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2,411,631 Patented Nov. 26, 1946 UNITED ‘STATE S PATENT OFFICE 2,411,631 STABLE, SUPERSATURATED SOLUT ONS SU OF OF THE SACCHARIDE DERIVATIVES HORMONE SERIE PRARENAL CORTICAL AKING SAME . AND PROCESS OF M Karl Miescher, Riehen, and Charles Meystre, Basel, Switzerland, assignors to Ciba Pharma ceutical Products Incorporated, Summit, N. J ., a corporation of New Jersey No Drawing. Application June 11, 1943, Serial No. 490,536. In Switzerland December 24, 1942 9 Claims. (Cl. 167-77) 2 amongst these physiologically occurring sugars According to K. Miescher, W. H. Fischer and Ch. Meystre (Helvetica Chimica Acta, vol. 25, in particular. The concentration of these sub page 40, 1942) , the solubility of desoxycorticoster one in water is increased about ten times to 0.12 exceed in general 20-25%. percent by converting it into the ?-glucoside. See also the Miescher et al. Patent No. 2,270,379, tically. The following examples illustrate the invention granted on Jan. 20, 1942. For practical purposes, however, in particular for injection therapy, often but are not to be regarded as limiting it in any renal cortical hormone series can be obtained if these derivatives are dissolved in aqueous solu tions of inert, easily water-soluble organic com one is brought into solution in 100 parts of a 10% d-glucose solution in water by heating in a boiling water-bath. The solution obtained is ?lled into stances is chosen as low as possible and does not The solutions obtained are to be used therapeu way, the parts being by weight: still more concentrated solutions are desired. It Example 1 10 has now been found that stable, super-saturated 1 part of the ?-d-glucoside of desoxycorticoster solutions of saccharide derivatives of the supra pounds containing. oxygen, with exclusion of any 15 ampules. The latter are sealed and sterilized in the usual way by heat. The ampules prepared in crystallization nucleus. this way remain clear and are very stable. No Such solutions remain surprisingly stable for a long time even at low temperatures; after the precipitation occurs on pouring the solution into addition of a small crystal of the saccharide de water. . rivative, however, crystallization of the super 20 Aqueous solutions of other sugars such as sucrose, lactose, etc. can also be used with the saturated solutions soon starts. The latter should therefore be stored in sealed ampules. If the so lutions prepared as described in the process are diluted with water, there is no separation of the same success. saccharide derivative contained. This is surpris ing as it is known that, for example, free desoxy corticosterone or barbituric acids which are brought into aqueous solution by means of suit Example 2 2 parts of the p-d-glucoside of desoxycortico sterone are dissolved in 100 parts of a 10% solu tion of glycol in water as in Example 1. The solu tion is ?lled into ampules andsterilized. Instead able hydrotropic agents, for example by means of 30 of glycol, other polyalcohols or their derivatives, urea, are precipitated immediately on dilution e. g. ethers, and also monoalcohols may be used. with water. ' The following saccharide derivatives of the su prarenal cortical hormone series may, for exam ple, be used: monosaccharide derivatives, such as Example 3 0.5 part of the ?-lactoside of desoxycorticoster one is dissolved in 100 parts of a 20% solution of the a- and B-glucosides, galactosides, mannosides 35 glycerine in water as described in Example 1. or arabinosides, polysaccharide derivatives such as maltosidcs, lactosides, lactosidoglucosides, etc. of, for example, desoxycorticosterone, corticoster one, dehydrocorticosterone, anhydrocorticoster one or corresponding compounds hydroxylated in 40 the l7-position. As solvents ior the saccharide derivatives The solution is ?lled into ampules and sterilized. It is stable even on cooling. ' Example 4 2 parts of the s-d-glucoside of corticosterone (prepared by reaction of corticosterone and tetra acetylbromoglucose in the presence of silver car bonate and saponi?cation of the tetra-acetate ob named, the following are suitable: aqueous solu tained) are dissolved hot in 100 parts of a 15% tions of mono- or poly-alcohols, such as glycol, glycerine, erythritol or mannitol, of monosac 45 aqueous d-glucose solution. The solution is ?lled into ampules and sterilized in the usual way charides and sugar-like polysaccharides, such as glucose, galactose, fructose, lactose, maltose, after sealing. It is stable. In a similar way, solutions of glucosides of sucrose or ra?inose and ?nally of further inert, easily water-soluble organic compounds contain 50 other active compounds of the suprarenal cortical hormone series, such as, for example, dehydrocor ing oxygen, such as dioxane or polymers of ethyl ene oxide, or of mixtures of such compounds. ticosterone, can be prepared. The glucosides Especially to be recommended on account of their themselves are obtained analogously to that of good tolerability are solutions of certain members corticosterone. A of the sugar series, i. e. of polyalcohols, mono What we claim is: ‘saccharides and sugar-like polysaccharides, and 2,411,631 a physiologically inert proportion of a saccharide, said hydrotropic agent being present in a concen tration sui?cient to eifect stabilization of the solu tion but not exceeding about 20-25%. »5. A stable, supersaturated aqueous solution of a monosaccharide derivative of the suprarenal cor tical hormone series containing, as hydrotropic agen , a physiologically inert proportion of a sac 10 the solution but not exceeding about 20—25%. 6. A stable, supersaturated aqueous solution ofca glucose derivative of the suprarenal cortical hor 15 mone series containing, as hydrotropic agent, a solution but not exceeding about 20-25%. 7. A stable, supersaturated aqueous solution of a I about 20—_25%. glucoside of desoxycorticosterone containing, as hydrotropic agent, a physiologically inert quantity of glucose, said hydrotropic agent being present 3. A process for the manufacture of 25 30 suprarenal cortical hydrotropie agent, I containing, hydrotropic agent, about 10% Of glucose. as 9. A stable, supersaturated aqueous solution of a glucoside of desoxycorticosterone containing, as hydrotropic agent, about 10% of glucose. ‘ KARL MIESCHER. CHARLES MEYSTRE.