US4786287A
Expired / Lapsed
US
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Process for decreasing residual aldehyde levels in implantable bioprosthetic tissue
Assignee: Baxter International Inc
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Filing: 1986-10-10
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Granted: 1988-11-22
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Expires: 2006-10-10
Abstract
Abstract Residual aldehyde levels in bioprosthetic tissue are reduced by contacting the tissue with a rinsing solution such that aldehyde which has diffused out of the tissue into the rinsing solution comes into contact with, and reacts with, an amine, thus causing further diffusion of aldehyde out of said tissue. The amine may be dissolved in said rinsing solution or may be immobilized on a solid support to which the rinsing solution is periodically or continuously exposed.
Inventors
- 👤 Aws S. Nashef
- 👤 Ronald Dieck
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 23:43
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3687; A01; A01N; A01N1/00; A01N1/10; A01N1/12; A01N1/122; A01N1/128; Y; Y10; Y10S; Y10S623/00; Y10S623/915; Y10S623/916
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
95 words
A method for decreasing residual tissue-fixing or tissue-sterilizing aldehyde levels in an implantable biological tissure previously contacted with said tissue-fixing or tissue-sterilizing aldehyde, comprising contacting said tissue with a rinsing solution to effect difusion of said aldehyde out of said tissue into said rinsing solution, said rinsing solution being water, saline or a buffered solution, and continuously or periodically contacting the rinsing solution with an aldehyde-reactive amine which is immobilized on a solid support, thus decreasing the concentration of said aldehyde in said rinsing solution and causing further diffusion of aldehyde out of said tissue.
Claim 2
Independent Claim
95 words
A method for decreasing residual tissue-fixing or tissue-sterilizing aldehyde levels in an implantable biological tissure previously contacted with said tissue-fixing or tissue-sterilizing aldehyde, comprising contacting said tissue with a rinsing solution to effect difusion of said aldehyde out of said tissue into said rinsing solution, said rinsing solution being water, saline or a buffered solution, and continuously or periodically contacting the rinsing solution with an aldehyde-reactive amine which is immobilized on a solid support, thus decreasing the concentration of said aldehyde in said rinsing solution and causing further diffusion of aldehyde out of said tissue.
Claim 3
Dependent Claim
30 words
The method of claim 1 wherein the concentration of amine in the rinsing solution is such that there is a stoichiometric excess of amino groups over the residual aldehyde groups.
Claim 4
Dependent Claim
22 words
The method of claim 2 wherein the rinsing solution comprises more than a 100-fold excess of amino groups over residual aldehyde groups.
Claim 5
Independent Claim
17 words
The method of claims 1 or 2 wherein the amine is a primary or a secondary amine.
Claim 6
Dependent Claim
15 words
The method of claim 4 wherein said amine is an aliphatic or aromatic primary amine.
Claim 7
Dependent Claim
12 words
The method of claim 5 wherein the amine is an amino acid.
Claim 8
Dependent Claim
10 words
The method of claim 5 wherein the amine is tris(hydromethyl)aminomethane.
Claim 9
Dependent Claim
21 words
The method of claim 1 wherein the aldehyde is selected from the group consisting of glutaraldehyde, formaldehyde, glyoxal, or dialdehyde starch.
Claim 10
Dependent Claim
10 words
The method of claim 8 wherein the aldehyde is glutaraldehyde.
Claim 11
Dependent Claim
32 words
The method of claim 1 or 2 wherein the tissue is immersed in a volume of rinsing solution which is sufficient to promote efficient diffusion of said aldehyde out of said tissue.
Claim 12
Dependent Claim
25 words
The method of claim 10 wherein the tissue is immersed in about 100 mls of the rinsing solution per 10 grams (wet weight) of tissue.
Claim 13
Independent Claim
25 words
The method of claims 1 or 2 wherein the temperature of the rinsing solution is maintained at between about 4° C. and about 45° C.
Claim 14
Dependent Claim
18 words
The method of claim 12 wherein the temperature of the rinsing solution is maintained at about 35±2° C.
Claim 15
Independent Claim
22 words
The method of claims 1 or 2 wherein the pH of the rinsing solution is maintained between about 7.0 and about 7.6.
Claim 16
Dependent Claim
15 words
The method of claim 14 wherein the pH is maintained between about 7.1 and 7.4.
Claim 17
Dependent Claim
29 words
The method of claim 1 wherein the bioprosthetic tissue is derived from a source selected from the group consisting of bovine, porcine, equine, ovine, kangaroo, rabbit, or human tissues.
Claim 18
Independent Claim
34 words
The method of claims 1 or 16 wherein the tissue is selected from the group consisting of pericardial tissue, dura mater, fascia lata, amnion, tendon, ligament, cartilage, collagen, arteries, veins, skin patches, and bone.
Claim 19
Dependent Claim
15 words
The method of claim 1 wherein the tissue is subjected to a calcification mitigation treatment.
Claim 20
Dependent Claim
14 words
The method of claim 1 wherein the tissue is subjected to a sterilization treatment.
Claim 21
Dependent Claim
34 words
The method of claim 1 or 2 wherein the tissue is contacted with the rinsing solution until residual aldehyde levels have been decreased to a level at which said bioprosthetic tissue is substantially non-cytotoxic.
Claim 22
Dependent Claim
18 words
The method of claim 20 wherein residual aldehyde levels have been decreased below about 1 part per million.
Claim 23
Dependent Claim
15 words
The method of claim 1 wherein said solid support is selected from agarose or polyacrylamide.
Claim 24
Dependent Claim
36 words
The method of claim 22 wherein said solid support is agarose activated by treatment with cyanogen bromide, and said amine is a diamine which is bound to said support by reaction with the bound cyanogen bromide.
Claim 25
Dependent Claim
37 words
The method of claim 22 wherein said solid support is agarose having a free carboxyl group-containing ligand attached thereto, and said amine is a diamine which is bound to said solid support using a carbodiimide coupling reagent.
Claim 26
Dependent Claim
16 words
The method of claim 23 or 24 wherein said diamine is ethylenediamine, lysine, hydroxylysine, or polylysine.
Claim 27
Dependent Claim
30 words
The method of claim 24 wherein said solid support having a free carboxyl group-containing ligand attached thereto is agarose having 6-amino-hexanoic acid coupled thereto, carboxymethyl agarose, or carboxyl terminal agarose.
Claim 28
Dependent Claim
46 words
The method of claim 22 wherein said solid support having an amine immobilized thereon is selected from the group consisting of agarose-butylamine, agarose-decylamine, agarose-ethylamine, agarose-adipic acid hydrazide, agarose having 1,6-diaminohexane coupled thereto, arginine-agarose, lysine-agarose, amino terminal agarose, aminoethyl polyacrylamide gels, or agarose having polylysine attached thereto.
Claim 29
Dependent Claim
31 words
The method of claim 1 wherein said free amino groups are present in an amount such that there is a stoichiometric excess of free amino groups over the residual aldehyde groups.
Claim 30
Dependent Claim
23 words
The method of claim 28 wherein said free amino groups are present in more than a 100-fold excess over the residual aldehyde groups.
Claim 31
Dependent Claim
30 words
The method of claim 1 wherein said amine immobilized on said support is added to said rinsing solution to form a slurry, and said tissue is immersed in the slurry.
Claim 32
Dependent Claim
33 words
The method of claim 30 wherein said tissue is immersed in about 100 mls. of said slurry per 10 grams (wet weight) of said tissue, and said slurry is circulated around said tissue.
Claim 33
Dependent Claim
12 words
The method of claim 1 wherein the rinsing solution is substantially amine-free.
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