Patent US5167960A successfully refreshed from Google Patents.
US5167960A
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US
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Hirudin-coated biocompatible substance
Assignee: Beth Israel Deaconess Medical Center
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Filing: 1988-08-03
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Granted: 1992-12-01
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Expires: 2008-08-03
Abstract
Abstract Disclosed is a biocompatible, thromboresistant substance useful for implantable and extracorpeoreal devices in contact with the vascular system, and methods for producing the same. The biocompatible, thromboresistant substance comprises a synthetic, biocompatible material, at least one biocompatible base coat layer adhered to at least one surface of the material, and a thrombogenesis inhibitor immobilized on the base coat layer via a component capable of binding the inhibitor. The thrombogenesis inhibitor is hirudin, or an active analog or fragment thereof.
Inventors
- 👤 Ralph K. Ito
- 👤 Frank W. LoGerfo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:03
CPC Classifications
A; A61; A61L; A61L17/00; A61L17/14; A61L33/00; A61L33/06; A61L33/12; A61L33/128; A61F; A61F2/00; A61F2/02; A61F2/04; A61F2/06; A61L27/00; A61L27/14; A61L27/22; A61L33/0005; A61L33/0011; A61L33/0029
Claims Analysis
Total Claims: 38
Claim 1
Independent Claim
64 words
A biocompatible, thromboresistent substance comprising: (a) a synthetic, polymeric, biocompatible material; (b) at least one biocompatible base coat layer adhered to at least one surface of said material; and (c) a thrombogenesis inhibitor immobilized on said base coat layer, said inhibitor being hirudin or an active analog or active fragment thereof, said base coat layer having a component capable of binding said thrombogenesis inhibitor.
Claim 2
Dependent Claim
64 words
A biocompatible, thromboresistent substance comprising: (a) a synthetic, polymeric, biocompatible material; (b) at least one biocompatible base coat layer adhered to at least one surface of said material; and (c) a thrombogenesis inhibitor immobilized on said base coat layer, said inhibitor being hirudin or an active analog or active fragment thereof, said base coat layer having a component capable of binding said thrombogenesis inhibitor.
Claim 3
Dependent Claim
27 words
The substance of claim 1 wherein said polymer is selected from the group consisting of polyethylene terphthalate, nylon, polyurathane, cross-linked collagen, polyglycolic acid, polytetrafluoroethylene, and mixtures thereof.
Claim 4
Dependent Claim
11 words
The substance of claim 2 wherein said polymer comprises polyethylene terphthalate.
Claim 5
Dependent Claim
31 words
The substance of claim 1 wherein said base coat layer comprises a component selected from the group consisting of a protein, peptide, lipoprotein, glycoprotein, glycosaminoglycan, hydrogel, synthetic polymer, and mixtures thereof.
Claim 6
Dependent Claim
16 words
The substance of claim 4 wherein said component of said base coat layer comprises a protein.
Claim 7
Dependent Claim
21 words
The substance of claim 5 wherein said protein is selected from the group consisting of serum albumin, fibronectin, and mixtures thereof.
Claim 8
Dependent Claim
12 words
The substance of claim 6 wherein said protein comprises bovine serum albumin.
Claim 9
Dependent Claim
12 words
The substance of claim 6 wherein said protein comprises human serum albumin.
Claim 10
Dependent Claim
10 words
The substance of claim 6 said protein comprises bovine fibronectin.
Claim 11
Dependent Claim
11 words
The substance of claim 6 wherein said protein comprises human fibronectin.
Claim 12
Dependent Claim
20 words
The substance of claim 1 further comprising a bifunctional cross-linking reagent linking said thrombogenesis inhibitor to said base coat layer.
Claim 13
Dependent Claim
12 words
The substance of claim 11 wherein said bifunctional cross-linking reagent is heterobifunctional.
Claim 14
Dependent Claim
12 words
The substance of claim 11 wherein said bifunctional cross-linking reagent is homobifunctional.
Claim 15
Dependent Claim
12 words
The substance of claim 12 wherein said heterobifunctinoal cross-linking reagent comprises SPDP.
Claim 16
Independent Claim
69 words
A method of producing a biocompatible, thromboresistant substance, said method comprising the steps of: (a) adhering at least one base coat layer to at least one surface of a synthetic, polymeric, biocompatible material, said base coat layer containing a component capable of binding a thrombogenesis inhibitor; and (b) immobilizing said thrombogenesis inhibitor to said base coat layer, said inhibitor being hirudin or an active analog or active fragment thereof.
Claim 17
Independent Claim
69 words
A method of producing a biocompatible, thromboresistant substance, said method comprising the steps of: (a) adhering at least one base coat layer to at least one surface of a synthetic, polymeric, biocompatible material, said base coat layer containing a component capable of binding a thrombogenesis inhibitor; and (b) immobilizing said thrombogenesis inhibitor to said base coat layer, said inhibitor being hirudin or an active analog or active fragment thereof.
Claim 18
Dependent Claim
56 words
The method of claim 15 wherein said adhering step comprises: (a) activating said material so as to enhance the binding of said base coat layer thereto; and (b) contacting said activated material with said base coat layer for a time sufficient to allow said component of said base coat layer to bind to said activated material.
Claim 19
Dependent Claim
48 words
The method of claim 15 wherein said adhering step comprises adhering a base coat layer to at least one surface of said material, said base coat layer containing a component selected from the group consisting of a protein, peptide, lipoprotein, glycoprotein, hydrogel, glycosaminoglycan, synthetic polymer, and mixtures thereof.
Claim 20
Dependent Claim
27 words
The method of claim 17 wherein said adhering step further comprises adhering a base coat layer containing a protein to at least one surface of said material.
Claim 21
Dependent Claim
43 words
The method of claim 18 wherein said adhering step further comprises adhering a base coat layer to at least one surface of said material, said base coat layer containing a protein selected from the group consisting of serum albumin, fibronectin, and mixtures thereof.
Claim 22
Dependent Claim
28 words
The method of claim 19 wherein said adhering step further comprises adhering a base coat layer containing human serum albumin to at least one surface of said material.
Claim 23
Dependent Claim
27 words
The method of claim 19 wherein said adhering further comprises adhering a base coat layer containing bovine serum albumin to at least one surface of said material.
Claim 24
Dependent Claim
27 words
The method of claim 19 wherein said adhering step further comprises adhering a base coat layer containing human fibronectin to at least one surface of said material.
Claim 25
Dependent Claim
27 words
The method of claim 19 wherein said adhering step further comprises adhering a base coat layer containing bovine fibronectin to at least one surface of said material.
Claim 26
Dependent Claim
63 words
The method of claim 16 wherein said activating step comprises the steps of: (a) treating said material with a solution that makes available for binding at least one chemically reactive group in said material; and (b) contacting said treated material with a solution containing a bifunctional cross-linking reagent for a time sufficient to allow binding of said chemically reactive group to said reagent.
Claim 27
Dependent Claim
40 words
The method of claim 24 wherein said treating step further comprises treating said material with a solution that makes available for binding at least one chemically active group in said material, said chemically active group being a carboxylic acid group.
Claim 28
Dependent Claim
31 words
The method of claim 15 further comprising the preliminary step of contacting said material with a solution which removes impurities thereon, said preliminary step being performed prior to said adhering step.
Claim 29
Dependent Claim
63 words
The method of claim 15 wherein said mobilizing step further comprises the steps of: (a) contacting said thrombogenesis inhibitor with a at least one molecule of a bifunctional cross-linking reagent for a time sufficient to allow linking of said reagent to said thrombogenesis inhibitor; and (b) binding said thrombogenesis inhibitor-linked reagent to said base coat, said linked thrombogenesis inhibitor having thrombogenesis inhibiting activity.
Claim 30
Dependent Claim
55 words
The method of claim 27 wherein said contacting step further comprises contacting said base coat with at least one molecule of said bifunctional cross-linking reagent for a time sufficient to allow linking of said agent to said base coat, and said binding step further includes binding said thrombogenesis inhibitor-linked reagent to said base coat-linked reagent.
Claim 31
Dependent Claim
40 words
The method of claim 27 wherein said contacting step further includes contacting said thrombogenesis inhibitor with at least one molecule of said bifunctional cross-linking reagent selected from the group consisting of heterobifunctional cross-linking reagents, homobifunctional cross-linking reagents, and mixtures thereof.
Claim 32
Dependent Claim
39 words
The method of claim 28 wherein said contacting step includes contacting said base coat with at least one molecule of said bifunctional cross-linking reagent selected from the group consisting of heterobifunctional cross-linking reagents, homobifunctional cross-linking reagents, and mixtures thereof.
Claim 33
Dependent Claim
59 words
The method of claim 30 further comprising the steps of: (a) reducing said base coat-linked reagent to expose a sulfhydryl group thereon; (b) adding said inhibitor-linked reagent to the exposed sulfhydryl group thereon; and (c) inducing a substitution reaction involving said sulfhydryl group and said inhibitor-linked reagent, said reaction resulting in linkage of said base coat to said inhibitor.
Claim 34
Dependent Claim
22 words
The method of claim 29 wherein said contacting step includes contacting said thrombogenesis inhibitor with the heterobifunctional cross-linking reagent, N-succinimidyl 3-(2-pyridylaithio)propionate (SPDP).
Claim 35
Dependent Claim
20 words
The method of claim 30 wherein said contacting step includes contacting said thrombogenesis inhibitor with the heterobifunctional crosslinking reagent, SPDP.
Claim 36
Dependent Claim
38 words
The method of claim 27 further comprising the additional step of subjecting said thromogenesis-linked reagent to a chromatographic procedure to remove impurities therein, said additional step being performed after said contacting step and prior to said binding step.
Claim 37
Independent Claim
73 words
A method of producing a biocompatible, thromboresistant substance, said method comprising the steps of: (a) immobilizing a thrombogenesis inhibitor to a base coat layer, said inhibitor being hirudin or an active analog or active fragment thereof, and said base coat layer containing a component capable of binding said thrombogenesis inhibitor; and (b) adhering said base coat layer linked to said thromogenesis inhibitor to at lest one surface of a synthetic, polymeric, biocompatible material.
Claim 38
Independent Claim
73 words
A method of producing a biocompatible, thromboresistant substance, said method comprising the steps of: (a) immobilizing a thrombogenesis inhibitor to a base coat layer, said inhibitor being hirudin or an active analog or active fragment thereof, and said base coat layer containing a component capable of binding said thrombogenesis inhibitor; and (b) adhering said base coat layer linked to said thromogenesis inhibitor to at lest one surface of a synthetic, polymeric, biocompatible material.
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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) | 1995-12-01 | 1996-06-01 | 1996-12-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-12-01 | 2000-06-01 | 2000-12-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-12-01 | 2004-06-01 | 2004-12-01 | $7700.00 | Window Closed / Lapsed |