US6521179B1
Expired / Lapsed
US
⏱️ 0.0 years remaining
Sterilization
Assignee: Biomedical Design Inc
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Filing: 2000-08-09
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Granted: 2003-02-18
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Expires: 2020-08-09
Abstract
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.
Inventors
- 👤 Jean-Marie Girardot
- 👤 Marie-Nadia Girardot
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 15:50
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3687; A01; A01N; A01N1/00; A61L2/00; A61L2/16; A61L2/18; A61L27/3691; A61L2103/00; A61L2103/05; Y; Y10; Y10S; Y10S623/00; Y10S623/915; Y10S623/92
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
120 words
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.
Claim 2
Dependent Claim
120 words
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.
Claim 3
Dependent Claim
26 words
The process for sterilization according to claim 1 wherein said coupling agent is present in said solution at a concentration of at least about 25 mM.
Claim 4
Dependent Claim
35 words
The process for sterilization according to claim 2 wherein said treatment is carried out at a temperature of about 25° to about 55° C. in the presence of an effective amount of a lower alkanol.
Claim 5
Dependent Claim
46 words
The process for sterilization according to claim 2 wherein said treatment is carried out at a temperature of at least about 35° C. in the absence of any effective amount of a lower alkanol and said treatment is carried out for at least about 24 hours.
Claim 6
Dependent Claim
27 words
The process for sterilization according to claim 2 wherein said protecting agent is present in said aqueous solution at a concentration of at least about 25 mM.
Claim 7
Dependent Claim
15 words
The process for sterilization according to claim 5 wherein said protecting agent includes a monoamine.
Claim 8
Dependent Claim
16 words
The process for sterilization according to claim 5 wherein said protecting agent includes a monocarboxylic acid.
Claim 9
Dependent Claim
42 words
The process for sterilization according to claim 1 wherein said coupling agent is present in said solution at a concentration of at least about 35 mM and said protecting agent is present at a concentration between about 50 and about 150 mM.
Claim 10
Dependent Claim
20 words
The process for sterilization according to claim 8 wherein said treatment is carried out for at least about 6 hours.
Claim 11
Dependent Claim
47 words
The process for sterilization according to claim 1 wherein said coupling agent is EDC which is present at a concentration of at least about 50 millimolar and said treatment is carried out for at least about 10 hours at a temperature of at least about 40° C.
Claim 12
Dependent Claim
112 words
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.
Claim 13
Dependent Claim
112 words
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.
Claim 14
Dependent Claim
27 words
The process for sterilization according to claim 11 wherein said aqueous solution contains said protecting agent at a concentration of between about 50 and about 150 mM.
Claim 15
Dependent Claim
20 words
The process for sterilization according to claim 11 wherein said protecting agent includes either a monoamine or a monocarboxylic acid.
Claim 16
Dependent Claim
59 words
The process for sterilization according to claim 11 wherein said solution contains EDC as said water-soluble coupling agent at a concentration of at least about 35 mM, wherein said treatment is carried out at between 40° C. and about 50° C. and wherein said treatment is carried out in the presence of at least about 50 mM of ethanolamine.
Claim 17
Dependent Claim
20 words
The process for sterilization according to claim 14 wherein said solution also contains at least about 50 mM of TRIS.
Claim 18
Dependent Claim
115 words
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.
Claim 19
Dependent Claim
115 words
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.
Claim 20
Dependent Claim
27 words
The process for sterilization according to claim 16 wherein said coupling agent and said protecting agent are present in an aqueous solution being used for said treatment.
Claim 21
Dependent Claim
19 words
The process for sterilization according to claim 17 wherein said protecting agent includes hydroxyproline, lactic acid or acetic acid.
Claim 22
Dependent Claim
41 words
The process for sterilization according to claim 17 wherein said biological tissue material is pretreated with said protecting agent at a concentration of at least about 10 mM and then rinsed before treatment with an aqueous solution of said coupling agent.
Claim 23
Dependent Claim
22 words
The process for sterilization according to claim 19 wherein said protecting agent is sulfo-NHS acetate, acetic anhydride, maleic anhydride or citraconic anhydride.
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