Surface modification of polymers via surface active and reactive end groups

Abstract

Polymer surface modification method comprising the steps of first forming a surface of primary reactive end groups tethered to the polymer chain ends during fabrication of an article, and then modifying the reactive surface with bio-active molecules, hydrophilic and hydrophobic monomers, oligomers, or polymers to attain specific surface properties. Alternatively, a multifunctional coupling agent can be used to couple the primary reactive group to a second reactive group capable of reacting with a functional group associated with bio-active molecules, hydrophilic and hydrophobic monomers, oligomers, and polymers to attain specific surface properties. The invention involves bringing reactive endgroups to the surface with surface active spacer attached to the polymer chain end. The surface active spacer allows the migration and enrichment of reactive end groups to the surface during fabrication. The invention provides medical devices having a bio-interface with anti-thrombogenic properties, lubricity, selective adsorption, and antimicrobial properties.

1 . A method of modifying a surface on a polymeric substrate selected from the group consisting of solid synthetic polymers, solid natural polymers, and hydrogels, comprising the steps of:
 fabricating an article from a polymeric body composed of polymeric molecules having first reactive endgroups linked to surface active spacers which surface active spacers comprise endgroups on said polymeric molecules and forming a surface of said first reactive endgroups linked to surface active spacers on said polymeric body; and   contacting said surface of said polymeric body with a compound containing at least one second reactive endgroup and at least one surface modifying moiety, selected from the group consisting of bio-active molecules, monomers, oligomers, polymers, organometallic molecules, and metal compounds, to react said at least one second reactive endgroup with a first reactive endgroup and link said at least one surface modifying moiety to one of said polymeric molecules by a covalent, coordination, or ionic bond.   
     
     
         2 . A method of modifying a surface on a polymeric substrate selected from the group consisting of solid synthetic polymers, solid natural polymers, and hydrogels, comprising the steps of:
 fabricating an article from a polymeric body composed of polymeric molecules having first reactive endgroups linked to surface active spacers which surface active spacers comprise endgroups on said polymeric molecules and forming a surface of said first reactive endgroups linked to surface active spacers on said polymeric body;   contacting the surface of said polymeric body with a compound containing at least one third reactive endgroup and at least one fourth reactive endgroup to react said at least one third reactive endgroup with a first reactive endgroup and thereby link said at least one fourth reactive endgroup to the polymeric molecules by a covalent or ionic bond; and   contacting the resulting surface of said polymeric body with a compound containing at least one second reactive group and at least one surface modifying moiety, selected from the group consisting of bio-active molecules, monomers, oligomers, polymers, organometallic molecules, and metal compounds, to react said at least one second reactive endgroup with said at least one fourth reactive endgroup and thereby link said at least one surface modifying moiety to one of said polymeric molecules by a covalent, coordination, or ionic bond.   
     
     
         3 . The method of  claim 1  or  2 , wherein the first reactive endgroups are tethered to surface active spacers as part of polymer chain ends such that the reactive endgroups are spontaneously brought to the surface of an article during the fabrication thereof by a fabrication method which includes thermal forming or solvent-based processing. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 3 , wherein the fabrication method includes thermal processing selected from extrusion, molding, casting, and multilayer processing including co-extrusion and over-molding on top of a base polymer to afford the fabricated article with the surface properties of the polymer containing surface active or reactive endgroups. 
     
     
         6 . The method of  claim 3 , wherein said chain ends are selected from the group consisting of linear polymer chain ends, side chain ends, hyper-branched chain ends, dentrimer chain ends, and chain ends of a polymer network. 
     
     
         7 . The method of  claim 1  or  2 , wherein the reactive endgroups are selected to be stable toward processing conditions used in fabricating the device or substrate by extrusion, injection molding, or annealing, or wherein the reactive endgroups are protected by protecting groups such that the functionality and the reactivity of the reactive endgroups are retained during the fabrication of the article, with the reactive endgroups being recovered by a de-protection reaction subsequent to surface formation. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1  or  2 , wherein the reactive endgroups are selected from the group consisting of vinyl groups, alkoxy silanes, silanes, epoxy groups, anhydrides, primary amino groups, secondary amino groups, carboxyl groups, aldehyde groups, ketone groups, azide groups, dienes, amide groups, isothiocyanate groups, isocyanate groups, halide groups, maleimides, hydroxysuccinimide esters, hydroxysulfosuccinimide esters, imido esters, hydrazines, aziridines, cyano groups, and alkynes. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1  or  2 , wherein the bioactive molecules are selected from the group consisting of chitosan, heparin, hyaluronic acid and its derivatives, antimicrobial agents, antibiotic agents, antithrombogenic agents, peptides, proteins, polypeptides, poly(amino acids), carbohydrates, contrast agents, drugs, glycosaminoglycans, and lubricious substances. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1  or  2 , wherein the substrate is selected from the group consisting of polyolefins, silicones, acrylic polymers and copolymers, methacrylic polymers and copolymers, fluoropolymers, vinyl polymers and copolymers, polyurethanes, polyurethaneureas, polyester urethanes, silicone polyurethanes, polyvinyl chlorides, polyamides, polyether amides, polyesters, epoxy polymers, polyimides, polyester amides, polyether amides, and silicone hydrogels. 
     
     
         17 . The method of  claim 1  or  2 , wherein said article is a medical device selected from the group consisting of medical tubing, intravenous bags and catheters, ophthalmic devices, blood filtration devices, cardiovascular devices, biosensors, orthopedic implants, and prostheses. 
     
     
         18 . A polymeric molecule having a surface modifying moiety linked to said polymeric molecule by a molecular linkage comprising the reaction product of a second reactive endgroup on a compound containing said second reactive endgroup and said surface modifying moiety with a first reactive endgroup which is linked to a surface active spacer that comprises an endgroup on said polymeric molecule. 
     
     
         19 . The polymeric molecule of  claim 18 , having the formula POLYMER-SPACER-XK-LINK1-Q, wherein
 POLYMER is a polymer,   SPACER is a surface active spacer linkage,   XK is formed by reacting a first reactive endgroup X with a second reactive endgroup K,   LINK1 is a compound containing a second reactive endgroup K and a surface modifying moiety, and   Q is a surface modifying moiety.   
     
     
         20 . The polymeric molecule of  claim 19 , wherein
 POLYMER is a polyolefin, silicone, acrylic polymer or copolymer, methacrylic polymer or copolymer, fluoropolymer, vinyl polymer or copolymer, polyurethane, polyurethaneurea, polyester urethane, silicone polyurethane, polyvinyl chloride, polyamide, polyether amide, polyester, epoxy polymer, polyimide, polyester amide, polyether amide, or silicone hydrogel,   SPACER is a divalent alkane, polyol, polyamine, polysiloxane, or fluorocarbon chain from 8 to 24 units in length,   XK comprises a Si—C bond, an Si—O—Si bond, a urethane linkage, a urea linkage, a carbamate linkage, an amine, an amide linkage, an imine, an enamine, an oxime, an amidine linkage, an iminoester linkage, a carbonate linkage, a C—C bond, an ether, an ester linkage, an acetal, a sulfonate, a sulfide, a sulfinate, a disulfide, a sulfonamide linkage, a thioester linkage, a thiocarbonate linkage, a phosphonamide linkage, or a heterocycle,   LINK1 is an aliphatic moiety or aromatic moiety having up to 12 carbon atoms, and   Q is a substituted or non-substituted, saturated or unsaturated alkyl chain, a polyether, a fluorinated polyether, a silicone chain, an organometallic moiety, chitosan, heparin, hyaluronic acid, an antimicrobial agent, an antithrombogenic agent, a peptide, a protein, a poly(amino acid), a carbohydrate, or a radio-imaging contrast agent.   
     
     
         21 . A polymeric molecule having a surface modifying moiety linked to said polymeric molecule by a molecular linkage comprising both the reaction product of a second reactive endgroup on a compound containing said second reactive endgroup and said surface modifying moiety with a fourth reactive endgroup on a compound containing third and fourth reactive endgroups and the reaction product of a third reactive endgroup on said compound containing third and fourth reactive endgroups with a first reactive endgroup which is linked to a surface active spacer that comprises an endgroup on said polymeric molecule. 
     
     
         22 . The polymeric molecule of  claim 21 , having the formula POLYMER-SPACER-XY-LINK1-ZK-LINK2-Q, wherein
 POLYMER is a polymer,   SPACER is a surface active spacer linkage,   XY is formed by reacting a first reactive endgroup X with a third reactive endgroup Y,   LINK1 is a compound containing a third reactive endgroup Y and a fourth reactive endgroup Z,   ZK is formed by reacting a fourth reactive endgroup Z with a third reactive endgroup K,   LINK2 is a compound containing a second reactive endgroup K and a surface modifying moiety, and   Q is a surface modifying moiety.   
     
     
         23 . The polymeric molecule of  claim 22 , wherein
 POLYMER is a polyolefin, silicone, acrylic polymer or copolymer, methacrylic polymer or copolymer, fluoropolymer, vinyl polymer or copolymer, polyurethane, polyurethaneurea, polyester urethane, silicone polyurethane, polyvinyl chloride, polyamide, polyether amide, polyester, epoxy polymer, polyimide, polyester amide, polyether amide, or silicone hydrogel,   SPACER is a divalent alkane, polyol, polyamine, polysiloxane, or fluorocarbon chain from 8 to 24 units in length,   XY comprises a Si—C bond, an Si—O—Si bond, a urethane linkage, a urea linkage, a carbamate linkage, an amine, an amide linkage, an imine, an enamine, an oxime, an amidine linkage, an iminoester linkage, a carbonate linkage, a C—C bond, an ether, an ester linkage, an acetal, a sulfonate, a sulfide, a sulfinate, a disulfide, a sulfonamide linkage, a thioester linkage, a thiocarbonate linkage, a phosphonamide linkage, or a heterocycle,   LINK1 is an aliphatic moiety or aromatic moiety having up to 12 carbon atoms,   ZK comprises a Si—C bond, an Si—O—Si bond, a urethane linkage, a urea linkage, a carbamate linkage, an amine, an amide linkage, an imine, an enamine, an oxime, an amidine linkage, an iminoester linkage, a carbonate linkage, a C—C bond, an ether, an ester linkage, an acetal, a sulfonate, a sulfide, a sulfinate, a disulfide, a sulfonamide linkage, a thioester linkage, a thiocarbonate linkage, a phosphonamide linkage, or a heterocycle,   LINK2 is an aliphatic moiety or aromatic moiety having up to 12 carbon atoms, and   Q is a substituted or non-substituted, saturated or unsaturated alkyl chain, a polyether, a fluorinated polyether, a silicone chain, an organometallic moiety, chitosan, heparin, hyaluronic acid, an antimicrobial agent, an antithrombogenic agent, a peptide, a protein, a poly(amino acid), a carbohydrate, or a radio-imaging contrast agent.   
     
     
         24 . A medical device selected from the group consisting of medical tubing, intravenous bags and catheters, ophthalmic devices, blood filtration devices, cardiovascular devices, biosensors, orthopedic implants, and prostheses, wherein all or a portion of said medical device is made from a polymeric molecule according to  claim 18  or  21 .