US6117979A
Expired / Lapsed
US
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Process for making a bioprosthetic device and implants produced therefrom
Assignee: JARO MICHAEL J
•
Filing: 1997-08-18
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Granted: 2000-09-12
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Expires: 2017-08-18
Abstract
Abstract Bioprosthetic devices made of collagen-based material having collagen amine groups and collagen carboxyl groups are provided as well as methods for their formation. The methods comprise combining an epoxy functionalized crosslinking agent with the collagen-based material in an aqueous medium at an acidic pH to react a portion of the collagen carboxyl groups with the epoxy functionalized crosslinking agent to form crosslinked collagen-based material comprising residual collagen carboxyl groups.
Inventors
- 👤 Marc Hendriks
- 👤 Michel Verhoeven
- 👤 Patrick Cahalan
- 👤 Raymond Zeeman
- 👤 Piet Dijkstra
- 👤 Jan Feijen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:24
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/50; A61L27/507; A61L27/14; A61L27/22; A61L27/24; A61L27/36; A61L27/3683; A61L27/3687; C; C08; C08H; C08H1/00; C08H1/06; A61F; A61F2310/00; A61F2310/00005; A61F2310/00365; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/84; Y10S623/00; Y10S623/90; Y10S623/901
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
65 words
A method for making a bioprosthetic device made of collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising combining an epoxy functionalized crosslinking agent with the collagen-based material in an aqueous medium at an acidic pH to react a portion of the collagen carboxyl groups with the epoxy functionalized crosslinking agent to form crosslinked collagen-based material comprising residual collagen carboxyl groups.
Claim 2
Independent Claim
65 words
A method for making a bioprosthetic device made of collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising combining an epoxy functionalized crosslinking agent with the collagen-based material in an aqueous medium at an acidic pH to react a portion of the collagen carboxyl groups with the epoxy functionalized crosslinking agent to form crosslinked collagen-based material comprising residual collagen carboxyl groups.
Claim 3
Dependent Claim
21 words
The method of claim 1 further including blocking at least a portion of the collagen amine groups with a blocking agent.
Claim 4
Dependent Claim
36 words
The method of claim 2 wherein the step of blocking at least a portion of the collagen amine groups is carried out before the step of combining an epoxy functionalized crosslinking agent with the collagen-based material.
Claim 5
Dependent Claim
27 words
The method of claim 2 wherein the blocking agent is selected from the group of an acylating agent, an aminating agent, and a biologically active derivative thereof.
Claim 6
Dependent Claim
36 words
The method of claim 4 wherein the step of blocking comprises contacting the collagen amine groups with an acylating agent selected from the group of an N-hydroxy succinimide ester, a p-nitrophenyl ester, 1-acetylimidazole, and citraconic anhydride.
Claim 7
Dependent Claim
30 words
The method of claim 2 wherein the step of blocking comprises contacting the collagen amine groups with an aminating agent selected from the group of an aldehyde and a ketone.
Claim 8
Dependent Claim
12 words
The method of claim 1 wherein the collagen-based material comprises whole tissue.
Claim 9
Dependent Claim
13 words
The method of claim 1 wherein the bioprosthetic implant is a heart valve.
Claim 10
Dependent Claim
33 words
The method of claim 1 further comprising a step of activating at least a portion of the residual collagen carboxyl groups to form activated carboxyl groups capable of reacting with collagen amine groups.
Claim 11
Dependent Claim
46 words
The method of claim 9 wherein the step of activating comprises reacting at least a portion of the residual collagen carboxyl groups with an activating agent selected from the group of a carbodiimide, an azide, 1,1'-carbonyldiimidazole, N,N'-disuccinimidyl carbonate, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, and 1,2-benzisoxazol-3-yl-diphenyl phosphate, N-ethyl-5-phenylisoxazolium-s'-sulfonate, and mixtures thereof.
Claim 12
Dependent Claim
12 words
The method of claim 10 wherein the activating agent is a carbodiimide.
Claim 13
Dependent Claim
14 words
The method of claim 11 wherein the carbodiimide is at least partially water soluble.
Claim 14
Dependent Claim
11 words
The method of claim 12 wherein the carbodiimide is 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide.HCl.
Claim 15
Dependent Claim
25 words
The method of claim 12 wherein the carbodiimide is selected from the group 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 16
Dependent Claim
28 words
The method of claim 9 wherein the step of activating comprises contacting the residual collagen carboxyl groups with an activating agent in the presence of a stabilizing agent.
Claim 17
Dependent Claim
26 words
The method of claim 15 wherein the stabilizing agent is selected from the group 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 18
Dependent Claim
21 words
The method of claim 9 wherein the step of activating comprises contacting the collagen carboxyl groups with a carbodiimide and N-hydroxysuccinimide.
Claim 19
Dependent Claim
27 words
The method of claim 9 wherein the step of activating comprises contacting the residual collagen carboxyl groups with an activating agent in the presence of a spacer.
Claim 20
Dependent Claim
15 words
The method of claim 1 wherein the epoxy functionalized crosslinking agent is a polyol polyglycidylether.
Claim 21
Dependent Claim
29 words
The method of claim 19 wherein the epoxy functionalized crosslinking agent is selected from the group of glycol diglycidyl ether, glycerol diglycidyl ether, glycerol triglycidyl ether, and butanediglycidyl ether.
Claim 22
Dependent Claim
43 words
The method of claim 19 wherein the epoxy functionalized crosslinking agent has the following formula: ##STR5## wherein R may be any substituent that does not interfere with the crosslinking process and/or diminish the solubility of the crosslinking agent in aqueous solutions and n=1-6.
Claim 23
Dependent Claim
42 words
The method of claim 1 wherein the epoxy functionalized crosslinking agent is selected from the group of polyglycidylether-functional molecules of polyethlyeneglycol, polypropyleneglycol, and polyethylene-propyleneglycol, for which the diglycidylether derivative can be represented by the following general formula: ##STR6## wherein x+z=0-70 and y=0-90.
Claim 24
Dependent Claim
16 words
The method of claim 1 wherein the epoxy functionalized crosslinking agent is a polyepoxy crosslinking agent.
Claim 25
Dependent Claim
14 words
The method of claim 23 wherein the polyepoxy crosslinking agent is a hydrophilic diepoxide.
Claim 26
Dependent Claim
18 words
The method of claim 1 wherein the pH of the aqueous medium is about pH=4.5 to about pH=6.
Claim 27
Dependent Claim
25 words
The method of claim 1 further including a step of reacting the residual collagen carboxyl groups with the collagen amine groups to form zero-length crosslinks.
Claim 28
Dependent Claim
31 words
The method of claim 1 further including a step of combining a spacer with the crosslinked collagen-based material comprising residual collagen carboxyl groups to form crosslinks between the collagen amine groups.
Claim 29
Independent Claim
93 words
A method for crosslinking collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: combining a diepoxy crosslinking agent with the collagen-based material in an aqueous medium at an acidic pH to react a portion of the collagen carboxyl groups with the diepoxy crosslinking agent to form crosslinked collagen-based material comprising residual collagen carboxyl groups; and contacting at least a portion of the residual collagen carboxyl groups with an activating agent in the presence of a stabilizing agent to form activated carboxyl groups capable of reacting with collagen amine groups.
Claim 30
Independent Claim
93 words
A method for crosslinking collagen-based material having collagen amine groups and collagen carboxyl groups, the method comprising: combining a diepoxy crosslinking agent with the collagen-based material in an aqueous medium at an acidic pH to react a portion of the collagen carboxyl groups with the diepoxy crosslinking agent to form crosslinked collagen-based material comprising residual collagen carboxyl groups; and contacting at least a portion of the residual collagen carboxyl groups with an activating agent in the presence of a stabilizing agent to form activated carboxyl groups capable of reacting with collagen amine groups.
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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) | 2003-09-12 | 2004-03-13 | 2004-09-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2007-09-12 | 2008-03-13 | 2008-09-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2011-09-12 | 2012-03-13 | 2012-09-12 | $7700.00 | Window Closed / Lapsed |