This section is from the book "A Treatise On Therapeutics, And Pharmacology Or Materia Medica Vol1", by George B. Wood. Also available from Amazon: Part 1 and Part 2.
Constituents* The most important of these are the alkaloids, quinia, cinchonia, quinidia, cinchonidia, quinicia and cinchonicia. Of these there are two distinct groups, one consisting of quinia, quinidia, and quinicia, all isomeric, and cinchonia, cinchonidia, and cinchonicia, which are also isomeric, but differ in composition from the first group. The last of each group, quinicia, namely, and cinchonicia, appear to result from the influence of heat upon the respective alkaloids with which they are isomeric, and, though they may possibly sometimes pre-exist in the bark, are more frequently the result of the chemical processes employed in the extraction of the others. The alkaloids are believed to exist in the bark chiefly in combination with kinic acid, in the form of soluble kinates, but partly also combined with colouring matter or tannic acid, fanning compounds insoluble in water, which, therefore, is of itself incompetent to exhaust all the virtues of bark. Other constituents are a bitter substance called kinovic bitter or kinovic acid, tannic acid, a red colouring matter called cinchonic red, a yellow colouring matter, resin, gum, starch, fatty matter, kinate of lime, etc.
* Since the publication of the first edition of this work, the subject of the cinchona alkaloids has been carefully investigated; and a general view of the results, somewhat different from the account of these alkaloids given in the former edition, is now presented in the text. (Note to the second edition).
Properties of the Alkaloids. The alkaloids are the active principles, and exist probably in all the varieties of bark, though in very different proportion. In the pale barks, cinchonia predominates; in the officinal yellow or Calisaya bark, quinia is most abundant; in the red, both these alkaloids are found in considerable proportion; while in the more active of the Carthagena barks, quinidia exists largely.
Quinia, which may be obtained by decomposing the sulphate by means of an alkali, is whitish, flocculent, crystallizable with difficulty, inodorous, and very bitter. It is fusible by heat without chemical change, is very slightly soluble in cold water, somewhat more so in boiling water, and very soluble in alcohol, ether, and the volatile and fixed oils. With the acids it forms crystallizable salts, of which there are two sets, one containing twice as much acid as the other. Different views are entertained of the equivalent constitution of these salts; some believing those containing the smaller proportion of acid to be sub-salts (with one eq. of acid and two eqs. of base), and those containing the larger proportion to be neutral (with one eq. of acid and one of base); while others consider the first set to be neutral (with one eq. of acid and one eq. of base), and the second to be super or bi-salts (with two eqs. of acid and one eq. of base). Thus, the two sulphates would be denominated by one party disulphate and sulphate of quinia, by the other sulphate and bisulphate. Of course, the equivalent of the alkaloid is stated differently, according to these different views; being 162 in accordance with the former, and double that number with the latter. Quinia is distinguished from all other substances, with the exception of its isomeric alkaloids, by the emerald-green colour which its solution, or that of its salts assumes, when treated, first with chlorine, and then with ammonia, and which changes to violet upon saturation with a dilute acid.
Quinidia, though isomeric with quinia, differs from that alkaloid in crystallizing readily, in being less soluble in ether, and in its influence on polarized light It differs also from this, and all the other cinchona alkaloids, in the circumstance, that a solution of its sulphate yields a white precipitate with solution of iodide of potassium. Its crystals effloresce on exposure to the air. It resembles quinia in its chemical relations with chlorine and ammonia.
Quinicia differs from quinia in being apparently quite uncrystallizable, and in its effects on polarized light; but agrees with it in composition, and in most of its chemical relations. It is, indeed, in all probability, the result of certain molecular changes produced in quinia by the influence of heat used in its extraction. It is not employed separately in a pure state.
Cinchonia may be prepared from the sulphate in the same manner as quinia from its sulphate. It is white, crystallizable, almost insoluble in cold water, very slightly soluble in boiling water, freely soluble in boiling alcohol, which deposits it on cooling, scarcely soluble in ether, and but slightly so in volatile or fixed oils. In consequence of its comparative insolubility, it is much less bitter than quinia; scarcely having any taste when first applied to the tongue, but becoming bitter in a short time as it dissolves; and its solutions are very bitter. By a moderate heat it melts, but is at the same time decomposed. It forms with the acids crystallizable salts, of which, as in the case of quinia, there are two sets, to which the same remarks are applicable as those made in reference to the salts of the latter alkaloid. Its equivalent is consequently given differently, either 154, or double that number. It is distinguished by affording a white precipitate, when its solution, or that of its salts, in chlorine water is treated with ammonia.
Cinchonidia bears the same relation to cinchonia that quinidia does to quinia. Like cinchonia it forms anhydrous crystals, which do not like those of quinidia effloresce in a warm air. It also agrees with its isomeric alkaloid in not producing a green colour with chlorine and ammonia; but is more soluble in ether than cinchonia, and differs in its influence on polarized light.
Cinchonicia, which is derived from cinchonia, is isomeric with it, and resembles it in chemical relations, but differs in being amorphous or uncrystallizable. Neither this, nor the preceding alkaloid is prepared separately for use, in a pure state, at least in any considerable quantity.
Under the name of quinidia or quinidine, an alkaloid substance was some time since brought into notice, and to some extent introduced into commerce, which Pasteur found to consist usually of the two alkaloids, named respectively quinidia and cinchonidia, but chiefly and sometimes exclusively of the latter. This has led to an unfortunate confusion of nomenclature; but the student should remember that what was commonly called quinidia in commerce, and still to a certain extent retains that name, is really in great measure cinchonidia. 'The nomenclature adopted here, after Pasteur, is necessary as expressive of the true relations of the several alkaloids.
The substance sometimes called quinoidine, which in its pure state is the amorphous quinia of Liebig, and is obtained from the mother waters left after the precipitation of sulphate of quinia, in the process for preparing that salt, is usually a mixture of quinicia and cinchonicia, and results from the reactions which take place in the process; the crystal-lizable alkaloids having been rendered, by molecular change, amorphous or uncrystallizable.
Chemical Relations and Incompatibilities. The alkalies and their carbonates, and the alkaline earths, precipitate the alkaloids from the infusion and decoction of bark; tannic acid, and all the astringent substances containing it, precipitate insoluble tannates of the alkaloids. By the reagents mentioned, therefore, the liquid aqueous preparations of bark are deprived of the active principles of that medicine; but, as the precipitated matter is active, the preparations, if the sediment be diffused through them, will still be efficient, though inelegant from their turbid-ness. The same may be said of the slight precipitates produced by the soluble salts of oxalic, tartaric, gallic, and acetic acids, in consequence of the difficult solubility of the compounds of these acids with the cinchona alkaloids. These precipitates, moreover, are redissolved by a slight excess of acid. Besides the precipitants mentioned, all of which disturb the relations of the active principles, there are many others, which, through reaction with the tannic acid often found in bark, or with other relatively inert constituents, form insoluble compounds, and occasion turbidness or deposition in the infusion. Among these are the soluble salts of lead, iron, zinc, silver, and mercury, tartar emetic, arsenious acid, and solutions of gelatin. Some of these act on certain varieties of bark, and not on others; as, for example, tartar emetic, which sometimes produces copious precipitates, and sometimes does not disturb the infusion. In consequence of the large proportion of kinate of lime in the Calisaya or officinal yellow bark, a strong infusion of this variety is precipitated by sulphate of soda, which does not affect most of the other barks. But the virtues of the infusion are not impaired by these reagents, as the active principles remain undisturbed; so that the incompatibility has reference, not to the Peruvian bark, but to the substance added.
Signs of Value. The taste affords some evidence of the strength of hark, which as a general rule, may be considered proportionate to the bitterness; but this test cannot be relied on with certainty; as in some inferior barks there is considerable bitterness, in consequence of the presence of kinovic acid, which has not the characteristic virtues of the medicine. The best method of testing any specimen of bark is to determine the percentage of the alkaloids contained in it, which is a pretty accurate measure of its medicinal activity. For the method of doing this, the reader is referred to the U. S. Dispensatory (12th ed.t p. 295).