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Colocynthis. U. S. (Br.) Colocynth.

Botanical name:

Colocyn. [Bitter Apple, Colocynth Apple]

"The dried pulp of the fruit of Citrullus Colocynthis (Linne) Schrader (Fam. Cucurbitacea), without the presence or admixture of more than 5 per cent. of seeds or more than 2 per cent. of epicarp." V. S. " Colocynth Pulp is the dried pulp of the fruit of Citrullus Colocynthis, Schrad., freed from seeds." Br.

Colocynthidis Pulpa, Br., Colocynth Pulp, Bitter Gourd, Apple, or Cucumber, Poma Colocynthidia; Coloquinte, Fr. Cod.; Pulpe de Coloquinte, Fr.; Fructus Colocynthidis, P. G.; Coloquintenapfel, Koloquintenmark, Koloquinten, G.; Coloquintide, It.: Coloquintida. Sp.

Colocynth is another one of those drugs which has given a great amount of trouble to manufacturers because the definition of the U. S. Pharmacopoeia, in previous revisions, simply stated that it was the "peeled dried fruit." Notwithstanding the fact that at the end of the description there was a statement that "the seeds should be separated and rejected" the powdered drug consisted frequently of the seeds as well as pulp. In order to avoid any misunderstanding the U. S. Pharmacopoeia has followed the British authority and defined Colocynth as the dried pulp. As it is not commercially possible to exclude the seeds entirely, a few being imbedded in the pulp itself, the Pharmacopoeia wisely allows a minimum of 5 per cent. of seeds. It is estimated that every 100 pounds of colocynth fruit will yield 30 pounds of pulp and about 70 pounds of seeds. Tunmann (Suedd. Apoth. Zeit., 1907, p. 503) states that the seeds do not contain medicinally active constituents. Francis (Proc. A. Ph. A., 1906, p. 336), on the other hand, says that if the seeds are first deprived of their fixed oil with benzin, dried and then extracted with 75 per cent. alcohol, the extract is almost as active as the U. S. P. product.

Citrullus Colocynthis, or bitter cucumber, is an annual plant, bearing considerable resemblance to the common watermelon. The stems, which are herbaceous and beset with rough hairs, trail upon the ground, or rise upon neighboring bodies, to which they attach themselves by their numerous tendrils. The leaves, which stand alternately on long petioles, are triangular, many-cleft, variously sinuated; obtuse, hairy, of a fine green color on the upper surface, rough and pale on the under. The flowers are yellow, and appear singly at the axils of the leaves. The fruit is a globular pepo, of the size of a small orange, yellow and smooth when ripe, and contains, within a hard, coriaceous rind, a white, spongy pulp, enclosing numerous ovate, compressed, white or brownish seeds.

The plant is a native of Turkey, and abounds in the islands of the Archipelago. It grows also in various parts of Africa and Asia. Burckhardt, in his travels across Nubia, found the country covered with it; Thunberg met with it at the Cape of Good Hope, and Ainslie says that it grows in many parts of Lower India, particularly in sandy places near the sea. It is said to be cultivated in Spain, the island of Cypress, Morocco and in the neighboring countries, and even to have been collected in Japan. Colocynth from the maritime plain between the mountains of Palestine and the Mediterranean is chiefly shipped from Jaffa, and is known as Turkish Colocynth. It is said to be of superior quality. The fruit is gathered in autumn, when it begins to become yellow, and, having been peeled, is dried quickly in a stove or in the sunshine. Thus prepared, it is imported from the Levant. Small quantities are said to be imported into England from Mogador in the form of brown, unpeeled globular gourds. The so-called Persian colocynth of the London markets is very small, and has apparently been compressed in a fresh state, so that the position of the seeds is perceptible through the dry pulp. The microscopic structure and the proportion of the pulp to the seed appear to be the same as in other colocynths. (P. J.) xvi, 107.) Colocynth has been grown in New Mexico, but, according to Sayre, the American colocynth possesses only about two-thirds the cathartic action of the Trieste variety.

Properties.—As found in commerce, colocynth is in whitish, globular berries, from 6 to 7 cm. in diameter, very light and spongy, and abounding in seeds which constitute three-fourths of their weight. The seeds are somewhat 'bitter, but possess little activity, and, according to Captain Lyon, are even used as food in the north of Africa. Nachtigal confirms this statement of Captain Lyon's, but with the qualification that, before being eaten, the seeds are deprived of their coating by some mechanical means, and the kernels are heated to the boiling point, then washed with cold water, dried, and powdered. Flückiger found a bitter principle in the testa, which accounts for its rejection as food, though rendering improper the rejection of the seed in preparing the extract. He found in the kernels about 45 per cent. of fixed oil and 18 per cent. of albumen. (A. J. P., 1872, 538.) They should be separated and rejected, the pulpy matter only being employed. The U. S. Pharmacopoeia thus describes colocynth; "Fruits, before the removal of the seeds, nearly globular, from 4 to 7 cm. in diameter, usually more or less crushed and in broken pieces, with occasional patches of the nearly smooth epicarp; yellowish-white or brownish; light, spongy; separable longitudinally when entire into three carpels, each containing, near the outer surface, the ovoid, compressed, yellowish seeds; odor slight; taste intensely bitter. The powder is yellowish-white or buff, consisting chiefly of fragments of parenchyma cells and an occasional fragment with tracheae; very few lignified tissues of the seed-coat, showing the characteristic stone cells which are nearly isodiametric, irregular, with either straight or undulate walls that are strongly lignified and possess simple pores; globules of fixed oil and aleurone grains very few. Powdered Colocynth must be made from colocynth pulp containing not more than 5 per cent. of seeds and, upon extraction with purified petroleum benzin, yields not more than 2 per cent. of fixed oil. Colocynth yields not more than 15 per cent. of ash." U. S.

"White, spongy, light fragments. The powdered Pulp exhibits abundant debris of large, thin-walled parenchymatous cells but no starch, and not more than an occasional sclerenchymatous cell or group of such cells. No odor; taste intensely bitter. Yields not more than 2 per cent. of fixed oil to petroleum spirit. Ash not less than 9 per cent." Br.

Barclay considers the estimation of ash in powdered colocynth useful in proving its freedom from seeds. The pulp yields from 8.6 to 14 per cent. of ash, the seeds from 2 to 4 per cent., the whole apple 4.6 per cent. (Am. Drug., 1896, 152.) Water and alcohol extract the virtues of colocynth. It is a matter of importance to be able to determine whether the drug miller who usually powders colocynth is careful to reject the seeds. If the seeds have been ground with the dried pulp, the microscope will show the presence of numerous albuminous granules derived from the cotyledons. (W. T. dark, P. J., vii, 509.) These are best found by putting a small amount of the powder on the glass slide, adding a drop of water, and gently rubbing the cover glass over it; fragments of the double-walled embryo sac show on the outer side elongated, more or less hexagonal, thin-walled cells, and on the inner side irregular, tabular, thick-walled cells. If powdered colocynth contains a large number of starch granules it has probably been adulterated. Power and Moore (Tr. Chem. Soc., xcvii, p. 99) have separated from colocynth an alkaloidal principle which has a violent purgative effect, but this is not the only active principle of the crude drug, because both ether and chloroform extracts of the resin, when free from the alkaloidal principle, were still purgative. They find also alpha-elaterin, but none of the active beta-elaterin. (See Elaterinum.) Vauquelin obtained the bitter principle of colocynth in a separate state, and called it colocynthin. According to Meissner, 100 parts of the dry pulp of colocynth contain 14.4 parts of colocynthin, 10.0 of extractive, 4.2 of fixed oil, 13.2 of a resinous substance insoluble in ether, 9.5 of gum, 3.0 of pectic acid (pectin), 17.6 of gummy extract derived from the lignin by means of potassium hydroxide, 2.7 of calcium phosphate, 3.0 of magnesium phosphate, and 19.0 of lignin, besides water. Walz supposed that he had found another peculiar principle, colocynthitin. It was obtained by treating with ether the alcoholic extract previously exhausted by water, decolorizing the ethereal solution with animal charcoal, evaporating to dryness, and dissolving the residue in anhydrous alcohol, which deposited it in crystals on spontaneous evaporation. It is white and tasteless, and is probably a resin. (N. Jahrbuch der Pharm., xvi, 10.) Colocynthin is obtained by boiling the pulp in water, evaporating the decoction, treating the extract thus procured with alcohol, evaporating the alcoholic solution, and submitting the residue, which consists of the bitter principle and potassium acetate, to the action of a little cold water, which dissolves the latter and leaves the greater part of the former untouched. Bastick obtained it by exhausting the pulp with cold water, heating the solution to ebullition, adding lead subacetate so long as a precipitate was produced, filtering the liquor when cold, adding diluted sulphuric acid gradually until it no longer occasioned a precipitate, boiling to expel free acetic acid, filtering to separate lead sulphate, evaporating cautiously nearly to dryness, extracting the colocynthin from the residue by strong alcohol, which left the salts, and finally evaporating the alcoholic solution.

The following process, employed by Walz, yields it in a purer state. Colocynth is exhausted by alcohol of sp. gr. 0.84, the tincture evaporated to dryness, the residue treated with water, and the solution precipitated first with lead acetate and afterwards with lead subacetate. The yellow filtered liquor is then treated with hydrogen sulphide to separate the lead, and, after filtration, with solution of tannic acid, which throws down a compound of tannic acid and colocynthin. This is dissolved in alcohol, the tannin thrown down by lead subacetate, the excess of lead separated, and the liquid digested with animal charcoal, filtered, and evaporated. The residue, washed with anhydrous ether, is pure colocynthin. This is yellowish, somewhat translucent, brittle and friable, fusible by a heat below 100° C. (212° F.), inflammable, more soluble in alcohol than in water, but capable of rendering the latter intensely bitter. Mouchon states that it is insoluble in ether. It is neither acid nor alkaline; but its aqueous solution gives with infusion of galls a copious white precipitate. Ahrends (Neue Arzneimittel, 1909) gives the synonym of this principle as citrullin and gives the formula as C56H84O23. Its formula, according to Walz, is C56H42O23. Upon the same authority it is a glucoside, being resolved by the action of sulphuric acid into sugar and a peculiar resinous substance termed colocynthein, to which he gives the formula C44H32O13. Henke doubts the probability of colocynthin being a glucoside, and states that it is uncrystallizable; he reviews the methods of previous investigators, and obtained by his own process but 0.66 per cent. of colocynthin. (A. Pharm., 1883, p. 200; A. J. P., 1883, p. 301.) According to Johannson, colocynthin, when heated with diluted sulphuric acid, yields colocynthein, elaterin, and bryonin. (A. J. P., 1885, p. 451.) An infusion of colocynth, made with boiling water, gelatinizes upon cooling. Neumann obtained from 768 parts of the pulp, treated first with alcohol and then with water, 168 parts of alcoholic and 216 of aqueous extract. (See also paper by George Wagner, Proc. A. Ph. A., 1893, 179.)

Uses.—The pulp of colocynth is a powerful drastic, hydragogue cathartic, producing, when given in large doses, violent griping, and sometimes bloody discharges, with dangerous inflammation of the bowels. Death has resulted from a teaspoonful and a half of the powder. (Christison.) Even in moderate doses it sometimes acts with much harshness, and it is therefore seldom prescribed alone. By some writers it is said to be diuretic. It was frequently employed by the ancient Greeks and the Arabians, though its drastic nature was not unknown to them. Among the moderns it is occasionally used in obstinate dropsy, and in various affections depending on disordered action of the brain. In combination with other cathartics it loses much of its violence, but retains its purgative energy, and in this form is extensively employed. The compound extract of colocynth is a favorite preparation with many practitioners, and, combined with calomel, extract of jalap, and gamboge, it forms a highly efficient and safe cathartic, especially useful in congestion of the portal circle and torpidity of the liver. (See Pilules Catharticae Composite.) It is best administered in minute division, effected by trituration with gum or farinaceous matter. The active principle has sometimes been employed, and, in the impure state in which it is prepared by the process of Emile Mouchon, may be given in the dose of a grain (0.065 Gm.).

Thunberg states that the fruit of C. Colocynthis, at the Cape of Good Hope, is rendered so mild by being properly pickled that it is eaten both by the natives and by the colonists; but, as it is thus employed before attaining perfect maturity, it is possible that the drastic principle may not have been developed.

Dose, one to five grains (0.065-0.32 Gm.).

Off. Prep.—Extractum Colocynthidis, U. S.; Extractum Colocynthidis Compositum (from Extract), U. S., Br.; Pilula Colocynthidis Composita, Br.; Pilula Colocynthidis et Hyoscyami (from Compound Pill), Br., (from Extract), N. F.; Pilulae Antidyspepticae (from Compound Extract), N. F.; Pilulae Catharticae Vegetabiles (from Compound Extract), N. F.; Pilulae Colocynthidis Composite (from Extract), N. F.; Pilulae Colocynthidis et Podophylli (from Compound Extract), N. F.; Pilulae Laxativae Post Partum (from Compound Extract), N. F.

The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.

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