Oleum Tiglii (U. S. P.)—Croton Oil.
The expressed fixed oil of the seeds of Croton Tiglium, Linné; Tiglium officinale, Klotzsch.
ILLUSTRATION: Bentley and Trimen, Med. Plants, 239.
Botanical Source.—Croton Tiglium is a middle-sized tree, the young branches of which are terete, smooth, shining, and somewhat furrowed toward the extremities. The leaves are alternate, petiolate, oval, oblong, acute, 3 to 5-nerved at the base, acuminate at the apex, with shallow, glandular serratures; thin, membranous, with 2 glands at their base, and covered when young with very minute, scattered hairs, dark-green above, and paler below. The petioles are about one-third the length of the leaf, channeled, having stellate hairs when quite young, but soon losing them. The flowers are downy, in erect, terminal racemes; male flowers at the apex, female below. The male flowers have a 5-cleft calyx, 5 lanceolate, woolly, straw-colored petals, and 15 distinct stamens; female have a 5-cleft, permanent calyx, with long and bifid styles. The fruit is a smooth, oblong, obtusely triangular capsule, about the size of a hazel-nut, closely covered with minute, stellate hairs, with 3 cells, each of which is completely filled with a solitary seed. The skin of the seeds is of a pale, dull-brown color, and overlies a harder, dark integument (L.—Wi.).
History and Preparation.—This tree is a native of the East Indies, growing in Ceylon, in the Molucca Islands, in China, etc., and is cultivated in Japan and European countries. The tree was probably first known in China. Its wood (lignum pavanae) and seeds (pini nuclei moluccani) were made known to the Europeans in 1578, by the Portuguese physician, Christobal Acosta. Like the various plants of this natural order, it is imbued in all its parts (root, bark, leaves, seeds) with a sharp, energetic, drastic cathartic element. The oil obtained from the seeds is the official part. The seeds are of an ovoid form, about the size of a pea, reddish-brown when recent, grayish-brown when old, sometimes brownish-black. They consist of a thin, brittle, ligneous shell; a delicate, white, membranous integument; and an oleaginous kernel composed of a pale, yellowish-white albumen, and a beautiful embryo, with large, leafy cotyledons. The oil, which constitutes about 50 to 60 per cent of the kernels, is obtained by removing the shells from the seeds, bruising these to a pulp, and subjecting the pulp to a strong pressure. By digesting the residue with sulphuric ether, filtering, and expelling the ether by a gentle heat, an additional quantity of oil is often obtained. The residual press-cakes must be burned up in order to guard against accidents that might possibly result from handling them. Or, the seeds may be extracted altogether with sulphuric ether, or with carbon disulphide, and the solvent evaporated. These methods, however, are not recognized by the U.S. P. A. H. Allen (Com. Org. Anal., Vol. II, Part I, 1899, p. 161) reports that extraction with ether removes three times as much oil as when the oil is expressed, or extracted with alcohol. Expression yields a pale oil, ether a light-brown, and alcohol a dark-brown oil, containing twice as much free acid as the specimens obtained by the other methods. Its saponification value is also much higher.
Description and Tests.—The croton oil of commerce is partly imported from India, and partly expressed in England from the imported seeds. English croton oil is of a reddish-brown color, and forms a uniform, transparent mixture with equal parts of absolute alcohol, without the aid of heat. The East Indian croton oil is pale-yellow, like Canada balsam, and mixed with equal parts of absolute alcohol, forms an opaque, milky solution, which is rendered transparent and uniform upon the application of heat. The East Indian is the official oil, and is described as "a pale-yellow or brownish-yellow, somewhat viscid, and slightly fluorescent liquid, having a slight, fatty odor, and a mild, oily, afterward acrid and burning taste (great caution is necessary in tasting). When applied to the skin, it produces rubefaction or a pustular eruption. Specific gravity, 0.940 to 0.960 at 15° C. (59° F.). It reddens blue litmus paper moistened with alcohol. When fresh, it is soluble in about 60 parts of alcohol, the solubility increasing by age. It is freely soluble in ether, chloroform, carbon disulphide, and in fixed or volatile oils. When gently heated with twice its volume of absolute alcohol, it forms a clear solution from which the oil usually separates on cooling"—( U. S. P.). The U. S. P. also directs that "croton oil should be kept in small, well-stoppered bottles, and should be handled with caution"—(U. S. P.).
Croton oil has the highest specific gravity (see above) of all fatty oils, except castor oil. It is also soluble in glacial acetic acid, and soluble in petroleum ether, while castor oil is insoluble in the latter solvent. Croton oil is intermediate between the drying and non-drying oils, and does not give the elaïdin reaction. Accordingly the U. S. P. directs that "if to 2 Cc. of the oil 1 Cc. of fuming nitric acid and 1 Cc. of water be added, and the mixture vigorously shaken, it should not solidify, either completely or partially, after standing for 1 or 2 days (absence of other non-drying oils)"—(U. S. P.). The presence of castor oil may probably be detected by its insolubility in petroleum ether.
It is stated that an oil not quite as active as the pure croton is obtained from the Barbadoes nuts, or the seeds of Curcas purgans, Adanson (Jatropha Curcas, Linné) (see Curcas); it is an active purgative in a dose of 3 to 5 drops. The seeds of the Croton pavanae, Hamilton, are likewise supposed to furnish some of the commercial croton oil. An inferior oil which has been recommended as a substitute for croton oil is obtained from the Caper spurge, or Garden spurge (Euphorbia Lathyris, Linné) of south Europe. It is extracted with carbon disulphide, and deposits a crystalline body on standing. Croton oblongifolius, Roxburgh, has similar seeds, while the seeds of Croton morifolius, of Mexico, yield an oil, mildly cathartic in 2 or 3-drop doses.
Chemical Composition.—I. THE SEEDS. These, according to Flückiger, consist of 31.6 per cent of husks, and 68.4 per cent of kernels, the latter containing from 50 to 60 per cent of croton oil. The husks hold about 1.65 per cent of oil (Zinnel, Amer. Jour. Pharm., 1890, p. 122). The seeds contain, beside the oil and the usual seed constituents, two powerfully poisonous albuminous bodies, croton-globulin and croton-albumin (Ufstrand, 1897). The poisonous principle remains to some extent in the press-cake (H. Stillmark's Dissertation, Ueber Ricin, 1889, p. 146).
II. THE OIL.—Croton oil was found by Schlippe (1858) to contain the glycelides of stearic, palmitic, lauric, myristic, and oleic acids, and a vesicating resinous principle crotonol. The additional angelic acid, of Schlippe, was found by Guenther and Fröhlich (1870) to differ from true angelic acid in melting point, and was named tiglinic acid. Schmitt and Berendes (1878) found this acid to be identical with Frankland and Duppa's methylcrotonic acid (C6H8O2), and also established the presence of isobutyric and isovaleric acids in croton oil. Acetic acid was previously shown by Guenther and Fröhlich to be present.
Regarding the active principles of croton oil, it has long been known (Nimmo, 1823) that alcohol differentiates the oil into an alcohol-soluble vesicant part and an alcohol-insoluble, purgative part (Harold Senier, Pharm., Jour. Trans., 1878, p. 705; and 1883, p. 446). In 1857, Buchheim and Krich, by saponification of the purgative portion, isolated therefrom a vesicant principle; hence a close relation must exist between the alcohol-soluble and insoluble portions of the oil. Kobert and von Hirschheydt, in 1890 (Ueber die Crotonol-säure, R. Buchheim's), came to the conclusion that the efficacy of the alcohol-soluble, vesicant part is due to the presence of free crotonoleic acid, a rather unstable body, while the alcohol-insoluble part contains it as a glyceride. The authors also demonstrated, by experiment, that the neutral oil (insoluble in alcohol) is decomposed by the pancreatic ferment, whereby the vesicating crotonoleic acid is liberated. More recently, Prof. W. R. Dunstan and Miss L. E. Boole (Pharm. Jour. Trans., 1895, p. 5) investigated crotonoleic acid. After separating therefrom some inert oily acids, the last fraction contained a powerfully vesicating resin, croton resin, a hard, light-yellow, brittle substance, nearly insoluble in water, readily soluble in alcohol, ether, and chloroform. Prolonged boiling with caustic alkalies destroys its vesicating power. (Adapted from an article on Croton Tiglium, by J. U. Lloyd, in The Western Druggist, April, 1898.)
Action, Medical Uses, and Dosage.—Croton oil is a powerful irritant and cathartic. In large doses it is a dangerous poison, occasioning emesis, painful gripings, hypercatharsis, and other serious symptoms. Its action is prompt, frequently causing catharsis within an hour; and, from the smallness of its dose, it is especially adapted to cases where medicines requiring large doses can not be given, as in trismus, coma, insanity, congestive apoplexy, etc. In most cases, catharsis may be produced by placing a drop or two on the back part of the tongue. It is principally used as a purgative when the bowels are very torpid; in comatose conditions as a revellant; and in dropsy as a hydragogue. It is admissible in obstinate constipation when no inflammation exists, and is the most efficient purgative in lead colic. It is likewise asserted that, irrespective of its cathartic property, it possesses efficacious influences in spasmodic and painful nervous affections. It may be used in all cases where prompt and active purgation is indicated. It is distinguished from other powerful cathartics by occasioning much borborygmus or rumbling of wind, by its action commencing speedily and ending soon, and by the purgative effect, however exhausting at the time, being followed by little debility. In certain forms of diarrhoea and other enteritic affections, I have derived great benefit by dissolving croton oil, ½ fluid drachm, in alcohol, 2 fluid ounces, and administering it in doses of from 5 to 15 drops, according to circumstances (J. King). Externally, it produces erythematic redness, intense burning, and an eruption of minute vesicles.
A croton-oil liniment is made by mixing 1 part of croton oil with 4 or 5 parts of olive oil, or 6 parts of turpentine; it is rubbed on the skin several times a day, to cause redness and a pustular eruption; it is very beneficial in follicular disease of the throat, affections of the larynx, bronchial vessels, and lungs, indolent tumors, and all painful attacks. The dose of croton oil is from 1 to 6 drops, which is best given on sugar, or made into a pill with crumb of bread, in order to avoid the disagreeable, acrid sensation it occasions in the throat, with a constant tendency to hawk, as well as to prevent nausea or vomiting. Four drops of the oil, thoroughly rubbed around the navel, will, it is said, produce catharsis. Croton oil is now seldom used externally; it was once very popular as a counter-irritant. Soubeiran recommends the following lozenges: Take of vanilla chocolate, ½ ounce; sugar, 2 drachms; starch, 40 grains; croton oil, 10 drops; mix thoroughly together, and form into 60 lozenges.