US6921811B2
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US
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Bioactive coating composition and methods
Assignee: Biosurface Engineering Technologies Inc
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Filing: 2001-07-31
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Granted: 2005-07-26
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Expires: 2021-07-31
Abstract
Abstract The present invention provides a bioactive coating composition, method and devices for bodily fluid-contacting surfaces. The coating comprises a complex of Formula II: wherein R 1 is an C 1-18 alkyl or C 6-32 aryl group, each R 2 is independently selected from the group consisting of C 1-18 alkyl and C 6-32 aryl, R 3 is N or O, n is a number from 1 to 10, and x in a number from 1 to about 30, directly bound to a heparin-activity molecule via covalent bonding, with one or more bioactive molecules bound to the heparin-activity molecule. The bioactive molecule may be an adhesive molecule such as fibronectin, a growth factor such as basic fibroblast growth factor, or any other bioactive molecule that binds, by any mechanism, to a heparin-activity molecule
Inventors
- 👤 Paul O. Zamora
- 👤 Ray Tsang
- 👤 Shigemasa Osaki
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 19:25
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/50; A61L27/54; A61L15/00; A61L15/16; A61L15/22; A61L15/28; A61L15/42; A61L15/44; A61L17/00; A61L17/005; A61L29/00; A61L29/14; A61L29/16; A61L31/00; A61L31/14; A61L31/16; A61L33/00; A61L33/0005; A61L33/0011; A61L2300/00; A61L2300/20; A61L2300/252; A61L2300/40; A61L2300/412; A61L2300/414; A61L2300/42; A61L2300/60; A61L2300/606; A61L2300/80; A61L2300/802
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
97 words
A coating composition for contacting surfaces of medical device, said composition comprising a molecule of Formula I: wherein R 1 is an C 1-18 alkyl or C 6-32 aryl group, each R 2 is independently selected from the group consisting of C 1-18 alkyl and C 6-32 aryl R 3 is N or O, n is a number from 1 to 10, and x is a number from 1 to about 30, bound to a heparin-activity molecule via a covalent bond, thereby forming a silyl-heparin covalent complex, with a bioactive molecule directly bound to the heparin-activity molecule.
Claim 2
Dependent Claim
97 words
A coating composition for contacting surfaces of medical device, said composition comprising a molecule of Formula I: wherein R 1 is an C 1-18 alkyl or C 6-32 aryl group, each R 2 is independently selected from the group consisting of C 1-18 alkyl and C 6-32 aryl R 3 is N or O, n is a number from 1 to 10, and x is a number from 1 to about 30, bound to a heparin-activity molecule via a covalent bond, thereby forming a silyl-heparin covalent complex, with a bioactive molecule directly bound to the heparin-activity molecule.
Claim 3
Dependent Claim
28 words
The composition according to claim 1 , wherein the silyl-heparin covalent complex has a disassociation rate from the contacting surface determined by the value of n and x.
Claim 4
Dependent Claim
21 words
The composition according to claim 1 , wherein the silyl-heparin covalent complex binds to the contacting surfaces via hydrophobic bonding interactions.
Claim 5
Dependent Claim
60 words
The composition according to claim 3 , wherein the heparin-activity molecule is heparin, heparan sulfate, hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, or a molecule including a mixture of variably sulfated polysaccharide chains composed of repeating units of D-glucosamine and either L-iduronic or D-glucuronic acids, salts of any of the foregoing and derivatives of any of the foregoing.
Claim 6
Dependent Claim
21 words
The composition according to claim 1 , wherein said bioactive molecule is directly bound to the heparin-activity molecule by affinity complexation.
Claim 7
Dependent Claim
16 words
The composition according to claim 1 , wherein the silyl-heparin covalent complex comprises [benzyl-bis(dimethylsilylmethyl)]-(N-heparinyl)-carbamate or [benzyl-tris(dimethylsilylmethyl)]-(N-heparinyl)-carbamate.
Claim 8
Dependent Claim
23 words
The composition according to claim 1 , wherein said bioactive molecule is an adhesive molecule, a growth factor molecule or a therapeutic molecule.
Claim 9
Dependent Claim
41 words
The composition according to claim 7 , wherein the adhesive molecule is fibronectin, laminin, vitronectin, thrombospondin, gelatin, polylysine, polyornithine, peptide polymers containing adhesive sequences and heparin binding sequences, sulfated complex carbohydrates, dextran sulfate, growth hormones, cytokines, lectins, or peptidic polymers thereof.
Claim 10
Dependent Claim
55 words
The composition according to claim 7 , wherein the growth factor molecule is fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, hepatocyte growth factor, placental growth factor, insulin-like growth factor, nerve growth factors and neurotrophins, heparin-binding epidermal growth factor, transforming growth factor-β, bone morphogenetic protein 2, osteogenic protein 1 or keratinocyte growth factor.
Claim 11
Dependent Claim
107 words
A medical device with at least one contacting surface for contacting bodily fluids, the surface having coated thereon a coating composition comprising a molecule of Formula I: wherein R 1 is an C 1-18 alkyl or C 6-32 aryl group, each R 2 is independently selected from the group consisting of C 1-18 alkyl and C 6-32 aryl, R 3 is N or O, n is a number from 1 to 10, and x is a number from 1 to about 30, directly bound to a heparin-activity molecule via covalent bonding, thereby forming a silyl-heparin covalent complex, with a bioactive molecule directly bound to the heparin-activity molecule.
Claim 12
Dependent Claim
107 words
A medical device with at least one contacting surface for contacting bodily fluids, the surface having coated thereon a coating composition comprising a molecule of Formula I: wherein R 1 is an C 1-18 alkyl or C 6-32 aryl group, each R 2 is independently selected from the group consisting of C 1-18 alkyl and C 6-32 aryl, R 3 is N or O, n is a number from 1 to 10, and x is a number from 1 to about 30, directly bound to a heparin-activity molecule via covalent bonding, thereby forming a silyl-heparin covalent complex, with a bioactive molecule directly bound to the heparin-activity molecule.
Claim 13
Dependent Claim
20 words
The device according to claim 10 , wherein the silyl-heparin covalent complex binds to the surface via hydrophobic bonding interactions.
Claim 14
Dependent Claim
27 words
The device according to claim 10 , wherein the silyl-heparin covalent complex has a disassociation rate from the surface determined by the value of n and x.
Claim 15
Dependent Claim
60 words
The device according to claim 10 , wherein the heparin-activity molecule is heparin, heparan sulfate, hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, or a molecule including a mixture of variably sulfated polysaccharide chains composed of repeating units of D-glucosamine and either L-iduronic or D-glucuronic acids, salts of any of the foregoing and derivatives of any of the foregoing.
Claim 16
Dependent Claim
21 words
The device according to claim 10 , wherein said bioactive molecule is directly bound to the heparin-activity molecule by affinity complexation.
Claim 17
Dependent Claim
16 words
The device according to claim 10 , wherein the silyl-heparin covalent complex comprises [benzyl-bis(dimethylsilylmethyl)]-(N-heparinyl)-carbamate or [benzyl-tris(dimethylsilylmethyl)]-(N-heparinyl)-carbamate.
Claim 18
Dependent Claim
38 words
The device according to claim 10 , wherein the device is a blood gas exchange device, blood filter, artificial blood vessel, artificial valve, prosthetic, blood shunt, catheter, bone replacement, cartilage replacement, suture, graft, catheter or nerve growth guide.
Claim 19
Dependent Claim
23 words
The device according to claim 10 , wherein said bioactive molecule is an adhesive molecule, a growth factor molecule or a therapeutic molecule.
Claim 20
Dependent Claim
41 words
The device according to claim 17 , wherein the adhesive molecule is fibronectin, laminin, vitronectin, thrombospondin, gelatin, polylysine, polyornithine, peptide polymers containing adhesive sequences and heparin binding sequences, sulfated complex carbohydrates, dextran sulfate, growth hormones, cytokines, lectins, or peptidic polymers thereof.
Claim 21
Dependent Claim
25 words
The device according to claim 17 , wherein the bioactive molecule is an adhesive molecule, whereby the contacting surface is non-thrombogenic and promotes cellular adhesion.
Claim 22
Dependent Claim
55 words
The device according to claim 17 , wherein the growth factor molecule is fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, hepatocyte growth factor, placental growth factor, insulin-like growth factor, nerve growth factors and neurotrophins, heparin-binding epidermal growth factor, transforming growth factor-β, bone morphogenetic protein 2, osteogenic protein 1 or keratinocyte growth factor.
Claim 23
Independent Claim
119 words
A method for coating a contacting surface of a medical device with a bioactive coating composition, comprising: providing a hydrophobic silyl moiety of Formula I wherein R 1 is an C 1-18 alkyl or C 6-32 aryl group, each R 2 is independently selected from the group consisting of C 1-18 alkyl and C 6-32 aryl, R 3 is N or O, and n is a number from 1 to 10 binding said silyl moiety to a heparin-activity molecule via covalent bonding, wherein x is from 1 to about 30 for each heparin-activity molecule, thereby forming a silyl-heparin complex, attaching the silyl-heparin complex to the contacting surface by hydrophobic interaction, and attaching a bioactive molecule to the heparin-activity molecule.
Claim 24
Independent Claim
119 words
A method for coating a contacting surface of a medical device with a bioactive coating composition, comprising: providing a hydrophobic silyl moiety of Formula I wherein R 1 is an C 1-18 alkyl or C 6-32 aryl group, each R 2 is independently selected from the group consisting of C 1-18 alkyl and C 6-32 aryl, R 3 is N or O, and n is a number from 1 to 10 binding said silyl moiety to a heparin-activity molecule via covalent bonding, wherein x is from 1 to about 30 for each heparin-activity molecule, thereby forming a silyl-heparin complex, attaching the silyl-heparin complex to the contacting surface by hydrophobic interaction, and attaching a bioactive molecule to the heparin-activity molecule.
Claim 25
Dependent Claim
26 words
The method of claim 21 , wherein the silyl-heparin complex has a disassociation rate from the contacting surface determined by the value of n and x.
Claim 26
Dependent Claim
59 words
The method of claim 21 , wherein the heparin-activity molecule is heparin, heparan sulfate, hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, or a molecule including a mixture of variably sulfated polysaccharide chains composed of repeating units of D-glucosamine and either L-iduronic or D-glucuronic acids, salts of any of the foregoing and derivatives of any of the foregoing.
Claim 27
Dependent Claim
19 words
The method of claim 21 , wherein the bioactive molecule is attached to the heparin-activity molecule by affinity complexation.
Claim 28
Dependent Claim
14 words
The method of claim 21 , wherein the silyl-heparin complex comprises [benzyl-bis(dimethylsilylmethyl)]-(N-heparinyl)-carbamate or [benzyl-tris(dimethylsilylmethyl)]-(N-heparinyl)-carbamate.
Claim 29
Dependent Claim
24 words
The method of claim 21 , wherein the bioactive molecule is an adhesive molecule, whereby the contacting surface is non-thrombogenic and promotes cellular adhesion.
Claim 30
Dependent Claim
22 words
The method of claim 21 , wherein the bioactive molecule is an adhesive molecule, a growth factor molecule or a therapeutic molecule.
Claim 31
Dependent Claim
40 words
The method of claim 27 , wherein the adhesive molecule is fibronectin, laminin, vitronectin, thrombospondin, gelatin, polylysine, polyornithine, peptide polymers containing adhesive sequences and heparin binding sequences, sulfated complex carbohydrates, dextran sulfate, growth hormones, cytokines, lectins, or peptidic polymers thereof.
Claim 32
Dependent Claim
54 words
The method of claim 27 , wherein the growth factor molecule is fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, hepatocyte growth factor, placental growth factor, insulin-like growth factor, nerve growth factors and neurotrophins, heparin-binding epidermal growth factor, transforming growth factor-β, bone morphogenetic protein 2, osteogenic protein 1 or keratinocyte growth factor.
References Cited (Backward Citations)
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