Hemocompatible polymers on hydrophobic porous polymers

Abstract

The present invention relates to providing a porous, hydrophobic polymer substrate with a hemocompatible substance. One embodiment of the present invention relates to the providing of expanded poly(tetrafluoroethylene) with one or more complexes of heparin, typically containing heparin in combination with a hydrophobic counter ion. The hemocompatible substance is dissolved in a mixture of solvents in which a first solvent wets the polymer substrate to be coated and the second solvent enhances the solubility of the hemocompatible substance material in the solvent mixture. Typical first solvents wetting a hydrophobic polymer substrate include non-polar such as hydrocholorofluorocarbons. Typical second solvents include polar solvents such as organic alcohols and ketones. Azeotropic mixtures of the second solvent in the first solvent are used in some embodiments of the present invention although second solvents may be employed in a range of concentration ranges from less than 0.1% up to saturation.

1 . A hemocompatible polymer substrate produced by:
 a) providing a porous hydrophobic polymer substrate,   b) providing a hemocompatible substance,   c) preparing a solution comprising a mixture of:
 a first solvent that wets the porous hydrophobic polymer substrate; 
 a second solvent that enhances the solubility of the hemocompatible substance in the solution; and 
 the hemocompatible substance; and; 
   d) contacting the surface of the porous hydrophobic polymer substrate with the solution thereby causing the hemocompatible substance to deposit onto the surface of the porous hydrophobic polymer substrate,   provided that the hemocompatible substance is not subjected to a dialdehyde cross-linking or dialdehyde stabilization step before in vivo use.   
     
     
         2 . The hemocompatible polymer substrate of  claim 1  wherein the hemocompatible substance is a complex of heparin and forms a coating on the surface of the porous hydrophobic polymer substrate. 
     
     
         3 . The hemocompatible polymer substrate of  claim 1  wherein the porous hydrophobic polymer substrate comprises an expanded poly(tetrafluoroethylene) material. 
     
     
         4 . The hemocompatible polymer substrate of  claim 1  wherein the second solvent particularly enhances solubility of the hemocompatible substance. 
     
     
         5 . The hemocompatible polymer substrate of  claim 1  wherein the porous hydrophobic polymer substrate composes a blood-contacting component of a medical device. 
     
     
         6 . The hemocompatible polymer substrate of  claim 1  wherein the porous hydrophobic polymer substrate includes at least one polymer material selected from the group consisting of porous polyethylene materials, porous polypropylene materials, porous polyurethane materials, porous polyacrylate materials, porous polymethacrylate materials and porous fluoropolymer materials. 
     
     
         7 . The hemocompatible polymer substrate of  claim 1  wherein the hemocompatible substance comprises ionic heparin and a hydrophobic counter ion. 
     
     
         8 . The hemocompatible polymer substrate of  claim 7  wherein the hydrophobic counter ion is a hydrophobic quaternary ammonium ion. 
     
     
         9 . The hemocompatible polymer substrate of  claim 7  wherein the hydrophobic counter ion is one or more of benzylalkonium ion and tridodecylmethylammonium ion. 
     
     
         10 . The hemocompatible polymer substrate of  claim 1  wherein the hemocompatible substance is deposited on the hydrophobic polymer substrate by dipping. 
     
     
         11 . A hemocompatible polymer substrate produced by:
 providing a porous hydrophobic polymer substrate,   providing a hemocompatible substance,   preparing a solution comprising a mixture of:
 a first solvent that wets the porous hydrophobic polymer substrate; 
 a second solvent that particularly enhances the solubility of the hemocompatible substance in the solution; and 
 the hemocompatible substance; and, 
   contacting the surface of the porous hydrophobic polymer substrate with the solution thereby causing the hemocompatible substance to deposit onto the surface of the porous hydrophobic polymer substrate.   
     
     
         12 . The hemocompatible polymer substrate of  claim 11  wherein the hemocompatible substance is a complex of heparin and forms a coating on the surface of the porous hydrophobic polymer substrate. 
     
     
         13 . The hemocompatible polymer substrate of  claim 11  wherein the porous hydrophobic polymer substrate comprises an expanded poly(tetrafluoroethylene) material. 
     
     
         14 . The hemocompatible polymer substrate of  claim 11  wherein the porous hydrophobic polymer substrate composes a blood-contacting component of a medical device. 
     
     
         15 . The hemocompatible polymer substrate of  claim 11  wherein the porous hydrophobic polymer substrate includes at least one polymer material selected from the group consisting of porous polyethylene materials, porous polypropylene materials, porous polyurethane materials, porous polyacrylate materials, porous polymethacrylate materials and porous fluoropolymer materials. 
     
     
         16 . The hemocompatible polymer substrate of  claim 11  wherein the hemocompatible substance comprises ionic heparin and a hydrophobic counter ion. 
     
     
         17 . The hemocompatible polymer substrate of  claim 16  wherein the hydrophobic counter ion is a hydrophobic quaternary ammonium ion. 
     
     
         18 . The hemocompatible polymer substrate of  claim 16  wherein the hydrophobic counter ion is one or more of benzylalkonium ion and tridodecylmethylammonium ion. 
     
     
         19 . The hemocompatible polymer substrate of  claim 11  wherein the hemocompatible substance is deposited on the hydrophobic polymer substrate by dipping. 
     
     
         20 . A hemocompatible polymer substrate produced by:
 a) providing a porous hydrophobic polymer substrate,   b) providing a hemocompatible substance,   c) preparing a solution comprising a mixture of:
 a first solvent that wets the porous hydrophobic polymer substrate; 
 a second solvent that enhances the solubility of the hemocompatible substance in the solution; and 
 the hemocompatible substance; and 
   d) contacting the surface of the porous hydrophobic polymer substrate with the solution thereby causing the hemocompatible substance to deposit onto the surface of the porous hydrophobic polymer substrate,   provided that where the mixture is a mixture of trichloro trifluoro ethanes, the amount of the mixture of trichloro trifluoro ethanes is 10 wt % or less.   
     
     
         21 . The hemocompatible polymer substrate of  claim 20  wherein the hemocompatible substance is a complex of heparin and forms a coating on the surface of the porous hydrophobic polymer substrate. 
     
     
         22 . The hemocompatible polymer substrate of  claim 20  wherein the porous hydrophobic polymer substrate comprises an expanded poly(tetrafluoroethylene) material. 
     
     
         23 . The hemocompatible polymer substrate of  claim 20  wherein the porous hydrophobic polymer substrate composes a blood-contacting component of a medical device. 
     
     
         24 . The hemocompatible polymer substrate of  claim 20  wherein the porous hydrophobic polymer substrate includes at least one polymer material selected from the group consisting of porous polyethylene materials, porous polypropylene materials, porous polyurethane materials, porous polyacrylate materials, porous polymethacrylate materials and porous fluoropolymer materials. 
     
     
         25 . The hemocompatible polymer substrate of  claim 20  wherein the hemocompatible substance comprises ionic heparin and a hydrophobic counter ion. 
     
     
         26 . The hemocompatible polymer substrate of  claim 25  wherein the hydrophobic counter ion is a hydrophobic quaternary ammonium ion. 
     
     
         27 . The hemocompatible polymer substrate of  claim 25  wherein the hydrophobic counter ion is one or more of benzylalkonium ion and tridodecylmethylammonium ion. 
     
     
         28 . The hemocompatible polymer substrate of  claim 20  wherein the hemocompatible substance is deposited on the hydrophobic polymer substrate by dipping. 
     
     
         29 . The hemocompatible polymer substrate of  claim 20  wherein the second solvent particularly enhances solubility of the hemocompatible substance. 
     
     
         30 . A hemocompatible polymer substrate produced by:
 a) providing a porous hydrophobic polymer substrate,   b) providing a hemocompatible substance,   c) preparing a solution comprising a mixture of:
 a first solvent that wets the porous hydrophobic polymer substrate; 
 a second solvent that enhances the solubility of the hemocompatible substance in the solution; and 
 the hemocompatible substance; and 
   d) contacting the surface of the porous hydrophobic polymer substrate with the solution thereby causing the hemocompatible substance to deposit onto the surface of the porous hydrophobic polymer substrate,   provided that the solution has a maximum ethanol content of 10 wt %.   
     
     
         31 . The hemocompatible polymer substrate of  claim 30  wherein the hemocompatible substance is a complex of heparin and forms a coating on the surface of the porous hydrophobic polymer substrate. 
     
     
         32 . The hemocompatible polymer substrate of  claim 30  wherein the porous hydrophobic polymer substrate comprises an expanded poly(tetrafluoroethylene) material. 
     
     
         33 . The hemocompatible polymer substrate of  claim 30  wherein the porous hydrophobic polymer substrate composes a blood-contacting component of a medical device. 
     
     
         34 . The hemocompatible polymer substrate of  claim 30  wherein the porous hydrophobic polymer substrate includes at least one polymer material selected from the group consisting of porous polyethylene materials, porous polypropylene materials, porous polyurethane materials, porous polyacrylate materials, porous polymethacrylate materials and porous fluoropolymer materials. 
     
     
         35 . The hemocompatible polymer substrate of  claim 30  wherein the hemocompatible substance comprises ionic heparin and a hydrophobic counter ion. 
     
     
         36 . The hemocompatible polymer substrate of  claim 35  wherein the hydrophobic counter ion is a hydrophobic quaternary ammonium ion. 
     
     
         37 . The hemocompatible polymer substrate of  claim 35  wherein the hydrophobic counter ion is one or more of benzylalkonium ion and tridodecylmethylammonium ion. 
     
     
         38 . The hemocompatible polymer substrate of  claim 30  wherein the hemocompatible substance is deposited on the hydrophobic polymer substrate by dipping. 
     
     
         39 . The hemocompatible polymer substrate of  claim 30  wherein the second solvent particularly enhances solubility of the hemocompatible substance.