REAGENT AND METHOD FOR PROVIDING COATINGS ON SURFACES

• US 20070292596A1
• Filed: 08/29/2007
• Published: 12/20/2007
• Est. Priority Date: 12/21/2001
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Duquette, Peter, Swan, Dale, Chudzik, Stephen, Everson, Terrence, Amos, Richard, Stucke, Sean, Chappa, Ralph
• Granted Patent: US 7,736,689 B2
• Time in Patent Office: Days
• US Class Current: 427/2.11
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C08F 220/54 Amides , e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
• CPC Class Codes: C08F 220/56 Acrylamide; Methacrylamide
• CPC Class Codes: C09D 4/00 Coating compositions, e.g. paints, varnishes or lacquers, based on organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond ; Coating compositions, based on monomers of macromolecular compounds of groups C09D183/00 - C09D183/16
• CPC Class Codes: Y10S 522/904 Monomer or polymer contains initiating group
• CPC Class Codes: Y10T 428/249991 Synthetic resin or natural rubbers
• CPC Class Codes: Y10T 428/249992 Linear or thermoplastic

Abstract

A grafting reagent and related method of using the reagent to form a polymeric layer on a support surface, and particularly a porous support surface, in a manner that provides and/or preserves desired properties (such as porosity) of the surface. The reagent and method can be used to provide a thin, conformable, uniform, uncrosslinked coating having desired properties onto the surface of a preformed, and particularly a porous, polymeric substrate. The method includes the steps of a) providing a porous support surface, b) providing a nonpolymeric grafting reagent comprising a photoinitator group, c) providing one or more polymerizable monomers adapted to be contacted with the surface, in the presence of the grafting reagent, and to be polymerized upon activation of the photoinitiator; and d) applying the grafting reagent and monomer(s) to the surface in a manner, and under conditions, suitable to coat the surface with the grafting reagent and to cause the polymerization of monomers to the surface upon activation of the grafting reagent.

Claims

1. A method of forming a polymeric coating on a support surface, the method comprising:

a) providing a support surface;

b) providing a nonpolymeric grafting reagent comprising at least one photoinitator group;

c) providing at least one polymerizable monomer solution adapted to be contacted with the surface, in the presence of the grafting reagent, and to be polymerized upon activation of the photoinitiator; and

d) applying the grafting reagent and monomer solution to the surface in a manner, and under conditions, suitable to coat the surface with the grafting reagent and to cause the polymerization of monomers to the surface upon activation of the grafting reagent.

2. A method according to claim 1 wherein the support surface comprises a porous support surface.

3. A method according to claim 1 wherein the reagent further comprises one or more latent reactive groups adapted to be activated in order to covalently attach the grafting reagent to the surface itself, upon activation of the latent reactive group(s).

4. A method according to claim 1 wherein the method is used to form a polymeric coating on the surface of less than about 100 nanometers in thickness.

5. A method according to claim 1 wherein the support surface comprises a material selected from the group consisting of polyolefins, polystyrenes, poly(alkyl)methacrylates and poly(alkyl)acrylates, polyacrylonitriles, poly(vinylacetates), poly(vinyl alcohols), chlorine-containing polymers such as poly(vinyl)chloride, polyoxymethylenes, polycarbonates, polyamides, polyimides, polyurethanes, polyvinylidene difluoride (PVDF), phenolics, amino-epoxy resins, polyesters, silicones, polyethylene terephthalates (PET), polyglycolic acids (PGA), poly-(p-phenyleneterephthalamides), polyphosphazenes, polypropylenes, parylenes, silanes, and silicone elastomers, as well as copolymers and combinations thereof.

6. A method according to claim 5 wherein the surface is provided by the surface of a device selected from medical devices for use within or upon the body and biomedical devices.

7. A method according to claim 6 wherein the medical devices are selected from long-term devices selected from the group consisting of grafts, stents, stent/graft combinations, valves, heart assist devices, shunts, and anastomoses devices;

catheters;

orthopedic devices selected from the group consisting of joint implants, fracture repair devices, and artificial tendons;

dental devices selected from the group consisting of dental implants and dental fracture repair devices;

intraocular lenses;

surgical devices selected from the group consisting of sutures and patches;

synthetic prostheses; and

artificial organs selected from the group consisting of artificial lung, kidney, and heart devices and short-term devices selected from the group consisting of vascular devices;

catheters selected from the group consisting of acute and chronic hemodialysis catheters, cooling/heating catheters, and percutaneous transluminal coronary angioplasty (PTCA) catheters; and

ophthalmic devices selected from the group consisting of contact lenses and glaucoma drain shunts.

8. A method according to claim 6 wherein the biomedical devices are selected from diagnostic slides selected from the group consisting of gene chips, DNA chip arrays, microarrays, protein chips, and fluorescence in situ hybridization (FISH) slides;

arrays, selected from the group consisting of cDNA arrays and oligonucleotide arrays;

blood sampling and testing components;

functionalized microspheres;

tubing and membranes;

blood bags, membranes, cell culture devices, chromatographic support materials, and biosensors.

9. A method according to claim 3 wherein the surface is provided with the polymeric coating prior to, during and/or following fabrication of the device itself and the photoinitiator and latent reactive groups are activated simultaneously to polymerize the monomers and attach the reagent to the surface.

10. A method according to claim 1 wherein the grafting reagent is selected from:

a) tetrakis(4-benzoylbenzyl ether), the tetrakis(4-benzoylbenzoate ester) of pentaerytluitol, and an acylated derivative of tetraphenylmethane, b) 4,5-bis(4-benzoylphenylmethyleneoxy)benzene-1,3-disulfonic acid dipotassium salt (DBDS), 2,5-bis(4-benzoylphenylmethyleneoxy)benzene-1,4-disulfonic acid dipotassium salt (DBHQ), and 2,5-bis(4-benzoylphenylmethyleneoxy)benzene-1-sulfonic acid mono (or di-) sodium salt; and

c) ethylenebis(4-benzoylbenzyldimethylammonium)dibromide (Diphoto-Diquat);

hexamethylenebis(4-benzoylbenzyldimethylammonium)dibromide (Diphoto-Diquat);

1,4-bis(4-benzoylbenzyl)-1,4-dimethylpiperazinediium dibromide (Diphoto-Diquat);

bis(4-benzoylbenzyl)hexamethylenetetraminediium dibromide (Diphoto-Diquat);

bis[2-(4-benzoylbenzyldimethylammonio)ethyl]-4-benzoylbenzylmethylammonium tribromide (Triphoto-Triquat);

4,4-bis(4-benzoylbenzyl)morpholinium bromide (Diphoto-Monoquat);

ethylenebis[(2-(4-benzoylbenzyldimethylammonio)ethyl)-4-benzoylbenzylmethylammonium]tetrabromide (Tetraphoto-Tetraquat);

1,1,4,4-tetrakis(4-benzoylbenzyl)piperazinediium Dibromide (Tetraphoto-Diquat); and

N,N-bis[2-(4-benzoylbenzyloxy)ethyl]-2-aminoethanesulfonic acid, sodium salt (Diphoto-Monosulfonate), and analogues thereof.

11. A method according to claim 1 wherein the polymerizable monomer is selected from:

a) neutral hydrophilic monomers selected from acrylamide, methacrylamide, N-alkylacrylamides, N-vinylpyrrolidinone, N-vinylacetamide, N-vinyl formamide, hydroxyethylacrylate, hydroxyethylmethacrylate, hydroxypropyl acrylate or methacrylate, glycerolmonomethacrylate, and glycerolmonoacrylate;

b) negatively charged hydrophilic functional monomers selected from acrylic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid, AMPS (acrylamidomethylpropane sulfonic acid), vinyl phosphoric acid, vinylbenzoic acid; and

c) positively charged monomers selected from 3-aminopropylmethacrylamide (APMA), methacrylamidopropyltrimethylammonium chloride (MAPTAC), N,N-dimethylaminoethylmethacrylate, N,N-diethylaminoethylacrylate,

and combinations thereof.

12. A method according to claim 1 wherein the polymerizable monomer comprises a macromeric polymerizable molecule selected from poly(ethylene glycol)monomethyacrylate, methoxypoly(ethylene glycol)monomethacrylate, poly(ethylene glycol)monoacrylate, methyacrylamidopoly(acrylamide), poly(acrylamide-co-3-methacrylamidopropylacrylamide), poly(vinylalcohol)methacrylate, poly(vinylalcohol)acrylate, and poly(vinylalcohol)dimethacrylate.

13. A method according to claim 1 wherein the polymeric coating provides an improved combination of properties selected from permeability, antithrombogenicity, lubricity, hemocompatibility, wettability/hydrophilicity, durability of attachment to the surface, biocompatibility, and reduced bacterial adhesion, as compared to a comparable polymeric coating formed by the attachment of preformed polymers.

14. A method according to claim 3 wherein the photoinitiator(s) and latent reactive group(s) are activated simultaneously to polymerize the monomers and attach the reagent to the surface.

15. A method of forming a polymeric coating on a support surface, the method comprising:

a) providing a porous support surface;

b) providing a nonpolymeric grafting reagent comprising at least one photoinitator group, and further comprising one or more latent reactive groups adapted to be activated in order to covalently attach the grafting reagent to the surface itself;

c) providing at least one polymerizable monomer solution adapted to be contacted with the surface, in the presence of the grafting reagent, and to be polymerized upon activation of the photoinitiator; and

d) applying the grafting reagent and monomer solution to the surface in a manner, and under conditions, suitable to coat the surface with the grafting reagent and to cause the polymerization of monomers to the surface upon activation of the grafting reagent and the covalent attachment of the reagent to the surface.

16. A method according to claim 15 wherein the photoinitiator(s) and latent reactive group(s) are activated simultaneously to polymerize the monomers and attach the reagent to the surface, to provide a polymeric coating on the surface of less than about 100 nanometers in thickness.

17. A method according to claim 15 wherein the support surface comprises a material selected from the group consisting of polyolefins, polystyrenes, poly(alkyl)methacrylates and poly(alkyl)acrylates, polyacrylonitriles, poly(vinylacetates), poly(vinyl alcohols), chlorine-containing polymers such as poly(vinyl)chloride, polyoxymethylenes, polycarbonates, polyamides, polyimides, polyurethanes, polyvinylidene difluoride (PVDF), phenolics, amino-epoxy resins, polyesters, silicones, polyethylene terephthalates (PET), polyglycolic acids (PGA), poly-(p-phenyleneterephthalamides), polyphosphazenes, polypropylenes, parylenes, silanes, and silicone elastomers, as well as copolymers and combinations thereof, and the grafting reagent is selected from:

a) tetrakis(4-benzoylbenzyl ether), the tetrakis(4-benzoylbenzoate ester) of pentaerythritol, and an acylated derivative of tetraphenylmethane,

b) 4,5-bis(4-benzoylphenylmethyleneoxy)benzene-1,3-disulfonic acid dipotassium salt (DBDS), 2,5-bis(4-benzoylphenylmethyleneoxy)benzene-1,4-disulfonic acid dipotassium salt (DBHQ), and 2,5-bis(4-benzoylphenylmethyleneoxy)benzene-1-sulfonic acid mono (or di-) sodium salt; and

c) ethylenebis(4-benzoylbenzyldimethylammonium) dibromide (Diphoto-Diquat);

hexamethylenebis(4-benzoylbenzyldimethylammonium) dibromide (Diphoto-Diquat);

1,4-bis(4-benzoylbenzyl)-1,4-dimethylpiperazinediium dibromide (Diphoto-Diquat);

bis(4-benzoylbenzyl)hexamethylenetetraminediium dibromide (Diphoto-Diquat);

bis[2-(4-benzoylbenzyldimethylammonio)ethyl]-4-benzoylbenzylmethylammonium tribromide (Triphoto-Triquat);

4,4-bis(4-benzoylbenzyl)morpholinium bromide (Diphoto-Monoquat);

ethylenebis[(2-(4-benzoylbenzyldimethylammonio)ethyl)-4-benzoylbenzylmethylammonium]tetrabromide (Tetraphoto-Tetraquat);

1,1,4,4-tetrakis(4-benzoylbenzyl)piperazinediium Dibromide (Tetraphoto-Diquat); and

N,N-bis[2-(4-benzoylbenzyloxy)ethyl]-2-aminoethanesulfonic acid, sodium salt (Diphoto-Monosulfonate), and analogues thereof.

18. A method according to claim 17 wherein the surface is provided by the surface of a device selected from medical devices for use within or upon the body and biomedical devices.

19. A method according to claim 18 wherein,

a) the medical devices are selected from long-term devices selected from the group consisting of grafts, stents, stent/graft combinations, valves, heart assist devices, shunts, and anastomoses devices;

catheters;

orthopedic devices selected from the group consisting of joint implants, fracture repair devices, and artificial tendons;

dental devices selected from the group consisting of dental implants and dental fracture repair devices;

intraocular lenses;

surgical devices selected from the group consisting of sutures and patches;

synthetic prostheses; and

artificial organs selected from the group consisting of artificial lung, kidney, and heart devices and short-term devices selected from the group consisting of vascular devices;

catheters selected from the group consisting of acute and chronic hemodialysis catheters, cooling/heating catheters, and percutaneous transluminal coronary angioplasty (PTCA) catheters; and

ophthalmic devices selected from the group consisting of contact lenses and glaucoma drain shunts; and

b) the biomedical devices are selected from diagnostic slides selected from the group consisting of gene chips, DNA chip arrays, microarrays, protein chips, and fluorescence in situ hybridization (FISH) slides;

arrays, selected from the group consisting of cDNA arrays and oligonucleotide arrays;

blood sampling and testing components;

functionalized microspheres;

tubing and membranes;

blood bags, membranes, cell culture devices, chromatographic support materials, and biosensors.

20. A method according to claim 17 wherein the polymerizable monomer is selected from:

a) neutral hydrophilic structural monomers selected from acrylamide, methacrylamide, N-alkylacrylamides, N-vinylpyrrolidinone, N-vinylacetamide, N-vinyl formamide, hydroxyethylacrylate, hydroxyethylmethacrylate, hydroxypropyl acrylate or methacrylate, glycerolmonomethacrylate, and glycerolmonoacrylate;

b) negatively charged hydrophilic functional monomers selected from acrylic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid, AMPS (acrylamidomethylpropane sulfonic acid), vinyl phosphoric acid, vinylbenzoic acid; and

c) positively charged monomers selected from 3-aminopropylmethacrylamide (APMA), methacrylamidopropyltrimethylammonium chloride (MAPTAC), N,N-dimethylaminoethylmethacrylate, N,N-diethylaminoethylacrylate,

and combinations thereof.

21-42. -42. (canceled)