Patent GB-776494-A (GB)
Title: New chemotherapeutic products and methods of preparing them
IPC: A61K31/63
Filed: 1955-05-18
Abstract: A process for the production of new chemotherapeutic products consists in combining sulphanilic acid amides, isonicotinic acid hydrazide and/or p-aminosalicylic acid or its alkali metal salts with saturated aliphatic or cyclic aminopolycarboxylic acids which are known to form metal complexes or with the alkali metal, alkaline earth metal, ammonium or amine salts of said aminopolycarboxylic acids, care being taken that the reaction components together contain at least one free carboxylic group. The combination is preferably effected at a pH between 3 and 8, the pH being adjusted by addition of alkali, ammonia, ethanolamines or aliphatic amines. Amino-polycarboxylic acids specified are nitrilotriacetic acid, ethylenediamine tetra-acetic acid, 1,2-diaminocyclohexane-N,N1-tetra-acetic acid and pyrrolidine-2.5-dicarboxylic acid-N-acetic acid.  In examples: (1) isonicotinic acid hydrazide and the disodium salt of ethylenediamine tetra-acetic acid are dissolved together in water to give a solution of pH 5; (2) a solution of isonicotinic acid hydrazide and ethylene diamine tetra-acetic acid (of pH 3.5) is evaporated to dryness and the products pressed into tablets, if desired with p-aminosalicylic acid or its sodium salt; (3) ethylenediamine tetra-acetic acid trisodium salt is dissolved in an aqueous solution of sulphanilamide which is evaporated to dryness or diluted for further use.  Further examples describe the preparation of similar aqueous solutions from (4) the acid calcium salt of ethylene diamine tetra-acetic acid, diethanolamine and isonicotinic acid hydrazide; (5) p-aminosalicylic acid, ethylenediamine tetra-acetic acid and diethanolamine; (6) p-aminosalicylic acid and the tetra-sodium salt of ethylene diamine tetra -acetic acid; (7) p-aminosalicylic acid and ethylenediamine tetra-acetic acid trisodium salt; (8) sodium p-aminosalicylate and the tri-sodium salt of ethylenediamine tetra-acetic acid; (9) ethylene-diamine tetracetic acid di-sodium salt and sodium p-aminosalicylate; (10) p-aminosalicylic acid, ethylenediamine-tetra -acetic acid and mono di- or tri-ethanolamine; (11) p-aminosalicylic acid and the trisodium salt of nitrilotriacetic acid; (12) nitrilotriacetic acid and isonicotinic acid with sodium hydroxide sufficient to give a pH of 7.5; (13) free nitrilotriacetic acid, the corresponding trisodium salt, p-aminosalicylic acid, isonicotinic acid hydrazide and sufficient sodium hydroxide to give a pH of 7.6. In some cases the solutions are evaporated to dryness.ALSO:Chemotherapeutic products which can be used in solution for injection purposes, or in the form of tablets, are obtained by combining sulphanilic acid amides, isonicotinic acid hydrazide and/or p-aminosalicyclic acid or its alkali metal salts with saturated aliphatic or cyclic aminoply-carboxylic acids which are known to form metal complexes or with the alkali metal, alkaline earth metal, ammonium or amine salts of such acids, care being taken that the reaction components together contain at least one carboxylic group. Aminopolycarboxylic acids specified are nitrilotriacetic acid, ethylenediamine tetra-acetic acid and pyrrolidine - 2,5 - dicarboxylic acid - N - acetic acid.  In examples (1) isonicotinic acid hydrazide and the disodium salt of ethylenediamine tetra-acetic acid are dissolved together in water to give a solution of pH 5; (2) a solution of isonicotinic acid hydrazide and ethylene diamine tetra-acetic acid is evaporated to dryness and the products pressed into tablets, if desired with p-aminosalicylic acid or its sodium salt; (3) ethylene diamine tetra-acetic acid trisodium salt is dissolved in an aqueous solution of sulphanilic acid which is evaporated to dryness or diluted for further use.  Further examples describe the preparation of similar solutions from (4) the acid calcium salt of ethylene diamine tetra-acetic acid, diethanolamine and isonicotinic acid hydrazide, (5) p-aminosalicylic acid, ethylenediamine tetraacetic acid and diethanolamine, (6) p-aminosalicylic acid and the tetra sodium salt of ethylene diamine tetra-acetic acid; (7) p-aminosalicylic acid and ethylene diamine tetra-acetic acid trisodium salt; (8) sodium p-aminosalicylate and the trisodium salt of ethylene diamine tetra-acetic acid; (9) ethylene diamine tetra-acetic acid disodium salt and sodium and sodium p-aminosalicylate; (10) p-aminosalicylic acid, ethylene diamine tetra-acetic acid and mono-, di-, or triethanolamine; (11) p-aminosalicylic acid and the trisodium salt of nitrilotriacetic acid; (12) nitrilotriacetic acid and isonicotinic acid with sodium hydroxide sufficient to give a pH of 7.5; (13) free nitrilotriacetic acid, the corresponding tri-sodium salt, p-aminosalicylic acid, isonicotinic acid hydrazide and sufficient sodium hydroxide to give a pH of 7.6.  In some cases the solutions are evaporated to dryness.