GB844434A - Insulin preparations and process for preparing same - Google Patents

Abstract

An injectable composition comprises insulin, glucagon and at least one of the metals zinc (preferred), cobalt, nickel, copper, manganese, aluminium and iron distributed in an aqueous medium, the composition having a pH of between about 2 and 9 (preferably 6 to 8). The glucagon is present in a quantity of at least 1% of the weight of insulin, and the insulin-glucagon weight ratio may be between 0,5:1 and 20:1 and the metal is present in a quantity of at least 0,3 and preferably about 1 to 10 mg. equivalents per gram of the insulin and glucagon together. Buffers, preservatives, isotonisation agents, substances which prolong the effect of the composition e.g. gelatin and dextrans, and compounds which form complexes with the metal present, e.g. malic and tartaric acids, a -amino acids, e.g. glycine, leucine, aspartic and glutamic acids may also be present. The compositions may be prepared by dissolving the glucagon and metal, e.g. as a salt with a pharmaceutically accepted amine e.g. acetate which is preferred in an acid solution of insulin and adjusting the pH e.g. to about 7,0 either rapidly to give an amorphous precipitate or slowly or stepwise to give a precipitate which is wholly or partially crystalline. The crystal size may be between 0,1 and 100m (preferably 10-40m ) and may be adjusted e.g. by grinding. Other mixing sequencies may be used, e.g. insulin, glucagon and the metal salt all in acid solution may be mixed and the pH subsequently adjusted e.g. to about 6,0. The insulin used may contain or be free from zinc.