CORTEX CINCHONÆ…

CORTEX CINCHONÆ

Cortex Peruvianus, Cortex Chinæ; Cinchona Bark, Peruvian Bark; F. Ecorce de Quinquina; G. Chinarinde.

=Botanical Origin=—The genus Cinchona constitutes together with Cascarilla (including Buena and Cosmibuena), Remijia, Ladenbergia, Macrocnemum, and about 30 other nearly allied genera, the well-characterized tribe Cinchoneæ of the order Rubiaceæ. This tribe consists of shrubs or trees with opposite leaves, 2-celled ovary, capsular fruit, and numerous minute, vertical or ascending, peltate, winged, albuminous seeds.

(=A.=) Remarks on the genus.—The genus Cinchona is distinguished by deciduous stipules, flowers in terminal panicles, 5-toothed superior calyx, tubular corolla expanding into 5 lobes fringed at the margin. The corolla is of an agreeable weak odour, and of a rosy or purplish hue or white. The fruit is a capsule of ovoid or subcylindrical form, dehiscing from the base (the fruit-stalk also splitting) into two valves, which are held together at the apex by the thick permanent calyx. The seeds, 30 to 40 in number, are imbricated vertically; they are flat, winged all round by a broad membrane, which is very irregularly toothed or lacerated at the edge.

The Cinchonas are evergreen, with finely-veined leaves, traversed by a strong midrib. The thick leafstalk, often of a fine red, is sometimes a sixth the length of the whole leaf, but usually shorter. The leaves are ovate, obovate, or nearly circular; in some species lanceolate, rarely cordate, always entire, glabrous or more rarely hirsute, often variable as to size and form in the same species.

Among the valuable species, several are distinguished by small pits called scrobiculi, situated on the under side of the leaf, in the axils of the veins which proceed from the midrib. These pits sometimes exude an astringent juice. In some species they are replaced by tufts of hair. The young leaves are sometimes purplish on the under side; in several species the full-grown foliage assumes before falling, rich tints of crimson or orange.

The species of Cinchona are so much alike that their definition is a matter of the utmost difficulty, and only to be accomplished by resorting to a number of characters which taken singly are of no great importance. Individual species are moreover frequently connected together by well-marked and permanent intermediate forms, so that according to the expression of Howard, the whole form a continuous series, the terminal members of which are scarcely more sharply separated from the allied genera, than from plants of their own series.

As to the number and value of the species known, there is some diversity of view. Weddell, in 1870, enumerated 33 species and 18 sub-species, besides numerous varieties and sub-varieties. Bentham and Hooker, in 1873, estimated the species as about 36.

Kuntze, in the book quoted at the end of the present article, proposed to reduce all the species to the four following:

1. Cinchona Weddelliana O. Kuntze, nearly answering to C. Calisaya Weddell.

2. C. Pavoniana O. Kuntze, including _C. micrantha_ Ruiz and Pavon and several allied plants.

3. C. Howardiana O. Kuntze, constituted of _C. succirubra_ Pavon and a few other species of former authors.

4. C. Pahudiana Howard.

Kuntze, who has examined the living Cinchonæ as cultivated in India, is of the opinion that all the numerous forms hitherto observed, both in the wild plants and in cultivation, are merely either belonging to the above four species or deriving from them chiefly by hybridation. Though much in favour of a reduction of the species, we are not yet prepared to accept Kuntze’s arrangement.

(=B.=) Area, Climate and Soil.—The Cinchonas are natives of South America, where they occur exclusively on the western side of the continent between 10° N. lat. and 22° S. lat., an area which includes portions of Venezuela, New Granada, Ecuador, Peru, and Bolivia.

The plants are found in the mountain regions, no species whatever being known to inhabit the low alluvial plains. In Peru and Bolivia, the region of the Cinchona forms a belt, 1300 miles in length, occupying the eastern slope of the Cordillera of the Andes.[1288] In Ecuador and New Granada, the tree is not strictly limited to the eastern slopes, but occurs on other of the Andine ranges.

The average altitude of the cinchoniferous region is given by Weddell as 5,000 to 8,000 feet above the sea-level. The highest limit, as noted by Karsten, is 11,000 feet. One valuable species, C. succirubra, occurs exceptionally as low as 2,600 feet. Generally, it may be said that the altitude of the Cinchona zone decreases in proportion as it recedes from the equator, and that the most valuable sorts are not found lower than 5,000 feet.

The climate of the tropical mountain regions in which the Cinchonas flourish, is extremely variable,—sunshine, showers, storms, and thick mist, alternating in rapid succession, yet with no very great range of temperature. A transient depression of the thermometer even to the freezing point, and not unfrequent hail-showers, may be borne without detriment by the more hardy species. Yet the mean temperature most favourable for the generality of species, appears to be 12 to 20° C. (54 to 68° F.)

Climatic agencies appear to influence the growth of Cinchona far more than the composition of the soil. Though the tree occurs in a great variety of geological formations, there is no distinct evidence that these conditions control in any marked manner either the development of the tree or the chemical constitution of its bark. Manure on the other hand, though not increasing perceptibly luxuriance of growth, has a decided effect in augmenting the richness of the bark in alkaloids.[1289]

(=C.=) Species yielding officinal barks.—The Cinchona Barks of commerce are produced by about a dozen species; of these barks the greater number are consumed solely in the manufacture of quinine. Those admitted for pharmaceutical use are afforded by the following species:—

1. Cinchona officinalis Hooker[1290]—A native of Ecuador and Peru, existing under several varieties. It forms a large tree, having lanceolate or ovate leaves, usually pointed, glabrous, and shining on the upper surface, and scrobiculate on the under. The flowers are small, pubescent and in short lax panicles, and are succeeded by oblong or lanceolate capsules, ½ an inch or more in length.

2. C. Calisaya Weddell—Discovered by Weddell in 1847,[1291] although its bark had been an object of commerce since the latter half of the previous century.

[1288] That is to say the eastern Cordillera, the western and lower range being called the Cordillera of the Coast; no Cinchonas grow on the latter.

[1289] Broughton, in Pharm. Journ. Jan. 4, 1873. 521.

[1290] Figured in Bot. Magazine, vol. 89 (1863) tab. 5364, including C. Condaminea Humb. et Bonpl. and C. Uritusinga Pavon.

[1291] Ann. des Sciences nat., Bot. x. (1848) 6, and Hist. nat. des Quinquinas, 1849, tab. 3, figured in Botanical Magazine, 1873. 6052, and 1879. 6434.

The tree inhabits the warmest woods of the declivities which border the valleys of Bolivia and South-eastern Peru, at an altitude of 5000 to 6000 feet above the sea-level. More precisely, the chief localities for the tree are the Bolivian provinces of Enquisivi, Yungas de la Paz, Larecaja or Sorata, Caupolican or Apolobamba, and Muñecas: thence it passes northward into the Peruvian province of Carabaya, suddenly ceasing on the confines of the valley of Sandia, although, as Weddell observed, the adjacent valleys are to all appearance precisely similar.

When well grown, C. Calisaya has a trunk often twice as thick as a man’s body, and a magnificent crown of foliage overtopping all other trees of the forest. It has ovate capsules of about the same length (½ an inch) as the elegant pinkish flowers, which are in large pyramidal panicles. The leaves are 3 to 6 inches long, of very variable form, but usually oblong and obtuse, rarely acute.

A variety named after Joseph de Jussieu who first noticed it, β. Josephiana, but known in the country as Ichu-Cascarilla or Cascarilla del Pajonal, differs from the preceding in that it is a shrub, 6 to 10 feet high, growing on the borders of mountain meadows and of thickets in the same regions as the larger form.

Other forms known in Bolivia as Calisaya zamba, morada, verde or alta, and blanca, have been distinguished by Weddell as varieties of C. Calisaya.

Towards the middle of the year 1865, Charles Ledger, an English traveller, obtained seeds of a superior Cinchona, which had been collected near Pelechuco, eastwards of the lake Titicaca, about 68° W. long. and 15° S. lat., in the Bolivian province of Caupolican. In the same year the seeds arrived in England, but were subsequently sold to the Dutch government, and raised with admirable success in Java, and a little later also in private plantations in British India. The bark of “Cinchona Ledgeriana” has since proved by far the most productive in quinine of all Cinchona Barks. The tree is a mere form of C. Calisaya.[1292]

3. C. succirubra Pavon,[1293]—a magnificent tree, 50 to 80 feet high, formerly growing in all the valleys of the Andes which debouch in the plain of Guayaquil. The tree is now almost entirely confined to the forests of Guaranda on the western declivities of Chimborazo, at 2,000 to 5,000 feet above the level of the sea.

The bark appears to have been appreciated in its native country at an early period, if we may conclude that the Red Bark mentioned by La Condamine in 1737 was that under notice. It would seem, however, to have scarcely reached Europe earlier than the second half of the last century.[1294] The tree has broadly oval leaves, attaining about a foot in length, nearly glabrous above, pubescent beneath, large terminal panicles of rosy flowers, succeeded by oblong capsules 1 to 1¼ inches long.

The other species of Cinchona, the bark of which is principally consumed by the manufacturers of quinine, will be found briefly noticed, together with the foregoing, in the conspectus at page 355.

=History=—The early native history of Cinchona is lost in obscurity. No undoubted proofs have been handed down, to show that the aborigines of South America had any acquaintance with the medicinal properties of the bark. But traditions are not wanting.

[1292] Ledger’s Calisaya is beautifully figured and exactly described in Howard’s Quinology of the East Indian Plantations, parts ii. and iii.

[1293] Figured in Howard’s Nueva Quinologia, art. Chinchona succirubra.

[1294] Howard, l.c. p. 9.

William Arrot,[1295] a Scotch surgeon who visited Peru in the early part of the last century, states that the opinion then current at Loxa was that the qualities and use of the barks of Cinchona were known to the Indians before any Spaniard came among them. Condamine, as well as Jussieu, heard the same statements, which appear to have been generally prevalent at the close of the 17th century.

It is noteworthy, on the other hand, that though the Peruvians tenaciously adhere to their traditional customs, they make no use at the present day of Cinchona bark, but actually regard its employment with repugnance.

Humboldt[1296] declares that at Loxa the natives would rather die than have recourse to what they consider so dangerous a remedy. Pöppig[1297] (1830) found a strong prejudice to prevail among the people of Huanuco against Cinchona as a remedy for fevers, and the same fact was observed farther north by Spruce[1298] in 1861. The latter traveller narrates, that it was impossible to convince the cascarilleros of Ecuador that their Red Bark could be wanted for any other purpose than dyeing cloth; and that even at Guayaquil there was a general dislike to the use of quinine.

Markham[1299] notices the curious fact that the wallets of the native itinerant doctors, who from father to son have plied their art since the days of the Incas, never contain cinchona bark.

Although Peru was discovered in 1513, and submitted to the Spanish yoke by the middle of the century, no mention has been found of the febrifuge bark with which the name of the country is connected, earlier than the commencement of the 17th century.

Joseph de Jussieu,[1300] who visited Loxa in 1739, relates that the use of the remedy was first made known to a Jesuit missionary, who being attacked by intermittent fever, was cured by the bark administered to him by an Indian cacique at Malacotas, a village near Loxa. The date of this event is not given. The same story is related of the Spanish corregidor of Loxa, Don Juan Lopez Canizares, who is said to have been cured of fever in 1630.

Eight years later, the wife of the viceroy of Peru, Luis Geronimo Fernandez de Cabrera y Bobadilla, fourth count of Chinchon, having been attacked with fever, the same corregidor of Loxa sent a packet of powdered bark to her physician Juan de Vega, assuring him of its efficacy in the treatment of “tertiana.” The drug fully bore out its reputation, and the countess Ana was cured.[1301] Upon her recovery, she caused to be collected large quantities of the bark, which she used to give away to those sick of fever, so that the medicine came to be called Polvo de la Condesa, i.e. The Countess’ Powder. It was certainly known in Spain the following year (1639), when it was first tried at Alcala de Henares near Madrid.[1302]

[1295] Phil Trans. xl. for 1737-38. 81.

[1296] Der Gesellsch. naturf. Freunde zu Berlin Magaz. i. (1807) 60.

[1297] Reise in Chile, Peru, etc. ii. (1836) 222.

[1298] Blue Book—East India Chinchona Plant, 1863. 74. 75.

[1299] Travels in Peru and India, 1862. 2.

[1300] Quoted by Weddell in his Hist. des Quinquinas, p. 15, from De Jussieu’s unpublished MS.—The town of Loxa or Loja was founded by the Spaniards in 1546.

[1301] The circumstances are fully narrated by La Condamine (Mém. de l’Acad. royale des Sciences, année 1738). But the cure of the countess was known in Europe much before this, for it is mentioned by Sebastiano Bado in his Anastasis, Corticis Peruviæ, seu Chinæ Chinæ defensio published at Genoa in 1663. When Bado wrote, it was a debated question whether the bark was introduced to Europe by the count of Chinchon or by the Jesuit Fathers.

[1302] Villerobel, quoted by Bado, op. cit. 202.

The introduction of Peruvian Bark into Europe is described by Chifflet, physician to the archduke Leopold of Austria, viceroy of the Netherlands and Burgundy, in his Pulvis Febrifugus Orbis Americani ventilatus, published at Brussels in 1653 (or 1651?). He says that among the wonders of the day, many reckon the tree growing in the kingdom of Peru, which the Spaniards call Polo de Calenturas, i.e. Lignum febrium. Its virtues reside chiefly in the bark, which is known as China febris, and which taken in powder drives off the febrile paroxysms. He further states, that during the last few years the bark has been imported into Spain, and thence sent to the Jesuit Cardinal Joannes de Lugo at Rome.[1303] Chifflet adds, that it has been carried from Italy to Belgium by the Jesuit Fathers going to the election of a general, but that it was also brought thither direct from Peru by Michael Belga, who had resided some years at Lima.

Chifflet, though candidly admitting the efficacy of the new drug when properly used, was not a strong advocate for it; and his publication started an acrimonious controversy, in which Honoratius Faber, a Jesuit (1655), Fonseca, physician to Pope Innocent X., Sebastiano Bado[1304] of Genoa (1656 and 1663), and Sturm (1659) appeared in defence of the febrifuge; while Plempius (1655), Glantz, an imperial physician of Ratisbon (1653), Godoy, physician to the king of Spain (1653), René Moreau (1655), Arbinet and others contended in an opposite sense.

From one of these disputants, Roland Sturm, a doctor of Louvain, who wrote in 1659,[1305] we learn that four years previously, some of the new febrifuge had been sent by the archduke Leopold to the Spanish ambassador at the Hague, and that he (Sturm) had been required to report upon it. He further states, that the medicine was known in Brussels and Antwerp as Pulvis Jesuiticus, because the Jesuit Fathers were in the habit of administering it gratis to indigent persons suffering from quartan fever; but that it was more commonly called Pulvis Peruanus or Peruvianam Febrifugum. At Rome it bore the name of Pulvis eminentissimi Cardinalis de Lugo, or Pulvis patrum; the Jesuits at Rome received it from the establishments of their order in Peru, and used to give it away to the poor in Cardinal de Lugo’s palace. In 1658 Sturm saw 20 doses sent to Paris which cost 60 florins. He gives a copy of the handbill[1306] of 1651 which the apothecaries of Rome used to distribute with the costly powder.

[1303] The cardinal belonged to a family of Seville, which town had the monopoly of the trade with America.

[1304] Bado in his Anastasis, lib. 3, quotes the opinion of many persons as coinciding with his own.

[1305] Febrifugi Peruviani Vindiciarum pars prior—Pulveris Historiam complectens ejusque vires et proprietates ...exhibens, Delphis, 1669. 12°.

[1306] It is in these words:—Modo di adoprare la Corteccia chiamata della Febre.—Questa Corteccia si porta dal Regno di Peru, e si chiama China, o vero China della febre, laquale si adopra per la febre quartans, e terzana, che venga con freddo: s’adropra in questo modo, cioè:

Se ne piglia dramme due, e si pista fina, con passarla per setaccio; e tre hore prima incirca, che debba venir la febre si mette in infusione in un bicchiero di vino bianco gagliardissimo, e quando il freddo commincia à venire, ò si sente qualche minimo principio, si prende tutta la presa preparata, e si mette il patiente in letto.

Avertasi, si potrà dare detta Corteccia nel modo sudetto nella febre terzana, quando quella sia fermata in stato di molti giorni.

L’esperienza continua, hà liberata quasi tutti quelli, che l’hanno presa, purgato prima bene il corpo, e per quattro giorni doppo non pigliar’ niuna sorte di medicamento, ma auvertasi di non darla se non con licenza delli Sig. Medici, acciò giudicano se sia in tempo à proposito di pigliarla.

The drug began to be known in England about 1655.[1307] The Mercurius Politicus one of the earliest English newspapers, contains in several of its numbers for 1658,[1308] a year remarkable for the prevalence in England of an epidemic remittent fever, advertisements offering for sale—“the excellent powder known by the name of the Jesuit’s Powder”—brought over by James Thomson, merchant of Antwerp.

Brady, professor of physic at Cambridge, prescribed bark about this time; and in 1660, Willis, a physician of great eminence, reported it as coming into daily use. This is also evidenced, with regard to the continent, by the pharmaceutical tariffs of the cities of Leipzig and Frankfurt of the year 1669, where “China Chinæ” has a place. ⅛ of an ounce (a “quint”) is quoted in the latter at 50 kreuzers (about 1s. 6d.), whereas the same quantity of opium is valued at 4 kreuzers,[1309] camphor 2 kreuzers, balsam of Peru 8 kreuzers.

Among those who contributed powerfully to the diffusion of the new medicine, was Robert Talbor alias Tabor. In his “Pyretologia” (see Appendix, T.) he by no means intimates that his method of cure depends on the use of bark. On the contrary, he cautions his readers against the dangerous effects of Jesuit’s Powder when administered by unskilful persons, yet admits that, properly given, it is a “noble and safe medicine.”

Talbor’s reputation increasing, he was appointed in 1678 physician in ordinary to Charles II., and in 1679, the king being ill of tertian fever at Windsor, Talbor cured him by his secret remedy.[1310] He acquired similar favour in France, and upon Talbor’s death (1681), Louis XIV. ordered the publication of his method of cure, which accordingly appeared by Nicolas de Blegny, surgeon to the king.[1311] This was immediately translated into English, under the title of The English Remedy: or, Talbor’s Wonderful Secret for Cureing of Agues and Feavers.—Sold by the Author Sir Robert Talbor to the most Christian King and since his Death, ordered by his Majesty to be published in French, for the benefit of his subjects, and now translated into English for Publick Good (Lond. 1682).

Cinchona bark was now accepted into the domain of regular medicine, though its efficacy was by no means universally acknowledged. It first appeared in the London Pharmacopœia in 1677, under the name of Cortex Peruanus.

[1307] So says Sir G. Baker, who has traced the introduction of Cinchona in a very able paper published in the Medical Transactions of the College of Physicians of London, iii. (1785) 141-216.

[1308] Namely No. 422. June 24-July 1; No. 426. July 22-29; No. 439. Oct. 21-28. No. 545. Dec. 9-16.—We have examined the copy at the British Museum.

[1309] Ph. Journ. vi. (1876) 1022.

[1310] In the Recueil for 1680, p. 275 (see appendix, Talbor) the king is said to have had another attack of fever at Windsor, for which he took “du Quinquina préparé,” which again cured him.

[1311] Le Remède anglais pour la guérison des fièvres, publié par ordre du Roy, avec les observations de Monsieur le premier Médecin de sa Majesté, sur la composition, les vertus, et l’usage de ce remède, par Nicolas de Blegny, Chirurgien ordinaire du corps de Monsieur, et Directeur de l’Académie des nouvelles découvertes de Médecine, Paris, 1682. 12°.

For the first accurate information on the botany of Cinchona, science is indebted to the French.[1312]

Charles-Marie de la Condamine, while occupied in common with Bouguer and Godin, as an astronomer from 1736 to 1743, in measuring the arc of a degree near Quito, availed himself of the opportunity to investigate the origin of the famous Peruvian Bark. On the 3rd and 4th of February, 1737, he visited the Sierra de Cajanuma, 2½ leagues from Loxa, and there collected specimens of the tree now known as Cinchona officinalis var. a. Condaminea. At that period the very large trees had already become rare, but there were still specimens having trunks thicker than a man’s body. Cajanuma was the home of the first cinchona bark brought to Europe; and in early times it enjoyed such a reputation, that certificates drawn up before a notary were provided as proof that parcels of bark were the produce of that favoured locality.

Joseph de Jussieu, botanist to the French expedition with which La Condamine was connected, gathered, near Loxa in 1739, a second Cinchona subsequently named by Vahl C. pubescens, a species of no medicinal value.

In 1742 Linnæus established the genus Cinchona,[1313] and in 1753 first described the species C. officinalis, recently restored and exactly characterized by Hooker, aided by specimens supplied to him by Mr. Howard.

The cinchona trees were believed to be confined to the region around Loxa, until 1752 when Miguel de Santisteban, superintendent of the mint at Santa Fé, discovered some species in the neighbourhood of Popayan and Pasto.

In 1761 José Celestino Mutis, physician to the Marquis de la Vega, viceroy of New Granada, arrived at Carthagena from Cadiz, and immediately set about collecting materials for writing a Flora of the country. This undertaking he carried on with untiring energy, especially from the year 1782 until the end of his life in 1808,—first for seven years at Real del Sapo and Mariquita at the foot of the Cordillera de Quindiu, and subsequently at Santa Fé de Bogotá. Mutis gave up his medical appointment in 1772, for the purpose of entering a religious order, and ten years later was entrusted by the Government with the establishment and direction of a large museum of natural history, first at Mariquita, afterwards at Santa Fé.

A position similar to that of Mutis in New Granada had also been conferred in 1777 on the botanists Hipolito Ruiz and José Pavon with regard to southern Peru, whence originated the well-known Flora Peruviana et Chilensis,[1314] as well as most important direct contributions to our knowledge on the subject of Cinchona.

About the same time (1776), Renquizo (Renquifo or Renjifo) found cinchona trees in the neighbourhood of Huanuco, in the central tract of Peru, whereby the monopoly of the district of Loxa was soon broken up.

[1312] Sur l’arbre de Quinquina par M. de la Condamine—Mém. de l’Académie royale des Sciences pour l’année 1738. pp. 226-243, with two plates.

[1313] Markham has vigorously contended that the name Cinchona should be altered to Chinchona as better commemorating the countess of Chinchon. But the inconvenience of changing so well-established a name and its many derivatives, has out-weighed these considerations.—See list of works relating to Cinchona at the end of the present article.

[1314] Published at Madrid, 1798-1802, in 4 volumes folio, with 425 plates.

Numerous and important quinological discoveries were subsequently made by Mutis, or rather by his pupils Caldas, Zea, and Restrepo,[1315] as well as on the other hand by Ruiz and Pavon, and their successors Tafalla and Manzanilla. Mutis did not bring his labours to any definite conclusion, and his extensive botanical collections and 5,000 coloured drawings, were sent to Madrid only in 1817, and there remained in a lamentable state of neglect.

Some of his observations first appeared in print in 1793-94, under the title of El Arcano de la Quina in the Diario, a local paper of Santa Fé, and were reprinted at Madrid in 1828 by Don Manuel Hernandez de Gregorio. The botanical descriptions of the cinchonas of New Granada, forming the fourth part of the Arcano, remained forgotten and lost to science until rescued by Markham and published in 1867.[1316] The drawings belonging to the descriptions were photographed and engraved a little later, and form part of Triana’s Nouvelles Etudes sur les Quinquinas, which appeared in 1870.

The two Peruvian botanists succeeded somewhat better in securing their results. Ruiz in 1792, in his Quinologia,[1317] and in 1801 conjointly with Pavon in a supplement thereto, brought together a portion of their important labours relating to cinchona. But an essential part called Nueva Quinologia,[1318] written between 1821 and 1826, remained unpublished; and after an oblivion of over thirty years, it came by purchase into the hands of Mr. John Eliot Howard, who published it, and with rare liberality enriched it with 27 magnificent coloured plates, mostly taken from the very specimens of Pavon lying in the herbarium of Madrid.

Between the pupils of Mutis on the one hand, and those of Ruiz and Pavon on the other, there arose an acrimonious controversy regarding their respective discoveries, which has been equitably summarized by Triana in the work just mentioned.

=Production=—The hardships of bark-collecting in the primeval forests of South America are of the severest kind, and undergone only by the half-civilized Indians and people of mixed race, in the pay of speculators or companies located in the towns. Those who are engaged in the business, especially the collectors themselves, are called Cascarilleros or Cascadores, from the Spanish word Cascara, bark. A major-domo at the head of the collectors directs the proceedings of the several bands in the forest itself, where provisions and afterwards the produce are stowed away in huts of slight construction.

Arrot in 1736, and Weddell and Karsten in our own day, have given from personal observation a striking picture of these operations.

[1315] “ ... Mutis n’avait qu’une notion inexacte et confuse du genre Cinchona et de ses véritables caractères; c’est en définitive qu’aucune de ses espèces, dans le sens strict du mot, n’a été reconnue ni découverte par lui.”—Triana, Nouv. Etudes, p. 8.

[1316] Markham, Chinchona Species of New Granada, Lond. 1867.

[1317] Quinologia, ó tratado de árbol de la Quina, ó Cascarilla, Madrid, 1792. 4°. pp. 103.

[1318] Supplemento á la Quinologia, Madrid, 1801. 4°. pp. 154.

The cascarillero having found his tree, has usually to free its stem from the luxuriant climbing and parasitic plants with which it is encircled. This done, he begins in most cases at once to remove, after a previous beating, the sapless layer of outer bark. In order to detach the valuable inner bark, longitudinal and transverse incisions are made as high as can be reached on the stem. The tree is then felled, and the peeling completed. In most cases, but especially if previously beaten, the bark separates easily from the wood. In many localities it has to be dried by a fire made on the floor of a hut, the bark being placed on hurdles above,—a most imperfect arrangement. In Southern Peru and Bolivia however, according to Weddell, even the thickest Calisaya bark is dried in the sun without requiring the aid of the fire.

The thinner bark as it dries rolls up into tubes or quills called canutos or canutillos, while the pieces stripped from the trunks are made to dry flat by being placed one upon another and loaded with weights, and are then known as plancha or tabla. The bark of the root was formerly neglected, but is now in several instances brought into the market.

After drying, the barks are either assorted, chiefly according to size, or all are packed without distinction in sacks or bales. In some places, as at Popayan, the bark is even stamped, in order to reduce its bulk as much as possible. The dealers in the export towns enclose the bark in serons[1319] of raw bullock-hide, which, contracting as it dries, tightly compresses the contents (100 lb. or more) of the package. In many places however wooden chests are used for the packing of bark.

=Conveyance to the Coast and Commercial Statistics=—The ports to which bark is conveyed for shipment to Europe are not very numerous.

Guayaquil on the Pacific coast is the most important for produce of Ecuador. The quantity shipped thence in 1871 was 7,859 quintals.[1320] Pitayo bark is largely exported from Buenaventura in the Bay of Choco further north.

Payta, the most northerly port of Peru, and Callao, the port of Lima, likewise export bark, the latter being the natural outlet for the barks of Central Peru from Huanuco to Cusco.

Islay, and more particularly Arica, receive the valuable barks of Carabaya and of the high valleys of Bolivia. In 1877 the export of Arica was equal to 5100 cwt.

The barks of Peru and Bolivia find an exceptional outlet also by the Amazon and its tributaries, and are shipped to Europe from port of Brazil. Howard[1321] has given an interesting account of one of the first attempts to utilize this eastern route, made by Senr. Pedro Rada in 1868.

There is a large export of the barks of New Granada, principally from Santa Marta, whence the shipments[1322] in 1871 were 3,415,149 lb.; and in 1872, 2,758,991 lb. From the neighbouring port of Savanilla, which represents the city of Barranquilla, the sea-terminus of the navigation of the Magdalena, the export of bark in 1871 was 1,043,835 lb., value £38,715;[1323] it amounted to 2 millions of kilogrammes in 1877. All Columbia is stated, in 1877, to have shipped 3½ millions of kilogrammes of bark; yet a good deal of the excellent barks of the Columbian State of Santander, especially those of the neighbourhood of Bucaramanga, find their way to Maracaibo, taking the name of that place.

[1319] From zurrón, the Spanish name for a pouch or game-bag.

[1320] Consular Reports, presented to Parliament, July 1872.

[1321] Seemann’s Journ. of Bot. vi. (1868) 323.

[1322] Consular Reports, August 1873. 743.

[1323] Ibid. August 1872.

Some Cinchona bark is also shipped from Venezuela by way of Puerto Cabello.

The quantity of bark appearing in the Annual Statement of Trade as “Peruvian Bark” imported into the United Kingdom in 1872, was 28,451 cwt., valued £285,620; of which 11,843 cwt. was shipped from New Granada, 4,668 cwt. from Ecuador, and 5,829 cwt. from Peru, the remainder being entered as from the ports of Chili, Brazil, Central America and other countries. The imports into the United Kingdom in 1876 were 26,021 cwt., valued at £272,154.

=Cultivation=—The reckless system of bark-cutting in the forests of South America, which has resulted in the utter extermination of the tree from many localities, has aroused the attention of the Old World, and has at length prompted serious efforts to cultivate the tree on a large scale in other countries.

The idea of cultivating Cinchonas out of their native regions was advanced by Ruiz in 1792, and by Fée of Strassburg in 1824.[1324] Royle[1325] pointed out in 1839 that suitable localities for the purpose might be found in the Neilgherry Hills and probably in many other parts of India, and argued indefatigably in favour of the introduction of the tree.

The subject was also urged in reference to Java in 1837 by Fritze, director of medical affairs in that island; in 1846 by Miquel, and subsequently by other Dutch botanists and chemists.[1326]

Living Cinchonas had been taken to Algeria as early as 1849, by the intervention of the Jesuits of Cusco, but their cultivation met with no success.

Weddell in 1848 brought cinchona seeds from South America to France, and strenuously insisted on the importance of cultivating the plant. His seeds, especially those of C. Calisaya, germinated at the Jardin des Plantes in Paris, and in June 1850, living seedlings were sent to Algeria; and in April 1852, through the Dutch Government, to Java.

The first important attempts at cinchona cultivation were made by the Dutch. Under the auspices of the Colonial Minister Pahud, afterwards Governor-General of the Dutch East Indies, the botanist Hasskarl was despatched to Peru for the purpose of obtaining seeds and plants. His mission was so far successful, that a collection of plants contained in 21 Wardian cases, was shipped in August 1854 from Callao, in a frigate sent expressly to receive them. Notwithstanding every care, the plants did not reach Java in good condition; and when Hasskarl resigned his appointment in 1856, he bequeathed to his successor Junghuhn only 167 young cinchonas, though 400 specimens had been shipped from South America.

[1324] Cours d’Hist. nat. pharmaceutique, ii. (1828) 252.

[1325] Illustrations of the Bot. of the Himalayan Mountains, i. (1839) 240.

[1326] According to K. W. van Gorkom, suggestions to the same end were made to the Dutch Government as early as 1829 by Reinwardt.

An impulse to the project of cinchona-planting was given in 1852 by Royle, in a report addressed to the East India Company, in which he pointed out that the Government of India were then spending more than £7,000 a year for Cinchona bark, in addition to about £25,000 for quinine.[1327]

After some unsatisfactory endeavours on the part of the British Government to obtain plants and seeds through the intervention of H. M. Consuls in South America, Mr. Markham offered his services, which were accepted. Markham, though not a professed botanist, was well qualified for the task by a previous acquaintance with the country and people of Peru and Bolivia, and by a knowledge of the Spanish and Quichua languages,—and even more so by a rare amount of zeal, intelligence, and forethought. Being fully aware of the difficulties of the undertaking, he earnestly insisted that nothing should be neglected which could ensure success; and in particular made repeated demands for a steam-vessel to convey the young plants across the Pacific to India, which unfortunately were not complied with. He further urged the desirableness of not confining operations to a single district, but of endeavouring to procure by different collectors all the more valuable species.

The prudence of this latter suggestion was evident, and Markham was enabled to engage the services of Richard Spruce, the distinguished botanist, then resident in Ecuador, who expressed his readiness to undertake a search for the Red Bark trees (C. succirubra) in the forests of Chimborazo. He also secured the co-operation of G. J. Pritchett for the neighbourhood of Huanuco, and of two skilful gardeners, John Weir and Robert Cross. The last named was employed in 1861 to procure seeds of C. officinalis from the Sierra de Cajanuma near Loxa, and in 1868-64 those of C. pitayensis from the province of Pitayo in Ecuador.[1328]

Markham reserved for himself the border-lands of Peru and Bolivia, in order to obtain C. Calisaya; and for this purpose started from Islay in March 1860. Arriving in the middle of April by way of Arequipa and Puno, at Curcero, the capital of the province of Carabaya, he made his way to the village of Sandia, near which he met with the first specimens of Cinchona in the form of the shrubby variety of C. Calisaya, termed Josephiana. He afterwards found the better variety a. vera, and also C. ovata R. et P., C. micrantha R. et P., and C. pubescens Vahl. Of these sorts, but chiefly of the first three, 456 plants were shipped at Islay in June 1860.

In consequence of the hostile attitude of the people, and the jealousy of the Bolivian Government, lest an important monopoly should be broken up, added to the difficulties arising from insalubrious climate and the want of roads, the obstacles encountered by Markham were very great, and no attempt could be made to wait for the ripening of the seeds of the Calisaya, which takes place in the month of August.[1329]

[1327] In 1870, the Indian Government purchased no less than 81,600 ounces of sulphate of quinine, besides 8,832 ounces of the sulphates of cinchonine, cinchonidine and quinidine. The quantities bought in subsequent years have been much smaller until the present year (1874).

[1328] Report on the Expedition to procure seeds of C. Condaminea (1862); also Report to the Under Secretary of State for India on the Pitayo Chinchona, by Robt. Cross, 1865.

[1329] Great difficulty was at first experienced in successfully conveying living Cinchona plants to India, even in Wardian cases; and the collections formed by Hasskarl, Markham, and Pritchett almost all perished after reaching their destination (Markham’s letter, 26 Feb. 1861). But the propagation by seed has proved very rapid.

The expedition of Spruce was successful, but was also attended with much difficulty and danger, of which there are vivid pictures in the interesting narratives by himself and by Cross, published in the Parliamentary Returns of 1863 and 1866.[1330]

The service entrusted, to Pritchett was also efficiently performed; and he succeeded in bringing to Southampton six cases containing plants of C. micrantha and C. nitida, besides a large supply of seeds.

Some important supplies of plants and seed for British India have likewise been obtained from the Dutch plantations in Java. Seeds of C. lancifolia, the tree affording the valuable bark of New Granada, were procured through Dr. Karsten.

Previously to the arrival in India of the first consignment of plants, careful inquiries were instituted from a meteorological and geological point of view, as to the localities most adapted for the cultivation. This resulted in the selection for the first trial of certain spots among the Neilgherry (or Nilgiri) Hills on the south-west coast of India and in the Madras Presidency. Of this district, the chief town is Ootocamund (or Utakamand), situated about 60 miles south of Mysore and the same distance from the Indian Ocean. Here the first plantation was established in a woody ravine, 7,000 feet above the sea-level, a spot pronounced by Mr. Markham to be exceedingly analogous, as respects vegetation and climate, to the Cinchona valleys of Carabaya. Other plantations were formed in the same neighbourhood, and so rapid was the propagation, that in September 1866, there were more than 1½ millions of Cinchona plants on the Neilgherry Hills alone.[1331] The species that grows best there is C. officinalis.

The number was stated to be in 1872, 2,639,285, not counting the trees of private planters. The largest are about 30 feet high, with trunks over 3 feet in girth. The area of the Government plantations on the Neilgherry Hills is 950 acres.[1332]

Plantations have also been made in the coffee-producing districts of Wynaad, and in Coorg, Travancore and Tinnevelly, in all instances, we believe, as private speculations.

Cinchona plantations have been established by the Government of India in the valleys of the Himalaya in British Sikkim,[1333] and some have been started in the same region by private enterprise. In the former there were on the 31st March 1870, more than 1½ millions of plants permanently placed, the species growing best being C. succirubra and C. Calisaya. The Cinchona plantation of Rungbi near Darjiling (British Sikkim) covered in 1872 2,000 acres. In the Kangra valley of the Western Himalaya, plantations have been commenced, as well as in the Bombay Presidency, and in British Burma.

[1330] Correspondence relating to the introduction of the Chinchona Plant into India, ordered by the House of Commons to be printed 20 March 1863 and 18 June 1866.

[1331] Blue Book (Chinchona Cultivation, 1870. p. 30).—A name that must always be remembered in connection with the Neilgherry plantations, is that of William Graham McIvor, who by his rare practical skill and sagacity in the cultivation and management of the tree, has rendered most signal services in its propagation in India.

[1332] Moral and material progress and condition of India during 1871-72, presented to Parliament 1873. p. 33.

[1333] The first annual Report dates from 1862 to 1863; I am indebted to Dr. King for that of 1876-1877.—F. A. F.

Ceylon offers favourable spots for the cultivation of Cinchona, in the mountain region which occupies the centre of the island, as at Hakgalle, near Neuera-Ellia, 5,000 feet above the sea, where a plantation was formed by Government in 1861. The production of bark has been taken up with spirit by the coffee-planters of Ceylon.

The Government of India has acted with the greatest liberality in distributing plants and seeds of Cinchona, and in promoting the cultivation of the tree among the people of India; and it has freely granted supplies of seed to other countries.

The plantations of Java commenced by Hasskarl, increased under Junghuhn’s management to such an extent, that in December 1862 there were 1,360,000 seedlings and young trees, among which however the more valuable species, as C. Calisaya, C. lancifolia, C. micrantha and C. succirubra, were by far the least numerous, whereas C. Pahudiana, of which the utility was by no means well established, amounted to over a million. The disproportionate multiplication of this last was chiefly due to its quickly yielding an abundance of seeds, and to its rapid and vigorous growth. Another defect in the early Dutch System of cultivation arose from the notion that the Cinchona requires to be grown in the shade of other trees, and to a less successful plan of multiplying by cuttings and layers.

These and other matters were the source of animated and often bitter discussions, which terminated on the one hand by the death of Junghuhn in 1864, and on the other by the skilful investigations of De Vry. This eminent chemist was despatched by the Government of Holland in 1857 to Java, that he might devote his chemical knowledge to the investigation of the natural productions of the island, including the then newly introduced Cinchona. It was March 16th, 1859, when Dr. de Vry laid before the governor-general, Mr. Pahud, the first crystals of sulphate of quinine he had prepared from bark grown in that island.

Under K. W. van Gorkom, who was appointed superintendent in 1864, the Dutch plantations have assumed a very prosperous state. J. C. Bernelot Moens,[1334] the present director, stated that at the end of 1878 the leading species was Calisaya in its various forms, including more than 400,000 plants of Ledger’s Calisaya. Numerous analyses of Bernelot Moens show a percentage of from 4½ to 10·6 of quinine in the latter variety. Some of them, however, in December 1878, afforded not more than 0·64 per cent. of quinine and 1·26 of cinchonidine.

The regular shipments of the barks from Java to the Amsterdam market are going on, and the barks are sold there with regard to the results of the government chemist’s analyses.

Cinchona Bark from the Indian plantations began to be brought into the London market in 1867,[1335] and now arrives in constantly increasing quantities.

The history of the transplantation of the Cinchona down to the year 1867 has been made the subject of the report of Soubeiran and Delondre mentioned at the end of the present article.

[1334] I am indebted to the Dutch administration for their interesting statistical documents relating to Cinchona.—F. A. F.

[1335] When I was in London, in August 1867, I went to Finsbury Place, to meet Mr. Spruce, and was happy enough to find there also Mr. Howard, who presented Mr. S. and myself with market samples of the first importation of C. succirubra, from Denison plantation, Ootacamund.—F. A. F.

=Description=—(=A.=) Of Cinchona Barks generally—In the development of their bark, the various species of Cinchona exhibit considerable diversity. Many are distinguished from an early stage by an abundant exfoliation of the outer surface, while in others this takes place to a smaller degree, or only as the bark becomes old. The external appearance of the bark varies therefore very much, by reason of the greater or less development of the suberous coat. The barks of young stems and branches have a greyish tint more or less intense, while the outer bark of old wood displays the more characteristic shades of brown or red, especially after removal of the corky layers.

In the living bark, these colours are very pale, and only acquire their final hue by exposure to the air, and drying. Some of them however are characteristic of individual species, or at least of certain groups, so that the distinctions originated by the bark-collectors of pale, yellow, red, etc.[1336] and adopted by druggists, are not without reason.

In texture, the barks vary in an important manner by reason of diversity in anatomical structure. Their fracture especially depends upon the number, size, and arrangement of the liber-fibres, as will be shown in our description of their microscopic characters.

The taste in all species is bitter and disagreeable, and in some there is in addition a decided astringency. Most species have no marked odour, at least in the dried state. But this is not the case in that of C. officinalis, the smell of which is characteristic.

(=B.=) Of the Barks used in pharmacy—For pharmaceutical preparations as distinguished from the pure alkaloids and their salts, the Cinchona barks employed are chiefly of three kinds.

1. Pale Cinchona Bark, Loxa Bark, Crown Bark[1337]—This bark, which previous to the use of Quinine and for long afterwards, was the ordinary Peruvian Bark of English medicine, is only found in the form of quills, which are occasionally as much as a foot in length, but are more often only a few inches or are reduced to still smaller fragments. The quills are from ¾ down to an ⅛ of an inch in diameter, often double, and variously twisted and shrunken. The thinnest bark is scarcely stouter than writing paper; the thickest may be ⅒ of an inch or more.[1338] The pieces have a blackish brown or dark greyish external surface, variously blotched with silver-grey, and often beset with large and beautiful lichens. The surface of some of the quills is longitudinally wrinkled and moderately smooth; but in the majority it is distinctly marked by transverse cracks, and is rough and harsh to the touch. The inner side is closely striated and of a bright yellowish-brown.

The bark breaks easily with a fracture which exhibits very short fibres on the inner side. It has a well-marked odour sui generis, and an astringent bitter taste. Though chiefly afforded by C. officinalis, some other species occasionally contribute to furnish the Loxa Bark of commerce as shown in the conspectus at p. 355.

[1336] The following are common terms in reference to the barks of Peru:—Amarilla (yellow), blanca (white), colorado or roja (red), naranjada (orange), negrilla (brown).

[1337] Cortex Cinchonæ pallidæ; F. Quinquina Loxa; G. Loxachina. The term Crown Bark was originally restricted to a superior sort of Loxa Bark, shipped for the use of the royal family of Spain.

[1338] In the old collections of the Royal College of Physicians, there are specimens of very thick Loxa Bark, of a quality quite unknown there at the present day. They are doubtless the produce of ancient trees, such as were noticed by La Condamine.

2. Calisaya Bark, Yellow Cinchona Bark.[1339]—This bark, which is the most important of those commonly used in medicine, is found in flat pieces (α.), and in quills (β.), both afforded by C. Calisaya Wedd., though usually imported separated.

α. Flat Calisaya—is in irregular flat pieces, a foot or more in length by 3 to 4 inches wide, but usually smaller, and ²/₁₀ to ⁴/₁₀ of an inch in thickness; devoid of suberous layers and consisting almost solely of liber, of uniform texture, compact and ponderous. Its colour is a rusty orange-brown, with darker stains on the outer surface. The latter is roughened with shallow longitudinal depressions, sometimes called digital furrows.[1340] The inner side has a wavy, close, fibrous texture. The bark breaks transversely with a fibrous fracture; the fibres of the broken ends are very short, easily detached, and with a lens are seen to be many of them faintly yellowish and translucent.

A well-marked variety, known as Bolivian Calisaya, is distinguished for its greater thinness, closer texture, and for containing numerous laticiferous ducts which are wanting in common flat Calisaya bark.

β. Quill Calisaya—is found in tubes ¾ to 1½ inch thick, often rolled up at both edges, thus forming double quills. They are always coated with a thick, rugged, corky layer, marked with deep longitudinal and transverse cracks, the edges of which are somewhat elevated. This suberous coat, which is silvery white or greyish, is easily detached, leaving its impression on the cinnamon-brown middle layer. The inner side is dark brown and finely fibrous. The transverse fracture is fibrous but very short. The same bark also occurs in quills of very small size, and is then not distinguishable with certainty from Loxa bark.

3. Red Cinchona Bark.—Though still retaining a place in the British Pharmacopœia, this is by far the least important of the Cinchona barks employed in pharmacy. But as the tree yielding it (C. succirubra) is now being cultivated on a large scale in India, the bark may probably come more freely into use.

Red Bark of large stems, which is the most esteemed kind, occurs in the form of flat or channelled pieces, sometimes as much as ½ an inch in thickness, coated with their suberous envelope which is rugged and warty. Its outermost layer in the young bark has a silvery appearance. The inner surface is close and fibrous and of a brick-red hue. The bark breaks with a short fibrous fracture.[1341]

(=C.=) Of the Barks not used in pharmacy—Among the non-officinal barks, the most important are afforded by Cinchona lancifolia Mutis and C. pitayensis Wedd., natives of the Cordilleras of Columbia.

These barks are largely imported and used for making quinine, the former under the name of Columbian, Carthagena, or Caqueta bark. It varies much in appearance, but is generally of an orange-brown; the corky coat, which scales off easily, is shining and whitish. The barks of C. lancifolia often occur in fine large quills or thick flattish pieces. Their anatomical structure agrees in all varieties which we have examined, in the remarkable number of thick-walled and tangentially-extended cells of the middle cortical layer and the medullary rays. In percentage of alkaloids, Carthagena barks are liable to great variation.

[1339] Cortex Cinchonæ flavæ, Cortex Chinæ regius; F. Quinquina Calisaya; G. Königschina.

[1340] From the notion that they resemble the marks left by drawing the fingers over wet clay.

[1341] Thick Red Bark that happens to have a very deep and brilliant tint is eagerly bought at a high price for the Paris market.

The Pitayo Barks are restricted to the south-western districts of Columbia,[1342] and are usually imported in short flattish fragments, or broken quills, of brownish rather than orange colour, mostly covered with a dull greyish or internally reddish cork. The middle cortical layer exhibits but few thick-walled cells; the liber is traversed by very wide medullary rays, and is provided with but a small number of widely scattered liber-fibres, which are rather thinner than in most other Cinchona barks. The Pitayo barks are usually rich in alkaloids, quinine prevailing. Cinchona pitayensis is one of the hardiest species of the valuable Cinchonas, and is therefore particularly suitable for cultivation, which however has not yet been carried out as largely as that of either C. officinalis or C. succirubra.

In the Conspectus on the next page, we have arranged the principal species of Cinchona, with short indications of the barks which some of them afford.[1343]

=Microscopic Structure=—The first examination of the minute structure of Cinchona barks is due to Weddell, whose observations have been recorded in one of his beautiful plates published in 1849.[1344] Since that time numerous other observers have laboured in the same field of research.

General Characters.—These barks, as contrasted with those of other trees, do not exhibit any great peculiarities of structure; and their features may be comprehended in the following statements. The epidermis, in the anatomical sense, occurs only in the youngest barks, which are not found in commerce. The corky layer, which replaces the epidermis, is constructed of the usual tabular cells. In some species as C. Calisaya, it separates easily, at least in the older bark, whereas in others as C. succirubra, the bark even of trunks is always coated with it. In several species the corky tissue is not only found on the surface, but strips of it occur also in the inner substance of the bark. In this case the portions of tissue external to the inner corky layers or bands are thrown off as bork-scales (periderm of Weddell). This peculiar form of suberous tissue[1345] was first examined (not in cinchona) in 1845 by H. von Mohl, who called it rhytidoma (Borke of the Germans). In C. Calisaya it is of constant occurrence, but not so usually in C. succirubra and some others; the rhytidoma therefore affords a good means of distinguishing several barks.

The inner portion of the bark exhibits a middle or primary layer (mesophlœum),[1346] made up of parenchyme; and a second inner layer or liber (endophlœum)[1347] displaying a much more complicated structure. The primary layer disappears if rhytidoma is formed: barks in which this is the case are therefore at last exclusively composed of liber, of which Flat Calisaya Bark is a good example.

[1342] Pitayo is an Indian village eastward of Popayan; see map of the country between Pasto and Bogotá in Blue Book (East India Chinchona Plant) 1866. 257.

[1343] Two species included by Weddell in his Notes sur les Quinquinas, namely C. Chomeliana Wedd. and C. barbacoensis Karst., have been omitted, as not in our opinion belonging to the genus.

[1344] Hist. nat. des Quinquinas, tab. ii.

[1345] Flückiger, Grundlagen, Berlin, 1872. 61. fig. 48.

[1346] Enveloppe ou tunique cellulaire of Weddell; Mittelrinde of the Germans.

[1347] In German Bast, or Phloëm of modern German botany.

CONSPECTUS OF THE PRINCIPAL SPECIES OF CINCHONA.

---------------------------------+----------------+-------------+------ SPECIES (EXCLUDING SUB-SPECIES | | | WHERE AND VARIETIES) | WHERE FIGURED. | NATIVE | CULTI- ACCORDING TO WEDDELL. | | COUNTRY. | VATED. ---------------------------------+----------------+-------------+------- I. Stirps Cinchonæ officinalis | | | 1. Cinchona officinalis Hook |Bot. Mag. 5804 |Ecuador |India, | | (Loxa) |Ceylon, | | |Java. 2. ” macrocalyx Pav. |Howard N. Q. |Peru | | | | 3. ” lucumæfolia Pav. | Do. |Ecuador, | | |Peru. | 4. ” lanceolata R. et P.(?)| Do. |Peru | 5. ” lancifolia Mutis |Karsten tab. 11.|New Granada |India | 12.| | 6. ” amygdalifolia Wedd. |Wedd. tab. 6. |Peru, Bolivia| | | | II. Stirps Cinchonæ rugosæ | | | 7. Cinchona pitayensis Wedd. |Karst. tab. 22. |New Granada |India |(C. Trianæ). |(Popayan) | 8. ” rugosa Pav. |Howard N. Q. |Peru | 9. ” Mutisii Lamb. | Do. |Ecuador | 10. ” hirsuta R. et P. |Wedd. tab. 21. |Peru | 11. ” carabayensis Wedd. |Wedd. tab. 19. |Peru, Bolivia| 12. ” Pahudiana How. |Howard N. Q. |Peru |India, | | |Java 13. ” asperifolia Wedd. |Wedd. tab. 20. |Bolivia | 14. ” umbellulifera Pav. |Howard N. Q. |Peru | 15. ” glandulifera R. et P. | Do. |Peru | 16. ” Humboldtiana Lamb. | Do. |Peru | | | | III. Stirps Cinchonæ micranthæ | | | 17. Cinchona australis Wedd. |Wedd. tab. 8. |South Bolivia| 18. ” scrobiculata H. et B. | Do. |Peru | 19. ” peruviana How. |Howard N. Q. |Peru |India 20. ” nitida R. et P. | Do. |Peru |India 21. ” micrantha R. et P. | Do. |Peru |India | | | IV. Stirps Cinchonæ Calisayæ | | | 22. Cinchona Calisaya Wedd. |Wedd. tab. 9. |Peru, Bolivia|India, | | |Ceylon, | | |Java, | | |Jamaica, | | |Mexico. 23. ” elliptica Wedd. | |Peru | | | (Carabaya) | | | | V. Stirps Cinchonæ ovatæ | | | 24. Cinchona purpurea R. et P. |Howard N. Q. |Peru | | | (Huamalica) | 25. ” rufinervis Wedd. | Do. |Peru, | | |Bolivia | 26. ” succirubra Pav. | Do. |Ecuador |India, | | |Ceylon, | | |Java, | | |Jamaica. 27. ” ovata R. et P. | Do. |Peru, |India(?), | |Bolivia |Java(?) 28. ” cordifolia Mutis |Karsten tab. 8. |New Granada, | | |Peru | | | | 29. ” tucujensis Karst. |Karsten tab. 9. |Venezuela | 30. ” pubescens Vahl |Wedd. tab. 16. |Ecuador, | | | Peru, | | |Bolivia | | | | 31. ” purpurascens Wedd. |Wedd. tab. 18 |Bolivia | ---------------------------------+----------------+-------------+

---------------------------------+------------------------------------ SPECIES (EXCLUDING SUB-SPECIES | AND VARIETIES) | PRODUCT ACCORDING TO WEDDELL. | ---------------------------------+------------------------------------ I. Stirps Cinchonæ officinalis | 1. Cinchona officinalis Hook | Loxa or Crown Bark, Pale Bark. | 2. ” macrocalyx Pav. | Ashy Crown Bark. The sub-species | C. Palton affords an important | sort called Palton Bark much | used in the manufacture of quinine. 3. ” lucumæfolia Pav. | | 4. ” lanceolata R. et P.(?)| Carthagena Bark, confounded with | Palton Bark, but is not so good. 5. ” lancifolia Mutis | Columbian Bark. Imported in large | quantities for manufacture of | quinine.The soft Columbian Bark is | produced by Howard’s var. | oblonga. | 6. ” amygdalifolia Wedd. | A poor bark, but not now imported. | II. Stirps Cinchonæ rugosæ | 7. Cinchona pitayensis Wedd. | Pitayo Bark. Very valuable; used by | makers of quinine; it is the chief | source of quinidine. | 8. ” rugosa Pav. | Bark unknown, probably valueless. 9. ” Mutisii Lamb. | Bark not in commerce, contains only | aricine. 10. ” hirsuta R. et P. | 11. ” carabayensis Wedd. | Bark not collected. 12. ” Pahudiana How. | A poor bark, yet of handsome | appearance; propagation of tree | discontinued. | 13. ” asperifolia Wedd. | Bark not collected. 14. ” umbellulifera Pav. | Bark not known as a distinct sort. 15. ” glandulifera R. et P. | Do. 16. ” Humboldtiana Lamb. | False Loxa Bark, Jaen Bark. A very | bad bark. | III. Stirps Cinchonæ micranthæ | 17. Cinchona australis Wedd. | An inferior bark, mixed with | Calisaya. 18. ” scrobiculata H. et B. | Bark formerly known as _Red | Cusco Bark_ or Santa Ana Bark. 19. ” peruviana How. | 20. ” nitida R. et P. | Grey Bark, Huanuco or Lima Bark. | Chiefly consumed on the Continent. 21. ” micrantha R. et P. | | IV. Stirps Cinchonæ Calisayæ | 22. Cinchona Calisaya Wedd. | Calisaya Bark, Bolivian Bark, | Yellow Bark. The tree exists under | many varieties, bark also very | variable. | 23. ” elliptica Wedd. | Carabaya Bark. Bark scarcely now | imported. C. sunsura Miq. | (flower and fruit unknown) | may perhaps be this species. | V. Stirps Cinchonæ ovatæ | 24. Cinchona purpurea R. et P. | Huamalies Bark. Not now Imported. | 25. ” rufinervis Wedd. | Bark, a kind of light Calisaya. | 26. ” succirubra Pav. | Red Bark. Largely cultivated in | British India. | 27. ” ovata R. et P. | Inferior Brown and Grey Barks. | 28. ” cordifolia Mutis | Columbian Bark (in part). Tree | exists under many varieties; bark | of some used in manufacture of | quinine. | 29. ” tucujensis Karst. | Maracaibo Bark. | 30. ” pubescens Vahl | Arica Bark (Cusco Bark from var. | Pelletieriana). Some of the | varieties contain aricine. | C. caloptera Miq. is probably | a var. of this species. | 31. ” purpurascens Wedd. | Bark unknown in commerce. ---------------------------------+-----------------------------------------

The liber is traversed by medullary rays, which in cinchona are mostly very obvious, and project more or less distinctly into the middle cortical tissue. The liber is separated by the medullary rays into wedges,[1348] which are constituted of a parenchymatous part and of yellow or orange fibres. The number, colour, shape, and size, but chiefly the arrangement of these fibres, confer a certain character common to all the barks of the group under consideration.

The liber-fibres[1349] are elongated and bluntly pointed at their ends, but never branched, mostly spindle-shaped, straight or slightly curved, and not exceeding in length 3 millimetres. They are consequently of a simpler structure than the analogous cells of most other officinal barks. They are about ¼ to ⅓ mm. thick, their transverse section exhibiting a quadrangular rather than a circular outline. Their walls are strongly thickened by numerous secondary deposits, the cavity being reduced to a narrow cleft, a structure which explains the brittleness of the fibres. The liber-fibres are either irregularly scattered in the liber-rays, or they form radial lines transversely intersected by narrow strips of parenchyme, or they are densely packed in short bundles. It is a peculiarity of cinchona barks that these bundles consist always of a few fibres (3 to 5 or 7), whereas in many other barks (as cinnamon) analogous bundles are made up of a large number of fibres. Barks provided with long bundles of the latter kind acquire therefrom a very fibrous fracture, whilst cinchona barks from their short and simple fibres exhibit a short fracture. It is rather granular in Calisaya bark, in which the fibres are almost isolated by parenchymatous tissue. In the bark of C. scrobiculata, a somewhat short fibrous fracture[1350] is due to the arrangement of the fibres in radial rows. In C. pubescens, the fibres are in short bundles and produce a rather woody fracture.

Besides the liber-fibres, there are some other cells contributing to the peculiarity of individual cinchona barks. This applies chiefly to the laticiferous ducts or vessels[1351] which are found in many sorts; they are scattered through the tissue intervening between the middle cortical layer and the liber, and consist of soft, elongated, unbranched cells, mostly exceeding in diameter the neighbouring parenchymatous cells.

As to the contents of the tissue of cinchona barks, crystallized alkaloids are not visible. Howard has published figures representing minute rounded aggregations of crystalline matter in the cells, which he supposes to be kinovates of the alkaloids; and also distinct acicular crystals which he holds to be of the same nature. These remarkable appearances are easily observable, yet only after sections of the bark have been boiled for a minute in weak caustic alkali and then washed with water; it may well be doubted whether they are strictly natural. The liquids which are capable of dissolving the alkaloids in the free state do not afford any if they are applied to the barks. The alkaloids being contained in the bark in the form of salts, the latter are decomposed by caustic lye, and the alkaloids set at liberty assume the crystallized state. This is in our opinion the origin of the crystals under notice.

[1348] Baststrahlen or Phloëmstrahlen of the Germans.

[1349] Fibres corticales of Weddell; Baströhren or Bastzellen in German.

[1350] Fracture filandreuse, Weddel; fädiger Bruch of the Germans.

[1351] Vaisseaux laticifères of Weddell; Milchsaftschläuche in German.

The greater number of the parenchymatous cells are loaded with small starch granules, or in young and fresh barks with chlorophyll. In several barks, as in that of C. lancifolia Mutis, numerous cells of the middle cortical layer and even of the medullary rays, are provided with somewhat thick walls, and contain either a soft brown mass or crystalline oxalate of calcium. These cells have therefore been called resin-cells and crystal-cells; they are mostly isolated, not forming extensive groups or zones, and their walls are not strongly thickened as in true sclerenchymatous tissue. If thin sections of the barks are moistened with dilute alcoholic perchloride of iron, the walls of the cells, except the fibres and the cork, assume a blackish-green due to cincho-tannic acid; this applies even to the starch granules.

Characters of particular sorts.—The modifications of general structure just described, are sufficient to impart a special character to the bark of many species of Cinchona, provided the bark is examined at its full development, the structural peculiarities being far from well-marked in young barks.

Thus it is not possible to point out any distinctive features for the Loxa Bark of commerce, because it is mostly taken from young wood. We may say of it, that neither resin-cells nor crystal-cells occur in its middle layer, that its laticiferous vessels become soon obliterated, and have indeed disappeared in the older quills; and that the liber-fibres form interrupted, not very regular, radial rows.

The quills of C. Calisaya display large laticiferous ducts, which are wanting in the flat bark. There is a peculiar sort of the latter called Bolivian Calisaya (already mentioned at p. 353), the flat pieces of which still possess very obvious laticiferous vessels. As to the liber-fibres of Calisaya bark, they are, as before stated (p. 356), scattered throughout the parenchymatous tissue or endophlœum. In the bark of C. scrobiculata, which might at first sight be confounded with Calisaya bark, the liber-fibres form radial, less interrupted rows. The microscope affords therefore the means of distinguishing these two barks.

The barks of C. succirubra are particularly rich in laticiferous ducts, mostly of considerable diameter, in which the formation of new parenchyme may not unfrequently be observed. The orange liber-fibres occurring in this bark are less numerous, more scattered, and of smaller size than in Calisaya. The fracture of Red Bark, especially the flat sort, is therefore more finely granular and not so coarse as that of Calisaya.

The structural characters of Cinchona barks may lastly be fully appreciated by examining barks of the allied genera Buena, Cascarilla and Ladenbergia, which were formerly known under the name of False Cinchona Barks. The microscope shows that the liber-fibres of the latter are soft, branched and long, densely packed into large bundles, imparting therefore a well-marked fibrous structure. The external appearance of these barks is widely different from that of true cinchona barks; none of them it would appear is now collected for the purpose of adulteration.

=Chemical Composition=—The most important and at the same time peculiar principles of Cinchona bark are the Alkaloids,—enumerated in the following table:—[1352]

Cinchonine C₂₀H₂₄N₂O. or, as proposed by Skraup (1878) C₁₉H₂₂N₂O. Cinchonidine (Quinidine of many writers) same formula. Quinine C₂₀H₂₄N₂O₂. Quinidine (Conquinine of Hesse) same formula. Quinamine C₁₉H₂₄N₂O₂. Conquinamine (Conchinamine) same formula.

B. A. Gomes[1353] of Lisbon (1810) first succeeded in obtaining active principles of cinchona, by treating an alcoholic extract of the bark with water, adding to the solution caustic potash, and crystallizing the precipitate from alcohol. The basic properties of the substance thus obtained, which Gomes called Cinchonino, were observed in the laboratory of Thénard by Houtou-Labillardière, and communicated to Pelletier and Caventou.[1354] Shortly before that time, Sertürner had asserted the existence of organic alkalis: and the French chemists, guided by that brilliant discovery, were enabled to show that the Cinchonino of Gomes belonged to the same class of substances. Pelletier and Caventou, however, speedily pointed out that it consisted of two distinct alkaloids, one of which they named Quinine, the other Cinchonine. In 1827 the Institut de France awarded to the two chemists for their discovery the Montyon prize of 10,000 francs (see page 57, note 4).

[1352] Hesse, in 1877, pointed out the existence of a series of new alkaloids existing in Cinchona. We refrain from repeating his statements, which will be found abstracted in the Yearbook of Pharm. 1878. 63.

[1353] Ensaio sobre o Cinchonino, e sobre sua influencia na virtude da quina e d’outras cascas.—Mem. da Acad. R. das Sciencias de Lisboa, iii. (1812) 202-217.

[1354] Ann. de Chim. et de Phys. xv. (1820) 292.

Cinchonidine (thus called by Pasteur in 1853) was first obtained and characterized under the name of Quinidine in 1847, by F. L. Winckler of Darmstadt, from Maracaibo Bark (C. tucujensis Karst.); and in 1852 it was more closely studied by Leers, still under the name of quinidine.

Cinchovatine, formerly stated to be a peculiar alkaloid, has been shown by Hesse in 1876 to agree with cinchonidine.

Quinidine is the name applied by Henry and Delondre to an alkaloid they obtained in 1833; its peculiar nature was not clearly proved until 1853, when Pasteur examined it, and 1857 when De Vry showed its identity with the Beta-quinine extracted in 1849 by Van Heijningnen from commercial quinoidin. The name quinidine having been since applied to different basic substances more or less pure, Hesse (1865) has proposed to replace it by that of Conquinine (Conchinin in German). The alkaloid is especially characteristic of the Pitayo barks, and also occurs in the Calisaya barks from Java.

Quinamine was discovered in 1872 by Hesse, in bark of C. succirubra cultivated at Darjiling in British Sikkim; it is also of common occurrence in the barks collected in Java. Conquinamine was extracted in 1873 by Hesse from old barks from British India.

Paricine is another basic substance discovered in 1845 by Winckler, in the bark of Buena hexandra Pohl. Hesse detected it along with quinamine in the bark of C. succirubra; its composition is not yet known.

Aricine, C₂₃H₂₆N₂O₄, and Cusconine, C₂₃H₂₆N₂O₄ + 2 OH₂, occur in the so-called false Cinchona barks of not ascertained botanic origin. These alkaloids differ in many respects from those of true Cinchona barks.[1355]

Pitoyine was pointed out by Peretti (1837), but Hesse has shown (1873) that the bark called China bicolorata Tecamez[1356] or Pitoya Bark from which it was obtained, is altogether destitute of alkaloid.

Lastly may be mentioned Paytine, C₂₁H₂₄N₂O + OH₂, a crystallizable alkaloid discovered in 1870 by Hesse in a white bark of uncertain origin.[1357] It is allied to quinamine and quinidine, but has not been met with in any known cinchona bark.

By heating for a length of time solutions of the cinchona alkaloids with an excess of some mineral acid, Pasteur (1753) obtained amorphous modifications of the natural bases. Quinine thus afforded Quinicine, having the same composition; cinchonine and cinchonidine furnished Cinchonicine, likewise agreeing in composition with the alkaloids from which it originates. These amorphous products may also be obtained by heating the natural bases in glycerin at 200° C., when a red substance is also formed. In quinine manufactories, amorphous alkaloids are constantly met with, being partly produced in the course of the manipulations to which the materials are subjected. Yet cinchona barks also afford amorphous alkaloids at the very outset of analysis, whence we must infer their existence in the living plant.

The name Quinoidine (or rather “Chinioïdin”) was applied by Sertürner (1829) to an uncrystallizable basic substance, which he prepared from cinchona barks, and found to be a peculiar alkaloid. The term has subsequently been bestowed upon a preparation which has found its way into commerce and medical practice, in the form of a dark brown brittle extractiform mass, softening below 100° C., and having usually a slight alkaline reaction. It is obtained in quinine factories by precipitating the brown mother-liquors with ammonia, and contains the amorphous alkaloids naturally occurring in the barks. Quinoidin should not be used unless, when previously dried at 100°, it proves to afford at least 70 per cent. of alkaloids soluble in ether.

Quinine and the allied alkaloids have not been met with in any appreciable amount in other parts of the cinchonas than the bark, nor has their presence been ascertained in other plants than those of the tribe Cinchoneæ.

[1355] Yearbook of Pharm. 1878. 59.

[1356] So called from Tecamez or Tacames, a small port of Ecuador in about lat. 1° N. The bark which was first noticed in Lambert’s Description of the Genus Cinchona, 1797. 30. tab. ii., is of unknown botanical origin. In its external appearance, as well as in its structure, this bark is widely different from any Cinchona bark.—See also Vogl, in the second pamphlet quoted at page 391. 10; Oberlin and Schlagdenhauffen, Journ. de Pharm. 28. (1878) 252.

[1357] Flückiger in Wiggers and Husemann, Jahresbericht for 1872. 132.

Characters of the Cinchona Alkaloids.

1. Quinine.—It is obtained from alcoholic solutions, in prisms of the composition C₂₀H₂₄N₂O₂ + 3 OH₂, fusing at 57° C. The crystals may be deprived of water by warming or exposure over oil of vitriol, and they fuse at 177° C. The anhydrous alkaloid is likewise crystallizable; it requires about 21 parts of ether for solution, but dissolves more readily in chloroform or absolute alcohol. These solutions deviate the ray of polarized light to the left, and so do likewise solutions of the salts of quinine. Yet one and the same quantity of alkaloid exhibits a very different rotatory power according to the solvent used, though the volume of the solution remain the same. Even the common sulphate differs in this respect from the two other sulphates of quinine. The same remark applies to the optical power of the other alkaloids.

If ten volumes of a solution of quinine, or of one of its salts, are mixed in a test tube with one volume of chlorine water, and a drop of ammonia is added, a brilliant green colour makes its appearance. In solutions rich in quinine, a green precipitate, Thalleioquin or Dalleiochine is produced; in solutions containing less than ¹/₁₀₀₀ of quinine, no precipitate is formed, but the fluid assumes a green even more beautiful than in a stronger solution. The test succeeds with a solution containing only one part of quinine in 5,000, and in a solution containing not more than ¹/₂₀₀₀ of quinine, if bromine is used instead of chlorine.[1358]

The bitter taste of quinine is not appreciable in solutions containing less than one part in 100,000. The blue fluorescence displayed by a solution of quinine in dilute sulphuric acid is observable in solutions containing much less than one part in 200,000 of water; yet it is not apparent in very strong solutions.

Besides the common medicinal sulphate, 2 C₂₀H₂₄N₂O₂ + SO₄H₂ + 8 OH₂, quinine forms two other crystallizable sulphates, namely the sulphate, C₂₀H₂₄N₂O₂ + SO₄H₂ + 7 OH₂, and a third having the composition C₂₀H₂₄N₂O₂ + 2 SO₄H₂ + 7 OH₂.

Herapath, at Bristol, showed in 1852 that quinine forms with sulphuric acid and iodine a peculiar compound, Iodo-sulphate of Quinine, having the composition (C₂₀H₂₄N₂O₂)₄ + 3 (SO₄H₂) + 2 HI + 4 I + 3 OH₂. As this substance possesses optical properties analogous to those of tourmaline, it was called by Haidinger, Herapathite. It may be easily obtained by dissolving sulphate of quinine in 10 parts of weak spirit of wine containing 5 per cent. of sulphuric acid, and adding an alcoholic solution of iodine until a black precipitate is no longer formed. This precipitate is collected on a filter and washed with alcohol; then dissolved in boiling spirit of wine and allowed to crystallize. The tabular crystals thus obtained are extremely remarkable on account of their dichroism and polarizing power, as well as for the sparing solubility, since they require 1000 parts of boiling water for solution; their sparing solubility in cold alcohol may be utilized for separating quinine from the other cinchona alkaloids and estimating its quantity.

2. Quinidine or Conquinine—forms crystals having the composition, C₂₀H₂₄N₂O₂ + 2 OH₂; the anhydrous alkaloid melts at 168° C., and requires about 30 parts of ether for solution. Its solutions are strongly dextrogyre; it agrees with quinine as regards bitterness, fluorescence and the thalleioquin test, and forms a neutral and an acid sulphate. The most striking character of quinidine is afforded by its hydriodate, the crystals of which require for solution at 15° C., 1250 parts of water or 110 parts of alcohol sp. gr. ·834. Quinidine may therefore be separated from the other alkaloids of bark by a solution of iodide of potassium which will precipitate the hydriodate. According to Hesse (1873), quinidine is further characterized by the fact that its sulphate is soluble in 20 parts of chloroform at 15° C., the sulphates of the other cinchona alkaloids being far less soluble in that liquid. The common medicinal sulphate of quinine, e.g., requires for solution 1000 parts of chloroform.

[1358] Pharm. Journ., May 11, 1872. 901.

3. Cinchonine.—This alkaloid forms crystals which are always anhydrous; they fuse at 257° C., and require about 400 parts of ether and 120 of spirit of wine for solution. Cinchonine further differs from quinine by its dextrogyre power, its want of fluorescence, and its non-susceptibility to the thalleioquin test. Its hydriodate is readily soluble in water, and still more so in alcohol whether dilute or strong.

4. Cinchonidine.—forms anhydrous crystals melting at 206° C., soluble in 76 parts of ether, or 20 of spirit of wine, then affording levogyre liquids, devoid of fluorescence, and not acquiring a green colour (thalleioquin) by means of chlorine water and ammonia. Hydrochlorate of cinchonidine forms pyramidal crystals of the monoclinic system, very different from the hydrochlorates of the allied alkaloids.

5. Quinamine.—The crystals are anhydrous, fuse at 172° C., and form at a temp. of 20°, with 32 parts of ether or 100 parts of spirit of wine, a dextrogyre solution. Quinamine is even to some extent soluble in boiling water, and abundantly in boiling ether, benzol, or petroleum ether. The solutions of quinamine do not stand the thalleioquin test, nor do they display fluorescence; in acid solution, the alkaloid is liable to be transformed into an amorphous state. Quinamine moistened with concentrated nitric acid, assumes like paytine a yellow coloration. Its hydriodate is readily soluble in boiling water, but very sparingly in cold water, especially in presence of iodide of potassium, in which respect it is allied to quinidine as well as to paytine.

The more important properties of the Cinchona alkaloids may be summarized as follows:—

a. Hydrated crystals are formed by Quinine, Quinidine, (or Conquinine). No hydrated crystals by Cinchonine, Cinchonidine, Quinamine.

b. Abundantly soluble in ether Quinine, Quinidine, Quinamine, and the amorphous alkaloids. Sparingly soluble in ether Cinchonidine. Almost insoluble in ether Cinchonine.

c. Levogyre solutions afforded by Quinine, Cinchonidine. Dextrogyre solutions by Cinchonine, Quinidine, Quinamine, Conquinamine, and the amorphous alkaloids.

d. Thalleioquin is formed by Quinine, Quinidine, and also by Quinicine. Thalleioquin cannot be obtained from Cinchonine, Cinchonidine, Quinamine, nor from Cinchonicine.

e. Fluorescence is displayed by solutions of Quinine, Quinidine. No fluorescence in solutions of pure Cinchonine, Cinchonidine, Quinamine.

=Proportion of Alkaloids in Cinchona Barks=—This is liable to very great variation. We know from the experiments of Hesse (1871), that the bark of C. pubescens Vahl is sometimes devoid of alkaloid.[1359] Similar observations made near Bogota upon C. pitayensis Wedd., C. corymbosa Karst., and C. lancifolia Mutis, are due to Karsten. He ascertained[1360] that barks of one district were sometimes devoid of quinine, while those of the same species from a neighbouring locality yielded 3½ to 4½ per cent. of sulphate of quinine.

[1359] Berichte der Deutschen Chem. Gesellschaft zu Berlin, 1871. 818.

[1360] Die medicinischen Chinarinden Neu-Granada’s, 17. 20. 39.

Another striking example is furnished by De Vry[1361] in his examination of quills of C. officinalis grown at Ootacamund, which he found to vary in percentage of alkaloids, from 11·96 (of which 9·1 per cent. was quinine) down to less than 1 per cent. An extremely remarkable variation has also been displayed, as already alluded to at p. 351, by Ledger’s Calisaya.

Among the innumerable published analyses of cinchona bark, there are a great number showing but a very small percentage of the useful principles, of which quinine, the most valuable of all, is not seldom altogether wanting. The highest yield on the other hand hitherto observed, was obtained by Broughton[1362] from a bark grown at Ootacamund. This bark afforded not less than 13½ per cent. of alkaloids, among which quinine was predominant. In Java too, Cinchona Ledgeriana (see pp. 341, 351) has proved since to afford much more alkaloid than any American barks; as much as 13·25 per cent. of quinine have been observed in its bark.

The few facts just mentioned show that it is impossible to state even approximately any constant percentage of alkaloids in any given bark. We may however say that good Flat Calisaya Bark, as offered in the drug trade for pharmaceutical preparations, contains at least 5 to 6 per cent. of quinine.

As to Crown or Loxa Bark, the Cortex Cinchonæ pallidæ of pharmacy, its merits are, to say the least, very uncertain. On its first introduction in the 17th century, when it was taken from the trunks and large branches of full-grown trees, it was doubtless an excellent medicinal bark; but the same cannot be said of much of that now found in commerce, which is to a large extent collected from very young wood.[1363] Some of the Crown Bark produced in India is however of extraordinary excellence, as shown by the recent experiments of De Vry.[1364]

As to Red Bark, the thick flat sort contains only 3 to 4 per cent. of alkaloids, but a large amount of coloring matter. The quill Red Bark of the Indian plantations is a much better drug, some of it yielding 5 to 10 per cent. of alkaloids, less than a third of which is quinine and a fourth cinchonidine, the remainder being cinchonine and sometimes also traces of quinidine (conquinine).

The variations in the amount of alkaloids relates not merely to their total percentage, but also to the proportion which one bears to another. Quinine and cinchonine are of the most frequent occurrence; cinchonidine is less usual, while quinidine is still less frequently met with and never in large amount. The experiments performed in India[1365] have already shown that external influences contribute in an important manner to the formation of this or that alkaloid; and it may even be hoped that the cultivators of cinchona will discover methods of promoting the formation of quinine and of reducing, if not of excluding, that of the less valuable alkaloids.

[1361] Pharm. Journ. Sept. 6, 1873. 181.

[1362] Blue Book—“East India Chinchona Plant,” 1870. 282; Yearbook of Pharmacy, 1871. 85.

[1363] See Howard’s analyses and observations, Pharm. Journ. xiv. (1855) 61-63.

[1364] Pharm. Journ. Sept. 6, 1873. 184.

[1365] Blue Book, 1870. 116. 188. 205.

Most salts of the alkaloids of cinchona afford a beautiful purple tar when they are heated in a test tube, and the same is also produced with the powdered bark, provided alkaloids be present. No other bark, as far as we know, yields a similar product of the dry distillation. It is not observed even in using true Cinchona barks, which are devoid of alkaloids. This method for ascertaining the presence of alkaloids in Cinchona barks has been proposed in 1858 by Grahe of Kasan. Hesse has improved Grahe’s test in the following way: he extracts the powdered bark with slightly acidulated water and dries up the liquid with a little of the powder. Grahe’s test at once shows whether a given bark contains Cinchona alkaloids or not.

=Acid principles of Cinchona Barks=—Count Claude de la Garaye[1366] observed (1746) a crystalline salt deposited in extract of cinchona bark, which salt was known for some time in France as Sel essential de la Garaye. Hermbstädt at Berlin (1785) showed it to be a salt of calcium, the peculiarity of whose acid was pointed out in 1790 by C. A. Hoffmann,[1367] an apothecary of Leer in Hanover, who termed it Chinasäure. The composition of this substance, which is the Kinic Acid of English chemists, was ascertained by Liebig in 1830 to be C₇H₁₂O₆, or now C₆H₇(OH)₄COOH. The acid forms large monoclinic prisms, fusible at 162° C., of a strong and pure acid taste, soluble in two parts of water, also in spirit of wine, but hardly in ether. The solutions are levogyre. Kinic acid appears to be present in every species, and also to occur in barks of allied genera; and in fact to be of somewhat wide distribution in the vegetable kingdom. By heating it or a kinate, interesting derivatives are obtained; thus, by means of peroxide of manganese and sulphuric acid, we get yellow crystals of Kinone or Quinone, C₆H₄O₂,—a reaction which may be used for ascertaining the presence of kinic acid. Kinic acid is devoid of any noteworthy physiological action.

Cincho-tannic Acid—is precipitated from a decoction of bark by acetate of lead, after the decoction has been freed from cinchona-red by means of magnesia. Dr. de Vry informed us that the Indian barks are usually richer in cincho-tannic acid; their cold infusion becomes turbid on addition of hydrochloric acid, which forms an insoluble compound with the former.

The cincho-tannate of lead decomposed by sulphuretted hydrogen, and the solution cautiously evaporated in vacuo, yields the acid as an amorphous, hygroscopic substance, readily soluble in water, alcohol, or ether. The solutions, especially in presence of an alkali, are quickly decomposed, a red flocculent matter, Cinchona-red, being produced. Solutions of cincho-tannic acid assume a greenish colour on addition of a ferric salt. By destructive distillation, cincho-tannic acid affords pyrocatechin.

Quinovic (or Chinovic) Acid, C₂₄H₃₈O₄, crystallizes in hexagonal scales which are sparingly soluble in cold alcohol, more readily in boiling alcohol, but not dissolved by water, ether, or chloroform. It occurs in cinchona barks, and has been met with by Rembold (1868) in the rhizome of Potentilla Tormentilla Sibth.

[1366] Chimie hydraulique, Paris, 1746. 114.

[1367] Crell’s Chem. Annalen, 1790, ii. 314-317.

=Other Constituents of Cinchona Barks=—Quinovic acid is accompanied by Quinovin (or Chinovin), C₃₀H₄₈O₈, an amorphous bitter substance, first obtained (1821) by Pelletier and Caventou under the name of Kinovic Acid, from China nova,[1368] in which it occurs combined with lime. Quinovin in alcoholic solution was shown in 1859 by Hlasiwetz to be resolved by means of hydrochloric gas into quinovic acid, C₂₄H₃₈O₄, and an uncrystallizable sugar, Mannitan, C₆H₁₂O₅, with subtraction of H₂O. The formation of quinovic acid takes place more easily, if quinovin is placed in contact with sodium amalgam and spirit of wine, when, after 12 hours, mannitan and quinovate of sodium are formed (Rochleder, 1867).

Quinovin, although an indifferent substance, may be removed from cinchona barks by weak caustic soda, from which it is precipitable by hydrochloric acid, together with quinovic acid and cinchona-red. Milk of lime then dissolves quinovin and quinovic acid, but not the red substance. Quinovic acid and quinovin again precipitated by an acid, may be separated by chloroform in which the latter only is soluble, or also by cold dilute alcohol sp. gr. about 0·926, quinovin being readily removed by this liquid.

Quinovin dissolves in boiling water; its solutions, as well as those of quinovic acid, are dextrogyre. Quinovin seems to be a constituent of almost every part of the cinchonas and the allied Cinchoneæ, although the amount of it in barks does not apparently exceed 2 per cent. It is accompanied by quinovic acid: both substances are stated to have tonic properties.

Cinchona-red, an amorphous substance to which the red hue of cinchona barks is due, is produced as shown by Rembold (1867), when cincho-tannic acid is boiled with dilute sulphuric acid, sugar being formed at the same time. By fusing cinchona-red with potash, protocatechuic acid, C₇H₆O₄, is produced. Cinchona-red is sparingly soluble in alcohol, abundantly in alkaline solutions, but neither in water nor in ether. Thick Red Bark in which it is abundant, affords it to the extent of over 10 per cent.

The Cinchona barks yield but a scanty percentage of ash, not exceeding 3 per cent., a fact well according with the small amount they contain of oxalate and kinate of calcium.

=Estimation of the Alkaloids in Cinchona Bark=—The microscope will enable us, as already shown, to ascertain whether a given bark is derived from Cinchona, but it can furnish no exact information as to the actual value of such bark as a drug.

Yet there is a very simple test by which the presence of a cinchona-alkaloid may be demonstrated. These alkaloids heated in a glass tube in the presence of a volatile acid or of substances capable of producing a volatile acid, evolve heavy vapours of a beautiful crimson colour, as mentioned p. 363.

[1368] The bark of Buena magnifolia Wedd., a tree with fragrant flowers and magnificent foliage, figured in Howard’s “Nueva Quinologia of Pavon” as Cinchona magnifolia. Its bark is destitute of alkaloids; it also used to appear occasionally in the London market since about the year 1820.—See also our article on Cortex Cascarillæ.

But to ascertain the real value of a cinchona bark, a quantitative estimation of the alkaloids is necessary. A good process for this operation has been given by De Vry.[1369] It is as follows:—Mix 20 grammes of powdered bark, dried at 100° C., with milk of lime (5 grm. slaked lime to 50 grm. water), dry the mixture slowly; by stirring it frequently, the cincho-tannic acid loses its solubility, being gradually transformed into cinchona-red. Then boil the dry powder with 200 cubic centimetres of alcohol 0·830 sp. gr. Pour the liquid on to a small filter, and afterwards the residual bark and lime mixed with 100 cub. cent. more alcohol. Wash the powder on the filter with 100 cub. cent. of spirit From the mixed liquids, about 370 cub. cent., separate the calcium by a few drops of weak sulphuric acid. Filter, distill off the spirit and pour into a capsule the residual liquid,—to which add a small quantity of spirit and water with which the distilling apparatus has been rinsed out. Let the capsule be now heated on a water-bath until all the spirit shall have been expelled; and let the remaining liquor which contains all the alkaloids in the form of acid sulphates be filtered. There will remain on the filter quinovic acid and fatty substances, which must be washed with slightly acidulated water. The filtrate and washings reduced to about 50 cub. cent., should be treated while still warm with caustic soda in excess. After cooling, this is decanted off from the precipitate, and then water added to it before throwing it on to a filter. It is then to be washed with the smallest quantity of water pressed between folds of blotting paper, removed therefrom and dried. The weight multiplied by 5 will indicate the percentage of mixed alkaloids in the bark.

[1369] Pharm. Journ. iv. (1873) 241, and Dr. de Vry’s papers mentioned at the end of the present article, p. 369; also private communications.

To separate the alkaloids from each other, treat the powdered mass with ten times its weight of ether. This will resolve it into two portions—(a) insoluble in ether, (b) soluble in ether.

(a.) This should be converted into neutral acetates, and to the solution there should be added iodide of potassium, which will possibly separate a little quinidine. After removal of the latter (if present), add solution of tartrate of potassium and sodium, which will throw down in a crystalline form tartrate of cinchonidine; from the mother-liquor, cinchonine may be precipitated by caustic soda.

(b.) The ether having been evaporated, the residue is to be dried at 100° C. and weighed. It may in many cases practically be considered as consisting of quinine only. If however the estimation of quinidine (conquinine) and quinamine is required, the residue, or a determined portion of it, should be dissolved in acetic acid just as much as will be necessary for affording a neutral solution. From this the hydroiodate of quinidine is precipitated by means of an alcoholic solution of iodide of potassium. In the filtrate quinine may be precipitated by adding a few drops of dilute sulphuric acid and an alcoholic tincture of iodine. The herapathite thus formed (see p. 360) is collected after a day, dried at 100° and weighed; it then contains 55 per cent. of quinine.

After adding a few drops of sulphurous acid, the alcohol should now be evaporated from the fluid from which the crystals of herapathite have been removed, and caustic lye added, by which the amorphous alkaloids will be precipitated, including quinamine if present.

=Uses=—Cinchona bark enjoys the reputation of being a most valuable remedy in fevers. But the uncertainty of its composition and its inconvenient bulk render it a far less eligible form of medicine than the alkaloids themselves. It is nevertheless much used as a general tonic in various pharmaceutical preparations.

As to the alkaloids, the only one which is in general use is quinine. The neglect of the others is a regrettable waste, which the result of recent investigations ought to obviate. In the year 1866 the Madras Government appointed a Medical Commission to test the respective efficacy in the treatment of fever, of Quinine, Quinidine, Cinchonine and Cinchonidine. Of the sulphates of these alkaloids, a due supply, specially prepared under Mr. Howard’s superintendence, was placed at the disposal of the Commission. From the report[1370] it appears that the number of cases of paroxysmal malarious fevers treated was 2472,—namely 846 with Quinine, 664 with Quinidine, 569 with Cinchonine, and 403 with Cinchonidine. Of these 2472 cases, 2445 were cured, and 27 failed. The difference in remedial value of the four alkaloids, as deduced from these experiments, may be thus stated:—

Quinidine—ratio of failure per 1000 cases treated 6 Quinine ” ” 7 Cinchonidine ” ” 10 Cinchonine ” ” 23

The Indian Government, acting on the recommendation of Mr. Howard, has officially advised (Dec. 16, 1873) the more free use India of cinchona alkaloids other than quinine, and especially of sulphate of cinchonidine, which is procurable in abundance from Red Bark.[1371] Quinidine on the other hand, which has proved the most valuable of all, is only obtainable from a few barks and in very limited amount.

Dr. de Vry since 1876 advocates the use of what he calls Quinetum. This preparation is obtained by exhausting the barks with slightly acidulated water, and precipitating the whole amount of alkaloids by caustic soda. In India the remedy is known as “the Febrifuge.”[1372]

=Adulteration=—There is not now any frequent importation of spurious cinchona barks, but the substitution of bad varieties for good is sufficiently common. To discriminate these in a positive manner by ascertaining the percentage of quinine, which is the chief criterion of value, recourse must be had to chemical analysis, a method of performing which has been described. Entirely worthless barks may be easily recognized by means of Grahe’s test (p. 363).

[1370] Blue Book—East India Cinchona Cultivation, 1870. pp. 156-172.—The report contains very interesting and important medical details. See also Dougal in Edin. Med. Journ. Sept. 1873.

[1371] We heard that the Government has purchased (April 1874) by tender between 300 and 400 lb. of cinchonidine.

[1372] Pharm. Journ. viii. (1878) 1060.

Modern Works relating to Cinchona.

The following enumeration has been drawn up for the sake of those desiring more ample information than is contained in the foregoing pages, but it has no pretension to be a complete list of all publications that have lately appeared on the subject.

Berg (Otto), _Chinarinden der pharmakognostischen Sammlung zu Berlin_. Berlin, 1865, 4°. 48 pages and 10 plates showing the microscopic structure of barks.

Bergen (Heinrich von), Monographie der China. Hamburg, 1826, 4°. 348 pages and 7 coloured plates representing the following barks:—China rubra, Huanuco, Calisaya, flava, Huamalies, Loxa, Jaen. An exhaustive work for its period in every direction.

Blue books—East India (Chinchona Plant). Folio.

=a.= _Copy of Correspondence relating to the introduction of the Chinchona Plant into India, and to proceedings connected with its cultivation from March 1852 to March 1863._ Ordered by the House of Commons to be printed, 20 March 1863. 272 pages.

Contains Correspondence of Royle, Markham, Spruce, Pritchett, Cross, McIvor, Andersen and others, illustrated by 5 maps.

=b.= _Copy of further Correspondence relating to the introduction of the Chinchona Plant into India, and to proceedings connected with its cultivation, from April 1863 to April 1866._ Ordered by the House of Commons to be printed, 18 June 1866. 379 pages.

Contains Monthly Reports of the plantations on the Neilgherry Hills; Annual Reports for 1863-64, 1864-65, with details of method of propagation and cultivation, barking, mossing, attacks of insects, illustrated by woodcuts and 4 plates; report of Cross’s journey to Pitayo, with map; Cinchona cultivation in Wynaad, Coorg, the Pulney Hills and Travancore, with map; in British Sikkim, the Kangra, Valley (Punjab), the Bombay Presidency, and Ceylon.

=c.= _Copy of all Correspondence between the Secretary of State for India and the Governor-General, and the Governors of Madras and Bombay, relating to the cultivation of Chinchona Plants, from April 1866 to April 1870._ Ordered by the House of Commons to be printed, 9 August 1870. 285 pages.

Contains reports on the Neilgherry and other plantations, with map; appointment of Mr. Broughton as analytical chemist, his reports and analyses; reports on the relative efficacy of the several cinchona alkaloids, on cinchona cultivation at Darjiling and in British Burma.

=d.= _Copies of the Chinchona Correspondence (in continuation of return of 1870), from August 1870 to July 1875._ Ordered by the House of Commons to be printed, 21 June 1877. 190 pages.

Contain also reports on the alkaloid manufactory in India, collection and shipment of barks, and analyses of barks.

Delondre (Augustin Pierre) et Bouchardat (Apollinaire), Quinologie, Paris, 1854, 4°. 48 pages, and 23 good coloured plates exhibiting all the barks then met with in commerce.

Delondre (Augustin), see Soubeiran.

Gorkom (K. W. van), Die Chinacultur auf Java, Leipzig, 1869, 61 pages. An account of the management of the Dutch plantation.

Hesse (Oswald). This chemist has summarized his elaborate researches on Cinchona in the German Dictionary of Chemistry, articles Chinin, Cinchonin, etc. 1876-1877.

Howard (John Eliot), _Illustrations of the Nueva Quinologia of Pavon_. London, 1862, folio, 163 pages and 30 beautiful coloured plates.—Figures of Cinchona mostly taken from Pavon’s specimens in the herbarium of Madrid, and three plates representing the structure of several barks.

Howard (J. E.), _Quinology of the East India Plantations_. London, 1869, folio x. and 43 pages, with 3 coloured plates exhibiting structural peculiarities of the barks of cultivated Cinchonæ.

Howard (J. E.) The same, parts ii. and iii., Lond. 1876, folio xiv. and 74 p., with 2 views, 2 black plates and 13 coloured figures of Cinchona Calisaya (Ledgeriana), C. officinalis, _C. pitayensis_, and others.

Karsten (Hermann), _Die medicinischen Chinarinden Neu-Granada’s_. Berlin, 1858, 8°. 71 pages, and 2 plates showing microscopic structure of a few barks. An English translation prepared under the supervision of Mr. Markham, has been printed by the India Office under the title of _Notes on the Medicinal Cinchona Barks of New Granada by H. Karsten_, 1861. The plates have not been reproduced.

Karsten (Hermann), _Floræ Columbiæ terrarumque adjacentium specimina selecta_. Berolini, 1858, folio. Beautiful coloured figures of various plants including Cinchona, under which name are several species usually referred to other genera. Only three parts have been published.

King (George), _A Manual of Cinchona cultivation in India_. Calcutta, 1876, 80 pages, small folio.

Kuntze (Otto), Cinchona. Arten, Hybriden and Cultur der Chininbäume. Leipzig, 1878. 124 pages and 3 plates. A review of this book will be found in the Archiv der Pharmacie, 213, (1878) 473-480.

McIvor (W. G.) _Notes on the propagation and cultivation of the medicinal Cinchonas or Peruvian bark trees._ Madras, 1867, 33 pages, 9 plates. The author explains the “motsing system” alluded to p. 362.

McIvor (William Graham), _A letter on the cultivation of Chinchona on the Nilgiris_. Ootacamund, 1876, 27 pages.

Markham (Clements Robert), _The Chinchona Species of New Granada, containing the botanical descriptions of the species examined by Drs. Mutis and Karsten; with some account of those botanists, and of the results of their labours_. London, 1867, 8°. 139 pages and 5 plates. The plates are not coloured, yet are good reduced copies of those contained in Karsten’s _Floræ Columbiæ_; they represent the following:—_Cinchona corymbosa_, C. Trianæ, C. lancifolia, C. cordifolia, C. tucujensis.

Markham. _A Memoir of the Lady Ana de Osorio, Countess of Chinchon, vice-queen of Peru_ (A.D. 1629-1639), _with a plea for the correct spelling of the Chinchona genus_. London, 1874, 4°. 99 pages, with a map, heraldic figures and views.

See also Hanbury, Science Papers, 1876, p. 475.

Miquel (Friedrich Anton Wilhelm), _De Cinchonæ speciebus quibusdam, adjectis iis quæ in Java coluntur. Commentatio ex Annalibus Musei Botanici Lugduno-Batavi exscripta._ Amstelodami, 1869,4°. 20 pages.

Oudemans (Anthony Cornelis), _Sur le pouvoir rotatoire spécifique des principaux alcaloïdes du quinquina_. Archives néerlandaises, x. (1875), 193-268, and xii. (1877).

Phoebus (Philipp), _Die Delondre-Bouchardat’schen China-Rinden_. Giessien, 1864, 8°. 75 pages and a table. The author gives a description without figures, of the microscopic structure of the type-specimens figured in Delondre and Bouchardat’s Quinologie.

Planchon (Gustave), Des Quinquinas. Paris et Montpellier, 1864, 8°. 150 pages. A description of the cinchonas and their barks. An English translation has been issued under the superintendence of Mr. Markham by the India Office, under the title of _Peruvian Barks by Gustave Planchon_. London, printed by Eyre and Spottiswoode, 1866.

Soubeiran (J. Léon) et Delondre (Augustin), _De l’introduction et de l’acclimation des Cinchonas dans les Indes néerlandaises et dans les Indes britanniques_. Paris, 1868, 8°. 165 pages.

Triana (Josè), Nouvelles études sur les Quinquinas. Paris, 1870, folio, 80 pages, and 33 plates. An interesting account of the labours of Mutis, illustrated by uncoloured copies of some of the drawings prepared by him in illustration of his unpublished _Quinologia de Bogotá_, especially of the several varieties of Cinchona lancifolia; also an enumeration and short descriptions of all the species of Cinchona, and of New Granadian plants (chiefly Cascarilla) formerly placed in that genus.

An abstract of the book will be found in Just’s Botanischer Jahresbericht für 1873, 484-494.

Vogl (August), _Chinarinden des Wiener Grosshandels und der Wiener Sammlungen_. Wien, 1867, 8°. 134 pages, no figures. A very exhaustive description of the microscopic structure of the barks occurring in the Vienna market, or preserved in the museums of that city.

Vogl (A.), _Beiträge zur Kenntniss der sogenannten falschen Chinarinden_. Wien, 1876, 4°. 26 pages, 7 microscopic sections.

Vrij (John Eliza de), Kinologische studiën. More than 30 papers published since 1868 in the _Nieuw Tijdschrift voor de Pharmacie in Nederland_. They are chiefly devoted to the chemistry of the barks from Java and British India.

Weddell (Hugh Algernon), _Histoire naturelle des Quinquinas, ou monographie du genre Cinchona, suivie d’une description du genre Cascarilla et de quelques autres plantes de la même tribu_. Paris, 1849, folio, 108 pages, 33 plates, and map. Excellent uncoloured figures of Cinchona and some allied genera, and beautiful coloured drawings of the officinal barks. Plate I. exhibits the anatomical structure of the plant; Plate II. that of the bark.

Weddell (H. A.), _Notes sur les Quinquinas, Extrait des Annales des Sciences naturelles_, 5ᵉ série, tomes xi. et xii. Paris, 1870, 8°. 75 pages. A systematic arrangement of the genus Cinchona, and description of its (33) species, accompanied by useful remarks on their barks. An English translation has been printed by the India Office with the title—_Notes on the Quinquinas by H. A. Weddell_, London, 1871, 8°. 64 pages. A German edition by Dr. F. A Flückiger has also appeared under the title _Uebersicht der Cinchonen von H. A. Weddell_. Schaffhausen and Berlin, 1871, 8°. 43 pages, with additions and indexes.

Spotted a typo or a problem in this chapter? Tell us

RADIX IPECACUANHÆ

Ipecacuanha Root, Ipecacuan; F. Racine d’Ipécacuanha annelee; G. Brechwurzel.

=Botanical Origin=—Cephaëlis[1373] Ipecacuanha A. Richard—This is a small shrub, 8 to 16 inches high, with an ascending, afterwards erect, simple stem, and somewhat creeping root, growing socially in moist and shady forests of South America, lying between 8° and 22° S. lat., especially in the Brazilian provinces of Pará, Maranhão, Pernambuco, Bahia, Espiritu Santo, Minas, Rio de Janeiro, and São Paulo. Within the last half century, it has been discovered in the vast interior province of Matto Grosso, chiefly in that part of it which forms the valley of the Rio Paraguay. From information given to Weddell,[1374] it would seem probable that the plant extends beyond the frontiers of Brazil to the Bolivian province of Chiquitos.

The root which is brought into commerce is furnished chiefly by the region lying between the towns of Cuyabá, Villa Bella, Villa Maria, and Diamantina in the province of Matto Grosso; but to some extent also by the woods in the neighbourhood of the German colony of Philadelphia on the Rio Todos os Santos, a tributary of the Mucury, north of Rio de Janeiro.

Prof. Balfour of Edinburgh, who has paid much attention to the propagation of ipecacuanha, finds that the plant exists under two varieties, of which he has published figures;[1375] they may be thus distinguished:

a. Stem woody, leaves of firm texture, elliptic or oval, wavy at the edges, with but few hairs on surface and margin. Long in cultivation: origin unknown.

b. Stem herbaceous, leaves less firm in texture, more hairy on margin, not wavy. Grows in the neighbourhood of Rio de Janeiro.

The plant cultivated in India seems disposed to run into several varieties, but according to the experience gained in Edinburgh, the diversity of form apparent in young plants tends to disappear with age.

=History=—In an account of Brazil, written by a Portuguese friar, who, it would seem, had resided in that country from about 1570 to 1600, and published by Purchas,[1376] mention is made of three remedies for the bloody flux, one of which is called Igpecaya or Pigaya; the drug here spoken of is probably that under notice.

[1373] I am informed by my friend Professor Müller of Geneva that in describing the Rubiaceæ for the Flora Brasiliensis he will include Cephaëlis Ipecacuanha in the genus Mapouria.—F. A. F.. March 1879.

[1374] Ann. des Sciences nat. Bot. xi. (1849) 193-202.

[1375] Trans. of Roy. Soc. of Edinb. xxvi. (1872) 781. plates 31-32.—Fig. in Bentley and Trimen, Med. Plants. part 15 (1876).

[1376] Purchas, His Pilgrimes, Lond. iv. (1625),—a treatise of Brasill, written by a Portugall which had long lived there, p. 1311.

Piso and Marcgraf[1377] in their scientific exploration of Brazil met with two kinds of ipecacuanha; the one provided with a brown root is Cephaëlis Ipecacuanha, which they figured. The root of the other variety, which they called Ipecacuanha blanca, is that of Richardsonia scabra (see page 376 below). Piso and Marcgraf described the virtues of these roots, apparently supposing them to be much the same as to their action. Although in common use in Brazil, ipecacuanha was not employed in Europe prior to the year 1672. At that date, a traveller named Legras brought from South America a quantity of the root to Paris, some of which came into the possession of the “maître appoticaire” Claquenelle.[1378] It would appear that the root was prescribed from the latter by Legras (said to have been himself acquainted with the practice of medicine[1379]), and also by Jean Adrien Helvetius, a young Dutch physician, then living in Paris. Yet no success at first was obtained, the drug being administered in too large doses. In 1680, a merchant of Paris named Garnier became possessed of 150 lb. of ipecacuanha, the valuable properties of which in dysentery he vaunted to his medical attendant Afforty, and to Helvetius. Garnier on his convalescence[1380] made a present of some of the new drug to Afforty, who attached to it but little importance. Helvetius, on the other hand, was induced to prescribe the root in cases of dysentery, which he did with the utmost success. It is stated by Eloy that Helvetius even caused placards to be affixed to the corners of the streets (about the year 1686), announcing his successful treatment with the new drug, supplies of which he obtained through Garnier from Spain, and sold as a secret medicine. The fame of the cures effected by Helvetius reached the French Court, and caused some trials of the drug to be made at the Hôtel Dieu. These having been fully successful, Louis XIV. accorded to Helvetius the sole right of vending his remedy.[1381] Subsequently several great personages, including the Dauphin of France, having experienced its benefit, the king consulted his physician, Antoine d’Aquin, and the well-known Jesuit Père François de Lachaise, who had become the King’s confessor in 1675. Through them was chiefly negotiated the purchase from Helvetius of his secret, for 1000 louis d’or, and made public in 1688. The right of Helvetius to this payment was disputed in law by Garnier, but maintained by a decision of the Châtelet of Paris.[1382]

The botanical source of ipecacuanha was the subject of much dispute until finally settled by Antonio Bernardino Gomez, a physician of the Portuguese navy, who brought authentic specimens from Brazil to Lisbon in the year 1800.[1383]

[1377] Hist. nat. Brasil. 1648. Piso, p. 101, Marcgraf, p. 17.

[1378] Pomet, Histoire générale des Drogues, i. (1694) 47.

[1379] Mérat and De Lens, Dict. de Mat. Méd. iii. (1831) 644, call Legras a physician, and say that Garnier brought himself the 150 lb. from abroad.

[1380] Eloy, Histoire générale de la Médecine. Mons. ii. (1778) 485, mentions a sick druggist, who presented Helvetius with the ipecacuanha. Garnier, according to Eloy, was a “Marchand chapelier.”—Leibnitz, in Ephemerid. Academ. Cæsareo-Leopold, 1696, Appendix, p. 6, miscalled the merchant Grenier.

[1381] An abstract of the royal patent is given by Leibnitz, l. c. 20 (date not added).

[1382] On the history of ipecacuanha, consult also Sprengel, Geschichte der Arzneykunde, iv. (1827) 542.—We have not seen the pamphlet quoted by Haller, Bibl. bot. ii. 17: Helvetius, Usage de l’Hipecacoanha. 4° (no date).

[1383] Trans. of Linn. Soc. vi. (1801) 137.

=Collection=[1384]—The ipecacuanha plant, Poaya of the Brazilians, grows in valleys, yet prefers spots which are rather too much raised to be inundated or swampy. Here it is found under the thick shade of ancient trees growing mostly in clumps. In collecting the root, the poayero, for so the collector of poaya is called, grasps in one handful if he can, all the stems of a clump, pushing under it obliquely into the soil a pointed stick to which he gives a see-saw motion. A lump of earth enclosing the roots is thus raised; and, if the operation has been well performed, those of the whole clump are got up almost unbroken. The poayero shakes off adhering soil, places the roots in a large bag which he carries with him, and goes on to seek other clumps. A good collector may thus get as much as 30 lb. of roots in the day; but generally a daily gathering does not exceed 10 or 12 lb., and there are many who scarcely get 6 or 8 lb. In the rainy season, the ground being lighter, the roots are removed more easily than in dry weather. The poayeros, who work in a sort of partnership, assemble in the evening, unite their gatherings, which having been weighed, are spread out to dig. Rapid drying is advantageous; the root is therefore exposed to sunshine as much as possible, and if the weather is favourable, it becomes dry in two or three days. But it has always to be placed under cover at night on account of the dew. When quite dry, it is broken into fragments, and shaken in a sieve in order to separate adherent sand and earth, and finally it is packed in bales for transport.

The harvest goes on all the year round, but is relaxed a little during the rains, on account of the difficulty of drying the produce. As fragments of the root grow most readily, complete extirpation of the plant in any one locality does not seem probable. The more intelligent poayeros of Matto Grosso are indeed wise enough intentionally to leave small bits of root in the place whence a clump has been dug, and even to close over the opening in the soil.

=Cultivation=—The importance in India of ipecacuanha as a remedy for dysentery, and the increasing costliness of the drug,[1385] have occasioned active measures to be taken for attempting its cultivation in that country. Though known for several years as a denizen of botanical gardens, the ipecacuanha plant has always been rare, owing to its slow growth and the difficulty attending its propagation.

It was discovered in 1869 by McNab, curator of the Botanical Garden of Edinburgh, that if the annulated part of the root of a growing ipecacuanha plant be cut into short pieces even only ¹/₁₆ of an inch thick, and placed in suitable soil, each piece will throw out a leaf-bud and become a separate plant. Lindsay, a gardener of the same establishment, further proved that the petiole of the leaf is capable of producing roots and buds, a discovery which has been utilized in the propagation of the plant at the Rungbi Cinchona plantation in Sikkim.

[1384] Abstracted from the interesting eye-witness account of Weddell, l. c.

[1385] The following are the average prices at which the drug was purchased wholesale, in London during three periods of ten years each:—

10 years ending 1850, average price 2_s._ 9½_d._ per lb. 10 ” 1860, ” 6_s._ 11½_d._ ” 10 ” 1870, ” 8_s. 8¼ d._ ”

In 1871, well-formed fruits were obtained from the ipecacuanha plants growing in the Edinburgh Botanical Garden: this was promoted by artificial fertilization, especially when the flowers of a plant producing long styles were fertilized with the pollen of one having short styles,—for Cephaëlis like Cinchona has dimorphic flowers.

With regard to the acclimatization of the plant in India, much difficulty has been encountered, and successful results are still problematical. The first plant was taken to Calcutta by Dr. King in 1866, and by 1868 had been increased to nine; but in 1870-71, it was reported that, notwithstanding every care, the plants could not be made to thrive. Three plants which had been sent to the Rungbi plantation in 1868, grew rather better; and by adopting the method of root propagation, they were increased by August 1871, to 300. Three consignments of plants, numbering in all 370, were received from Scotland in 1871-72, besides a smaller number from the Royal Gardens, Kew. From these various collections, the propagation has been so extensive, that on 31 March 1873, there were 6,719 young plants in Sikkim, in addition to about 500 in Calcutta, and much more in 1874.

The ipecacuanha plant in India has been tried under a variety of conditions as regards sun and shade, but thus far with only a moderate amount of success. The best results are those that have been obtained at Rungbi, 3000 feet above the sea, where the plants, placed in glazed frames, were reported in May 1873 as in the most healthy condition.[1386]

=Description=—The stem creeps a little below the surface of the soil, emitting a small number of slightly branching contorted roots, a few inches long. These roots when young are very slender and thread-like, but grow gradually knotty and become by degrees invested with a very thick bark, transversely corrugated or ringed. Close examination of the dry root shows that the bark is raised in narrow warty ridges, which sometimes run entirely round the root, sometimes encircle only half its circumference. The whole surface is moreover minutely wrinkled longitudinally. The rings or corrugations of a full sized root number about 20 in an inch; not unfrequently they are deep enough to penetrate to the wood.

The root attains a maximum diameter of about ²/₁₀ of an inch; but as imported, a large proportion of it is much smaller. The woody central part is scarcely ¹/₂₀ of an inch in diameter, subcylindrical, sometimes striated, and devoid of pith.

Ipecacuanha is of a dusky grey hue, occasionally of a dull ferruginous brown. The root is hard, breaks short and granular (not fibrous), exhibiting a resinous, waxy, or farinaceous interior, white or greyish. The bark, which constitutes 75 to 80 per cent. of the entire root, may be easily separated from the less brittle wood. It has a bitterish taste and faint, musty smell; when freshly dried it is probably much more odorous. The wood is almost tasteless. In the drug of commerce the roots are always much broken, and there is often a considerable separation of bark from wood; portions of the non-annulated, woody, subterraneous stem are always present.

[1386] Annual Report of the Royal Botanical Gardens, Calcutta, 31 May 1873—from which we have abstracted many of the foregoing particulars. The report for 1876-1877 is by no means favourable to the prospects of Cephaëlis in India.

During the last few years there has been imported into London a variety of ipecacuanha, distinguished as Carthagena or New Granada Ipecacuanha, and differing from the Brazilian drug chiefly in being of larger size. Thus, while the maximum diameter of the annulated roots of Brazilian ipecacuanha is about ²/₁₀ of an inch, corresponding roots of the New Granada variety attain nearly ³/₁₀. The latter, moreover, has a distinct radiate arrangement of the wood, due to a greater developement of the medullary rays, and is rather less conspicuously annulated. Lefort (1869) has shown that the New Granada drug is a little less rich in emetine than the ipecacuanha of Brazil.

Mr. R. B. White, of Medellin in the valley of the Cauca, New Granada, near which place the drug has been collected, has been good enough to send us herbarium specimens of the plant with roots attached; they agree entirely with Cephaëlis Ipecacuanha.

=Microscopic Structure=—The root is coated with a thin layer of brown cork-cells; the interior cortical tissue is made up of a uniform parenchyme, in which medullary rays cannot be distinguished. In the woody column they are obvious; the prevailing tissue consists of short pitted vessels. The cortical parenchyme and the medullary rays are loaded with small starch granules. Some cells of the interior part of the bark contain however only bundles of acicular crystals of oxalate of calcium.

=Chemical Composition=—The peculiar principles of ipecacuanha are Emetine and Ipecacuanhic Acid, together with a minute proportion of a fœtid volatile oil. The activity of the drug appears to be due solely to the alkaloid, which taken internally is a potent emetic.

Emetine, discovered in 1817 by Pelletier and Magendie, is a bitter substance with distinct alkaline reaction, amorphous in the free state as well as in most of its salts; we have succeeded in preparing a crystallized hydrochlorate.

The root yields of the alkaloid less than 1 per cent.; the numerous higher estimates that have been given relate to impure emetine, or have been arrived at by some defective methods of analysis.[1387]

[1387] See the results obtained by Richard and Barruel, by Magendie and Pelletier, and by Attfield, as recorded by the last named chemist in Proceedings of the British Pharmaceutical Conference for 1869. 37-39.

The formula assigned to emetine by Reich (1863) was C₂₀H₃₀N₂O, that given by Glénard (1875) C₁₅H₂₂NO₂, and lastly that found in 1877 by Lefort and F. Würtz, C₂₈H₄₀N₂O₅.

The alkaloid may be obtained by drying the powdered bark of the root with a little milk of lime, and exhausting the mixture with boiling chloroform, petroleum-benzin or ether. It is a white powder turning brown on exposure to light and softening at 70° C. Emetine assumes an intense and permanent yellow colour with solution of chlorinated lime and a little acetic acid, as shown by Power (1877). A solution containing but ¹/₆₀₀₀ of emetine still displays that reaction. We found the alkaloid to be destitute of rotatory power, at least in the chloroform solution.

The above reactions may be easily shown thus:—Take 10 grains of powdered ipecacuanha, and mix them with 3 grains of quicklime and a few drops of water. Dry the mixture in the water bath and transfer it to a vial containing 2 fluid drachms of chloroform: agitate frequently, then filter into a capsule containing a minute quantity of acetic acid, and allow the chloroform to evaporate. Two drops of water now added will afford a nearly colourless solution of emetine, which, placed in a watch-glass, will readily give amorphous precipitates upon addition of a saturated solution of nitrate of potassium, or of tannic acid, or of a solution of mercuric iodide in iodide of potassium. To the nitrate Power’s test may be further applied.

If the wood separated as exactly as possible from the bark is used, and the experiment performed in the same way, the solution will reveal only traces of emetine. By addition of nitrate of potassium, no precipitate is then produced, but tannic acid or the potassico-mercuric iodate afford a slight turbidity. This experiment confirms the observation that the bark is the seat of the alkaloid, as might indeed be inferred from the fact that the wood is nearly tasteless.

Ipecacuanhic Acid, regarded by Pelletier as gallic acid, but recognised in 1850 as a peculiar substance by Willigk,[1388] is reddish-brown, amorphous, bitter, and very hygroscopic. It is related to caffetannic and kinic acids; Reich has shown it to be a glucoside.

Ipecacuanha contains also, according to Reich, small proportions of resin, fat, albumin, and fermentable and crystallizable sugar; also gum and a large quantity of pectin. The bark yielded about 30 per cent., and the wood more than 7 per cent. of starch.

=Commerce=—The imports of ipecacuanha into the United Kingdom in 1870 amounted to 62,952 lb., valued at £16,639.[1389]

=Uses=—Ipecacuanha is given as an emetic, but much more often in small doses as an expectorant and diaphoretic. In India it has proved of late a most important remedy for dysentery. Since the year 1858 when the administration of ipecacuanha in large (30 grains) doses began to be adopted, the mortality in the cases treated for this complaint has greatly diminished.[1390]

=Adulteration and Substitutes=—It can hardly be said that ipecacuanha as at present imported is ever adulterated. Although it may contain an undue proportion of the woody stems of the plant, it is not fraudulently admixed with other roots. But it very often arrives much deteriorated by damp: we have the authority of an experienced druggist for saying that at least three packages out of every four offered in the London drug sales, have either been damaged by sea-water or by damp during their transit to the coast.

Several roots have been described as False Ipecacuanha, but we know not one that would not be readily distinguished at first sight by any druggist of average knowledge and experience.

In Brazil the word Poaya is applied to emetic roots of plants of at least six genera, belonging to the orders Rubiaceæ, Violarieæ, and Polygaleæ; while in the same country, the name Ipecacuanha is used for various species of Ionidium[1391] as well as for Cephaëlis.

[1388] Gmelin, Chemistry, xv. (1862) 523.

[1389] Annual Statement of the Trade and Navigation of the U.K. for 1870.—The more recent issues of this return have been simplified to such an extent that drugs are for the greater part included under one head.

[1390] In the Madras Presidency, the death-rate from dysentery was 71 per 1000 cases treated: under the new method of treatment, it has been reduced to 13·5. In Bengal it has fallen from 88·2 to 28·8 per 1000.—Supplement to the Gazette of India, January 23, 1869.

[1391] As Ionidium Ipecacuanha Vent., I. Poaya St. Hil., I. parviflorum Vent., the first of which affords the Poaya branca or White Ipecacuanha of the Brazilians.—See C.F.P. von Martius, Specimen Mat. Med. Bras. 1824; A. de St. Hilaire, Plantes usuelles des Brésiliens, 1827-28.

Some of these roots, which are occasionally brought to Europe under the notion that they may find a market, have been described and figured by pharmacologists. We shall notice only the following:—

1. Large Striated Ipecacuanha—This is the root of Psychotria emetica Mutis (Rubiaceæ), a native of New Granada. It is considerably stouter than true ipecacuanha, but consists like the latter of a woody column covered with a thick brownish bark. The latter, though marked here and there with constrictions and fissures, is not annulated like ipecacuanha, but has very evident longitudinal furrows. But its most remarkable character is that it remains soft and moist, tough to the knife, even after many years; and the cut surface has a dull violet hue. The root has a sweetish taste and abounds in sugar;[1392] its decoction is not rendered blue by iodine, nor is any starch to be detected by means of the microscope. The drug occasionally appears in the London market.

2. Small Striated Ipecacuanha—This drug in outward appearance closely resembles the preceding, but is usually of smaller size, sometimes much smaller and in short pieces tapering towards either end. It also differs in being brittle, abounding in starch, and having its woody column provided with numerous pores, easily visible under a lens. Prof. Planchon[1393] of Paris, who has particularly examined both varieties of Striated Ipecacuanha, is of opinion that the drug under notice may be derived from some species of Richardsonia.

3. Undulated Ipecacuanha—The root thus called is that of Richardia scabra L. (Richardsonia scabra St. Hilaire), a plant of the same order as Cephaëlis, very common in Brazil, where it grows in cultivated ground and sandy places, or by roadsides, and even in the less frequented streets of Rio de Janeiro. Authentic specimens have been forwarded to us by Mr. Glaziou of Rio de Janeiro, and Mr. J. Correa de Méllo of Campinas; and we have also had ample supplies of the plant cultivated by us near London and at Strassburg, where Richardsonia succeeds in the open air.

The root in the fresh state is pure white, but by drying becomes of a deep iron-grey. In the Brazilian specimens, there is a short crown emitting as many as a dozen prostrate stems; below this there is generally, as in true ipecacuanha, a naked woody portion, which extends downwards into a thicker root, ²/₁₀ of an inch in diameter, and six or more inches long. This part of the root is marked by deep fissures on alternate sides, which give it a knotty, sinuous, or undulating outline. It has a brittle, very thick bark, white and farinaceous within, surrounding a strong flexible slender woody column. The root has an earthy odour not altogether unlike that of ipecacuanha, and a slightly sweet taste. It affords no evidence of emetine when tested in the manners described at p. 374, and can therefore easily be distinguished from the true drug.

[1392] Attfield in Pharm. Journ. xi. (1870) 140.

[1393] Journ. de Pharm. xvi. (1872) 405: xvii. 19.

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VALERIANACEÆ

RADIX VALERIANÆ.

Valerian Root; F. Racine de Valériane; G. Baldrianwurzel.

=Botanical Origin=—Valeriana officinalis L., an herbaceous perennial plant, growing throughout Europe from Spain to Iceland, the North Cape and the Crimea, and extending over Northern Asia to the coasts of Manchuria. The plant is found in plains and uplands, ascending even in Sweden to 1200 feet above the sea-level.

In England, valerian is cultivated in many villages[1394] near Chesterfield in Derbyshire, the wild plant which occurs in the neighbourhood not being sufficiently plentiful to supply the demand.

In Vermont, New Hampshire and New York, as well as in Holland, the plant is grown to some extent, but by far the largest supply would appear to be grown in the environs of the German town Cölleda, not far from Leipzig.

Valerian is propagated by separating the young plants which are developed at the end of runners emitted from the rootstock.

The wild plant, according to the situation it inhabits, exhibits several divergent forms. Among eight or more varieties noticed by botanists,[1395] we may especially distinguish α. major with a comparatively tall stem and all the leaves toothed, β. minor (V. angustifolia Tausch) with entire or slightly dentate leaves, and also V. sambucifolia Mikan, having only 4 or 5 pairs of leaflets.

=History=—The plant which the Greeks and Romans called Φοῦ or Phu, and which Dioscorides and Pliny describe as a sort of wild nard, is usually held to be some species of valerian.[1396]

The word Valeriana is not found in the classical authors. We first meet with it in the 9th or 10th century, at which period and for long afterwards, it was used as synonymous with Phu or Fu.

Thus in the writings of Isaac Judæus[1397] occurs the following:—“Fu id est valeriana, melior rubea et tenuis et quæ venit de Armenia et est diversa in sua complexione....”

Constantinus Africanus[1398]—“Fu, id est valeriana. Naturam habet sicut spica nardi....”

The word Valeriane occurs in the recipes of the Anglo-Saxon leeches written as early as the 11th century.[1399] Valeriana, Amantilla and Fu are used as synonymous in the Alphita, a mediæval vocabulary of the school of Salernum.[1400]

Saladinus[1401] of Ascoli directs (circa A.D. 1450) the collection in the month of August of “radices fu id est valerianæ.”

[1394] Namely Ashover, Woolley Moor, Morton, Stretton, Higham, Shirland, Pilsley, North and South Wingfield, and Brackenfield. From the produce of these villages, one wholesale dealer in Chesterfield obtained in 1872 about 6 tons (13,440 lb.) of root.

[1395] Regel, Tentamen Floræ Ussuriensis, 1862 (Mém. de l’Académie de St. Pétersbourg).

[1396] V. officinalis L. and nine other species occur in Asia Minor (Tehihatcheff).

[1397] Opera Omnia, Lugd. 1515, cap. 45.—It must be remembered that this is a translation from the Arabic. How the word in question stands in the original we have no means of knowing.

[1398] De omnibus medico cognitu necessariis, Basil. 1539. 348.

[1399] Leechdoms, Wortcunning and Starcraft of early England, iii. (1866) 6. 136.

[1400] S. de Renzi, Collectio Salernitana, iii. (1854) 271-322.

[1401] Compendium Aromatariorum, Bonon. 1488.

Valerian was anciently called in English Setwall, a name properly applied to Zedoary; and the root was so much valued for its medicinal virtues, that as Gerarde[1402] (1567) remarks, the poorer classes in the north of England esteemed “no broths, pottage, or physicall meats” to be worth anything without it. Its odour, now considered intolerable, was not so regarded in the 16th century, when it was absolutely the custom to lay the root among clothes as a perfume[1403] in the same way as those of Valeriana celtica L. and the Himalayan valerians are still used in the East.

Some of the names applied to valerian in Northern and Central Europe are remarkable. Thus in Scandinavia we find Velandsrot, Velamsrot, Vandelrot (Swedish); Vendelród, Venderód, Vendingsród (Norwegian); and Velandsurt (Danish)—names all signifying Vandels’ root.[1404] Valerian is also called in Danish Danmarks græs. Among the German-speaking population of Switzerland, a similar word to the last, namely Tannmark, is applied to valerian. The Denemarcha mentioned by St. Hildegard,[1405] about A.D. 1160, is the same. These names seem to point to some connexion with Northern Europe which we are wholly unable to explain.

Pentz, a pharmaceutical assistant at Pyrmont, was the first, in 1829, to draw attention to the acid reaction of the distilled water of valerian. Another German assistant, Grote, at Verden, showed in 1831 that the acidity was by no means due to acetic acid, but to a peculiar kind of acid. The latter was identified in 1843 by Dumas with the acid artificially obtained from amylic alcohol and that extracted in 1817 by Chevreul from the fat of dolphins.

=Description=—The valerian root of the shops consists of an upright rhizome of the thickness of the little finger, emitting a few short horizontal branches, besides numerous slender rootlets.[1406] The rhizome is naturally very short, and is rendered still more so by the practice of cutting it in order to facilitate drying. The rootlets, which are generally 3 to 4 inches long, attain ⅒ of an inch in diameter, tapering and dividing into slender fibres towards their extremities. They are shrivelled, very brittle, and, as well as the rhizome, of a dull, earthy brown. When broken transversely, they display a dark epidermis, forming part of a thick white bark which surrounds a slender woody column. The interior of the rhizome is compact, firm and horny, but when old becomes hollow, a portion of the tissue remaining however in the form of transverse septa.

The drug has a peculiar, somewhat terebinthinous and camphor-like odour, and a bitterish, aromatic taste. The root when just taken from the ground has no distinctive smell, but acquires its characteristic odour as it dries.

=Microscopic Structure=[1407]—In the rhizome as well as in the rootlets, the cortical part is separated from the central column by a dark cambial zone; the medullary rays are not distinctly obvious. In old rootstocks, sclerenchymatous cells are met with in the cortical tissue.

[1402] Herball, 1636. 1078.

[1403] Turner’s Herball, part 3 (1568) 76; Langham, Garden of Health, 1633. 598.

[1404] H. Jenssen-Tusch, Nordiske Plantenavne, Kjöbenhavn, 1867. 258.

[1405] Physica, Argent. 1533. 62.

[1406] The morphological peculiarities of valerian root are well explained in Irmisch, Beitrag zur Naturgeschichte der einheimischen Valeriana-Arten, Halle, 1854, 44 pages, 4°, 4 plates.

[1407] The structure of the rhizomes and root of the different species of valerian has been discussed by Joannes Chatin in his Etudes sur les Valérianées, Paris, 1872, illustrated by 14 beautiful plates.

The parenchyme of the drug is loaded with small starch granules, brownish grains of tannic matter and drops of essential oil. Numerous oil ducts are met with in the outer layer of the tissue.

=Chemical Composition=—Volatile oil is contained in the dry root to the extent of ½ to 2 per cent., yet on an average appears scarcely to exceed ⁴/₅ per cent. This variation in quantity is partly explained by the influence of locality, a dry, stony soil yielding a root richer in oil than one that is moist and fertile. In the latter the plant may be distinguished as the variety sambucifolia, which has a less vigorous root, devoid of runners.

Schoonbroodt[1408] has shown that the most important influence is the recent condition of the root. He states that if the root is submitted to distillation when perfectly fresh, it yields a neutral water and a large quantity of essential oil. The latter has but a very faint odour, but by exposure to the air it slowly acidifies, especially if a little alkali is added, and acquires a strong smell. Valerianic Acid which is thus formed amounts to 6 per mille of the fresh root. The dried root yields a distillate of decided valerian odour, containing valerianic acid, but in proportion not exceeding 4 per mille of the root calculated as fresh.

The oil of valerian is of a very peculiar yellowish or brownish, sometimes even almost a little greenish hue, and possessing the characteristic odour of the drug. We found it to deviate the plane of polarization from 11° to 13° to the left when examined by Wild’s Polaristrobometer in a column of 50 millimetres. By submitting it to fractional distillation we noticed[1409] that it affords a magnificent blue fraction. A superb violet or blue colour is produced if one drop of the crude oil dissolved in about 20 drops of bisulphide of carbon is mixed with 1 drop of nitric acid 1·20 sp. gr. Other colorations are produced if bromine or concentrated sulphuric acid are used;[1410] even the tincture of valerian displays similar reactions.

Bruylants (1878) has isolated from oil of valerian—1st. A hydrocarbon, C₁₀H₁₆, boiling at 157° C., yielding a crystallized compound with HCl. 2nd. The liquid compound C₁₀H₁₈O, which by means of chromic acid affords common camphor and formic, acetic and valerianic acids, which are met with in old valerian root, owing no doubt to the slow oxidation of the compound C₁₀H₁₈O. 3rd. There is also present a crystallizable compound of the same composition, which is probably identical with the camphor of Dryobalanops aromatica (see our article on Camphora). It would appear that this substance is of alcoholic nature, being combined in the root with the 3 organic acids mentioned under 2nd. On distilling, these compound ethers are resolved partly into the alcohol C₁₀H₁₈O (borneol) and the acids. This decomposition is fully performed, if the root is macerated with alkaline water, and then, on distilling, a slight excess of sulphuric acid is added. 4th. At about 300° a greenish portion is coming over, which can be obtained colourless by again rectifying it. This oil assumes intense colorations if it is shaken with concentrated mineral acids; it becomes blue by distilling it over potash.

[1408] Journ. de Médecine de Bruxelles, 1867 and 1868; Jahresbericht of Wiggers and Husemann, 1869. 17.

[1409] Archiv der Pharmacie, 209 (1876).

[1410] Jahresbericht of Wiggers and Husemann, 1871. 462.

Valerianic acid as afforded by the root is not agreeing with normal valerianic acid. It is, more exactly, isovalerianic acid, or isopropyl-acetic acid: (CH₃)₂CH·CH₂COOH, which is produced by Valeriana as well as by Archangelica officinalis and Viburnum Opulus. The same acid also may be obtained from the fat of Dolphinus globiceps.

After the root has been submitted to the distillation of the oil, there is found a strongly acid residue containing malic acid, resin, and sugar,—the last capable, according to Schoonbroodt, of reducing cupric oxide.

=Uses=—Valerian is employed as a stimulant and antispasmodic.

=Substitutes=—In the London market there has been offered “Kesso” the root of Patrinia scabiosaefolia Link,[1411] a Japanese herb of the order Valerianaceæ. This drug consists of a very short rootstock giving off a large number of rootlets about 5 inches long and ⅒ of an inch in diameter. By the absence of a well-marked upright rhizome in this Japanese Valerian it is widely differing from our Valerian, although at first sight it agrees to some extent with it. As to the odour and taste we find Kesso almost identical with true Valerian.

The less aromatic and now disused root of Valeriana Phu L. consists of a thicker rhizome which lies in the earth obliquely; it is less closely annulated and rooted at the bottom only. It resembles by no means true Valerian.

[1411] According to Holmes, Ph. J. x. (1879) 22.

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COMPOSITÆ

RADIX INULÆ.

Radix Enulæ, Radix Helenii; Elecampane;[1412] F. Racine d’Aunée; G. Alantwurzel.

=Botanical Origin=—Inula Helenium L.—This stately perennial plant is very widely distributed, occurring scattered throughout the whole of central and southern Europe, and extending eastward to the Caucasus, Southern Siberia and the Himalaya. It is found here and there apparently wild in the south of England and Ireland, as well as in Southern Norway and in Finland (Schübeler).

Elecampane was formerly cultivated in gardens as a medicinal and culinary plant, and in this manner has wandered to North America. In Holland and some parts of England and Switzerland, it is cultivated on a somewhat larger scale, most largely probably near Cölleda (see p. 377).

[1412] A corruption of Enula Campana, the latter word referring to the growth of the plant in Campania (Italy).

=History=—The plant was known to the ancient writers on agriculture and natural history, and even the Roman poets were acquainted with it, and mention Inula as affording a root used both as a medicine and a condiment. Vegetius Renatus, about the beginning of the 5th century, calls it Inula Campana, and St. Isidore in the beginning of the 7th names it as Inula, adding—“quam Alam rustici vocant.” It is frequently mentioned in the Anglo-Saxon writings on medicine current in England prior to the Norman Conquest; it is also the “marchalan” of the Welsh Physicians[1413] of the 13th century and was generally well known during the middle ages. Not only was its root much employed as a medicine, but it was also candied and eaten as a sweetmeat.

=Description=—For pharmaceutical use, the root is taken from plants two or three years old; when more advanced, it becomes too woody. The principle mass of the root is a very thick short crown, dividing below into several fleshy branches of which the larger are an inch or two in diameter, covered with a pale yellow bark, internally whitish, and juicy. The smaller roots are dried entire; the larger are variously sliced, which occasions them to curl up irregularly. When dried, they are of a light grey, brittle, horny, smooth-fractured. Cut transversely the young root exhibits an indistinct radiate structure, with a somewhat darker cambial zone separating the thick bark from the woody nucleus. The pith is not sharply defined, and is often porous and hollow. In the older roots the bark is relatively much thinner, and the internal substance is nearly uniform. Elecampane root has a weak aromatic odour suggestive of orris and camphor, and a slightly bitter, not unpleasant, aromatic taste.

=Microscopic Structure=—The medullary rays, both of the woody column and the inner part of the bark (endophlœum), exhibit large balsam-ducts. In the fresh root they contain an aromatic liquid, which as it dries deposits crystals of helenin, probably derived from the essential oil. The parenchymatous cells of the drug are loaded with inulin in the form of splinter-like fragments, devoid of any peculiar structure.

=Chemical Composition=—It was observed by Le Febvre, as early as 1660, that when the root of elecampane is subjected to distillation with water a crystallizable substance collects in the head of the receiver from which it speedily passes on as the operation proceeds. Similar crystals may also be observed after carefully heating a thin slice of the root, and are even found as a natural efflorescence on the surface of root that has been long kept. They can be extracted from the root by means of alcohol and precipitated with water. Kallen (1874, 1876) showed that the crystals chiefly consist of the anhydride, C₁₅H₂₀O₂, of alantic acid, melting at 66° C. The anhydride, which is very little aromatic, can easily be sublimed, although it begins to boil only at 275°, yet not without decomposition. Alantic anhydride dissolves in caustic lye, but on saturating the solution with an acid, alantic acid, C₁₅H₂₂O₃, separates. It is not present in the root.

The anhydride is accompanied by a small quantity of Helenin, C₆H₈O, and Alantcamphor (i.e. Elecampane-camphor). The crystals of helenin have a slightly (?) bitterish taste, but no odour, and melt at 110°. The camphor, occurring in but very small amount, has not yet been analyzed; it agrees probably with the formula C₁₀H₁₆O; it melts at 64° C., and in taste and smell is suggestive of peppermint. It is very difficult entirely to remove helenin from alantcamphor, these substances being soluble to nearly the same extent in alcohol or ether. By distilling the second of them with pentasulphide of phosphorus, Cymene, C₁₀H₁₄, was obtained.

[1413] Meddygon Myddfai, p. 61. 284. 311 (see Appendix).

By distilling the root under notice with water, the alantic anhydride is chiefly obtained, but impregnated with Alantol, C₁₀H₁₆O (probably). The latter can be removed from the crystals by pressing them between folds of bibulous paper. On submitting this again to distillation, alantol is obtained as an aromatic liquid, boiling at 200°.

The substance most abundantly contained in elecampane root is Inulin, discovered in it by Valentine Rose at Berlin in 1804. It has the same composition as starch, C₆H₁₀O₅, but stands to a certain extent in opposition to that substance, which it replaces in the root-system of Compositæ. In living plants, inulin is dissolved in the watery juice, and on drying is deposited within the cells in amorphous masses, which in polarized light are inactive, and are not coloured by iodine. There are various other characters, by which inulin differs from starch. Thus for instance, inulin readily dissolves in about 3 parts of boiling water; the solution is perfectly clear and fluid, not paste-like; but on cooling deposits nearly all the inulin. The solution is levogyre and is easily transformed into uncrystallizable sugar. With nitric acid, inulin affords no explosive compound as starch does.

Sachs showed in 1864 that by immersing the roots of elecampane, or Dahlia variabilis or of many other perennial Compositæ, in alcohol or glycerin, inulin may be precipitated in a crystalline form. Its globular aggregates of needle-shaped crystals (“sphæro-crystals”) then exhibit under the polarizing microscope a cross similar to that displayed by starch grains.

The amount of inulin varies according to the season, but is most abundant in the autumn. Of the various sources for it, the richest appears to be elecampane. Dragendorff, who has made it the subject of a very exhaustive treatise,[1414] obtained from the root in October not less than 44 per cent., but in spring only 19 per cent.

In the roots of the Compositæ inulin is accompanied, according to Popp,[1415] by two closely allied substances, Synanthrose, C₁₂H₂₂O₁₁ + H₂O, and Inuloïd, C₆H₁₀O₅ + H₂O. Synanthrose is soluble in dilute alcohol, devoid of any rotatory power, and deliquescent. Inuloïd is much more readily soluble in water than inulin. Both these substances are probably present in elecampane.

Inulin is widely distributed in the perennial roots of compositæ, and has also been met with in the natural orders Campanulaceæ, Goodenovieæ (or Goodeniaceæ), Lobeliaceæ, Stylidieæ, and lastly by Kraus (1879) in the root of Ionidium Ipecacuanha St. Hilaire, Violaceæ; the formerly so-called Ipecacuanha alba lignosa (see p. 375, note 4).

=Uses=—Elecampane is an aromatic tonic, but as a medicine is now obsolete. It is chiefly sold for veterinary practice. In France and Switzerland (Neuchâtel), it is employed in the distillation of Absinthe.

=Substitutes=—Dioscorides in speaking of Costus root states that it is often mixed with that of elecampane of Kommagene (north-western Syria). The former, derived from Aplotaxis[1416] auriculata DC. (A. Lappa Decaisne, Aucklandia Costus Falconer), is remarkably similar to elecampane both in external appearance and structure. Costus is an important spice, incense and medicine in the east from the antiquity down to the present day;[1417] it would be of great interest to examine it chemically with regard to elecampane.

[1414] Materialien zu einer Monographie des Inulins, St. Petersburg, 1870. 141 pages—See also Prantl’s paper on Inulin, as abstracted in Pharm. Journ. Sept. 1871. 262.

[1415] Wiggers and Husemann, Jahresbericht for 1870. 68.

[1416] Bentham and Hooker unite this plant with Saussurea.

[1417] See Cooke, Pharm. Journ. viii. (1877) 41; Flückiger, ibid. 121.

RADIX PYRETHRI.

Pellitory Root, Pellitory of Spain; F. Pyrèthre-salivaire; G. Bertramwurzel.

=Botanical Origin=—Anacylus Pyrethrum DC. (Anthemis Pyrethrum L.), a low perennial plant with small, much divided leaves, and a radiate flower resembling a large daisy. It is a native of northern Africa, especially Algeria, growing on the high plateaux that intervene between the fertile coast regions and the desert.

=History=—The πύρεθρον of Dioscorides was an umbelliferous plant, the determination of which must be left to conjecture. The pellitory of modern times was familiar to the Arabian writers on medicine, one of whom, Ibn Baytar, describes it very correctly from specimens gathered by himself near the city of Constantine in Algeria. The plant, says he, called by the Berbers sandasab, is found nowhere but in Western Africa, from which region it is carried to other countries.[1418]

Pellitory root is a favourite remedy in the East, and has long been an article of export by way of Egypt to India. An Arabic name for it is Aāqarqarhā or Akulkara[1419], a word which, under slight variations, is found in the principal languages of India. In Germany, pellitory was known as early as the 12th century; it is named in the oldest printed works on materia medica. In the 13th century “pellitory of Spain” (Pelydr ysbain) was a proved “remedy for the toothache” with the Welsh physicians.[1420]

=Description=—The root as found in the shops is simple, 3 to 4 inches long by ⅜ to ⁴/₈ of an inch thick, cylindrical, or tapering, sometimes terminated at top by the bristly remains of leaves, and having only a few hair-like rootlets. It has a brown, rough, shrivelled surface, is compact and brittle, the fractured surface being radiate and destitute of pith. The bark, at most ¹/₂₅ of an inch thick, adheres closely to the wood, a narrow zone of cambium intervening. The woody column is traversed by large medullary rays in which, as in the bark, numerous dark resin-ducts are scattered. The root has a slight aromatic smell, and a persistent, pungent taste, exciting a singular tingling sensation, and a remarkable flow of saliva. The drug is very liable to the attacks of insects.

=Microscopic Structure=—The cortical part of this root is remarkable on account of its suberous layer, which is partly made up of sclerenchyme (thick-walled cells). Balsam-ducts (oil-cells) occur as well in the middle cortical layer as in the medullary rays. Most of the parenchymatous cells are loaded with lumps of inulin; pellitory in fact is one of those roots most abounding in that substance.

[1418] Sontheimer’s translation, ii. (1842) 179.

[1419] Haq’recarcha; see Steinschneider, in Rohlfs’ Archiv für Geschichte der Medicin (1879) 342.

[1420] Meddygon Myddfai (see Appendix) 184. 292. 374.

=Chemical Composition=—Pellitory has been analysed by several chemists, whose labours have shown that its pungent taste is due in great part to a resin, not yet fully examined. The root also contains a little volatile oil besides, sugar, gum, and a trace of tannic acid. The so-called Pyrethrin is a mixed substance.

=Commerce=—The root is collected chiefly in Algeria and is exported from Oran and to a smaller extent from Algiers. But from the information we have received from Colonel Playfair, British Consul-General for Algeria, and from Mr. Wood, British Consul at Tunis, it appears that the greater part is shipped from Tunis to Leghorn and Egypt. Mr. Wood was informed that the drug is imported from the frontier town of Tebessa in Algeria into the regency of Tunis, to the extent of 500 cantars (50,000 lb.) per annum.

Bombay imported in the year 1871-72, 740 cwt. of this drug, of which more than half was shipped to other ports of India.[1421]

=Uses=—Chiefly employed as a sialogogue for the relief of toothache, occasionally in the form of tincture as a stimulant and rubefacient.

=Substitute=—In Germany, Russia and Scandinavia, African pellitory is replaced by the root of Anacyclus officinarum Hayne, an annual herb long cultivated in Prussia and Saxony.[1422] Its root of a light grey is only half as thick as that of A. Pyrethrum, and is always abundantly provided with adherent remains of stalks and leaves. It is quite as pungent as that of the perennial species.

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FLORES ANTHEMIDIS

Chamomile Flowers; F. Fleurs de Camomille Romaine; G. Römische Kamillen.

=Botanical Origin=—Anthemis nobilis L., the Common or Roman Chamomile, a small creeping perennial plant, throwing up in the latter part of the summer solitary flowerheads.

It is abundant on the commons in the neighbourhood of London, and generally throughout the south of England; and extends to Ireland, but is not a native of Scotland, except the islands of Bute and Cumbrae, where Anthemis is stated to grow wild. It is plentiful in the west and centre of France, Spain, Portugal, Italy, and Dalmatia; and occurs as a doubtful native in Southern and Central Russia.

=History=—The identification of the chamomile in the classical and other ancient authors seems to be impossible, on account of the large number of allied plants having similar inflorescence.

The chamomile has been cultivated for centuries in English gardens, the flowers being a common domestic medicine. The double variety was well known in the 16th century.

The plant was introduced, according to Gesner, into Germany from Spain about the close of the middle ages. Tragus first designated it Chamomilla nobilis,[1423] and Joachim Camerarius (1598), who had observed its abundance near Rome, gave it the name of Roman Chamomile.

[1421] Statement of the Trade and Navigation of the Presidency of Bombay in 1871-72, pt. ii. 19. 98.

[1422] For further information on the medicinal species of Anacyclus, see a paper by Dr. P. Ascherson in Bonplandia, 15 April 1858.

[1423] De Stirpium ..., 1552. 149.—In Germany the epithet edel (= nobilis) is frequently used in popular botany to designate useful or remarkable plants. Tragus may have been induced to bestow it on the species under notice, on account of its superiority to Matricaria Camomilla, the so-called Common Chamomile of the Germans.

Porta, about the year 1604,[1424] states that 100 pounds of Flores Chamœmeli yielded 2 drachmæ of a green volatile oil; we suppose he distilled the flowers under notice.

=Production=—The camomile is cultivated at Mitcham, near London, the land applied to this purpose being in 1864 about 55 acres, and the yield reckoned at about 4 cwt. per acre. The flowers are carefully gathered, and dried by artificial heat; and fetch a high price in the market.[1425]

The plant is grown on a large scale at Kieritzsch, between Leipzig and Altenburg, and near Zeiz and Borna, all in Saxony; and likewise to some extent in Belgium and France.

=Description=—The chamomile flowers found in commerce are never those of the wild plant, but are produced by a variety in which the tubular florets have all, or for the greater part been converted into ligulate florets. In the flowers of some localities this conversion has been less complete, and such flowers having a somewhat yellow centre, are called by druggists Single Chamomiles; while those in which all the florets are ligulate and white, are known as Double Chamomiles.

Chamomile flowers have the general structure found in the order Compositæ. They are ½ to ¾ of an inch across, and consist of a hemispherical involucre about ⅜ of an inch in diameter, composed of a number of nearly equal bracts, scarious at the margin. The receptacle is solid, conical, about ¼ of an inch in height, beset with thin, concave, blunt, narrow, chaffy scales, from the bases of which grow the numerous florets. In the wild plant, the outer of these, to the number of 12 or more, are white, narrow, strap-shaped, and slightly toothed at the apex. The central or disc florets are yellow and tubular, with a somewhat bell-shaped summit from which project the two reflexed stigmas. In the cultivated plant, the ligulate florets predominate, or replace entirely the tubular. The florets which are wholly destitute of pappus are reflexed, so that the capitulum when dried has the aspect of a little white ball. Minute oil-glands are sparingly scattered over the tubular portion of the florets of either kind. The flowers of chamomile, as well as the green parts of the plant, have a strong aroma, and a very bitter taste.

In trade, dried chamomile flowers are esteemed in proportion as they are of large size, very double, and of a good white—the last named quality being due in great measure to fine dry weather during the flowering period. Flowers that are buff or brownish, or only partially double, command a lower price.

=Chemical Composition=—Chamomile flowers yield from 0·6 to 0·8 per cent. of essential oil,[1426] which is at first of a pale blue, but becomes yellowish-brown in the course of a few months.

At Mitcham, oil of chamomile is usually distilled from the entire plant, after the best flowers have been gathered. The oil has a shade of green, to remove which it is exposed to sunlight; it thus acquires a brownish-yellow colour, at the same time throwing down a considerable deposit.

[1424] De distillatione, Romæ, 1608. 83.

[1425] About £9 per cwt., Foreign Chamomiles being worth from £3 to £4.

[1426] Information obligingly given by Messrs. Schimmel & Co., Leipzig. The oil distilled by them was examined in Prof. Fittig’s laboratory, Strassburg.

The investigations of several chemists, performed in 1878-79 in Fittig’s laboratory, have shown the oil to contain the following constituents:—At 147-148° C. isobutylic ethers and hydrocarbons are distilling, at 177° angelicate of isobutyl, at 200°-201° angelicate of isamyl, at 204°-205° tiglinate of isamyl (both these compound ethers answering to the formula C₅H₇O·OC₅H₁₁). In the residual portion hexylic alcohol, C₆H₁₃OH, and an alcohol of the formula C₁₀H₁₆O, are met with, both probably occurring in the form of compound ethers. By decomposing the angelicates and the tiglinate above named with potash, angelic acid, C₅H₈O₂, and tiglinic (or methylcrotonic) acid, isomeric to the former, are obtained to the extent of about 30 or more per cent. of the crude oil. In the oil examined by Fittig, angelic acid was prevailing; from another specimen E. Schmidt (1879) obtained but very little of it, tiglinic acid was by far prevailing (see also article Oleum Crotonis).

We have performed some experiments in order to isolate the bitter principle, but have not succeeded in obtaining it in a satisfactory state of purity; it forms a brown extract, apparently a glucoside. We can also confirm the statement that no alkaloid is present.

=Uses=—An infusion or an extract of chamomile is often used as a bitter stomachic and tonic.

=Adulteration and Substitution=—The flowerheads of Matricaria Chamomilla L., designated in Germany Common Chamomiles (gemeine Kamillen), are sometimes asked for in this country. In aspect as well as in odour, they are very different from the chamomiles of English pharmacy; they are quite single, not bitter, and have the receptacle devoid of scales and hollow.

A cultivated variety of Chrysanthemum Parthenium Pers., or Feverfew, with the florets all ligulate, and some scales on the receptacle (not having the receptacle naked, as in the wild form), common in gardens,[1427] has flowerheads exceedingly like double chamomiles. But they may be distinguished from the latter by their convex or nearly flat receptacle, with the scales lanceolate and acute, and less membranous.

The chamomiles of the Indian bazaars which are brought from Persia and known as Bābūnah, are (as we infer from the statement of Royle) the flowers of Matricaria suaveolens L., a slender form of M. Chamomilla, growing in Southern Russia, Persia, Southern Siberia, also in North America.

The fresh wild plant of Anthemis nobilis L., pulled up from the ground, is sold in London for making extract, a proceeding highly reprehensible supposing the extract to be sold for medicinal use.

[1427] Is not this plant the Anthemis? parthenioides Bernh., of which De Candolle says (Prod. vi. 7)—“ ... simillima Mat. Parthenio, sed paleis inter flores instructa. Ferè semper plena in hortis occurrit, et forte ideo paleæ receptaculi ex luxuriante statu ortæ ut in Chrysanthemi indico et sinensi ...”?

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SANTONICA

Flores Cinæ, Semen Cinæ,[1428] _Semen Santonicæ_, Semen Zedoariæ, _Semen Contra_, Semen Sanctum; Wormseed; F. Semen-contra, Semencine, Barbotine; G. Wurmsamen, Zitwersamen.

=Botanical Origin=—Artemisia maritima, var. a. Stechmanniana Besser[1429] (A. Lercheana Karel. et Kiril, in Herbb. Kew, et Mus. Brit.; A. maritima var. a. pauciflora Weber, quoad Ledebour, Flor. Ross. ii. 570).

Artemisiæ of the section Seriphidium assume great diversity of form:[1430] they have been the object of attentive study on the part of the Russian botanists Besser (1834-35) and Ledebour (1844-46), whose researches have resulted in the union of many supposed species, under the head of the Linnæan Artemisia maritima. This plant has an extremely wide distribution in the northern hemisphere of the old world, occurring mostly in saltish soils. It is found in the salt marshes of the British Islands, on the coasts of the Baltic, of France and the Mediterranean, and on saline soils in Hungary and Podolia; thence it extends eastward, covering immense tracts in Southern Russia, the regions of the Caspian, and Central Siberia, to Chinese Mongolia.

The particular variety which furnishes at least the chief part of the drug, is a low, shrubby, aromatic plant, distinguished by its very small, erect, ovoid flowerheads, having oblong, obtuse, involucral scales, the interior scales being scarious. The stem in its upper half is a fastigiate, thyrsoid panicle, crowned with flowerheads. The localities for the plant are the neighbourhood of the Don, the regions of the lower Volga near Sarepta and Zaritzyn, and the Kirghiz deserts.

The drug, which consists of the minute, unopened flowerheads, is collected in large quantities, as we are informed by Björklund (1867), on the vast plains or steppes of the Kirghiz, in the northern part of Turkestan. It was formerly gathered about Sarepta, a German colony in the Government of Saratov, but from direct information we have (1872) received, it appears to be obtained there no longer.

The emporium for wormseed is the great fair of Nishnei-Novgorod (July 15th to Aug. 27th), whence the drug is conveyed to Moscow, St. Petersburg, and Western Europe.

Wormseed is found in the Indian bazaars. A specimen received by us from Bombay does not materially differ in form from the Russian drug, but is slightly shaggy and mixed with tomentose stalks. It is probably brought from Afghanistan and Cabul.[1431]

Wilkomm[1432] has described, as mother plant of wormseed, an Artemisia which he calls A. Cina. It was obtained in Turkestan by Prof. Petzholdt, who received it from the people gathering the drug. The specimen kindly communicated to us by Prof. Willkomm has flowerheads which do not entirely resemble the wormseed of trade, in that they have fewer scales, but their number may be somewhat varying.

[1428] From the Italian semenzina, the diminutive of semenza (seed).

[1429] W. S. Besser in Bulletin de la Soc. imp. des Naturalistes de Moscou, vii. (1834) 31.—A specimen of the plant in question labelled in Besser’s handwriting, with a memorandum that it is collected for medicinal use, is in the Herbarium of the Royal Gardens, Kew. It completely agrees with the Semen Cinæ of Russian and German commerce. This remark also applies to a specimen of A. Lercheana Karel. et Kiril. in the same herbarium.

[1430] “Si aliæ Artemisiæ multùm variant, Seriphidia inconstantiâ formarum omnes superant....”—Besser.

[1431] Artemisia No. 3201, Herb. Griffith, Afghanistan, in the Kew Herbarium has capitules precisely agreeing with this Bombay drug.

[1432] Bot. Zeitung, 1 März 1872. 130; Pharm. Journ. 23 March 1872. 772 (abstract).

=History=—Several species of Absinthium are mentioned by Dioscorides, one of which called Ἀψίνθιον Θαλάσσιον or Σέριϕον, having very small seeds (capitules), and growing in Cappadocia, he states to be taken in honey as a remedy for ascarides and lumbrici: one can hardly doubt but that this is the modern wormseed. Another species is described by the same author as being called Σαντόνιον, from its growing in the country of the Santones in Gaul (the modern Saintonge); he asserts it to resemble σέριϕον in its properties.

In an epistle on intestinal worms attributed to Alexander Trallianus,[1433] who practised medicine with great success at Rome in the 6th century, the use is recommended of a decoction of Absinthium marinum (θαλασσία ἀψίνθη) as a cure for ascarides and round worms.

Semen sanctum vel Alexandrinum is mentioned as a vermifuge for children by Saladinus about A.D. 1450, and by Ruellius, Dodonæus, the Bauhins, and other naturalists of the 16th century. Tragus[1434] mentions that it is imported by way of Genoa. Its ancient reputation has been fully maintained in modern times, and in the form partly of Santonin, the drug is still extensively employed.

=Description=—Good samples of the drug consist almost exclusively of entire, unopened flowerheads or capitules, which are so minute that it requires about 90 to make up the weight of one grain. In samples less pure, there is an admixture of stalks, and portions of a small pinnate leaf. The flowerheads are of an elliptic or oblong form, about ⅒ of an inch long, greenish yellow when new, brown if long kept; they grow singly, less frequently in pairs, on short stalks, and are formed of about 18 oblong, obtuse, concave scales, closely imbricated. This involucre is much narrowed at the base in consequence of the lowermost scales being considerably shorter than the rest. The capitule is sometimes associated with a few of the upper leaves of the stem, which are short, narrow, and simple. Notwithstanding its compactness, the capitule is somewhat ridged and angular,[1435] from the involuclar scales having a strong, central nerve or keel. The middle portion of each scale is covered with minute, yellow, sessile glands, which are wanting on the transparent scarious edge. The latter is marked with extremely fine striæ and is quite glabrous; in the young state the keel bears a few woolly colourless hairs, but at maturity the whole flowerhead is shining and nearly glabrous.[1436] The florets number from 3 to 5; they have (in the bud) an ovoid corolla, glandular in its lower portion, a little longer than the ovary, which is destitude of pappus.

[1433] Contained in a work by Hieronymus Mercurialis, entitled Variarum Lectionum libri quatuor, Venet. 1570; also in Puschmann’s edition of Alexander (see Appendix), i. 238. 240.

[1434] In Brunfels (De vera herbarum cognitione), Argentorati, 1531. 196.

[1435] Maceration in water, which restores the natural shape of the flowerheads, shows that this shrunken, angular form is not found in the growing plant.

[1436] Yet too much stress must not be laid on this character, for as Besser remarks—“periclinii squamæ in uno loco tomento brevi plus minusve canæ, in aliis nudæ, imo nitidæ.”

Wormseed when rubbed in the hand exhales a powerful and agreeable odour, resembling cajuput oil and camphor; it has a bitter aromatic taste.

=Chemical Composition=—Wormseed yields from 1 to 2 per cent. of essential oil, having its characteristic smell and taste. The oil is slightly levogyrate and chiefly consists of the liquid C₁₀H₁₈O, accompanied by a small amount of hydrocarbon. The former has the odour of the drug, yet rather more agreeable; sp. gr. 0·913 at 20° C. It boils without decomposition at 173°-174°, but in presence of P₂O₅ or P₂S₅ abundantly yields cymol (see p. 333). The latter had already been observed by Völckel (1854) under the name of cinene or cynene, yet he assigned to it the formula C₁₂H₉; Hirzel (1854) called it cinæbene.

The water which distills over carries with it volatile acids of the fatty series, also angelic acid (see pp. 313, 386).

The substance to which the remarkable action of wormseed on the human body[1437] is due is Santonin, C₁₅H₁₈O₃. It was discovered in 1830 by Kahler, an apothecary of Düsseldorf, who gave a very brief notice of it in the Archiv der Pharmacie of Brandes (xxxiv. 318). Immediately afterwards Augustus Alms, a druggist’s assistant at Penzlin in the grand duchy of Mecklenburg-Schwerin, knowing nothing of Kahler’s discovery, obtained the same substance and named it Santonin. Alms recommended it to the medical profession, pointing out that it is the anthelminthic principle of wormseed.[1438] Santonin constitutes from 1½ to 2 per cent. of the drug, but appears to diminish in quantity very considerably as the flowers open. It is easily extracted by milk of lime, for, though not an acid and but sparingly soluble in water even at a boiling heat, it is capable of combining with bases. With lime it forms then santoninate of calcium, which is readily soluble in water. On addition of hydrochloric acid, santoninic acid, C₁₅H₂₀O₄, separates, but parts with OH₂, santonin being thus immediately reproduced. Similar facts have been recorded with regard to alantic acid (see p. 381).

Santonin forms crystals of the orthorhombic system, melting at 170°, which are inodorous, but have a bitter taste, especially when dissolved in chloroform or alcohol.[1439] They are colourless, but when exposed to daylight, or to the blue or violet rays, but not to the other colours of the spectrum, they assume a yellow hue, and split into irregular fragments. This change, which takes place even under water, alcohol or ether, is not accompanied by any chemical alteration. This behaviour of santonin when exposed to light, resembles that of erythrocentaurin, C₂₇H₂₄O₈. The latter has been obtained by means of ether, from the alcoholic extract of Erythræa Centaurium, and of some other Gentianaceæ. Méhu (1866) has shown that the colourless crystals of that substance when exposed to sunlight, assume a brilliant red colour, without undergoing any chemical alteration. The colourless solutions of this body in chloroform or alcohol yield the original substance. Yet as to santonin, Sestini and Cannizzaro (1876) have shown, that its dilute alcoholic solution, on long exposure to sunlight, affords a compound ether of photosantonic acid, namely C₁₅H₁₃O₄(C₂H₅)₂.

[1437] As the affected vision, so that objects appear as if seen through a yellow medium. Other effects are recorded by Stillé (Therapeutics and Mat. Med. ii. 641).

[1438] The paper of Alms being contained in the very same periodical (p. 319) as that of Kahler (and further in vol. xxxix. 190), affords additional evidence of the independence of the discovery.

[1439] Its ready solubility in 3 or 4 parts of chloroform renders its estimation easy when mixed with sugar, as in a santonin lozenge.

Wormseed contains, in addition to the above described bodies, resin, sugar, waxy fat, salts of calcium and potassium, and malic acid; when carefully selected and dried, it yielded us 6·5 per cent. of ash, rich in silica.

=Commerce=—Ludwig of St. Petersburg has stated that the imports of wormseed into that city were about as follows:—In 1862, 7400 cwt.; in 1863, 10,500 cwt.; in 1864, 11,400 cwt. The drug was brought from the Kirghiz steppes by Semipalatinsk and by Orenburg.

=Uses=—The drug is employed exclusively for its anthelminthic properties, partly in the form of santonin. It proves of special efficacy for the dislodgement of Ascaris lumbricoides.

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RADIX ARNICÆ

Rhizoma Arnicæ, Arnica Root; F. Racine d’Arnica; G. Arnicawurzel.

=Botanical Origin=—Arnica montana L., a perennial plant growing in meadows throughout the northern and central regions of the northern hemisphere, but not reaching the British Islands. In western and central Europe it is an inhabitant of the mountains, but in colder countries it grows in the plains.

In high latitudes, as in Arctic Asia and America, a peculiar form of the plant distinguished by narrow, almost linear leaves has been named A. angustifolia Vahl; but numerous transitional forms prove its identity with the ordinary A. montana of Europe.

=History=—The older botanists as Matthiolus, Gesner, Camerarius, Tabernæmontanus, and Clusius were acquainted with Arnica and had some knowledge of its medicinal powers, which appear to have been expressly recommended, towards the end of the 16th century, by Franz Joël, professor of Greifswald, Germany.[1440] All parts of the plant were no doubt popular remedies in Germany at an early period, but Arnica was only introduced into regular medicine on the recommendation of Johann Michael Fehr of Schweinfurt and of several other physicians.[1441] But for enthusiastic laudation of the new remedy, all these writers fall far short of Collin of Vienna, who imagined that in Arnica he had found a European plant possessing all the virtues of Peruvian Bark.[1442] In his hands fevers and agues gave way under its use, and more than 1000 patients in the Pazman Hospital were alleged to have been cured of intermittents by an electuary of the flowers, between 1771 and 1774. Such happy results were not obtained by other physicians.

[1440] Sprengel, Geschichte der Arzneykunde, iv. (1827) 546.

[1441] Fehr, De Arnica lapsorum panacea, in Ephemerid. nat. cur. Dec. 1, (1678, 1679) No. 2. p. 22 (“usus est in radice, foliis et floribus”).—G. A. de la Marche, Dissertatio, Halæ Magdeburg, 1744.

[1442] Heinrich Joseph Collin, Heilkräfte des Wolverley, Breslau, 1777 (translation); also Arnicæ, in febribus et aliis morbis putridis vires,—in the Anni Medici of Störck and Collin, ed. nov., Amstel., iii. (1779) 133.

Arnica (herba, flos, radix) had a place in the London Pharmacopœia of 1788, but it soon fell out of notice, so that Woodville writing in 1790, remarks that he had been unable to procure the plant from any of the London druggists. Of late years it has gained some popular notoriety as an application in the form of tincture, for preventing the blackness of bruises, but in England it is rarely prescribed internally.

=Description=—The arnic root of pharmacy consists of a slender, contorted, dark brown rootstock, an inch or two long, emitting from its under side an abundance of wiry simple roots, 3, 4 or more inches in length; it usually bears the remains of the rosette of characteristic, ovate, coriaceous leaves, which are 3-to 5-nerved, ciliated at the margin, and slightly pubescent on their upper surface. It has a faintly aromatic, herby smell, and a rather acrid taste.

=Microscopic Structure=—On a transverse section, the rootstock exhibits a large pith surrounded by a strong woody ring. In the innermost part of the cortical layer, large oil-ducts are found corresponding to the fibro-vascular bundles. Neither starch granules, inulin, or oxalate of calcium are visible in the tissue. The rootlets are of a different structural character, but also contain oil-ducts.

=Chemical Composition=—Several chemists have occupied themselves in endeavouring to isolate the active principle of arnica. Bastick described (1851) a substance which he obtained in minute quantity from the flowers and named Arnicine. He states it to possess alkaline properties, to be non-volatile, slightly soluble in water, more so in alcohol or ether; when neutralized with hydrochloric acid, it forms a crystalline salt.

The Arnicin extracted by Walz (1861) both from the root and flowers of arnica is a different substance; it is an amorphous yellow mass of acrid taste, slightly soluble in water, freely in alcohol or ether, and dissolving also in alkaline solutions. It is precipitable from its alcoholic solution by tannic acid or by water. Walz assigns to arnicin the formula C₂₀H₃₀O₄; other chemists that of C₃₅H₅₄O₇. Arnicin has not yet been proved a glucoside, although it is decomposed by dilute acids.

Sigel (1873) obtained from dried arnica root about ½ per cent. of essential oil, and 1 per cent. from the fresh; the oil of the latter had a sp. gr. of 0·999 at 18° C. The oil was found to be a mixture of various bodies, the principle being dimethylic ether of thymohydroquinone

{OCH₃ C₁₀H₁₂ { , boiling at about 235°. {OCH₃

The water from which the oil separates contains isobutyric acid, probably also a little angelic and formic acid; but neither capronic nor caprylic acid, which had been pointed out by Walz.

Arnica root contains inulin, which Dragendorff extracted from it to the extent of about 10 per cent.

=Uses=—Arnica is used chiefly in the form of tincture as a popular application to bruises and chilblains; internally it is occasionally prescribed as a stimulant and diaphoretic.

=Adulteration=—Arnica root has been met with[1443] adulterated with the root of Geum urbanum L., a common herbaceous plant of the order Rosaceæ. The latter is thicker than the rhizome of arnica, being ³/₁₀ to ⁴/₁₀ of an inch in diameter; it is a true root, furnished on all sides with rootlets, and has an astringent taste. The leaves of Geum are pinnate and quite unlike those of arnica.

[1443] Holmes in Pharm. Journ., April 11, 1874. 810.

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FLORES ARNICÆ

=Botanical Origin=—See preceding article.

=History=—The flowers probably in the first line attracted the attention of popular medicine in Germany, as we pointed out, page 390.

=Description=—Arnica montana produces large, handsome, orange-yellow flowers, solitary at the summit of the stem or branches. The involucral scales of the capitulum (20 to 24) are of equal length, but are imbricated, forming a double row. They are very hairy, the shorter hairs being tipped with viscid glands. The receptacle is chaffy, ¼ of an inch in diameter, with about 20 ligulate florets, and of tubular a much larger number. The ligulate florets, an inch in length, are oblong, toothed at the apex, and traversed by about 10 parallel veins. The achenes are brown and hairy, crowned by pappus consisting of a single row of whitish barbed hairs.

The receptacle is usually inhabited by a fly, Trypeta arnicivora Löw[1444]; the Pharmacopœia Germania (1872) therefore ordered the florets to be deprived of the involucre and receptacle—“flosculi a peranthodio liberati.” From a chemical point of view the usefulness of this direction may be doubted.

[1444] Figured in Nees von Esenbeck’s Plantæ medicinales, Düsseldorf, ii. (1833) fol. 39.

Arnica flowers have a weak, not unpleasant odour; they were formerly used in making the tincture, but as the British Pharmacopœia now directs that preparation to be made with the root, they have almost gone out of use in Great Britain.

=Chemical Composition=—The flowers appear to be rather richer in arnicin than the root, and are said to be equal if not superior to it in medicinal powers; yet the essential oil they contain is not the same. It is obtained in but extremely small amount and has a greenish or blue coloration. Hesse (1864) has proved that the flowers are devoid of a peculiar volatile alkaloid which had been supposed to be present in them.

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RADIX TARAXACI

Dandelion Root, Taraxacum Root; F. Pissenlit; G. Löwenzahnwurzel.

=Botanical Origin=—Taraxacum officinale Wiggers T. Dens-leonis Desf., Leontodon Taraxacum L., a plant of the northern hemisphere, found over the whole of Europe, Central and Northern Asia, and North America, extending to the Arctic regions. It varies under a considerable number of forms, several of which have been regarded as distinct species. In many districts it is a troublesome weed.

=History=—Though the common Dandelion is a plant which must have been well known to the ancients, no indubitable reference to it can be traced in the classical authors of Greece and Italy; it is thought that ἀθάκη of Theophrast and others means it. The word Taraxacum is however usually regarded as of Greek origin;[1445] we have first met with as Tarakhshagun in the works of the Arabian physicians, who speak of it as a sort of Wild Endive. It is thus mentioned by Rhazes in the 10th, and by Avicenna in the 11th century.

The name Dens Leonis, an equivalent of which is found in nearly all the languages of Europe, is stated in the herbal of Johann von Cube[1446] to have been bestowed on this plant by one Wilhelm, a surgeon, who held it in great esteem; but of this personage and of the period during which he lived we have sought information in vain, and we may remember that Dens Leonis (“Dant y Llew”) is already met with in the Welsh medicine of the 13th century.[1447]

Dandelion was also much valued as medicine in the time of Gerarde and Parkinson, and is still extensively employed.

=Collection=—In England, taraxacum root is considered to be in perfection for extract in the month of November, the juice at that period affording an ampler and better product than at any other. Bentley contends that it is more bitter in March, and most of all in July, and that at the former period at least it should be preferred.

=Description=—The root is perennial, and tapering, simple, or slightly branched, attaining in a good soil a length of a foot or more, and half an inch to an inch in diameter. Old roots divide at the crown into several heads. The root is fleshy and brittle; externally of a pale brown, internally white, and abounding in an inodorous milky juice of bitter taste. It shrinks very much in drying, losing in weight about 76 per cent.[1448]

Dried dandelion root is half an inch or less in thickness, dark brown, shrivelled with wrinkles running lengthwise often in a spiral direction; when quite dry, it breaks easily with a short corky fracture, showing a very thick white bark, surrounding a woody column. The latter is yellowish, very porous, without pith or rays. A rather broad but indistinct cambium-zone separates the wood from the bark, which latter exhibits numerous well-defined concentric layers. The root has a bitterish taste.

=Microscopic Structure=—On the longitudinal section, especially in a tangential direction, the brownish zones are seen to contain laticiferous vessels, only about 2 mkm. in diameter. These traverse their zones in a vertical direction, giving off numerous lateral branches, which however remain always confined to their zone. Within each of these zones, the lacticiferous vessels form consequently an anastomosing net. We may say that the root is thus vertically traversed by about 10 to 20 concentric rings of lacticiferous vessels.[1449] They may be made beautifully evident by means of anilin-blue, with which a thin longitudinal section of the fresh root may be moistened. The root must be allowed to partially dry, but only till the milky juice coagulates; the thin slice then energetically absorbs the colouring matter.[1450]

[1445] Perhaps from τράζυνον or τρόξμνον signifying Wild Lettuce; according to some, from τάραξις, a disease of the eye which the plant was used to cure, or from the verb τάρασσω, I disturb.

[1446] Herbarius zu teutsch und von aller handt kreuteren, Augspurg, 1488. cap. clii.

[1447] The Physicians of Myddvai, 284 (see Appendix).

[1448] Thus 5496 lb. of the washed root afforded of dry only 1277 lb., or 23·2 per cent.—Information communicated by Messrs. Allen and Hanburys, London.

[1449] For further particulars about them, see Vogl, Sitzungsber. der Wiener Akademie, vi. (1863) 668 with plate; Hanstein, Milchsaftgefässe und verwandte Organe der Rinde, Berlin, 1864. 72. 73. pl. ix.

[1450] The reader who is not familiar with this process may refer to a paper by Pocklington in Pharm. Journ. April 13, 1872. 822.

The tissue of the dried root is loaded with inulin, which does not occur in the solid form in the living plant. The woody part of taraxacum root is made up of large scalariform vessels accompanied by parenchymatous tissue, the former much prevailing.

=Chemical Composition=—The fresh milky juice of dandelion is bitter and neutral, but it soon acquires an acid reaction and reddish brown tint, at the same time coagulating with separation of masses of what has been called by Kromayer (1861), Leontodonium. This chemist, by treating this substance with hot water, obtained a bitter solution yielding an active (?) principle to animal charcoal, from which it was removed by means of boiling spirit of wine. After the evaporation of the alcohol, Kromayer purified the liquid by addition of basic acetate of lead, saturation of the filtered solution with sulphuretted hydrogen and evaporation to dryness. The residue then yielded to ether an acrid resin, and left a colourless amorphous mass of intensely bitter taste, named by Kromayer Taraxacin. Polex (1839) obtained apparently the same principle in warty crystals; he simply boiled the milky juice with water and allowed the concentrated decoction to evaporate.

The portion of the “Leontodonium,” not dissolved by water, yields to alcohol a crystalline substance, Kromayer’s Taraxacerin, C₈H₁₆O. It resembles lactucerin and has in alcoholic solution an acrid taste. How far the medicinal value of dandelion is dependent on the substances thus extracted, is not yet known.

Dragendorff (1870) obtained from the root gathered near Dorpat in October and dried at 100° C., 24 per cent. of Inulin and some sugar. The root collected in March from the same place yielded only 1·74 per cent. of inulin, 17 of uncrystallizable sugar and 18·7 of Levulin. The last named substance, discovered by Dragendorff, has the same composition as inulin, but dissolves in cold water; the solution tastes sweetish, and is devoid of any rotatory power. Inulin is often to be seen as a glistening powder when extract of taraxacum is dissolved in water.

T. and H. Smith of Edinburgh (1849) have shown that the juice of the root by a short exposure to the air undergoes a sort of fermentation which results in the abundant formation of Mannite, not a trace of which is obtainable from the perfectly fresh root. Sugar which readily underwent the vinous fermentation was found by the same chemists in considerable quantity.

The leaves and stalks of dandelion (but not the roots) were found by Marmé (1864) to afford the Inosite, C₆H₁₂O + 2 OH.

The root collected in the meadows near Bern immediately before flowering, carefully washed and dried at 100° C., yielded us 5·24 per cent. of ash, which we found to consist of carbonates, phosphates, sulphates, and in smaller quantity also of chlorides.

=Uses=—Taraxacum is much employed as a mild laxative and tonic, especially in hepatic disorders.

=Adulteration=—The roots of Leontodon hispidus L. (Common Hawkbit) have occasionally been supplied by fraudulent herb-gatherers in place of dandelion. Both plants have runcinate leaves, but those of hawkbit are hairy, while those of dandelion are smooth. The (fresh) root of the former is tough, breaking with difficulty and rarely exuding any milky juice.[1451]

The dried root of dandelion is exceedingly liable to the attacks of maggots, and should not be kept beyond one season.

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HERBA LACTUCÆ VIROSÆ

Prickly Lettuce; F. Laitue vireuse; G. Giftlattich.

=Botanical Origin=—Lactuca virosa L.,[1452] a tall herb occurring on stony ground, banks and roadsides, throughout Western, Central and Southern Europe. It is abundant in the Spanish Peninsula and in France, but in Britain is only thinly scattered, reaching its northern limit in the south-eastern Highlands of Scotland.

=History=—The introduction of this lettuce into modern medicine is due to Collin (the celebrated physician of Vienna, mentioned in our article on Rad. Arnicæ, p. 390), who about the year 1771 recommended the inspissated juice in the treatment of dropsy. In long standing cases, this extract was given to the extent of half an ounce a day.

The College of Physicians of Edinburgh inserted Lactuca virosa L. in their pharmacopœia of 1792, while in England its place was taken by the Garden Lettuce, L. sativa L. The Authors of the British Pharmacopœia of 1867 have discarded the latter, and directed that Extractum Lactucæ shall be prepared by inspissating the juice of L. virosa.

=Description=—The plant is biennial, producing in its first year depressed obovate undivided leaves, and in its second a solitary upright stem, 3 to 5 feet high, bearing a pinacle of small, pale yellow flowers, resembling those of the Garden Lettuce. The stem, which is cylindrical and a little prickly below, has scattered leaves growing horizontally; they are of a glaucous green, ovate-oblong, often somewhat lobed, auricled, clasping, with the margin provided with irregular spinescent teeth, and midrib white and prickly. The whole plant abounds in a bitter, milky juice of strong, unpleasant, opiate smell.

=Chemical Composition=—We are not aware of any modern chemical examination having been made of Lactuca virosa. The more important constituents of the plant are those found in Lactucarium, to the article on which the reader is referred.

=Uses=—The inspissated expressed juice of the fresh plant is reputed narcotic and diuretic, but is probably nearly inert.

[1451] Giles, Pharm. Journ. xi. (1851) 107.

[1452] Bentham unites this plant with L. Scariola L., but in most works on botany they are maintained as distinct species.

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LACTUCARIUM

Lactucarium, Lettuce Opium, Thridace;[1453] F. and G. Lactucarium.

=Botanical Origin=—The species of Lactuca from which lactucarium is obtained, are three or four in number, namely—

1. Lactuca virosa L., described in the foregoing article.

2. L. Scariola L., a plant very nearly allied to the preceding and perhaps a variety of it, but having the foliage less abundant, more glaucous, leaves more sharply lobed, much more erect and almost parallel with the stem. It has the same geographical range as L. virosa.

3. L. altissima Bieb., a native of the Caucasus, now cultivated in Auvergne in France for yielding lactucarium. It is a gigantic herb, having when cultivated a height of 9 feet and a stem 1½ inches in diameter. Prof. G. Planchon believes it to be a mere variety of L. Scariola L.

4. L. sativa L., the common Garden Lettuce.[1454]

=History=—Dr. Coxe of Philadelphia was the first to suggest that the juice of the lettuce, collected in the same manner as opium is collected from the poppy, might be usefully employed in medicine. The result of his experiments on the juice which he thus obtained from the garden lettuce (L. sativa L.), and called Lettuce Opium, was published in 1799.[1455]

The experiments of Coxe were continued some years later by Duncan, Young, Anderson, Scudamore and others in Scotland, and by Bidault de Villiers and numerous observers in France. The production of lactucarium in Auvergne was commenced[1456] by Aubergier, pharmacien of Clermont-Ferrand, about 1841.

=Secretion=—All the green parts of the plant are traversed by a system of vessels, which when wounded, especially during the period of flowering, instantly exude a white milky juice. The stem, at first solid and fleshy but subsequently hollow, owes its rigidity to a circle of about 30 fibro-vascular bundles, each of which includes a cylinder of cambium. At the boundary between this tissue and the primary cortical parenchyme, is situated the system of milk-vessels, exhibiting on transverse section a single or double circle of thin-walled tubes, the cavities of which contain dark brown masses of coagulated juice. In longitudinal section, they appear branched and transversely bound together, as in the milk-vessels of taraxacum. The larger of these tubes, 35 mkm. in diameter, correspond pretty regularly in position with the vascular bundles. Each of the latter is also separated from the pith by a band or arch of cambium, in the circumference of which isolated smaller milk-vessels occur.

The system of milk-vessels[1457] is therefore double, belonging to the pith on the one side, and to the bark on the other, the two being separated by juiceless wood. The milk-vessels of the bark are covered by only 2 to 6 rows of parenchyme-cells of the middle bark, rapidly decreasing in size from within outwards, and these are protected by a not very thick-walled epidermis. Hence it is easy to understand how the slightest puncture or incision may reach the very richest milk-cells.

[1453] The term Thridace is also applied to Extract of Lettuce.

[1454] The authors of the French Codex of 1866 name as the source of lactucarium that form of the garden lettuce which has been called by DeCandolle Lactuca capitata. Maisch has obtained lactucarium from L. elongata Mühl. (Am. Journ. of Pharm. 1869. 148).

[1455] Inquiry into the comparative effects of the Opium officinarum, extracted from the Papaver somniferum or White Poppy of Linnæus, and that procured from the Lactuca sativa or Common cultivated Lettuce of the same author.—Transact. of the American Philosophical Society, iv. (1799) 387.

[1456] Comptes Rendus, xv. (1842) 923.

[1457] Beautifully delineated by Hanstein in the work referred to at p. 352, note 2; see also Trécul, Ann. des Sciences nat. Bot. v. (1866) 69; Dippel, Entstehung der Milchsaftgefässe, Rotterdam, 1865. tab. 1. fig. 17.

The drops of milky juice, when exposed to the air, quickly harden to small yellowish-brown masses, whitish within.

=Collection and Description=—Lactucarium has been especially collected since about the year 1845, in the neighbourhood of the small town of Zell on the Mosel between Coblenz and Trèves in Rhenish Prussia. The introduction of this industry is due to Mr. Goeris, apothecary of that place, to whom we are indebted for the following information, and for some further particulars, to Mr. Meurer of Zell.

The plant is grown in gardens, where it produces a stem only in its second year. In May just before it flowers, its stem is cut off at about a foot below the top, after which a transverse slice is taken off daily until September. The juice, which is pure white but readily becomes brown on the surface, is collected from the wounded top by the finger, and transferred to hemispherical earthen cups, in which it quickly hardens so that it can be turned out. It is then dried in the sunshine until it can be cut into four pieces, when the drying is completed by exposure to the air for some weeks on frames.

At Zell, 300 to 400 kilogrammes (661 to 882 lb.) of lactucarium are annually produced; the whole district furnishes at best but 20 quintals annually. The price the drug fetches on the spot varies from 4 to 10 thalers per kilogramme (about 6_s._ to 14_s._ per lb.) In the Eifel district, where lactucarium was formerly collected, none is now produced.

As found in trade, German lactucarium consists of angular pieces formed as already described, but rendered more or less shrunken and irregular by loss of moisture and by fracture. Externally they are of a dull reddish-brown, internally opaque and wax-like, and when recent, of a creamy white. By exposure to the air, this white becomes yellow and then brown. Lactucarium has a strong unpleasant odour, suggestive of opium, and a very bitter taste.

The lactucarium produced by Aubergier of Clermont-Ferrand is of excellent quality, but does not appear to differ from that obtained on the Mosel, except that it is in circular cakes about 1½ inches in diameter, instead of in angular lumps.

Scotch lactucarium, which was formerly the only sort found in the market, is still (1872) met with. Mr. Fairgrieve, who produces it in the neighbourhood of Edinburgh, collects the juice into little tin vessels, in which it quickly thickens; it is then turned out and dried with a gentle heat, the drug being broken up as the process of drying goes on. It is thus obtained in irregular earthy-looking lumps of a deep brown hue, of which the larger may be about an inch in length. In smell, it exactly resembles the drug collected on the Continent.[1458]

[1458] We are indebted to Mr. H. C. Baildon for a specimen of Scotch lactucarium collected about the year 1844, and to Messrs. T. and H. Smith for a sample of Mr. Fairgrieve’s article.

We have also before us Austrian lactucarium, prepared at Waidhofen on the Thaya, where about 35 kilogrammes are annually produced. It is in fine tears of vigorous smell.

We are unacquainted with Russian lactucarium, which has been quoted at a very high price in some continental lists.

=Chemical Composition=—Lactucarium is a mixture of very different organic substances, together with 8 to 10 per cent. of inorganic matter. It is not completely taken up by any solvent, and when heated merely softens but does not melt. Nearly half the weight of lactucarium consists of a substance called Lactucerin or Lactucon, which in our opinion is closely allied to if not identical with similar substances occurring in numerous milky juices. Lactucerin as afforded by the drug under examination is probably a mixture of several bodies. It may be obtained by exhausting lactucarium with boiling alcohol sp. gr. 0·830; it is deposited in crystals, which when duly purified have the form of slender colourless, microscopic needles. Lactucerin is an inodorous, tasteless substance, insoluble in water, but dissolving in ether and in oils both fixed and volatile, not quite so readily either in benzol, or in bisulphide of carbon. We found it to melt at 232° C. and to agree with the formula C₁₉H₃₀O; Franchimont (1879) assigns to it the formula C₁₄H₂₄O, melting point 296°.

Euphorbon (see Euphorbium), echicerin (see Cortex Alstoniæ), taraxacerin (p. 394), the cynanchol, C₁₅H₂₄O, extracted in 1875 by Buttleroff from Cynanchum acutum L., are remarkably analogous to lactucerin.

In the lactucarium of Zell, we further met with a large amount of a substance which is readily soluble in bisulphide of carbon. It is an amorphous mass, melting below 100°, separating from alcohol as a syrupy mass.

Cold alcohol, as well as boiling water, takes out of lactucarium about 0·3 per cent. of a crystallizable bitter substance, Lactucin, C₁₁H₁₂O₃H₂O, which although it reduces alkaline cupric tartrate, is not a glucoside. It may be best obtained by means of dialyse. Lactucin forms white pearly scales, readily soluble in acetic acid, but insoluble in ether. It loses its bitterness when treated with an alkali.

From the mother-liquors that have yielded lactucin, Ludwig, in 1847, obtained Lactucic Acid, as an amorphous light yellow mass, becoming crystalline after long standing. Lastly lactucarium has further afforded in small quantity an amorphous substance named Lactucopicrin, C₄₄H₆₄O₂₁, apparently produced from lactucin by oxidation; it is stated by Kromayer (1862) to be soluble in water or alcohol, and to be very bitter.

Of the widely diffused constituents of plants, lactucarium contains caoutchouc (40-50 per cent.), gum, oxalic, citric, malic and succinic acids, sugar, mannite, and asparagin, together with potassium, calcium and magnesium salts of nitric and phosphoric acids. We obtained crystals of nitrate of potassium by concentrating the aqueous decoction of lactucarium. On distillation with water, a volatile oil having the odour of lactucarium passes over in very small quantity.

=Uses=—The soporific powers universally ascribed in ancient times to the lettuce are supposed to exist in a concentrated form in lactucarium. Yet numerous experiments have failed to show that this substance possesses more than very slight sedative properties, if indeed it is not absolutely inert.[1459]

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