Resina Podophylli. U. S. (Br.) Resin of Podophyllum. Res. Podoph. [Podophyllin]
Podophylli Resina, Br.; Podophyllum Resin; Resin of May-Apple; Resine de Podophyllum Peltatum, Fr. Cod.; Podophyllinum, P. G.; Podophyllin, Podophyllumharz, G.; Podofillina, It.; Podofilino, Sp.
"Podophyllum, in No. 60 powder, one thousand grammes [or 35 ounces av., 120 grains]; Hydrochloric Acid, ten mils [or 162 minims]; Alcohol, Water, each, a sufficient quantity. Moisten the powder with five hundred mils [or 16 fluidounces, 435 minims] of alcohol, and pack it 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 forty-eight hours. Then allow the percolation to proceed, gradually adding alcohol, until the percolate ceases to produce more than a slight turbidity when dropped into water. Distil off the alcohol until the percolate is reduced to the consistence of a thin syrup, and pour this slowly, with constant stirring, into one thousand mils [or 33 fluid-ounces, 6 ½ fluidrachms] of water, mixed with the hydrochloric acid and cooled to a temperature below 10° C. (50° F.). When the precipitate has subsided, decant the supernatant liquid, and wash the precipitate twice, by decantation, with fresh portions of one thousand mils [or 33 fluidounces, 6 ½ fluidrachms] 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, protected from the light. Should it coalesce during the drying, or aggregate into lumps having a glossy surface, break it into pieces, and powder it in a mortar. Preserve it in well-closed containers, protected from light." U. S.
"Podophyllum Rhizome, in No. 40 powder, 1000 grammes; Alcohol (90 per cent.), Distilled Water, Hydrochloric Acid, of each a sufficient quantity. Exhaust the Podophyllum with the Alcohol by percolation; recover the greater part of the alcohol by distillation; pour the resulting liquid into eight times its volume of Distilled Water acidified with one twenty-fourth of its volume of Hydrochloric Acid, constantly stirring; after twenty-four hours collect the deposited resin, wash with Distilled Water, and dry at a temperature not exceeding 40° C. (104°F.)." Br.
The British Pharmacopoeia (1885) abandoned the use of hydrochloric acid, as it is not necessary if the tincture is evaporated to the consistence of thick honey. Hydrochloric acid was directed in the 1898 revision as it seems to aid the precipitation when the tincture is not so concentrated. The color and yield of resin of Podophyllum may be made to vary by adding alum, acids, or other substances to the water. It darkens if dried with the aid of heat, and its color is indeed no indication whatever of its quality. The average yield of resin is about 5 per cent.
Resin of Podophyllum has usually a light-brown color, an acrid bitter taste, and a slight odor of the rhizome. It consists of two resins, one soluble both in ether and alcohol, the other in alcohol only. The resin extracted by ether constitutes, according to John W. Cadbury, 75 per cent. of the whole (A. J. P., July, 1858, p. 301), according to Harvey Alien, 80 per cent. (Ibid., May, 1859, p. 206.)
For further description of the composition of these resins see Podophyllum. Gordon and Merrell (Proc. A. Ph. A., 1902, p. 343) have proposed a method of valuing resin of podophyllum, based upon the content of picro-podophyllin and submit a method of assay.
Properties.—It is officially described as "an amorphous powder varying in color from light brown to greenish-yellow, turning darker when subjected to a temperature exceeding 25° C. (77° F.), or when exposed to light. It has a slight, peculiar odor and a faintly bitter taste. It is very irritating to the eyes, and to mucous membrane. It is soluble in alcohol with only a slight opalescence. The alcoholic solution is faintly acid to litmus. Not less than 75 per cent. of Resin of Podophyllum is soluble in ether and not less than 65 per cent. is soluble in chloroform. A hot aqueous solution of Resin of Podophyllum deposits most of its contents on cooling, and if the cooled liquid is filtered, the filtrate has a bitter taste, and turns brown upon the addition of a few drops of ferric chloride T.S. It is soluble in potassium or sodium hydroxide T.S., forming a deep yellow liquid, which gradually becomes darker on standing, and from which the Resin is reprecipitated by acids. Add 0.4 G-m. of Resin of Podophyllum to 3 mils of 60 per cent. alcohol, introduce 0.5 mil of potassium hydroxide T.S., and gently shake the mixture; it does not gelatinize (difference from Resin obtained from Podophyllum Emodi). Resin of Podophyllum yields not more than 1.5 per cent. of ash." U. S.
"An amorphous powder, varying in color from pale yellow to deep orange-brown. Taste bitter. Entirely or almost entirely soluble in alcohol (90 per cent.) and in solution of ammonia; precipitated from the former solution by water, from the latter by acids. Partly soluble in ether. Ash not more than 1 per cent." Br.
The official resin is soluble in alkaline solutions, from which it is precipitated by acids, in this respect differing strikingly from the resins of jalap and scammony. It is insoluble in oil of turpentine. For discussion of the solubilities of the fresh resin, see G. M. Beringer (A. J. P., 1894, 11). The name Podophyllin, given to it by the eclectic practitioners, who have long' been in the habit of using this resin, is inappropriate, and should be abandoned.
Lohmann (Proc. N. J. Pharm. Assoc., 1896, 51) states that the fresh drug does not yield as large a percentage of resin as the same drug would if tested after being stored for several years; his experiments led him to the conclusion that in the order of value of resin of podophyllum obtained by various methods, that made by precipitation with water alone came first, that made by the U. S. P. process second, and that made by precipitation with solution of alum last. Dohme and Kelly (D. C., 1903, 251), replying to statements in a paper by Lohmann (Proc. A. Ph. A., 1903, 317) regarding the yield of resin from Podophyllum, state that: 1, the yield from the method of pouring an alcoholic extract into water was 5 per cent.; 2, from pouring an alcoholic extract into acidulated water 5.5 per cent., and 3, from pouring an alcoholic extract into acidulated water containing 5 per cent. of alum, 4.9 per cent. See also Podophyllum. The color by process 1, is grayish-white; 2, light brown; 3, greenish-yellow. The value of resin of podophyllum is accurately estimated by the percentage of podophyllotoxin that it yields. Nearly all of the resin of podophyllum in commerce is made by the alum process, has a deep yellow color and is not wholly soluble in alcohol.
There has been much difference of opinion as to the relative activity of the two resins composing it, some maintaining that both are active, others that the activity resides mainly, if not exclusively, in the resin soluble in ether. It is difficult to resist the evidence of the experiments of Cadbury, who states in the paper above referred to that, while half a grain of the ethereal resin acted energetically, and a cathartic effect was produced by even one-fourth of a grain, the portion insoluble in that menstruum was given in the dose of one grain without any effect whatever. Moreover, this evidence was subsequently confirmed by the experiments of F. B. Power. (A. J. P., xlvi, 227.) It is asserted by Power, and confirmed by Maisch (Ibid; 226), that the purgative principle of Podophyllum is soluble in hot water. The researches of Power (A. J. P., l, p. 369), Maisch (P. J., 1880, p. 621), Quereschi (Ber. d. Chem. Ges., xii, p. 683), and Podwyssotzki have established the fact that Podophyllum does not contain berberine or any alkaloid, and that its activity is due to principles in the resins. (See Podophyllum.)
Uses.—Resin of Podophyllum is a mixture of the active and inert principles of the rhizome. Resin of Podophyllum is a powerful cathartic, occasionally producing some griping and nausea, but capable of being favorably modified by combination, and of being very usefully employed in connection with other cathartics, to give them increased energy. It was at one time supposed to be especially cholagogue, but this belief has been of late discredited. A small proportion of extract of belladonna or hyoscyamus mitigates its irritant action. Care must be taken in handling it in quantity, as it is a powerful irritant, frequently producing conjunctivitis.
Dose, one-eighth to one-fourth of a grain (0.008-0.016 Gm.).
Off. Prep.—Tinctura Podophylli, Br.; Pilulae Aloes et Podophylli Compositae, N. F.; Pilulae Aloes, Hydrargyri et Podophylli, N. F.; Pilulae Aloini Compositae, N. F.; Pilulae. Catharticae Vegetabiles, N. F.; Pilulae Colocynthidis et Podophylli, N. F.; Pilulae Laxativae Post Partum, N. F.