Patent ID: 7884181

Claim:
A method for preparing a pharmaceutical product comprising Asp B28 human insulin, protamine, Zn ++ , an isotonicity agent, a phenolic compound, and salt in the amount of from about 7mM to about 40mM, wherein the weight ratio of dissolved to crystalline Asp B28 human insulin is 30:70, said method comprising the steps of: a) providing an acidic solution comprising insulin Asp B28 human, a source of zinc, a suitable amount of protamine, optionally further comprising a phenolic compound, and/or an isotonicity agent, and/or salt, b) providing an alkaline solution comprising a substance which acts as a buffer at physiological pH, and optionally further comprising salt, and/or a phenolic compound and/or isotonicity agent, c) mixing the acidic and alkaline solutions, d) leaving the mixture to form the pharmaceutical composition which comprises a soluble phase comprising the dissolved Asp B28 human insulin, and a phase with the crystalline Asp B28 human insulin, wherein the crystallization mixture contains from about 20% to about 85% of the total amount of phenolic compound in the end product, e) adding the remaining phenolic compound and optionally adjusting pH and optionally adding remaining salt, and/or isotonicity agent, wherein the phenolic compound is selected from the group consisting of phenol, m-cresol, or a mixture thereof, and wherein m-cresol is only added in step e).