Pharmaceutical formulations for IGF/IGFBP

Abstract

New pharmaceutical formulations for IGF/IGFBP complex are disclosed. IGF/IGFBP complex, preferably rhIGF-I/IGFBP-3 complex is formulated with bulking agents and optionally buffer salts, but without added osmolyte salts. Also disclosed are lyophilized formulations for IGF/IGFBP complex.

1 . A pharmaceutical formulation for insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) complex; comprising: 
 IGF/IGFBP complex;    a bulking agent; and    ph buffer salts,    wherein said formulation contains no added osmolyte salts.    
     
     
         2 . The formulation of  claim 1 , wherein said pH buffer salts comprise sodium succinate.  
     
     
         3 . The formulation of  claim 2 , wherein said pH buffer salts are at a concentration of less than about 40 millimolar (mM).  
     
     
         4 . The formulation of  claim 3 , wherein said ph buffer salts are at a concentration of less than about 20 mM.  
     
     
         5 . The formulation of  claim 2 , wherein said pH buffer salts are at a concentration of less than 10 mM.  
     
     
         6 . The formulation of  claim 1 , wherein said formulation has a pH of about 5.5 to 6.5.  
     
     
         7 . The formulation of  claim 1 , wherein said bulking agent comprises mannitol.  
     
     
         8 . The formulation of  claim 1 , wherein said bulking agent comprises sorbitol.  
     
     
         9 . The formulation of  claim 1  wherein said bulking agent comprises sucrose.  
     
     
         10 . The formulation of  claim 1  wherein said bulking agent comprises mannitol and sucrose.  
     
     
         11 . The formulation of  claim 1 , wherein said bulking agent is present at about 6% (w/v).  
     
     
         12 . The formulation of  claim 11  wherein said mannitol is present at about 3.6% (w/v) and said sucrose is present at about 2.4% (w/v).  
     
     
         13 . The formulation of  claim 1  wherein said formulation further comprises a non-ionic surfactant.  
     
     
         14 . The formulation of  claim 1  wherein said IGFBP is IGFBP-3.  
     
     
         15 . The formulation of  claim 1  wherein said IGF is IGF-I.  
     
     
         16 . The formulation of  claim 15  wherein said IGFBP is IGFBP-3.  
     
     
         17 . The formulation of  claim 1 , wherein said formulation further comprises a preservative.  
     
     
         18 . The formulation of  claim 17 , wherein said preservative is benzyl alcohol.  
     
     
         19 . The formulation of  claim 10 , wherein said IGF/IGFBP is 50 milligrams per milliliter (mg/ml), said mannitol is 1.5% (w/v), and said sucrose is 1% (w/v).  
     
     
         20 . The formulation of  claim 10 , wherein said IGF/IGFBP is 100 mg/ml, said mannitol is 3% (w/v) and said sucrose is 2% (w/v).  
     
     
         21 . A pharmaceutical formulation for insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) complex, comprising: 
 IGF/IGFBP complex; and    a bulking agent,    wherein said formulation contains no added osmolyte salts and no added pH buffer salts.    
     
     
         22 . The formulation of  claim 21  wherein said bulking agent is mannitol.  
     
     
         23 . The formulation of  claim 21  wherein said bulking agent is sorbitol.  
     
     
         24 . The formulation of  claim 21  wherein said bulking agent is sucrose.  
     
     
         25 . The formulation of  claim 21  wherein said bulking agent comprises mannitol and sucrose.  
     
     
         26 . The formulation of  claim 21 , wherein said bulking agent is present at about 6% (w/v).  
     
     
         27 . The formulation of  claim 26  wherein said mannitol is present at about 3.6% (w/v) and said sucrose is present at about 2.4% (w/v).  
     
     
         28 . The formulation of  claim 21  wherein said formulation further comprises a non-ionic surfactant.  
     
     
         29 . The formulation of  claim 21  wherein said IGF is IGF-I.  
     
     
         30 . The formulation of  claim 21  wherein said IGFBP is IGFBP-3.  
     
     
         31 . The formulation of  claim 29  wherein said IGFBP is IGFBP-3.  
     
     
         32 . The formulation of  claim 21 , wherein said formulation further comprises a preservative.  
     
     
         33 . The formulation of  claim 32 , wherein said preservative is benzyl alcohol.  
     
     
         34 . The formulation of  claim 1 , wherein said formulation is lyophilized.  
     
     
         35 . The formulation of  claim 21 , wherein said formulation is lyophilized.  
     
     
         36 . A lyophilized pharmaceutical formulation for insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) complex, produced by: 
 forming a mixture comprising IGF, IGFBP, a bulking agent, and pH buffer salts, wherein said mixture lacks any added osmolyte salts; and    lyophilizing said mixture to form a lyophilized formulation of IGF, IGFBP, a bulking agent, and pH buffer salts.    
     
     
         37 . A lyophilized pharmaceutical formulation for insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) complex, produced by: 
 forming a mixture comprising IGF, IGFBP, and a bulking agent, wherein said mixture lacks any added osmolyte salts; and    lyophilizing said mixture to form a lyophilized formulation of IGF, IGFBP, and a bulking agent.