Patent GB-764185-A (GB)
Title: Therapeutically active double salts of dicarboxylic acids and salicylic acid derivatives
IPC: C07C65/05
Filed: 1953-11-10
Abstract: The invention comprises double salts of the general formula <FORM:0764185/IV(b)/1> wherein R1 is an alkylene radical, M is an alkaline earth metal (including magnesium), and R2 is the residue of salicylic acid or an active derivative thereof, i.e. a substituted salicyclic acid in which the therapeutic properties of the unsubstituted acid are substantially retained or increased such as p-aminosalicylic acid or 5-hydroxy salicylic acid.  The compounds are made by forming a mixed salt by reacting together an alkaline earth metal oxide, hydroxide or salt, a monophenylalkyl hydrogen succinate and salicylic acid or an active derivative thereof, drying and pulverizing the product, moistening the resulting powder with an aqueous dispersion of an equivalent amount of a monophenylalkyl hydrogen succinate, adding an equivalent amount of lithium carbonate and drying the product under reduced pressure.  Suitably the alkaline earth compound, for example calcium or magnesium carbonate is reacted with the monophenylalkyl hydrogen succinate and salicylic acid or an active derivative thereof in an aqueous medium at an elevated temperature, the mixed salt is purified by washing with water and, if desired, recrystallization from an organic solvent such as acetone, the moist product is dried under reduced pressure at a temperature not exceeding 55 DEG  C. and is then treated with the lithium salt of the phenylalkyl hydrogen succinate.  The products are used as therapeutic agents either alone or admixed with other pharmaceuticals.  In examples: (1) phenylethyl hydrogen succinate salicylic acid and calcium carbonate are heated together in aqueous dispersion and the product is combined with lithium phenylethyl succinate with simultaneous admixture of aneurine hydrochloride; (2) the calcium mixed salt of p-aminosalicylic acid and phenylethyl hydrogen succinate is made and combined with lithium phenylethyl succinate as in (1) and (3), the magnesium mixed salt of phenylpropyl hydrogen succinate and gentisinic acid is made and combined with lithium phenylethyl succinate.ALSO:Therapeutic compositions comprise double salts of the general formula:- <FORM:0764185/VI/1> (see Group IV(b)) wherein R1 is an alkylene radical, M is an alkylene earth metal (including magnesium) and R2 is the residue of salicylic acid or an active derivative thereof, i.e. a substituted salicylic acid in which the therapeutic properties of the unsubstituted acid are substantially retained or increased such as p-aminosalicylic acid or 5 - hydroxysalicylic acid, admixed with a carrier and optionally with one or more vitamins, for example the vitamin B complex, vitamin B1 or vitamin C. The compositions are suitably made by forming a mixed salt by reacting an alkaline earth metal oxide, hydroxide or salt such as calcium or magnesium carbonate with a mono-phenylalkyl hydrogen succinate and salicylic acid, drying and powdering the product, moistening the powder with an aqueous dispersion of monophenylalkyl hydrogen succinate, adding lithium carbonate together with one or more vitamins if desired and preparing tablets or dragees from the finished mixture.  In examples (1) the calcium mixed salt of salicylic acid and mono-phenyl-ethyl hydrogen succinate is mixed with a solution of mono-phenylethyl hydrogen succinate, lithium carbonate and aneurine hydrochloride and the dried product is mixed with starch and talcum and made up into tablets; (2) the calcium mixed salt of p - amino - salicylic acid and mono - phenylethyl hydrogen succinate is mixed with lithium carbonate, mono-phenylethyl hydrogen succinate and aneurine hydrochloride as in (1) and made into tablets with glucose and talcum and (3) the magnesium mixed salt of mono-phenylpropyl hydrogen succinate and gentisinic acid is mixed with mono - phenylethyl hydrogen succinate, lithium carbonate and vitamin C and made into tablets as in (1).