Sterilization
First Claim
1. A process for sterilization of biological tissue material, which process comprisestreating such material with an aqueous solution containing (a) an amount of a water-soluble coupling agent capable of creating amide bonds that is effective to achieve sterilization and (b) an amount of a protecting agent which is effective to complex with potentially reactive amine or carboxyl moieties on the biological tissue material so as to deter such complexed moieties from taking part in an amide-forming cross-linking reaction and thereby limit the amount of cross-linking, and maintaining such treatment for a time and at a temperature which is sufficient to achieve penetration of said coupling agent into the cells of microorganisms carried by such material and effectively kill such microorganisms.
1 Assignment
0 Petitions
Accused Products
Abstract
Allograft tissue prostheses, as well as tissue valves for replacement of defective heart valves and other tissue-engineered products (TEPs), are effectively sterilized by treatment with a coupling agent known to create amide linkages between amines and carboxylic acids in the presence of a protecting agent. The sterilization treatment preferably employs EDC as a water-soluble coupling agent, plus a water-soluble protecting agent which complexes with potentially reactive amine or carboxyl moieties on the biological tissue, in the optional presence of isopropanol or an equivalent alkanol. One preferred sterilization treatment process uses a buffered aqueous solution where a hydroxymonoamine buffer, such as TRIS plus ethanolamine, provides both the buffering effect and the protecting agents, effectively complexing with potentially reactive carboxyl moieties on the tissue. The treatment is particularly advantageous for sterilizing fresh biological tissue where substantial cross-linking that would alter physical properties of the tissue is undesirable or any tissues or TEPs where a controllable amount of cross-linking is desired.
142 Citations
20 Claims
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1. A process for sterilization of biological tissue material, which process comprises
treating such material with an aqueous solution containing (a) an amount of a water-soluble coupling agent capable of creating amide bonds that is effective to achieve sterilization and (b) an amount of a protecting agent which is effective to complex with potentially reactive amine or carboxyl moieties on the biological tissue material so as to deter such complexed moieties from taking part in an amide-forming cross-linking reaction and thereby limit the amount of cross-linking, and maintaining such treatment for a time and at a temperature which is sufficient to achieve penetration of said coupling agent into the cells of microorganisms carried by such material and effectively kill such microorganisms.
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11. A process for sterilization of biological tissue, which process comprises treating such biological tissue at a temperature of at least about 35°
- C. with an aqueous solution containing an effective amount of a lower alkanol and a concentration of at least about 25 mM of a water-soluble coupling agent that is capable of creating amide bonds and maintaining said treatment, in the presence of an effective amount of a protecting agent which complexes with either amine or carboxyl moieties and thereby deters cross-linking, for a period so as to effectively kill any bacteria and spores carried by such biological tissue, whereby contemporaneous cross-linking of the biological material can be controlled as desired.
- View Dependent Claims (12, 13, 14, 15)
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16. A process for sterilization of biological tissue material, which process comprises
treating such material with a protecting agent which is effective to complex with potentially reactive amine or carboxyl moieties on the biological tissue material so as to deter such complexed moieties from taking part in an amide-forming cross-linking reaction and thereby limit the amount of cross-linking, treating such material with a water-soluble coupling agent capable of creating amide bonds that is effective to achieve sterilization, and maintaining such treatment with said coupling agent for a time and at a temperature which is sufficient to achieve penetration of said coupling agent into the cells of microorganisms carried by such material and effectively kill such microorganisms.
Specification