US6143354A
Expired / Lapsed
US
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One-step method for attachment of biomolecules to substrate surfaces
Assignee: Medtronic Inc
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Filing: 1999-02-08
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Granted: 2000-11-07
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Expires: 2019-02-08
Abstract
Abstract A method of modifying the surface characteristics of a substrate, particularly a polymeric material. The method involves grafting ethylenically unsaturated monomers and attaching biomolecules, such as heparin, to the surface of the substrate, such as a polymeric material, in one step using an oxidizing metal, such as ceric ions.
Inventors
- 👤 Edouard Koulik
- 👤 Michel Verhoeven
- 👤 Patrick Cahalan
- 👤 Linda Cahalan
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:40
CPC Classifications
A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0011; A61L27/00; A61L27/28; A61L27/34
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
69 words
A method of making a medical device having a biomolecule immobilized on a substrate surface of a solid polymeric material containing less than 10% water, the method comprising contacting the substrate surface with a reaction mixture comprising a biomolecule, a source of oxidizing metal ions, and an ethylenically unsaturated monomer, the contacting step occurring tinder conditions effective to immobilize the biomolecule on the substrate surface in a one-step reaction.
Claim 2
Independent Claim
69 words
A method of making a medical device having a biomolecule immobilized on a substrate surface of a solid polymeric material containing less than 10% water, the method comprising contacting the substrate surface with a reaction mixture comprising a biomolecule, a source of oxidizing metal ions, and an ethylenically unsaturated monomer, the contacting step occurring tinder conditions effective to immobilize the biomolecule on the substrate surface in a one-step reaction.
Claim 3
Dependent Claim
45 words
The method of claim 1, wherein the contacting step further comprises immersing the substrate in the reaction mixture, the reaction mixture comprising an aqueous solution comprising one or more biomolecules, one or more sources of oxidizing metal ions, and one or more ethylenically unsaturated monomers.
Claim 4
Dependent Claim
79 words
The method of claim 2, wherein the reaction mixture further comprises: one or more biomolecules in an amount of at least about 0.02 wt-%, based on the total weight of the reaction mixture; oxidizing metal ions at a concentration of at least about 0.001 M, based on the total volume of the reaction mixture; and one or more ethylenically unsaturated monomers in an amount of at least about 10 wt-%, based on the total weight of the reaction mixture.
Claim 5
Dependent Claim
82 words
The method of claim 3, wherein the reaction mixture further comprises: one or more biomolecules in an amount of no more than about 1.0 wt-%, based on the total weight of the reaction mixture; oxidizing metal ions at a concentration of no more than about 0.01 M, based on the total volume of the reaction mixture; and one or more ethylenically unsaturated monomers in an amount of no more than about 50 wt-% based on the total weight of the reaction mixture.
Claim 6
Dependent Claim
38 words
The method of claim 1, wherein the contacting step further comprises contacting the substrate surface with the reaction mixture in a liquid carrier at a temperature of at least about 10° C. for at least about 15 minutes.
Claim 7
Dependent Claim
11 words
The method of claim 5, wherein the liquid carrier composes water.
Claim 8
Dependent Claim
11 words
The method of claim 5, wherein the temperature is room temperature.
Claim 9
Dependent Claim
64 words
The method of claim 1, wherein the biomolecule is selected from the group consisting of an antibacterial agent, an antimicrobial agent, an anticoagulant, an antithrombotic agent, an antiplatelet agent, an anti-inflammatory, an enzyme, a catalyst, a hormone, a growth factor, a drug, a vitamin, an antibody, an antigen, a nucleic acid, a dye, a DNA, an RNA, a protein, a peptide, and mixtures thereof.
Claim 10
Dependent Claim
14 words
The method of claim 8, wherein the biomolecule is synthetically derived or naturally occurring.
Claim 11
Dependent Claim
14 words
The method of claim 8, wherein the biomolecule comprises heparin or a salt thereof.
Claim 12
Dependent Claim
16 words
The method of claim 1, wherein the substrate comprises a solid organic polymer or a metal.
Claim 13
Dependent Claim
41 words
The method of claim 11, wherein the substrate comprises a solid organic polymer and the method further includes preactivating the substrate surface prior to the contacting step, wherein the preactivating step comprises one of corona treating, ozone treating, and acid etching.
Claim 14
Dependent Claim
16 words
The method of claim 11, wherein the substrate comprises a metal surface coated with a vinylsilane.
Claim 15
Dependent Claim
33 words
The method of claim 1, wherein the substrate comprises a solid organic polymer comprising moieties selected from the group consisting of carbonyl, carboxyl, hydroxyl, amino, mercapto, urethane, ether, hydroperoxide groups, and combinations thereof.
Claim 16
Dependent Claim
36 words
The method of claim 14, wherein the substrate comprises a polymer selected from the group consisting of a polyurethane, a polyolefin, a silicone, a fluoropolymer, a polyester, a polyether, a polyamide, and blends and copolymers thereof.
Claim 17
Dependent Claim
16 words
The method of claim 15, wherein the substrate comprises a polyurethane or a polyether block amide.
Claim 18
Dependent Claim
66 words
The method of claim 1, wherein the contacting step further comprises contacting the substrate with the reaction mixture, the reaction mixture comprising oxidizing metal ions introduced into the reaction mixture in the form of a ceric salt selected from the group consisting of ceric nitrate, ceric sulfate, ceric ammonium nitrate, ceric ammonium sulfate, ceric ammonium pyrophosphate, ceric iodate, ceric salts of organic acids, and mixtures thereof.
Claim 19
Dependent Claim
26 words
The method of claim 1, wherein the ethylenically unsaturated monomer is selected from the group consisting of a mono-vinyl monomer, a di-vinyl monomer, and mixtures thereof.
Claim 20
Dependent Claim
27 words
The method of claim 18, wherein the ethylenically unsaturated monomer is selected from the group consisting of a vinyl monomer, an acrylate, a methacrylate, and mixtures thereof.
Claim 21
Dependent Claim
43 words
The method of claim 19, wherein the ethylenically unsaturated monomer is selected from the group consisting of n-vinylpyrrolidone, styrene, acrylonitrile, acrylamide, N,N-methylene diacrylamide, aminopropyl acrylate, aminoethyl acrylate, ethylacrylate, acrylic acid, polyethyleneglycol methacrylate, hydroxyethyl methacrylate, glycidyl methacrylate, butyl methacrylate, methacrylic acid, and mixtures thereof.
Claim 22
Dependent Claim
11 words
The method of claim 1, wherein the surface formed is biocompatible.
Claim 23
Independent Claim
71 words
A method of modifying the surface characteristics of a solid polymeric material containing less than 10% water, the solid polymeric material comprising a substrate surface, the method comprising contacting the substrate surface of the solid polymeric material with a reaction mixture comprising a biomolecule, oxidizing metal ions, and an ethylenically unsaturated monomer, the contacting step occurring under conditions effective to immobilize the biomolecule on the substrate surface in a one-step process.
Claim 24
Independent Claim
71 words
A method of modifying the surface characteristics of a solid polymeric material containing less than 10% water, the solid polymeric material comprising a substrate surface, the method comprising contacting the substrate surface of the solid polymeric material with a reaction mixture comprising a biomolecule, oxidizing metal ions, and an ethylenically unsaturated monomer, the contacting step occurring under conditions effective to immobilize the biomolecule on the substrate surface in a one-step process.
Claim 25
Dependent Claim
83 words
The method of claim 22, wherein the reaction mixture comprises: a liquid carrier; a biomolecule in an amount of about 0.02 wt-% to about 1.0 wt-%, based on the total weight of the reaction mixture; Ce 4+ ions at a concentration of about 0.001 M to about 0.01 M, based on the total volume of the reaction mixture; and an ethylenically unsaturated monomer in an amount of about 10 wt-% to about 50 wt-%, based on the total weight of the reaction mixture.
Claim 26
Dependent Claim
33 words
The method of claim 23, wherein the contacting step comprises contacting the substrate surface with the reaction mixture at a temperature of at least about 10° C. for at least about 15 minutes.
Claim 27
Dependent Claim
11 words
The method of claim 24, wherein the temperature is room temperature.
Claim 28
Dependent Claim
21 words
The method of claim 22, wherein the biomolecule is heparin or a salt thereof and the ethylenically unsaturated monomer is acrylamide.
Claim 29
Independent Claim
59 words
A method of modifying the surface characteristics of a metal surface coated with a vinylsilane, the method comprising contacting the metal surface coated with a vinylsilane with a reaction mixture comprising a biomolecule, oxidizing metal ions, and an ethylenically unsaturated monomer, the contacting step occurring under conditions effective to immobilize the biomolecule on the surface in a one-step process.
Claim 30
Independent Claim
59 words
A method of modifying the surface characteristics of a metal surface coated with a vinylsilane, the method comprising contacting the metal surface coated with a vinylsilane with a reaction mixture comprising a biomolecule, oxidizing metal ions, and an ethylenically unsaturated monomer, the contacting step occurring under conditions effective to immobilize the biomolecule on the surface in a one-step process.
Claim 31
Independent Claim
85 words
A method of delivering a biologically active agent, the method comprising contacting a substrate surface of a solid polymeric material containing less than 10% water with a reaction mixture comprising the biologically active agent, oxidizing metal ions, and an ethylenically unsaturated monomer under conditions effective to immobilize the biologically active agent on the substrate surface in a one-step reaction process; and contacting the substrate surface having the biologically active agent attached thereto to a physiological solution under conditions effective to release the biologically active agent.
Claim 32
Independent Claim
85 words
A method of delivering a biologically active agent, the method comprising contacting a substrate surface of a solid polymeric material containing less than 10% water with a reaction mixture comprising the biologically active agent, oxidizing metal ions, and an ethylenically unsaturated monomer under conditions effective to immobilize the biologically active agent on the substrate surface in a one-step reaction process; and contacting the substrate surface having the biologically active agent attached thereto to a physiological solution under conditions effective to release the biologically active agent.
Claim 33
Dependent Claim
11 words
A modified polymeric material preparable by the method of claim 22.
Claim 34
Dependent Claim
10 words
A medical device preparable by the method of claim 1.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2003-11-07 | 2004-05-08 | 2004-11-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2007-11-07 | 2008-05-08 | 2008-11-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2011-11-07 | 2012-05-08 | 2012-11-07 | $7700.00 | Window Closed / Lapsed |