Method of treating human growth hormone mediated condition

Abstract

A stable pharmaceutically acceptable aqueous formulation containing human growth hormone, a buffer, a non-ionic surfactant, and, optionally, a neutral salt, mannitol, or, a preservative, is disclosed. Also disclosed are associated means and methods for preparing, storing, and using such formulations.

1 - 41 . (canceled) 
     
     
         42 . A method for treating a human growth hormone-mediated condition, the method comprising
 administering to subject in need thereof an effective amount of an aqueous formulation comprising:
 a) at least about 0.1 mg/ml of human growth hormone; 
 b) a buffer having a concentration in the range of about 2 mM to about 50 mM; 
 c) a non-ionic surfactant in the range of from a 0.1% (w/v) to about 5% (w/v); 
 d) optionally, mannitol, 
 e) optionally, a neutral salt at a concentration adjusted to near isotonicity, and 
 f) optionally, a preservative. 
   
     
     
         43 . The method of  claim 42 , wherein the human growth hormone-mediated condition is idiopathic short stature, Turner's syndrome, or chronic kidney disease. 
     
     
         44 . The method of  claim 42 , wherein amount of buffer is adjusted to provide a pH of from about 4 to 8. 
     
     
         45 . The method of  claim 42 , wherein the non-ionic surfactant is a poloxamer. 
     
     
         46 . The method of  claim 42 , wherein the non-ionic surfactant is polysorbate. 
     
     
         47 . The method of  claim 46 , wherein the polysorbate is polysorbate 20 or polysorbate 80 in the range of from a 0.1% (w/v) to about 1% (w/v). 
     
     
         48 . A method of preventing denaturation of a human growth hormone formulation, the method comprising mixing an aqueous solution of human growth hormone and a non-ionic surfactant in the range of 0.1-5% (w/v). 
     
     
         49 . The method of  claim 48  wherein the non-ionic surfactant is a polysorbate. 
     
     
         50 . The method of  claim 48  wherein the poloxamer is poloxamer 188 or 184. 
     
     
         51 . The method of  claim 49  wherein the polysorbate is polysorbate 20 or polysorbate 80. 
     
     
         52 . An aqueous formulation of human growth hormone comprising:
 a) at least about 0.1 mg/ml of human growth hormone;   b) a buffer having a concentration in the range of about 2 mM to about 50 mM;   c) a non-ionic surfactant in the range of from a 0.1% (w/v) to about 5% (w/v);   d) optionally, mannitol,   e) optionally, a neutral salt at a concentration adjusted to near isotonicity, and   f) optionally, a preservative.   
     
     
         53 . The formulation of  claim 52  wherein amount of buffer is adjusted to provide a pH of from about 4 to 8. 
     
     
         54 . The formulation of  claim 52  wherein the non-ionic surfactant is a poloxamer. 
     
     
         55 . The formulation of  claim 52  wherein the non-ionic surfactant is polysorbate. 
     
     
         56 . The formulation of  claim 54  wherein the poloxamer is poloxamer 188 or poloxamer 184 in the range of from a 0.1% (w/v) to about 1% (w/v). 
     
     
         57 . The formulation of  claim 55  wherein the polysorbate is polysorbate 20 or polysorbate 80 in the range of from a 0.1% (w/v) to about 1% (w/v). 
     
     
         58 . The formulation of  claim 52  wherein the concentration of mannitol is about 5 mg/ml to about 50 mg/ml. 
     
     
         59 . The formulation of  claim 53  wherein the buffer is an alkali metal citrate buffer. 
     
     
         60 . The formulation of  claim 53  wherein the buffer is selected from the group consisting of phosphate, Tris, succinate, acetate, or histidine buffers. 
     
     
         61 . The formulation of  claim 52  wherein the formulation is sterile filtered using a 0.2 micron pore size sterilized membrane filter.