular to the end, however, one learns that “Sukro-Serum” is not a “serum” in the ordinary sense but apparently it is a solution of ordinary sugar (sucrose). “Sukro-Serum is a sterilized, specially prepared solution of Saccharose.”

Sukro-Serum has been advertised (N. Y. Med. Jour., Sept. 6, 1919) as an “INTRAMUSCULAR INJECTION FOR TUBERCULOSIS” “... ready for use in cases of Pulmonary and general Tuberculosis” with the assertion that “It is quite certain that in the near future Sukro-Serum will be largely used and its value fully recognized.” The circular received from the Anglo-French Drug Co. contains quotations from an article by Professor Lo Monaco in the British Medical Journal (Aug. 24, 1918) setting forth the merits of intramuscular injections of sucrose in tuberculosis. It is recommended that “Néocaine-Surrénine” (which the Anglo-French Drug Co. supplies) be used for the control of pain when Sukro-Serum is injected.

The circular enclosed with a package of “Aphlegmatol,” purchased from G. Giambalvo & Co., contained the following with reference to the composition of this preparation:

“A solution of Hydrats of Carbon After the formula of Prof. D. Lo Monaco, Director of the Institut of Physiological Chemistry of the University of Rome. Contents: Sucrose (C₁₂H₂₂O₁₁) Glucose and Galactose (C₆H₁₂O₆).”

The package contained ampules of thin, fragile, brown colored glass, containing approximately 2-1/2 c.c. of light, clear, amber colored, thick, sticky fluid, having a distinct caramel odor. Reaction p↓{H} = 5.0. A reducing substance (probably glucose) amounting to 7.4 per cent. was found by using Benedict’s method for estimating glucose quantitatively; after hydrolysis with hydrochloric acid, 55.5 per cent. glucose was found. There was no reaction for albumin. No attempt was made to identify the sugars, as it seemed probable that in the preparation caramel had been produced.

The circular which accompanied the package of Aphlegmatol contained the following information (spelling and composition as in original) about its use and effects:

To be emploied where a large bronchial secretion is present in the respiratory branches disease. The secretion will diminish and, in non complicated cases, it will completely disappear.

Fever, cough, hemottisis, night perspiration, vomiting and difficulty of breathing are, in the meantime, diminuished.

Aphlegmatol acts also as a riconstituent, being itself a nurrishing composition, improves the digestive function of the body and increases the arterial pressure.

5 c.c. (2 Phials) of Aphlegmatol per day must be injected intramuscularly in the Gluteus.

If the patient wishes two injections may be made, one at the right immediately followed by a second one at the left.

The cure must not be interrupted untill sometime after expectoration has disappeared, which result may be obtained only after fifty or sixty days, in the meantime the patient must be controlled by his home physician, especialy when thermal elevation of the body takes place.

Improvement will be manifested on or about the tenth day of the first injection.

In the advertising circular, which is apparently intended for general distribution, much the same information is given as in the sheet enclosed with the ampules, except that in the directions we find: “If the injections are painful--especially in cases where patients are very emaciated--physicians are advised to inject together with Aphlegmatol, as an anesthetic, a vial with 1 c.c. solution of Stovain at 3%.” The advertising for Aphlegmatol contains many misspelled words and appears to be the work of those ignorant of the English language.

Tuberculosis is a widespread disease and a majority of the uninformed are only too willing and ready to try such a “cure.” The preparations appear to be nothing more than concentrated solutions of sugar. It is probable that a small amount of the cane sugar might be inverted to glucose and fructose, but experiments have shown that cane sugar subcutaneously administered in the small amounts used in this instance is largely excreted in the urine unchanged. Less is known about galactose, but the evidence available would indicate that galactose is largely excreted in the urine unchanged when given subcutaneously. Glucose would be absorbed as such, and in the amounts under consideration, used by the system much the same as when given by mouth.--(From The Journal A. M. A., Aug. 21, 1920.)

SUPSALVS NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report declaring Supsalvs (Anglo-French Drug Company) inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Supsalvs are advertised by the Anglo-French Drug Company as “stable suppositories of ‘606’ (of French manufacture)” with the claim that by the rectal administration of these suppositories the effects of arsphenamine may be obtained. The asserted efficacy of Supsalvs medication is based in part on the claim that for these suppositories an excipient was found which mixes with the cocoa butter base “to form an assimilable emulsion.”

“The active principle and the vehicle being bound to one another, the mucous membrane is able to absorb both simultaneously and progressively in the form of an organic emulsion.”

As no information was furnished the Council by the Anglo-French Drug Company on the origin or quality of the arsphenamine used in the preparation of Supsalvs or the character of the vehicle which was “bound” to the arsphenamine in such a way as to permit the absorption of this combination in the form of an “organic emulsion,” the firm was requested to furnish: (1) Evidence that the arsphenamine used in Supsalvs complies with the N. N. R. standards and that deterioration of it does not occur in the preparation of the suppositories or on keeping. (2) The identity of the ingredients composing the suppository.

The Anglo-French Drug Company did not supply the requested evidence and consequently the Council judged the preparation on the basis of the information received from the company, and that contained in the available advertising and circulars. It found Supsalvs inadmissible to New and Nonofficial Remedies, first because the quality of the medicament contained in the suppositories has not been established, and second because the claimed efficacy of this preparation as a means of securing the effects of arsphenamine lacks substantiating proof.

During the past few years some French physicians have reported favorably on the intrarectal administration of arsphenamine. Boyd and Joseph at Panama published (The Journal, Aug. 17, 1918, p. 521) an enthusiastic report on intrarectal injection of arsphenamine but did not refer to its use in the form of suppositories. In a comprehensive report, on the “Treatment of Syphilis” (Quarterly Journal of Medicine, July, 1917) L. W. Harrison stated that arsphenamine (Salvarsan) in the shape of an enema is definitely less effective than intravenously and that “Neisser and the vast majority of workers can see no value in the rectal method.” Schamberg and Hirschler (A Safe and Efficient Intensive Method of Treating Syphilis, Therapeutic Gazette, November, 1919, p. 761) have given a rather thorough trial of this method; the results were most disappointing: “A certain or rather uncertain amount of arsphenamine is absorbed into the blood, but the quantity is obviously too small to be at all comparable in its effect with the intravenous administration. Our conclusions are that the rectal administration of arsphenamine or neoarsphenamine is an extremely feeble method of administering these drugs.”

The report of the Special Committee on the Manufacture, Biological History and Clinical Administration of Salvarsan and Other Substances of the British National Health Insurance Medical Research Committee contains the following: “The rectal method of administration, either in the form of solution or as suppositories, has been advocated by a few observers mainly for cases in which there is difficulty in the adoption of the intravenous method. The experiments made by Mills at Rochester Row show that three enemata of ‘606’ (0.6 Gm. in each) on successive days failed to produce any effect on the spironemes in the lesions. The general opinion of experienced workers is that the rectal method is ineffective, and in this view the Committee concur.”--(From The Journal A. M. A., Oct. 30, 1920.)

HYPODERMIC SOLUTION NO. 13, IRON, ARSENIC AND PHOSPHORUS COMPOUND NOT ACCEPTED FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Hypodermic Solution No. 13, Iron, Arsenic and Phosphorus Compound (Burdick-Abel Laboratory) is said to contain in each c.c.:

Ferrous citrate 0.06 Gm. Sodium cacodylate 0.06 Gm. Sodium glycerophosphate 0.1 Gm. Chloretone 0.005 Gm.

The preparation is advertised as “the old reliable hematinic” which is “indicated in all forms of anemia, where both red and white cells are low.” It is for hypodermic or intramuscular administration. The product is inadmissible to New and Nonofficial Remedies because:

1. It does not contain ferrous citrate as claimed. Instead the iron is in the ferric condition, apparently in the form of the unofficial and unstandardized “iron citrate green” for which there is no evidence of superiority over the official iron and ammonium citrate.[134]

[134] Iron Citrate Green, The Journal A. M. A., Jan. 12, 1917, p. 135; Reports Council Pharm. and Chem., 1916, p. 42.

2. Its name gives no information on the form in which the iron, the arsenic and the phosphorus occur therein. The term “arsenic” does not indicate whether the mild cacodylate or the potent arsenous oxid is being administered nor does the term “phosphorus” tell the physician that he is administering the practically inert sodium glycerophosphate.[135]--(From The Journal A. M. A., Nov. 13, 1920.)

[135] Glycerophosphates, The Journal A. M. A., Sept. 30, 1916, p. 1033; Reports Council Pharm. and Chem., 1916, p. 32. Sodium glycerophosphates. Reports Council Pharm. and Chem., 1916, p. 52.

PARATHESIN NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

The local anesthetic ethyl paraminobenzoate was first introduced as “Anesthesin” or “Anæsthesin.” Ethyl paraminobenzoate is not patented in the United States and it may be manufactured, therefore, by any firm which chooses to do so. In order that a common name by which to designate the drug might be available, the Council coined the name “Benzocaine,” as being short and easily remembered, but yet suggestive of its composition and character (“benzo” to indicate its derivation from benzoic acid and “caine” to indicate its cocaine-like properties). As the term “anesthesin” had become a common name for the drug, the Council recognized this as a synonym for benzocaine.

One of the accepted brands for benzocaine is “Anesthesin,” manufactured by the H. A. Metz Laboratories, Inc. (see New and Nonofficial Remedies, 1920, p. 33). However, on April 19, 1920, the Metz Laboratories requested that its product be recognized under the designation of “Parathesin.” As the use of one substance under several names causes confusion and retards rational therapeutics, the Council’s rules provide against the recognition of proprietary names for nonproprietary, established drugs. In view of this and because the legitimate interests of the manufacturer may be safeguarded by appending his name or initials to the common name, benzocaine or anesthesin, the Council voted not to recognize the designation “Parathesin.”--(From The Journal A. M. A., Nov. 13, 1920.)

CHLORLYPTUS

Report of the Council on Pharmacy and Chemistry

The condensed report on Chlorlyptus which follows and also a complete detailed report was sent to the proprietor, Jan. 9, 1920. In reply he requested that publication be postponed pending the submission of further clinical evidence. As after nine months this evidence had not been received the Council has authorized publication of its report.

W. A. Puckner, Secretary.

Chlorlyptus is manufactured by Chas. A. Weeks, trading as the Weeks Chemical Company, Philadelphia. It is prepared by chlorinating eucalyptus oil until it has bound 30 per cent. of chlorin, the chlorin being in relatively stable combination. It is claimed that Chlorlyptus is a new “chlorinated antiseptic,” highly efficient as a wound antiseptic and at the same time nonirritant and nontoxic. Chlorlyptus is offered for use in the treatment of local infections of all types, as well as of burns, and also as an antiseptic in the alimentary and genito-urinary tracts.

The claims were based largely on reports of investigations made by Philip B. Hawk and his collaborators. These reports the referee of the committee in charge of Chlorlyptus considered incomplete and unconvincing. Being advised of this Mr. Weeks caused further investigations to be made. Some of the information was checked and extended by the A. M. A. Chemical Laboratory and by the referee.

The laboratory side of the investigation may now be considered as complete. The results show that Chlorlyptus is a feeble antiseptic of the aromatic oil type, considerably weaker than eucalyptus oil, both as to therapeutic and toxic qualities. The chlorin contained in it is bound too firmly to have any action; in fact, the chlorination appears to have accomplished nothing more than a considerable destruction or weakening of the eucalyptus oil. As far as the referee can judge, this object could have been accomplished just as effectively by diluting ordinary eucalyptus oil with some indifferent solvent.

The manufacturer of Chlorlyptus contends that if the experimental findings are against his product, it should be judged by the clinical data. The clinical evidence, however, is not decisive. It shows that wounds healed and infections were prevented or successfully combated in cases in which Chlorlyptus was used in combination with good surgery, but it does not show how much of the result was due to the surgery and how much, if any, to the use of Chlorlyptus. Even if it were granted as probable that the Chlorlyptus contributed to the favorable outcome, it would still be a question whether it equals other established antiseptics, or whether it possesses any material advantages over diluted eucalyptus oil. Until these points are established the clinical reports cannot offset the unfavorable results of the laboratory investigation.

The manufacturer has endeavored to obtain more convincing clinical reports, but the lack of success in this direction during the past nine months gives little encouragement that acceptable clinical evidence will be available within a reasonable time.

Believing that the information which has been obtained should be made available to the profession, the Council authorized publication of this statement and also of the detailed report. The Council voted not to accept Chlorlyptus for New and Nonofficial Remedies because of the unfavorable results of the laboratory investigation, but with the agreement that the product would receive further consideration should more convincing clinical data become available.

I. DETAILED REPORTS

Summarized Reports

CHEMICAL NATURE OF CHLORLYPTUS

Chlorlyptus is prepared by chlorinating eucalyptus oil until it has bound 30 per cent. of chlorin. “Chlorlyptol” is prepared in an analogous manner from eucalyptol. There has been some confusion as to the composition; but the principal constituent is now stated to be “a dichloride of eucalyptus oil,” to which the formula C₁₀H₁₆OCl₂ has been assigned. It differs from the “chlorinated eucalyptus oil,” as ordinarily used for making dichloramin-T solutions, and which contains only 2/3 per cent. of chlorin.

AVAILABILITY OF CHLORIN IN CHLORLYPTUS

The chlorin content of chlorlyptus is almost entirely firmly bound, and therefore not “available,” in contrast to the group of so-called chlorinated antiseptics (i. e., the hypochlorite and chloramin type). For instance, it does not directly liberate iodin from iodid. It contains a very small quantity of free hydrochloric acid, or perhaps some acid esters, and liberates a little more on prolonged contact with water; but the total quantity liberated under reasonable conditions is very small. According to Hawk’s data, they correspond only to 1/8 per cent. HCl even after standing with water overnight and to only 1/5 per cent. of HCl after two weeks. The referee has shown that this quantity of acid has no therapeutic significance.

The “bound” chlorin of chlorlyptus, being chemically inactive, would have no more practical significance than the bound chlorin in common salt. The “ozone” said to be used during the preparation, to expel the HCl, has also practically disappeared, to judge by the slowness with which iodin is liberated from potassium iodid.

ACID FORMATION

Some constituents of chlorlyptus hydrolyze slowly and to a slight degree with the liberation of a trace of free hydrochloric acid. According to the data of Hawk’s report, the free acidity, in term of HCl, is 1/12 per cent. On standing with water over night, this increases to 1/8 per cent.

On this basis, Hawk proposed a theory that the claimed antiseptic effects of chlorlyptus are due to the continuous liberation of hydrochloric acid.

Experiments by the referee show this to be untenable. The traces of acid are neutralized and absorbed by the tissues so rapidly that an acid reaction is not maintained. These experiments are described in the appendix.

They were submitted to the manufacturers, who in the name of Mr. Weeks (May 9, 1919) concede this conclusion and state that “there is no doubt that the referee’s statements as to action in mouth, contact with living tissue and improbability that the acidity is effectively antiseptic is correct, and I am willing to accept the referee’s statement as conclusive in this respect.”

BACTERIAL CULTURE EXPERIMENTS

Mr. Weeks submitted a statement by Hawk to the effect that chlorlyptus has a phenol coefficient of 2.6, determined by the standard Hygienic Laboratory procedure.

He also quotes Rockefeller War Hospital that chlorlyptus kills Staphylococcus aureus in concentra of 1 dram: 1 gallon (about 1:1,000), but not in more dilute solutions.

More recently, he presented a more comprehensive report by Rivas, which is reproduced in the appendix. The essential results are tabulated herewith. This tabulation shows that chlorlyptus fails to kill the organisms after an hour’s exposure of the following concentrations:

Typhoid in bouillon, 10 per cent. of chlorlyptus. Staphylococci in pus, 5 per cent. of chlorlyptus. Staphylococci in serum, 1 per cent. of chlorlyptus.

It seems to the referee that a substance that is ineffective with an hour’s exposure to these concentrations is not at all likely to kill or check bacteria under clinical conditions. In other words, it is not an antiseptic in the ordinary sense.

The referee is not impressed by the superior power attributed by Rivas to chlorlyptus in the presence of pus. Inefficiency of 10 per cent. for one-half hour or of 5 per cent. for two hours seems a failure rather than a success. The referee also notes the absence of any data as to the relative efficiency of chlorlyptus against staphylococci in pus and in bouillon. The data on serum indicate that chlorlyptus is much weaker than phenol and show that it is less effective in the presence of pus than in other mediums.

The referee fails to grasp the bearing of the oil experiments on any clinical condition. Moreover, the inconstant results mentioned by Rivas suggest the possibility that the incorporation of the bacteria in oil may have prevented their effective distribution in the culture medium. If any significance is to be attached to these experiments, they should be checked by controls, without antiseptics.

SUMMARY OF RIVAS’ IN VITRO EXPERIMENTS

==================================================================== Minimal Maximal Germicidal Not Germicidal Concentrations Concentrations

Typhoid Bacilli in Bouillon: Chlorlyptus (Exp. 3) 10%, 2 to 4 hours 10% for 1 hour 5% for 2 hours Eucalyptus oil (Exp. 1) 5% within 5 minutes No data Phenol (Exp. 5) 1% within 10 min. No data

Streptococci and Staphylococci in Olive Oil: Chlorlyptus (Exps. 7 and 8) 1%, almost at once, No data sometimes Eucalyptus oil No data No data Phenol (Exps. 9 and 10) 1%, almost at once, No data

Staphylococci in Pus: Chlorlyptus (Exp. 11) 10% for 1 hour 10% for 1/2 hour 5% for 2 hours Eucalyptus oil No data No data Phenol No data No data

Staphylococci in Human Blood Serum: Chlorlyptus (Exp. 12) 5% in 1 hour 1% in 1 hour Eucalyptus oil No data No data Phenol 5% almost at once 1% in 1 hour --------------------------------------------------------------------

INFECTION EXPERIMENTS IN VIVO

Dr. Rivas reports two series of experiments, in each of which three guinea-pigs received staphylococcus suspensions in the peritoneum. One guinea-pig in each series was left untreated; the others received injections of chlorlyptus into the peritoneum at various intervals.

The following results were obtained:

==================================================== Chlorlyptus Results

Exp. 19, No. 1 None Survived Exp. 20, No. 1 None Died Exp. 19, No. 2 At once Died Exp. 19, No. 3 After 24 hours Survived Exp. 20, No. 2 After 18 hours Died Exp. 20, No. 3 After 24 hours Died ----------------------------------------------------

This shows mortalities of:

1 in 2, i. e., 50 per cent., without chlorlyptus. 3 in 4, i. e., 75 per cent., with chlorlyptus.

It is doubtful whether so small a series of experiments on so variable a phenomenon as is infection should receive any serious consideration. So far as they go, they would indicate that chlorlyptus is useless or worse.

TOXICITY

The referee determined the acute toxicity of chlorlyptus by hypodermic injection of oily solutions into white rats. Comparative experiments were made with ordinary eucalyptus oil. The details are given in the appendix. The end-results may be summarized as follows:

================================================================== Survived Chlorlyptus Eucalyptus Oil

1.56 c.c. 3.75 c.c. 5.00 c.c. 6.25 c.c. 1.25 c.c. 8.65 c.c. 2.5 c.c. (3 days)

Died (in days) 12.5 c.c. (1 day) 3.75 c.c. (3 days) 12.5 c.c. (1 day) 5.00 c.c. (3 days) 18.75 c.c. (1 day) 6.25 c.c. (1-1/2 days)

M. F. D. 8.75 to 12.5 c.c. per kg. 1.25 to 2.5 c.c. per kg. ------------------------------------------------------------------

Fatality.--The doses are calculated for cubic centimeters of the undiluted drugs per kilogram of rat.

Dr. Rivas reports a series of toxicity experiments on guinea-pigs. Assuming a uniform weight of 400 gm. per animal, his results (details in appendix) may be summarized as:

================================================================== Minimal Maximal Fatal Dose Survived Dose C.c. per Kg. C.c. per Kg.

Chlorlyptus, peritoneal (Exp. 14) 7.5 c.c. 5.0 c.c. Chlorlyptus, pleural (Exp. 15) 5.0 c.c. 2.5 c.c. Eucalyptus oil, peritoneal (Exp. 16) 2.5 c.c. No Data Eucalyptus oil, pleural (Exp. 16) 1.25 c.c. No Data Dichloramin-T, peritoneal (Exp. 16) 1.25 c.c. No Data ------------------------------------------------------------------

The comparative toxicity in the various series is therefore approximately as follows:

======================================================== Chlorlyptus : Eucalyptus

Referee, rats, hypodermic 1/5 : 1 Rivas guinea-pig, peritoneal 1/3 : 1 Rivas guinea-pig, pleural 1/4 : 1 --------------------------------------------------------

Evidently, the toxicity of chlorlyptus is about one-fourth of that of eucalyptus oil. The difference is considerable, but not fundamental. Moreover, the symptoms of chlorlyptus resemble the characteristics of eucalyptus oil.

According to the tabulation of Barker and Rowntree,[136] the mean fatal dose of eucalyptus oil for man, in the twenty-nine clinical cases reported in the literature, is about 20 c.c. If the toxicity ratio of the two substances were the same as for the rat experiments (a rather hazardous assumption), the fatal dose of chlorlyptus for man would be about 80 c.c.

[136] Barker and Rowntree (Bull. Johns Hopkins Hospital =29=:215, 221 [Oct.] 1918) obtained the following results with eucalyptus oil:

Cat, hypodermic; survived 3 c.c. per kg.; killed by 5.5 c.c. per kg.

Cat, intraperitoneal; killed by 5 c.c. per kg.

Dog, hypodermic; survived 1.3 c.c. per kg.

They quote from Browning that the following doses, c.c. per kilogram, are not fatal: frogs, 0.5; rabbits, 1 to 5; guinea-pigs, 1.

IRRITATION

Rivas’s Experiment 14 shows that chlorlyptus gives very definite irritation, apparently similar to that produced in Experiment 16 by eucalyptus oil in one-fourth the dose.

Incidentally, the referee may add from personal experience that the “chlorlyptus oil, 5 per cent. Cl” is markedly irritating in the nostrils, although marked “non-irritating” on the label.

II. APPENDIX: SPECIAL REPORTS

A. COMPARISON OF CHLORLYPTUS WITH CHLORINATED EUCALYPTOL

From the Chemical Laboratory of the American Medical Association

According to the label, “Chlorlyptus” is a “Synthatized Chlorinated Oil of Eucalyptos, with Acid Reaction, containing approximately 30 per cent. Chlorine and possesses excellent Germicidal Properties, when made under our special process.” It is manufactured by the Weeks Chemical Company, Philadelphia, Pa. This product was submitted to the Council on Pharmacy and Chemistry by the manufacturers, and in turn the Laboratory was asked to examine it with the idea of comparing it with the nonproprietary brands of “chlorinated eucalyptol” (used as a solvent for dichloramine-T; see New and Nonofficial Remedies, 1919, p. 70). In the submission, certain tests were described, most of which were followed. Among the statements given under the chemical properties of chlorlyptus are:

“On distillation, chlorlyptus begins to boil at about 100 C. The temperature rises as the distillation continues, accompanied by the decomposition of the chlorlyptus and the evolution of hydrochloric acid and chlorine.”

“When brought into contact with water, chlorlyptus undergoes a process of hydrolysis ...”

Notwithstanding the foregoing the statement is made on the label that chlorlyptus “is a Stable Compound, not affected by heat, light or water.”

The following comparisons of chlorlyptus, chlorinated eucalyptol-Abbott and chlorinated eucalyptol-Squibb were made:

Chlorlyptus is a viscous, dark brown liquid, with an acrid odor and having a specific gravity of 1.2098. Chlorinated eucalyptol-Abbott is a mobile, light yellow liquid, with a eucalyptus odor, having a specific gravity of 0.9317. Chlorinated eucalyptol-Squibb is a mobile, colorless liquid, and its specific gravity is 0.9303.

An alcoholic solution of silver nitrate added to an alcoholic solution of chlorlyptus yields a heavy precipitate of silver chloride. In the case of the Abbott chlorinated eucalyptol a slight turbidity is caused by this test; the Squibb product shows no reaction.

A 10 per cent. solution of potassium iodide is overlaid with an equal volume of chlorlyptus. Iodine is slowly liberated, being noticeable in one-half hour. With chlorinated eucalyptol-Abbott, a trace of free iodine is discernible after four hours, while with chlorinated eucalyptol-Squibb there is no free iodine present. When the respective products are shaken with an alcoholic solution of potassium iodide, no iodine is immediately liberated, thus showing the absence of “active chlorine” (difference from the hypochlorite derivatives).

When chlorlyptus is dissolved in concentrated sulphuric acid, some blackening occurs and the odor of hydrogen chloride is very noticeable. Both the Abbott and Squibb brands of chlorinated eucalyptol give a reddish mixture, with no perceptible evolution of hydrogen chloride, and still retain the characteristic eucalyptol odor.

On heating, chlorlyptus decomposes and begins to boil at from 103 to 105 C. Then a higher fraction comes over at 178 C. The distillate has a sharp odor, is acid, and frees very little iodine from potassium iodide. Chlorinated eucalyptol-Abbott does not seem to decompose. Some gaseous substance is given off at 80 C, but the liquid distills at 173 C. The distillate has no acid odor, is neutral, and liberates no iodine from potassium iodide. (In both cases the distillation was not carried to completion, approximately only about half of the volume being distilled over.)

PRELIMINARY TESTS ON CHLORLYPTUS AND CHLORINATED EUCALYPTOL

====================================================================== Chlorinated Chlorinated Chlorlyptus Eucalyptol-Abbot Eucalyptol-Squibb

Odor Acrid Like eucalyptus Like eucalyptus

Density and Dark brown; Light yellow; Colorless; color viscous, mobile; lighter mobile; lighter heavier than water than water than water

AgNO₃ added Heavy ppt. Slight turbidity Clear to alcoholic solution

Equal parts Gives free Gives free iodin No free iodin with KI iodin slowly, in 4 hours; in 4 hours solution noticeable not much in 1/2 hour

Equal parts Much iodin Small amount of No free iodin with 10% KI, immediately free iodin in in 3 hours 10% KIO₃ few numbers; solution does not noticeably increase

Equal parts Some blackening; Reddish mixture; Same with conc. odor of HCl no HCl; H₂SO₄ eucalyptol odor

Alcohol KI No iodin Same Same as Abbott liberated product

Heating Decomposes and Apparently does not boils at decompose; some 103-105 C.; gas given off then higher when T=80; the fraction comes liquid distilled over at 178 C.; at 173 C.; the distillate has distillate did sharp odor, is not have much acid, but frees odor; no HCl very little gas detected; I₂ from KI; no I₂ from distillation KI; distillate not completed was neutral (distillation not completed) ----------------------------------------------------------------------

The addition of chlorlyptus to a mixture of 10 per cent. potassium iodide, 10 per cent. potassium iodate solution, brings about the liberation of iodine, increasing perceptibly on standing. This shows that the hydrogen chloride is gradually split off, and in time will cause a solution having a considerable degree of acidity. When this test is carried out on chlorinated eucalyptol-Abbott, a small amount of iodine is liberated in a few minutes but does not increase, showing a slight initial acidity without further hydrolysis. Chlorinated eucalyptol-Squibb yields no free iodine after standing three hours.

When the chlorine content of chlorlyptus is determined according to the method of Carius, the amount is found to be 29.6 per cent. (The manufacturers give a method of determining chlorine by Hunter’s fusion method. It is believed that in this method hydrogen chloride may be lost, and this opinion is substantiated by the firm’s statement, “Chlorlyptus analyzed in this manner shows approximately 25 per cent. of chlorine.”) The chlorine content of chlorinated eucalyptol-Abbott is found to be 0.67 per cent., and that of the Squibb brand to be 0.62 per cent. (about one-fiftieth as much as in chlorlyptus).

To sum up: Chlorlyptus differs from chlorinated eucalyptol in odor, color, density, in reaction to silver nitrate, potassium iodide, sulphuric acid and the aqueous solution of potassium iodate and potassium iodide. The distillation of the two products occurs differently. Chlorlyptus contains nearly 30 per cent. of chlorine, which is approximately fifty times as much as in chlorinated eucalyptol. Thus it appears to have considerable chlorine in the negative form (Cl^-) which may be relatively easily split off as hydrogen chloride.

B. THE PERSISTENCE OF THE ACID

Reaction of Chlorlyptus in the Body

BY THE REFEREE

This “chlorinated ozonized eucalyptus oil” is distinctly acid to litmus paper. It is claimed that further quantities of acid are liberated on contact with water. This is credited with producing a continuous acid reaction on the surface of tissues to which the oil may be applied and this in turn is stated to be antiseptic or germicidal.

This theoretical speculation does not take into account the large quantity of reserve alkali in the body by which it combats attempts to alter its normal reaction. It is therefore not convincing, unless it is supported by direct evidence.

In the absence of such data on the part of the promoters of the preparation, experiments were made to determine whether the oil preserves its acid reaction in contact with mucous and serous membranes. The answers were clearly in the negative.

In the mouth, the reaction becomes neutral within ten or fifteen minutes; in the pleura and peritoneum within half an hour, and probably in much shorter periods.

More detailed data follow:

SERIES A: BEHAVIOR IN THE MOUTH; HOMO

EXPERIMENT.--Chlorlyptus and to less extent Chlorlyptus Oil, are acid to litmus. They are applied:

(a) Drop to litmus paper and this to gums.

(b) Several drops directly to tongue.

The reaction to litmus paper is tried from time to time.

RESULTS.--(a) Applied to gums on litmus paper:

Chlorlyptus: Red color becomes gradually feebler and does not spread on the paper.

Chlorlyptus Oil: Turns blue in a few minutes.

(b) Dropped on tongue:

Chlorlyptus: Acid taste at once. Does not increase, but on contrary, becomes less.

Litmus applied after ten minutes: not acid.

Litmus applied after five minutes: distinctly acid.

Chlorlyptus, 1/3 c.c.: After six minutes, litmus very red.

After ten minutes, faintly red.

After fifteen minutes, blue.

Chlorlyptus Oil, 1 c.c.

After three minutes, faintly red.

After eight minutes, neutral.

CONCLUSIONS.--On contact with living tissues, the acid of chlorlyptus is rapidly neutralized and absorbed.

The surface is neutral within ten or fifteen minutes.

It is therefore very improbable that the acidity is effectively antiseptic.

A comparison of chlorlyptus with dilute acetic acid shows that the chlorlyptus does not maintain the acidity even as well as 1 per cent. acetic acid.

===================================================================== Acetic Acid Chlorlyptus

Tongue, a drop of 5 per cent.; still Neutral between five slightly acid to litmus after ten minutes; and ten minutes taste almost gone in two minutes

Gums, a few drops between cheeks and gums: Neutral between ten Five per cent. still strongly acid in and fifteen minutes twelve minutes; distinctly acid in seventeen minutes. One per cent. still strongly acid in twenty-one minutes ---------------------------------------------------------------------

CHLORLYPTUS: REACTION (LITMUS PAPER) ON CONTACT WITH TISSUE

====================================================================== Serial When Quantity, Time Blue Symptoms or No. Animal Injected C.c. of Death Litmus Toxicity

1 Rat Pleura 1 1/2 hour Remains blue None; killed; pleura not congested; lung spec. = 21; slight congestion 2 Rat Pleura <1 1 hour Remains blue Negative 3 Rat Pleura 1 23 min. Remains blue Almost at once bad gasping respiration and died in 23 m.; heart distend.; possibly injection penetrated lung Peritoneum 1 23 min. Turns red 4 Rabbit Pleura 1 .... ...... Died overnight 5 Dog Pleura 1 1/4 hour Remains blue 20 m. p. m. Peritoneum 1 1/4 hour Remains blue 20 m. p. m. 6 Dog Pleura 1 3 min. Remains blue 45 m. p. m. Peritoneum 1 3 min. Remains blue 45 m. p. m. 7 Dog Pleura 1 20 min. Remains blue 20 m. p. m. Peritoneum 1 20 min. Remains blue 20 m. p. m.

SERIES B: SEROUS MEMBRANES

In these experiments, 1 c.c. of chlorlyptus was injected into the pleura or peritoneum. After a stated time, the animal was killed, and the reaction of the pleural or peritoneal surface was tested with blue litmus paper. The results are shown in the table.

C. TOXICITY EXPERIMENTS

By the Referee

TECHNIC

White rats were injected hypodermically with chlorlyptus or with eucalyptus oil, diluted with olive oil in the ratio of 1:4. The larger doses were divided between two or more sites of injection.

DETAILED PROTOCOLS

Hypodermic injections in white rats. Drugs diluted with 3 parts of olive oil. Doses are given as cubic centimeters of pure drug per kilogram of rat.

A. EUCALYPTUS SERIES

EXPERIMENT 1.--1.25 c.c.; injected VII.9.19: Active; walks about. No depression at any time. VII.10.19. Appears normal.

EXPERIMENT 2.--2.5 c.c.; injected VI.30.19: Quiet--not very depressed, reflexes good (six hours).

VII.1.19--Active--reflexes good, eats moderately.

VII.2.19--Animal acts normal--eats moderately, reflexes good; active (a.m.). Later in day, depressed.

VII.4.19--Died during night of VII.3.19.

EXPERIMENT 3.--3.75 c.c.; injected VI.24.19: Quiet; depressed; pain reflex diminished. Animal lay on ventral surface, not supported by legs. Will get on to feet very sluggishly if turned on side (twenty-four hours). Does not eat.

VI.26.19--Depressed slightly; pain reflex present.

VI.27.19--Fairly active; eats a little.

VI.28.19--Depressed.

Died during night of VI.29.19 (three days).

EXPERIMENT 4.--5 c.c.; injected VI.24.19: Quiet; markedly depressed (one hour). Does not get on feet when turned on side; ataxia well marked. Slight watery secretion in eyes. Reflexes diminished. Does not eat (twenty-four hours).

VI.26.19--Heart slowed and arrhythmic. Animal lies on side. Unable to walk; markedly depressed.

VI.27.19--Lies on side; does not eat. Died during night of VI.27.19 (three days).

EXPERIMENT 5.--6.25 c.c.; injected VI.24.19: Quiet; very markedly depressed. Heart and respiration greatly slowed. Lies on side; tears in eyes; does not eat (twenty-four hours).

VI.25.19--Temperature subnormal; cold to touch; tail stiffened and straight.

Died during night of VI.25.19 (one and one-half days).

Postmortem: Lungs congested. Liver pale in color. Spleen very dark red. Kidneys normal. Other organs normal.

B. CHLORLYPTUS EXPERIMENTS

EXPERIMENT 1.--1.56 c.c.; injected VI.24.19: Rather restless for an hour. Active during next four hours and following twenty-four. Eats well, reflexes good. Acts normal on VII.1.19 and since VI.26.19.

EXPERIMENT 2.--3.75 c.c.; injected VI.24.19: More quiet; active during next twenty-four hours. Reflex all right. Eats well; normal VII.1.19, since VI.26.19.

EXPERIMENT 3.--5 c.c.; injected VI.24.19: Quiet; defecation in four hours. Rather quiet for six hours. Eats well. Reflexes good; normal VII.1.19, since VI.26.19.

EXPERIMENT 4.--6.25 c.c.; injected VI.24.19: Quiet and breathing labored in four hours; active after twenty-four hours. Eats well. Somewhat depressed on VI.26.19; pain reflex present. On VI.26.19, eats well and fairly active. Active and eats, VI.27.19. Appears normal, VII.1.19.

EXPERIMENT 5.--8.75 c.c.; injected VI.30.19: Rather quiet during next two hours. Morning of VII.1.19, lies on stomach; quiet; does not eat very much. Pain reflexes good. VII.2.19, still depressed; does not eat. Appears normal, VII.3.19.

EXPERIMENT 6.--12.5 c.c.; injected VI.25.19: Quiet, but reflexes good; more quiet and depressed after several hours. Some loss of oil from wound. Died night of VI.25.19 (one day). Tail stiff. Temperature low.

Postmortem: Lungs markedly congested. Spleen and liver dark red. One kidney congested. Other viscera normal.

EXPERIMENT 7.--12.5 c.c.; injected VII.9.19: Quiet for one-half hour; 1.5 hours twitching of muscles of whole body, lies on side, ataxia present. Died night of VII.9.19 (one day).

EXPERIMENT 8.--18.75 c.c.; injected VI.25.19: Quiet; reflexes good (three hours). Some loss of oil. Depressed and turns on side (six hours). Died night of VI.25.19 (one day).

Postmortem: Lungs congested. Spleen and liver very dark red. Right kidney much darker red. Viscera normal.

D. REPORT OF DR. D. RIVAS

The following are the results of experiments conducted by me, during the past four months, on the germicidal action of chlorlyptus (chlorinated oil of eucalyptus, principal constituent C₁₀H₁₇OCl₂) in vitro and in vivo, and comparison also with carbolic acid, oil of eucalyptus and dichloramine in test for irritation and toxicity.

Germicidal Action.--Based on the results obtained, chlorlyptus when used in a 5 per cent. paraffin oil solution was found to be a mild germicidal against typhoid B, streptococcus and staphylococcus when these organisms were suspended in ordinary bouillon culture or sterile salt solutions.

The germicidal action was found stronger when these micro-organisms were suspended in a sterile oily or lipoid substance, such as olive oil. The results of these experiments were not constant, owing probably to the imperfect suspension of the bacteria. Thus, while in some of the experiments chlorlyptus in 1 per cent. oil solution destroyed these micro-organisms, in other cases the same strength solution failed to give same result in same time.

The increased germicidal action of chlorlyptus on bacterial suspensions in olive oil may be accounted for by the fact that chlorlyptus is soluble in olive oil and not an admixture, as in the case of paraffin oil.

Chlorlyptus is not a coagulant, as are germicides of the phenol or hypochlorite types, and the germicidal action is therefore not strictly comparable.

The germicidal action of chlorlyptus oil solution, on pathogenic bacteria, on streptococcus and staphylococcus, suspended in pus, was found to be stronger than when these micro-organisms were suspended in ordinary bouillon culture or sterile salt solution. In one of the experiments, similar results were obtained when these micro-organisms were suspended in olive oil, chlorlyptus showing marked germicidal action.

Irritation and Toxicity.--The irritating action was found to be relatively mild in tests on laboratory animals. Thus, from 0.5 to 1 c.c. of chlorlyptus in paraffin oil 5 per cent. solution, injected into peritoneal or pleural cavities of guinea-pigs weighing 400 gm. was found to be without any appreciable disturbance in the health of the animal, and in some cases the injection of as much as 2 c.c. did not kill the animal.

Therapeutic Action.--Guinea-pigs were inoculated with purulent material containing streptococcus, staphylococcus and B. coli in peritoneal and pleural cavities respectively, and after six hours 1 c.c. of chlorlyptus 5 per cent. in paraffin oil solution was injected. Other infected animals were similarly treated twenty-four hours after inoculation, and another series forty-eight hours after inoculation. In some of these cases the animals died from shock but in a clearly defined series in which the injection of 1 c.c. of the chlorlyptus solution was made in the peritoneum of the guinea-pigs twenty-four hours after the inoculation, the animals lived. The control animal, inoculated with the purulent material and not treated with chlorlyptus oil solution, died.

In consideration that the injection of chlorlyptus oil solution [sic, referee] were made [? referee] in the peritoneal cavity this substance is apt to affect the vital organs in the abdominal cavity. It is my belief that in case of wall abscess of chronic inflammation, by limiting the action of chlorlyptus to the infected area, preventing at the same time the infection of the vital organs, chlorlyptus, because of its non-irritating quality, can be used effectively as an antiseptic.

CONCLUSIONS

1. Chlorlyptus is a mild and relatively nonirritating antiseptic of marked action on pus and suppuration.

2. When bacteria were suspended in olive oil or in pus, chlorlyptus showed marked germicidal action.

3. Chlorlyptus can be injected into the peritoneum or the pleural cavities of guinea-pigs in the proportion of 1 c.c. per 400 gm. of body weight without detriment to the animal.

4. Chlorlyptus in 5 per cent. oil solution (taking Clause 3 as comparison) can perhaps be injected in man as an antiseptic agent when there is a walled-in abscess in the peritoneum or pleural cavity where there is drainage, in the proportion of 0.5 to 1 c.c. per pound of body weight with good result.

REPORT ON THE GERMICIDAL ACTION OF CHLORLYPTUS ON PATHOGENIC BACTERIA IN VITRO AND IN VIVO

EXPERIMENT 1.--The germicidal action of eucalyptus oil.--Typhoid bacillus was destroyed in less than five minutes when exposed to the action of a 5 per cent. suspension of oil of eucalyptus. The exposure for four hours in a 5 per cent. suspension of chlorlyptus in paraffin oil was without effect on typhoid bacillus. It requires an exposure of two to four hours in a 10 per cent. suspension of chlorlyptus in paraffin oil to destroy typhoid bacillus.

EXPERIMENT 2.--Bacilliary action of chlorlyptus on the growth of pathogenic bacteria.--Typhoid and anthrax bacilli were selected for the experiment. Two series of five tubes each were made. The culture medium used was nutrient bouillon. Chlorlyptus was added in the following proportions: Tube 1, 1:10; Tube 2, 1:100; Tube 3, 1:1,000; Tube 4, 1:10,000, and Tube 5, 1:100,000. One series was inoculated with typhoid bacillus. All tubes were incubated for three days at 37 C.

Chlorlyptus inhibited the growth of typhoid bacillus when added to the bouillon in the proportions of 1:10. The growth of anthrax bacillus was inhibited by chlorlyptus when it was added in the proportions of 1:10, 1:100 and 1:1,000, as shown in the accompanying table. [The table was not submitted.--Ed.] In one instance the growth was markedly inhibited by chlorlyptus when added in the proportion of 1:10,000.

EXPERIMENT 3.--Germicidal action of chlorlyptus on typhoid bacillus.--Bouillon cultures of typhoid bacillus forty-eight hours old, and a suspension of forty-eight-hour agar cultures of typhoid bacillus in sterile salt solution were used for the experiment. Chlorlyptus was added in the proportion of 1:1,000; 1:1,500; 1:100; 2 per cent.; 3 per cent.; 4 per cent.; 5 per cent. and 10 per cent., respectively.

Inoculations were made in trypsinized peptone bouillon after the addition of chlorlyptus at different intervals, namely: at once, after five minutes, after ten minutes, after fifteen minutes, after thirty minutes, after one hour and after two hours, and tubes incubated at 37 C. for forty-eight hours.

Result: Growth was shown in all tubes except those in which chlorlyptus was added in the proportion of 10 per cent. and after the action of the antiseptic for two hours or longer.

EXPERIMENT 4.--Inhibitory action of chlorlyptus in the growth of typhoid bacillus.--Chlorlyptus was added to sterile bouillon in the proportion of 1:100, 1:1,000, 1:10,000 and 1:100,000, and incubated for forty-eight hours at 37 C. to eliminate any possible contamination of the bouillon during the manipulations. All tubes were found sterile and inoculated with typhoid bacillus.

Result: All tubes were found sterile again after being inoculated with typhoid bacillus and incubated at 37 C. for forty-eight hours, which shows chlorlyptus inhibited and the growth of typhoid bacillus in bouillon when this antiseptic was added in the proportions of 1:100 to 1:100,000.

Remarks: In another experiment made, chlorlyptus showed a weaker inhibitory action on the growth of typhoid bacillus.

EXPERIMENT 5.--Germicidal action of carbolic acid.--The technic was the same as that outlined in Experiment 1. except that carbolic acid was used instead of chlorlyptus.

Result: Carbolic acid showed a distinct germicidal action on typhoid bacillus in the proportions of 1 per cent. in ten minutes.

EXPERIMENT 6.--Action of nitrogen gas on the growth of typhoid bacillus in bouillon and nutrient agar when chlorlyptus was added to this culture medium.--Chlorlyptus was added to the bouillon in the proportions of 1:100, 1:1,000, 1:10,000 and 1:100,000, as outlined in Experiment 2; also to agar kept melted at 45 C. Tubes were inoculated with typhoid bacillus; plates were made of the inoculated agar tubes; all plates and tubes were incubated at 37 C. for forty-eight hours in an atmosphere of nitrogen gas.

Duplicate experiments were made with cultures of typhoid bacillus as above in bouillon and agar plates containing the same amount of chlorlyptus and incubated at 37 C. in ordinary atmosphere as control.

Result: Nitrogen gas did not show any appreciable increase of the germicidal action of typhoid bacillus when grown in medium containing chlorlyptus. Growth was about the same in cultures supplied with nitrogen gas as in those growing in ordinary atmosphere.

EXPERIMENT 7.--Germicidal action of chlorlyptus on pyogenic bacteria suspended in an oily medium.--Experiment with streptococcus: Cultures of streptococcus in blood agar three days old were suspended in olive oil (sterile), and chlorlyptus was added in the proportions of 1, 5 and 10 per cent. and inoculated in trypsinized bouillon at different intervals, namely: at once, after five minutes, after ten minutes, after fifteen minutes, after thirty minutes, and after one hour. Tubes were incubated at 37 C. for forty-eight hours.

Result: All tubes remained sterile. The germicidal action of chlorlyptus on streptococcus suspended in oil was almost at once and with certainty after five minutes when added in the proportion of 1, 5 and 10 per cent.

EXPERIMENT 8.--Germicidal action of chlorlyptus on staphylococcus, suspended in sterile olive oil.--The technic employed was the same as in Experiment 5, except that a culture of staphylococcus was used.

Result: All tubes remained sterile. The germicidal action of chlorlyptus was almost at once in the proportions of 1, 5 and 10 per cent.

Remarks: By repeating this experiment the result showed some variations. The discrepancy was probably due to an imperfect suspension of the micro-organism in the oil.

EXPERIMENT 9.--Germicidal action of carbolic acid on streptococcus suspended in olive oil.--The technic employed was the same as in Experiment 5, except that carbolic acid was used instead of chlorlyptus.

Result: The germicidal action of carbolic acid of streptococcus suspended in olive oil was almost at once in the proportions of 1, 5 and 10.

EXPERIMENT 10.--Germicidal action of chlorlyptus on staphylococcus.--The technic employed was the same as in Experiment 6 except that the carbolic acid was used instead of chlorlyptus.

Result: The germicidal action of carbolic acid on staphylococcus suspended in olive oil was almost at once, in proportions of 1, 5 and 10 per cent.

EXPERIMENT 11.--Germicidal action of chlorlyptus on pyogenic bacteria suspended in pus.--Chlorlyptus was added to sterile pus in the proportions of 1, 5 and 10 per cent., and then inoculated with staphylococcus and cultures were made in bouillon at once, after five minutes, after ten minutes, after fifteen minutes, after thirty minutes, after one hour and after two hours, respectively, and tubes incubated for forty-eight hours at 37 C.

Result: Growth was shown in all tubes except those inoculated from tubes in which chlorlyptus was added in the proportions of 10 per cent. after one hour.

EXPERIMENT 12.--Germicidal action of chlorlyptus on streptococcus suspended in sterile human blood serum.--Staphylococcus culture in agar forty-eight hours old was suspended in sterile human blood serum, and to the suspension chlorlyptus 5 per cent. in paraffin oil was added in the proportions of 1, 5 and 10 per cent. Inoculations were made at intervals, at once, after five minutes, after ten minutes, after fifteen minutes and after one hour in trypsinized bouillon. Tubes were incubated at 37 C. for forty-eight hours.

Result: Chlorlyptus showed inhibitory action on the growth of staphylococcus in the strength of 10 per cent., but did not produce complete sterilization. Similar results were shown with the 5 per cent., and in the 1 per cent. chlorlyptus did not show any inhibitory action at all.

EXPERIMENT 13.--Germicidal action of carbolic acid on staphylococcus suspended in human blood serum (sterile).--The technic employed was the same as in Experiment 10 except that carbolic acid was used instead of chlorlyptus.

Result: Carbolic acid produced a complete sterilization in the strength of 10 per cent. almost at once, and with certainty after five minutes. Similar results were produced with the 5 per cent. The 1 per cent. carbolic acid did not show any appreciable germicidal action on staphylococcus.

EXPERIMENT 14.--Toxic and irritant action of chlorlyptus.--Six normal guinea-pigs were used for the experiment. Guinea-Pig 1 was injected peritoneally with 1 c.c. of chlorlyptus, Guinea-Pig 2 with 2 c.c. of chlorlyptus, Guinea-Pig 3 with 3 c.c. of chlorlyptus, Guinea-Pig 4 with 4 c.c. and Guinea-Pig 5 with 5 c.c. 5 per cent. respectively. Guinea-Pig 6 was used as a control and not injected.

Result: Guinea-Pigs 1 and 2 did not show any appreciable disturbance. Guinea-Pig 3 was sick for four days, after which it gradually recovered but it became sick again after one week and died ten days after the injection. Guinea-Pig 4 died over night. Guinea-Pig 5 died six hours after injection. Guinea-Pig 5 was injected at 11:30 with 5 c.c. chlorlyptus. Ten minutes after the injection it was lying relaxed, respiration and heart normal, conjunctive reflex present. One hour after the injection the animal seemed to present symptoms resembling those of narcosis: respiration and heart were normal. After four hours there was no change in the condition of the guinea-pig except that the respiration was irregular. Five and a half hours after it showed prostration with irregular respiration and heart action. Six hours after injection the animal was dead.

Autopsy: The peritoneum showed a congestion and a fibrinous exudation, amount of liquid increased, some part of which was probably chlorlyptus unabsorbed. Spleen about normal, liver congested, kidney about normal, suprarenal glands about normal, lungs normal, pleural cavity obtained no exudation, heart soft, flabby and congested.

EXPERIMENT 15.--Toxic and irritant action of chlorlyptus when injected into the pleural cavity.--Six normal guinea-pigs used for the experiment. Chlorlyptus was injected in the pleural cavity as follows: Guinea-Pig 1, 0.5 c.c.; Guinea-Pig 2, 1 c.c.; Guinea-Pig 3, 2 c.c.; Guinea-Pig 4, 3 c.c., and Guinea-Pig 5, 4 c.c. Guinea-Pig 6 was used as a control.

Result: Guinea-Pigs 1 and 2 recovered about four hours after injection. Guinea-Pig 3 died three days after and Guinea-Pigs 4 and 5 four and two hours after, respectively.

Conclusions: Guinea-pigs weighing on the average of 400 gm. may be injected peritoneally with one or two c.c. or intrapleurally with 0.5 to 1 c.c. of chlorlyptus without having fatal results from the injection.

EXPERIMENT 16.--Toxic and irritant action of eucalyptus oil.--Three normal guinea-pigs were used for the experiment. Guinea-Pig 1 was injected with 1 c.c. of oil of eucalyptus in the peritoneum, and Guinea-Pig 2 with 0.5 c.c. in the pleural cavity. Guinea-Pig 3 was used as a control.

Result: Guinea-Pig 1 died about three hours after injection, and Guinea-Pig 2 about two hours after the injection.

Autopsy: Both guinea-pigs showed marked congestion and a moderate degree of exudate in the peritoneum.

EXPERIMENT 17.--Toxic and virulent action of eucalyptus.--Three normal guinea-pigs were selected for the experiment, as in Experiment 16. The injection was made in the pleural cavity. Guinea-Pig 1 was injected with 0.5 c.c. and Guinea-Pig 2 with 1 c.c. of eucalyptus oil.

Result: Guinea-Pig 1 died the following day, and Guinea-Pig 2 one hour after the injection.

EXPERIMENT 18.--Toxic and irritant action of dichloramin-T, 0.5 per cent. in chlorcozane.--One guinea-pig was used for each experiment. Guinea-Pig 1 was injected with 0.5 c.c. and Guinea-Pig 2 with 1 c.c. of dichloramin-T peritoneally.

Result: Both animals became restless immediately after the injection, and died twelve hours after of acute hemorrhagic peritonitis.

EXPERIMENT 19.--Effect of chlorlyptus on staphylococcus suspended in salt solution and one of that solution injected into the peritoneum of the guinea-pig.--Three guinea-pigs were used for the experiment. Guinea-Pig 1 was injected with 0.5 c.c. of staphylococcus suspension as control. Guinea-Pig 2 was given the same, and immediately after received 1 c.c. of chlorlyptus. Guinea-Pig 3 was injected with the same amount, and chlorlyptus was injected twenty-four hours after injection.

Results: Guinea-Pig 1 was sick and weak with loss of appetite for some days, but gradually recovered. Guinea-Pig 2 died over night.

Autopsy: There was a large amount of exudate in the peritoneal cavity, irritation of the intestine, and other signs of acute inflammation. A moderate degree of congestion; spleen not enlarged; liver showed cloudy swelling and fibrinous exudate; lungs and heart about normal except for a moderate degree of congestion but no exudate. Guinea-Pig 3 was sick for some days, but recovered gradually one week after.

EXPERIMENT 20.--Effect of chlorlyptus in vivo on staphylococcus.--The experiment was conducted in the same way as in Experiment 17, but 2 c.c. were used instead of 1 c.c.

Result: Guinea-Pig 1 was injected with 2 c.c. staphylococcus suspension and died over night. Autopsy showed that the animal died of acute peritonitis. The peritoneum showed some fibrinous exudate and mesenteric vessels. Guinea-Pig 2 was injected with 2 c.c. of staphylococcus, and eighteen hours after was injected with 1 c.c. of chlorlyptus. The animal died two weeks after injection. Guinea-Pig 3 was injected with 2 c.c. staphylococcus suspension, and twenty-four hours after with 1 c.c. of chlorlyptus. The Guinea-Pig died ten days after. Autopsy revealed bronchopneumonia of the left lung and acute miliary abscess in the liver.

--(From The Journal A. M. A., Nov. 27, 1920, with additions.)

AQUAZONE (OXYGEN WATER)

Report of the Council on Pharmacy and Chemistry

Aquazone is stated by the Aquazone Laboratories, Inc., Los Angeles, California, to be a supersaturated solution of oxygen in water, carrying approximately five and one-half times as much dissolved oxygen as ordinary water. In an advertising booklet, it is suggested that Aquazone is of value in the treatment of influenza, pneumonia, typhoid, Bright’s disease and kindred disorders. It was also stated therein that in the treatment of fevers it lowers the temperature, and that the administration of three bottles of Aquazone (representing 0.033 gm.--1-1/2 grain--of oxygen) is of value for “preventive and tonic purposes.”

The evidence which the Aquazone Laboratories submitted did not show that the effects were other than those which might be obtained from the administration of ordinary potable water. The Council declared Aquazone inadmissible to New and Nonofficial Remedies, because the therapeutic claims made for it were unwarranted, and because its use is irrational for the reason that oxygen given by stomach in this way is of little or no value.--(Abstracted from Reports of Council on Pharmacy and Chemistry, 1920, p. 50.)

COAGULEN-CIBA OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report announcing the deletion of Coagulen-Ciba from New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Coagulen-Ciba, a product of the Society of Chemical Industry, Basle, Switzerland, was admitted to New and Nonofficial Remedies in 1915. It is stated to be an extract prepared from blood platelets and to contain thromboplastic substances (cytozym, thrombokinase, thrombozym) mixed with lactose. Extensive clinical reports appeared to justify its acceptance for New and Nonofficial Remedies with Fibrin Ferments and Thromboplastic substances.

In 1918, Dr. Arthur D. Hirschfelder reported to the Council that of a number of specimens of Coagulen-Ciba examined by him, failed to accelerate the coagulation time of blood.

In view of Dr. Hirschfelder’s findings, the Therapeutic Research Committee of the Council invited Dr. P. J. Hanzlik to undertake an exhaustive investigation of thromboplastic substances, the Council, in the meantime temporarily retaining Coagulen in New and Nonofficial Remedies until the investigation was completed.

The following report on the eligibility of Coagulen-Ciba was made to the Council by Dr. Hanzlik:

Object: To test the claims of thromboplastic and hemostatic activities.

Claims: Coagulen is alleged to be a “physiological styptic prepared from the natural coagulants of animal food contained in the blood platelets. It has the characteristics of a lipoid.” (If cephalin is meant it is difficult to understand why platelets should be selected in preference to other abundantly supplied organs such as brains).

“Coagulen is indicated in all cases of external and internal hemorrhage due to a deficiency of the coagulating power of the blood: epistaxis, hemophilia, hemorrhage from gastric or duodenal ulcer, melaena neonatorum, hemorrhage from the gums, the lungs, the bladder, the uterus, hemorrhage during or after operations (turbinectomy, tonsillectomy). It has also been used as a prophylactic before operations, likely to produce severe hemorrhage.”

“In cases of true hemophilia one application of 5 grains of coagulen usually suffices to control the hemorrhage.” “In gastric and intestinal hemorrhage the internal administration of coagulen will be found effective.” “In bonegrafting, plastic surgery, dentistry and nose and throat surgery the application of a 10 per cent. solution of Coagulen will be found to be of valuable assistance in controlling hemorrhage and oozing.”

“It is a non-toxic and non-irritating powder to which a certain amount of sugar has been added, with a view to ensuring its prompt solution in water or physiological sodium chloride solution.”

Description: “Coagulen is a yellowish granular powder with but slight odor, a sweet taste and is readily soluble in water or a normal salt solution.” The dry Coagulen obtained corresponds to the description claimed. Old specimens show the presence of dark brown particles. Coagulen is marketed in 3 forms: (1) as dry powder containing lactose, which, it is claimed, facilitates solution in water; (2) as 3 per cent. sterile solution in ampoules;[137] (3) tablets.

[137] An ampoule labeled as follows: “Coagulen-Ciba, 20 c.c. in sterile solution ready for use. To be shaken. Importé de Suisse. Op. No. 968” was found to measure only 15 c.c. Another ampoule with the same label and Op. No. 9641 contained considerable sediment.

Methods of Study: The alleged thromboplastic activity was tested by the method of Howell and a modification of this method by Fenger as described in “New and Nonofficial Remedies.” In the Howell method dog or cat blood is used, while beef blood at body temperature is used in Fenger’s method. In other respects the methods are essentially the same. Briefly these consist of noting the acceleration of coagulation time in a mixture of equal parts of serum and the thromboplastic agent to which about an equal part of oxalate plasma is added. Under these conditions cephalin causes clotting in about 1 minute or even less as compared with 20 to 30 minutes or more of the control.

The effects were compared with freshly prepared cephalin and other thromboplastic agents, using saline (0.9 per cent. NaCl) as control. The effect of different concentrations was also studied.

The literature of the manufacturers claims that Coagulen is harmless. This was tested by making intravenous and subcutaneous injections into guinea-pigs, using saline and cephalin as controls.

Bloods of 4 different species were used, namely, cat, dog, beef and human. Dog’s peptonized blood and plasma were also tried.

The 15 different tests that were made in vitro were carried out with 3 different samples of fresh dry Coagulen (from manufacturer), 2 old samples (one from Council on Pharmacy and Chemistry and one of our own), 3 fresh specimens of sterile solution in ampoules (from manufacturer), one old specimen and 4 small ampoules (Council on Pharmacy and Chemistry).

The tablets were not tested since these are made from dry Coagulen and the results would hardly be expected to show anything different.

Results: The results obtained may be briefly summarized as follows: (1) 0.1 per cent. to 5 per cent. Coagulen did not accelerate the coagulation time of blood and oxalate plasmas in the majority of tests any more than the controls of saline, while 0.1 per cent. cephalin was found to shorten the coagulation time from 1/3 to 1/2.

(2) There was no difference between the behavior of old and fresh specimens.

(3) No acceleration of coagulation in vitro was observed even with the highest concentrations tried, namely 25 and 50 per cent.

(4) Irrigations made with fresh dry coagulen in solution and sterile solution in ampoules on superficial bleeding from the foot-pads of 3 normal and peptonized dogs and local application to hemorrhages from dissected femoral arteries and bone and liver wounds of 3 dogs showed that coagulen was no more active than normal saline.

Toxicity: Subcutaneous and intravenous injections of different doses of Coagulen solutions (fresh ampoules) and dry Coagulen in solution in 8 guinea-pigs produced definite anaphylactoid symptoms with injury to the circulatory and respiratory systems as indicated by cardiac dilatation, abdominal congestion and pulmonary hemorrhages, congestion, distention and sometimes thrombi. On the other hand, the control animals injected with saline and cephalin remained practically unharmed.

Conclusions: The results obtained justify the following conclusions:

(1) Coagulen is entirely inactive as a thromboplastic and hemostatic agent.

(2) Coagulen is distinctly injurious when injected systemically.

(3) The claims of hemostatic efficiency and harmlessness for Coagulen by the manufacturer appear exaggerated and unjustified.

Recommendations: Because of its uncertain composition, the possible dangers when injected systemically, and its inactivity as a thromboplastic and hemostatic agent when tested by several different methods, Coagulen merits no recognition as a therapeutic agent for inclusion in New and Nonofficial Remedies.

The detail evidences used as the basis of this brief report concerning Coagulen will be published shortly in the Journal of Pharmacology,[138] together with the results with other thromboplastic agents.

[138] Since the report was sent to the manufacturers, the results have been published. Hanzlik, P. J., and Weidenthal, C. M., Plasma and Blood Clotting Efficiency of Thromboplastic Agents in Vitro and their Stability, J. Pharmacol. and Exper. Therap. =14=:157 (October) 1919; Hanzlik, P. J., Karsner, H. T., and Fetterman, J., Anaphylactoid Conditions, J. Pharmacol. and Exper. Therap. =14=:189 (Oct.) 1919; Hanzlik, P. J., Karsner, H. T., and Fetterman, F., Anaphylactoid Phenomena from Thromboplastic Agents, J. Pharmacol. and Exper. Therap. =14=:229 (Nov.) 1919.

The preceding report was sent to the American agent for the Society of Chemical Industry, Sept. 8, 1919.

In reply the American agent, Ciba Co., Inc., on March 22, 1920, sent the Council “some additional clinical reports on the use of Coagulen-Ciba in the treatment of Hemorrhages supporting our claims of the merits of Coagulen-Ciba.”

The material submitted by the Ciba Co., contains no objective evidence for or against the efficiency of Coagulen-Ciba but merely opinions. As a rule these opinions are favorable though conditional and hedging and quite unconvincing. Nothing was submitted to offset or challenge the findings of Dr. Hanzlik’s report.

Since the evidence indicates that Coagulen-Ciba has little, if any, efficacy as a hemostatic, the Council directed its omission from New and Nonofficial Remedies.--(From Reports of Council on Pharmacy and Chemistry, 1920, p. 53.)

FERRIC CACODYLATE OMITTED FROM NEW AND NONOFFICIAL REMEDIES

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the report which appears below, explaining the omission of ferric cacodylate from New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Iron cacodylate, the ferric salt of cacodylic acid, was admitted to New and Nonofficial Remedies in 1917. It is required to contain from 39.7 to 44.9 per cent. of arsenic (As).

The following statement of the action, uses and dosage of iron cacodylate appears in the 1920 edition of New and Nonofficial Remedies:

“Actions and Uses.--Ferric Cacodylate has the properties of iron salts and of arsenic. Its use has been proposed in conditions in which the effects of iron and the mild arsenic action of cacodylates is desired.

“Dosage.--from 0.015 to 0.1 Gm. (1/4 to 1-1/2 grains).”

The period for which the iron cacodylate preparations now in New and Nonofficial Remedies were accepted coming to an end with the close of 1920, the Council decided to determine if sufficient evidence for the value of ferric cacodylate has accumulated to warrant its continued recognition. The following is the report of the referee of the Committee on Therapeutics to whom the matter was assigned:

“As far as the Referee knows, the only claim that Iron Cacodylate has as a therapeutic agent is that it forms a convenient method for the administration of Iron and Cacodylate (while there is no reason why a drug should not be given by mouth, usually intramuscularly, and apparently it has recently been given intravenously). The effects to be expected from its use are those of iron and arsenic.

“Granted that iron and arsenic are valuable therapeutic agents, Iron Cacodylate is not a satisfactory preparation in which to administer these drugs for the following reasons:

“1. It would appear that Cacodylates are not the best form in which to administer arsenic. Cacodylates in therapeutic doses exert but a feeble action. Small quantities may be reduced to cacodyl (CH₂)₄As₂, and varying amounts to inorganic arsenic. The amount transformed to arsenic is apparently unknown and probably varies in different individuals. On these grounds alone the use of the cacodylates where an arsenic effect is desired seems dubious.

“2. The amounts of iron and cacodylates contained in the doses recommended are small when compared with the usual doses of either iron or cacodylate. The amount of iron in the Iron Cacodylate preparations is small, about .0036 gram per dose, while the preparations admitted to ‘Useful Drugs’ contain much larger amounts per dose recommended. The list follows:

Massa Ferri Carbonates Fe per dose .042 gm. Pilulae Ferri Carbonates " .058 gm. Tinctura Ferri Chloride " .022 gm. Ferri et Ammonii Citrae " .042 gm.

“The approximate amount of arsenic in Iron Cacodylate in the commonly recommended doses varies from .012 gm. to 0.024 gm., while the amount of arsenic in Sodium Cacodylate in the recommended doses varies between .021 and .35 gms. It would seem that a much more rational method of administration of these two drugs would be separately, in which case a better control over the dosage is possible.

“3. The Referee has been unable to secure reliable clinical evidence that Iron Cacodylate is a serviceable preparation. A search of the available literature for the past fifteen years has been made, also Drs. Edsall, Longcope, Stengel, Hoover, Phillips and Miller have been consulted. These physicians know nothing of its use.

“4. In view of the above, it appears to the Referee that Iron Cacodylate is an irrational and useless method of the administration of iron and arsenic.”

The Council adopted the report of the referee and directed that iron cacodylate be omitted from the 1921 edition of New and Nonofficial Remedies.--(From Reports of Council on Pharmacy and Chemistry, 1920, p. 62.)

LIBRADOL

Report of the Council on Pharmacy and Chemistry

The Council has authorized for publication the following report which explains why Libradol was found ineligible for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Libradol is manufactured by Lloyd Bros., Cincinnati. According to a circular (a “readily removable” label) which accompanies the trade package, its “uses” are: “In colds, croup and acute bronchitis. In local congestions; in lung trouble, in acute inflammations of this or any other organ, especially if pain or soreness be present. In lumbago, sciatica, or in rheumatic pains of the joints or muscles. Applied to the forehead, it induces sleep.”

Libradol is offered in two forms, “Libradol Mild” for infants and supersensitive persons which is said to be “destitute of drug energy” and Libradol “Regular” which is “highly medicated,” the “constituents” being “DRACONTIUM, SANGUINARIA, CEPHAELIS, MELALEUCA, LOBELIA, LAURUS, CAPSICUM, TOBACCO.”

According to a circular, “The sanitary plasma Libradol” is a “homogeneous, highly medicated, and exceedingly potent compound, in plastic form,” which “carries the energies of its drug constituents and the high antiseptic qualities of Laurus Camphora and Melaleuca.” It is stated: “The Drug Influence of Libradol is necessarily different from that of any known single member of the Materia Medica. But yet, no mystery either in medicine or of pharmacy is claimed as a part of its composition or process of manufacture. It is a thing peculiar to itself, the result of the study of the drugs from which it is derived and compounded. These drugs may be studied at leisure by whoever cares to do so....”

The following information bearing on the composition of Libradol was furnished by Lloyd Brothers in response to a request from the Council to aid in the consideration of the preparation:

“‘Compound Lobelia Powder’ has been, since 1852, official in the American Dispensatory, in the first edition of which (1852) its formula is given, as follows:

“‘Take of Lobelia, in powder, twelve ounces; Bloodroot and Skunk Cabbage, in powder, of each, six ounces; Ipecacuanha, eight ounces; Capsicus, in powder, two ounces. Mix them.’

“This preparation came increasingly into demand with the Eclectic profession, the principal use for which it was first employed (as an emetic), being finally displaced by its local application in bronchial pneumonia troubles, when sprinkled on a greased cloth and applied to the chest.”

“In 1898, Dr. Finley Ellingwood petitioned Lloyd Brothers to make for him, in plasma form, ready for application, a compound carrying the ingredients of the old ‘Compound Lobelia Powder,’ strengthened by the addition of Melaleuca leucadendron, Laurus camphora and Nicotiana tabacum. Experiments not very encouraging in a pharmaceutical sense were made, and it was not until repeated requests had been made that a product was at last satisfactorily prepared and forwarded to Dr. Ellingwood (1900), with no thought other than that of serving him personally in his practice. This product he used and commended to his professional friends, and under his commendation it came into professional demand.”

An examination of the information submitted by Lloyd Brothers showed Libradol to be in conflict with the principles and rules that govern in the acceptance of articles for New and Nonofficial Remedies as follows:

Composition (Rule 1).--The information which has been received gives little idea of the actual composition of the preparation; for example, the statement that Libradol “carries the energies of its drug constituents and the high antiseptic qualities of Laurus Camphora and Melaleuca” gives no indication as to the part or parts of the Laurus Camphora or Melaleuca employed. If the statement is correct, that Libradol “is a homogeneous, highly medicated, and exceedingly potent compound,” it is essential that the several potent ingredients be stated clearly and not merely hinted at by their qualities. Other conflicts with Rule 1 might be enumerated, but the foregoing citations state the direct conflict; and this has not been removed, although an inquiry was sent to Lloyd Brothers for a statement of the amount of each potent ingredient in a given quantity of Libradol.

Indirect Advertising (Rule 4).--The recommendation for the use of Libradol in the treatment of colds, bronchitis, lumbago, sciatica and rheumatic pains, which accompanies the trade package, is prone to lead the public to depend on it in cases where definite treatment is imperative.

Unwarranted Therapeutic Claims (Rule 6).--Libradol is recommended in a great variety of conditions and is especially claimed not only to relieve pain, but to remove the cause of pain. This is explained as follows: “In the study of the physiological action of many drugs, it was found that the constituent remedies in this combination exercised a most salutary influence, not only upon the sensibility of the nerves involved, but upon the capillary circulation within the diseased area, the muscular structures therein included, and, subsequently, upon the course of the advancement of the congestive and inflammatory processes, and upon secretion, exudation, adhesion, induration, hypertrophy, suppuration and excretion.”

Granting, for the sake of argument, that carefully controlled experimental clinical evidence were available to substantiate this statement with reference to a single case of pain, the statement would be misleading when considered as a general explanation of the preparation’s relieving pain by removing the cause of pain when taken in connection with the conditions for which it is recommended and in which pain is even a minor symptom. Still, if pain were relieved in these cases by removing the cause, the patient would be cured of the conditions which give rise to the pain, and these include: “Acute pain in the chest;... acute inflammation in the chest;... persistent local pain;...” (This might be interpreted as including tuberculosis; pneumonia; cancer, and appendicitis.) “lumbago; sciatica; articular rheumatism” (gonorrheal infections?).

Name (Rule 8).--The name, derived from Dolar and Liber, suggests the claimed action of the preparation (the relief of pain) rather than the drugs said to be presented by it.

Irrational Composition (Rule 10).--It is quite possible that Libradol will relieve pain in certain instances and that the drug constituents present in Libradol “Regular” make this more effective than “Libradol Mild” which is “destitute of drug energy”; this, however, is no justification for the use by physicians of a cataplasm containing or made from skunk cabbage, bloodroot, ipecac, melaleuca (oil of cajeput?), lobelia, laurus comphora (camphor?), capsicum and tobacco. The combination is thoroughly irrational and a reminder of a past century. Further, the Council knows of no evidence to support the following claims:

“As a stimulant Capsicum has the power of neutralizing depressant remedies like Lobelia and Tobacco.”

“Our association of its desirable constituents with those of Lobelia, in connection with the modifying influence of Capsicum, Melaleuca, and Laurus Camphora, permits a more free use in Libradol than would be possible were it to be employed alone.”

“Capsicum, Melaleuca, and Laurus Camphora in Libradol tend to counteract the excessive relaxative and depressant effects of Lobelia.”

“The great value of Melaleuca in Libradol is its quality of modifying and controlling the action of the associated energetic constituents of the drugs Tobacco and Lobelia, which reduce congestion and inflammation, but which would, unsupported, be too depressant.”

Libradol is inadmissible to New and Nonofficial Remedies because its composition is complex, irrational and semi-secret, and because its name and the unwarranted therapeutic recommendations made for it will lead to its ill-advised use.--(From Reports of Council on Pharmacy and Chemistry, 1920, p. 65.)

HELMITOL OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Helmitol is hexamethylenamin methylencitrate. It was introduced with the claim that it was superior to hexamethylenamin--which acts in acid fluids only--in that it is equally efficient whether the urine is alkaline or acid.

In 1918 The Bayer Company, which then marketed the product in the United States, was notified that the Council questioned the claims made for Helmitol and desired evidence to substantiate them. In 1919 the same notification was sent the Winthrop Chemical Company, which in the meantime had secured control of the product. Pending the submission of the evidence, the Council continued the acceptance of Helmitol for New and Nonofficial Remedies with the statement that the actions and uses of hexamethylenamin anhydromethylencitrate were those of hexamethylenamin.

W. A. Puckner, Secretary.

The following report on Helmitol was made by the referee in charge of hexamethylenamin compounds and preparations, adopted by the Council and sent the Winthrop Chemical Company:

“Helmitol is a compound of anhydromethylencitric acid and hexamethylenamin. It was introduced with the claim that it would be antiseptic even in alkaline urine. The Council did not entirely trust the evidence, but continued to list Helmitol in N. N. R., merely as a salt of hexamethylenamin, until satisfactory data should become available. These have now been furnished by Hanzlik (Journal of Urology =4=:145) who has shown that:

“1. The alkalinity required to split off formaldehyd from anhydromethylencitric acid is greater than exists in the urine, even in advanced ammoniacal fermentation.

“2. Even if any formaldehyd were liberated in ammoniacal fermentation, it would at once become inactive by combining with ammonia.

“3. Urine after the administration of anhydromethylencitric acid actually putrefies readily.

“4. Less than 5 per cent. of the anhydromethylencitric radical reaches the urine, the remainder being destroyed in the body.

“The only reason for the existence of Helmitol was this claim of antiseptic action in alkaline and putrefying urines. Since this has been disproved, there remains no reason for retaining Helmitol in N. N. R.; on the contrary, its retention would only tend to continue the fallacy on which it is based.

“It is, therefore, recommended that Helmitol be no longer listed with New and Nonofficial Remedies, and that this report be published, after the usual submission to the manufacturers.”

In accordance with the recommendation of the report, the Council has directed the omission of Helmitol from New and Nonofficial Remedies and has authorized the publication of this report.--(From The Journal A. M. A., Jan. 22, 1921.)

SPIROCIDE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

“Spirocide” (The Spirocide Corporation of New York) is advertised as a new and successful treatment of syphilis by fumigation and inhalation. According to the information presented to the Council, Spirocide is a mechanical mixture of metallic mercury 25 per cent., copper sulphate 25 per cent., cypress cones 20 per cent., henna 20 per cent., nut gall 5 per cent., and dried pomegranate 5 per cent. It is supplied in the form of greenish-gray tablets weighing about 10 gm. each, and containing, therefore, about 2.5 gm. (about 38 grains) of mercury. It is sold in packages of six tablets.

The following directions for its use are contained in a pamphlet recently distributed:

“Spirocide is administered by means of fumigation and inhalation. The patient is disrobed to the waist and placed in a light chair, preferably with arms. A pastil or tablet of Spirocide is placed on a small plate, or open receptacle, after being ignited by holding in a gas or alcohol flame for a minute or so until it begins to smoulder. The plate with the burning Spirocide is then placed on the floor between the patient’s feet or just under the chair. A small shelf or platform between the lower rounds of the chair is an excellent location for the plate containing the burning mass. When all is in position a sheet should be thrown over the patient and arranged to enclose the whole. The patient should breathe naturally and inhale the vapor, which will rise and fill the canopy surrounding him. The treatment will require 15 to 30 minutes, or until the Spirocide is burned up. The patient may complain at first of a slight choking sensation, and there may be some tendency to cough. This can be removed by raising the sheet long enough to let in a little clear air. The eyes should be closed or lightly bandaged to avoid smarting.”

Experiments conducted in the A. M. A. Chemical Laboratory show that Spirocide, when ignited, burns slowly with consequent volatilization of mercury. The several organic constituents serve as fuel and the copper sulphate possibly acts as a regulator of the combustion. During the burning process the cypress cones, henna, etc., are consumed but most, if not all, the copper remains behind, the mercury only being vaporized. It is asserted in the advertising pamphlet that Spirocide is indicated in all stages of syphilis, primary, secondary and tertiary, and in all its complications or sequelae. In these varying conditions one tablet daily or every other day is recommended until six treatments have been taken, though it is stated that “occasionally, depending on the severity or the duration of the disease, it may be wise to give nine treatments, the last three at intervals of two, three or more days.”

Some of the results which it is claimed are obtained with Spirocide are:

“At the completion of this course of treatment with Spirocide, all signs or evidences of syphilis are removed, and in ten days to three months all Wassermann tests prove negative. Any further treatments than the original course of fumigations are rarely needed. Wassermann’s will be found uniformly negative after a period which, according to the patient, may vary from ten days to three months. These results have been obtained in cases in which Salvarsan and kindred preparations have been employed without the slightest benefit.”

In a letter to the Council the “scientific observer” of the Spirocide Corporation declared:

“We do not claim that the vaporization method is new. We do claim, however, that this combination of mercury produces more rapid volatilization, certain absorption and undoubted effect than any form of mercury administered by any method known to science without the usual danger. That this is so we are willing to prove by comparison with other methods both by ourselves and many observers scattered over the United States....”

To determine the validity of the claims made for Spirocide, the Corporation was asked to present the evidence which it offered. In reply, the corporation’s “scientific observer,” Dr. J. Lewengood, submitted 83 case reports from a number of different observers, including those from military hospitals and a state institution, and also a reprint of an article published by him in the New York Medical Journal, Feb. 21, 1920, wherein were reported eight cases which received “Spirocide Treatment.” In no case were controls with other methods of mercury administration carried out.

This material the Council sent to two recognized syphilographers for an opinion. One of the consultants reported that of the 83 cases, 20 dealt with patients who had also received arsphenamin medication and, therefore, these 20 cases could not be considered as evidence concerning the value of Spirocide. As to the remaining cases, he found on the whole that the history and data furnished were far from sufficient to warrant the claims made. In many of the cases emphasis was laid on the Wassermann test, as though this test were the only thing to be considered in a case of syphilis. He pointed out that in one case the reaction changed from negative to strongly positive after six treatments and that in several cases the phenomena reported cannot be explained by anything else than a desire to get a negative blood test. For example, one case had Spirocide treatment and a Wassermann, 1 plus, 55 days after; the author then reports that 19 days later the reaction had become negative and, therefore, the change must be due to Spirocide. In several of the cases reported it is even questionable if the patients were syphilitic. The consultant concluded that the evidence submitted by the Spirocide Corporation failed to prove the claims made for Spirocide. He pointed out on the other hand that patients readily become salivated from the use of Spirocide, often after 8 or 10 treatments.

The second consultant replied that in his opinion the claim that Spirocide produces more “undoubted effect than any form of mercury administered by any method known to science without the usual danger,” was not substantiated. He believed that it was not as effective as some other methods, that the dosage is not as exact, and, therefore, it is not as free from danger when the drug is pushed.

The Council’s two consultants were also asked whether or not, in their opinion, the administration of mercury by inhalation is a method which the Council should endorse to the extent of recognizing a preparation based on this principle. This inquiry was also sent to the members of the editorial board of the Archives of Dermatology and Syphilology. Five replies were received. One advised a thorough study of the different methods of administering mercury by inhalation. The other four were opposed to such recognition on the ground that as the dosage is not exact the effects, therefore, are not certain.

In consideration of the opinions expressed by its consultants, the Council declared Spirocide inadmissible to New and Nonofficial Remedies because (1) the claims made for it are unproved and unwarranted, (2) the routine use of an inexact method for the administration of mercury is detrimental to sound therapy and (3) the name is not descriptive of its composition, thus failing to remind the physician who uses these pastils that he is administering metallic mercury.--(From The Journal A. M. A., Jan. 22, 1921.)

DIGIFOLIN-CIBA NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized the publication of the following report, declaring Digifolin-Ciba inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Digifolin-Ciba is a product of the Society of Chemical Industry of Basle, Switzerland. It is marketed in the United States by the Ciba Company, 91 Barclay Street, New York City. It is claimed that Digifolin-Ciba is “a preparation of digitalis leaves that has been freed from the useless and harmful principles such as Digitonin (saponin), coloring and inert matter, etc., but does contain all the really valuable, therapeutically active constituents of the leaves, namely: digitoxin and digitalein in their natural proportions.” There is no evidence that digifolin contains all of the glucosides of digitalis as they exist in the leaf, and it is extremely improbable that this is the case because one cannot remove saponin without altering the other active principles of digitalis.

The Ciba Company sends out the following pamphlets relating to Digifolin:

“‘Concerning Digifolin-Ciba, A New Preparation of Digitalis,’ by C. Hartung, M.D., Ph.D. Extracts from the work ‘Ueber Digifolin, Ein Neues Digitalis-Praeparat’ in the Munich Medical Weekly, No. 36, page 1944, 1912.”

“‘Digitoxin Contents of Digifolin-Ciba,’ by C. Hartung, M.D., Ph.D., Basle, Switzerland. Reprints from the Pharmaceutical Post, 1913. No. 34, page 357. No. 40, page 431.”

“‘Pharmacological Tests of Digitalis,’ by M. J. Chevalier, Chef Des Travaux Pratiques de Pharmacologie et Matiere Medicale, Faculte De Medecine De Paris. Report Presented to the Societe de Therapeutique at Their Meeting, May 28, 1913.”

In the reprint “Concerning Digifolin, ‘Ciba.’” Hartung lays stress on the presence of harmful and inert substances present in the leaf and galenical preparations with the direct or implied statement that digifolin has an advantage in that these are absent from it. This is misleading. It is true that Boehm whom Hartung cites, found saponin to be irritating, but Boehm states that it required 100 mg. per kilogram of body weight to induce vomiting after its oral administration. Furthermore, saponin is present in traces only in infusion of digitalis, so that the therapeutic dose contains a wholly negligible amount of it.

The following occurs in “Pharmacological Tests of Digitalis,” by M. J. Chevalier:

“Hartung’s Digifolin merits our attention, especially because it seems to possess all the pharmacodynamic properties of galenic preparations of digitalis without showing any of their disadvantages.”

This claim scarcely needs comment, since it is well established that the chief “disadvantages” of digitalis are inherent in the principles which produce the desired effects of digitalis and may be avoided to a large extent by a carefully regulated dosage of any digitalis preparation. In short, the advertising for Digifolin asserts that this digitalis preparation has all the advantages of digitalis itself, but none of its disadvantages. This claim has been refuted so frequently that manufacturers must be aware that it is untenable. Further the claims now made for Digifolin are essentially those made nearly four years ago at which time the attention of the American agent was called to their unwarranted character.

The Council declared Digifolin-Ciba inadmissible to New and Nonofficial Remedies because the therapeutic claims advanced for it are misleading and unwarranted.--(From The Journal A. M. A., April 2, 1921.)

SOME OF LOESER’S INTRAVENOUS SOLUTIONS

Report of the Council on Pharmacy and Chemistry

The Council has authorized the publication of the following report on “Loeser’s Intravenous Solution of Hexamethylenamin,” “Loeser’s Intravenous Solution of Hexamethylenamin and Sodium Iodid,” “Loeser’s Intravenous Solution of Sodium Salicylate,” “Loeser’s Intravenous Solution of Salicylate and Iodid,” “Loeser’s Intravenous Solution of Sodium Iodid” and “Loeser’s Intravenous Solution of Mercury Bichlorid,” put out by the New York Intravenous Laboratory, Inc.

W. A. Puckner, Secretary.

The intravenous solutions of “Hexamethylenamin,” “Hexamethylenamin and Sodium Iodid,” “Sodium Salicylate,” “Sodium Salicylate and Sodium Iodid,” “Sodium Iodid” and “Mercuric Chlorid” marketed by the New York Intravenous Laboratory, Inc., are solutions of official substances sold under their official names. They would, therefore, be outside the scope of the Council, were it not that special and general therapeutic claims are made for them. Such special claims, for instance, are contained in an advertisement in the Illinois Medical Journal for Oct. 20, 1920, which gives, under the various drugs, a list of diseases in which the drugs are said to be “indicated.” The Council is unable to agree with some of these recommendations. The fundamental objection, however, is the general claim of superiority and safety of the intravenous method.

The intravenous solutions named above would naturally have little sale if such special claims were not made for them. While the claims may not be made directly, they are carried by such display phrases as “For the progressive physician seeking improved clinical results” and “A safe practical office technique.”

The Council continues to hold that intravenous medication, generally, is not as safe as oral medication even with relatively harmless substances (a fact again illustrated by the results of Hanzlik and Karsner, 1920, Journal Pharmacology and Experimental Therapeutics, 14, 379), and that it does not give “improved clinical results” except under rather narrowly confined circumstances--namely, if the drug undergoes decomposition in the alimentary tract, if it is not absorbed, if it causes serious direct local reaction or if time is an urgent element. Each intravenous preparation for which advantage over oral administration is claimed, directly or by implication, must be examined from these points of view.

The Council has recognized intravenous preparations which satisfied these requirements. It is evident, however, that hexamethylenamin, sodium iodid and sodium salicylate do not. When given orally they do not undergo material decomposition in the digestive tract, they are rapidly absorbed, they cause no direct local reaction, and in the conditions in which they are used the hour or so which is required for absorption is immaterial, especially as they are used continuously for some time. Mercuric chlorid does indeed produce some local irritation, but there is as yet no convincing evidence that its intravenous injection causes less injury than oral administration. More experience under controlled conditions is needed before the intravenous use of mercuric chlorid can be approved. Especially objectionable are the fixed proportion mixtures of sodium iodid with sodium salicylate and with hexamethylenamin. The dosage of all three drugs has to be adapted to individual conditions. This is impossible when giving them in fixed proportions.

The Council voted not to accept “Loeser’s Intravenous Solution of Hexamethylenamin,” “Loeser’s Intravenous Solution of Hexamethylenamin and Sodium Iodid,” “Loeser’s Intravenous Solution of Sodium Salicylate,” “Loeser’s Intravenous Solution of Salicylate and Iodid,” “Loeser’s Intravenous Solution Sodium Iodid” and “Loeser’s Intravenous Solution of Mercury Bichlorid” for New and Nonofficial Remedies because they are sold under misleading claims regarding their alleged safety and efficiency. In view of this fundamental objection the individual claims for each preparation were not passed on.--(From The Journal A. M. A., April 16, 1921.)

“NATIONAL IODINE SOLUTION” NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

“National Iodine Solution” is a proprietary sold by the National Drug Co., Philadelphia, Pa. From inquiries received by the Council on Pharmacy and Chemistry it is evident that the product is extensively brought to the attention of physicians by means of circulars. The name implies that it is a solution of iodin and the inference is given that it has the advantages of iodin without the disadvantages.

COMPOSITION

In view of the foregoing, the Council took up the investigation of “National Iodine Solution,” and in turn asked the A. M. A. Chemical Laboratory to analyze it. The chemist’s report follows:

According to the label of National Iodine Solution, “each fluidounce represents three grains Proteo-albuminoid compound of iodin (National)”; also an alcohol declaration of 7 per cent. is made. Otherwise no information is given as to the composition either of the “solution” or of “Proteo-albuminoid compound of Iodine.”

Each bottle contained about 115 c.c. (nearly 4 ounces) of a yellowish solution, acid in reaction, having an odor resembling witch hazel; its specific gravity at 25 C. was 0.9860. Qualitative tests indicated the presence of zinc, alcohol, sulphate, an iodin compound (the solution gave tests which indicated a very small amount of free iodin; most of the iodin was in the form of ordinary iodid), a small amount of vegetable extractives, and traces of aluminum and potassium. If any protein was present, it was in amounts too small to be identified, though a small amount of a nitrogenous compound was present. The amount of solids in “National Iodine Solution” was equivalent to 0.72 per cent, and the amount of ash, to 0.2 per cent. Quantitative estimations yielded the following:

Alcohol (by volume) 7.0 per cent. Zinc (Zn++) 0.096 per cent. Iodin (free and combined) 0.029 per cent. Sulphate (SO₄--) 0.146 per cent. Protein (N × 6.36) 0.012 per cent.

The above findings indicate that each 100 c.c. contains about 7 c.c. of alcohol, 0.5 gram of zinc sulphate U. S. P. (ZnSO₄+7H₂O.), 0.03 gram of iodin, 0.01 gram of protein (calculated as such from nitrogen times the factor 6.36) and some hamamelis water. Expressed in equivalent apothecary terms, each fluidounce contains essentially:

Zinc sulphate 2-1/3 grains Iodin (free and combined) 1/8 grain Protein 1/25 grain Alcohol 34 minims

This amount of alcohol is equivalent to about 3-1/2 fluidrams of witch hazel water. Although the label states that each fluidounce contains three grains of “proteo-albuminoid compound of iodine,” yet the sum of the protein (calculated from nitrogen content) and iodin components is equivalent to less than 1/5 grain.

“National Iodine Solution” appears to be very similar to “Gonocol” (The National Drug Co., Philadelphia, Pa.), which was analyzed by the Bureau of Chemistry of the U. S. Department of Agriculture. The bureau stated that “it [Gonocol] consisted essentially of an aqueous solution of zinc sulphate, hamamelis water, a small amount of alcohol, 0.38 grain of iodin, and 0.36 grain of protein per fluidounce.”

It is evident that “National Iodine Solution” is not a solution of free elementary iodin as the name suggests; instead it appears to be a solution of zinc sulphate in witch hazel water containing less than 0.03 per cent. of combined iodin and not more than a trace of free iodin. “National Iodine Solution” is one more to be added to that already long list of proprietaries which makes capital of the high esteem in which physicians hold iodin.

THE CLAIMS

An advertising circular sent to physicians begins:

“Dear Doctor: We beg to suggest a line of treatment while using National Iodine Solution which our many years of experience has proven to us to give the best and quickest results in the treatment of inflammation of the urethral tract ...”

In it are given directions for the treatment of “acute gonorrhea, male,” “anterior urethritis,” “anterior-posterior urethritis,” “ardor urinæ and chordee,” etc., by means of National Iodine Solution and other proprietaries of the National Drug Company’s make. In fact the solution is claimed to be “Indicated in All Conditions of Urethra Accompanied by a Discharge.”

COMMENT AND CONCLUSIONS

The therapeutic claims made for “National Iodine Solution” are unwarranted. Such a solution is not indicated in all conditions of the urethra accompanied by discharge. The advice contained in the circular is equivalent to mail-order treatment of gonorrhea.

It is of interest to note that the claims for an identical or a similar solution prepared by the National Drug Company as a treatment for gonorrhea and intended for use by the laity, has been adjudged misbranded by the federal authorities (Notice of Judgment No. 8150, issued Jan. 25, 1921) in that it misled and deceived the purchaser or purchasers thereof in the statements regarding the therapeutic or curative effects of the article, which falsely and fraudulently represent it to be indicated in all conditions of the urethra accompanied with a discharge, “whereas in truth and in fact it was not.”

The Council would emphasize that if physicians give heed to advertising such as that sent out by the National Drug Company for this preparation the medical profession cannot with good grace protest against the routine treatment of venereal diseases by quacks and “patent medicine” venders.--(From The Journal A. M. A., June 4, 1921.)

MON-ARSONE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Mon-Arsone is offered by the Harmer Laboratories Company as “a new and non-toxic arsenical for the treatment of syphilis.” In the advertisements for Mon-Arsone it has been claimed that with this drug “the toxic, corrosive and uncertain reactions attending the use of arsphenamine have been entirely eliminated” and that “it has a therapeutic value equal to arsphenamine, but extensive case reports fail to record the slightest toxic reaction following its use.”

According to the manufacturers, Mons-Arsone is disodiumethylarsonate, the sodium salt of ethylarsonic acid, derived from arsenic acid by replacement of one hydroxyl group by the ethyl group--AsO(CH₂CH₃)(OH)₂. Mons-Arsone is related to sodium cacodylate, which is the sodium salt of dimethyl-arsenic acid--AsO(CH₃)₂OH--derived from arsenic acid by replacement of two hydroxyl groups by two methyl groups. Ethylarsonic acid and its potassium salt were described by La Coste[139] more than thirty-five years ago, and the use of the sodium salt of methylarsonic acid was proposed in France some years ago. The Harmer Laboratories Company claims originality for Mons-Arsone in that it was the first to prepare the sodium salt of ethylarsonic acid and to propose its therapeutic use.

[139] La Coste: Annalen der Chemie (Liebig’s) 208: 34.

It was reported several years ago by Castelli[140] that sodium cacodylate and the sodium salt of methyl arsenic acid were devoid of effect on experimental trypanosomiasis and spirochete infections. Careful clinical observations in this country by H. J. Nichols[141] and H. N. Cole[142] have demonstrated the inefficacy of sodium cacodylate in the treatment of human syphilis.

[140] Castelli, G.: Arch. f. Schiffs- u. Tropen-Hyg. 16: 605, 1912.

[141] Nichols, H. J.: Salvarsan and Sodium Cacodylate, J. A. M. A. 56: 492 (Feb. 18) 1911.

[142] Cole, H. N.: A Study of Sodium Cacodylate in the Treatment of Syphilis, J. A. M. A. 67: 2012 (Dec. 30) 1916.

Animal experiments carried out in the U. S. Hygienic Laboratory by Voegtlin and Smith[143] show that Mon-Arsone is devoid of any practical trypanocidal action. Thus the “therapeutic ratio” (the ratio of the minimal effective dose to the lethal dose) was about 1, that is, it was effective therapeutically only in approximately fatal doses; the therapeutic ratio for arsphenamine in similar conditions was 17, and that of neoarsphenamine, 28.

[143] Voegtlin, Carl, and Smith, H. W.: J. Pharmacol. and Exper. Therap. 16: 449, 1921.

The findings that sodium dimethylarsenate (sodium cacodylate), sodium methylarsenate, and sodium ethylarsenate are devoid of any practical trypanocidal action and the conclusion that sodium cacodylate is inefficient in the treatment of human syphilis does not prove that Mon-Arsone is without effect on the disease. These findings, however, certainly demand convincing therapeutic evidence to warrant the recommendation for the use of the drug in the treatment of syphilis--particularly because the drug is proposed as a substitute for arsphenamine, the value of which is established.

When the Council first took up the consideration of Mon-Arsone, the only evidence for the claim that it “has a therapeutic value at least equal to that of arsphenamine” consisted, with one exception, of reports from those who had experimented with the drug for the Harmer Laboratories Company, including a report by B. L. Wright, L. A. Kennell, and L. M. Hussey,[144] the latter of the Harmer Laboratories Company. These reports appeared to show that the administration of Mon-Arsone caused less reaction than arsphenamine, and that the immediate effects, judged by clinical symptoms and the response to the Wassermann test, appeared to be good. These trials extended over too short a period of time to permit judgment as to the permanence of the results. A report by an independent observer seemed to indicate that Mon-Arsone does not have the sterilizing action on syphilitic lesions which it is usually believed arsphenamine exercises.

[144] Wright, B. L.; Kennell, L. A., and Hussey, L. M.: M. Rec. 97: 607 (April 10) 1920.

After examining the available evidence, the Council advised the Harmer Laboratories Company that the claim that Mon-Arsone has a therapeutic value equal to arsphenamine appeared unwarranted; that, in the opinion of the Council, Mon-Arsone should not be used except under conditions that justify the experimental trial of an unproved drug, and should not be used in a routine way until the permanence of its effects has been established; and consequently any advertising propaganda for the drug by the Harmer Laboratories Company was to be deprecated.

In its reply the Harmer Laboratories Company admitted that its advertising claim, that Mon-Arsone was at least equal to arsphenamine therapeutically, had been based on reports on fifty cases and on additional reports that were beginning to come in at that time. The Harmer Laboratories Company submitted a list of hospitals and physicians using Mon-Arsone. A letter of inquiry sent by the Council to those who, according to the names in the list supplied by the Harmer Laboratories Company, had used Mon-Arsone, brought seven replies.

The clinical evidence contained in these replies was to the effect that Mon-Arsone had been used in the various types of syphilis and that there was a certain beneficial effect, both clinically and as shown by the Wassermann reaction. In certain instances the Wassermann reaction changed from a four plus to a negative reaction. The reports showed that the efficiency of Mon-Arsone as compared with that of arsphenamine preparations has not been adequately studied. One physician who has used Mon-Arsone extensively reports that in many of the cases treated there seemed to be nearly as good results from the use of Mon-Arsone as is frequently obtained in the use of arsphenamine. He reports, however, that it was necessary in eleven out of one hundred cases to change from Mon-Arsone to neoarsphenamine.

In view of the fact that there is definite lack of evidence to show that Mon-Arsone is the equal of arsphenamine therapeutically, and because of the reports that in some cases it is inferior, Mon-Arsone should not be used in the treatment of syphilis generally until its therapeutic status has been more rigidly investigated and conclusive evidence of its superiority to arsphenamine preparations obtained.

The Council voted not to admit Mon-Arsone to New and Nonofficial Remedies and reaffirmed its conclusion that the claim that Mon-Arsone has a therapeutic value equal to that of arsphenamine is premature and unwarranted; that Mon-Arsone should not be used except under conditions that justify the experimental trial of an unproved drug; and that the advertising propaganda for the drug by the Harmer Laboratories Company is to be deprecated.

* * * * *

When the preceding report was sent to the Harmer Laboratories Company, the firm submitted a reply in which it was stated:

1. That in certain instances patients improved under Mon-Arsone who, previously, had not improved under arsphenamine, and that this should be taken to offset the report of the one hundred cases in which the use of Mon-Arsone had to be abandoned in 11 per cent. of the cases.

2. That the Harmer Laboratories Company has abandoned the claim that Mon-Arsone is therapeutically equal to arsphenamine and that it now furnishes the drug to such men as care to use it simply on the basis of its special and useful characteristics.

The Council heartily endorses the recent warning against the use of untried medicaments which was issued by the U. S. Public Health Service.[145]

[145] J. A. M. A. June 12, 1920, p. 1654.

Since the Council’s report was prepared a report on the effects of Mon-Arsone on experimental syphilis has been published by Nichols,[146] from the Division of Laboratories, Army Medical School, which concludes:

1. Disodium-ethylarsinate, or mon-arsone, tested on rabbits infected with syphilis shows no spirocheticidal power. The tissues are fatally poisoned as soon as or before the spirochetes are affected.

“2. For its practical use in syphilis there is no such germicidal basis as exists in case of the arsphenamine group.”--(From The Journal A. M. A., June 18, 1921.)

[146] Nichols, H. J.: The Spirocheticidal Value of Disodium Ethyl Arsenate (Mon-Arsone), J. A. M. A. 76: 1335 (May 14) 1921.

OXYL-IODIDE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

“Oxyl-Iodide” (Eli Lilly and Co.) is said to be the hydroiodid of cinchophen and the claim is made that it exerts the effects of cinchophen and of iodid. Because of inquiries which have been received the Council decided to determine the eligibility of “Oxyl-Iodide” for New and Nonofficial Remedies. Dr. P. J. Hanzlik--formerly Associate Professor of Pharmacology at Western Reserve University School of Medicine, now Professor of Pharmacology at Leland Stanford Junior University Medical School--who has made a study of the action of salicylates and cinchophen, was asked to report on the therapeutic value and the rationality of “Oxyl-Iodide.” This he consented to do and his report appears below.

After considering Doctor Hanzlik’s report, the Council declared “Oxyl-Iodide” inadmissible to New and Nonofficial Remedies because it is an irrational combination, marketed under claims that are unproved and consequently unwarranted.

W. A. Puckner, Secretary.

“Oxyl-Iodide,” marketed by Eli Lilly & Co., is claimed to be the hydroiodid of phenylcinchoninic acid, containing 33 per cent. of iodin and 67 per cent. of phenylcinchoninic acid (cinchophen). Its solubility resembles that of cinchophen, being low in water and acid mediums, and higher in the presence of alkalis. Whether “oxyl-iodide” is decomposed into its constituents in the presence of alkalis does not appear to have been determined. However, if this were the case, the intestine, after administration of “oxyl-iodide,” would contain cinchophen and sodium iodid in the same forms as if these agents were administered individually so that nothing would be gained by administering “oxyl-iodide.” Being, like cinchophen, practically insoluble in acid mediums, “oxyl-iodide” would have no advantage over the latter so far as gastric irritation is concerned.

DOSAGE

The dosage advised is from one to three tablets containing 3 grains (0.2 gm.) each of “oxyl-iodide.” The total dosage would depend on the condition to be treated. In rheumatic fever, which requires a full therapeutic or so-called, “toxic” dose of cinchophen, about 12 to 13 gm. would be administered intensively. Since each tablet of “oxyl-iodide” contains 0.13 gm. of cinchophen, the total number of tablets of “oxyl-iodide” required would be 100, or two and one-half bottles of forty tablets each. At the same time the patient would receive 6.6 gm. of iodin (as iodid). This might be distinctly objectionable because of the production of the disagreeable symptoms of iodism in some persons, and indicates that the fixed proportion of the iodin constituent would be objectionable.

Even a smaller dosage, such as 5 gm. of cinchophen, which gives partial relief in rheumatism and similar conditions, would still require a patient to take a full bottle, or forty tablets, of “oxyl-iodide,” and at the same time about 2.7 gm. of iodin would have to be ingested.

Furthermore, rheumatic fever, the arthritides, gout and related conditions in which cinchophen is indicated do not require iodid. Therefore, “oxyl-iodide” would not be the remedy of choice in these conditions, and its use would be irrational and illogical.

ACTIONS

No data on the pharmacologic actions of “oxyl-iodide” are presented in the manufacturer’s literature. Presumably, the compound would exhibit the actions of its individual components, i. e., cinchophen and iodin (as iodid), though probably less efficiently, owing to its low solubility. This is also indicated by the following statements of the manufacturer: “The analgesic action of ‘oxyl-iodide’ is gradual. A word of caution is necessary to those who may expect immediate relief from pain.” Therefore, why use “oxyl-iodide” in place of more dependable analgesics, such as salicylate or cinchophen. The following statements appear far-fetched: “There is a stimulation of the endocrines which is perhaps more marked in the thyroid gland, although it is probably shared by the pituitary and other glands which function in a chain-like control.... There is stimulation of cells with increased flow of secretion, visibly demonstrated by the nasal mucous membrane after ‘oxyl-iodide’ has been taken for some time. The general action on mucous membranes favors elimination of toxins and waste products.”

It is probable that “oxyl-iodide” acts as a uric acid eliminant, though there is no reason to suppose that it is more effective than cinchophen alone. No data are given for this in the manufacturer’s literature.

USES

Successful use of “oxyl-iodide” is claimed in brachial and sciatic neuritis, lumbago, muscular rheumatism, arthritis deformans, chronic arthritis (“... in some instances were apparently cured”), subacute bronchitis, circumflex neuritis, traumatic orchitis, eczema and rheumatism. However, a careful reading of the protocols of seven cases, representing these conditions, gives an unfavorable impression as to the real contribution to the recovery by, or value received from, “oxyl-iodide.” Summarized, the opinions as quoted by the manufacturers in support of their claims for “oxyl-iodide” are briefly as follows:

Case 1. “Of course, the case is not complete yet, but I am looking for continued betterment.”

Case 2. “For two weeks past her improvement has been marvelous.”

Case 3. “The joints are still enlarged and we do not hope to clear them entirely....”

Case 4. “Undoubtedly, removal of the kidney had much to do with improvement.”

Case 5. “I think I have gotten very good results.”

Case 6. “Some apparent benefit.”

Case 7. “She is practically free from pain, and the muscle and joint stiffness is now slight.”

These inconclusive opinions certainly do not agree with the favorable impression which other portions of the manufacturer’s literature create. If the factor of natural recovery in the conditions represented by these seven cases is given due weight, little, if anything, is left to the credit of “oxyl-iodide.” Such clinical evidence as is supplied by the manufacturer indicates that the therapeutic efficiency of “oxyl-iodide” is doubtful, and not an improvement over either cinchophen or iodid.

IODISM

Iodism cannot be avoided by the use of “oxyl-iodide,” for the manufacturer’s literature states that “the dosage of ‘oxyl-iodide’ may be pushed to iodism as manifested by skin symptoms.... To avoid iodism there should be an occasional interruption of treatment.” “Oxyl-iodide,” therefore, has no advantage over ordinary sodium iodid to avoid iodism. Usually, the conditions which require cinchophen do not require the simultaneous administration of iodids, and vice versa. If administration of iodid and cinchophen together should be indicated or desirable, these can be given separately with the added advantage that the iodid can be easily reduced or withdrawn in case iodism supervenes, and the cinchophen could be continued if necessary. Since conditions do not arise frequently enough to warrant the use of iodid and cinchophen together, the existence of such a product as “oxyl-iodide” is unwarranted.

Finally, the manufacturer himself recognizes that phenylcinchoninic acid (cinchophen) can take the place of “oxyl-iodide.” Under “dosage,” the circular states: “A few patients may be idiosyncratic to the iodides and find they cannot take ‘oxyl-iodide.’ For the latter chloroxyl, the hydrochloride of phenylcinchoninic acid, is recommended.” The action of the hydrochlorid of phenylcinchoninic acid does not differ, of course, from that of cinchophen. The difficulties of assigning a clear-cut, definite, therapeutic rôle to “oxyl-iodide” in order to justify its existence, alongside well-known and tried remedies are self-evident.

CONCLUSION

“Oxyl-iodide” is pharmacologically and therapeutically an illogical, irrational and unjustified substitute for cinchophen and iodids. The conditions which require the administration of cinchophen do not as a rule require the administration of iodid and vice versa. If it is desirable to secure the effects of iodid and cinchophen together, these can be more conveniently and advantageously administered as separate agents, permitting in that way a better control of their actions. This cannot be accomplished with “oxyl-iodide,” in which the proportion of iodid and cinchophen are fixed. Symptoms of iodism cannot be avoided by the administration of “oxyl-iodide.” The objective evidences for its actions and uses are totally lacking; and the clinical opinions concerning its therapeutic benefits in different disease conditions are inconclusive and hedging, and, if anything, contradictory to the favorable impressions which the language of the advertising matter is likely to create.--(From The Journal A. M. A., July 2, 1921.)

QUASSIA COMPOUND TABLETS

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, declaring that Quassia Compound Tablets (Flint, Eaton and Company) are inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Quassia Compound Tablets, marketed by Flint, Eaton and Company, Decatur, Ill., according to the label on a trade package submitted to the Council, contain in each tablet:

Quassia 3/4 grain Aloin 1/4 grain Chionanthus 1 grain Ipecac 1/16 grain Wahoo 3/4 grain Podophyllin 1/4 grain Nux Vomica 1/2 grain Gingerine q. s. Cascara 1/3 grain

In the advertising the “Cascara” of the label is replaced by the indefinite term “Cascarin” and the “Gingerine q. s.” by “Carminative Antigripe q. s.” Flint, Eaton and Company informed the Council that “Carminative Antigripe is C. P. Sodium Sulphite of which each tablet contains 1/4 grain.” The tablets were treated with dilute hydrochloric acid and the odor of sulphur dioxid became apparent. This shows that the company’s statement to the Council, that the tablets contain a sulphite, is correct and the formula on the label is incorrect.

In the advertising for this preparation we read:

“A careful study of this formula [which formula? That on the label or that in the general advertising?--COUNCIL] will reveal the outstanding fact that, while there are several drugs employed, each ingredient is there for a purpose and all do splendid teamwork. If your patient is constipated because the stomach is not sufficiently energetic, the Quassia stimulates that organ to an increased secretion of digestive fluids and sets it to working normally. If the liver be sluggish, the Chionanthus and Wahoo prompt it to increased activity. Chionanthus has no superior for producing a sustained healthy hepatic condition. Should the bowels be slow and uncertain, the small doses of Aloin, Cascarin and Podophyllin stimulate to free peristaltic action, while the Nux Vomica sets the nervous system right. We use an effective Antigripe so that there is no griping.”

It is absurd to suppose that a complex mixture of drugs in fixed proportions can have the actions claimed for Quassia Compound Tablets. As regards the claim that “Chionanthus has no superior for producing a sustained healthy hepatic condition,” it was brought out in a report of the Council on “Some Unimportant Drugs” (Reports of Council on Pharmacy and Chemistry, 1912, p. 36) that the “claims for this remedy [Chionanthus] are not supported by experimental evidence and the clinical reports of its use fail to show indications of discriminating critical observation. It is not noticed by most pharmacologic authorities.”

Of Wahoo (Euonymus N. F.) the “Epitome of the U. S. P. and N. F.” says: “Actions and Uses.--Obsolete cathartic; toxic digitalis effects. Caption: the uncertain absorption of this drug makes its use inadvisable.”

Quassia Compound Tablets (Flint, Eaton and Company) are inadmissible to New and Nonofficial Remedies because (1) they contain drugs of unproved value; (2) their composition is needlessly complex, and, therefore irrational; (3) unwarranted therapeutic claims are made for them; (4) the name is misleading and not descriptive of their composition, and (5) the statement of their composition is indefinite and incorrect.--(From The Journal A. M. A., July 9, 1921.)

TOXICIDE

Report of the Council on Pharmacy and Chemistry

The Council has authorized the publication of the following report:

W. A. Puckner, Secretary.

Toxicide (Toxicide Laboratories, Chicago) is alleged to be a remedy which “increases systemic resistance,” is “used for immunizing against septic infections” and “is indicated in any case of septic infection, capable of inducing inflammation and pus formation, regardless of location or kind of tissue involved.” The following statements bearing on the composition of the preparation are furnished by the manufacturers:

“Toxicide contains Lachesis 12X, Tarantula 6X, Psorinum (special) 15X, Silicia 6X and Excipient q. s. (the excipient is sweet milk).

“These remedies are combined in the sweet milk and put through a process of development, which produces the curative agent which we call ‘Toxicide’ ...

“Put up in tablet form, sugar coated and colored red.”

No information is given as to the proportions, either relative or actual, of the ingredients. Neither is any information given regarding the “process of development” to which the mixture is subjected, nor the amount of the finished mixture which is contained in Toxicide tablets.

The Toxicide Laboratories present the following “theory”:

“In combining these remedies and processing with milk, we develop a latent immunizing active principle, which usually controls the most virulently, active, septic infections promptly.”

There is no evidence, however, that any effort has been made to demonstrate the presence of a “latent immunizing active principle” by scientific methods of modern immunology. The following claims for the use of Toxicide appear on the label:

“Acne, boils, carbuncles, furuncles and abscesses of the most virulent types usually begin to show improvement within 4 to 12 hours after beginning administration.

“In badly infected wounds, Toxicide will check the further destruction of live tissue and should always be given for a few days before and after operations on pus cases.

“For gunshot wounds and other conditions difficult to sterilize or drain, Toxicide is the ideal remedy.

“For abscesses existing or threatened in any obscure location, the middle ear, the mastoid, the frontal or any accessory sinuses, Toxicide is of inestimable value.

“If administered early, in fractures, compound or simple, or for laceration and other injuries, inflammation, swelling, soreness and destruction of tissue will be greatly mitigated.”

In support of these claims there are offered letters from physicians who have used Toxicide with good results. None of these testimonials present evidence that the reported effects were due to Toxicide. The asserted--and highly improbable--action of Toxicide could be determined only by an extensive series of carefully controlled clinical trials--and such evidence is entirely lacking. In fact, the claims appear to have no better basis than the coincidence which is stated to have led to the discovery of the “remedy”; namely, that a boil on the neck disappeared shortly after the administration of Toxicide!

The Council finds Toxicide inadmissible to New and Nonofficial Remedies because (1) the identity and amount of the potent constituent or constituents have not been furnished; (2) the preparation is advertised indirectly to the public; (3) the name “Toxicide” is therapeutically suggestive, and (4) the therapeutic claims, being unsubstantiated by evidence, are unwarranted.

[Editorial Comment.--It seems rather preposterous that a scientific body, such as the Council on Pharmacy and Chemistry, should have to waste its time in investigating and reporting on such an obviously unscientific product as “Toxicide.” So long, however, as there are physicians who will take preparations of this sort seriously, the Council feels that it is its duty to report on such products. The problem, in fact, was well stated in a letter addressed to the editor some months ago by the secretary of a county medical society who had just received a visit from a representative of the Toxicide Laboratories and who sent to The Journal some of the advertising matter that he had received from the same source. This physician wrote:

“I do not wish to trouble you with this kind of material, usually deposited safely in my waste paper basket, but the enclosed was handed to me today by a ‘bird’ who is calling on all the doctors and making strong statements. When he claimed that ‘Toxicide’ is being used in the Presbyterian Hospital, Chicago, and that the Council on Pharmacy and Chemistry is considering it seriously, etc., etc., I wish to know whether I am missing any real good thing. If it has any real virtue, I would like to know about it, but if it has not, it seems to me that something ought to be done to head him off as some doctors are sure to fall for some of it.”

The Toxicide Laboratories is, apparently, merely a trade name used by the alleged originator of “Toxicide,” J. F. Ruckel, M.D. According to our records, Ruckel was born in 1860 and was graduated by the Chicago Homeopathic Medical College in 1886. He claims to have originated Toxicide about twenty years ago and to have prescribed it “in over 3,000 cases.” In addition to Toxicide, the Toxicide Laboratories also put out “Dianasiac for Nymphomania and Satyriasis” and “Somnosine for Insomnia.”]--(From The Journal A. M. A., Oct. 8, 1921.)

PIL. MIXED TREATMENT (CHICHESTER)

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report:

W. A. Puckner, Secretary.

“Pil. Mixed Treatment (Chichester)” is a proprietary preparation of the Hillside Chemical Co., Newburgh, N. Y. It is sold in the form of pills, each said to contain 1/20 grain of mercuric iodid and 5 grains of potassium iodid.

In 1907 the Council examined the therapeutic claims advanced for this preparation and found that they were unwarranted, exaggerated and misleading. It found, also, many misleading statements in regard to the product itself. Furthermore, the A. M. A. Chemical Laboratory found the pills to be “short weight” in potassium iodid content.

At the time that the Council examined Pil. Mixed Treatment (Chichester), a dermatologist of recognized standing, to whom the “literature” for this product had been submitted for an opinion, made the following report:

“Assuming that this pill contains what is claimed for it, one-twentieth (1/20) of a grain of biniodid of mercury and five (5) grains of potassium iodid, it presents neither an original nor a very useful formula.

“The literature furnished by the company abounds in suggestions that the mixture, as they prepare it, represents some unusual potency which is not possessed by the ordinary mixture of these same drugs in the same proportion. These suggestions may of course be dismissed without consideration. There is nothing mysterious in a mixture of potassium iodid and biniodid of mercury and this formula is no more entitled to special consideration than any other pill or tablet of the same composition prepared by any reputable pharmaceutical firm.

“The formula of this pill, however, does not represent a good combination. It is offered for use both during the active secondary period of syphilis and for tertiary lesions. The pill does not contain enough mercury to be an efficient remedy for secondary syphilis and not enough potassium iodid to be satisfactory in the treatment of tertiary lesions. It is neither fish, flesh, fowl, nor good red herring. A patient with secondary syphilis should not be dosed all the time with potassium iodid and for the treatment of tertiary lesions he should have a very much larger quantity of potassium iodid than can be given in these pills without giving toxic doses of mercury.

“The statement that this pill ‘does not impair the appetite nor disturb digestion and is well borne by patients who cannot tolerate iodids otherwise administered’ is a bald claim which cannot be justified by experience. The most unsatisfactory way of administering potassium iodid is in solid form. A patient who can stand potassium iodid in pill form, as it is furnished in this preparation, can stand it in any form in which it is ever administered.

“In short this preparation is neither agreeable nor efficient. The greatest objection to it is its inefficiency, for it is offered as an adequate preparation for the treatment of syphilis in all of its stages, whereas it is neither satisfactory for the treatment of secondary syphilis nor of tertiary lesions.”

During the fourteen years which have elapsed since the Council’s first examination of Pil. Mixed Treatment (Chichester), arsphenamin has been added to the syphilographer’s armamentarium and much has been learned about syphilis and its treatment. While there exist differences of opinion as to the exact value of arsphenamin in the treatment of syphilis and there are even some who desist from the use of arsenic compounds of any kind, no syphilographer of standing countenances the routine treatment of syphilis with a fixed combination of mercuric iodid and potassium iodid. The use of Pil. Mixed Treatment (Chichester) is on a par with the use of certain “blood purifiers” which were advocated at a time when the treatment of syphilis was a baffling problem.

PRESENT DAY CLAIMS

The present advertising, which reads as if it had been written in the heyday of proprietary license, is, in effect, an invitation to treat syphilis in its various stages and manifestations with Pil. Mixed Treatment (Chichester). If heeded by those who read the advertising of the Hillside Chemical Co., it will result in much harm to the public and the profession. For this reason, the present report of the Council is published as a protest against any advertising propaganda advocating the routine treatment of a disease which requires that each case be studied carefully so that prompt and efficient measures may be applied to the various manifestations of the disease.

The following advertisement appeared recently in several medical journals:

“Medicine is an Exact Science--on Paper Only!” Every general practitioner of medicine is called upon to treat Syphilis occasionally. He cannot depend upon the use of arsenicals alone. In most cases, “mixed treatment” the giving of mercury and iodides is required to get satisfactory results. PIL. MIXED TREATMENT (CHICHESTER) accurately and successfully meets the indications and assures definite action. Important advantages:

Ready solubility of mercury in combination with Potassium Iodide.

Avoidance of gastric, buccal or intestinal disturbance.

Easy administration, can be taken at any time, anywhere.

Economical, both drugs in one combination.

Accurate adjustment of dosage to each individual case.

Full physiological action--assured by purity of content.

Secrecy--patient or friends do not know nature of medicine. Pil Mixed Treatment (Chichester) has been time tested and trial proven. It needs no introduction to the thousands of physicians who prescribe or dispense it.

While the advertisement does not directly so advise, yet it is a subtle invitation to the general practitioner to use Pil. Mixed Treatment (Chichester) and thus save himself and his patient the time and inconvenience which the rational treatment of syphilis imposes. A circular “The Treatment of Syphilis Simplified and Improved” begins:

“No therapeutic fact is more conspicuously and decisively established than that a radical cure of syphilis can be effected by the continuous administration, from the period of development, of a proper combination of mercury with iodine.”

Continuing, it is admitted that mercury is the most efficacious drug in the primary and secondary stages of syphilis and iodin in the tertiary stage, but it is asserted that:

“... it is now granted by all syphilologists that the antiluetic action of these drugs is immeasurably augmented by properly combining them, and that the best results are obtained when they are conjunctively administered throughout the entire course of the disease.”

Arguing along the same lines, this circular continues:

“... it was not until mercury and iodine in the form of Pil. Mixed Treatment (Chichester) was evolved that the marked advantages of the combined employment of these drugs in the various stages of syphilis became a scientific certainty.”

Further we are asked to believe that:

“Because of the greatly increased potency of mercury and iodine when combined, as in Pil. Mixed Treatment (Chichester), the foremost syphilologists are now agreed that the employment of these drugs in such form should be enjoined as soon as the disease develops, and should be thus continued until a cure has been effected; in other words, Pil. Mixed Treatment (Chichester) should be made the sole antisyphilitic medication throughout all stages of the disease.”

The circular illustrates the extent to which our knowledge of drugs may be distorted and misrepresented and the public health jeopardized in the exploitation of a proprietary medicine.

PROPRIETARY CLAIMS

In its advertising, the Hillside Chemical Co. claims that Pil. Mixed Treatment (Chichester) both as to formula and method of preparation “in the incapsulated powder form” was “brought to the notice of the profession by Dr. W. R. Chichester of New York, an eminent Syphilographer and recognized authority in the therapeutics of Syphilis.” It is claimed that this pill “is perfectly soluble, tasteless, nonirritant, and therefore well adapted to a sensitive stomach.” It is claimed that the pill “is always preferable to one extemporaneously prepared, which, even if identical in composition, often gives negative results.”

An examination made in the chemical laboratory of the association to determine if the product now marketed contains the claimed amount of potassium iodid indicated that this was the case. The chemist who made this examination commented as follows on the claim that in this pill, potassium iodid is rendered tasteless, that the pill is “perfectly soluble” and that extemporaneous pills of “identical ... composition often give negative results.”

“That the potassium iodid has been rendered tasteless is false, naturally; the pills when placed in the mouth, after removal of the coating, have the characteristic taste of alkali iodids. The claim that the pills are entirely soluble is incorrect; they contain a large amount of insoluble material, probably kaolin. The assertion that an extemporaneous compound prescription even if identical in composition with the Chichester pill is often inert, is absurd and a reprehensible attack by suggestion of the ideal that the physician shall write his prescription to meet the individual needs of his patient and that the pharmacist shall compound the prescriptions of the physician as they are required. It should also be pointed out that while much is said about the potassium iodid in the Chichester pill being in powdered form, the pill mass is solid and very slowly soluble and the claim of being in powdered form is, if immaterial, also incorrect.”

As to the asserted standing of the alleged discoverer of the formula for Pil. Mixed Treatment: Dr. William R. Chichester appears to have lived and practiced in New York since 1886 or longer, but the claim that he is an “eminent syphilographer” seems to have originated with the exploiters of “Pil. Mixed Treatment.” Search failed to show the name of W. R. Chichester among authors of textbooks of syphilis or any other branch of medicine or among authors of contemporary literature in the Index Medicus from 1907 down to the present; nor did a search of the catalogue to the Surgeon-General’s Library reveal W. R. Chichester as ever having published anything on syphilis or any other subject.

Pil. Mixed Treatment (Chichester) is sold under therapeutic claims which are unwarranted and misleading. The preparation well illustrates the abuses which are connected with the exploitation as proprietaries of established drugs or mixtures of established drugs.--(From The Journal A. M. A., Oct. 22, 1921.)

ATOPHAN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report explaining why Atophan has been omitted from New and Nonofficial Remedies. Schering and Glatz, Inc., the firm which markets this brand of cinchophen in the United States, has refused to place either the U. S. Pharmacopeial name, “Phenylcinchoninic Acid (Acidum Phenylcinchoninicum)” or the N. N. R. name, “Cinchophen,” on the label and in the advertising matter so as to make the identity of the product clear to physicians. Furthermore, the product is sold under therapeutic claims which the Council holds to be exaggerated and unwarranted.

W. A. Puckner, Secretary.

COMMERCIAL HISTORY OF CINCHOPHEN

The substance, 2-phenyl-quinolin-4-carboxylic acid, was described by Doebner and Gieseke in 1887 (Ann. d. Chem. [Liebig’s] =242=:291). The therapeutic properties of this compound were described by Nicolaier and Dohrn in 1908 (Deutsch. Arch. f. klin. Med. =93=:331). Subsequently the product was placed on the market and extensively advertised by the Chemische Fabrik auf Actien (vorm. E. Schering), Berlin, Germany. This firm also took out a patent in the United States on its production and in 1911 secured a U. S. trademark on the name “Atophan.” In 1912 Atophan was passed on by the Council and admitted to New and Nonofficial Remedies.

When the government of the United States took charge of German-owned patents during the World War, the Federal Trade Commission, and later the Chemical Foundation, Inc., issued licenses to American firms whereby these were authorized to manufacture the compound. In the meantime, Schering and Glatz, Inc., who had been the U. S. representatives for the Chemische Fabrik auf Actien, also undertook to supply the drug, but did not obtain a license from the boards in charge of German patents. Also, this firm secured, in 1919, a trademark of the word “Atophan,” apparently after the German-owned trademark had been canceled.

The drug “Atophan” was admitted to the U. S. Pharmacopeia as “Phenylcinchoninic Acid (Acidum Phenylcinchoninicum).” As this name proved too cumbersome, the Council on Pharmacy and Chemistry coined the abbreviated name “Cinchophen” for it, and this name is now used by all the firms which are marketing the product in the United States, with the exception of Schering and Glatz, Inc., who use the term “Atophan,” first owned by the Chemische Fabrik auf Actien.

ATOPHAN, A BRAND OF CINCHOPHEN

Because of the confusion which is bound to arise from giving various names to one drug, the Council selects a common name and provides standards of identity, purity and strength for any drug which, by reason of the absence or lapse of patent rights or for other reason, is open to manufacture by more than one firm. The Council, then, will accept such article only if it is marketed under the title adopted for New and Nonofficial Remedies. The rules provide, however, that when the Council adopts a common name for an article that has been admitted under another name, such article will be retained in New and Nonofficial Remedies under the older name if the Council name is given prominence on the label and in the circulars and advertisements, in order to avoid confusion. Accordingly, when the period of acceptance for Atophan in New and Nonofficial Remedies was about to expire, Schering and Glatz were notified that Atophan could be retained in that publication only on condition that the name, “Cinchophen,” or else the pharmacopeial name, “Phenylcinchoninic Acid (Acidum Phenylcinchoninicum)” be placed on the label and used in the circulars and advertising.

UNWARRANTED THERAPEUTIC CLAIMS FOR ATOPHAN

At the time that the Council asked Schering and Glatz to adopt cinchophen or phenylcinchoninic acid as a synonym for Atophan, the firm was also requested to omit from future advertising a number of therapeutic claims to which the Council was obliged to take exception. Schering and Glatz refused the first request and made no definite promise with regard to the second. The Council, therefore, directed the omission of Atophan from New and Nonofficial Remedies, 1921.

The advertising to which the Council took exception does not appear to be distributed at present. A pamphlet has been sent out, however, which is equally objectionable. It contains unwarranted therapeutic claims and suggests that Atophan be used in conditions in which it is not indicated. For instance:

“No longer the vague, hypothetical, ‘test-tube demonstrated’ principle of uric acid elimination by solution, but a definite, scientifically and clinically established, physiologic stimulation of the uric acid excretion. Performed innocuously and controllable to a nicety by dosage and by urine and blood tests.”

The “innocuousness” of Atophan has not been proved; on the other hand there is evidence that it is not innocuous, as the recent investigations of Hanzlik and Scott and their collaborators (Cinchophen, Neocinchophen and Novaspirin in Rheumatic Fever, J. A. M. A. 76: 1728 [June 18] 1921) show that it may injure the kidney.

The circular also contains the following:

“No longer, hit and miss relief of pain at the expense of the heart, the intestines, the kidneys and the nervous system, but the promptest and most reliable analgesic, anti-inflammatory and decongestive action so far known, with notable freedom from heart depressant, renal irritant, constipating and cumulative toxic by-effects. No contraindications, except chronic nephritis and the presence of kidney concretions.”

This is misleading. The drug depresses the circulation, injures the kidney and produces symptoms of salicylism or “toxicity.” It is not the promptest and most reliable analgesic; morphin is superior and salicylate is just as efficient. The phrase “decongestive action” is vague. Treatment of pulmonary congestion from phosgene, and congestion of the conjunctiva in mustard oil chemosis of cats, with large doses of Atophan was ineffective; in fact, it proved distinctly harmful. This was shown by such workers as Laqueur and Magnus, and Heubner and Gildemeister (Ztschr. f. d. ges. exper. Med. =13=:200, 1921). It is incorrect to ascribe “decongestive” or “anticongestive” action in the true sense to Atophan (cinchophen). The principal assets of the salicylate-cinchophen class of drugs in the treatment of rheumatism and gout are their analgesic and antipyretic qualities.

The claim is made:

“In Rheumatic and Gouty Disorders, whether of the well-known muscular and arthritic type, or their Eye, Ear, Nose and Throat manifestations.”

The suggestion that Atophan is indicated in “their Eye, Ear, Nose and Throat manifestations” is a vague generalization without definite meaning, but nevertheless calculated to impress physicians and promote the sale of Atophan for common and minor ailments. Rhinitis and sore throat are, of course, self-limited conditions which require chiefly good habits, personal and general hygiene as prophylactic measures, and simple hot baths with rest, instead of medication, for symptomatic relief. When it comes to ear and eye conditions, Atophan certainly would do no good in otitis media, panophthalmitis, choroiditis, retinitis, etc.

The administration of Atophan is proposed “in Migrains, Hemicrania, Eyestrain, etc., often vaguely grouped as ‘Headaches.’” Eyestrain and headaches are vague symptoms often arising from numerous causes that require no medication, but rather good habits, hygiene and similar corrective measures. There is always the possibility of habituation from the use of drugs for such common and vague symptoms, resulting eventually in more harm than good to the patient.

The use of Atophan is proposed “In Influenza (Grippe) for the ready alleviation of the respiratory congestion, pain and stiffness of limbs and back.” Probably the entire claim is without warrant, since influenza is a self-limited disease. Atophan might relieve pain in the joints, reduce the fever, etc., but at the same time it would tend to impair the functional efficiency of the heart, which may be impaired already by the disease. Cardiac failure is one of the causes of death in influenza. The recommendation for “alleviating respiratory congestion” is certainly without warrant, since in actual trial in pulmonary congestion by Magnus et al., Atophan was found to be deleterious and not beneficial. Phosgenized cats are probably as good a test object for the alleged decongestive action of Atophan as anything could be, since, according to Underhill and Ringer (J. A. M. A. =75=:1531, 1920) the pathological physiology of the circulation and respiration in phosgene poisoning and influenza are nearly identical.

Further, Atophan is recommended “In Pyorrhea Alveolaris as a systemic support to local and specific measures.” Atophan is not indicated here. Pyorrhea requires local medication, if anything at all. It could exert no local beneficial effects in this condition; indeed, the employment of Atophan might lead to irritation. Good dental treatment is more essential than medication.

Finally, Schering and Glatz advise Atophan “In Eczema, Pruritus and similar irritant and itching Skin Diseases with lowered blood alkalinity.” The assumption that blood alkalinity is lowered in irritant and itching disease is unsupported by evidence in medical literature and the recommendation is incorrect and misleading. Neither does Atophan alter the reaction of the blood. Amelioration in these capricious conditions occurs without medication so that any relief that might be obtained could not be attributed to Atophan. The entire paragraph is misleading and will undoubtedly tend to extend the use of Atophan in conditions for which it is not suited.--(From Reports of Council on Pharmacy and Chemistry, 1921, p. 8.)

UROTROPIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Urotropin is a proprietary name applied to the substance which is known in chemical literature as hexamethylenetetramin and which is designated hexamethylenamine in the U. S. Pharmacopeia. The Council has authorized publication of the following report explaining that Urotropin was omitted from New and Nonofficial Remedies because Schering & Glatz, Inc. (the firm that markets this brand of hexamethylenamin in the United States), refused to place the U. S. Pharmacopeia name Hexamethylenamine (hexamethylenamina) on the label and in its advertising so as to make clear to physicians the identity of the product, and, furthermore, because it was sold under therapeutic claims which the Council held unwarranted.

W. A. Puckner, Secretary.

Commercial History of Hexamethylenamin

This substance which is generally referred to in chemical literature as hexamethylenetetramin, the cyclic condensation product of formaldehyd and ammonia, appears to have been described first in 1860 (Butlerow: Ann. d. Chem. =115=:322, 1860). Subsequently, numerous references to the preparation, properties and constitution of the substance appeared in chemical literature.

Hexamethylenetetramin is said to have been first used for therapeutic purposes by G. Bardet, who, in 1894, reported to the Société de Thérapeutique that he believed this substance to be a uric acid solvent. At about the same period, A. Nicolaier, who gave Bardet credit for suggesting the use of hexamethylenetetramin as a uric acid solvent, announced the discovery of its antiseptic action (Centralbl. f. d. med. Wissensch. =32=:897, 1894; Deutsche med. Wchnschr. =21=:541, 1895). Shortly thereafter as a result of Nicolaier’s publication, the Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, Germany, began to offer the product to the medical profession under the trademarked and nondescriptive name “Urotropine.” In the United States, it was marketed by Schering and Glatz, who then were acting as American agents for the Schering works of Germany.

It soon became evident that hexamethylenetetramin was a valuable drug. As the substance was introduced at a time when new “synthetic” drugs were rapidly appearing and when unlimited and uncritical confidence was placed in them, and before the medical profession became skeptical of the claims advanced by manufacturers for their respective “discoveries,” it was not long before this new drug was placed on the market by many firms, each applying its own name and often keeping the chemical character of it in the background. Some of the names which were thus applied to hexamethylenamin were Cystogen, Aminoform, Formin, Uritone, Urisol, {and} Cystamine.

In 1907 the late Prof. J. O. Schlotterbeck, then a member of the Council, protested against the confusion caused by the marketing of a given drug under different names. He stated that it was not uncommon for a physician to prescribe two or more of these identical substances in the same mixture, expecting to get the combined action of different urinary antiseptics; also, that patients had been treated first with hexamethylenamin under one name and later by the same substance under another name (The Journal, Jan. 19, 1907, p. 241).

Hexamethylenetetramin was admitted to the eighth revision of the U. S. Pharmacopeia. In part because of this official recognition and standardization and in part because the extravagant reports of its virtues had been largely discounted, physicians have in general prescribed the drug by its pharmacopeial name, with one notable exception: Urotropin. One reason for this is that Urotropin was the first proprietary brand of hexamethylenetetramin introduced, a second reason is that through the extensive and persistent advertising of the proprietary name under which the substance was introduced, it has become firmly fixed in the minds of many physicians. The other is that the product was claimed to be of greater purity than the product sold under the pharmacopeial or other name although no evidence confirmatory of this claim has ever been published. On the other hand, Daniel Base, as long ago as 1907, found that hexamethylenamin sold under its pharmacopeial name is just as pure as when sold under proprietary names. When, in 1907, urotropin was admitted to New and Nonofficial Remedies, the published description showed that it was manufactured by the Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, and that Schering and Glatz were the United States agents. In 1919, the description was revised to show that Schering and Glatz were no longer selling the German product.

As it is the general practice to omit articles that are admitted to the U. S. Pharmacopeia for the reason that their quality is guaranteed under the federal Food and Drugs Act and because pharmacopeial nonproprietary articles are rarely advertised with claims that require the Council’s control, yet, in the case of Urotropin, it was retained because it was sold under a name not recognized in the pharmacopeia and because special (proprietary) claims were made for it.

Urotropin Marketed Under Unwarranted Therapeutic Claims

The period for which Urotropin stood “Accepted” expired with the close of 1921. To determine its continued eligibility for New and Nonofficial Remedies, the Council examined the labels and circular matter sent by Schering and Glatz for the purpose and also a booklet “Urotropin,” subsequently sent by the firm to physicians.

It was found that the pamphlet contained a number of unwarranted statements. Particularly objectionable are the claims made for the use of Urotropin as an antiseptic in body fluids that are alkaline, such as the cerebrospinal fluid, bile, aqueous humor of the eye, saliva, the excretions caused by middle ear infection and other excretions of the nasal, bronchial, laryngeal and mucous membranes. The lack of efficacy of hexamethylenamin in alkaline secretions is generally admitted and the clinical references to the use of hexamethylenamin in the pamphlet are obsolete. In the introduction to the pamphlet, Schering and Glatz state that they are well acquainted with the scientific research work discrediting the efficiency of hexamethylenamin in nonacid mediums, but that they feel that the accumulated evidence for its efficacy in such conditions should not be “brushed aside.” However, the pamphlet is not made up of quotations, but of unqualified statements. With one exception, all references to the antiseptic properties of the drug in alkaline mediums are previous to 1913, that is, before the importance of reaction of the medium was fully appreciated. To quote these earlier articles without regard to the later work, which in most eyes discredited them, constitutes in effect an exploitation of this brand of hexamethylenamin under unwarranted therapeutic claims.

Urotropin a Brand of Hexamethylenamine, U. S. P.

In consideration of the confusion which arises from the application of different names to an identical article, the rules of the Council provide that when an article which has been accepted for New and Nonofficial Remedies is admitted to the U. S. Pharmacopeia under another name, it will be retained, provided the official name is given prominence on the label and in the advertising of such article. Neither the label nor the advertising for Urotropin gives prominence to the pharmacopeial name as a synonym nor indeed does it bring out the fact that Urotropin is a brand of hexamethylenamine, U. S. P. Schering and Glatz, Inc., was advised that Urotropin could be retained in New and Nonofficial Remedies only on condition that the objections to the therapeutic recommendations were removed and on agreement that the U. S. P. name appear on the labels and circular matter. The firm did not offer to make the product eligible for continued recognition; accordingly the Council directed the omission of Urotropin because of conflict with Rule 6 (Unwarranted Therapeutic Claims) and with Rule 8 (Objectionable Names).--(From Reports of Council on Pharmacy and Chemistry, 1921, p 71.)

STYPTYSATE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, declaring Styptysate (Ernst Hischoff Co., Inc.) inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Styptysate, according to the advertisement of Ernst Bischoff Co., Inc., New York, is “obtained by dialysis from Bursa Pastoris (Sheppard’s [sic!] Purse).” It is claimed to be “The Remedy For Hemorrhages,” to be “Superior to Ergot and Hydrastis,” “of particular advantage in Menorrhagia and Metrorrhagia” and to have been “found of great value in vesical hemorrhages and hemorrhages from mucous membranes in general.” The Styptysate label bears the synonym “Dialysate Herba Bursa Pastoris”; the statement that it contains “alcohol 11 per cent.” and that it is “made in Germany.” No other statement of the composition or strength of “Styptysate” is furnished nor is the name of the German manufacturer disclosed.

In an advertising circular entitled “Styptysate, a New Reliable Hemostatic,” it is declared that in recent years the plant, Shepherd’s Purse (Capsella bursa pastoris), “has been submitted to clinical tests in the form of a concentrated dialysate, known as Styptysate, by Loewy, Oppenheim, Krummacher and others, and that their reports coincide in regard to Styptysate as a hemostatic par excellence, particularly in uterine hemorrhages, even in cases where ergot and hydrastis had failed to produce satisfactory results.” The circular also reprints some “short clinical reports” without reference to their authorship; one ascribed to Krummacher and two ascribed to “B.H.M., Kansas City, Mo.,” and the following references: “A. Krummacher, M.D., Monthly Review for Obstetrics and Gynecology, Berlin, Vol. XLIX, 4, and Vol. LII.” “H. Oppenheim, M.D., Medical Clinic, Berlin, 1920, 35.”

Shepherd’s Purse is a weed common in the United States and in Europe. Like most other herbs, it has some reputation as a folk medicine. It is used by eclectics and homeopaths, being included in the Homeopathic Pharmacopeia of the United States. Shepherd’s Purse receives no consideration at the hands of the authors of standard works on materia medica, pharmacology or therapeutics.

From an examination of recent German medical publications, it appears that the use of Shepherd’s Purse was proposed as a substitute for ergot and hydrastis, when the latter drugs became scarce in Germany. These publications, in the main, emanate from those in the employ of pharmaceutical firms and deal with proprietary preparations or they are written by physicians who used these proprietary preparations at the solicitation of the manufacturers. For this reason the reported results must be accepted with reserve.

One of the proprietary preparations discussed in the German publications is Styptysate, manufactured by Isalfabrik Johannes Buerger, Wernigerode. It is said to be produced by submitting the juice of fresh Shepherd’s Purse to dialysis and preserving the dialysate by the addition of alcohol. There is no statement as to the drug strength or the chemical or biological standards, if any, used in its manufacture; hence, the preparation is essentially a secret one. As first produced, the preparation seems to have been fortified by the addition of cotarnin: the dose was then given as ten to fifteen drops. Later, as the cost of cotarnin went up, this drug was omitted, and the drug strength increased; the dose of the new preparation is given as twenty-five to thirty drops. Just what relation, if any, the Styptysate of Ernst Bischoff Co., Inc., bears to that of the Isalfabrik Johannes Buerger, Wernigerode, cannot be determined from the Bischoff advertising. If it has any relationship the announcement that no narcotic order is required when ordering Styptysate would indicate that the new preparation is supplied; the old one with its addition of cotarnin would require a narcotic order. On the other hand, the recommended dose of the cotarnin-free preparation is twenty-five to thirty-drops, whereas the product sold by Bischoff and Co. is to be given in doses of ten to fifteen drops--that is, in the amount proposed for the cotarnin-fortified product.

What justification is there for the claim that Styptysate has been submitted to clinical tests by Loewy, Oppenheim and Krummacher and found to be a hemostatic par excellence and efficient even where ergot had failed to give satisfactory results? Loewy (Zentralblatt für Gynäcologie =42=:920, 1921) made some pharmacologic tests on guinea-pigs with the cotarnin-containing preparation, but reported no clinical trials. Hans Oppenheim (Medizinische Klinik, Aug. 29, 1920, p. 906) reported that he was agreeably surprised at the excellent results (vorzueglichem Erfolg) obtained with the drug but he did not assert that it is superior to ergot.

Krummacher reported on thirteen cases of profuse menstruation in which the patients were treated with Styptysate, using for a part, the preparation containing cotarnin and for the other a preparation without cotarnin. He reported as good results with the cotarnin-free preparation in larger dosage, as with the cotarnin-containing preparation in smaller dosage. Krummacher did not compare Styptysate with ergot. Some of Krummacher’s cases are quoted, with some typographical errors, in the Bischoff circular.

On the assumption that the product discussed in German publications is the Styptysate marketed in the United States, the best that can be said for it is, that during a shortage of ergot it was used in place of that established drug. There is no evidence to warrant the use of this indefinite proprietary in place of the biologically standardized fluidextract of ergot or other standardized ergot preparations.

Styptysate (Ernst Bischoff and Co., Inc.) is inadmissible to New and Nonofficial Remedies because its composition is semisecret and indefinite and there is no evidence that its uniformity and strength is controlled (Rules 1 and 2); further, it is inadmissible because the therapeutic claims advanced for it are exaggerated and unwarranted (Rule 6) and because there is no evidence that it possesses any advantage over established drugs such as the biologically standardized fluidextract of ergot or the definite ergot preparations admitted to New and Nonofficial Remedies.--(From The Journal A. M. A., Feb. 11, 1922.)

LIPOIDAL SUBSTANCES (HOROVITZ) NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report declaring Lipoidal Substances (Horovitz) inadmissible to New and Nonofficial Remedies because its composition is essentially secret and because the curative claims made for it are unsubstantiated and, therefore, unwarranted.

W. A. Puckner, Secretary.

In the advertising of the Horovitz Biochemic Laboratories Co. (A. S. Horovitz, president) we read:

“Horovitz proves by careful paralleled investigations of normal and of pathological tissues, both in addiction disease and in other diseases, that in patients suffering from narcotic addiction disease there is an inactivity of the lymph-glands due to the use of the drug and that the system is not supplied with the necessary fats.” “Horovitz further found that the lipoidal content of the cerebro-spinal system varies in strict accordance with the pathological processes introduced by infection or by alkaloids. Furthermore, he has found that the lipoids of various other organs, as well as those of the THERMORnervous system, may be extracted and consumed by the administration of narcotic alkaloids.”

It is further stated in the advertising that:

“After a long and very careful research investigation, Dr. Horovitz worked out a method of rational treatment for narcotic addiction disease which involves the restoration of the lipoids, which have been lost through the action of the drug, and of the toxins, by means of a combination of lipoidal substance from various plant lipoids in the form of a sterile solution. This preparation not only replaces the lipoids lost by the tissues, but also protects the nerve tissues, from attacks by the toxins elaborated during the use of narcotics, and, this by detoxicating the tissues, brings about permanent freedom from the craving of narcotics, instead of the temporary relief afforded by other methods of treatment.”

The “combination of lipoidal substance of various plant lipoids” which was worked out by Horovitz, the Horovitz Biochemic Laboratories offer as “Lipoidal Substances.” This preparation is supplied in ampoules said to contain 1 c.c. of solution. The treatment with “Lipoidal Substances” consists, first, in the complete withdrawal of the narcotic; second, in free catharsis; and third, in the intramuscular injection of the preparation. The initial dose is given as 8 to 12 minims repeated with increase of 3 to 4 minims every three hours during the first day. On the second, third and fourth day 16 minims is to be given twice a day and “from the fifth day until the medication is stopped (usually 28 to 35 days) it will be necessary usually to give but 1 injection of 16 minims each day.”

In a request for the admission of its preparation to New and Nonofficial Remedies, the Horovitz Biochemic Laboratories Co. stated:

“The composition of Lipoidal Substance is (a) Lipoids of plant origin, (b) Vitamines (water soluble) of plant origin, (c) Non-specific plant proteins, (d) Preservatives--None.”

While the communication abounded in generalities, it gave neither the identity nor character of the lipoids, of the vitamins nor of the nonspecific protein, nor their quantities or methods for their control. The firm presented no evidence that the injection of “Lipoidal Substances” produced any effect other than by suggestion. Also, while a long list of references to publications bearing on lipoids was submitted (many of which had no bearing on the subject under consideration) there was no reference to the work of Horovitz quoted in the firm’s advertising.

After examining the information which had been submitted, the Council requested the manufacturer to supply:

1. Information as to the character (identity) of the several ingredients contained in the preparation that it marketed, the amount of each ingredient so far as known and the method used for their control.

2. Evidence that the administration of “Lipoidal Substances” is of value in the treatment of drug addiction.

3. Evidence for the claims that the “researches” of Horovitz have proved that “in patients suffering from narcotic addiction disease there is an inactivity of the lymph-glands ... and the system is not supplied with the necessary fats” and that “lipoidal content of the cerebro-spinal system varies in strict accordance with the pathological processes introduced by infection or by alkaloids” and that “the lipoids of various other organs as well as those of the nervous system, may be extracted and consumed by the administration of narcotic alkaloids.”

The Horovitz Biochemic Laboratories replied that the requested information would be supplied in about two weeks. At the expiration of three months the promised information and evidence had not been received; neither had any reports to show the value of the treatment come to the attention of the Council. The Council, accordingly, declared “Lipoidal Substances” (Horovitz Biochemic Laboratories) inadmissible to New and Nonofficial Remedies because the composition is essentially secret and because the curative claims are unsubstantiated and unwarranted.--(From The Journal A. M. A., Feb. 25, 1922.)

YEAST PREPARATIONS AND VITAMIN B CONCENTRATES

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following principles as a guide in the consideration of yeast preparations and vitamin B concentrates for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

1. The claim that deficiency of vitamin B and diseases resulting therefrom are common conditions in the United States is not at this time supported by adequate acceptable evidence.

2. The claim that yeast preparations or extracts are, in principle or in general, essentially more effective or more practical or more available means of administering vitamins than the commonly available vitamin-containing foods is not at this time supported by adequate acceptable evidence. (Any claims for superiority made for such products proposed for inclusion in New and Nonofficial Remedies must be presented in detail and passed on specially by the Council.)

3. The claim that therapy with yeast or yeast preparations has as yet more than an experimental status is not at this time supported by adequate acceptable evidence.

Preparations for which such claims are made, directly or by implication or in one-sided quotations, in advertisements or letters or by salesmen, cannot be admitted to or retained in New and Nonofficial Remedies.--(From The Journal A. M. A., April 15, 1922.)

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