Patent US5295146A successfully refreshed from Google Patents.
US6861211B2
Expired / Lapsed
US
⏱️ 0.0 years remaining
Stabilization of implantable bioprosthetic devices
Assignee: Children's Hospital of Philadelphia
•
Filing: 2001-08-22
•
Granted: 2005-03-01
•
Expires: 2021-08-22
Abstract
Abstract The invention relates to methods of stabilizing glycosaminoglycans in a biological tissue (e.g. a bioprosthetic implant) in conjunction with cross-linking of protein in the tissue. The methods of the invention improve the mechanical integrity of the device and improves its stability in vivo. The invention also includes biological tissues having stabilized glycosaminoglycans and cross-linked proteins and kits for preparing such tissues.
Inventors
- 👤 Robert J. Levy
- 👤 Narendra Vyavahare
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:20
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3687; A61L27/14; A61L27/20; A61L27/22; A61L27/24; A61L27/38; A61L27/50; A61L27/507; A61F; A61F2/00; A61F2/02; A61F2/30; A61F2/30756; A61L2430/00; A61L2430/40
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
90 words
A method of treating on implantable biological tissue, said method comprising stabilizing glycosaminoglycans on the tissue and cross-linking proteins on the tissue, wherein the glycosaminoglycans stabilizing comprises contacting the tissue with (a) a water-soluble carbodiimide composition having a pH of 6.9 to 7.9 or (b) a carbohydrate oxidizing agent and a bi-functional carbohydrate-protein linking agent, and the proteins cross-linking comprises contacting the tissue with a cross-linking reagent, wherein the cross linking reagent is a member selected from the group consisting of glutaraldehyde, formaldehyde, a dialdehyde, carbodiimide, and a polyepoxy ether.
Claim 2
Independent Claim
90 words
A method of treating on implantable biological tissue, said method comprising stabilizing glycosaminoglycans on the tissue and cross-linking proteins on the tissue, wherein the glycosaminoglycans stabilizing comprises contacting the tissue with (a) a water-soluble carbodiimide composition having a pH of 6.9 to 7.9 or (b) a carbohydrate oxidizing agent and a bi-functional carbohydrate-protein linking agent, and the proteins cross-linking comprises contacting the tissue with a cross-linking reagent, wherein the cross linking reagent is a member selected from the group consisting of glutaraldehyde, formaldehyde, a dialdehyde, carbodiimide, and a polyepoxy ether.
Claim 3
Dependent Claim
14 words
The method of claim 1 , wherein said glycosaminoglycans are endogenous to the tissue.
Claim 4
Dependent Claim
17 words
The method of claim 2 , wherein the tissue is a part of an implantable bioprosthetic device.
Claim 5
Dependent Claim
50 words
The method of claim 3 , wherein said device is selected from the group consisting of a heart valve prosthesis, a vascular graft, a skin graft, a dura mater graft, a cartilage graft, a cartilage implant, a pericardium graft, a urinary bladder prosthesis, a ligament prosthesis, and a tendon prosthesis.
Claim 6
Dependent Claim
14 words
The method of claim 4 , wherein said device is a heart valve prosthesis.
Claim 7
Dependent Claim
29 words
The method of claim 5 , wherein said heart valve prosthesis is selected from the group consisting of a porcine heart valve and a bovine pericardium-derived heart valve prosthesis.
Claim 8
Dependent Claim
23 words
The method of claim 1 , wherein the stabilization of glycosaminoglycans on the tissue is achieved prior to cross-linking proteins on the tissue.
Claim 9
Dependent Claim
82 words
The method of claim 7 , wherein a) the difference between i) the thermal shrinkage temperature of the tissue after contacting the tissue with said carbodiimide and ii) the thermal shrinkage temperature of the tissue prior to contacting the tissue with said carbodiimide is less than half of b) the difference between i) the thermal shrinkage temperature of the tissue after cross-linking proteins on the tissue and ii) the thermal shrinkage temperature of the tissue prior to cross-linking proteins on the tissue.
Claim 10
Dependent Claim
13 words
The method of claim 1 , wherein said carbodiimide is 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide.
Claim 11
Dependent Claim
11 words
A biological tissue treated by the method of claim 1 .
Claim 12
Dependent Claim
42 words
The method of claim 1 , wherein the stabilizing of glycosaminoglycans on the tissue is achieved by contacting the tissue with the carbohydrate oxidizing agent to generate aldehyde groups on said glycosaminoglycans and contacting the tissue with a bi-functional carbohydrate-protein linking agent.
Claim 13
Dependent Claim
25 words
The method of claim 11 , wherein said carbohydrate oxidizing agent is selected from the group consisting of bromine, periodate, nitric acid, and lead tetraacetate.
Claim 14
Dependent Claim
28 words
The method of claim 11 , wherein the bi-functional carbohydrate-protein linking agent is a member selected from the group consisting of glutaraldehyde, a diamine, and an azido hydrazide.
Claim 15
Dependent Claim
15 words
The method of claim 1 , wherein the cross-linking comprises contacting the tissue with glutaraldehyde.
Claim 16
Dependent Claim
26 words
The method of claim 1 , wherein the cross-linking comprises contacting the tissue with glutaraldehyde, provided that the cross-linking is performed after the stabilizing of glycosaminoglycans.
Claim 17
Dependent Claim
58 words
The method of claim 1 , wherein the stabilizing comprises contacting the tissue with a water-soluble carbodiimide composition having a pH of 6.9 to 7.9, and the cross-linking comprises contacting the tissue with a cross-linking reagent, wherein the cross-linking reagent is a member selected from the group consisting of glutaraldehyde, formaldehyde, a dialdehyde, carbodiimide, and a polyepoxy ether.
Claim 18
Independent Claim
52 words
A method of treating an implantable biological tissue, said method comprising stabilizing glycosaminoglycans on the tissue and cross-linking proteins on the tissue, wherein the glycosaminoglycans stabilizing comprises contacting the tissue with a water-soluble carbodiimide composition having a pH of 6.9 to 7.9, and wherein the cross-linking comprises contacting the tissue with glutaraldehyde.
Claim 19
Independent Claim
52 words
A method of treating an implantable biological tissue, said method comprising stabilizing glycosaminoglycans on the tissue and cross-linking proteins on the tissue, wherein the glycosaminoglycans stabilizing comprises contacting the tissue with a water-soluble carbodiimide composition having a pH of 6.9 to 7.9, and wherein the cross-linking comprises contacting the tissue with glutaraldehyde.
Claim 20
Dependent Claim
11 words
A biological tissue treated by the method of claim 17 .
Claim 21
Independent Claim
54 words
A method of treating an implantable biological tissue, said method comprising stabilizing glycosaminoglycans on the tissue and cross-linking proteins on the tissue, wherein the glycosaminoglycans stabilizing comprises (i) contacting the tissue with periodate and (ii) contacting the tissue with a bi-functional carbohydrate-protein linking agent and wherein the cross-linking comprises contacting the tissue with glutaraldehyde.
Claim 22
Independent Claim
54 words
A method of treating an implantable biological tissue, said method comprising stabilizing glycosaminoglycans on the tissue and cross-linking proteins on the tissue, wherein the glycosaminoglycans stabilizing comprises (i) contacting the tissue with periodate and (ii) contacting the tissue with a bi-functional carbohydrate-protein linking agent and wherein the cross-linking comprises contacting the tissue with glutaraldehyde.
Claim 23
Dependent Claim
11 words
A biological tissue treated by the method of claim 19 .
References Cited (Backward Citations)
US4378224A
Cited
US4931546A
Cited
US4880429A
Cited
US5660692A
Cited
US5447536A
Cited
US5865849A
Cited
US5919472A
Cited
US5782931A
Cited
US5891196A
Cited
US6166184A
Cited
US6017741A
Cited
US6214054B1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2008-02-29 | 2008-08-30 | 2009-03-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2012-02-29 | 2012-08-30 | 2013-03-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2016-02-29 | 2016-08-30 | 2017-03-01 | $7700.00 | Window Closed / Lapsed |