US6166184A
Expired / Lapsed
US
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Process for making a bioprosthetic device
Assignee: Medtronic Inc
•
Filing: 1997-08-18
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Granted: 2000-12-26
•
Expires: 2017-08-18
Abstract
Abstract Methods for making bioprosthetic devices made of collagen-based material having collagen amine groups and collagen carboxyl groups are provided. The methods include blocking at least a portion of the collagen amine groups with a blocking agent, activating at least a portion of the collagen carboxyl groups after blocking at least a portion of the collagen amine groups to form activated carboxyl groups, and contacting the activated collagen carboxyl groups with a polyfunctional spacer to crosslink the collagen-based material.
Inventors
- 👤 Marc Hendriks
- 👤 Verhoeven Michel
- 👤 Patrick Cahalan
- 👤 Mark W. Torrianni
- 👤 Linda Cahalan
- 👤 Benedicte Fouache
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:36
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3687; C; C08; C08H; C08H1/00; C08H1/06
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
78 words
A method for making a bioprosthetic device made of collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: blocking at least a portion of the collagen amine groups with a blocking agent; activating at least a portion of the collagen carboxyl groups after blocking at least a portion of the collagen amine groups to form activated carboxyl groups; and contacting the activated collagen carboxyl groups with a polyfunctional spacer to crosslink the collagen-based material.
Claim 2
Independent Claim
78 words
A method for making a bioprosthetic device made of collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: blocking at least a portion of the collagen amine groups with a blocking agent; activating at least a portion of the collagen carboxyl groups after blocking at least a portion of the collagen amine groups to form activated carboxyl groups; and contacting the activated collagen carboxyl groups with a polyfunctional spacer to crosslink the collagen-based material.
Claim 3
Dependent Claim
28 words
The method of claim 1, wherein the blocking agent is selected from the group consisting of an acylating agent, an aminating agent, and a biologically active derivative thereof.
Claim 4
Dependent Claim
20 words
The method of claim 2 wherein the step of blocking comprises contacting the collagen amine groups with an acylating agent.
Claim 5
Dependent Claim
27 words
The method of claim 3, wherein the acylating agent is selected from the group consisting of an N-hydroxy succinimide ester, a p-nitrophenyl ester, 1-acetylimidazole, and citraconic anhydride.
Claim 6
Dependent Claim
35 words
The method of claim 4, wherein the acylating agent is selected from the group consisting of acetic acid N-hydroxysuccinimide ester, sulfo-NHS-acetate, propionic acid N-hydroxysuccinimide ester, p-nitrophenyl formate, p-nitrophenyl acetate, p-nitrophenyl butyrate, 1-acetylimidazole, and citraconic anhydride.
Claim 7
Dependent Claim
20 words
The method of claim 2 wherein the step of blocking comprises contacting the collagen amine groups with an aminating agent.
Claim 8
Dependent Claim
15 words
The method of claim 6 wherein the aminating agent is an aldehyde or a ketone.
Claim 9
Dependent Claim
13 words
The method of claim 7 wherein the aminating agent is a monofunctional aldehyde.
Claim 10
Dependent Claim
20 words
The method of claim 8, wherein the monofunctional aldehyde is selected from the group consisting of propanal, butanal, and hexanal.
Claim 11
Dependent Claim
27 words
The method of claim 6 wherein the step of blocking comprises contacting the collagen amine groups with an aminating agent in the presence of a reducing agent.
Claim 12
Dependent Claim
26 words
The method of claim 10 wherein the reducing agent is selected from the group of sodium cyanoborohydride, sodium borohydride, dimethylamine borane, trimethylamine borane, and morpholine borane.
Claim 13
Dependent Claim
12 words
The method of claim 1 wherein the collagen-based material comprises whole tissue.
Claim 14
Dependent Claim
13 words
The method of claim 1, wherein the bioprosthetic device is a heart valve.
Claim 15
Dependent Claim
15 words
The method of claim 1 wherein each step is carried out in an aqueous solution.
Claim 16
Dependent Claim
21 words
The method of claim 1 wherein the step of blocking comprises blocking at least about 75% of the collagen amine groups.
Claim 17
Dependent Claim
21 words
The method of claim 15 wherein the step of blocking comprises blocking at least about 80% of the collagen amine groups.
Claim 18
Dependent Claim
21 words
The method of claim 16 wherein the step of blocking comprises blocking at least about 90% of the collagen amine groups.
Claim 19
Dependent Claim
41 words
The method of claim 1, wherein the step of activating comprises contacting the collagen carboxyl groups with an activating agent selected from the group consisting of a carbodiimide, an azide, 1,1'-carbonyldiimidazole, N,N'-disuccinimidyl carbonate, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, 1,2-benzisoxazol-3-yl-diphenyl phosphate, and N-ethyl-5-phenylisoxazolium-s'-sulfonate, and mixtures thereof.
Claim 20
Dependent Claim
12 words
The method of claim 18 wherein the activating agent is a carbodiimide.
Claim 21
Dependent Claim
11 words
The method of claim 19, wherein the carbodiimide is water soluble.
Claim 22
Dependent Claim
10 words
The method of claim 20 wherein the carbodiimide is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.HCl.
Claim 23
Dependent Claim
24 words
The method of claim 19, wherein the carbodiimide is selected from the group consisting of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.HCl, cyanamide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate, and mixtures thereof.
Claim 24
Dependent Claim
27 words
The method of claim 1 wherein the step of activating comprises contacting the collagen carboxyl groups with an activating agent in the presence of a stabilizing agent.
Claim 25
Dependent Claim
27 words
The method of claim 23, wherein the stabilizing agent is selected from the group consisting of N-hydroxysuccinimide, N-hydroxybenzotriazole, N-hydroxy-5-norbornene-endo-2,3-dicarboximide, 4-dimethylaminopyridine, the sulfo-derivative of N-hydroxysuccinimide, and mixtures thereof.
Claim 26
Dependent Claim
21 words
The method of claim 23 wherein the step of activating comprises contacting the collagen carboxyl groups with a carbodiimide and N-hydroxysuccinimide.
Claim 27
Dependent Claim
34 words
The method of claim 1, wherein the step of reacting the activated collagen carboxyl groups with a polyfunctional spacer comprises reacting the activated collagen carboxyl groups with a polyfunctional spacer and a diamine spacer.
Claim 28
Dependent Claim
11 words
The method of claim 26 wherein the diamine spacer is hydrophilic.
Claim 29
Dependent Claim
25 words
The method of claim 27, wherein the diamine spacer is selected from the group consisting of polyethyleneglycol spacers, polypropyleneglycol spacers, polyethylene-propyleneglycol spacers, and mixtures thereof.
Claim 30
Dependent Claim
31 words
The method of claim 28 wherein the hydrophilic diamine spacer is represented by the following general formula: H.sub.2 N--CH(CH.sub.3)--CH.sub.2 --[OCH.sub.2 CH(CH.sub.3)].sub.x --[OCH.sub.2 CH.sub.2 ].sub.y --[OCH.sub.2 CH(CH.sub.3)].sub.z --NH.sub.2 wherein: x+z=0-70 and y=0-90.
Claim 31
Dependent Claim
9 words
The method of claim 29 wherein x+z=0-35 and y=0-45.
Claim 32
Independent Claim
85 words
A method for crosslinking collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: blocking at least a portion of the collagen amine groups with a blocking agent to form blocked amine groups; contacting the collagen-based material having the blocked amine groups with a polyfunctional spacer for a time sufficient for the spacer to penetrate the collagen-based material; and activating at least a portion of the collagen carboxyl groups of the collagen-based material toward the polyfunctional spacer to crosslink the collagen-based material.
Claim 33
Independent Claim
85 words
A method for crosslinking collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: blocking at least a portion of the collagen amine groups with a blocking agent to form blocked amine groups; contacting the collagen-based material having the blocked amine groups with a polyfunctional spacer for a time sufficient for the spacer to penetrate the collagen-based material; and activating at least a portion of the collagen carboxyl groups of the collagen-based material toward the polyfunctional spacer to crosslink the collagen-based material.
Claim 34
Dependent Claim
20 words
The method of claim 31 wherein the step of blocking comprises contacting the collagen amine groups with an acylating agent.
Claim 35
Dependent Claim
35 words
The method of claim 32, wherein the acylating agent is selected from the group consisting of acetic acid N-hydroxysuccinimide ester, sulfo-NHS-acetate, propionic acid N-hydroxysuccinimide ester, p-nitrophenyl formate, p-nitrophenyl acetate, p-nitrophenyl butyrate, 1-acetylimidazole, and citraconic anhydride.
Claim 36
Dependent Claim
20 words
The method of claim 31 wherein the step of blocking comprises contacting the collagen amine groups with an aminating agent.
Claim 37
Dependent Claim
15 words
The method of claim 34 wherein the aminating agent is an aldehyde or a ketone.
Claim 38
Dependent Claim
21 words
The method of claim 31 wherein the step of blocking comprises blocking at least about 75% of the collagen amine groups.
Claim 39
Dependent Claim
41 words
The method of claim 31, wherein the step of activating comprises contacting the collagen carboxyl groups with an activating agent selected from the group consisting of a carbodiimide, an azide, 1,1'-carbonyldiimidazole, N,N'-disuccinimidyl carbonate, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, 1,2-benzisoxazol-3-yl-diphenyl phosphate, and N-ethyl-5-phenylisoxazolium-s'-sulfonate, and mixtures thereof.
Claim 40
Dependent Claim
12 words
The method of claim 37 wherein the activating agent is a carbodiimide.
Claim 41
Dependent Claim
21 words
The method of claim 38 wherein the step of activating comprises contacting the collagen carboxyl groups with a carbodiimide and N-hydroxysuccinimide.
Claim 42
Dependent Claim
14 words
The method of claim 31 wherein the polyfunctional spacer is a hydrophilic bifunctional spacer.
Claim 43
Dependent Claim
30 words
The method of claim 31 wherein the hydrophilic spacer is represented by the following general formula: H.sub.2 N--CH(CH.sub.3)--CH.sub.2 --[OCH.sub.2 CH(CH.sub.3)].sub.x --[OCH.sub.2 CH.sub.2 ].sub.y --[OCH.sub.2 CH(CH.sub.3)].sub.z --NH.sub.2 wherein: x+z=0-70 and y=0-90.
Claim 44
Independent Claim
97 words
A method for crosslinking collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: blocking at least a portion of the collagen amine groups with a blocking agent to form blocked amine groups; contacting the collagen-based material having the blocked amine groups with a hydrophilic bifunctional spacer represented by the following general formula: H.sub.2 N--CH(CH.sub.3)--CH.sub.2 --[OCH.sub.2 CH(CH.sub.3)].sub.x --[OCH.sub.2 CH.sub.2 ].sub.y --[OCH.sub.2 CH(CH.sub.3)].sub.z --NH.sub.2 wherein: x+z=0-70 and y=0-90; and activating at least a portion of the collagen carboxyl groups of the collagen-based material toward the bifunctional spacer with a carbodiimide to crosslink the collagen-based material.
Claim 45
Independent Claim
97 words
A method for crosslinking collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: blocking at least a portion of the collagen amine groups with a blocking agent to form blocked amine groups; contacting the collagen-based material having the blocked amine groups with a hydrophilic bifunctional spacer represented by the following general formula: H.sub.2 N--CH(CH.sub.3)--CH.sub.2 --[OCH.sub.2 CH(CH.sub.3)].sub.x --[OCH.sub.2 CH.sub.2 ].sub.y --[OCH.sub.2 CH(CH.sub.3)].sub.z --NH.sub.2 wherein: x+z=0-70 and y=0-90; and activating at least a portion of the collagen carboxyl groups of the collagen-based material toward the bifunctional spacer with a carbodiimide to crosslink the collagen-based material.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2003-12-26 | 2004-06-26 | 2004-12-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2007-12-26 | 2008-06-26 | 2008-12-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2011-12-26 | 2012-06-26 | 2012-12-26 | $7700.00 | Window Closed / Lapsed |