By GEORGE W. KENNEDY.
Read before the American Pharmaceutical Association.
Query 21. Is there any difference in the laxative action of Rhamnus Purshiana and Rhamnus Catharticus?
Experiments undertaken with the view of answering this query require considerable time and labor, since a number of important points are to be taken into consideration in order to be able to reach a satisfactory conclusion, and the omission of either one will cause more or less uncertainty in the results. One of these results is the proof that the two drugs under consideration require somewhat different menstruums for stable liquid preparations, since the menstruum which will thoroughly exhaust the virtues of one of the drugs and hold the principles in perfect solution, will not answer for the other. In order to ascertain if possible the relative strength of these two drugs the fluid extracts were believed to be the most convenient and satisfactory form for experimentation, and they were prepared as follows:
|Take of||the bark in moderately fine powder||16 ounces|
|Alcohol (95 per cent.)||11 fluidounces|
Mix the above fluids, moisten the powder with a portion of the mixture, pack properly in a glass conical shaped percolator, cover the surface of the powder with a disc of paper, and add the remaining menstruum. When the liquid begins to drop from the percolator, close the lower orifice with a cork, and leaving closely covered the percolator, to prevent evaporation set it aside in a moderately warm room for four days. The cork is then removed, more menstruum, composed of eleven fluidounces of alcohol and five fluidounces of water, is added gradually, and the percolation continued until twenty-four fluidounces are obtained of which the first thirteen are reserved; the remainder is carefully evaporated to two fluidounces, then add one fluidounce of alcohol, and mix with the reserved portion.
This menstruum is not sufficiently strong in alcohol to make a permanent preparation of Rhamnus Catharticus; but by increasing the alcohol in the above formula to twelve fluidounces in the pint, excellent results were obtained and no precipitation of any consequence took place in the fluid extract after standing for several months. When made of the weaker alcoholic menstruum a deposit took place shortly after the preparation was finished, but none occurred in the fluid extract of Rhamnus Purshiana, which was made about nine months ago. The taste of the two preparations differs somewhat; while that of Rhamnus Catharticus is unquestionably very bitter, yet it is not near so strong as the bitterness of the Rhamnus Purshiana.
To satisfy myself that the drugs were thoroughly exhausted the powders were administered and found to have no laxative properties whatever. The precipitate alluded to above, a portion of which I collected by decantation, was of a brownish color and dissolved completely in liquor potassae, with a deep purplish-red color, characteristic of the resin. By the addition of dilute acetic acid the purplish-red color of the alkaline solution was immediately destroyed, and a brownish colored mass thrown down, which was thrown into a filter, repeatedly washed with water, and dried. It is soluble in alcohol, diluted alcohol, and the alkalies, insoluble in chloroform and ether, and nearly so in water, thus corresponding in appearance and tests with the rhamno-cathartin found in the juice of the buckthorn berries by Binswanger, in 1849. Repeated attempts to crystallize this substance were not successful. On being administered in four grain doses it had a decided cathartic action, and in doses of three grains was strongly laxative.
The separation of this substance from the fluid extract induced me to investigate the subject a little deeper than at first intended. Accordingly a small quantity of the resin was made from each bark by a process noticed below, and the yield ascertained, as well as the medicinal action. In the meantime the fluid extracts were placed at the disposal of several of my medical friends who rendered me valuable aid and reported their conclusions, which agree so closely in the more important points, that it would be superfluous to give them all in detail.
The following report from Dr. I. D. Wiltrout, of Hudson, Wis., appears to cover the subject quite thoroughly:
"The samples of fluid extract of Rhamnus Catharticus and Rhamnus Purshiana given me for trial have more than met my highest expectations. I used these preparations in cases of constipation characterized by atony, or paresis of the muscular coat of the bowels, induced by a catarrhal condition of the stomach and small intestines. They gave free evacuations in small doses, say from 30 to 50 drops, with no pain, and materially improved the appetite. The evident action is upon the nerve terminals and in this way reflectly stimulating muscular contractibility and glandular secretions. The common experience was that a diminished dose was needed to assure the daily purpose. I also used the remedies on women in whom the colon was allowed to distend from neglect and inattention; in all instances they were efficient. I think these remedies might be usefully prescribed with aloes when there is no pelvic or uterine difficulty, and thus act on the whole bowel. I have prescribed these remedies in combination with the phosphate of sodium in chronic constipation, attributable to a bilious condition. It wonderfully accelerates the action of the phosphate and arrests a sick headache promptly, and does not deplete the system. I think these remedies have a wide province and if the extracts are always as reliable as those you sent, will be used in the cases enumerated. I have prescribed these remedies in a large number of cases and my conclusions as to their relative strength is, that a smaller quantity of the Rhamnus Purshiana is required both as a laxative and as a cathartic, but it is a little nauseating."
In regard to the squeamish action of the drug noticed by Dr. Wiltrout, in the Cascara Sagrada, this has likewise been observed in the bark of the Rhamnus Frangula the first year after gathering, but when two or three years old retains only the purgative power, and is much similar in its effect to that of rhubarb, consequently most authorities forbid its use until two years from the time it is gathered, and the Norwegian Pharmacopoeia requires the bark to be kept one year before it is used medicinally. The glucosic fermentation which is now admitted to take place by age in the Frangula, may likewise take place in the Purshiana. On this point I am unable to give an answer as I could not ascertain the age of the bark operated on.
The resins of both species were obtained from the concentrated alcoholic tinctures by adding them with constant stirring to water, when subsidence bad taken place, decanting the supernatant liquids, washing the precipitates twice by decantation, with fresh portions of water, and drying them.
Eight ounces of the bark was operated on in each case. The bark of Rhamnus Purshiana yielded 250 grains, or about 6 3/10 per cent. of resin, which is dark in color and almost black, but if dissolved in caustic potash solution and precipitated by diluted acetic acid it is of a brown color. It is very bitter, of a granular appearance, and contains a small quantity of a yellow fixed oil, which on a piece of white paper produces a greasy stain. The resin is soluble in alcohol, diluted alcohol, in sulphuric acid with a reddish brown color, and in liquor potassae, with a purplish red color; it is insoluble in chloroform and ether. In doses of 1 to 3 grains it acted as a laxative and cathartic. The extractive matter obtained by evaporating the water used in precipitating the resin amounted to 1 1/2 ounces, or 18 5/10 per cent., making a total yield of both of 24 8/10 per cent. The watery extract is of a dark reddish brown color, when perfectly dry breaks with a snap, the fracture being glossy, but when exposed to damp air it becomes soft and sticky; it has an intensely lasting bitter taste, much stronger than the precipitated resin, and its physiological action is similar, 2 to 3 grain doses having laxative effects, and 5 grains acting as a cathartic. It is soluble in a large quantity of water, freely so in dilute alcohol, sparing soluble in alcohol, and almost insoluble in chloroform and ether; with sulphuric acid it forms a reddish brown solution, and with liquor potassa, makes a clear solution of purplish red color.
The yield of resin from the Rhamnus Catharticus is not so large as from the former, 8 ounces yielding 160 grains or 4 1/6 per cent., and by evaporating the aqueous fluid used in precipitating the resin 210 grains or 5 5/10 per cent., making a total of 370 grains or 9 2/3 per cent. The resin is found to be soluble in diluted alcohol, alcohol, in liquor potassae with a claret wine color, in sulphuric acid with a red color; also in ether and chloroform, but insoluble in water. The aqueous extract was soluble in water, sparingly soluble in alcohol, soluble in dilute alcohol, insoluble in ether and chloroform, soluble in liquor potassae with a purplish red color and in sulphuric acid with a reddish brown color. As to the laxative and cathartic properties of these two I found the resin decidedly the stronger, requiring 3 grains for a laxative action, while the aqueous extract required 4 to 5 grains to have the same effect.
From the above observations on the resins and extracts obtained from these barks, I would unhesitatingly conclude that the preparations manufactured from Rhamnus Purshiana are decidedly the more active. Before closing I desire to return my thanks to Messrs. Parke, Davis & Co., of Detroit, Mich., who kindly accommodated me with material to make these investigations.
The American Journal of Pharmacy, Vol. 57, 1885, was edited by John M. Maisch.