Glutaraldehyde-fixed bioprostheses
First Claim
1. A glutaraldehyde-fixed bioprosthesis manufactured by the 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) rinsing the tissue to remove residual glutaraldehyde such that the tissue is activated carboxyl moieties on the tissue free of exogenous compounds that 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 collagen molecules of the tissue to activated carboxyl moieties capable of reacting with amino groups;
e)contacting the tissue 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 there 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 multifunctional 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.
92 Citations
19 Claims
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1. A glutaraldehyde-fixed bioprosthesis manufactured by the 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) rinsing the tissue to remove residual glutaraldehyde such that the tissue is activated carboxyl moieties on the tissue free of exogenous compounds that 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 collagen molecules of the tissue to activated carboxyl moieties capable of reacting with amino groups; e)contacting the tissue 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 (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A glutaraldehyde-fixed collagenous bioprosthesis prepared by a 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 that would deter the subsequent formation of activated carboxyl moieties on the bioprosthesis; b) reacting at least some of the carboxyl groups present on collagen molecules of the bioprosthesis with a carboxyl activating agent to convert at least some of the carboxyl groups into activated carboxyl moieties; and
,c) reacting a carboxyl-free compound with said activated carboxyl moieties, thereby forming carboxyl-free side groups on the collagen molecules of the bioprosthesis. - View Dependent Claims (2, 15, 16, 17, 18, 19)
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Specification