By JULIUS JUNGMANN.
(Condensed from the author's Inaugural Essay.)
[The author gives a good botanical description of the plant and its habitat; he describes the drug, refers to its introduction in medicine, and reviews the analyses made since 1809 to the present time, when he proceeds to his own experiments. The thesis was accompanied by specimens of most of the principles isolated.]
A quantity of coarsely powdered Uva ursi leaves was exhausted with cold water by percolation, the infusion heated to the boiling point, strained, it, greenish flocculent coagulum of albumen was left on the strainer; the infusion, after having been more concentrated, was treated with freshly prepared hydrated oxide of lead, until it would no longer produce a precipitate; this was separated by a filter. The filtrate still more concentrated by evaporation, was divided into two parts, the first was set aside in a warm place to evaporate spontaneously, the second was treated with strong alcohol; this produced a bulky precipitate of gummy matter, which was removed by filtration; the alcoholic filtrate was again divided into two portions, the first set aside to evaporate spontaneously, the second evaporated to a syrup and then treated with ether; the different ethereal solutions were mixed and evaporated at common temperature. The residue consisted of a mass of nearly colorless prismatic crystals of considerable size, of a bitter slightly acrid taste, with a small quantity of resinous matter of peculiarly disagreeable odor adhering—Ericolin.
They could be easily purified by either washing them with ether, which would dissolve out the resin, or else by dissolving them in a small quantity of boiling water, filtering and recrystalizing; thus purified from water they were inodorous, not near as large, but small needles having a silky lustre.
The alcoholic solution yielded a dark colored extract nearly black; this was redissolved in alcohol and treated with animal charcoal, filtered and again evaporated spontaneously; yielded, after being pressed and dried, yellowish white crystals of a flocculent character having no odor.
The aqueous solution, which had been set aside in a warm place was found, after about two weeks standing, to consist of a soft extractive mass covered all over the surface with small white crystals, very difficult to remove on account of the large amount of black, gummy extractive adhering to it. The crystals contained in this mass could only be obtained after long and repeated treatment with animal charcoal; to remove coloring matter and other impurities, it might be purified by precipitating the coloring matter by a solution of alum, but this mode of proceeding can only be recommended when arbutin is the only object in view, otherwise it is objectionable, as it complicates the process. A quicker way, however, to obtain the crystals, I found to be by treating the extractive mixture with a mixture of alcohol and ether, in which they readily dissolve, leaving behind nearly all the impurities; as thus obtained the crystals have, in their moist condition, a yellowish color, becoming nearly white when dried; they possessed the same properties as those obtained previously.
All the crystals obtained by these different processes proved to be arbutin, the discovery of which was first announced by Kawalier in 1852.
A second quantity of leaves was reduced to a coarse powder, decocted with water, the decoction strained and precipitated with neutral acetate of lead, the precipitated lead salt was filtered off and the filtrate was treated with basic acetate of lead, until a precipitate was no longer produced, this being filtered out. Sulphuretted hydrogen gas was passed in the filtrate until all the lead was precipitated; the sulphuret of lead was then removed by a filter, and the excess of hydrosulphuric acid by heating the filtrate; this was evaporated to a soft extract, redissolved in water, treated with animal charcoal, then again filtered and evaporated and, while hot, set aside. After about 24 hours standing the bottom of the vessel was covered with bunches of small crystalline needles of arbutin; these were pressed and dried between filtering paper and purified by redissolving them in a small quantity of boiling water, and again allowing the crystals to separate; these when pressed and dried, consisted of small prismatic needles having a silvery lustre. This second process for obtaining the arbutin is in the main points the original one of Kawalier, except that he does not precipitate with basic acetate of lead, which, however, removes nearly all the gum and coloring matter, and thereby facilitates the crystallization to some extent.
Arbutin generally crystalizes from ether in prismatic needles of considerable size and perfectly colorless from an alcoholic solution, in small acicular crystals of a white color, and in small bunches of needles from water; it is neutral in its behaviour, very soluble in warm or hot water, less in cold water or alcohol, more in hot alcohol, very sparingly in ether; a concentrated solution of arbutin is precipitated by strong alcohol or ether added to it, but the precipitate rapidly disappears on shaking. Concentrated sulphuric acid or hydrochloric acid added to the crystals on a small plate, gradually dissolves them without change of color. With nitric acid the crystals first turned black, and then slowly dissolved, the acid assuming a yellow color and giving off fumes of nitrous acid. Arbutin in aqueous solution does not affect in alkaline solution of sulphate of copper, the salts of lead, acetate and subacetate do not precipitate it, salts of iron have no effect upon it; other reagents for organic bodies as tannic and gallic acid, bichloride of mercury, nitrate of silver, iodide of potassium and bichloride of platinum were tried without any results.
While experimenting with these reagents, I accidently found a very characteristic and remarkable test for arbutin; when a solution of arbutin in water is rendered alkaline by ammonia, or any other caustic or carbonated alkali, and then phosphomolybdic acid is added, a blue color is produced; in strong solutions the coloration is of a deep azure blue, but the bluish hue can be observed even in very dilute solutions. One grain of arbutin was distinctly indicated in twenty pints of water (1 in 140,000); this reaction does not occur with molybdate of ammonia, nor does it take place when phosphoric or phosphomolybdic acid is acted upon by an alkali alone.
A solution of arbutin may be perfectly colorless but still impure when to an impure solution of arbutin, ammonia or any caustic or carbonated alkali is added, a deeper, sometimes orange color is produced, while a solution of pure arbutin is not affected in this way.
[The autbor now describes the composition and glucoside nature of arbutin and the mode of obtaining hydrokinone, the literature on the subject being reviewed and compared with his experiments.]
E. C. Hughes, in an essay on Uva ursi, published in the American Journal of Pharmacy, 1847, describes a crystalline principle which he obtained from the leaves and to which he gave the name "Ursin." This ursin, although it has not been noticed in European literature, has received some attention, and has generally been regarded as a distinct principle in American works. As this was obtained before the known existence of arbutin, and as its mode of preparation is similar to that of arbutin, I was led to suppose that the two might perhaps be identical; to satisfy myself, I prepared some ursin according to Hughes' method, which consists in maceration and percolation of the leaves with cold water, precipitating the tannin by a solution of gelatin, filtering and evaporating to dryness, treating the remaining extract by strong alcohol, the alcoholic solution with animal charcoal, filtering and evaporating spontaneously. By this process an acicular crystalline mass, to which a small quantity of resin adhered, was obtained having nearly all the properties of arbutin; the solution rendered alkaline, produced a blue color with phosphosmolybdic acid, and it yielded, when boiled with dilute sulphuric acid, the same product of decomposition, hydrokinone, besides separating ericolin.
Hughes states, however, that his ursin was precipitated by carbonate of potassa, and by the solution of subacetate of lead, while it was not affected by the tincture of chloride of iron; but as he uses a solution of gelatin to precipitate the infusion or the leaves, he only gets rid of the tannic acid while the gallic acid remains in solution, and is afterwards obtained together with the arbutin, (his ursin). A solution of this mixture, then, of course precipitates with basic acetate of lead, but then it ought to be affected by the salts of iron; but the tincture which he used is a very uncertain test, owing to the free acid it contains, which does not indicate small quantities, as in this case, while the solution of subacetate of lead precipitates even the smallest trace of gallic acid. Carbonate of potassa would produce a slight change in the color, but an actual precipitation did not take place. The ursin of Hughes must therefore be considered as an impure arbutin.
[The author then minutely describes the action of nitric acid on arbutin and the production of binitro-arbutin, discovered by Strecker; also, the decomposition of this compound into sugar and binitro-hydrokinone, after which the effect of chlorine upon arbutin is considered.]
Arbutin has also been found abundantly in Chimaphila umbellata, and it probably exists in a number of ericaceous plants. Its medical properties have never been practically applied; it was at one time believed to represent the diuretic properties of Uva ursi, and Hughes states that one grain of his ursin proved a powerful diuretic. The celebrated pharmocologist, Dr. Schroff of Vienna, who experimented with pure arbutin, states, however, that it possesses no diuretic properties at all; he gave it in doses as high as eight grains, and could not detect it in the urine.
When the mother-liquor from arbutin is heated with a dilute acid, (sulphuric or muriatic) a resinous body separates, which has received the name of cricolin; this again is a glucoside, which, when treated with a dilute acid, splits into grape sugar, and an odorous substance having the character of a volatile oil, ericinol; both have been noticed already by Kawalier in his investigation. In preparing ericolin from the mother liquor of arbutin, I found that a portion of ericolin is decomposed as soon as it forms into ericinol, giving rise to the strong disagreeable odor of the latter. Ericolin is a dark brown resin, becoming somewhat lighter when dried and rubbed to powder; its chemical composition is C68H56O42. Its decomposition into C is shown by the following:
|C68H46O42+8HO =||C20H16O2 +||4C12H12O12.|
[The literature on ericinol and ericolin is now reviewed, and their occurrence in different plants spoken of. The precipitate, obtained, with hydrated oxide of lead was found to contain tannin, gallic and malic acids, but to be free from tartaric and citric acids. The precipitate obtained by adding alcohol in a concentrated infusion of the leaves, contained gum, glucose and a lime salt. The leaves, previously exhausted with water, were treated with ether, and Trominsdorff's urson was prepared from the ethereal tincture (see Am. Journ. Ph., 1854.)].
Trommsdorff's process directs the ethereal extract to be washed by ether before treating with alcohol; this removes, besides the coloring matter, some fatty matter; but when operating upon larger quantities, I believe that animal charcoal will answer the same purpose. Another way to prepare urson is to percolate the leaves, previously exhausted by water with strong alcohol; the dark green tincture deposits already on standing a large quantity of nearly white urson, which only needs recrystallizing; the remainder of the tincture is evaporated, treated with water, and then washed with ether and recrystallized from alcohol. Urson, when pure, possesses neither odor nor taste; it is insoluble in water, sparingly soluble in alcohol and ether. It is not affected by alkalies or dilute acids.
Concentrated sulphuric acid turns it black and gradually carbonizes it, the acid assuming a red color. Concentrated nitric acid turns. it yellow, gradually dissolving it, giving off nitrous acid. When heated, urson melts into an amorphous transparent mass; at a still higher temperature it boils and sublimes in a test tube unchanged. Its medical properties have as yet not been ascertained, at least no physiological experiments have been made with it, and very probably it is entirely inert. A small quantity of volatile oil was found in the aqueous solution of the ethereal extract, besides some tannic and gallic acids.
The organic constituents of Uva ursi as obtained by this investigation, therefore, are:
Arbutin, and its product of decomposition, hydrokinone; ericolin, ericinol, urson; (ursin, the diuretic principle of Hughes, was found to be impure arbutin;) tannic, gallic and malic acids, then a small quantity of volatile oil, fatty matter, wax, gum, sugar, albumen, coloring matter, etc.
The test for arbutin may perhaps serve for finding this principle, in plants, without isolating it, for, an infusion of Uva ursi, when diluted with sufficient water to make it perfectly colorless, and then rendered alkaline, produces, on the addition of phosphomolybdic acid, the blue reaction due to arbutin; when the alkali (ammonia) is added to the diluted colorless infusion, a color (orange) again appears, owing to the astringent acids present; this color must also be removed by again diluting it with water, before the final addition of the phosphomolybdic acid.
This test cannot be applied to a strong infusion because phosphomolybdic acid reacts with tannic and gallic acids green, and the blue color cannot then be observed.
The American Journal of Pharmacy, Vol. XLIII, 1871, was edited by William Procter, Jr. (Issues 1-4) and John M. Maisch (Issues 5-12).