Methods for mitigating calcification and improving durability in glutaraldehyde-fixed bioprostheses and articles manufactured by such methods
First Claim
1. A method for preparing a glutaraldehyde-fixed collagenous bioprosthesis having mitigated propensity for calcification, said method comprising the steps of:
- a) providing a collagen-containing tissue;
b) contacting said tissue with glutaraldehyde to form a glutaraldehyde cross-linked tissue;
c) rising the tissue to remove residual glutaraldehyde such that the tissue is free of exogenous compounds which would deter the subsequent formation of activated carboxyl moieties on the tissue;
d) contacting the glutaraldehyde cross-linked tissue with a carboxyl activator compound capable of converting at least some of the carboxyl groups present on the collagen molecules of the tissue to activated carboxyl moieties capable of reacting with amino groups;
e) contacting the tissue from step d) with a compound that will react with the activated carboxyl moieties to form noncarboxyl side groups on the collagen molecules; and
, thereafter;
f) again contacting said tissue with glutaraldehyde.
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Accused Products
Abstract
Methods for treating glutaraldehyde-fixed collagenous tissues to mitigate their propensity for subsequent calcification and to improve durability. Collagenous tissues which have been harvested and cross-linked by glutaraldehyde are exposed to a carboxyl activating agent to convert the free carboxyl (COOH) groups of the collagen molecules to activated carboxyl moieties (e.g., o-acylisourea). Thereafter, the collagenous tissue is exposed to a compound capable of reacting with the activated carboxyl moieties (e.g., o-acylisourea) to form non-carboxyl side groups. Monofunctional and multi-functional amines are examples of compounds which may be utilized to react with the activated carboxyl moieties to form such non-carboxyl side groups. Thereafter, the collagenous tissue is again exposed to glutaraldehyde. If the non-carboxyl side groups have functional amino groups (NH2), such additional exposure to glutaraldehyde will result in additional glutaraldehyde cross-linking of the collagen molecules and resultant improvement of durability.
160 Citations
33 Claims
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1. A method for preparing a glutaraldehyde-fixed collagenous bioprosthesis having mitigated propensity for calcification, said method comprising the steps of:
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a) providing a collagen-containing tissue; b) contacting said tissue with glutaraldehyde to form a glutaraldehyde cross-linked tissue; c) rising the tissue to remove residual glutaraldehyde such that the tissue is free of exogenous compounds which would deter the subsequent formation of activated carboxyl moieties on the tissue; d) contacting the glutaraldehyde cross-linked tissue with a carboxyl activator compound capable of converting at least some of the carboxyl groups present on the collagen molecules of the tissue to activated carboxyl moieties capable of reacting with amino groups; e) contacting the tissue from step d) with a compound that will react with the activated carboxyl moieties to form noncarboxyl side groups on the collagen molecules; and
, thereafter;f) again contacting said tissue with glutaraldehyde. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A method for treating a glutaraldehyde-fixed collagenous bioprosthesis to decrease its propensity for subsequent calcification, said method comprising the steps of:
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a) providing a collagenous bioprosthesis which has been cross-linked with glutaraldehyde and is free of exogenous compounds which would deter the subsequent formation of activated carboxyl moieties on the tissue; b) contacting at least some of the carboxyl groups present on collagen molecules of the cross-linked bioprosthesis with a carboxyl activating agent to convert at least some of the carboxyl groups into activated carboxyl moieties; and
,c) their contacting a carboxyl-free compound with said activated carboxyl moieties to form carboxyl-free side groups on the collagen molecules of the bioprosthesis. - View Dependent Claims (15, 16, 17, 18, 19)
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20. A method for preparing a glutaraldehyde-fixed collagenous tissue, said method comprising the steps of:
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a) providing a collagen-containing tissue; b) contacting said tissue with glutaraldehyde to form glutaraldehyde cross-linkages between collagen molecules within the tissue; c) contacting the glutaraldehyde cross-linked tissue with a carboxyl activator compound capable of converting at least some of the carboxyl groups present on the collagen molecules of the tissue to activated carboxyl moieties capable of reacting with amino groups; d) contacting the tissue with a carboxyl-free monoamine that will react with the activated carboxyl moieties to form noncarboxyl side groups on the collagen molecules; and
, thereafter;e) again contacting said tissue with glutaraldehyde. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27)
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28. A method for treating a glutaraldehyde-fixed collagenous tissue to decrease its propensity for subsequent calcification, said method comprising the steps of:
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a) providing a collagenous tissue which has been cross-linked with glutaraldehyde; b) reacting at least some of the carboxyl groups present on collagen molecules of the tissue with a carboxyl activating agent to convert at least some of the carboxyl groups into activated carboxyl moieties; and
,c) reacting a carboxyl-free monoamine with said activated carboxyl moieties to form carboxyl-free side groups on the collagen molecules of the tissue. - View Dependent Claims (29, 30, 31, 32, 33)
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Specification