NEW INSULIN DERIVATIVES WITH A STRONGLY SLOW PROFILE TIME / ACTION

摘要

1. An insulin analogue of the formula I! ! where A-1 corresponds to Lys, Arg or an amino group; ! A0 corresponds to Lys, Arg, or a chemical bond; ! A1 corresponds to Arg or Gly; ! A5 corresponds to Asp, Glu or Gln; ! A15 corresponds to Asp, Glu or Gln; ! A18 corresponds to Asp, Glu or Asn; ! A21 corresponds to Ala, Ser, Thr or Gly; ! B-1 corresponds to Asp, Glu or an amino group; ! B0 corresponds to Asp, Glu or a chemical bond; ! B1 corresponds to Asp, Glu, Phe or a chemical bond; ! B3 corresponds to Asp, Glu or Asn; ! B4 corresponds to Asp, Glu or Gln; ! B29 corresponds to Arg, Lys or an amino acid of a selected group containing the following amino acids: Phe, Ala, Thr, Ser, Val, Leu, Glu or Asp, or a chemical bond; ! B30 corresponds to Thr or a chemical bond; ! B31 corresponds to Arg, Lys or a chemical bond; ! B32 corresponds to Arg amide or Lys amide,! where no more than one amino acid residue of the group containing A5, A15, A18, B-1, B0, B1, B2, B3 and B4, simultaneously and independently from the others, corresponds to Asp or Glu. ! 2. The insulin analogue according to claim 1, where A-1 corresponds to Arg. ! 3. The insulin analogue according to claim 1, where A0 corresponds to Arg. ! 4. The insulin analogue according to claim 1, where A5 corresponds to Glu. ! 5. The insulin analogue according to claim 1, where A15 corresponds to Glu. ! 6. The insulin analogue according to claim 1, where A18 corresponds to Asp. ! 7. The insulin analogue according to claim 1, where A8 corresponds to His. ! 8. The insulin analogue according to claim 1, where A21 corresponds to Gly. ! 9. The insulin analogue according to claim 1, where B0 corresponds to Glu. ! 10. The insulin analogue according to claim 1, where B3 corresponds to Asp. ! 11. The insulin analogue according to claim 1, where B4 corresponds to Glu. ! 12. The insulin analogue according to claim 1, where B30 corresponds to Arg. ! 13. The insulin analogue according to claim 1, where B30 corresponds to Lys. ! 14. The insulin analogue according to claim 1, containing the following compounds:! Arg (A-1), Arg (A0), Glu (A5), His (A8), Gly (A21), Arg (B30) -NH2-human insulin ! Arg (A-1), Arg (A0), Glu (A5), His (A8), Gly (A21), Lys (B30) -NH2-human insulin,! Arg (A-1), Arg (A0), Glu