Anti-infective functionalized surfaces and methods of making same

Abstract

Devices are provided which are functionalized to include surface regions having anti-infective agents. Methods are provided for functionalizing various material surfaces to include active surface regions for binding anti-infective agents. Methods are provided by which anti-infective moieties or agents are bonded to functionalized surfaces.

1 . A method of providing a surface with an anti-infective agent comprising functionalizing the surface with a functional group effective to bind an anti-infective agent thereto and binding the functional group with the anti-infective agent. 
   
   
       2 . The method of  claim 1  wherein the surface is selected from a metal, alloy, polymer, plastic, ceramic, silicon, glass, fabric, and a material with at least one acidic proton. 
   
   
       3 . The method of  claim 1 , wherein the anti-infective agent is selected from the group consisting of disinfectants, antiseptics and antibiotics. 
   
   
       4 . The method of  claim 1 , wherein the anti-infective agent is a disinfectant selected from hypochlorites, chloramines, dichloroisocyanurate and trichloroisocyanurate, wet chlorine, chlorine dioxide, peracetic acid, potassium persulfate, sodium perborate, sodium percarbonate and urea perhydrate, iodpovidone, iodine tincture, iodinated nonionic surfactants, ethanol, n-propanol and isopropanol and mixtures thereof; 2-phenoxyethanol and 1- and 2-phenoxypropanol, cresols, hexachlorophene, triclosan, trichlorophenol, tribromophenol, pentachlorophenol, Dibromol and salts thereof, benzalkonium chloride, cetyl trimethylammonium bromide or chloride, didecyldimethylammonium chloride, cetylpyridinium chloride, benzethonium chloride, chlorhexidine, glucoprotamine, octenidine dihydrochloride; ozone and permanganate solutions; colloidal silver, silver nitrate, mercury chloride, phenylmercury salts, copper, copper sulfate, copper oxide-chloride, phosphoric acid, nitric acid, sulfuric acid, amidosulfuric acid, toluenesulfonic acid, sodium hydroxide, potassium hydroxide and calcium hydroxide. 
   
   
       5 . The method of  claim 1  wherein the anti-infective agent is selected from Daquin's solution, 0.5% sodium hypochlorite solution which is pH-adjusted to pH 7-8, potassium hypochlorite solution which is pH-adjusted to pH 7-8, 0.5-1% solution of sodium benzenesulfochloramide, iodopovidone, urea perhydrate solution, pH-buffered 0.1-0.25% peracetic acid solution, alcohols, weak organic acids selected from the group consisting of sorbic acid, benzoic acid, lactic acid and salicylic acid; hexachlorophene, triclosan, Dibromol, 0.05-0.5% benzalkonium, 0.5-4% chlorhexidine and 0.1-2% octenidine. 
   
   
       6 . The method of  claim 1  wherein the anti-infective agent is at least one of a quaternary ammonium compound, choline, a choline derivative, a quaternary ammonium dendrimer, silver, copper, a cationic species, a peptide, an antibody, an antibiotic, an imidazole derivative, a nitrofuran derivative, a steroid, chlorhexidine, a phenol compound, an epoxide, a polymer and/or polypeptide which has anti-infective properties, a zinc oxide, a titanium oxides, a zeolite, a silicate, calcium hydroxide, iodine, sodium hypochlorite, a sulfite, and a sulfates. 
   
   
       7 . The method of  claim 1  wherein the anti-infective agent is copper. 
   
   
       8 . The method of  claim 1  wherein the anti-infective agent is silver. 
   
   
       9 . The method of  claim 1 , wherein the anti-infective agent is an acid functionalized anti-infective agent. 
   
   
       10 . The method of  claim 9  wherein the acid is an organophosphonic acid. 
   
   
       11 . The method of  claim 9  wherein the acid is selected from the group consisting of carboxylic, sulfonic, sulfinic, phosphinic, phosphoric, and hydroxamic acid. 
   
   
       12 . The method of  claim 1  wherein the anti-infective agent is introduced to the functionalized surface by covalent bonding, evaporative, sputter or immersion, deposition. 
   
   
       13 . The method of  claim 1  wherein the surface includes a metal or a polymer and the step of functionalizing comprises bonding thereto an oxide, alkoxide, or mixed oxide/alkoxide layer using an alkoxide precursor, wherein the functionalized polymer surface is operable to covalently bond an anti-infective agent thereto. 
   
   
       14 . The method according to  claim 1  wherein the surface is a metal or a polymer and the step of functionalizing comprises a) contacting a metal alkoxide with the surface; and b) subjecting the metal alkoxide to conditions adequate to form an oxide, alkoxide, or mixed oxide/alkoxide adhesion layer on the surface, the conditions selected from one or more of the group consisting of pyrolysis, microwaving, complete hydrolysis and partial hydrolysis; and the step of binding the functional group with a reactive group of the anti-infective agent comprises contacting an anti-infective agent with the oxide adhesion layer. 
   
   
       15 . The process according to  claim 14 , wherein step a) comprises vapor deposition or immersion deposition. 
   
   
       16 . The method of  claim 14 , wherein step b) comprises heating the metal alkoxide to between about 50° C. and the upper working temperature of the polymer. 
   
   
       17 . The method of  claim 14 , wherein the metal alkoxide is zirconium tetra(tert-butoxide), silicon tetra(tert-butoxide), titanium tetra(tert-butoxide), and calcium bis(2-methoxy-ethoxide. 
   
   
       18 . The method of  claim 14 , wherein the metal in the metal alkoxide is a Group 3-6 or Group 13-14 transition metal. 
   
   
       19 . The method of  claim 14 , wherein the alkoxide is selected from the group consisting of ethoxide, propoxide, iso-propoxide, butoxide, iso-butoxide, tert-butoxide and fluorinated alkoxide. 
   
   
       20 . The method of  claim 14 , comprising reacting the oxide adhesion layer with an anti-infective agent selected from the group consisting of disinfectants, antiseptics and antibiotics. 
   
   
       21 . The method of  claim 14 , wherein the anti-infective agent is a disinfectant selected from hypochlorites, chloramines, dichloroisocyanurate and trichloroisocyanurate, wet chlorine, chlorine dioxide, peracetic acid, potassium persulfate, sodium perborate, sodium percarbonate and urea perhydrate, iodpovidone, iodine tincture, iodinated nonionic surfactants, ethanol, n-propanol and isopropanol and mixtures thereof; 2-phenoxyethanol and 1- and 2-phenoxypropanol, cresols, hexachlorophene, triclosan, trichlorophenol, tribromophenol, pentachlorophenol, Dibromol and salts thereof, benzalkonium chloride, cetyl trimethylammonium bromide or chloride, didecyldimethylammonium chloride, cetylpyridinium chloride, benzethonium chloride, chlorhexidine, glucoprotamine, octenidine dihydrochloride; ozone and permanganate solutions; colloidal silver, silver nitrate, mercury chloride, phenylmercury salts, copper, copper sulfate, copper oxide-chloride, phosphoric acid, nitric acid, sulfuric acid, amidosulfuric acid, toluenesulfonic acid, sodium hydroxide, potassium hydroxide and calcium hydroxide. 
   
   
       22 . The method of  claim 14  wherein the anti-infective agent is selected from Daquin's solution, 0.5% sodium hypochlorite solution which is pH-adjusted to pH 7-8, potassium hypochlorite solution which is pH-adjusted to pH 7-8, 0.5-1% solution of sodium benzenesulfochloramide, iodopovidone, urea perhydrate solution, pH-buffered 0.1-0.25% peracetic acid solution, alcohols, weak organic acids selected from the group consisting of sorbic acid, benzoic acid, lactic acid and salicylic acid; hexachlorophene, triclosan, Dibromol, 0.05-0.5% benzalkonium, 0.5-4% chlorhexidine and 0.1-2% octenidine. 
   
   
       23 . The method of  claim 14  wherein the anti-infective agent is at least one of a quaternary ammonium compound, choline, a choline derivative, a quaternary ammonium dendrimer, silver, copper, a cationic species, a peptide, an antibody, an antibiotic, an imidazole derivative, a nitrofuran derivative, a steroid, chlorhexidine, a phenol compound, an epoxide, a polymer and/or polypeptide which has anti-infective properties, a zinc oxide, a titanium oxides, a zeolite, a silicate, calcium hydroxide, iodine, sodium hypochlorite, a sulfite, and a sulfates. 
   
   
       24 . The method according to  claim 23  wherein the anti-infective agent is copper. 
   
   
       25 . The method according to  claim 23  wherein the anti-infective agent is silver. 
   
   
       26 . The method according to  claim 14  wherein the anti-infective agent is introduced to the oxide adhesion layer by covalent bonding, evaporative, sputter, immersion or extractive deposition. 
   
   
       27 . The method according to  claim 14 , comprising optionally subjecting the oxide adhesion layer to complete or partial hydrolysis prior to deposition of the anti-infective agent. 
   
   
       28 . The method according to  claim 14 , wherein the adhesion layer is continuous. 
   
   
       29 . The method of  claim 14 , wherein the polymer surface contains a surface coordinating group that is capable of coordinating with the metal atom of the metal alkoxide. 
   
   
       30 . The method of  claim 14 , wherein the polymer is selected from the group consisting of polyamides, polyurethanes, polyureas, polyesters, polyketones, polyimides, polysulfides, polysulfoxides, polysulfones, polythiophenes, polypyridines, polypyrroles, polyethers, silicones, polysiloxanes, polysaccharides, fluoropolymers, amides, imides, polypeptides, polyethylene, polystyrene, polypropylene, glass reinforced epoxies, liquid crystal polymers, thermoplastics, bismaleimide-triazine (BT) resins, benzocyclobutene polymers, Ajinomoto Buildup Films (ABF), low coefficient of thermal expansion (CTE) films of glass and epoxies, and composites including these polymers. 
   
   
       31 . The method of  claim 14 , wherein the polymer is selected from the group consisting of polyethylene terephthalate (PET), polyetheretherketones (PEEK), polyetherketoneketones (PEKK), and nylon. 
   
   
       32 . The method of  claim 14 , comprising disposing an adhesion layer of a metal oxide, alkoxide, or mixed oxide/alkoxide on the surface, treating the adhesion layer with a phosphonic acid to provide a phosphonate monolayer thereon, derivatizing the phosphonate monolayer and contacting the monolayer with an anti-infective agent. 
   
   
       33 . The method of  claim 32  wherein the anti-infective agent is a quaternary alkylammonium moiety. 
   
   
       34 . The method of  claim 1  wherein the surface contains silicon, and the step of functionalizing comprises forming a self-assembled film of an organophosphonic acid bound to a native or synthesized oxide-coated silicon surface as a film of a corresponding phosphonate. 
   
   
       35 . The method of  claim 1  wherein the step of functionalizing comprises forming a peptide-modified surface-bound phosphonate film thereon. 
   
   
       36 . The method of  claim 1 , wherein the step of functionalizing comprises forming a phosphonate monolayer on the surface, immersing the surface in a solution of 3-(maleimido)propanoic acid N-hydroxysuccinimide ester and then in an aqueous solution of an active peptide to derivatize the phosphonate monolayer. 
   
   
       37 . The method of  claim 1 , comprising bonding a self-assembled phosphonate monolayer to a native oxide surface of a metal, alloy, metalloid, or ceramic, treating the self-assembled phosphonate monolayer to provide a distal amino functional group bonded to the oxide, and quaternizing the distal amino group to provide a quaternary alkylammonium moiety covalently bonded to the metal surface through the phosphonate interface. 
   
   
       38 . The method of  claim 1 , comprising bonding a self-assembled phosphonate monolayer to a native oxide surface of a metal, alloy, metalloid, or ceramic, treating the self-assembled phosphonate monolayer to provide an anti-infective agent bonded to the oxide. 
   
   
       39 . The methods of  claim 37  wherein the metal is selected from titanium, stainless steel, cobalt chrome, nickel, molybdenum, tantalum, zirconium, magnesium, manganese, niobium; and alloys thereof. 
   
   
       40 . A device having an anti-infective surface, the surface comprising a functionalizing layer disposed thereon and an anti-infective agent disposed on the functionalizing layer, the functionalizing layer comprising at least one moiety or functional group capable of binding the anti-infective agent thereto and at least one moiety or functional group capable of binding the functionalizing layer to the surface. 
   
   
       41 . The device of  claim 40  wherein the surface is selected from a metal, alloy, polymer, plastic, ceramic, silicon, glass, fabric, and a material with at least one acidic proton. 
   
   
       42 . The device of  claim 40 , wherein the anti-infective agent is selected from the group consisting of disinfectants, antiseptics and antibiotics. 
   
   
       43 . The device of  claim 40 , wherein the anti-infective agent is a disinfectant selected from hypochlorites, chloramines, dichloroisocyanurate and trichloroisocyanurate, wet chlorine, chlorine dioxide, peracetic acid, potassium persulfate, sodium perborate, sodium percarbonate and urea perhydrate, iodpovidone, iodine tincture, iodinated nonionic surfactants, ethanol, n-propanol and isopropanol and mixtures thereof; 2-phenoxyethanol and 1- and 2-phenoxypropanol, cresols, hexachlorophene, triclosan, trichlorophenol, tribromophenol, pentachlorophenol, Dibromol and salts thereof, benzalkonium chloride, cetyl trimethylammonium bromide or chloride, didecyldimethylammonium chloride, cetylpyridinium chloride, benzethonium chloride, chlorhexidine, glucoprotamine, octenidine dihydrochloride; ozone and permanganate solutions; colloidal silver, silver nitrate, mercury chloride, phenylmercury salts, copper, copper sulfate, copper oxide-chloride, phosphoric acid, nitric acid, sulfuric acid, amidosulfuric acid, toluenesulfonic acid, sodium hydroxide, potassium hydroxide and calcium hydroxide. 
   
   
       44 . The device of  claim 40  wherein the anti-infective agent is selected from Daquin's solution, 0.5% sodium hypochlorite solution which is pH-adjusted to pH 7-8, potassium hypochlorite solution which is pH-adjusted to pH 7-8, 0.5-1% solution of sodium benzenesulfochloramide, iodopovidone, urea perhydrate solution, pH-buffered 0.1-0.25% peracetic acid solution, alcohols, weak organic acids selected from the group consisting of sorbic acid, benzoic acid, lactic acid and salicylic acid; hexachlorophene, triclosan, Dibromol, 0.05-0.5% benzalkonium, 0.5-4% chlorhexidine and 0.1-2% octenidine and an acid functionalized anti-infective agent. 
   
   
       45 . The device of  claim 40  wherein the anti-infective agent is at least one of a quaternary ammonium compound, choline, a choline derivative, a quaternary ammonium dendrimer, silver, copper, a cationic species, a peptide, an antibody, an antibiotic, an imidazole derivative, a nitrofuran derivative, a steroid, chlorhexidine, a phenol compound, an epoxide, a polymer and/or polypeptide which has anti-infective properties, a zinc oxide, a titanium oxides, a zeolite, a silicate, calcium hydroxide, iodine, sodium hypochlorite, a sulfite, and a sulfate. 
   
   
       46 . The device of  claim 40  wherein the anti-infective agent is copper. 
   
   
       47 . The device of  claim 40  wherein the anti-infective agent is silver. 
   
   
       48 . The device of  claim 40  wherein the surface includes a polymer and the functionalizing layer comprises a phosphonate monolayer, wherein the functionalized polymer surface is covalently bound to the anti-infective agent. 
   
   
       49 . The device of  claim 48  wherein the phosphonate monolayer is attached to an oxide, alkoxide, or mixed oxide/alkoxide layer deposited onto the polymer and derived from a metal alkoxide. 
   
   
       50 . The device of  claim 49  where the oxide, alkoxide, or mixed oxide/alkoxide layer comprises a metal alkoxide selected from zirconium tetra(tert-butoxide), silicon tetra(tert-butoxide), titanium tetra(tert-butoxide), and calcium bis(2-methoxy-ethoxide. 
   
   
       51 . The device of  claim 50 , wherein the metal in the metal alkoxide is selected from a Group 3-6 and Group 13-14 transition metal. 
   
   
       52 . The device of  claim 49 , wherein the alkoxide is selected from the group consisting of ethoxide, propoxide, iso-propoxide, butoxide, iso-butoxide, tert-butoxide and fluorinated alkoxide. 
   
   
       53 . The device of  claim 48 , wherein the anti-infective agent is a disinfectant selected from hypochlorites, chloramines, dichloroisocyanurate and trichloroisocyanurate, wet chlorine, chlorine dioxide, peracetic acid, potassium persulfate, sodium perborate, sodium percarbonate and urea perhydrate, iodpovidone, iodine tincture, iodinated nonionic surfactants, ethanol, n-propanol and isopropanol and mixtures thereof; 2-phenoxyethanol and 1- and 2-phenoxypropanol, cresols, hexachlorophene, triclosan, trichlorophenol, tribromophenol, pentachlorophenol, Dibromol and salts thereof, benzalkonium chloride, cetyl trimethylammonium bromide or chloride, didecyldimethylammonium chloride, cetylpyridinium chloride, benzethonium chloride, chlorhexidine, glucoprotamine, octenidine dihydrochloride; ozone and permanganate solutions; colloidal silver, silver nitrate, mercury chloride, phenylmercury salts, copper, copper sulfate, copper oxide-chloride, phosphoric acid, nitric acid, sulfuric acid, amidosulfuric acid, toluenesulfonic acid, sodium hydroxide, potassium hydroxide and calcium hydroxide. 
   
   
       54 . The device of  claim 48  wherein the anti-infective agent is selected from Daquin's solution, 0.5% sodium hypochlorite solution which is pH-adjusted to pH 7-8, potassium hypochlorite solution which is pH-adjusted to pH 7-8, 0.5-1% solution of sodium benzenesulfochloramide, iodopovidone, urea perhydrate solution, pH-buffered 0.1-0.25% peracetic acid solution, alcohols, weak organic acids selected from the group consisting of sorbic acid, benzoic acid, lactic acid and salicylic acid; hexachlorophene, triclosan, Dibromol, 0.05-0.5% benzalkonium, 0.5-4% chlorhexidine and 0.1-2% octenidine. 
   
   
       55 . The device of  claim 48  wherein the anti-infective agent is at least one of a quaternary ammonium compound, choline, a choline derivative, a quaternary ammonium dendrimer, silver, copper, a cationic species, a peptide, an antibody, an antibiotic, an imidazole derivative, a nitrofuran derivative, a steroid, chlorhexidine, a phenol compound, an epoxide, a polymer and/or polypeptide which has anti-infective properties, a zinc oxide, a titanium oxides, a zeolite, a silicate, calcium hydroxide, iodine, sodium hypochlorite, a sulfite, and a sulfates. 
   
   
       56 . The device of  claim 48  wherein the anti-infective agent is copper. 
   
   
       57 . The device of  claim 48  wherein the anti-infective agent is silver. 
   
   
       58 . The method of  claim 40 , wherein the anti-infective agent is an acid functionalized anti-infective agent. 
   
   
       59 . The method of  claim 40  wherein the acid is an organophosphonic acid. 
   
   
       60 . The method of  claim 40  wherein the acid is selected from the group consisting of carboxylic, sulfonic, sulfinic, phosphinic, phosphoric, and hydroxamic acid. 
   
   
       61 . The device of  claim 48 , wherein the adhesion layer is continuous. 
   
   
       62 . The device of  claim 48 , wherein the polymer contains a surface coordinating group that is capable of coordinating with a metal atom of a metal oxide. 
   
   
       63 . The device of  claim 48 , wherein the polymer is selected from the group consisting of polyamides, polyurethanes, polyureas, polyesters, polyketones, polyimides, polysulfides, polysulfoxides, polysulfones, polythiophenes, polypyridines, polypyrroles, polyethers, silicones, polysiloxanes, polysaccharides, fluoropolymers, amides, imides, polypeptides, polyethylene, polystyrene, polypropylene, glass reinforced epoxies, liquid crystal polymers, thermoplastics, bismaleimide-triazine (BT) resins, benzocyclobutene polymers, Ajinomoto Buildup Films (ABF), low coefficient of thermal expansion (CTE) films of glass and epoxies, and composites including these polymers. 
   
   
       64 . The device of  claim 48 , wherein the polymer is selected from the group consisting of polyethylene terephthalate (PET), polyetheretherketones (PEEK), polyetherketoneketones (PEKK), and nylon. 
   
   
       65 . The device of  claim 48 , wherein the surface is polyetheretherketone (PEEK) and the functionalizing layer is a derivatized phosphonate monolayer disposed on the PEEK or PEKK surface. 
   
   
       66 . The device of  claim 48  wherein the anti-infective agent is a quaternary alkylammonium moiety. 
   
   
       67 . The device of  claim 40  comprising a self-assembled phosphonate monolayer bonded to a native oxide surface of a metal, alloy, metalloid, or ceramic, wherein the self-assembled phosphonate monolayer is operable to bond an anti-infective agent. 
   
   
       68 . The device of  claim 40 , the functionalizing layer comprising a phosphonate monolayer bonded to a native oxide surface of a metal, the phosphonate monolayer comprising at least one distal amino functional group bonded to the metal, and a quaternary alkylammonium moiety covalently bonded to the metal surface through the phosphonate interface. 
   
   
       69 . The device of  claim 67  wherein the metal is selected from titanium, stainless steel, cobalt chrome, nickel, molybdenum, tantalum, zirconium, magnesium, manganese, niobium, and alloys thereof. 
   
   
       70 . The device of  claim 40  comprising a medical device. 
   
   
       71 . The device of  claim 70  comprising an implantable or percutaneous medical device 
   
   
       72 . The device of  claim 70  comprising an endoscopic, arthroscopic, or laproscopic medical device. 
   
   
       73 . The device of  claim 70  comprising a cardiac, cardiovascular, or vascular medical device. 
   
   
       74 . The device of  claim 40  selected from the group non-woven meshes, woven meshes, foams, cloth, and fabrics. 
   
   
       75 . The device of  claim 70  comprising an orthopedic, orthopedic trauma, or spine medical device. 
   
   
       76 . The device of  claim 70  selected from the group of general surgical devices and implants selected from drainage catheters, shunts, tapes, meshes, ropes, cables, wires, sutures, skin and tissue staples, burn sheets, external fixation devices; and temporary/non-permanent implants. 
   
   
       77 . The device of  claim 40  wherein the functionalizing layer is disposed on the surface in a pattern or micropattern. 
   
   
       78 . The device of  claim 40  wherein the anti-infective agent is disposed on the functionalizing layer in a pattern or micropattern. 
   
   
       79 . The device of  claim 40  wherein the functionalizing layer includes at least two different regions of functionalization. 
   
   
       80 . The device of  claim 40 , wherein the anti-infective agent layer is continuous. 
   
   
       81 . The device of  claim 40 , wherein the surface is a polymer, and the polymer is selected from the group consisting of polyamides, polyurethanes, polyureas, polyesters, polyketones, polyimides, polysulfides, polysulfoxides, polysulfones, polythiophenes, polypyridines, polypyrroles, polyethers, polyetheretherketones, polyetherketoneketones, silicones, polysiloxanes, polysaccharides, fluoropolymers, amides, imides, polypeptides, polyethylene, polystyrene, polypropylene, glass reinforced epoxies, liquid crystal polymers, thermoplastics, bismaleimide-triazine (BT) resins, benzocyclobutene polymers, Ajinomoto Buildup Films (ABF), low coefficient of thermal expansion (CTE) films of glass and epoxies, and composites including these polymers.