Drug release stent coating

Abstract

A method of coating implantable open lattice metallic stent prosthesis is disclosed which includes sequentially applying a plurality of relatively thin outer layers of a coating composition comprising a solvent mixture of uncured polymeric silicone material and crosslinker and finely divided biologically active species, possibly of controlled average particle size, to form a coating on each stent surface. The coatings are cured in situ and the coated, cured prosthesis are sterilized in a step that includes preferred pretreatment with argon gas plasma and exposure to gamma radiation electron beam, ethylene oxide, steam.

We claim:  
     
         1 . A method of coating an implantable prosthesis with a layer comprising an hydrophobic elastomeric material incorporating an amount of biologically active material therein for timed delivery therefrom comprising the steps of: 
 (a) applying a formulation containing polymeric material in solvent mixture and an amount of finely divided biologically active species;    (b) curing said polymeric material; and    (c) wherein the average particle size of the finely divided biological species in said coating formulation is selected to affect delivery kinetics.    
     
     
         2 . The method of  claim 1  wherein the elastomeric material is selected from the group consisting of silicones, polyurethanes, polyamide elastomers, ethylene vinyl acetate copolymers, polyolefin elastomers, EPDM rubbers and combinations thereof.  
     
     
         3 . The method of  claim 1  wherein the biologically active material has an average particle size ≦ about 15 μm.  
     
     
         4 . The method of  claim 2  wherein the biologically active material includes heparin.  
     
     
         5 . The method of  claim 4  wherein the layer comprises about 25-45 weight percent biologically active material.  
     
     
         6 . The method of  claim 1  wherein the biologically active material has an average particle size ≦10 μm.  
     
     
         7 . The method of  claim 6  wherein the biologically active material includes heparin.  
     
     
         8 . A method of controlling the kinetics of an eluting (biologically active) particulate material incorporated in a polymeric coating in an implantable prosthesis comprising the step of controlling the average particle size below a designated maximum size.  
     
     
         9 . The method of  claim 7  wherein said biologically active material is heparin and the average particle size is ≦ about 15 μm.  
     
     
         10 . The method of  claim 9  wherein the layer comprises about 25-45 weight percent biologically active material.  
     
     
         11 . A method of controlling the kinetics of an eluting (biologically active) particulate material incorporated in a polymer coating in an implantable prosthesis comprising the steps of selecting an average particle size and a drug load to produce desired delivery kinetics.  
     
     
         12 . The method of  claim 11  further comprising the steps of selecting an average particle size and a drug load to produce a substantially smooth surface on the prosthesis.  
     
     
         13 . The method of  claim 11  wherein the layer comprises about 25-45 weight percent biologically active material.  
     
     
         14 . The method of  claim 13  wherein said biologically active material is heparin and the average particle size is ≦ about 15 μm.  
     
     
         15 . A coated implantable prosthesis having an external surface covered with a conformal coating comprising a hydrophobic elastomeric material incorporating an amount of biologically active material in particulate form dispersed therein for timed delivery therefrom wherein the delivery kinetics thereof is controlled at least in part by variations in parameters selected from the group consisting of average particle size and concentration of dispersed material in said coating or a combination thereof.  
     
     
         16 . The device of  claim 15  wherein the delivery kinetics are controlled by variations in particle size.  
     
     
         17 . The device of  claim 15  wherein the elastomeric material is selected from the group consisting of silicones, polyurethanes, polyamide elastomers, ethylene vinyl acetate copolymers, polyolefin elastomers, EPDM rubbers and combinations thereof.  
     
     
         18 . The device of  claim 15  wherein the biologically active material has an average particle size ≦ about 15 μm.  
     
     
         19 . The device of  claim 18  wherein the biologically active material includes heparin.  
     
     
         20 . The device of  claim 15  wherein the layer comprises about 25-45 weight percent biologically active material.  
     
     
         21 . The device of  claim 15  wherein the biologically active material has an average particle size ≦10 μm.  
     
     
         22 . The device of  claim 21  wherein the biologically active material includes heparin.  
     
     
         23 . The device of  claim 15  wherein the layer comprises about 25-45 weight percent biologically active material and wherein the biologically active material is heparin having an average particle size ≦10 microns.