Patent US5061750A successfully refreshed from Google Patents.
US5061750A
Expired / Lapsed
US
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Covalent attachment of anticoagulants and the like onto biomaterials
Assignee: Cordis Corp
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Filing: 1990-07-18
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Granted: 1991-10-29
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Expires: 2010-07-18
Abstract
Abstract A substrate for medical devices and a process for making the substrate is provided, the substrate having on at least part of its surface a blood-compatible surface produced by coupling a physiologically active substance to the surface. The physiologically active substance is one having an inhibitory effect on the formation of blood clots and/or is capable of breaking down blood clots formed. The physiologically active substance is bonded to a polyacid, and the polyacid is attached to the surface by a covalent bond.
Inventors
- 👤 Jan Feijen
- 👤 Gerardus H. M. Engbers
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 15:24
CPC Classifications
A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0011; A61L33/0029; A61L33/0047
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
209 words
In a substrate component of a synthetic medical device, said substrate component having a polymeric surface, at least a part of said polymeric substrate surface being for contacting blood when the medical device is in use, said blood-contacting polymeric substrate surface having a physiologically active substance which has an inhibitory effect on the formation of blood clots or is capable of breaking down blood clots formed, wherein the improvement comprises: said physiologically active substrate is graft bonded to said polymeric substrate surface through a polyacid link chain moiety, said polyacid being a polymer containing from between about 1000 and 10,000 monomeric units which contain a carboxyl group, said bond being through a plurality of said monomeric unit carboxyl groups of the polyacid, said link chain polyacid is bonded to said polymeric substrate surface by a chemical bond, and said chemical bond is a covalent bond between a functional group of the link chain polyacid and a functional group of said polymeric substrate surface; and said physiologically active substance is selected from the group consisting of a substrate having an anti-coagulant effect, a non-synthetic substance having a fibrinolytic activity, a substance having a blood platelet aggregation inhibiting effect, a substance having a blood platelet adhesion inhibiting effect, and combinations thereof.
Claim 2
Dependent Claim
209 words
In a substrate component of a synthetic medical device, said substrate component having a polymeric surface, at least a part of said polymeric substrate surface being for contacting blood when the medical device is in use, said blood-contacting polymeric substrate surface having a physiologically active substance which has an inhibitory effect on the formation of blood clots or is capable of breaking down blood clots formed, wherein the improvement comprises: said physiologically active substrate is graft bonded to said polymeric substrate surface through a polyacid link chain moiety, said polyacid being a polymer containing from between about 1000 and 10,000 monomeric units which contain a carboxyl group, said bond being through a plurality of said monomeric unit carboxyl groups of the polyacid, said link chain polyacid is bonded to said polymeric substrate surface by a chemical bond, and said chemical bond is a covalent bond between a functional group of the link chain polyacid and a functional group of said polymeric substrate surface; and said physiologically active substance is selected from the group consisting of a substrate having an anti-coagulant effect, a non-synthetic substance having a fibrinolytic activity, a substance having a blood platelet aggregation inhibiting effect, a substance having a blood platelet adhesion inhibiting effect, and combinations thereof.
Claim 3
Dependent Claim
16 words
The substrate as claimed in claim 1, wherein said polyacid is soluble in an aqueous medium.
Claim 4
Dependent Claim
21 words
The substrate as claimed in claim 1, wherein said polyacid includes an aliphatic main chain to which carboxylic groups are attached.
Claim 5
Dependent Claim
16 words
The substrate as claimed in claim 3, wherein said polyacid is polyacrylic acid or polymethacrylic acid.
Claim 6
Dependent Claim
13 words
The substrate as claimed in claim 2, wherein said polyacid is polyaspartic acid.
Claim 7
Dependent Claim
13 words
The substrate as claimed in claim 2, wherein said polyacid is polyglutamic acid.
Claim 8
Dependent Claim
12 words
The substrate as claimed in claim 1, wherein said polyacid is cross-linked.
Claim 9
Dependent Claim
21 words
The substrate as claimed in claim 1, wherein said physiologically active substance is bonded to the polyacid via a spacer compound.
Claim 10
Dependent Claim
21 words
The substrate as claimed in claim 8, wherein said spacer compound is a compound containing more than one NH 2 group.
Claim 11
Dependent Claim
17 words
The substrate as claimed in claim 9, wherein said spacer compound is polyethylene containing terminal amino groups.
Claim 12
Dependent Claim
18 words
The substrate as claimed in claim 9, wherein said spacer compound is a protein containing terminal amino groups.
Claim 13
Dependent Claim
33 words
The substrate as claimed in claim 1, wherein said physiologically active substance is selected from the group consisting of a heparin, a heparin compound, heparinous material, a prostaglandin, urokinase, streptokinase and combinations thereof.
Claim 14
Dependent Claim
29 words
The substrate as claimed in claim 12, wherein said physiologically active substance is a heparin with a high affinity for anti-thrombin III and/or a low interaction with blood platelets.
Claim 15
Independent Claim
109 words
A method of making a medical device, at least a part of a surface of the substrate having a physiologically active substance which has an inhibitory effect on the formation of blood clots or is capable of breaking down blood clots formed wherein the method comprises: a preliminary stage in which a number of functional groups are bonded to the substrate surface by being liberated from or introduced at the substrate surface; a first stag in which the functional group bonded to the substrate surface is covalently coupled to a polyacid; and a second stage after said first stage wherein a physiologically active substance is bonded to the polyacid.
Claim 16
Independent Claim
109 words
A method of making a medical device, at least a part of a surface of the substrate having a physiologically active substance which has an inhibitory effect on the formation of blood clots or is capable of breaking down blood clots formed wherein the method comprises: a preliminary stage in which a number of functional groups are bonded to the substrate surface by being liberated from or introduced at the substrate surface; a first stag in which the functional group bonded to the substrate surface is covalently coupled to a polyacid; and a second stage after said first stage wherein a physiologically active substance is bonded to the polyacid.
Claim 17
Dependent Claim
40 words
The method as claimed in claim 14 further including a step of attaching a spacer compound to the polyacid and to the physiologically active substance so that the physiologically active substance is bonded to the polyacid via the spacer compound.
Claim 18
Dependent Claim
48 words
The method as claimed in claim 15, wherein said step of attaching a spacer compound utilizes a spacer compound containing more than one amino group, and wherein one of the amino groups attaches to the polyacid and another of the amino groups attaches to the physiologically active compound.
Claim 19
Dependent Claim
20 words
The method as claimed in claim 14, wherein the preliminary stage includes directly attaching the polyacid to the substrate surface.
Claim 20
Dependent Claim
26 words
The method as claimed in claim 17, wherein said polyacid is formed by polymerizing a monomer from the substrate surface, which monomer includes a COOH group.
Claim 21
Dependent Claim
22 words
The method as claimed in claim 17, wherein said direct attaching of the polyacid to the substrate surface includes a graft reaction.
Claim 22
Dependent Claim
21 words
The method as claimed in claim 14, wherein said graft reaction includes reacting a polyacid that has a C═C double bond.
Claim 23
Dependent Claim
24 words
The method as claimed in claim 14, wherein said first stage includes using a polyacid containing two or more carboxyl groups per monomer unit.
Claim 24
Dependent Claim
19 words
The method as claimed in claim 14, wherein said first stage includes using an activated precursor of the polyacid.
Claim 25
Dependent Claim
18 words
The method as claimed in claim 22 wherein said activated precursor of the polyacid is a polyacid anhydride.
Claim 26
Dependent Claim
58 words
The method as claimed in claim 15, wherein said step of attaching a spacer compound includes providing a heparin containing a terminal aldehyde group as the physiologically active substance and providing a spacer compound containing more than one amino group, further including coupling said physiologically active substance to said spacer compound in the presence of a reducing agent.
Claim 27
Dependent Claim
78 words
The method as claimed in claim 24, wherein said heparin containing a terminal aldehyde group is first reacted with an excess of the spacer compound containing more than one amino group in the presence of the reducing agent to form a resulting reaction product, pre-activating carboxylic acid groups of the polyacid, and coupling said resulting reaction product to the polyacid whose carboxylic acid groups have been pre-activated, said coupling being via another amino group of the spacer compound.
Claim 28
Dependent Claim
16 words
The method as claimed in claim 24, further including using sodium cyanoborohydride as the reducing agent.
Claim 29
Dependent Claim
30 words
The method as claimed in claim 14, further including using a coupling agent in the first stage during coupling of the polyacid with an amino group as the functional group.
Claim 30
Dependent Claim
14 words
The method as claimed in claim 27 wherein the coupling agent is a carbodiimide.
Claim 31
Dependent Claim
33 words
The method as claimed in claim 15, wherein said attaching of the spacer compound containing more than one amino group to the polyacid is carried out in the presence of a coupling agent.
Claim 32
Dependent Claim
33 words
The method as claimed in claim 29, wherein the coupling agent is selected from the group consisting of a carbodiimide and another coupling agent for forming an amide group according to peptide chemistry.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-10-28 | 1995-04-29 | 1995-10-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-10-28 | 1999-04-29 | 1999-10-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-10-28 | 2003-04-29 | 2003-10-29 | $7700.00 | Window Closed / Lapsed |