[image:12588 align=left hspace=1][image:15169 align=left hspace=1]Preparations: Compound Tincture of Colchicum - Tincture of Colchicum Seed - Extract of Colchicum Root - Fluid Extract of Colchicum Root - Fluid Extract of Colchicum Seed - Wine of Colchicum Root - Wine of Colchicum Seed
The corm and seeds of Colchicum autumnale, Linné.
COMMON NAME: Meadow saffron.
ILLUSTRATION: Bentley and Trimen, Med. Plants, 287.
Botanical Source.—This plant has a large, ovate, solid, fleshy corm (tuber, according to some authors). The leaves are dark-green, very smooth, obtuse, above a foot long, 1 1/2 inches broad, keeled, and produced in the spring along with the capsules. The flowers are several, radical, leafless, and bright purple, with a long, white tube appearing in the autumn without the leaves. The capsules 3 and distinct, though forming together a single, oblong, elliptical fruit, with intermediate fissures. The seeds are whitish and polished (L.).
History.—Colchicum grows in meadows and low, rich soils in many parts of Europe, and is common to England. The herb is annual, but the bulb is annual or perennial, according to the manner in which the plant is propagated, which may be from the seed, by the formation of a single mature bulb from a parent bulb, or by the separation of several immature bulbs from the parent. A brief reference to its mode of development may be useful: "In June or July a new bulb about the size of a grain of wheat is formed at the lower end of the old one, in close approximation with its radicles; this little bulb increases with rapidity, and at the same time sends up a leafless flower-stem. Toward the first of October a lilac, or pale-purple, flower springs from the ground, the germen remaining at the base of the corolla tube, but the leaves do not appear until early in the ensuing spring, at which time the germen, consisting of 3 many-seeded caesures, is elevated, and the seeds are matured during midsummer, after which the plant speedily withers. While the flower is rising in the autumn, the bulb is very small, but in the winter it grows rapidly, being in April as large as a chestnut, and attaining its greatest size, about that of a small apricot, in July. It is now a year old, and the herb having matured its seed, is withering away, but a new bulb appears at the lower end, close to its junction with the radicles or root proper, and passes through a similar succession of changes; while the old parent bulb gradually becomes more spongy and watery, but retains its size until the following April, the second spring of its own existence, when it quickly decays"(C.).
Description.—COLCHICI RADIX (U. S. P.), Colchicum root. "About 25 Mm. (1 inch) long, ovoid, flattish, and with a groove on one side; externally brownish and wrinkled; internally white and solid; often in transverse slices, reniform in shape, and, breaking with a short, mealy fracture; inodorous; taste sweetish, bitter, and somewhat acrid"—(U. S. P).
COLCHICI SEMEN (U. S. P.), Colchicum seed.—"Subglobular, about 2 Mm. ( 1/12 inch) thick, very slightly pointed at the hilum; reddish-brown, finely pitted, internally whitish; very hard and tough; inodorous; taste bitter and somewhat acrid"—(U. S. P.).
The seeds and the bulb are the official parts of the plant. The bulbs are usually collected about the beginning of July, but are said to attain their greatest perfection while the plant is flowering, or just after blossoming, at which time colchicum should be gathered for medicinal use. The odor is hircine (stinking like a goat), and the taste bitter, acrid, and nauseous. In drying, the bulb is usually cut into thin transverse slices, having first been stripped of its external dark brownish-black membranous tegument, and is dried quickly; sometimes it is dried entire. Good colchicum bulbs, when dried, are capable of changing their color to blue if softened with distilled vinegar, and then touched with tincture of guaiacum. Stained or mouldy bulbs should be rejected. Their virtues are imparted to alcohol, vinegar, or wine. The acetic tincture is often preferred to the vinous, as it is not so liable to change or decomposition. Acids render the vinous tincture drastic, while alkalies render its operation milder. The decoction of the fresh bulb forms, with a solution of iodine, a deep-blue precipitate (iodide of starch); with perchloride of iron, a faint bluish tint (gallate of iron); with subacetate of lead, or mercurous nitrate, a copious white precipitate; with nitrate of silver, a white precipitate, which soon becomes black; with tannin, a very slight, dirty-looking precipitate; and with a solution of gelatin, a slight haziness (R). It was formerly supposed that the medicinal virtues of the seeds resided in the husk or cortical part, and it was advised not to bruise them in making the tincture, but experiments have proved that the bruised seeds yield the strongest tincture. Their properties are similar with those of the bulb, and, as they are considered more uniform in strength than the bulb, they are usually preferred.
Chemical Composition.—Of general plant constituents, colchicum bulbs contain gum, starch (more than one-fourth their weight), sugar, resin, tannin, and water (as high as 70 per cent). A volatile principle present in the fresh bulb, and to which its odor is due, is dissipated in drying. Fatty oil occurs in the seeds; Flückiger found 6.6 per cent, Rosenwasser 8.4 per cent. The peculiar constituent, common to all parts of the plant (bulbs, seeds, and flowers), is colchicine, concerning which there has been much discussion. Pelletier and Caventou (1820) thought it identical with veratrine, but Geiger and Hesse demonstrated it to be different. These and other investigators, however, describe it as a crystallizable body, but colchicine, as now established through the researches of Aschoff, Bley, Oberlin, Hübler, Maisch, Hertel, and Zeisel, can not be obtained in crystalline form. Oberlin, in 1856, made the discovery that, by evaporation of an acidulated solution of colchicine, a crystallizable body is formed, to which he affixed the name colchicëine. This is most probably the substance described by the earlier chemists. Hübler, in 1865, arrived at the conclusion that colchicine and colchicëine were isomeric bodies, which was proved erroneous by the more recent investigations of Zeisel.
Hertel, in 1881, gave a process for the extraction of colchicine from the seeds, by which be obtained 0.4 per cent of pure colchicine. Aschoff had previously obtained about 0.2 per cent from seeds and 0.085 per cent from the bulb. Hertel also investigated the resinous coloring matter accompanying colchicine, to which he gave the name colchico-resin. He found it to be a decomposition product of colchicine due to exposure to the air, or to higher temperature, in a moist condition. He found it especially in the dead leaves surrounding the tubers, and in dried seeds and tubers. Beta-colchico-resin he observed in the process of making colchicëine from colchicine by means of diluted hydrochloric acid. Houdès, in 1885, concluded that he obtained crystallized colchicine, a point that S. Zeisel had, however, cleared, in 1883, by demonstrating that colchicine crystallizes from chloroformic solutions in the form of a chloroform compound. To Zeisel and Johanny (1888) is finally due the credit of having established the accurate formulae for colchicine and colchicëine, and the chemical relationship the substances bear to each other.
Colchicine (C22H25NO6, or C15H9[OCH3]3.NHCH3CO.COOCH3) is the methyl-ester of colchicëine (2C21H28NO6+H2O, or C15H9.[OCH3]3.NHCH3CO.COOH), the latter (crystallizable) body being formed by heating colchicine with dilute mineral acids, whereby methyl alcohol is split off. The question whether colchicine is an alkaloid, has been much debated. It is certain, however, that colchicine has weak basic properties, and yields precipitates with some alkaloidal reagents, yet, as a rule, it does not combine with acids to form a salt. Zeisel succeeded in establishing an exception by forming a double salt with gold chloride. Zeisel's colchicine melts at 143° C. (282.6° F.), Hertel describes colchicine as a sulphur-yellow body, impossible to crystallize, possessing a very slight alkaline reaction, but very indifferent body, the only noteworthy and insoluble compound being that with tannic acid. Colchicine is soluble in water, alcohol, and chloroform, hardly soluble in ether and benzol. Nitric acid has been recommended as the best reagent for the detection of colchicine, yielding a violet coloration. A mixture of nitric and sulphuric acids produces a series of colors changing from green to dark blue, violet and yellow (Amer. Jour. Pharm., 1888, p. 569).
Colchicëine is described by Hertel as occurring in white and odorless crystals, readily soluble in alcohol, chloroform, and caustic potash, with yellow color; the fusing point is 150° C. (298° F.). With ferric chloride it yields a beautiful green coloration even in greatly diluted solution. The alcoholic solution feebly reddens litmus. Zeisel states that it has the double character of a weak base and an acid, which behavior its formula sufficiently explains. Like colchicine, it forms a double salt with gold chloride. Hübler, on the other hand, has prepared salts of colchicëine with bases. With the exception of the salts with alkalies, these compounds are insoluble in water, but soluble in alcohol and chloroform.
Apocolchicëine was obtained by Zeisel (1883) by heating colchicëine with diluted hydrochloric acid, methyl chloride being disengaged in the reaction. It has both basic and acid properties, and was first observed as a by-product, and obtained from colchicine in the preparation of colchicëine. H. Warnecke found in colchicum seeds 2.66 per cent of ash.
Action, Medical Uses, and Dosage.—Colchicum in small doses is stimulant, increasing the secretions of the skin, kidneys, liver, and bowels. Epigastric heat, eructations, and a sense of nausea accompany the administration of a large dose or several moderate doses. If the medicine be continued a coated tongue, anorexia, colicky pains, intestinal gurgling, and diarrhoea may result. Large doses occasion bilious vomiting, colic, tenesmus, and bloody mucoid evacuations, accompanied with anal heat. Toxic doses act as an acronarcotic poison, producing violent gastro-intestinal symptoms much like those of cholera-headache, vomiting, griping pain in the bowels, diarrhoea, painful cramps of the muscles and feet, collapse, decreased circulation, and death, probably from cardiac syncope. Colchicine is a powerful poison, and should rarely be used. Medicinally, colchicum is sedative, cathartic, diuretic, and emetic. Used in gout and gouty rheumatism, dropsy, palpitation of the heart, gonorrhoea, enlarged prostate, etc. Care must be had in its employment. It sometimes increases the uric acid in the urine of arthritic patients; and has been beneficially employed in febrile, inflammatory, and nervous affections, and in chronic bronchial complaints. Equal parts of tincture of colchicum and laudanum have been found efficient in some cases of gonorrhoea. The reputation of colchicum rests most largely upon its value in gout and the conditions hinging upon a gouty diathesis. It is, perhaps, better adapted to acute than chronic gout. By its eliminative powers it removes from the system the morbid material upon which the gout depends. As a rule many of the failures to remedy this condition have been due to the fact that too large doses of colchicum have been employed. The dose will vary, however, some cases requiring larger doses than others, but in all cases the administration should be short of producing a free action from the bowels, the best effects being obtained from its slow and silent action. As a remedy for rheumatism it has been less employed. In cardiac rheumatism it may be alternated with the alkalies where the latter are indicated. The wine of colchicum may be given in 10-drop doses, or drop doses of specific colchicum may be given every 4 hours. As a rheumatism remedy it acts equally well in the acute and chronic conditions, provided the temperature and pulse be first brought almost to normal by means of other agents. Tearing muscular pain is the indication for it. It is efficient in rheumatic iritis and in chronic rheumatism when there is effusion into the joints and tearing pain aggravated by heat, and the joints present a swollen condition. Dysmenorrhoea and hepatic enlargements are also remedied by it when associated with a gouty diathesis. Large doses should never be used, and the action of the drug should always be carefully watched. Prof. Scudder employed small doses for intestinal disturbances with gaseous accumulation, as in colic from intestinal irritation. It has been used in subacute and chronic sciatica where the pain is "sharp-shooting, tearing, or dull-aching" from back to hip and down the leg, fever being absent. "It is not the kind of pain so much as its position" (Dr. L. A. Kelley).
A good acetic tincture may be made by macerating 1 1/2 ounces of the dried bulb, or seeds, in 12 fluid ounces of the strongest vinegar for 14 days. Then filter and keep in well-stoppered bottles. The dose for an adult is from 10 to 60 drops as often as may be required. An acetic extract may be prepared, containing all the powers of the plant, by rubbing the fresh bulbs to a pulp to the quantity of a pound, and gradually adding acetic acid, 3 fluid ounces. Express the liquid, and evaporate it in an earthen vessel not glazed with lead, to the proper consistence; the dose is from 1 to 3 grains, 3 or 4 times a day. Dose of the dried bulb, from 1 to 10 grains, gradually increased every 4 or 6 hours, till the influence of the medicine is obtained. Wine of colchicum, 10 to 20 drops; English wine of colchicum, 5 to 10 drops; tincture of root, 10 to 60 drops; tincture of seed, 10 to 40 drops; specific colchicum 1 to 10 drops; colchicine, 1/120 grain twice a day.
Specific Indications and Uses.—Gout; gouty diathesis; rheumatism, pain tearing and aggravated by heat, to be used after sedation has been accomplished; pain in course of the nerves; gouty headaches with swellings of joints, constipation, and nervousness; sudden tearing pain from back to hip, and down limbs, without fever.
King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.