Method of promoting natural bypass

Abstract

An angiogenic factor comprising a mixture of proteins derived from bone. The angiogenic protein mixture is produced by a series of steps that allow the proteins to be kept in solution. The angiogenic mixture of bone proteins is produced by a multi-step process that includes at least one ultrafiltration step, an anion exchange chromatography step, a cation exchange chromatography step and a high performance liquid chromatography (HPLC) purification step.

1 .- 30 . (canceled)  
   
   
       31 . A composition, comprising: 
 a mixture of proteins derived from ground bone comprising an amount of at least two growth factors selected from the group consisting of bone morphogenic protein-2 (BMP-2), bone morphogenic protein-3 (BMP-3), bone morphogenic protein-4 (BMP-4), bone morphogenic protein-5 (BMP-5), bone morphogenic protein-6 (BMP-6), bone morphogenic protein-7 (BMP-7), transforming growth factor 1 (TGF-β1), transforming growth factor β2 (TGF-β2), transforming growth factor β3 (TGF-β3) and fibroblast growth factor 1 (FGF-1) effective to promote angiogenesis in soft tissue in a mammal.    
   
   
       32 . The composition of claim  1 , wherein the mixture of proteins further comprises a growth factor selected from the group consisting of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), transforming growth factor α (TGF-α), and platelet-derived growth factor (PDGF).  
   
   
       33 . The composition of claim  1 , further comprising a preservative or an adjuvant.  
   
   
       34 . The composition of claim  1 , wherein the mixture or proteins comprises BMP-2, BMP-3, BMP-7, TGF-β, and FGF-1.  
   
   
       35 . The composition of claim  1 , further comprising a carrier selected from the group consisting of polylactic acid, polyglycolic acid, copolymers of lactic acid and glycolic acid, collagen, polyoxyalkylene ether copolymer surfactant, and polyvinylpyrrolidone.  
   
   
       36 . The composition of claim  5 , wherein the carrier is polyvinylpyrrolidone.  
   
   
       37 . The composition of claim  5 , wherein the composition contains 10 μg of the mixture of proteins per 0.1 cc of polyvinylpyrrolidone or 100 μg of the mixture of proteins per 0.1 cc of polyvinylpyrrolidone.