Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives

Abstract

Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives are disclosed.

1 . A pharmaceutical formulation comprising 
 (a) at least one analogue and/or derivative of insulin;   (b) Zn(II);   (c) sorbitol; and   (d) optionally protamine.   
     
     
         2 . The pharmaceutical formulation according to  claim 1 , wherein the pharmaceutical formulation is an aqueous pharmaceutical formulation. 
     
     
         3 . The pharmaceutical formulation according to  claim 1 , wherein the pharmaceutical formulation has a pH value in the range from 6.0 to 9.0. 
     
     
         4 . The pharmaceutical formulation according to  claim 3 , wherein the pharmaceutical formulation has a pH value in the range from 7.0 to 7.8. 
     
     
         5 . The pharmaceutical formulation according to  claim 1 , wherein the analogue of insulin is selected from the group consisting of insulin aspart, insulin lispro and insulin glulisine. 
     
     
         6 . The pharmaceutical formulation according to  claim 1   , wherein the derivative of insulin is insulin detemir and/or insulin degludec.   
     
     
         7 . The pharmaceutical formulation according to  claim 1 , wherein the analogue and/or derivative of insulin is present in a concentration from 10 U/mL to 1000 U/mL. 
     
     
         8 . The pharmaceutical formulation according to  claim 1 , wherein Zn(II) is present in a concentration from 0.0100 to 0.0600 mg / 100 U of the analogue and/or derivative of insulin. 
     
     
         9 . The pharmaceutical formulation according to  claim 1 , wherein the pharmaceutical formulation further contains sodium chloride. 
     
     
         10 . The pharmaceutical formulation according to  claim 9 , wherein sodium chloride is present in a concentration from 0.01 to 6.0 mg/mL. 
     
     
         11 . The pharmaceutical formulation according to  claim 1 , wherein protamine is present in a concentration from 0.1 to 0.5 mg/mL. 
     
     
         12 . The pharmaceutical formulation according to  claim 1 , wherein the pharmaceutical formulation comprises one or more further active pharmaceutical ingredients. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The pharmaceutical formulation according to  claim 1 , wherein the pharmaceutical formulation comprises more than one analogue and/or derivative of insulin, wherein one analogue and/or derivative of insulin is a fast acting insulin and one analogue and/or derivative of insulin is a long acting insulin. 
     
     
         16 - 18 . (canceled) 
     
     
         19 . A process for preparing the pharmaceutical formulation according to  claim 1 , wherein the components are mixed together in the form of a solution or suspension, the pH is adjusted to reach a desired pH and water is added to reach a final volume. 
     
     
         20 . A kit comprising one or more separate packages of
 (a) the pharmaceutical formulation according to  claim 1 ; and   (b) a medical device.   
     
     
         21 . A kit comprising one or more separate packages of
 (a) the pharmaceutical formulation according to  claim 1 ; and   (b) at least one further active pharmaceutical ingredient; and   (c) optionally a medical device.   
     
     
         22 - 28 . (canceled) 
     
     
         29 . A method of treating diabetes mellitus in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the pharmaceutical formulation of  claim 1 . 
     
     
         30 . A method of treating hyperglycemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the pharmaceutical formulation of  claim 1 . 
     
     
         31 . A method of lowering blood glucose levels in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the pharmaceutical formulation of  claim 1 . 
     
     
         32 . A medical device comprising the pharmaceutical formulation of  claim 1 , for administering the pharmaceutical formulation to an animal and/or human.