Methods for administering FGF18

Abstract

FGF18 is known to stimulate the proliferation of chondrocytes, resulting in increased cartilage formation. When hyaluronic acid is administered in addition to FGF18, the effects on chondrocyte proliferation and production of matrix were found to be greater than administration of FGF18 or hyaluronic acid alone.

We claim:  
     
         1 . A composition for intraarticular delivery of chondrogenic polypeptides comprising a pharmaceutically acceptable admixture comprising FGF18 and hyaluronic acid.  
     
     
         2 . The composition of  claim 1  further comprising a negatively charged carrier.  
     
     
         3 . The composition of  claim 2  wherein said carrier is selected from the group consisting of low molecular weight hyaluronans, high molecular weight hyaluronans, sulfated proteoglycans, B-cyclodextrin tetradecasulphate, hydroxyapatite, alginate microspheres, chitosans, and methylcellulose.  
     
     
         4 . The composition of  claim 1  wherein said composition is a time-release formulation.  
     
     
         5 . The composition of  claim 4  wherein said time-release formulation comprises a matrix selected from the group consisting of a solution, a gel, a paste, or a putty.  
     
     
         6 . The composition of  claim 4  wherein said time-release formulation comprises a reservoir system.  
     
     
         7 . The composition of  claim 1  further comprising chondrocytes wherein said chondrocytes have been cultured in the presence of FGF18 prior to intraarticular administration.  
     
     
         8 . The composition of  claim 1  further comprising an anti-inflammatory drug.  
     
     
         9 . A method for increasing chondrocyte proliferation in a joint of a mammal in need thereof comprising the step of administering into a synovial cavity a pharmaceutically acceptable admixture comprising FGF18 and hyaluronic acid.  
     
     
         10 . The method of  claim 9  wherein said administration comprises injection.  
     
     
         11 . The method of  claim 9  wherein said administration comprises surgical implantation.  
     
     
         12 . The method of  claim 9  wherein said admixture further comprises a negatively-charged carrier selected from the group consisting of low molecular weight hyaluronans, high molecular weight hyaluronans, sulfated proteoglycans, B-cyclodextrin tetradecasulphate, hydroxyapatite, alginate microspheres, chitosans, and methylcellulose.  
     
     
         13 . The method of  claim 9  where said admixture is a time-release formulation.  
     
     
         14 . The method of  claim 13  wherein said time-release formulation comprises a matrix selected from the group consisting of a solution, a gel, a paste, or a putty.  
     
     
         15 . The method of  claim 13  wherein said time-release formulation comprises a reservoir system.  
     
     
         16 . The method of  claim 9  wherein said admixture further comprises an anti-inflammatory drug.  
     
     
         17 . The method of  claim 9  further comprising the steps of allowing growth of new cartilage tissue and surgically contouring the new cartilage surface.  
     
     
         18 . A method of treating osteoarthritis in a mammal comprising the steps of administering into a synovial cavity a pharmaceutically acceptable admixture comprising FGF18 and hyaluronic acid.  
     
     
         19 . The method of  claim 18  wherein said administration comprises injection.  
     
     
         20 . The method of  claim 18  wherein said administration comprises surgical implantation.  
     
     
         21 . The method of  claim 18  wherein said admixture further comprises a negatively-charged carrier selected from the group consisting of low molecular weight hyaluronans, high molecular weight hyaluronans, sulfated proteoglycans, B-cyclodextrin tetradecasulphate, hydroxyapatite, alginate microspheres, chitosans, and methylcellulose.  
     
     
         22 . The method of  claim 18  where said admixture is a time-release formulation.  
     
     
         23 . The method of  claim 22  wherein said time-release formulation comprises a matrix selected from the group consisting of a solution, a gel, a paste, or a putty.  
     
     
         24 . The method of  claim 22  wherein said time-release formulation comprises a reservoir system.  
     
     
         25 . The method of  claim 18  wherein said admixture further comprises an anti-inflammatory drug.  
     
     
         26 . The method of  claim 18  further comprising the steps of allowing growth of new cartilage tissue and surgically contouring the new cartilage surface.