"A fixed oil expressed from the seeds of Croton Tiglium Linné (Fam. Euphorbiaceae). Preserve it in small, well-stoppered bottles, protected from light." U. S. "Croton Oil is the Oil expressed from the seeds of Croton Tiglium, Linn." Br.
Oleum Crotonis, Br.; Huile de Croton Tiglium, Fr. Cod.; Huile de Graines de Tilly, Fr.; Oleum Crotonis, P. G.; Krotonöl, G.; Olio di crotontiglio. It.; Aceite de croton tiglio, Aceite de grano tiglio, Sp.
Croton Tiglium Willd. is a small tree or shrub, with a few spreading branches, bearing alternate petiolate leaves, which are ovate, acuminate, serrate, smooth, of a dark-green color on the upper surface, paler beneath, and furnished with two glands at the base. The flowers are in erect terminal racemes, scarcely as long as the leaf—the lower being female, the upper male—with straw-colored petals. The fruit is a smooth capsule, about the size of a filbert, with three cells, each containing a single seed.
The tree is a native of Hindostan, Ceylon, the Moluccas, and other parts of India. It is pervaded by an acrid purgative principle, probably analogous to that found in other plants belonging to the family of Euphorbiaceae. Rumphius says that the root is employed in Amboyna, in the dose of a few grains, as a drastic purge in dropsy, and, according to the same author, the leaves are so acrid that when chewed and swallowed they excite inflammation in the lips, mouth, and throat, and along the whole course of the alimentary canal. The wood is said in small doses to be diaphoretic, in larger, purgative and emetic. But the seeds are the most active part. These have been long used in India as a powerful purgative, and were employed so early as 1630 in Europe, under the names of grana Molucca and grana tiglia. But in consequence of their violent effects they fell into neglect, and had ceased to be ranked among medicines, when, at a comparatively recent period, attention was again called to them by the writings of some English physicians in India. They are now imported for their oil, which is the only official product of the plant. It is probable that most if not all of the Crotons are purgatives. The oil of the Mexican Croton morifolius is said to be mildly purgative in doses of two or three minims (0.12-0.2 mil). In India, under the name of Kowli seeds (Kuli seeds), are used certain beans, which have been referred by authorities to the Croton oblongifolius Roxb., and also to the C. persimilis Mull. Arg. (See Ph, Rev., Oct., 1896.) Kowli seeds reach a length of 2.1 cm., a breadth of 1.2 cm., a thickness of 0.8 cm., ovate, having pointed ends with a marked caruncle. The outer side shows the grayish-brown crusty seed coat with irregular rough longitudinal stripes; the cross-section shows a large endosperm, in the middle the embryo of considerable size with flat cotyledons. Besides the fatty oil and protoplasm, the cells of the endosperm show longitudinally very large aleurone grains, which contain a considerable number of small globoids and badly formed crystalloids.
The seeds of the C. Tiglium resemble castor beans in size and general structure. They are oblong, rounded at the extremities, with two faces, the dorsal considerably more convex than the ventral, separated from each other by longitudinal ridges, and each divided by a similar longitudinal ridge, so that the whole seed presents an irregular quadrangular figure. Sometimes their ventral surface is flat, with a longitudinal groove, owing to the presence of only two seeds in the capsule, the groove being produced by the central column or axis. The shell is covered with a soft, yellowish-brown epidermis, beneath which the surface is black and smooth, and, as the epidermis is often partially removed by friction during their carriage, the seeds as they come to us are frequently mottled, and sometimes nearly black. The kernel or endosperm is yellowish-brown, and abounds in oil. In India the seeds are prepared for use? by submitting them to slight torref action, by which the shell is rendered more easily separable. In the dose of one or two grains (0.065 or 0.13 G-m.) the kernel purges severely.
The oil is obtained by expression from the seeds, previously deprived of the shell. It may also be separated by decoction in water, or by the action of ether, or carbon disulphide, which dissolves the oil and leaves it behind when evaporated. Guibourt recommends, after the first expression, to digest the residue with alcohol at a temperature of 48.8° to 60° C. (120°-140° F.), and then submit it to a new expression. The. alcohol is to be separated by distillation from the oil, which is then to be mixed with the first product. Great care must be used, during this distillation, to prevent blistering the unprotected skin of the operator.
Extraction by Ether.—Having washed and dried the seeds, grind them in a coffee mill, and form a soft paste with ether. Introduce this into a narrow percolation tube, and gradually pour ether upon it until it is exhausted. Evaporate the ether by means of a water bath, and filter the remaining oil.
Extraction with Carbon Disulphide.—The seeds, well bruised, are introduced into a bottle with three times their weight of carbon disulphide, well rectified; the mixture is allowed to stand, with frequent agitation, for 24 hours; the whole is then poured upon a cloth and rapidly expressed. The residue is similarly treated with twice its weight of the disulphide, and expressed, after standing as before. The products of the two macerations are mixed, then filtered in a covered funnel, and finally submitted to distillation, by means of a water bath, in a glass retort, at the temperature of 71.1° or 76.6° C. (160° or 170° F.). The disulphide should be recovered by condensing its vapor in a refrigerated receiver. The oil is to be poured into a dish, to show that it contains none of the disulphide, and then introduced into a bottle and closely stoppered.
Properties.—The seeds consist of 64 per cent. of kernel and 36 of envelope. From the seeds imported into England, about 22 per cent. of oil is obtained by simple expression. Guibourt, by his process, obtained 52 per cent. from the kernels, equivalent to about 35 per cent. from the seeds. Croton oil consists chiefly of the glycerides of stearic, palmitic, myristic, kluric, and oleic acids. There are also present, in the form of glycerin ethers, the more volatile acids, as formic, acetic, isobutyric, and isovalerianic acids. The volatile part of the acid yielded by croton oil contains, moreover, an acid of the oleic series, named by Geuther and Frolich tiglic or tiglinic acid) C5H8O2. It is isomeric with angelic acid, but the melting points (angelic acid 45° C. (113° F.), tiglic acid 64° C. (147.2° F.)) and the boiling points (angelic acid 185° C. (365° F.), tiglic acid 198.5° C. (389.3° F.)) differ. Crotonic acid, C4H6O2, was thought by Schlippe to be present, but later investigation does not confirm the statement. Crotonol, announced by Schlippe as the vesicating principle of the oil, has likewise been found only by the discoverer.
In 1823 John Nimmo, of Glasgow, found that about 45 per cent. of croton oil is soluble in alcohol, the insoluble 55 per cent. being inert. Recent researches have shown that the percentage of soluble portion varies greatly. (See also below.) In this soluble portion Buchheim found an acid, crotonolic acid or crotonoleic acid, which he believed to be the active principle. It is an oily substance, readily decomposable, having the character of a weak acid, and forming various salts. It is freely soluble in alcohol, and is extremely irritant to the skin and the mucous membrane. As pointed out in 1889 by Stilhnark and Robert, croton seeds contain one or snore toxic albuminoids, which have been especially studied under the name of crotin by Elf strand. Dimstan and Boole (Proc. Roy. Soc. London, lxiii, 1895) found that crotonoleic acid, prepared by the method of Kobert and Hirscheydt, is a mixture of inactive oily acids and a resinous substance having extraordinary power as a vesicant, for which they have proposed the name of croton resin, assigning to it the empirical formula C13H18O4, and the molecular formula (C13H18O4)2, or C36H36O8. It is described as a hard, pale yellow resin, nearly insoluble in water, and benzene, but readily dissolved by alcohol, ether, and chloroform. It is neither a glyceride, a ketone, nor an aldehyde.
Crotonoleic acid may be readily prepared by treating the portion of croton oil soluble in alcohol with a hot saturated solution of baryta in a water bath, washing the stiff white paste that forms with cold distilled water to remove excess of baryta and barium compounds with acetic, butyric, and tiglic acids, repeatedly treating with water, and lastly agitating with ether, which takes up only the barium oleate and crotonoleate. The crotonoleate is separated by dissolving it out in alcohol, decomposing it carefully with sulphuric acid, and the solution containing the free acids carefully evaporated. (See also Robert's Arbeiten, 1890, p. 30.)
Crotin is described as a yellowish powder, yielding about 21 per cent. of ash, soluble in water, and possessed of such active poisonous properties that the subcutaneous lethal dose for the rabbit is from 0.05 to 0.08 Gm. per kilo. It attacks the blood corpuscles as well as the centric nervous system, and, indeed, probably affects all protoplasm. (On Some Toxic Albumins, Upsala, 1897.)
Croton oil, as found in commerce, varies greatly in color, from a pale yellow to a dark reddish-brown. That imported from India is usually pale, that expressed in Europe dark, like the deepest-colored sherry. Its consistence is rather viscid, and is increased by time. Its odor is faint, but peculiar, its taste hot and acrid, leaving in the mouth a disagreeable sensation which continues for many hours. It is officially described as " a pale yellow or brownish-yellow, somewhat viscid and slightly fluorescent liquid, having a slight, characteristic odor. Great caution is necessary in tasting it, and it must be handled carefully as it causes a pustular eruption, when applied to the skin. It is slightly soluble in alcohol, the solubility increasing with age; freely soluble in ether, chloroform, or in fixed or volatile oils. It is acid to litmus paper previously moistened with alcohol. Specific gravity: 0.935 to 0.950 at 25° C. (77° F.). When gently heated with twice its volume of dehydrated alcohol, it forms a 1 part each of cacao butter and white wax in a small glass flask, and then adding 2 parts; of croton oil, taking care to close the orifice of the flask at once with a cork. When the mixture begins to get thick, it is poured into cylindrical moulds, where it speedily solidifies. These crayons may be made of a thickness of about 8 or 9 millimeters (1/3 inch), and may be covered with tin foil to protect them from change. (N. R., May, 1877.)
The oil is most conveniently administered in the form of pill. A safe and convenient plan is to make two drops into four pills with crumb of bread, and to give one every hour until they operate. The oil may also be given in emulsion.
Crotonoleic acid has been shown by Kobert to be a very active irritant poison, much more harsh and severe in its influence than croton oil itself. Hirscheydt has found that its salts injected into the blood are extremely powerful depressants to the circulation. It has appeared in commerce, but after trial has been found by Hirscheydt to act badly as a practical remedy. It probably also varies greatly in purity. Ten milligrams were found by Hirscheydt to be very uncertain in their purgative effect, while large doses commonly produced excessive gastro-intestinal irritation. The superiority of croton oil over the acid probably depends upon the fact that the acid exists in it chiefly in combination with glycerin, and that this crotonoleic glyceride acts with comparative kindness because of the slow decomposition and setting free of the acid which occur in the intestines. This being the case, it follows as a corollary that old, acid croton oil must be more irritant than the fresher and nearly neutral oil. Robert has confirmed this conclusion by actual trial, and asserts that the neutral oil should always be preferred in practice, and that the acid oil should be rejected.
Dose, one-half to two minims (0.03-0.12 mil).
Off. Prep.—Linimentum Crotonis, Br.; Collodium Tiglii, N. F.; Linimentum Tiglii, N. F.; Linimentum Tiglii Compositum, N. F.; Pilulae Aloes, Hydrargyri et Scammonii Compositae, N.F.
The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.