Metallic composite coatings for delivery of therapeutic agents from the surface of implantable devices

Abstract

A metallic composite coating, and methods for forming same, for an implantable medical device is disclosed. The composite coating comprises at least one metal or metallic tie layer formed on the surface of the device, followed by an electroless electrochemical cladding of one or more additional layers over the tie layer. One or more therapeutic or biologically active agents are co-deposited with at least one of the electroless electrochemical claddings.

1 . A method of forming a bioactive composite coating on a device comprising the steps of: 
 providing an electrolytic solution comprising metal ions;    contacting the device with the electrolytic solution;    applying an electric charge across the device to form a first layer on the device;    providing an electrochemical solution comprising metal ions and a biologically active agent; and    contacting the device having said first layer with the electrochemical solution to form a second bioactive metal composite layer on the device.    
     
     
         2 . The method according to  claim 1  wherein the device has a surface and said surface is etched prior to contact with the electrolytic solution.  
     
     
         3 . The method according to  claim 1  wherein the steps of contacting the device with the electrolytic solution and applying an electric charge across the device, are repeated so as to form another layer intermediate of said first layer and said second bioactive metal composite layer.  
     
     
         4 . The method according to  claim 1  wherein the electrochemical solution is an electroless electrochemical solution.  
     
     
         5 . The method according to  claim 1  further comprising the step of forming a top layer over the second bioactive metal composite layer.  
     
     
         6 . The method according to  claim 5  wherein the top layer comprises a metal.  
     
     
         7 . The method according to  claim 5  wherein the top layer comprises a polymeric material.  
     
     
         8 . The method according to  claim 1  wherein the metal ions are selected from the group consisting of ions of nickel, cobalt, copper, gold, silver, platinum, chromium, palladium, and molybdenum.  
     
     
         9 . The method according to  claim 1  wherein the metal ions in both solutions are the same.  
     
     
         10 . The method according to  claim 1  wherein the metal ions in the electrolytic solution and the metal ions in the electrochemical solutions are derived from metal salts.  
     
     
         11 . The method according to  claim 1  wherein the electrochemical solutions further comprises a reducing agent.  
     
     
         12 . The method according to  claim 11  wherein the reducing agent comprises phosphorous or boron.  
     
     
         13 . The method according to  claim 1  wherein said biologically active agent is selected from the group consisting of anti-restenosis compounds, anti-inflammatory compounds, anti-thrombogenic compounds, genes and growth factors.  
     
     
         14 . A method of forming a composite coating, having one or more therapeutic agents, on an implantable structure comprising the steps of: 
 providing a first electrochemical solution containing metal ions and a reducing agent;    contacting the implantable structure with said first electrochemical solution to form a first metallic matrix layer on the implantable structure;    providing a second electrochemical solution containing metal ions, a reducing agent and one or more therapeutic agents; and    contacting the implantable structure, having said first metallic matrix layer, with the second electrochemical solution to form a second metallic matrix layer containing said one or more therapeutic agents on the implantable structure.    
     
     
         15 . The method according to  claim 14  wherein the first and second electrochemical solutions are electroless electrochemical solutions.  
     
     
         16 . The method according to  claim 14  further comprising the step of forming a top layer over the second metallic matrix layer.  
     
     
         17 . The method according to  claim 16  wherein the top layer comprises a metal.  
     
     
         18 . The method according to  claim 16  wherein the top layer comprises a polymeric material.  
     
     
         19 . The method according to  claim 14  wherein the metal ions are selected from the group consisting of ions of nickel, cobalt, copper, gold, silver, platinum, chromium, palladium, and molybdenum.  
     
     
         20 . The method according to  claim 14  wherein the metal ions in the first and second electrochemical solutions are the same.  
     
     
         21 . The method according to  claim 14  wherein the metal ions in the first and second electrochemical solutions are derived from metal salts.  
     
     
         22 . The method according to  claim 14  wherein the electrochemical solutions further comprise a reducing agent.  
     
     
         23 . The method according to  claim 22  wherein the reducing agent comprises phosphorous or boron.  
     
     
         24 . The method according to  claim 14  wherein said one or more therapeutic agents is one or more substances selected from the group consisting of anti-restenosis compounds, anti-inflammatory compounds, anti-thrombogenic compounds, genes and growth factors.  
     
     
         25 . A method of forming a bioactive composite coating on a device comprising the steps of: 
 providing an electrolytic solution containing metal ions;    contacting the device with the electrolytic solution;    applying an electric charge across the device to form a first layer on the device;    providing a first electrochemical solution containing metal ions and a reducing agent;    contacting the device with said first electrochemical solution to form a second layer on the device;    providing a second electrochemical solution containing metal ions, a reducing agent and at least one biologically active agent; and    contacting the device, having said first layer and said second layer, with the second electrochemical solution to form a third bioactive metal composite layer on the device.    
     
     
         26 . The method according to  claim 25  wherein the steps of contacting the device with the electrolytic solution and applying an electric charge across the device, are repeated so as to form another layer intermediate of said first layer and said second layer.  
     
     
         27 . The method according to  claim 25  wherein the device has a surface and said surface is etched prior to contact with the electrolytic solution.  
     
     
         28 . The method according to  claim 25  wherein the device has a surface and said surface is etched prior to each step of contact with the electrolytic solution.  
     
     
         29 . The method according to  claim 25  wherein the first and second electrochemical solutions are electroless electrochemical solutions.  
     
     
         30 . The method according to  claim 25  further comprising the step of forming a top layer over the third bioactive metal composite layer.  
     
     
         31 . The method according to  claim 30  wherein the top layer comprises a metal.  
     
     
         32 . The method according to  claim 30  wherein the top layer comprises a polymeric material.  
     
     
         33 . The method according to  claim 25  wherein the metal ions are selected from the group consisting of ions of nickel, cobalt, copper, gold, silver, platinum, chromium, palladium, and molybdenum.  
     
     
         34 . The method according to  claim 25  wherein the metal ions in all solutions are the same.  
     
     
         35 . The method according to  claim 25  wherein the metal ions in the electrolytic solution and the metal ions in the first and second electrochemical solutions are derived from metal salts.  
     
     
         36 . The method according to  claim 25  wherein the first and second electrochemical solutions further comprise a reducing agent.  
     
     
         37 . The method according to  claim 36  wherein the reducing agent comprises phosphorous or boron.  
     
     
         38 . The method according to  claim 25  wherein said at least one biologically active agent is selected from the group consisting of anti-restenosis compounds, anti-inflammatory compounds, anti-thrombogenic compounds, genes and growth factors.  
     
     
         39 . A method of forming a composite coating, having one or more therapeutic agents, on an implantable structure having a surface, comprising the steps of: 
 providing an electrochemical solution containing metal ions and one or more therapeutic agents;    contacting the implantable structure with said electrochemical solution to form a composite coating including a metallic matrix and said one or more therapeutic agents within said metallic matrix; and    wherein the surface of the implantable structure is not sensitized prior to contact with electrochemical solution.    
     
     
         40 . The method according to  claim 39  wherein the implantable structure does not have a catalyst deposited on the surface prior to contact with the electrochemical solution.  
     
     
         41 . A method of forming a bioactive composite coating on a device having a surface, comprising the steps of: 
 providing an electrochemical solution containing metal ions and at least one biologically active agent;    contacting the surface of the device with said electrochemical solution to form a bioactive composite coating including a metallic matrix and said at least one or biologically active agent within said metallic matrix; and    wherein the device does not have a catalyst deposited on the surface prior to contact with the electrochemical solution.    
     
     
         42 . The method according to  claim 41  wherein the surface of the device is not sensitized prior to contact with electrochemical solution.