Abstract: The invention provides processes for obtaining a precursor for insulin, analogs or derivatives thereof having correctly bonded cystine bridges. The process involves solubilizing a precursor of insulin, insulin analog or derivatives in an aqueous solution or a buffer containing cysteine or cysteine hydrochloride and one or more of chaotropic auxiliary. The solubilized precursors are refolded by adding diluent to the solubilized mixture (reverse dilution). Further, the solubilized precursors, wherein the concentration of precursor in reaction mixture is more than 0.65 g/liter can also be refolded by diluting the reaction mixture with a diluent optionally comprising about 5-40% v/v of one or more of alcoholic or aprotic solvents.

Abstract: The invention provides processes for obtaining a precursor for insulin, analogs or derivatives thereof having correctly bonded cystine bridges. The process involves solubilizing a precursor of insulin, insulin analog or derivatives in an aqueous solution or a buffer containing cysteine or cysteine hydrochloride and one or more of chaotropic auxiliary. The solubilized precursors are refolded by adding diluent to the solubilized mixture (reverse dilution). Further, the solubilized precursors, wherein the concentration of precursor in reaction mixture is more than 0.65 g/litre can also be refolded by diluting the reaction mixture with a diluent optionally comprising about 5-40% v/v of one or more of alcoholic or aprotic solvents.