GB852584A - Biguanide compositions - Google Patents

Abstract

Biguanides of the general formula: <FORM:0852584/IV(b)/1> (wherein (a) R1 represents an n-butyl or n-pentyl group and R2 represents hydrogen, (b) R1 represents a benzyl or b -phenylethyl group optionally substituted in the nucleus by bromine, chlorine or a methoxy group and R2 represents hydrogen, (c) R1 represents a benzyl group and R2 a methyl group, or (d) R1 and R2 jointly form a pentamethylene or hexamethylene group) are prepared in the form of hydrochlorides by fusing equivalent quantities of dicyandiamide and the hydrochloride of an amine R1R2NH. The hydrochloride may be isolated by recrystallization of the fusion mixture, or, where this gives a poor yield, the nitrate of the biguanide may be precipitated by adding excess of aqueous sodium nitrate to an aqueous solution of the fusion mixture. Alternatively the biguanide may be precipitated as the free base by addition of caustic soda, and the base may be converted to any desired salt. m-Bromobenzylamine is prepared by converting m-bromobenzoyl chloride to m-bromobenzamide and reducing this with LiAlH4.ALSO:Compositions for treating diabetes mellitus by oral administration comprise a biguanide of the general formula: <FORM:0852584/VI/1> or a salt thereof, (wherein (a) R1 represents an n-butyl or n-pentyl group and R2 represents hydrogen, or (b) R1 represents a benzyl or b -phenylethyl group which may be substituted in the nucleus by bromine, chlorine or a methoxy group and R2 represents hydrogen, or (c) R1 represents a benzyl group and R2 a methyl group, or (d) R1 with R2 forms a methylene chain containing 5 or 6 carbon atoms) together with one or more innocuous solid substances chemically inert to the biguanide. Specified salts are the hydrochloride, hydrobromide, nitrate, phosphate, sulphate, acetate, citrate, malate, tartrate, lactate, glycolate, beta-ethoxypropionate and salts with thiophylline, 8-chlorothiophylline, saccharin, phthalimide, succinimide, benzoxazine-2,4 dione, oxazolidine-2,4-dione, barbituric acid and 1-butyl-3-p-methylbenzenesulphonylurea. The compositions are advantageously in the form of tablets or hard gelatin capsules.