Long-Acting Formulations of Insulin

Abstract

The application relates to an aqueous pharmaceutical formulation comprising 200-1000 U/mL [equimolar to 200-1000 IU human insulin] of insulin glargine.

1 . An aqueous pharmaceutical formulation comprising 200-500 U/mL of insulin glargine [equimolar to 200-500 IU human insulin]. 
     
     
         2 . The aqueous pharmaceutical formulation of  claim 1  comprising 200 U/mL of insulin glargine [equimolar to 200 IU human insulin]. 
     
     
         3 . The aqueous pharmaceutical formulation of  claim 1  comprising 500 U/mL of insulin glargine [equimolar to 500 IU human insulin]. 
     
     
         4 . The aqueous pharmaceutical formulation of  claim 1  further comprising at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20. 
     
     
         5 . The aqueous pharmaceutical formulation of  claim 4  further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%. 
     
     
         6 . The aqueous pharmaceutical formulation of  claim 5 , wherein the zinc is present in the form of zinc chloride. 
     
     
         7 . The aqueous pharmaceutical formulation of  claim 1 , wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6. 
     
     
         8 . The aqueous pharmaceutical formulation of  claim 7 , wherein the pH of the aqueous pharmaceutical formulation is 4.0. 
     
     
         9 . An aqueous pharmaceutical formulation comprising 200 U/mL of insulin glargine [equimolar to 200 IU human insulin] wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6. 
     
     
         10 . The aqueous pharmaceutical formulation of  claim 9 , wherein the pH of the aqueous pharmaceutical formulation is 4.0. 
     
     
         11 . The aqueous pharmaceutical formulation of  claim 9  further comprising at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20. 
     
     
         12 . The aqueous pharmaceutical formulation of  claim 11  further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%. 
     
     
         13 . The aqueous pharmaceutical formulation of  claim 12 , wherein the zinc is present in the form of zinc chloride. 
     
     
         14 . The aqueous pharmaceutical formulation of  claim 1 , wherein the pharmacokinetic profile and the pharmacodynamic profile of the aqueous pharmaceutical formulation following administration to a patient are flatter than the pharmacokinetic profile and the pharmacodynamic profile of an aqueous pharmaceutical formulation comprising 100 U/mL of insulin glargine, and wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6. 
     
     
         15 . The aqueous pharmaceutical formulation of  claim 14 , wherein the pH of the aqueous pharmaceutical formulation is 4.0. 
     
     
         16 . The aqueous pharmaceutical formulation of  claim 14  further comprising at least one excipient selected from the group consisting of zinc ion, m-cresol, glycerol, and polysorbate 20. 
     
     
         17 . The aqueous pharmaceutical formulation of  claim 16  further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%. 
     
     
         18 . The aqueous pharmaceutical formulation of  claim 17 , wherein the zinc is present in the form of zinc chloride. 
     
     
         19 . The aqueous pharmaceutical formulation of  claim 1 , wherein the aqueous pharmaceutical formulation provides a peakless long acting basal insulin, and wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6. 
     
     
         20 . The aqueous pharmaceutical formulation of  claim 1 , wherein the aqueous pharmaceutical formulation exhibits an extended duration of exposure of insulin glargine than an aqueous pharmaceutical formulation comprising 100 U/mL insulin glargine, and wherein the pH of the aqueous formulation is between 3.4 and 4.6.