Patent GB-1033844-A (GB)
Title: Combinations of aluminum-chelating therapeutic adjuvants and aluminum chelates and process for making and using the same
IPC: C07C51/41
Filed: 1964-09-03
Abstract: Aluminium chelates, having the empirical formula <FORM:1033844/C2/1> wherein m, n, x, y are numbers whose sum balances the positive valences of the aluminium and metal M, which represents a non-toxic alkali or alkaline-earth metal or bismuth, m + y is the total number of gram atoms of the metal M, m + n is the total number of gram molecular weights of the a - or b -hydroxy alphatic carboxylic acid, R being the residue thereof, and m is from 1 to 3, n from 0 to 3, and y from 0 to 1.5, are prepared by reacting an appropriate aluminium compound, e.g. an alkali metal aluminate or aluminium hydroxide or Al2(OH)xCly, where x + y = 6 and x and y are at least 1, with a suitable a - or b -aliphatic hydroxy carboxylic acid, e.g. lactic, glycolic, gluconic, trihydroxy glutaric, citryl trigluconic, tartaric, malic, citric, citramalic or tetrahydroxy adipic acid.  In typical examples: a sodium aluminium lactate chelate (weight ratio lactic acid: aluminium 2.5: 1) was prepared by reacting sodium aluminate with a lactic acid-sodium lactate solution in water; a sodium aluminium chlorhydroxy lactate was prepared by mixing Al2(OH)5Cl with lactic acid in water, adding NaOH to adjust pH to 6.2, and evaporating water therefrom; magnesium aluminium hydroxy lactate was prepared by mixing aluminium hydroxide gel with lactic acid in deionized water, adding magnesium carbonate to the heated aqueous solution, and evaporating water to leave a dry solid.ALSO:Therapeutic antacid compositions consist of an aluminium-chelating therapeutic agent having at least one radical (e.g. a hydroxyl, keto carboxyl, ester, amino or amido group) available for chelation with aluminium and an aluminium chelate of an a - or b -hydroxy aliphatic carboxylic acid, having a pH in aqueous solution of about 3 to about 9, and having the empirical formula <FORM:1033844/A5-A6/1> wherein m, n, x, and y are numbers whose sum balances the positive valences of the metal M and aluminium, m + n equals the total number of gram molecular weights of the hydroxy aliphatic carboxylic acid, m + y equals the total number of gram atoms of the metal, m is from 1 to 3, n is from 0 to 3, y is from 0 to 1.5, M is a non-toxic alkali or alkaline earth metal or bismuth, and R represents the residue of the hydroxy aliphatic carboxylic acid, which has at least one hydroxy group and at least one carboxylic acid group for each one to six carbon atoms, the aluminium chelate being present in an amount to maintain the pH of artificial gastric juice (as determined by the Holbert, Noble, and Grote test method) from about 3 to about 9 for at least one hour.  The hydroxy aliphatic carboxylic acid residue may be derived from lactic, glycolic, gluconic, trihydroxy glutaric, citryl trigluconic, tartaric, malic, citric, citramalic or tetrahydroxy adipic acid. Preferred aluminium chelating therapeutic agents are anticholinergics e.g. diethyl (2-hydroxyethyl) methyl ammonium a -phenyl cyclohexaneglycolate bromide, scopolamine methyl bromide, (3-carbamoyl-3, 3-diphenylpropyl) diisopropylmethyl ammonium iodide; antispasmodics e.g. atropine sulphate, 2-diethylaminoethyl diphenylacetate hydrochloride, meperidine hydrochloride; analgesics and antipyretics e.g. aspirin, acetophenetidin, optionally with citrated caffeine, sodium acetylsalicylate, salicylic acid, salicylamide, acetanilide and 41-hydroxyacetanilide; sedatives and hypnotics e.g. phenobarbital, barbital, 2-monobromoisovalerylurea, scopolamine hydrobromide; antitubercular preparations e.g. p-amino-salicylic acid, 2-ethylthioisomicotinamide; diuretics e.g. aminophylline; antirheumatics e.g. p-amino benzoic acid together with salicylates; antianaemia agents e.g. ferrous gluconate; anti-hypercholesterimia agents e.g. nicotinic acid; urinary antiseptics e.g. mandelic acid.  The compositions may be orally administered in standard solid or liquid dosage unit forms with conventional excipients.