Monomeric insulin analog formulations
First Claim
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1. A parenteral pharmaceutical insulin analog-protamine formulation, consisting essentially of:
- a monomeric insulin analog, protamine, zinc, and a phenolic derivative;
wherein a monomeric insulin analog is human insulin wherein Pro at position B28 is substituted with Lys, Leu, Val, or Ala;
Lys at position B29 is Lys or Pro;
des(B28-B30)-human insulin;
or des(B27)-human insulin.
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Abstract
The present invention discloses various parenteral pharmaceutical formulations, which comprise: a monomeric insulin analog, zinc, protamine, and phenolic derivative. The analog formulations provide a prolonged duration of action. A process for preparing insulin analog-protamine formulations is also described.
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Citations
21 Claims
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1. A parenteral pharmaceutical insulin analog-protamine formulation, consisting essentially of:
- a monomeric insulin analog, protamine, zinc, and a phenolic derivative;
wherein a monomeric insulin analog is human insulin wherein Pro at position B28 is substituted with Lys, Leu, Val, or Ala;
Lys at position B29 is Lys or Pro;
des(B28-B30)-human insulin;
or des(B27)-human insulin. - View Dependent Claims (2, 3, 4, 20, 21)
- a monomeric insulin analog, protamine, zinc, and a phenolic derivative;
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5. A parenteral pharmaceutical formulation, which comprises:
- a monomeric insulin analog, about an isophane ratio of protamine, about 0.35 to about 0.9% zinc by weight, and a phenolic derivative;
wherein a monomeric insulin analog is human insulin wherein Pro at position B28 is substituted with, Lys, Leu, Val, or Ala;
Lys at position B29 is Lys or Pro;
des(B28-B30)-human insulin or des(B27)-human insulin. - View Dependent Claims (12)
- a monomeric insulin analog, about an isophane ratio of protamine, about 0.35 to about 0.9% zinc by weight, and a phenolic derivative;
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6. A parenteral pharmaceutical formulation, consisting essentially of:
- LysB28 ProB29 -human insulin, about 0.27 to about 0.32 mg protamine/100 U of insulin analog, about 0.35 to about 0.9% zinc by weight, and a phenolic derivative.
- View Dependent Claims (7, 8, 9, 10, 11)
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13. A process for preparing LysB28 ProB29 -human insulin-protamine crystals, which comprises:
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combining an aqueous solution of LysB28 ProB29 -human insulin in a hexamer association state, and a protamine solution at a temperature from about 8°
C. to about 17°
C. to form crystals;said aqueous solution comprising from about 0.35 to about 0.9% zinc by weight, LysB28 ProB29 -human insulin, and a phenolic derivative at a pH of about 7.1 to about 7.6; said protamine solution comprising protamine at a pH of about 7.1 to about 7.6 such that the final concentration of protamine is about 0.27 to about 0.32 mg protamine/100 U of insulin analog provided that the process is carried out in less than 4 mg/mL sodium chloride. - View Dependent Claims (14, 15)
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16. A parenteral pharmaceutical formulation, which comprises:
- a mixture of soluble monomeric insulin analog and insulin analog-NPD crystals, in an aqueous diluent wherein the ratio of the two insulin analogs is about 1;
99-99;
1 by volume insulin analog-NPD to soluble monomeric insulin analog, and wherein said soluble monomeric insulin analog is human insulin wherein Pro at position B28 is substituted with Lys, Leu, Val, or Ala;
Lys at position B29 is Lys or Pro;
des(B28-B30)-human insulin or des(B27)-human insulin. - View Dependent Claims (17, 18, 19)
- a mixture of soluble monomeric insulin analog and insulin analog-NPD crystals, in an aqueous diluent wherein the ratio of the two insulin analogs is about 1;
Specification