I.—PHÆNOGAMOUS OR FLOWERING PLANTS. (continued 11)

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.

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.

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.

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.

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]

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.

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.

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.

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.

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.

CONSPECTUS OF THE PRINCIPAL SPECIES OF CINCHONA.

SPECIES (EXCLUDING SUB-SPECIES AND VARIETIES) ACCORDING TO WEDDELL. WHERE FIGURED. NATIVE COUNTRY. WHERE CULTIVATED. PRODUCT.

I. Stirps Cinchonæ officinalis

1. Cinchona officinalis Hook Bot. Mag. 5804 Ecuador (Loxa) India, Ceylon, Java. Loxa or Crown Bark, Pale Bark.

2. ” macrocalyx Pav. Howard N. Q. Peru 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. Do. Ecuador, Peru.

4. ” lanceolata R. et P.(?) Do. Peru Carthagena Bark, confounded with Palton Bark, but is not so good.

5. ” lancifolia Mutis Karsten tab. 11. 12. New Granada India Columbian Bark. Imported in large quantities for manufacture of quinine.The soft Columbian Bark is produced by Howard’s var. _oblonga_.

6. ” amygdalifolia Wedd. Wedd. tab. 6. Peru, Bolivia A poor bark, but not now imported.

II. Stirps Cinchonæ rugosæ

7. Cinchona pitayensis Wedd. Karst. tab. 22. (C. Trianæ). New Granada (Popayan) India Pitayo Bark. Very valuable; used by makers of quinine; it is the chief source of quinidine.

8. ” rugosa Pav. Howard N. Q. Peru Bark unknown, probably valueless.

9. ” Mutisii Lamb. Do. Ecuador Bark not in commerce, contains only aricine.

10. ” hirsuta R. et P. Wedd. tab. 21. Peru

11. ” carabayensis Wedd. Wedd. tab. 19. Peru, Bolivia Bark not collected.

12. ” Pahudiana How. Howard N. Q. Peru India, Java A poor bark, yet of handsome appearance; propagation of tree discontinued.

13. ” asperifolia Wedd. Wedd. tab. 20. Bolivia Bark not collected.

14. ” umbellulifera Pav. Howard N. Q. Peru Bark not known as a distinct sort.

15. ” glandulifera R. et P. Do. Peru Do.

16. ” Humboldtiana Lamb. Do. Peru False Loxa Bark, Jaen Bark. A very bad bark.

III. Stirps Cinchonæ micranthæ

17. Cinchona australis Wedd. Wedd. tab. 8. South Bolivia An inferior bark, mixed with Calisaya.

18. ” scrobiculata H. et B. Do. Peru Bark formerly known as Red Cusco Bark or Santa Ana Bark.

19. ” peruviana How. Howard N. Q. Peru

20. ” nitida R. et P. Do. Peru India Grey Bark, Huanuco or Lima Bark. Chiefly consumed on the Continent.

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. Calisaya Bark, Bolivian Bark, Yellow Bark. The tree exists under many varieties, bark also very variable.

23. ” elliptica Wedd. Do. Peru (Carabaya) 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. Howard N. Q. Peru (Huamalica) Huamalies Bark. Not now Imported.

25. ” rufinervis Wedd. Do. Peru, Bolivia Bark, a kind of light Calisaya.

26. ” succirubra Pav. Do. Ecuador India, Ceylon, Java, Jamaica. Red Bark. Largely cultivated in British India.

27. ” ovata R. et P. Do. Peru, Bolivia India(?), Java(?) Inferior Brown and Grey Barks.

28. ” cordifolia Mutis Karsten tab. 8. New Granada, Peru Columbian Bark (in part). Tree exists under many varieties; bark of some used in manufacture of quinine.

29. ” tucujensis Karst. Karsten tab. 9. Venezuela Maracaibo Bark.

30. ” pubescens Vahl Wedd. tab. 16. Ecuador, Peru, Bolivia 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. Wedd. tab. 18 Bolivia 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.

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).

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.

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.

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

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.

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.

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.

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.

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.

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). 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 “mossing 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 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 Flora 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 (José), 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.

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.

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]

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.

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.

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]

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.

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.

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.”

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.