Granatum (U. S. P.)—Pomegranate.
The bark of the stem and root of Punica Granatum, Linné "—(U. S. P.).
COMMON NAME: Pomegranate root-bark.
ILLUSTRATION: Bentley and Trimen, Med. Plants, 113.
Botanical Source.—Pomegranate is a small tree or shrub, with spinescent branchlets. The leaves are opposite, oblong, inclining to lanceolate, entire, smooth, with no marginal vein, 2 or 3 inches long, by 5 or 10 lines wide, obtuse, deciduous, shortly petioled, rarely verticillate or alternate, and often axillary and fascicled. The flowers are large, red, 2 or 3, nearly sessile, on somewhat terminal branchlets. Calyx turbinate, 5-cleft, thick, pale, and succulent; aestivation valvate. The corolla consists of 5 much crumpled, membranous petals. The stamens are numerous, inserted on the calyx, filaments distinct; anthers yellow. The ovary is roundish and inferior; the style simple and filiform; the stigma globular and capitate. The fruit is a large, globose pericarp, the size of a small muskmelon, leathery, crowned by the prominent hardened tube of the calyx, divided horizontally into 2 parts by a very irregular, confused dissepiment; the lower division 3-celled, the upper 5 to 9-celled; dissepiments membranaceous; placentae in the lower division at the bottom; in the upper stretching from the side of the fruit to the middle. The seeds are numerous, angular and covered with a bright red, succulent, acrid coat. Embryo oblong; radicle short and acute; cotyledons foliaceous and spirally convolute (L.—W.).
History.—The pomegranate grows on the Mediterranean shores, Persia, China, and other countries of Asia, and has been naturalized in the West Indies, and other civilized countries in warm latitudes. It has splendid, dark-scarlet flowers, often doubled, which appear in July and August. Ɣ The flowers, called balaustion, by the ancients, have a slightly styptic taste, without odor, and their infusion gives a deep bluish-black precipitate with ferric salts. The saliva is colored a violet-red upon chewing them. Both tannic and gallic acids enter into their composition. In some foreign Pharmacopoeias, they, together with the seeds, are recognized as official. The rose-colored, juicy, acid pulp is edible, and is very grateful to febrile patients. The bark of root and stem is the only part employed in this country. The rind of the fruit was also official with us formerly. The fruit varies in size and flavor, that of the West Indies becoming the most perfect. The root is large, ligneous, knotty and hard. Its wood is not used in medicine. In this country the pomegranate shrub grows out of doors as far north as Washington, D. C. (Coville).
Description and Chemical Composition.—GRANATI FRUCTUS CORTEX. The rind of the fruit (Granati fructus cortex), when dry, is brown externally, yellow within, about a line in thickness, smooth or finely tuberculated, hard, dry, brittle, in irregular fragments, inodorous, and of a very astringent, somewhat bitter taste. Its infusion gives an abundant, dark-bluish precipitate with the salts of iron. Analysis showed 18.8 per cent of tannin, 17.1 of mucilage, 10.8 of extractive matter, 30 of lignin, a trace of resin, and 29.9 of moisture.
GRANATI RADICIS CORTEX.—The bark of the root (Granati radicis cortex) is described by the U. S. P. as follows. "In thin quills or fragments, from 5 to 10 Cm. (2 to 4 inches) long, and from 1 to 3 Mm. (1/25 to ⅛ inch) thick; outer surface yellowish-gray, somewhat warty, or longitudinally and reticulately ridged; the stem-bark often partly covered with blackish lichens, the thicker pieces of the root-bark more or less scaly externally; inner surface smooth, finely striate, grayish-yellow; fracture short, granular, greenish-yellow; indistinctly radiate; inodorous; taste astringent, very slightly bitter"—(U. S. P.).
Ɣ The bitterness of the bark is nearly lost by drying. When chewed, it tinges the saliva yellow. Its infusion yields a deep-blue precipitate with the salts of iron, a yellowish-white one with a solution of gelatin, a grayish-yellow with con rosive sublimate, and caustic potash or ammonia colors it purple. Paper which has been colored yellow by the moistened inner face of the bark, changes to blue by the action of sulphate of iron, and to a delicate rose color, which is evanescent, by nitric acid. These changes do not occur with the bark of barberry, or of boxroot, which are sometimes fraudulently mixed with it; the box bark is nearly white, very bitter, but not astringent, and its infusion is not precipitated by salts of iron (Guibourt-Planchon, Hist. des Drogues Simples, 1876, Vol. III, p. 280). The barberry bark likewise very much resembles the pomegranate, but is very bitter and not astringent, and is not affected by the salts of iron, solution of isinglass, corrosive sublimate, or caustic potash The ligneous part of pomegranate root is inert, and should, therefore, be always separated from the bark.
Pomegranate bark contains about 20 per cent of tannin, which was believed by Rembold (1867) to consist of two astringent principles, one being gallotannic acid, the other punicotannic acid (C20H16O13), peculiar to this bark. Diluted sulphuric acid hydrolyzed it into sugar and ellagic acid (C14H8O9) (Flückiger, Pharmacognosie, 1891). The presence of gallic acid and mannit has been observed by various authors (Jahresb. der Pharm., 1867, p. 139). The bark leaves from 10.5 to 16.5 per cent of ash. It also contains a yellow coloring matter (see above). The anthelmintic properties of pomegranate bark are due to the presence of several (4) alkaloids, discovered by Tanret in 1878 and 1880 (Amer. Jour. Pharm., 1880, p. 416), and to which he gave the collective name pelletierine, in honor of the celebrated French chemist Pelletier (1788-1842). C. J. Bender (1885) proposes the more euphonic name punicine. By mixing the powdered bark with milk of lime, exhausting with water, shaking with chloroform, and abstracting this solution with diluted acid, a solution of the 4 alkaloids is obtained. From this solution sodium bicarbonate liberates methylpelletierine and pseudopelletierine, which are removed by chloroform; the addition of caustic potash then gets free pelletierine and isopelletierine.
PELLETIERINE (C16H30N2O2) is a colorless liquid, of specific gravity 0.988, rapidly absorbs oxygen, and resinifies. It boils at 195° C. (383° F.), is soluble in 20 parts of cold water, and mixes in all proportions with ether, alcohol, and chloroform. Its salts are crystallizable, but give off the base upon heating either dry or in solution. Its sulphate is laevo-rotatory. Isopelletierine (C16H30N2O2) is a liquid optically inactive, forming salts with acids. Density, solubilities, and boiling point are the same as with its preceding isomer. Its sulphate is deliquescent and optically inactive. Methylpelletierine (C18H34N2O2) is a liquid whose boiling point is 215° C. (419° F.). Its hydrochlorate is dextrogyre. The alkaloid dissolves in 25 times its weight of water at 12° C. (53.6° F.), and is soluble in alcohol, ether, and chloroform. Pseudopelletierine (C18H30N2O2) is a crystalline body, fusing at 46° C. (114.8° F.), is optically inactive, soluble in water, alcohol, ether, and chloroform. The chemistry of this base (called also granatonin) was investigated more recently by Ciamician and Silber (see Jahresb. der Pharm., 1893, p. 532, and 1894, p. 526).
Tanret recommended the tannate of pelletierine as the most efficient form of application. The bark of the stem contains principally pelletierine, while in the root-bark methylpelletierine predominates (Flückiger, 1891). As to the yield in total alkaloids, W. Stoeder (1894) obtained from Java root-bark from 1.29 to 1.86 per cent of hydrochlorates of alkaloids, the white-flowering variety yielding the most alkaloid. In 1890 (Jahresb. der Pharm.), the same author had obtained a yield as high as 3.75 per cent of hydrochlorates from the white-flowering variety. On the other hand, E. Aweng (ibid., 1890), observed that the alkaloid may entirely disappear from the commercial bark upon storing.
Action, Medical Uses, and Dosage.—The flowers and rind of the fruit are astringent and have been used for arresting chronic mucous discharges, passive hemorrhages, aphthous disorders of the mouth, night sweats, colliquative diarrhoea, etc., but are now seldom employed. The rind has also been found serviceable in intermittent fever and tapeworm. The bark of the root possesses anthelmintic properties, and is chiefly serviceable in tapeworm. The bark of the wild pomegranate is considered by the French to be more active than the cultivated plant, and the fresh bark is more active than an old bark. It may be given in powder but the decoction is more frequently used. Pomegranate is one of the oldest of drugs, having been used from time immemorial. The bark and its alkaloid pelletierine, are now by common consent, acknowledged as specifics for the removal of tapeworm. Dizziness, imperfect vision, sleepiness, or faintness, benumbing of the extremities, and occasionally convulsions have been produced by it. Foy, as well as Brenton, recommend to prepare the decoction by placing 2 ounces of the root in 1 ½ or 2 pints of water, and boiling down to 1 pint; this is to be strained, and from 2 to 4 fluid ounces given for a dose every half hour or hour, until the pint of the decoction has been taken. It commonly occasions several stools, an increased flow of urine, or nausea and vomiting, owing, it is supposed, to the agitation into which the worm is thrown from its presence. Sometimes joints of the worm begin to come away in less than an hour after the last dose. But often the doses must be repeated several successive mornings before they take effect, and it is right to repeat them occasionally for 4 or 5 days after the joints have ceased to come away. Laxatives should be administered from time to time. It is said to act with the greatest certainty when the joints of the worm come away naturally. The dose of the rind or flowers in powder, is from 20 to 40 grains, and in decoction from 1 to 3 fluid ounces. Eclectic physicians, as a rule, follow Prof. Locke's method of administering granatum. According to Dr. Locke, it is the best remedy for the removal of the worm, but as ordinarily recommended, the dose is too small. Its great drawback is its tendency to make the patient vomit, which may, in a measure, be prevented by administering a little lemon juice and keeping the patient quiet. When vomiting can be prevented, it seldom or never fails to bring the worm whole. Prof. Locke's method is as follows: Press 8 ounces (av.) of the coarse bark (not powdered), into a vessel, and pour upon it 3 pints of boiling water. Boil, strain, and then boil this down until the finished product will measure 1 pint. First prepare the patient by giving him at night a brisk cathartic, such as the antibilious physic, and in the morning allow a light breakfast. At about 10 o'clock in the forenoon administer 4 fluid ounces of the decoction. For the purpose of causing it to pass quickly into the intestines and thereby prevent its absorption as much as possible, a fluid drachm of fluid extract of jalap with a drop of oil of anise or cinnamon may be added to the dose. In 2 or 3 hours repeat this dose in the same manner. When its action begins give an enema to hasten its operation (see Locke's Syllabus of Mat. Med.). Should this treatment fail the first time, it may be repeated another day. As to treatment with the alkaloid the sulphate of pelletierine was first employed, but was superseded by the tannate which, on account of being tasteless and having less of a tendency to provoke nausea or vomiting, seems the preferable form to employ. The patient should have a light diet, preferably milk, the night previous to taking the medicine. Single doses of about 7 grains are now administered upon an empty stomach, the patient being kept quiet in a reclining posture. The dose is usually preceded by a drink of water, and followed at regular intervals by more water. A purgative, like fluid extract or compound tincture of jalap, is administered about 2 hours after taking the pelletierine tannate. Some prefer castor oil as an evacuant. To insure the passage of the worm entire it should be received into a vessel of warm water, which will prevent its separation into segments.
There seems to be a diversity of opinion regarding the effects of pelletierine upon the system. Undoubtedly it acts pronouncedly upon the nervous system, causing motor paralysis, while the contractility of the muscular fibers and sensation remain unaffected. Its action has been compared to that of curare (Dujardin-Beaumetz). Temporary general paralysis is said to have occurred in a woman after a dose of 5 grains. Marked congestion of the retina and diplopia are asserted to have followed the subcutaneous injection of 6 grains of the alkaloid. On account of its action upon the ocular nerves, it has been successfully used in paralytic states of the sixth and third cranial nerves. While many contend that it has a powerful control over certain of the nervous functions, others declare it innocuous. As great diversity exists in regard to dosage as to its effects. The dose of pelletierine has been given as ranging from ½ to 8 grains; the sulphate in about 5-grain doses; the tannate in doses of from 5 to 23 grains, about 7 grains being the average dose. Pelletierine preparations are usually sold in solution containing enough for one dose. Dose of pomegranate flowers or rind, 20 to 40 grains.
Specific Indications and Uses.—Taeniacide and taeniafuge for the destruction and expulsion of tapeworm (Taenia Solium).