Pleiotrophin-based compositions for enhancing connective tissue repair

Abstract

The present invention is directed to bioactive composition that induce the repair of damaged or diseased connective tissues upon contact of the damaged or diseased tissues with the composition in vivo. More particularly the present invention is directed to the use of a composition comprising an effective amount of pleiotrophin to enhance the repair of damaged or diseased bone and cartilage tissues.

We claim:  
     
         1 . A composition for enhancing the growth of connective tissue, said composition comprising a delivery vehicle and a bioactive mixture comprising an effective amount of substantially pure pleiotrophin.  
     
     
         2 . The composition of  claim 1 , wherein the connective tissue is bone.  
     
     
         3 . The composition of  claim 1 , wherein the delivery vehicle comprises a polymer matrix formed from a biocompatible polymer.  
     
     
         4 . The composition of  claim 1 , wherein the polymer matrix comprises a polymer selected from the group consisting of polyesters, ionomers, poly(amino acids), polyvinyl acetate, polyacrylates, polyorthoesters, polyanhydrides, collagens, fibrins, starches, alginate, and hyaluronic acid.  
     
     
         5 . The composition of  claim 1 , further comprising a mineral salt selected from the group consisting essentially of tricalcium phosphate, hydroxyapatite, and gypsum.  
     
     
         6 . The composition of  claim 1 , wherein the polymer matrix comprises a biodegradable polymer.  
     
     
         7 . The composition of  claim 6 , wherein the biodegradable polymer is selected from the group consisting of collagens and polyester ionomers.  
     
     
         8 . The composition of  claim 1 , further comprising additional growth factors, growth factor binding proteins, or eukaryotic cells.  
     
     
         9 . The use of isolated pleiotrophin in the preparation of a composition useful for inducing growth of connective tissue at an in vivo site in need of said growth.  
     
     
         10 . The use of isolated pleiotrophin in accordance with  claim 9 , wherein the pleiotrophin is combined with a biocompatible matrix to form an implantable composition.  
     
     
         11 . The use of isolated pleiotrophin in accordance with  claim 9 , wherein the connective tissue is bone.  
     
     
         12 . A method for inducing localized connective tissue growth at a predetermined in vivo site of a vertebrate species, said method comprising 
 contacting said site with a composition comprising substantially purified pleiotrophin, in an amount effective to induce connective tissue growth, and a pharmaceutically acceptable carrier.    
     
     
         13 . The method of  claim 12 , wherein the composition is in fluid form and the site is contacted by injection of the composition.  
     
     
         14 . The method of  claim 12 , wherein the composition further comprises a biocompatible polymer matrix.  
     
     
         15 . The method of  claim 14 , wherein the polymer matrix comprises a polymer selected from the group consisting of polyesters, ionomers, poly(amino acids), polyvinyl acetate, polyacrylates, polyorthoesters, polyanhydrides, collagens, fibrins, starches, alginate and hyaluronic acid.  
     
     
         16 . The method of  claim 12 , wherein the pharmaceutically acceptable carrier comprises a mineral salt, or metal or glass compound.  
     
     
         17 . The method of  claim 16 , wherein the mineral salt is selected from the group consisting essentially of tricalcium phosphate, hydroxyapatite and gypsum.  
     
     
         18 . The method of  claim 14 , wherein the polymer matrix comprises a biodegradable polymer.  
     
     
         19 . The method of  claim 18 , wherein the biodegradable polymer is selected from the group consisting of collagens and polyester ionomers.  
     
     
         20 . The method of  claim 14 , wherein the composition is surgically implanted at the site.  
     
     
         21 . The method of  claim 12 , wherein the composition is provided in a time-release delivery vehicle.  
     
     
         22 . The method of  claim 12 , wherein the connective tissue is bone.  
     
     
         23 . A method for treating a pathogenic condition in a connective tissue in a warm-blooded vertebrate, said method comprising 
 administering a composition systemically to said warm-blooded vertebrate, wherein the composition comprises substantially purified pleiotrophin, in an amount effective to induce endogenous tissue growth, and a pharmaceutically acceptable carrier.    
     
     
         24 . The method of  claim 23 , wherein the composition is administered by parenteral injection.  
     
     
         25 . The method of  claim 23  wherein the connective tissue is bone.  
     
     
         26 . The method of  claim 25 , wherein the pathogenic condition is osteoporosis.