US6561970B1
Expired / Lapsed
US
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Methods for treating implantable biological tissues to mitigate the calcification thereof and bioprosthetic articles treated by such methods
Assignee: Edwards Lifesciences Corp
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Filing: 1996-12-12
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Granted: 2003-05-13
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Expires: 2016-12-12
Abstract
Abstract A method for treating fixed biological tissue inhibits calcification of the biological tissue following implantation thereof in a mammalian body. The method includes placing the biological tissue in contact with glutaraldehyde and then heating the glutaraldehyde. Alternatively, methods other than heating (e.g., chemical or mechanical means), for effecting polymerization of the glutaraldehyde may also be utilized. Alternatively, the tissue may be heat treated prior to fixing thereof. Alternatively, methods other than glutaraldehyde may also be used for fixing the tissue. The biological tissue may be so treated at any time prior to implantation thereof in a mammalian body.
Inventors
- 👤 Sophie M. Carpentier
- 👤 Alain F. Carpentier
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 20:09
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3687; A61L27/3604; A61L2400/00; A61L2400/02; Y; Y10; Y10S; Y10S623/00; Y10S623/915
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
78 words
A method for treating bovine pericardium tissue or porcine tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising the steps of: fixing the tissue; after fixing, heat treating the tissue in a fixative at a temperature of between about 35-55° C. for a period of between 4-22 weeks; and sterilizing the tissue after fixing and prior to heat treating in a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate.
Claim 2
Independent Claim
78 words
A method for treating bovine pericardium tissue or porcine tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising the steps of: fixing the tissue; after fixing, heat treating the tissue in a fixative at a temperature of between about 35-55° C. for a period of between 4-22 weeks; and sterilizing the tissue after fixing and prior to heat treating in a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate.
Claim 3
Dependent Claim
74 words
The method of claim 1 , wherein the step of fixing includes placing the tissue in contact with an approximately 0.625% solution of glutaraldehyde comprising: a) approximately 26 ml/l glutaraldehyde; b) approximately 4.863 g/l HEPES buffer; c) approximately 2.65 g/l MgCl 2 .6H 2 O; d) approximately 4.71 g/l NaCl; and e) balance of solution double filtered H 2 O; wherein the method further includes adjusting the pH of the solution to approximately 7.4.
Claim 4
Dependent Claim
12 words
The method of claim 1 , wherein the period is several months.
Claim 5
Dependent Claim
24 words
The method of claim 1 , comprising the additional step of storing the tissue after sterilizing and then performing the heat treatment during storage.
Claim 6
Dependent Claim
31 words
The method of claim 1 wherein the fixative is glutaraldehyde and wherein the heat treating further includes: placing the tissue in a glutaraldehyde-containing antimineralization solution; and heating the glutaraldehyde-containing antimineralization solution.
Claim 7
Dependent Claim
31 words
The method of claim 1 wherein the fixative is glutaraldehyde and wherein the heat treating further includes disposing the tissue in a solution of glutaraldehyde and heating the solution of glutaraldehyde.
Claim 8
Dependent Claim
12 words
The method of claim 6 , wherein the period is several months.
Claim 9
Dependent Claim
68 words
The method of claim 6 , wherein the solution of glutaraldehyde is an approximately 0.625% solution of glutaraldehyde comprising: a) approximately 26 ml/l glutaraldehyde; b) approximately 4.863 g/l HEPES buffer; c) approximately 2.65 g/l MgCl 2 .6H 2 O; d) approximately 4.71 g/l NaCl; and e) balance of solution double filtered H 2 O; wherein the method further includes adjusting the pH of the solution to approximately 7.4.
Claim 10
Independent Claim
76 words
A method for treating biological tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising: fixing the tissue in a solution comprising a fixative agent; storing the tissue in a solution comprising a fixative agent; heating the stored tissue in said solution to a temperature between about 35-55° C.; and prior to storing the tissue, sterilizing the tissue in a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate.
Claim 11
Independent Claim
76 words
A method for treating biological tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising: fixing the tissue in a solution comprising a fixative agent; storing the tissue in a solution comprising a fixative agent; heating the stored tissue in said solution to a temperature between about 35-55° C.; and prior to storing the tissue, sterilizing the tissue in a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate.
Claim 12
Dependent Claim
29 words
A method according to claim 9 , wherein the tissue is heat treated in a solution selected from the group consisting of a physiologic solution and a glutaraldehyde solution.
Claim 13
Dependent Claim
34 words
A method according to claim 9 , wherein the step of heating the stored tissue is carried out for a period of time in the range of about a few seconds to 22 weeks.
Claim 14
Dependent Claim
32 words
A method according to claim 11 , wherein the step of heating the stored tissues is carried out for a period of time in the range of about 4 to 22 weeks.
Claim 15
Independent Claim
61 words
A method for treating biological tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising: heat treating the tissue; sterilizing the tissue separately from the heat treating step by contacting the tissue with a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate; and fixing the tissue in a solution comprising a fixative agent.
Claim 16
Independent Claim
61 words
A method for treating biological tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising: heat treating the tissue; sterilizing the tissue separately from the heat treating step by contacting the tissue with a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate; and fixing the tissue in a solution comprising a fixative agent.
Claim 17
Dependent Claim
29 words
A method according to claim 13 , wherein the tissue is heat treated in a solution selected from the group consisting of a physiologic solution and a glutaraldehyde solution.
Claim 18
Dependent Claim
34 words
A method according to claim 13 , wherein the step of heating the stored tissue is carried out for a period of time in the range of about a few seconds to 22 weeks.
Claim 19
Dependent Claim
32 words
A method according to claim 15 , wherein the step of heating the stored tissues is carried out for a period of time in the range of about 4 to 22 weeks.
Claim 20
Dependent Claim
23 words
A method according to claim 13 , wherein the tissue is heat treated at a temperature in the range of about 35-55° C.
Claim 21
Independent Claim
71 words
A method for treating biological tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising: heat treating the tissue prior to implantation; fixing the tissue in a solution comprising a fixative agent during the heat treating step; and sterilizing the tissue in a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate, storing the tissue, and wherein the heat treating is performing during storage.
Claim 22
Independent Claim
71 words
A method for treating biological tissue to inhibit calcification of the tissue following implantation in a mammalian body, the method comprising: heat treating the tissue prior to implantation; fixing the tissue in a solution comprising a fixative agent during the heat treating step; and sterilizing the tissue in a solution comprising an alcohol, formaldehyde and polyoxyethylene 20 sorbitan monooleate, storing the tissue, and wherein the heat treating is performing during storage.
Claim 23
Dependent Claim
29 words
A method according to claim 18 , wherein the tissue is heat treated in a solution selected from the group consisting of a physiologic solution and a glutaraldehyde solution.
Claim 24
Dependent Claim
34 words
A method according to claim 18 , wherein the step of heating the stored tissue is carried out for a period of time in the range of about a few seconds to 22 weeks.
Claim 25
Dependent Claim
32 words
A method according to claim 20 , wherein the step of heating the stored tissues is carried out for a period of time in the range of about 4 to 22 weeks.
Claim 26
Dependent Claim
13 words
A method according to claim 21 , wherein the period is several months.
Claim 27
Dependent Claim
23 words
A method according to claim 21 , wherein the tissue is heat treated at a temperature in the range of about 35-55° C.
Claim 28
Dependent Claim
23 words
A method according to claim 18 , wherein the tissue is heat treated at a temperature in the range of about 35-55° C.
Claim 29
Dependent Claim
16 words
A method according to claim 18 , wherein the tissue is fresh prior to heat treating.
Claim 30
Dependent Claim
16 words
A method according to claim 18 , wherein the tissue is fixed prior to heat treating.
Claim 31
Dependent Claim
27 words
A method according to claim 18 , wherein the heat treating further includes disposing the tissue in a solution of glutaraldehyde and heating the solution of glutaraldehyde.
Claim 32
Dependent Claim
68 words
The method of claim 27 , wherein the solution of glutaraldehyde comprises an approximately 0.625% solution of glutaraldehyde comprising: a) approximately 26 ml/l glutaraldehyde; b) approximately 4.863 g/l HEPES buffer; c) approximately 2.65 g/l MgCl 2 .6H 2 O; d) approximately 4.71 g/l NaCl; and e) balance of solution double filtered H 2 O; wherein the method further includes adjusting the pH of the solution to approximately 7.4.
Claim 33
Dependent Claim
27 words
A method according to claim 18 , wherein the heat treating further includes: placing the tissue in a glutaraldehyde-containing antimineralization solution; and heating the glutaraldehyde-containing antimineralization solution.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2006-05-12 | 2006-11-11 | 2007-05-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2010-05-12 | 2010-11-11 | 2011-05-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2014-05-12 | 2014-11-11 | 2015-05-13 | $7700.00 | Window Closed / Lapsed |