INSULIN DERIVATIVE INCREASED IN ZINC BOND

PROBLEM TO BE SOLVED: To obtain the subject new derivative having a specific amino acid sequence containing a cyclic structure, having increased zinc bonding force, forming a stable complex containing Zn , having a delayed-type acting profile by hypodermic injection and useful for treatment, etc., of diabetes mellitus. SOLUTION: This new insulin derivative (salt) is represented by the formula [R is phenylalanine residue or H; R3 and Y are each an amino acid residue capable of genetically coding; Z is an amino acid residue His or a peptide having 2-35 amino acid residues containing 1-5 histidine residues and capable of genetically coding; the residues A2 to A20 respectively correspond to an amino acid sequence of A chain of human insulin, an animal insulin or insulin derivatives; B2 to B29 respectively correspond to an amino acid sequence of B chain of human insulin, animal insulin or insulin derivatives]. The objective insulin derivative has increased zinc bonding force, compared with human insulin and forms a stable complex containing insulin hexamer and Zn and is suitable for production, etc., of medicines for treating diabetes mellitus.