GB1076219A — Parenteral iron preparations

USPTO Abstract

A non-ionic iron-carbohydrate complex is formed of 1 mol. of ferric hydroxide and 1 mol. of a complex-forming agent consisting of a mixture of sorbitol (about 0.4 mol.), gluconic acid (about 0.3 mol.) and a polyglucose (about 0.3 mol.), the polyglucose comprising dextrin, dextran, hydrogenated dextrin or hydrogenated dextran having intrinsic viscosity 0.01-0.025 at 25 DEG C., and average molecular weights 500-1200. The hydrogenated polyglucoses are substantially non-reducing to Somogyi reagent. The complex is made by treating 1 mol. of a trivalent iron compound in aqueous solution with about 2 mols. of complex-forming agent having the molar ratio of sorbitol: gluconic acid: polyglucose about 1.15: 0.40: 0.5, and heating the mixture at an alkalene pH. In one embodiment, aqueous solutions of ferric chloride and alkali are added to an aqueous solution of carbohydrate at 60 DEG C., and the reaction mixture (pH 9-9.5) heated to boiling for 5-30 minutes. Alternatively, a carbohydrate solution and alkali are added to an aqueous suspension of freshly-precipitated ferric hydroxide. In a further embodiment, an acid-complex is made by adding to aqueous ferric chloride, at room temperature, aqueous carbohydrate solution and sufficient sodium carbonate or bicarbonate solution to produce a pH of 2.5, increasing the pH to about 9.5 by addition of sodium hydroxide and heating to boiling. The complex is isolated by precipitation from the cooled and neutralized solution. The complex may contain 21-26% iron and aqueous solutions containing 5-10% iron may be formed therefrom for therapeutic use (Divisions A5-A6). The hydrogenation of dextrin is described.ALSO:A non-ionic iron-carbohydrate complex is formed of 1 mol of ferric hydroxide and 1 mol of a complex-forming agent consisting of a mixture of sorbitol (about 0.4 mol), gluconic acid (about 0.3 mol) and a polyglucose (about 0.3 mol), the polyglucose comprising dextrin, dextran, hydrogenated dextrin or hydrogenated dextran having intrinsic viscosity 0.01-0.025 at 25 DEG C., and average molecular weights 500-1200. The hydrogenated polyglucoses are substantially non-reducing to Somogyi reagent. The complex is made by treating 1 mol of a trivalent iron compound in aqueous solution with about 2 mols of complex-forming agent having the molar ratin of sorbitol : gluconic acid : polyglucose about 1.15:0.40:0.5, and heating the mixture at an alkaline pH. In one embodiment, aqueous solutions of ferric chloride and alkali are added to an aqueous solution of carbohydrate at 60 DEG C., and the reaction mixture (pH 9-9.5) heated to boiling for 5-30 minutes. Alternatively, a carbohydrate solution and alkali are added to an aqueous suspension of freshly-precipitated ferric hydroxide. In a further embodiment, an acid-complex is made by adding to aqueous carbohydrate solution and sufficient sodium carbonate or bicarbonate solution to produce a pH of 2.5, increasing the pH to about 9.5 by addition of sodium hydroxide and heating to boiling. The complex is isolated by precipitation from the cooled and neutralized solution. The complex may contain 21-26% iron and aqueous solutions containing 5-10% iron may be formed therefrom for therapeutic use (Division A5-A6). The hydrogenation of dextrin is described.ALSO:A therapeutic iron preparation comprises an aqueous solution of a non-ionic iron-carbohydrate complex formed of 1 mol of ferric hydroxide and 1 mol of a complex-forming agent consisting of a mixture of sorbitol (about 0.4 mol), gluconic acid (about 0.3 mol) and a poly glucose (about 0.3 mol), the poly-glucose comprising dextrin, dextran, hydrogenated dextrin or hydrogenated dextran having intrinsic viscosity 0.01-0.25 at 25 DEG C and average molecular weight 500-1200. The solution, which may contain 5-10% iron, are administered by intramuscular injection.