Insulin derivative

A method of treating diabetes in a patient in need of such a treatment by the use of a therapeutically effective amount of an insulin derivative having a formula

• wherein Ins is a parent insulin moiety and Q1-Q2-[CH2]n—X1—[CH2]n-Q3-[CH2]n—X2—[CH2]n-Q4-[CH2]n—X3—[CH2]n-Q5-[CH2]n—Z is a substituent and where the Ins is attached to the substituent via an amide bond between the α-amino group of the N-terminal amino acid residue of the B chain of Ins or an ε-amino group of a Lys residue present in the A or B chain of Ins and a CO group in Q1 or Q2 of the substituent;
• Q1 is selected from the group consisting of:
• an amino acid residue, which residue forms, with its carboxylic acid group, an amide group together with the α-amino group of the N-terminal amino acid residue of the B chain of Ins or together with the ε-amino group of a Lys residue present in the A or B chain of Ins,
• a chain composed of two, three or four α-amino acid residues as specified above linked together via amide bonds, which chain is linked via an amide bond to the α-amino group of the N-terminal amino acid residue of the B chain of Ins or to the ε-amino group of a Lys residue present in the A or B chain of Ins, and
• a bond
• Q2 is selected from the group consisting of:
• —CO—(CH2)2—NH—(CH2)2—,
• —CO—CH2—NH—CH2—,
• —CO—(CH2)p—NR1—(CH2)p′—, and
• where n′=1-6, where R1 and R2, independently of each other can be H, —CH3 or —(CH2)1-6—CH3, and where p and p′ independently of each other can be 1-6;
• Q3 is —(CH2)m— where m is an integer in the range of 6 to 32;
• X1 is selected from the group consisting of:
• O,
• —C═O, and
• NCOR1, where R1 can be H, —CH3 or —(CH2)1-6—CH3, and
• where R is hydrogen, C1-3-alkyl, C2-3-alkenyl or C2-3-alkynyl;
• Q4, Q5, X2 and X3 are bonds and all n are zero;
• and
• Z is —COOH and any Zn2+ complex thereof.