US5019393A
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Biocompatible substance with thromboresistance
Assignee: Beth Israel Deaconess Medical Center
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Filing: 1988-08-03
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Granted: 1991-05-28
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Expires: 2008-08-03
Abstract
Abstract Disclosed is a biocompatible, thromboresistant substance useful for implantable and extracorporeal 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 streptokinase, urokinase, tissue plasminogen activator, ATPase, 5'-nucleotidase, and active fragments and active analogs thereof.
Inventors
- 👤 Ralph K. Ito
- 👤 Frank W. LoGerfo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 20:17
CPC Classifications
A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0047; A61L33/0011; A61L33/0029
Claims Analysis
Total Claims: 40
Claim 1
Independent Claim
68 words
A biocompatible substance with thromboresistance 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 thrombogenesis inhibitor being other than hirudin or an active analog or fragment of hirudin, said base coat layer having a component capable of binding said thrombogenesis inhibitor.
Claim 2
Dependent Claim
68 words
A biocompatible substance with thromboresistance 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 thrombogenesis inhibitor being other than hirudin or an active analog or fragment of hirudin, said base coat layer having a component capable of binding said thrombogenesis inhibitor.
Claim 3
Dependent Claim
36 words
The substance of claim 1 wherein said thrombogenesis inhibitor is an inhibitor selected from the group consisting of streptokinase, urokinase, tissue plasminogen activator, ATPase, ADPase, 5'-nucleotidase, and active fragments, and active analogs thereof, and mixtures thereof.
Claim 4
Dependent Claim
26 words
The substance of claim 1 wherein said polymer is selected from the group consisting of Dacron, nylon, polyurethane, cross-linked collagen, polyglycolic acid, polytetrafluoroethylene, and mixtures thereof.
Claim 5
Dependent Claim
11 words
The substance of claim 3 wherein said polymer comprises polyethylene terphthalate.
Claim 6
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 7
Dependent Claim
16 words
The substance of claim 5 wherein said component of said base coat layer comprises a protein.
Claim 8
Dependent Claim
21 words
The substance of claim 6 wherein said protein is selected from the group consisting of serum albumin, fibronectin, and mixtures thereof.
Claim 9
Dependent Claim
12 words
The substance of claim 7 wherein said protein comprises bovine serum albumin.
Claim 10
Dependent Claim
12 words
The substance of claim 7 wherein said protein comprises human serum albumin.
Claim 11
Dependent Claim
11 words
The substance of claim 7 wherein said protein comprises bovine fibronectin.
Claim 12
Dependent Claim
11 words
The substance of claim 7 wherein said protein comprises human fibronectin.
Claim 13
Dependent Claim
25 words
The substance of claim 1 further comprising at least one molecule of a bifunctional cross-linking reagent linking said thrombogenesis inhibitor to said base coat layer.
Claim 14
Dependent Claim
12 words
The substance of claim 12 wherein said bifunctional cross-linking reagent is heterobifunctional.
Claim 15
Dependent Claim
12 words
The substance of claim 12 wherein said bifunctional cross-linking reagent is homobifunctional.
Claim 16
Dependent Claim
12 words
The substance of claim 13 wherein said heterobifunctional cross-linking reagent comprises SPDP.
Claim 17
Independent Claim
74 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 said base coat layer thereto; and (b) immobilizing a thrombogenesis inhibitor on said adhered base coat layer, said thrombogenesis inhibitor being other than hirudin or an analog or fragment of hirudin.
Claim 18
Independent Claim
74 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 said base coat layer thereto; and (b) immobilizing a thrombogenesis inhibitor on said adhered base coat layer, said thrombogenesis inhibitor being other than hirudin or an analog or fragment of hirudin.
Claim 19
Dependent Claim
39 words
The method of claim 16 wherein said immobilizing step further comprises immobilizing a thrombogenesis inhibitor selected from the group consisting of streptokinase, urokinase, tissue plasminogen activator, ATPase, ADPase, 5'-nucleotidase, and active fragments, and active analogs thereof, and mixtures thereof.
Claim 20
Dependent Claim
56 words
The method of claim 16 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 21
Dependent Claim
50 words
The method of claim 18 wherein said adhering step comprises adhering a base coat to at least one surface of a synthetic, polymeric, biocompatible material, said base coat layer containing a component selected from the group consisting of a protein, peptide, lipoprotein, glycoprotein, glycosaminoglycan, hydrogel, synthetic polymers, and mixtures thereof.
Claim 22
Dependent Claim
27 words
The method of claim 19 wherein said adhering step further comprises adhering a base coat layer containing a protein to at least one surface of said material.
Claim 23
Dependent Claim
43 words
The method of claim 20 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 24
Dependent Claim
28 words
The method of claim 21 wherein said adhering step further comprises adhering a base coat layer containing human serum albumin to at least one surface of said material.
Claim 25
Dependent Claim
28 words
The method of claim 21 wherein said adhering step further comprises adhering a base coat layer containing bovine serum albumin to at least one surface of said material.
Claim 26
Dependent Claim
27 words
The method of claim 21 wherein said adhering step further comprises adhering a base coat layer containing human fibronectin to at least one surface of said material.
Claim 27
Dependent Claim
27 words
The method of claim 21 wherein said adhering step further comprises adhering a base coat layer containing bovine fibronectin to at least one surface of said material.
Claim 28
Dependent Claim
61 words
The method of claim 18 wherein said activating step comprises the steps of: (a) treating said material with a solution that makes available for binding at least one chemically active 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 group to said reagent.
Claim 29
Dependent Claim
31 words
The method of claim 26 wherein said treating step further comprises treating said material with a solution that makes available for binding at least one carboxylic acid group in said material.
Claim 30
Dependent Claim
31 words
The method of claim 18 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 31
Dependent Claim
56 words
The method of claim 18 wherein said immobilizing 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 layer.
Claim 32
Dependent Claim
55 words
The method of claim 29 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 33
Dependent Claim
40 words
The method of claim 29 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 34
Dependent Claim
39 words
The method of claim 30 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 35
Dependent Claim
60 words
The method of claim 30 further comprising the steps of: (a) reducing said base coat-linked reagent to expose a first sulfhydryl group thereon; (b) adding said inhibitor-linked reagent to said 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 36
Dependent Claim
22 words
The method of claim 31 wherein said contacting step includes contacting said thrombogenesis inhibitor with the heterobifunctional cross-linking reagent, N-succinimidyl 3-(2-pyridylaithio)propionate (SPDP).
Claim 37
Dependent Claim
20 words
The method of claim 32 wherein said contacting step includes contacting said thrombogenesis inhibitor with the heterobifunctional crosslinking reagent, SPDP.
Claim 38
Dependent Claim
38 words
The method of claim 29 further comprising the additional step of subjecting said throbogenesis-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 39
Independent Claim
75 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 other than hirudin or an active analog or fragment of hirudin, and said base coat layer containing a component capable of binding said thrombogenesis inhibitor; and (b) adhering said base coat layer linked to said thrombogenesis inhibitor to at least one surface of a synthetic, polymeric, biocompatible material.
Claim 40
Independent Claim
75 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 other than hirudin or an active analog or fragment of hirudin, and said base coat layer containing a component capable of binding said thrombogenesis inhibitor; and (b) adhering said base coat layer linked to said thrombogenesis inhibitor to at least 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) | 1994-05-27 | 1994-11-26 | 1995-05-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-05-27 | 1998-11-26 | 1999-05-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-05-27 | 2002-11-26 | 2003-05-28 | $7700.00 | Window Closed / Lapsed |