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Resina Podophylli (U. S. P.)—Resin of Podophyllum.

Botanical name:

Preparations: Compound Pills of Resin of Podophyllum - Compound Powder of Resin of Podophyllum - Trituration of Podophyllin - Trituration of Santonin and Podophyllin - Troches of Resin of Podophyllum
Related entry: Podophyllum (U. S. P.)—Podophyllum - Oleoresinae.—Oleoresins

SYNONYMS: Podophyllin, Resin of mandrake, Resin of May-apple.

Preparation.—The U. S. P. process for preparing podophyllin is as follows: "Podophyllum, in No. 60 powder, one thousand grammes (1000 Gm.) [2 lbs. av., 3 ozs., 120 grs.]; hydrochloric acid, ten cubic centimeters (10 Cc.) [162♏]; alcohol, water, each, a sufficient quantity. Moisten the powder with four hundred and eighty cubic centimeters (480 Cc.) [16 fl℥, 111♏] of alcohol, and pack it firmly in a cylindrical percolator; then add enough alcohol to saturate the powder and leave a stratum above it. When the liquid begins to drop from the percolator, close the lower orifice, and, having closely covered the percolator, macerate for 48 hours. Then allow the percolation to proceed, gradually adding alcohol, until sixteen hundred cubic centimeters (1600 Cc.) [54 fl℥, 49♏] of tincture are obtained, or until the tincture ceases to produce more than a slight turbidity when dropped into water. Distill off the alcohol, by means of a water-bath, until the tincture is reduced to a syrupy consistence, and pour it slowly, with constant stirring, into one thousand cubic centimeters (1000 Cc.) [33 fl℥, 391♏] of water, previously cooled to a temperature below 10° C. (50° F.), and mixed with the hydrochloric acid. When the precipitate has subsided, decant the supernatant liquid, and wash the precipitate twice, by decantation, with fresh portions of cold water. Spread it, in a thin layer, upon a strainer, and dry the resin by exposure to the air in a cool place. Should it coalesce during the drying, or aggregate into lumps having a varnish-like surface, it should be removed, broken in pieces, and rubbed in a mortar. As this is liable to happen during warm weather, resin of podophyllum is preferably made during the cold season"—(U. S. P.).

The original process of this Dispensatory directs us to take of strong tincture of mandrake root (see Resinae), 1 pint; water, acidulated with 18 fluid drachms of hydrochloric acid, 1 gallon. Mix the tincture and the acidulated water together, allow the mixture to stand for 24 hours, or until there is no further precipitate, collect the precipitate on a filter, wash it with water, and then allow it to dry in a warm place not exceeding 26.6° or 29.4° C. (80° or 85° F.). Or, the alcohol may first be removed by evaporation in a warm bath, and the resin then be allowed to precipitate. The resin has also been obtained by precipitation without heat, by adding a solution of alum to a saturated tincture of the root. This makes a yellow alum lake. Podophyllin prepared by means of alum has never been popular with Eclectic physicians.

History.—The resin of podophyllum has enjoyed a far more extensive use in medicine than the crude drug from which it is prepared. Though official in the U. S. P., and, strange to say, now more extensively used by members of the regular school of medicine than by our own practitioners, podophyllin is an Eclectic drug, having been first discovered and introduced to the profession by Prof. John King. (Podophyllin was the first of the" Eclectic" resinoids, being discovered by Prof. John King, in 1835, and quickly followed by him with cimicifugin and the oleoresins of iris and aletris. These substances were introduced to commerce by the late W. S. Merrell, who took pains to at once bring them before the commercial world. The firm of B. Keith & Co., of New York, followed, and made a specialty of "resinoids." Grover Coe contributed to the movement by his widely-distributed book—Concentrated Organic Medicines. But the history of "American resinoids" would make a volume, and can not be undertaken herein. We have, therefore, carried from former editions of this work, Prof. King's remarks verbatim, and append this note only.) The practitioners of the old school employ this resin in nearly all of their vegetable cathartic pills. Of its introduction, Prof. John King says: "This valuable agent I had the honor of introducing to the profession 26 years since. In 1835, Iwas first led to an examination of the resinous principle of this plant, as well as of the iris, cimicifuga, aletris, and several other plants, in consequence of some information given me by Prof. Tully, of Yale College, New Haven, Conn., relative to the resinous constituent of the Cimicifuga racemosa. And since August, 1835, I have prepared and used, more or less in my practice, in the treatment of various forms of disease, the resins of podophyllum, iris, cimicifuga, alcoholic extract of aletris, and several other medicinal plants. In July, 1844, I first called public attention to the resins of podophyllum and iris, in the New York Philosophical Medical Journal, Vol. I, No. 7, pp. 157-161, in which I recommended the mandrake resin in combination with an alkali, for hepatic diseases, scrofula, dropsy, leucorrhoea, syphilis, gonorrhoea, gleet, obstructed menstruation, etc., but of which it appears but little notice was taken by the profession. In April, 1846, I again called the attention of the profession to this, as well as many other concentrated preparations, in the Western Medical Reformer, Vol. V, No. 12, pp. 175-178. Now, as dates are the only reliable source of correct information in such matters, unless some one can show an earlier notice of these articles, and of their practical utility, than the above, their claims will naturally be considered doubtful. The credit of first preparing resin of podophyllum, and other concentrated preparations, for the use of the profession generally, it being part of his avocation, belongs to Mr. W. S. Merrell, druggist and chemist, of Cincinnati, who first manufactured it in June, 1847, since which time it has become an indispensable and highly important American remedy, and is used by all classes of physicians, being generally preferred to mercurials by those who have fairly tested it" (J. King, in College Journal, 1857, p. 557).

Prof. King further adds: "I am indebted to the late F. D. Hill & Co., of Cincinnati (A.D., 1852), for the following process of manufacturing resin of podophyllum. Exhaust coarsely powdered mandrake root with alcohol, by percolation. Place the saturated tincture in a still, and distill off the alcohol; the residue will be a dark fluid of the consistence of molasses; sometimes it is thicker, and when this is the case add a small portion of it to some water, and if it does not form a yellow-whitish precipitate, a small quantity of alcohol must be added to it, or enough to cause the light precipitate. Then warm the thick residual fluid, and slowly pour it into three times its volume of cold water, which must be constantly agitated during the process. If poured in too fast, or without agitation, the fluid will fall to the bottom unchanged. Allow it to stand for 24 hours, at which time nearly all the resin of podophyllum will be precipitated, the addition of a sufficient quantity of muriatic acid will precipitate the remainder. The precipitated resin of podophyllum, of a whitish-yellow color, is now to be removed and placed on a linen filter, and washed several times with water, to remove any remaining acid, gum, etc., after which it is to be placed in thin layers on paper, and dried in a room of a temperature between 65° and 90° F., or, if in summer, at the natural atmospheric temperature. It becomes a shade or two darker by drying in this manner, but if artificial heat be employed to hasten the process, or a higher temperature, the resin becomes quite dark."

Description.—Resin of podophyllin varies in color according to its mode of precipitation, being, when precipitated by heat, dark-brown; and when by acid, a light brownish-yellow; or greenish-olive if by alum. It is insoluble in water, oil of turpentine, and diluted nitric acid; soluble in alcohol. By partial oxidation of the resin, soon after its preparation, a portion of podophyllum resin ceases to be dissolved by alcohol. From 3 to 6 per cent of resin is obtained from the mandrake root.

J. U. Lloyd has previously printed the following description of podophyllin: "As made by precipitation of the residue of a pure alcoholic tincture in cold distilled water it presents the following characteristics: If alcohol is present, the resin separates as a light-colored, porous powder. If it be not present, the resin precipitates in a dark, nearly black, resinous cake. This, when powdered, is of a dark-gray, or often nearly brown color, and is the description preferred by Prof. King. If the alcoholic percolate be poured into alum water instead of pure water, the resin precipitates of a bright-yellow color, and dries easily. This yellow podophyllin is in reality an alum lake, and, while it is easier to make it (for it dries like chalk) than to make the pure resin, it has been strongly opposed by Prof. King, and has never been recognized by the Pharmacopoeia of the United States. Podophyllin has a strong odor of May-apple, and is intensely active when made without alum."

As described by the U. S. P., resin of podophyllin occurs as "an amorphous powder, varying in color from grayish-white to pale-greenish-yellow or yellowish-green, turning darker when exposed to a heat over 35° C. (95° F.); having a slight, peculiar odor, and a peculiar, faintly bitter taste. Permanent in the air. Its alcoholic solution has a faintly acid reaction. Soluble in alcohol in all proportions; ether dissolves 15 to 20 per cent of it; boiling water dissolves about 80 per cent, and deposits most of it again on cooling, the remaining, clear, aqueous solution having a bitter taste, and turning brown on the addition of ferric chloride T.S. Resin of podophyllum is also soluble in potassium or sodium hydrate T.S., forming a deep-yellow liquid, which gradually becomes darker, and from which the resin is reprecipitated by acids"—(U. S. P.). Mr. G. M. Beringer (Amer. Jour. Pharm., 1894, p. 9) points out that the pharmacopoeial statement regarding the solubility of the resin in ether is erroneous, and the statement of its solubility in boiling water (adopted from experiments by Prof. F. B. Power, 1877), due to abnormal experimentation. The solubility of the resin in ether is about 80 per cent, and in boiling water about 23 per cent. These conclusions are confirmed by Nagelvoort (ibid., 1894, p. 279). According to Beringer, chloroform dissolves about 80 per cent of the resin.

Chemical Composition.—For details regarding the chemistry of resin of podophyllum (podophyllin), we refer the reader to the article Podophyllum. The name podophyllin was not coined by Eclectics, but was suggested by Mr. J. P. Hodgson. Podophyllin may be assayed for podophyllotoxin by extracting 1 Gm. with cold chloroform, evaporating the greater portion of the solvent, and pouring the solution into 20 volumes of petroleum ether. The podophyllotoxin is collected on a tared filter, dried, and weighed. A. Kremel found commercial samples of resin of podophyllum to yield from 20 to 30 per cent of podophyllotoxin (Amer. Jour. Pharm., 1889, p. 177).

Action, Medical Uses, and Dosage.—Podophyllin possesses the cathartic properties of the crude drug in an exalted degree. While it is slow in action, it is certain in its results. Some persons are so susceptible to the action of the drug, that a dose of 1/2 grain will actively purge them. The ordinary cathartic dose of this resin generally requires from 4 to 8 hours to act, but this action is quite persistent, often producing copious alvine discharges for 1 or 2 days, and when over leaves the intestines in a normal condition, seldom being followed by the after-constipation so common from the use of ordinary purgatives. As with the crude drug the cathartic action of podophyllin is increased by common salt. From 4 to 8 grains operate as an active emeto-cathartic, with griping, nausea, prostration, and watery stools; from 2 to 4 grains, as a drastic cathartic, with nausea and griping; from 1/2 to 2 grains generally operates as an active cathartic, leaving the bowels in a soluble condition; in very small doses, it is gently aperient and alterative. In doses of 1/2 or 1 grain, it is one of our most valuable cholagogue cathartics, operating mildly, yet effectually, arousing the whole biliary and digestive apparatus to a normal action, and which is very persistent in its character. "The action of this resin in affections of the liver has been doubted or denied by some practitioners, but, as we think, on erroneous grounds, judging from the beneficial results following its use in these affections, whether those results be due to direct influence upon the liver, or to an indirect one. Certainly, its effects in this class of diseases, are superior to those of the so-termed cholagogue mercurials" (J. King). It likewise exerts a favorable influence on the cutaneous functions, producing and maintaining a constant moisture on the skin. In doses of from 1/8 to 1/2 grain, or rather in sufficient doses not to purge, it acts as a powerful alterative, and will induce ptyalism in some persons. This drug should not be given in bulk, but should be combined with ginger, hyoscyamus, leptandra, or resin of caulophyllum, or some form of alkali, which renders it less liable to nauseate or gripe. Should catharsis be too severe, an alkaline solution, with aromatics, by mouth or enema, will check it. A popular and good method of preparation is that of triturating it with milk sugar (lactin). This not only obviates, to a certain extent, its irritant action, but singularly increases its purgative qualities. During its administration, all articles of food difficult of digestion should be avoided. According to Prof. Locke, podophyllin prepared by alum water is apt to gripe. Eclectics long made use of this agent in those cases where mercurials were used by other practitioners, and found the result vastly in favor of resin of podophyllum. It appeared to fulfil all the indications for which mercurials were recommended and used.

It is not, however, for its cathartic use that podophyllin is most valued by the Eclectic profession, but rather for its specific effect when given in small doses. Properly administered it is a stimulant to the sympathetic nervous system, acting principally upon the parts supplied by the solar plexus. It improves digestion and blood-making and stimulates normal excretion. For its action upon the liver, repeated small doses of the trituration (1 to 100), or a daily pill of podophyllin (1/20 grain) and hydrastin (1/4 grain) is much to be preferred to its cathartic dose. It should be given in the same manner when its action on the pancreas and spleen is desired.

Few physicians appreciate the action of this drug, in small doses, in gastric and intestinal disorders. It exerts a peculiarly specific action on all forms of stomach and bowel trouble with atony, characterized by full and relaxed tissues, with mucous discharge. The case is never one of loss of function from irritability, but from atony. In the summer disorders of children, especially cholera infantum, it will be often indicated, and is quick to restore normal action when the bowels are loose, with passages of mucoid, slimy material. The movements of the child are sluggish, the tongue is coated a dirty yellowish-white, the superficial veins are full, and the countenance is dull and expressionless. In many cases of chronic disease, associated with feeble digestive power, which is but little improved by the ordinary stomach tonic, this remedy will render excellent service. The trouble is usually atony of the upper part of the small intestines, and the stimulant dose of triturated podophyllin overcomes the difficulty. Podophyllin is a favorite anti-constipation remedy. It is equally valuable in costiveness of the young child and in the aged. In very young babies this trouble will yield to: Rx Podophyllin, 2d dec. trit., grs. xxx; brown sugar, ℨii; aqua, ℥iv. Mix. Sig. Teaspoonful, 4 times a day. For adults the daily use of from 1 to 2 of the podophyllin and hydrastin pills (1/20 and 1/4 grain) will generally be sufficient to overcome the trouble. The cathartic dose should never be employed for the relief of costiveness, or when a cholagogue action is required. When the stools are hard and grayish-white or clay-colored, and float upon water, the remedy is peculiarly effective, as it is also in dry stools, with tympanitic abdomen and wandering, colicky pains. Flatulent colic of children, when associated with constipation, will readily yield to small doses of this drug, while, as a remedy for dysentery and both acute and chronic diarrhoea, accompanied by portal sluggishness and hepatic torpor, few remedies will excel it. Dyspepsia, with atony and thickened mucous membranes secreting abundantly, calls for stimulant doses of podophyllin. The head feels full, the tissues and veins appear full and doughy, the skin is sodden, and a dirty coating covers the tongue from tip to base. Rx Podophyllin, 1/20 grain, 3 times a day. Cardialgia, accompanied with constipation, yields to the trituration (1 to 100). This drug has been justly valued in hepatic disorders. In that state ordinarily known as "biliousness," this drug or specific iris can usually be depended upon. Indeed, they act very nicely in combination. There is dizziness, a bitter taste, the stools show an absence of bile, and greenish, bitter material is vomited. The remedy is often indicated in both acute and chronic hepatitis, though usually contraindicated in inflammations of the gastro-intestinal tract. Fullness in the region of the liver, with aching under the scapulae and in the back of the neck, with dizziness, usually calls for this drug. In icteric states, with clay-colored stools, it may be alternated with chionanthus. The unpleasantness attendant upon the retention or passage of biliary calculi, is frequently relieved by this agent. There is great pain in the region of the gall bladder coursing to the left and downward. Sometimes there is constipation, as often diarrhoea. There is a bad taste, and the patient is often jaundiced. Rx Podophyllin, gr. ij, at night, followed in the morning with a large quantity of olive oil. In hemorrhoids, dependent on biliary insufficiency with portal inactivity, it may be given in alternation with sulphur, the podophyllin being particularly desired when there is constipation with tenesmus. The small dose alone is required, from 1/20 to 1/10 grain, 3 or 4 times a day.

Podophyllin may do good service in those forms of cough characterized by bronchorrhoea, especially if it be associated with gastric catarrh. Here minute doses of sulphur are also valuable. In heart disease, when aggravated by hepatic inactivity and portal torpor, the cardiac remedy will be rendered more efficient if associated with minute doses of this drug. It has long been recognized as a remedy for rheumatism, when the patient is sallow and inactive, presents fullness of tissue, and complains of dull pain and heaviness in the right hypochondrium. In renal disorders, when the general specific indications for its use are present, it will restore the secretory power of the kidneys. Podophyllin has long enjoyed the reputation of exerting a powerful action upon the whole glandular system. For a long time it was, and is still with many, a favorite remedy in syphilitic manifestations. For persistent pustular conditions, eczema and cracked or fissured skin, Ellingwood declares it a good remedy. It acts powerfully as an alterative, one of the best in the whole domain of medicine, at the same time aiding and improving the digestive process.

Podophyllin is a remedy for pain, according to Prof. Scudder—that deep-seated pain in the ischiatic notches. It has served a good purpose in inflammations (when not of the digestive tract), accompanied with great constipation. Here the cathartic action is required, as it is also in the forming stage of febrile diseases, with the exception of typhoid fever. Still, if indicative fullness be present, the small dose will assist very materially in overcoming these disorders. For its derivative action in brain disorders, large doses will be necessary, as is also the case in dropsy. In malarial troubles, small doses of podophyllin should be alternated, or given with cinchona. For all of the preceding uses specific podophyllum may also be used, but the dose must be correspondingly larger. For the gastric disorders many prefer it to the resin. Cathartic doses are required in biliary calculi, apoplexy, dropsy, and in some forms of inflammation. Younkin advises cathartic doses (1/6 grain, every 2 hours, with 10 grains of potassium bitartrate) for the relief of gonorrheal epididymitis. The dose of podophyllin, as a cathartic, is from 1/2 to 2 grains; as an alterative and stimulant, 1/100 to 1/10 grain; as a cholagogue, 1/20 to 1/10 grain. A good form in most disorders requiring the small dose, is the following: Rx Podophyllin trituration (1 in 100), grs. v to xxx; aqua, ℥iv. Dose, 1 teaspoonful, every 1 to 3 hours.

Specific Indications and Uses.—Podophyllin is specifically indicated by fullness of tissues, fullness of veins, sodden, expressionless countenance, dizziness, tongue coated dirty yellowish-white, heavy headaches, indisposition to bodily exertion, intestinal atony, with sense of weight and fullness, full open pulse; "pain deep in ischiatic notches," and as an ideal cholagogue; clay-colored stools, floating upon water; stools, hard, dry, and accompanied with distended abdomen and colicky pain. It is contraindicated by pinched features, and small, wiry pulse, or when the pulse has a sharp stroke.

King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.

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