METHODS AND REAGENTS FOR PREPARING BIOMOLECULE-CONTAINING COATINGS
Polymeric coatings that include coupled biomolecules are formed on the surface of articles, such as medical devices. A coated layer that includes a synthetic polymer including a reactive group is formed on a surface and then a biomolecule is attached to the reactive group. The synthetic polymer can be an acrylate polymer or an amine-containing polymer having pendent photoreactive groups.
1 . An article having a biomolecule-containing coating, the coating comprising:
(a) a coated layer comprising an adherent acrylate polymer comprising a pendent first reactive group, wherein the acrylate polymer has a solubility in tetrahydrofuran in the range of 1 mg/mL to 100 mg/mL; and
(b) a coated layer comprising a biomolecule, wherein the biomolecule is coupled to the acrylate polymer via the first reactive group.
2 . The article of claim 1 wherein the acrylate polymer is a selected from the group of alkyl(meth)acrylate polymers and aromatic(meth)acrylate polymers.
3 . The article of claim 2 wherein the acrylate polymer comprises an alkyl(meth)acrylate polymer having an alkyl chain length from 2 to 4 carbons.
4 . The article of claim 3 wherein the acrylate polymer comprises a butyl(meth)acrylate polymer.
5 . The article of claim 1 wherein the first reactive group is an amine-reactive group.
6 . The article of claim 5 wherein the first reactive group is selected from N-oxysuccinimide, isothiocyanate, bromoacetyl, epoxide, and trimethylsilane.
7 . The article of claim 6 wherein the acrylate polymer is formed by copolymerizing an acrylate monomer with a monomer comprising (a) a group selected from N-oxysuccinimide, isothiocyanate, bromoacetyl, epoxide, and trimethylsilane; and (b) a vinyl group.
8 . The article of claim 1 wherein 20% or less of the monomers of the acrylate polymer include first reactive groups.
9 . The article of claim 1 wherein 5% or greater of the monomers of the acrylate polymer include first reactive groups.
10 . The article of claim 1 wherein 5% to 20% of the monomers of the acrylate polymer include first reactive groups.
11 . The article of claim 1 wherein the biomolecule comprises a biocompatible agent.
12 . The article of claim 1 wherein the biomolecule comprises a polypeptide.
13 . The article of claim 1 wherein the biomolecule comprises a polysaccharide.
14 . The article of claim 13 wherein the biomolecule is heparin.
15 . The article of claim 14 having a surface heparin activity of 5 mU/cm 2 or greater.
16 . The article of claim 1 which is an implantable medical device.
17 . The article of claim 1 wherein the first coated layer further comprises a bioactive agent that is not coupled to the adherent acrylate polymer.
18 . The medical article of claim 17 wherein the bioactive agent is selected from the group consisting of anti-proliferative agents, an anti-mitotics, and antibiotics.
19 . A method for providing a coating to a medical device comprising the steps of:
(a) obtaining a medical device having a coated layer adhered to the surface of the medical device and comprising an adherent acrylate polymer comprising a pendent first reactive group, wherein the acrylate polymer has a solubility in tetrahydrofuran in the range of 1 mg/mL to 100 mg/mL; and
(b) disposing a coating composition on the coated layer that comprises the acrylate polymer, wherein the coating composition comprises a biomolecule, and wherein the biomolecule is reacted with the first reactive group to couple to the biomolecule to the acrylate polymer.
20 . An implantable medical device having a coating with heparin activity of 5 mU/cm 2 or greater, the coating comprising:
(a) a coated layer comprising an adherent acrylate polymer comprising a pendent first reactive group, wherein the acrylate polymer has a solubility in tetrahydrofuran in the range of 1 mg/mL to 100 mg/mL; and
(b) heparin coupled to the acrylate polymer via the first reactive group.
21 . The article of claim 1 , wherein the acrylate polymer has a solubility in tetrahydrofuran in the range of 10 mg/mL to 50 mg/mL.