US5674298A
Expired / Lapsed
US
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Calcification-resistant bioprosthetic tissue and methods of making same
Assignee: University of Michigan (System)
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Filing: 1995-06-07
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Granted: 1997-10-07
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Expires: 2015-06-07
Abstract
Abstract Naturally-derived bioprosthetic materials are treated with epoxide crosslinking agents. In some embodiments, the tissue is crosslinked with low molecular weight epoxides in aqueous solutions at high pH levels. In other embodiments, the tissue is crosslinked at physiologic pH levels with epoxide crosslinking agents catalyzed with tertiary or quaternary amines, such as Tris or imidazole. In an advantageous embodiment, bioprosthetic tissue is crosslinked and derivatized with an anticalcification agent, such as a polyphosphonate anticalcification agent, using a polyphosphonate:polyepoxide monoadduct.
Inventors
- 👤 Robert J. Levy
- 👤 Eyal Lerner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 20:21
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3687; A61L27/50; A61L2400/00; A61L2400/02; A61L2430/00; A61L2430/40; Y; Y10; Y10S; Y10S623/00; Y10S623/92; Y10S623/921
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
70 words
A method of cross-linking bioprosthetic tissue comprising the steps of: (a) adding a polyphosphonate anticalcification agent to an excess of a polyepoxide to form a solution of polyphosphonate:polyepoxide monoadduct and excess polyepoxide; (b) diluting said solution with water; and (c) subjecting bioprosthetic tissue to the diluted solution for a time sufficient to crosslink the bioprosthetic tissue with the excess polyepoxide and to derivatize irreversibly the bioprosthetic tissue with the monoadduct.
Claim 2
Independent Claim
70 words
A method of cross-linking bioprosthetic tissue comprising the steps of: (a) adding a polyphosphonate anticalcification agent to an excess of a polyepoxide to form a solution of polyphosphonate:polyepoxide monoadduct and excess polyepoxide; (b) diluting said solution with water; and (c) subjecting bioprosthetic tissue to the diluted solution for a time sufficient to crosslink the bioprosthetic tissue with the excess polyepoxide and to derivatize irreversibly the bioprosthetic tissue with the monoadduct.
Claim 3
Dependent Claim
17 words
The method of claim 1 wherein the molar ratio of polyphosphonate to polyepoxide is at least 1:2.
Claim 4
Dependent Claim
15 words
The method of claim 2 wherein the molar ratio of polyphosphonate to polyepoxide is 1:10.
Claim 5
Dependent Claim
28 words
The method of claim 1 wherein the solution of step (b) is diluted to have a concentration of the monoadduct plus excess polyepoxide ranging from 0.005M to 0.5M.
Claim 6
Dependent Claim
13 words
The method of claim 4 wherein the concentration of the monoadduct is 0.1M.
Claim 7
Dependent Claim
26 words
The method of claim 7 wherein the diluted solution is buffered with a catalytic amine to a physiologic pH in the range of 7.0 to 8.0.
Claim 8
Dependent Claim
19 words
The method of claim 6 wherein the catalytic amine is selected from the group consisting of Tris and imidazole.
Claim 9
Dependent Claim
22 words
The method of claim 7 comprising the further step of treating the bioprosthetic tissue with glutaraldehyde prior to said step of subjecting.
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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) | 2000-10-06 | 2001-04-07 | 2001-10-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-10-06 | 2005-04-07 | 2005-10-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-10-06 | 2009-04-07 | 2009-10-07 | $7700.00 | Window Closed / Lapsed |