Patent GB-395405-A (GB)
Title: Process for the manufacture of stable acridine salt solutions
IPC: C07D219/08
Filed: 1932-01-15
Abstract: Aqueous solutions for injection purposes are manufactured by incorporating a reducing substance, other than a carbohydrate, with a salt or solution of a salt of an aminoacridine or aminoacridinium compound other than the salts of 3 : 6-diaminoacridine or 3 : 6-diamino-10-alkylacridinium or double compounds thereof.  Suitable acridine compounds are the salts of substitution products of 3 : 6-diaminoacridine and 3 : 6 - diamino - 10 - alkylacridinium compounds and of other aminoacridines or acridinium compounds or their substitution products or the corresponding double compounds. As reducing substances may be employed the salts of sulphurous, hydrosulphurous or sulphoxylic acids, as such or in the form of derivatives, e.g. compounds with aldehydes or ketones, also hydrazines and hydroxylamines, or mixtures thereof.  Compounds advantageous for therapeutical application, e.g. glucose, adrenaline, acid amides, glycerine, pyridine, methylene blue, calcium chloride or silver salts, may also be added.  Examples describe the preparation of solutions containing: (1) 2 : 7-dimethyl-3 : 6-diamino-10-methylacridinium chloride, 2 : 7-dimethyl-3 : 6-diaminoacridine hydrochloride, sodium bisulphite and sodium sulphite; (2) 2 : 7 : 9-trimethyl-3 : 6-diamino-10-methylacridinium chloride, acetone bisulphite and glucose; (3) 2 : 7 : 9-trimethyl-3 : 6-diaminoacridine p  hydrochloride, phenylhydrazine acetate and glucose (to render the solution isotonic to blood); (4) 2-methyl-3-amino-6-dimethylamino - 10 - methylacridinium sulphomethylate (obtainable by condensation of formic acid with N-dimethyl-m-phenylenediamine and 4-methyl-1 : 3-phenylenediamine and subsequent alkylation with methyl sulphate) and sodium sulphite, with or without silver sulphate, methylene blue or pyridine; (5) 2 : 7 - dimethyl - 3 - amino - 6-dimethylamino-10-methylacridinium chloride, acetone bisulphite, sodium sulphite and glucose or an acid amide; (6) 2 : 7-dimethyl-3 : 6-tetramethyldiamino-10-methylacridinium chloride (obtainable by condensation of formic acid with 4-methyl-3-N-dimethylaminoaniline, alkylation with methyl sulphate and saponification with hydrochloric acid), hydroxylamine and sodium hydrosulphite; (7) 2 : 7-dimethyl-3-amino-6-dimethylamino-10-methylacridinium chloride, sodium bisulphite and sodium sulphite.  The Specification as open to inspection under Sect. 91 describes also the preparation of tablets by mixing the substances employed in (7) with ureas, sugars or other water soluble admixtures.  This subject-matter does not appear in the Specification as accepted.ALSO:Aqueous solutions for injection purposes are manufactured by incorporating a reducing substance, other than a carbohydrate, with a salt or solution of a salt of an aminoacridine or aminoacridinium compound other than the salts of 3 : 6-diaminoacridine or 3 : 6-diamino-10-alkylacridinium or double compounds thereof.  Suitable acridine compounds are the salts of substitution products of 3 : 6-diaminoacridine and 3 : 6-diamino-10-alkylacridinium compounds and of other aminoacridines or aminoacridinium compounds or their substitution products or the corresponding double compounds.  As reducing substances may be employed the salts of sulphurous, hydrosulphurous or sulphoxylic acids, as such or in the form of derivatives, e.g. compounds with aldehydes or ketones, also hydrazines and hydroxylamines, or mixtures thereof.  Compounds advantageous for therapeutic application, e.g. glucose, adrenaline, acid amides, glycerine, pyridine, methylene blue, calcium chloride or silver salts, may also be added.  Examples describe the preparation of solutions containing: (1) 2 : 7-dimethyl-3 : 6-diamino-10-methylacridinium chloride, 2 : 7-dimethyl-3 : 6-diaminoacridine hydrochloride, sodium bisulphite and sodium sulphite; (2) 2 : 7 : 9-trimethyl-3 : 6-diamino-10-methylacridinium chloride, acetone bisulphite and glucose; (3) 2 : 7 : 9-trimethyl-3 : 6-diaminoacridine hydrochloride, phenylhydrazine acetate and glucose (to render the solution isotonic to blood); (4) 2-methyl-3-amino-6-dimethylamino - 10-methylacridinium sulphomethylate and sodium sulphite, with or without silver sulphate, methylene blue or pyridine; (5) 2 : 7-dimethyl-3-amino-6-dimethyl-amino-10-methylacridinium chloride, acetone bisulphite, sodium sulphite and glucose or an acid amide; (6) 2 : 7-dimethyl-3 : 6-tetra-methyldiamino-10-methylacridinium chloride, hydroxylamine and sodium hydrosulphite; (7) 2 : 7-dimethyl-3-amino-6-dimethylamino-10-methylacridinium chloride, sodium bisulphite and sodium sulphite.  The Specification as open to inspection under Sect. 91 describes also the preparation of tablets by mixing the substances employed in (7) with ureas, sugars or other water-soluble admixtures.  This subject-matter does not appear in the Specification as accepted.