| 摘要 |
An insulin analogue contains one or more modifications at a distinct protein surface comprising one or more of the residues at position B13, B17, A12, A13, and/or A17. Formulations of the above analogues at successive strengths U-100 to U-1000 in soluble solutions a at least pH value in the range 6.8-8.0 either in the presence of zinc ions at a molar ratio of 2.2-10 zinc ions per six insulin analogue monomers or in the presence of fewer than 1 zinc ions per six insulin analogue monomers. Use of the above formulation in an insulin pump functionally integrated with a continuous glucose monitor and computer-based control algorithm as a closed-loop system. A method of treating a patient with diabetes mellitus comprises administering a physiologically effective amount of the insulin analogue to a patient by means of intravenous, intraperitoneal, or subcutaneous injection. |
| 主权项 |
1. An insulin analogue containing at least one substitution relative to wild type insulin comprising a substitution at a position selected from the group consisting of:
an Ala, Asp, His, or Leu substitution at B13, a Glu, Gln, Ala, His, Trp or Tyr substitution at B17, an Ala, Thr, Asp, Asn, Glu, Gln, His or Tyr substitution at A12, an Ala, Glu, Gln, His, Tyr, Phe or Trp substitution at A13, and an Ala, Gln, His, Trp, or Tyr substitution at A17. |
