Colchici cormus. U. S., Br.;Colchici semen. U. S. (Br.)
Colchici cormus. U. S., Br.
Colchicum corm. Colch. Corm. [Colchici Radix, U. S. 1890, Colchicum Root]
"The dried corm of Colchicum autumnale Linne (Fam. Liliaceae), yielding not less than 0.35 per cent. of colchicine." U. S. "Colchicum Corm is the fresh corm of Colchicum autumnale, Linn., collected in early summer; or the same deprived of its coats, sliced transversely, and dried at a temperature not exceeding 65° C. (149° F.)." Br.
Bulbus s. Tuber Colchici; Meadow-Saffron Root; Bulbe de Colchique, Fr. Cod.; Bulbe de Colchique, de Safran batard. Fr.; Zeitlosenknollen, G.; Bulbo di colchico, It.; Bulbo de colquico, Sp.
Colchici semen. U. S. (Br.)
Colchicum seed. Colch. Sem. [Colchici Semen P. I.]
"The dried seeds of Colchicum autumnale Linne (Pam. Liliaceae), yielding not less than 0.45 per cent. of colchicine." U. S. " Colchicum Seeds are the dried ripe seeds of Colchicum autumnale, Linn." Br.
Colchici Semina, Br.; Colchicum Seeds; Semences de Colchique, Fr. Cod.; Semence de Colchique, Fr.; Semen Colchici, P. G.; Zeitlosensamen, G.; Semi di colchico, It.; Semilla de colquico, Sp.
Colchicum autumnale, often called meadow saffron, is a perennial bulbous plant, the leaves of which appear in spring, and the flowers in autumn. Its manner of growth is peculiar, and deserves notice as connected in same measure with its medicinal efficacy. In the latter part of summer, a new bulb, or corm, as the part is now called, begins to form at the lateral inferior portion of the old one, which receives the young offshoot in its bosom and embraces it half round. The new plant sends out roots from its base, and is .furnished with a radical spathe, which is cylindrical, tubular, cloven at top on one side, and half under ground. In September, from two to six flowers, of a lilac or pale-purple color, emerge from the spathe, unaccompanied by leaves. The corolla consists of a tube from 10 to 12 cm. long, concealed for two-thirds of its length in the ground, and of a limb divided into six segments. The flowers perish by the end of October, and the rudiments of the fruit remain under ground until the following spring, when they rise upon a stem above the surface, in the form of a three-lobed three-celled capsule. The leaves of the new plant appear at the same time, so that in fact they follow the flower instead of preceding it, as might be inferred from the order of the seasons in which they respectively show themselves. The leaves are radical, spear-shaped, erect, numerous, about 12 cm. long, and 2.5 cm. broad at the base. In the meantime, the new corm has been increasing at the expense of the old one, which, having performed its appointed office, perishes; while the former, after attaining its full growth, sends forth shoots, and in its turn decays. The old corm in its second spring, and a little before it perishes, sometimes puts forth one or more small corms, which are the sources of new plants. The usual method of propagating colchicum is by planting the bulbs about August or September in deep rich soil, about 2 or 3 inches below the surface and about 3 inches apart in the row. (D. C., 1912, p. 134.)
C. autumnale is a native of the temperate parts of Europe and of Northern Africa, growing in moist pastures and meadows. Attempts have been made to introduce its culture into this country, but with no great success, though small quantities of the corm, of apparently good quality, have entered commerce. The flowers possess virtues similar to those of the corm and are recognized by the French Codex.
COLCHICI CORMUS.—The medicinal virtue of the corm depends much upon the season at which it is collected. Early in the spring it is too young to have fully developed its peculiar properties, and late in the fall it has become exhausted by the nourishment afforded to the new plant. The proper period for its collection is from the early part of June, when it has usually attained perfection, to the middle of August, when the offset appears. It may be owing, in part, to this inequality at different seasons that entirely opposite reports have been given of its powers. Krapf ate whole corms without inconvenience; Haller found them entirely void of taste and acrimony, and we are told that in Carniola the peasants use them as food with impunity in the autumn. On the other hand, there can be no doubt of its highly irritating and poisonous nature, when fully developed, under ordinary circumstances. Perhaps soil and climate may have some influence in modifying its character.
Christison found the roots collected in April to be more bitter than those gathered in July, and conjectures that the common opinion of their superior efficacy at the latter season may not be well founded. Schroff states, as the result of his observation, that the autumnal root is much stronger than that dug in the summer. (See A J. P., xxix, 324.)
The corm is often used in the fresh state in the countries where it grows, as it is apt to be injured in drying, unless the process is carefully conducted. The usual plan is to cut the corm, as soon as possible after it has been dug up, into thin transverse slices, which are spread out separately upon paper or perforated trays and dried with a moderate heat. The reason for drying it quickly after removal from the ground is that it otherwise begins to vegetate, and a change in its chemical nature takes place; and such is its retentiveness of life that, if not cut in slices, it is liable to undergo a partial vegetation even during the drying process. Houlton recommends that the corm be stripped of its dry coating, carefully deprived of the bud or young bulb, and then dried whole. It is owing to the high vitality of the bud that the corm is so apt to vegetate. During desiccation there is great loss of weight, 70 per cent. being the average for a number of years in the laboratory of Alien & Hanburys, in London.
The recent bulb or corm of C. autumnale resembles that of the tulip in shape and size, and is covered with a brown membranous coat. Internally it is solid, white and fleshy, and, when cut transversely, yields, if mature, an acrid milky juice. There is often a small lateral projection from its base, which is the bud for the development of a new plant; this bud is frequently broken off in drying. When dried, and deprived of its external membranous covering, the corm is of an ash-brown color, convex on one side, and somewhat flattened on the other, where it is marked by a deep groove extending from the base to the summit. As found in commerce, it is always in the dried state, sometimes in segments made by vertical sections of the bulb, but generally in transverse circular slices. The U. S. Pharmacopoeia describes the corm as follows: "Usually in reniform, transverse or in ovate, longitudinal slices; from 2 to 5 mm. in thickness; flat surfaces whitish, slightly roughened, and of a crystalline appearance under a hand lens; epidermis thin, light brown and finely wrinkled; fracture short and mealy, odor slight; taste bitter and somewhat acrid. The powder is light brown or grayish-brown; starch grains numerous, single or 2- to 6-compound, the individual grains varying from spherical or ovoid to polygonal, and marked with a triangular or star-shaped, central cleft, the grains being from 0.003 to 0.03 mm. in diameter; tracheae few and with spiral or scalariform thickenings; occasional fragments of epidermal cells with thin, reddish-brown walls. Colchicum Corm yields not more than 6 per cent. of ash.
"Assay.—Proceed as directed under Colchici Semen, using 15 Gm. of Colchicum Corm." U.S.
"Fresh corm about thirty-five millimetres long and twenty-five millimetres broad, somewhat conical, hollowed on one side where a new corm is in process of development, and rounded on the other; covered with a thin brown membranous outer coat, and an inner reddish-yellow one; internally white and solid, and when cut yielding a whitish, turbid juice of a disagreeable odor and bitter taste. Dried slices two or three millimetres thick, yellowish at their circumference, somewhat reniform in outline; firm, whitish, amylaceous; breaking readily with a short fracture. No odor; taste bitter." Br.
The cut surface is white and of an amylaceous aspect. Examined with the microscope, the corm is seen to be composed of large irregular cells, full of ovoid, angular, sometimes compound, starch grains, and interspersed with spiral vessels in vascular bundles. The odor of the recent corm is said to be hircine. It is diminished, but not lost, by drying. The taste is bitter, hot, and acrid.
Colchicum corm contains the alkaloid colchicine, C22H25NO6, which was made official in the U. S. P.; see Colchicina. Colchicine is the active principle and as much as 0.4 per cent. is found in good specimens of the corm; the official requirement is that not less than 0.35 per cent. shall be present, to be determined by assay. See Assay for Colchicum Seed, p. 371.
A. T. Thompson states that the milky juice of fresh colchicum produces a fine blue color if rubbed with the tincture of guaiac, and that the same effect is Obtained from an acetic solution of the dried corm. He considered the appearance of this color, when the slices were rubbed with a little distilled vinegar and tincture of guaiac, a proof that the drug was good and had been well dried. J. M. Maclagan has shown that this change of color is produced with the albumen, which is not affected if previously coagulated; so that the value of the test consists simply in proving that the drying has not been effected at a heat above 82.3° C. (180° F.), or the temperature at which albumen coagulates. It is probable that this color reaction is not due to the albumen itself, but to an oxidizing enzyme or oxydase which would be susceptible to the same decomposing influences as albumen. A very deep or large notch in the circumference of the slices is an unfavorable sign, as' it indicates that the bulb has been somewhat exhausted in the nourishment of the offset. The decoction yields a deep blue precipitate with solution of iodine, white precipitates with lead acetate and subacetate, mercurous nitrate, and silver nitrate, and a slight precipitate with tincture of galls. The value of colchicum is best tested by its bitterness. For method of assaying colchicum, by K. Schwickerath, see Ph. Rund., 1893, 282. Important improvements have been made in the assay by Bredemann. (Ap. Ztg., 1903, 18, Nos. 93, 94, 95.)
COLCHICI SEMEN.—The seeds of the meadow-saffron ripen in summer, and should be collected about the end of July or beginning of August. They never arrive at maturity in plants cultivated in a dry soil or in confined gardens. (Williams.) They are officially described as follows: " Ovoid or irregularly globular, more or less pointed at the hilum; from 2 to 3 mm. in diameter; when fresh, several seeds cohering, externally dark brown, finely pitted; tough and of almost bony hardness; internally whitish or light brown; nearly inodorous; taste bitter and somewhat acrid. Under the microscope, transverse sections of Colchicum seed show a seed-coat of a few more or less collapsed cells with thin reddish-brown walls; an endosperm, making up most of the seed, consisting of cells with rather thick, porous walls, the lumina containing oil globules and aleurone grains, the latter being from 0.003 to 0.015 mm. in diameter; a small embryo, the beaked portion, or caruncle, containing numerous, somewhat ovoid, ellipsoidal or polygonal starch grains, from 0.005 to 0.016 mm. in diameter. Colchicum Seed yields not more than 8 per cent. of ash." U. S.
"About two and a half millimetres in diameter, subglobular, slightly pointed at the hilum, rough and of a dull reddish-brown color, minutely pitted, very hard and tough. Endosperm oily; its cells with thickened walls and large pits. No odor; taste bitter and acrid." Br.
They are chiefly composed of a gray horny endosperm constituted of very thick-walled cells, and surrounded by a closely adherent testa. The leafless embryo is very small, and is situated close to the surface opposite the strophiole. Williams, of Ipswich, England, first brought them into notice in 1820 as superior to the corm. Schroff, however, has found that their activity is inferior to that of the dried corm dug in autumn. (A. J. P., xxix, 324.) A fluid-extract and tincture of the seeds are directed in the U. S. Pharmacopoeia. Their dose is slightly less than that of the similar preparations made from the corm. The seeds and powder are very seldom adulterated. Judd, however, reports examining a powder which contained fully 50 per cent. of powdered foenugreek seed. (Bull. A. Ph. A., 1909, p. 193.)
The U. S. Pharmacopoeia IX directs that colchicum seed should contain not less than 0.45 per cent. of colchicine, to be determined by the following process:
Assay of Colchicum Seed.—"Introduce 15 Gm. of Colchicum Seed, in No. 60 powder, into a 500 mil flask, and add 10 mils of solution of lead subacetate and 290 mils of distilled water. Weigh the flask and contents, and digest the mixture at from 60° to 70° C. (140°-158° F.) for three hours, with occasional agitation. Cool, add distilled water to restore the original weight and filter off 200 mils. Add 0.75 Gm. of sodium phosphate to the clear filtrate, shake the mixture frequently during half an hour, and filter off 100 mils representing 5 Gm. of Colchicum Seed. Shake out the alkaloid from the filtrate with chloroform until completely extracted, as shown by testing with iodine T.S. (in place of the usual mercuric potassium iodide T.S.), and evaporate the chloroform solution; add about 1 mil of alcohol and again evaporate. Repeat this operation once more and dry the residue to constant weight at 100° C. (212° F.). To this weighed residue contained in a flask add 5 mils of tenth-normal sulphuric acid V.S. and 5 mils of distilled water and heat the mixture for ten minutes at 70° C. (158° F.). Now filter the liquid through a pledget of purified cotton, wash the flask and cotton with distilled water, reject the filtrate and washings and remove as much of the water from the cotton as possible. Dissolve any insoluble residue that may remain on the cotton by washing it first with a little alcohol and then with ether; collect the alcohol-ether washings in the flask, evaporate, and dry the residue to constant weight at 100° C. (212° F.). Deduct this weight from the weight of residue previously obtained. The difference will be the weight of colchicine obtained from 5 Gm. of Colchicum Seed (see Proximate Assays, Part III)." U.S.
Uses.—The investigations into the physiological action of Colchicum have not as yet yielded a very clear explanation of its therapeutic effects. Dixon and Maiden (J. P., 1908, xxxviii, p. 50) have found that it is an active stimulant to the unstriped muscle, increasing intestinal and uterine contractions and bronchial tonus. After large doses it depresses the vasomotor system, causing a marked fall in the blood pressure. When injected subcutaneously in. somewhat smaller doses it produces a transient decrease in the number of leukocytes followed after twenty-four hours by an enormous increase, the alterations being especially notable in the number of polymorphonuclear corpuscles. These effects appear to be the result of an action upon the bone marrow. Jackson and Blackfan (J. A. M. A., 1906, xlvii) find an increased output of uric acid under its influence, but they believe this is due rather to an increased formation than a more active elimination, but Denis (J. P. Ex. T., 1915, vii, 609) was unable to detect any change in the amount of uric acid either in the urine or blood.
The poisonous properties of colchicum were known to the ancients, but, while it is generally supposed that the hermodactyls were derived from some species of the genus, the use of meadow-saffron cannot be certainly traced back further than the sixteenth century. Although it has from time to time been recommended for various complaints, it is used to-day only in the treatment of gout. There is considerable clinical evidence that full doses of colchicum administered during the acute attack of a podagra will often abort it. The treatment, however, is not without serious danger-and most clinicians urge caution in the use of colchicum during the attack. It appears also to be of service in those more chronic conditions of disturbed metabolism known variously as uric acid diathesis or lithemia.
In preparing colchicum pharmaceutically, if it be desired to retain the colchicine unchanged, both acids and alkalies should be avoided and as far as possible also heat. As pointed out below, under various conditions colchicine may be decomposed into colchiceine, colchicinic acid, and various allied products. Whether these derivatives of colchicine possess the therapeutic virtues of the natural alkaloid is uncertain, but Fuehner (A. E. P. P., 1913, lxxii, p. 228) has shown that colchiceine is very much less toxic than colchicine.
When taken internally in therapeutic dose, colchicum usually produces no other symptoms than intestinal pains and looseness of the bowels. In some rare cases it is said to give rise to copious diuresis or diaphoresis instead of purging. When larger amounts are exhibited, the purging is more pronounced, and there may be also vomiting. With these 'symptoms there may be some depression, which seems to be due to the gastro-intestinal irritation rather than to the direct action of the poison. In an overdose, it may produce dangerous and even fatal effects. Excessive nausea and vomiting, abdominal pains, purging and tenesmus, great thirst, sinking of the pulse, coldness of the extremities, and general prostration, with occasional symptoms of nervous derangement, such as headache, delirium, and stupor, are among the results of its poisonous action. A peculiarity of its influence is that when its dose is increased beyond a certain point there is not a corresponding increase in the rapidity of the fatal issue. This is probably because it kills not by a direct influence upon the heart or the nervous system, but by causing gastro-enteritis. On post-mortem examination the alimentary mucous membrane is found much inflamed.
Dose, of the dried corm and seed, from two to eight grains (0.13-0.52 Gm.), which may be repeated every four or six hours until its effects are obtained.
Off. Prep.—Colchicum corm.—Extractum Colchici Cormi, U. S. (Br.); Vinum Colchici, Br.; Fluidextractum Colchici Cormi, N. F.; Vinum Colchici Cormi, N. F.