Liquid insulin formulations and methods relating thereto

Abstract

Liquid formulations of insulin that contain physically and chemically stable insulin but do not contain preservatives or stabilizers are provided. The formulations also lack surfactants. The formulations are useful for various modes of delivery including pulmonary delivery.

What is claimed is: 
     
         1 . An insulin formulation, comprising:
 insulin at a minimal concentration of 1-13 mM;   a salt at a concentration of 50-150 mM;   a pH buffering agent at a concentration of 3-24 mM;   zinc at a ratio of 1.9-2.7 zinc ions per insulin hexamer; and   a pH in the range of 7.2 to 8.0,   wherein the formulation does not contain preservatives or stabilizers.   
     
     
         2 . The formulation of  claim 1 , wherein the insulin is human insulin. 
     
     
         3 . The formulation of  claim 1 , wherein the formulation comprises at least 30 mg/mL insulin. 
     
     
         4 . The formulation of  claim 1 , wherein the formulation comprises 10-30 mg/mL insulin. 
     
     
         5 . The formulation of  claim 1 , wherein the insulin concentration is about 30 mg/mL and the pH is about 7.55. 
     
     
         6 . The formulation of  claim 1 , wherein the salt is a chloride salt. 
     
     
         7 . The formulation of  claim 1 , wherein the salt is NaCl. 
     
     
         8 . The formulation of  claim 1 , wherein the pH buffering agent comprises citrate. 
     
     
         9 . The formulation of  claim 1 , wherein the tonicity (ionic strength) of the formulation is 100-300 mOsm. 
     
     
         10 . The formulation of  claim 1 , wherein the formulation is administrable by inhalation or injection. 
     
     
         11 . The formulation of  claim 1 , wherein the formulation is administrable by an inhalation device. 
     
     
         12 . The formulation of  claim 1 , wherein the formulation is aerosolizable. 
     
     
         13 . The formulation of  claim 1 , wherein the formulation does not contain surfactants. 
     
     
         14 . A unit dose of the pharmaceutically acceptable formulation of  claim 1 . 
     
     
         15 . A method of treating a subject with diabetes mellitus, comprising administering to a subject having diabetes mellitus a therapeutically effective amount of the formulation according to  claim 1 , wherein the formulation is administered to the subject via inhalation or injection.