Patent GB-611106-A (GB)
Title: Process of producing water soluble substances having both bacteriostatic and vasoconstrictive qualities
IPC: A61K31/16
Filed: 1945-06-12
Abstract: Water - soluble salts of N1 - acyl - p - aminobenzenesulphonamides with phenylalkylamines and phenylalkylolamines are prepared by the reaction of the sulphonamide and the amine in the presence of a solvent such as methanol or ethanol.  The products may be isolated in the solid form, but for therapeutic purposes aqueous solutions, in which the sulphanilamide compounds are preferably in excess, may be prepared by mixing the amine and the sulpha drug or a salt of the amine and a metallic salt of the sulpha drug, in situ.  In examples: (1) sulphacetamide (N1-acetyl-p-aminobenzenesulphonamide) is treated with ephedrine in methyl alcohol; the ephedrine salts of N3-propionyl-, N1-acryloyl-, N1-crotonyl-, N1-benzoyl- and N1-3 : 4-dimethylbenzoyl-p-aminobenzenesulphonamide may be similarly prepared and also the salts of desoxyephedrine, pseudoephedrine, 3 : 4 - dihydroxyphenylpropanolamine, a  - hydroxy-b -methylaminoethyl-3-hydroxybenzene and adrenalin; (3) sulphacetamide and ephedrine are admixed in aqueous solution and (4) the sodium salt of sulphacetamide in excess is admixed with ephedrine sulphate in aqueous solution with the addition of a small amount of sodium thiosulphate as an antioxidant.  Samples have been furnished under Sect. 2 (5) of the pseudoephedrine salt of N1-acetylsulphanilamide, the desoxyephedrine salt of N1-acetylsulphanilamide and the ephedrine salts of N1-nonoyl-, N1-dodecanoyl-, N1-palmitoyl-, N1 - D 9 - undecenoyl- and N1 - benzoyl - sulphanilamide.  Reference has been directed by the Comptroller to Specification 595,592.ALSO:Compositions used in solution for the treatment of the nasal mucosa and having both bacteriostatic and vasoconstrictive properties comprise substantially neutral water soluble salts of N1-acyl-p-amino benzenesulphonamides with phenylalkylamines or phenylalkylolamines admixed with an extending medium.  The compositions may be prepared in situ by adding the sulpha drug or a metallic salt thereof (preferarably in excess) to the amine or amine salt, in the desired amount of water.  Suitable amines are ephedrine, desoxyephedrine, 3:4-dihidroxyphenyl propanolamine, a -hydroxy-b -methylaminoethyl-3-hydroxybenzene and andrenalin. Suitable sulphanilamide compounds are the N1-acetyl-N1-propionyl-, N1-acryloyl-, N1-crotonyl- N1-benzoyl- and N1-3:4-dimethyl benzoyl-p-aminobenzene suphonamides.  In examples: (2) and (3) the ephedrine salt of sulphacetamide is dissolved in water, (4) ephedrine sulphate is added to a solution of sulphacetamide in aqueous sodium hydroxide and a small amount of sodium thiosulphate is added as a stabilizer; (5) a composition similar to that of (4) is prepared using an aqueous solution of methyl-p-hydroxybenzoate and rendering isotonic by the addition of sodium chloride; (6) desoxyephedrine chloride is used in place of ephedrine sulphate in (5); and (7) sodium metabisulphate is used in place of sodium thiosulphate in (5). Samples have been furnished under Sect. 2(5) of the pseudoephedrine salt of N1-acetylsulphanilamide, the desoxyephedrine salt of N1-acetylsulphanilamide and the ephedrine salts of N1-nonoyl-, N1-dodecanoyl, N1-palmitoyl-, N1-D  9-undecenoyl- and N1-benzoyle-, sulphanilamide.  Reference has been directed by the Comptroller of Specification 595,592.