Method for attachment of biomolecules to medical device surfaces
First Claim
1. A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of:
- (a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety;
(b) combining the amide moiety with an amine forming agent to form an amine-functional surface;
(c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface;
(d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an aldehyde moiety formed by combining a periodate with a 2-aminoalcohol moiety, an aldehyde moiety formed by combining a periodate with a 1,2-dihydroxy moiety, an epoxide moiety, an isocyanate moiety, a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety and a carboxylate moiety; and
(e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
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Accused Products
Abstract
Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule such as a glycoprotein having an unsubstituted amide moiety is combined with an amine forming agent to form an amine-functional biomolecule. The amine-functional biomolecule is combined with a medical device surface having a chemical moiety such as aldehyde, epoxide, isocyanate, 1,2-dicarbonyl, phosphate, sulphate or carboxylate to form a chemical bond immobilizing the biomolecule on the surface. The chemical bond may be combined with a reducing agent or a stabilizing agent. The aldehyde moiety may be formed by combining a periodate with a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety. Alternatively, an amine-functional medical device surface is combined with a biomolecule having a chemical moiety that reacts with an amine moiety. In another embodiment, the amine-functional biomolecule is converted to a guanidino-functional biomolecule and is combined with a medical device surface having a chemical moiety that reacts with a guanidino moiety. Alternatively, an amine-functional medical device surface is converted to a guanidino-functional surface and is combined with a biomolecule having the chemical moiety. Biomolecules may be crosslinked by combining the amine-functional or guanidino-functional biomolecule with a biomolecule having a chemical moiety that forms a chemical bond with an amine moiety or a guanidino moiety.
120 Citations
53 Claims
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1. A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of:
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(a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety;
(b) combining the amide moiety with an amine forming agent to form an amine-functional surface;
(c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface;
(d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an aldehyde moiety formed by combining a periodate with a 2-aminoalcohol moiety, an aldehyde moiety formed by combining a periodate with a 1,2-dihydroxy moiety, an epoxide moiety, an isocyanate moiety, a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety and a carboxylate moiety; and
(e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating. - View Dependent Claims (2, 3, 4)
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5. A method of forming a coating on a surface of a medical device, the method comprising the steps of:
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(a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety;
(b) combining the amide moiety with an amine forming agent to form an amine-functional surface;
(c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface;
(d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety, and a carboxylate moiety; and
(e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating. - View Dependent Claims (6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of:
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(a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety;
(b) combining the amide moiety with an amine forming agent to form an amine-functional surface;
(c) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an epoxide moiety and an isocyanate moiety; and
(d) combining the chemical moiety with the surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24)
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25. A method of forming a crosslinked coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of:
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(a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising unsubstituted amide moieties;
(b) combining the amide moieties with an amine forming agent to form amine moieties;
(c) providing biomolecules having at least one chemically reactive moiety selected from the group consisting of a 1,2-dihydroxy moiety and a 2-aminoalcohol moiety, combining periodate with the biomolecules to oxidize the chemically reactive moiety to form aldehyde moieties;
(d) combining the biomolecules with the surface;
(e) allowing the aldehyde moieties to combine with the amine moieties to form imine moieties; and
(f) reacting the imine moieties with a reducing agent to form amine linkages, the amine linkages immobilizing and crosslinking the biomolecules on the surface, the immobilized and crosslinked biomolecules forming the coating. - View Dependent Claims (26, 27, 28, 29, 30, 31, 32, 33, 34)
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35. A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of:
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(a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety;
(b) combining the amide moiety with an amine forming agent selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene to form an amine-functional surface;
(c) providing a biomolecule, the biomolecule comprising a 2-aminoalcohol moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 2-aminoalcohol moiety to form an aldehyde moiety;
(d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety; and
(e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44)
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45. A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of:
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(a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety;
(b) combining the amide moiety with an amine forming agent selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene to form an amine-functional surface;
(c) providing a biomolecule, the biomolecule comprising a 1,2-dihydroxy moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 1,2-dihydroxy moiety to form an aldehyde moiety;
(d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety; and
(e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating. - View Dependent Claims (46, 47, 48, 49, 50, 51, 52, 53)
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Specification