Rapid-acting insulin compositions

Abstract

The invention is a pharmaceutical composition of human insulin or insulin analog that includes citrate, treprostinil and stabilizing agents, that has faster pharmacokinetic and/or pharmacodynamic action than commercial formulations of existing insulin analog products and that is stable for commercial use.

1 - 33 . (canceled) 
     
     
         34 . A pharmaceutical composition comprising:
 a. an insulin;   b. citrate, in a concentration from about 5 to about 25 mM;   c. treprostinil, in a concentration from about 0.04 to about 20 μg/mL; and   d. zinc, in a concentration sufficient to provide at least 2 zinc ions per six molecules of insulin;   and having a pH of about 7.0 to about 7.8 at room temperature.   
     
     
         35 . The pharmaceutical composition of  claim 34  wherein the zinc concentration is from about 0.2 to about 2 mM. 
     
     
         36 . The pharmaceutical composition of  claim 34 , wherein the zinc concentration is from about 0.6 to about 0.8 mM. 
     
     
         37 . The pharmaceutical composition of  claim 36 , further comprising magnesium chloride. 
     
     
         38 . The pharmaceutical composition of  claim 37  wherein the concentration of magnesium chloride is about 5 mM. 
     
     
         39 . The pharmaceutical composition of  claim 38  wherein the insulin is insulin lispro. 
     
     
         40 . The pharmaceutical composition of  claim 39  wherein the insulin lispro is present in a concentration from about 100 to about 200 U/mL. 
     
     
         41 . The pharmaceutical composition of  claim 40  further comprising glycerol. 
     
     
         42 . The pharmaceutical composition of  claim 41  wherein the concentration of glycerol is about 12 mg/mL. 
     
     
         43 . The pharmaceutical composition of  claim 42  further comprising a preservative. 
     
     
         44 . The pharmaceutical composition of  claim 43  wherein the preservative is m-cresol. 
     
     
         45 . The pharmaceutical composition of  claim 44  wherein the concentration of m-cresol is about 3.15 mg/mL. 
     
     
         46 . The pharmaceutical composition of  claim 45  wherein the pharmaceutical composition is stable for at least 24 months at 2-8° C. 
     
     
         47 . The pharmaceutical composition of  claim 46  wherein the pharmaceutical composition is stable for up to 28 days at temperatures of up to 30° C. 
     
     
         48 . The pharmaceutical composition of  claim 34  wherein the pharmaceutical composition does not contain EDTA. 
     
     
         49 . The pharmaceutical composition of  claim 34  wherein the pharmaceutical composition does not contain any additional vasodilatory agent. 
     
     
         50 . The pharmaceutical composition of  claim 34  wherein the pharmaceutical composition does not contain any oligosaccharides. 
     
     
         51 . The pharmaceutical composition of  claim 34  wherein:
 a. the insulin is insulin lispro, and is present in a concentration from about 100 to about 200 U/mL; 
 b. citrate is in a concentration of about 15 mM; 
 c. treprostinil is in a concentration of about 1 μg/mL; 
 d. zinc is in a concentration from about 0.6 to about 0.8 mM; 
 
       and wherein the pharmaceutical composition further comprises:
 e. m-cresol, in a concentration of about 3.15 mg/mL; 
 f. glycerol, in a concentration of about 12 mM; and 
 g. magnesium chloride, in a concentration of about 5 mM; 
 and wherein the pharmaceutical composition does not contain EDTA, any additional vasodilatory agents or any oligosaccharides.