GB751425A - Manufacture of injectable insulin preparations with protracted effect - Google Patents

Abstract

An injectable insulin preparation having protracted effect comprises a sterile suspension of amorphous zinc protamine insulin in an aqueous medium of pH between 6 and 8, the suspension being free from any substance capable of forming a slightly soluble zinc compound or complex at pH 7. The zinc may be wholly or partly replaced by cadmium, cobalt, nickel, copper, manganese or iron in divalent form or mixtures thereof, and the protamine by histone, surfen or rivanol. The suspension contains protamine in amount not exceeding that necessary for precipitation of the insulin e.g. 2 to 5 mg per 1000 I.U. insulin, and the zinc in amount greater than 0,25 mg per 1000 I.U. insulin. The starting material which may be amorphous or crystalline insulin may provide the whole or part of the zinc content of the final suspension. The protamine, insulin and zinc compound e.g. chloride, sulphate, nitrate, hydroxide, oxide, acetate, may be mixed in any sequence in the aqueous medium which may also contain buffer substances e.g. acetate, barbital, borate, maleate, preserving agents e.g. methyl- or propyl-p-hydroxybenzoate, phenyl mercuric acetate, and isotonic substances e.g. glucose, sodium chloride, glycerol, to form sterile suspensions. Suitable protamines are salmidrine, clupeine, scombrine, sturine, thymine, cyprinine and cyclopterine which may be in the form of salts of inorganic or organic acids.