Cinchona
CINCHONA, the generic name of a number of trees which belong to the natural order Rubiaceae. Botanically the genus includes trees of varying size, some reaching an altitude of 80 ft. and upwards, with evergreen leaves and deciduous stipules. The flowers are arranged in panicles, white or pinkish in colour, with a pleasant odour, the calyx being 5-toothed superior, and the corolla tubular, 5-lobed and fringed at the margin. The stamens are 5, almost concealed by the tubular corolla, and the ovary terminates in a fleshy disk. The fruit is an ovoid or subcylindrical capsule, splitting from the base, and held together at the apex. The numerous seeds are flat and winged all round. About 40 species have been distinguished, but of these not more than about a dozen have been economically utilized. The plants are natives of the western mountainous regions of South America, their geographical range extending from 10° N. to 22° S. lat.; and they flourish generally at an elevation of from 5000 to 8000 ft. above sea-level, although some have been noted growing as high up as 11,000 ft., and others have been found down to 2600 ft.
The trees are valued solely on account of their bark, which long has been the source of the most valuable febrifuge or antipyretic medicine, quinine (q.v.), that has ever been discovered. The earliest well-authenticated instance of the medicinal use of cinchona bark is found in the year 1638, when the countess of Chinchon (hence the name), the wife of the governor of Peru, was cured of an attack of fever by its administration. The medicine was recommended in her case by the corregidor of Loxa, who was said himself to have practically experienced its supreme virtues eight years earlier. A knowledge of the bark was disseminated throughout Europe by members of the Jesuit brotherhood, whence it also became generally known as Jesuits' bark. According to another account, this name arose from its value having been first discovered to a Jesuit missionary who, when prostrate with fever, was cured by the administration of the bark by a South American Indian. In each of the above instances the fever was no doubt malaria.
The procuring of the bark in the dense forests of New Granada, Ecuador, Peru and Bolivia is a work of great toil and hardship to the Indian cascarilleros or cascadores engaged in the pursuit. The trees grow isolated or in small clumps, which have to be searched out by the experienced cascarillero, who laboriously cuts his way through the dense forest ta the spot where he discovers a tree. Having freed the stem from adhering parasites and twining plants, he proceeds, by beating and cutting oblong pieces, to detach the stem bark as far as is within his reach. The tree is then felled, and the entire bark of stem and branches secured. The bark of the smaller branches, as it dries, curls up, forming "quills," the thicker masses from the stems constituting the "flat" bark of commerce. The drying, packing and transport of the bark are all operations of a laborious description conducted under most disadvantageous conditions.
The enormous medicinal consumption of these barks, and the wasteful and reckless manner of procuring them in America long ago, caused serious and well-grounded apprehension that the native forests would quickly become exhausted. The attention of European communities was early directed to the necessity of securing steady and permanent supplies by introducing the more valuable species into localities likely to be favourable to their cultivation. The first actual attempt to rear plants was made in Algeria in 1849; but the effort was not successful. In 1854 the Dutch government seriously undertook the task of introducing the trees into the island of Java, and an expedition for that purpose was fitted out on an adequate scale. Several hundreds of young trees were obtained, of which a small proportion was successfully landed and planted in Java; and as the result of great attention the cultivation of cinchona plantations in that island became highly prosperous and promising. The desirability of introducing cinchonas into the East Indies was urged in a memorial addressed to the East India Company between 1838 and 1842 by Sir Robert Christison and backed by Dr Forbes Royle; but no active step was taken till 1852, when, again on the motion of Dr Royle, some efforts to obtain plants were made through consular agents. In the end the question was seriously taken up, and Sir Clements R. Markham was appointed to head an expedition to obtain young trees from South America and convey them to India. The transference of the plants was attended with considerable difficulty, but in 1861 under his superintendence a consignment of plants was planted in a favourable situation in the Nilgiri Hills. For several years subsequently additional supplies of plants of various species were obtained from different regions of South America, and some were also procured from the Dutch plantations in Java. Now the culture has spread over a wide area in southern India, in Ceylon, on the slopes of the Himalayas, and in British Burma, and has become widely spread through the tropics generally. The species grown are principally Cinchona officinalis, C. Calisaya, C. succirubra, C. pitayensis, and C. Pahudiana, some agreeing with certain soils and climates better than others, while the yield of alkaloids and the relative proportions of the different alkaloids differ in each species.
The official "bark" of the British Pharmacopoeia is that of Cinchona succirubra or red bark. It is imported in the form of quills or recurved pieces, with a rough brown outer surface and a deep red inner surface, forming a reddish brown odourless powder, which has a bitter, astringent taste. The British Pharmacopoeia directs that the bark, when used to make the various medicinal preparations, shall contain not less than 5 nor more than 6% of total alkaloids, of which at least one-half is to be constituted by quinine and cinchonidine. The preparations of this bark are four: a liquid extract, standardized to contain 5% of total alkaloids; an acid infusion; a tincture standardized to contain 1% of total alkaloids; and a compound tincture which must possess one-half the alkaloidal strength of the last. The only purpose for which these preparations of cinchona bark should be used is as tonics; and even when this is the desired action there are many reasons why the alkaloid should be preferred, even though the recent introduction of standardization removes one of the chief objections to their use.
The pharmacology of red bark, dependent as it is almost entirely upon the contained quinine, will not here be discussed (see Quinine). But the composition of cinchona bark is a matter of importance and interest. The bark contains, in the first place, five alkaloids, of which all but quinine may here be dealt with. Quinidine, C20H24N2O2, is isomeric with quinine, from which it differs in crystallizing in prisms instead of needles, in being dextro- and not laevo-rotatory, and in being insoluble in ammonia except in much excess. Cinchonine has the formula C19H22N2O, quinine being methoxy cinchonine, i.e. C19H21(OCH3)N2O. It occurs in inodorous, bitter, colourless prisms; unlike the two alkaloids already named, does not yield a green colour with chlorine water and ammonia; is dextro-rotatory; not fluorescent, and practically insoluble in ammonia and in ether. A fourth alkaloid, cinchonidine, is isomeric with cinchonine, which yields it when boiled with amyl alcoholic potash, but is laevo-rotatory, slightly soluble in ether, and faintly fluorescent. When red bark is extracted with dilute hydrochloric acid, the product filtered, and excess of sodium hydrate added thereto, quinine and quinidine are precipitated: on concentrating the mother liquor, cinchonine falls down, and on further concentration with addition of still more alkali, cinchonidine is thrown out. Yellow bark, which is not official, yields 3% of quinine, and pale bark about 10% of total alkaloids, of which hardly any is quinine, cinchonine and quinidine being its chief constituents. The various forms of bark also yield a very small quantity of an unimportant alkaloid, conquinamine. In addition to the above, red bark contains quinic acid, C7H12O6, which is closely allied to benzoic acid and is excreted in the urine as hippuric acid. There also occurs chinovic acid, derived from a glucoside chinovin, which occurs as such in the bark. Besides a trace of volatile oil which gives the bark its characteristic odour, and cinchona red (the bark pigment), there occurs about 2% of cincho-tannic acid, closely allied to tannic acid and giving the bark its astringent property. Cinchona is never used, however, in order to obtain an astringent action.
The importance of recognizing the complex and inconstant composition of cinchona bark lies, as in so many other instances, in this - that the physician who employs it can have only a very imperfect knowledge of the drug he is using. The latest work on the action of these alkaloids has shown that cinchonine has a tendency to produce convulsions in certain patients, and that this action is a still more marked feature of cinchonidine and cinchonamine. Even small doses administered to epileptics increase the number of their attacks. They will probably be classified later among the convulsive poisons. The use of cinchona bark and its preparations, now that definite active principles can be readily obtained and precisely studied, is almost entirely to be deprecated. Quinidine is almost as powerful an antidote to malaria as quinine; cinchonidine has about two-thirds the power of quinine, and cinchonine less than one-half.
Note - this article incorporates content from Encyclopaedia Britannica, Eleventh Edition, (1910-1911)
