Patent GB-682443-A (GB)
Title: Improvements in or relating to cevitamic acid derivatives of therapeutic compounds
IPC: A61K31/375
Filed: 1948-02-23
Abstract: Ascorbates of procaine, cocaine, atropine and strychine are made by reacting l-ascorbic acid with the corresponding free base in a solvent, preferably an organic solvent (e.g. methanol) under anhydrous conditions.  A second organic solvent miscible with the first (e.g. chloroform or acetone) may then be added to precipitate the salt formed.  The Specification as open to inspection under Sect. 91 refers to the reaction between ascorbic acid (or its salts) and basic organic compounds (or their salts) in general; the products may be salts, addition products, or esters where an alkylol group is present.  There may be used sulphanilamide and its derivatives such as N1-acyl-sulphanilamides (e.g. acetyl, propionyl, valeryl, benzoyl), sulphanilyl-alkylolamides (e.g. with ethanol, propanol, butanol and higher alkylol groups), sulphapyridine, sulphathiazole, sulphathiodiazole, sulphadiazine and sulphamerazine-heterocyclic amino compounds such as 2 : 6 - diamino - 2 - ethylpyridine (sic); toxic amines such as putrescine, cadaverine and tyramine; alkaloids such as quinine, quinidine, cinchonine and their derivatives; purine and pyrimidine compounds such as theophylline, theobromine, caffeine, adenine, adenosine, guanine, guanosine, thymine, cytidine and uridine. Such ascorbates are made by the above method, zinc chloride being useful as catalyst.  Further examples are given of the reaction between ascorbic acid and acetylamino-benzene sulphochloride, sulphanilamide, sulphanil - ethanolamide (giving both salt and ester-salt), sulphathiazole, sulphadiazine and sulphamerazine. There are also mentioned the ascorbic acid esters of acylamino-benzene-sulphonalkylolamides.  The preparation of sulphanil-alkylolamides is described by reacting acetylsulphanilyl chloride with the alkylolamine and hydrolysing the acetylamino group before or after reaction with ascorbic acid. The preparation of acetylsulphanil-ethanolamide and sulphanil-ethanolamide is exemplified.  Similarly the p-nitro-compound may be used and the nitro group subsequently reduced, e.g. with activated hydrogen.  This subject-matter does not appear in the Specification as accepted.ALSO:The Specification as open to inspection under Sect. 91 mentions the reaction between ascorbic acid (or its salts) and basic azo compounds (or their salts) such as 3 : 6-diamino-2-methyl-5-phenylazopyridine, 2 : 6 - diamino - 3 - pyridyl - azopyridine and similar compounds substituted by halogen, hydroxy, alkoxy, alkyl or aryl groups.  This subject-matter does not appear in the Specification as accepted.ALSO:l-Ascorbates of procaine, cocaine, atropine and strychnine are less irritant and more soluble than the free bases and may be administered orally or parenterally or applied to open wounds.  The Specification as open to inspection under Sect. 91, refers to similar compounds of ascorbic acid with therapeutic nitrogen compounds; the products may be salts, addition products or esters. Thus there may be used sulphanilamide and its derivatives such as N1-acylsulphanilamides, sulphanilyl-alkylolamides, sulphapyridine, sulphathiazole, sulphathiodiazole, sulphadiazine and sulphamerazine; heterocyclic amino compounds such as 2:6-diamino-2-ethylpyridine (sic); azo compounds such as 3:6-diamino-2-methyl-5-phenylazopyridine, 2 : 6-diamino-3-pyridylazopyridine and their substituted derivatives; toxic amines such as putrescine, cadaverine and tyramine; alkaloids such as quinine, quinidine, cinchonine and their derivatives; purine and pyrimidine compounds such as theophylline, theobromine, caffeine, adenine, adenosine, guanine, guanosine, thymine, cytidine and uridine.  The ascorbates may be applied as tablets, powders or aqueous solutions.  This subject-matter does not appear in the Specification as accepted.