Patent US5516532A successfully refreshed from Google Patents.
US5516532A
Expired / Lapsed
US
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Injectable non-immunogenic cartilage and bone preparation
Assignee: MMC/GATX PARTNERSHIP NO 1
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Filing: 1994-08-05
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Granted: 1996-05-14
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Expires: 2014-08-05
Abstract
Abstract Ground bone or cartilage particles are demineralized by extraction with a low ionic strength buffer such as 20 mM HEPES containing a chelating agent and protease inhibitors, then extracted with an acidic solution such as 0.3M citric acid, pH 4.0, containing protease inhibitors. The extracted material generally contains less than 2% by weight phosphate and less than 100 mM calcium. The phosphate content can be further reduced by treatment of the matrix with acid phosphatase, which removes residual organic phosphate. The material is useful in a method of treatment of vesicouretal reflux and other disorders where a bulking agent is effective is correcting the defect.
Inventors
- 👤 Anthony Atala
- 👤 Samy Ashkar
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:50
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3691; A61K; A61K35/00; A61K35/12; A61K35/32; A61L24/00; A61L24/0005; A61L24/001; A61L24/0031; A61L27/3604; A61L27/3608; A61L27/3612; A61L27/3687; A61L27/50; A61F; A61F2/00; A61F2/02; A61F2/30; A61F2/30756; Y; Y10; Y10S; Y10S623/00; Y10S623/915; Y10S623/919
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
145 words
A method for correcting a tissue defect without the creation of new tissue comprising administering to a patient in need of treatment thereof a demineralized organic matrix in an amount effective to correct the tissue defect without creation of new tissue, wherein the organic matrix is prepared by grinding growing bone or cartilage to form particles having a diameter of between approximately 80 and 200 microns, leaching the calcium and other divalent ions from the growing bone or cartilage with a buffered aqueous chelating solutionat at a temperature less than 15° C. to produce a leached solid, extracting the leached solid with an acidic solution containing protease inhibitors at a temperature less than 15° C., further extracting the leached, extracted solid with a 1M salt solution to produce an organic matrix containing less than 2% by weight of phosphate and less than 100 mM calcium.
Claim 2
Independent Claim
145 words
A method for correcting a tissue defect without the creation of new tissue comprising administering to a patient in need of treatment thereof a demineralized organic matrix in an amount effective to correct the tissue defect without creation of new tissue, wherein the organic matrix is prepared by grinding growing bone or cartilage to form particles having a diameter of between approximately 80 and 200 microns, leaching the calcium and other divalent ions from the growing bone or cartilage with a buffered aqueous chelating solutionat at a temperature less than 15° C. to produce a leached solid, extracting the leached solid with an acidic solution containing protease inhibitors at a temperature less than 15° C., further extracting the leached, extracted solid with a 1M salt solution to produce an organic matrix containing less than 2% by weight of phosphate and less than 100 mM calcium.
Claim 3
Dependent Claim
27 words
The method of claim 1 wherein the matrix is prepared by treatment with acid phosphatase to remove phosphate remaining after leaching with aqueous chelating and salt solutions.
Claim 4
Dependent Claim
15 words
The method of claim 1 wherein the matrix is suspended in a pharmaceutically acceptable carrier.
Claim 5
Dependent Claim
23 words
The method of claim 3 wherein the carrier is selected from the group consisting of buffered aqueous solutions and biocompatible, biodegradable polymer solutions.
Claim 6
Dependent Claim
19 words
The method of claim 4 wherein the polymer is crosslinked in vivo to form a hydrogel encapsulating the matrix.
Claim 7
Dependent Claim
37 words
The method of claim 4 wherein the polymer is selected from the group consisting of polysaccharides, polyphosphazenes, polyacrylates, and polyethylene oxide-polypropylene glycol block copolymers which are crosslinked by temperature or pH, polyvinylpyrrolidone, fibrin glue and hyaluronic acid.
Claim 8
Dependent Claim
14 words
The method of claim 1 wherein the matrix is administered to correct vesicoureteral reflux.
Claim 9
Dependent Claim
13 words
The method of claim 1 wherein the matrix is administered to correct incontinence.
Claim 10
Dependent Claim
20 words
The method of claim 1 wherein the matrix is to block tubes for the purpose of sterillization of an individual.
Claim 11
Independent Claim
132 words
A method for preparing a demineralized organic matrix for correcting a tissue defect without creation of new tissue from growing bone or cartilage comprising grinding growing bone or cartilage to form particles having a diameter of between approximately 80 and 200 microns, leaching the calcium and other divalent ions from the growing bone or cartilage with a buffered aqueous chelating solution at at a temperature less than 15° C. to produce a leached solid, extracting the leached solid with an acidic solution containing protease inhibitors at a temperature less than 15° C., and further extracting the extracted, leached solid with a 1M salt solution at a temperature of less than 15° C. to produce a demineralized organic matrix containing less than 2% by weight of phosphate and less than 100 mM calcium.
Claim 12
Independent Claim
132 words
A method for preparing a demineralized organic matrix for correcting a tissue defect without creation of new tissue from growing bone or cartilage comprising grinding growing bone or cartilage to form particles having a diameter of between approximately 80 and 200 microns, leaching the calcium and other divalent ions from the growing bone or cartilage with a buffered aqueous chelating solution at at a temperature less than 15° C. to produce a leached solid, extracting the leached solid with an acidic solution containing protease inhibitors at a temperature less than 15° C., and further extracting the extracted, leached solid with a 1M salt solution at a temperature of less than 15° C. to produce a demineralized organic matrix containing less than 2% by weight of phosphate and less than 100 mM calcium.
Claim 13
Dependent Claim
29 words
The method of claim 10 further comprising treating the demineralized matrix with acid phosphatase to decrease the phosphate content of the resulting matrix to less than 1% by weight.
Claim 14
Dependent Claim
15 words
The method of claim 10 wherein the chelating agent is an aqueous solution of EDTA.
Claim 15
Dependent Claim
14 words
The method of claim 10 wherein the salt solution is a sodium chloride solution.
Claim 16
Dependent Claim
12 words
The method of claim 10 wherein the matrix is prepared from cartilage.
Claim 17
Dependent Claim
12 words
The method of claim 10 wherein the matrix is prepared from bone.
Claim 18
Dependent Claim
127 words
A demineralized organic matrix for correcting a tissue defect without creation of new tissue prepared by the method comprising grinding growing bone or cartilage to form particles having a diameter of between approximately 80 and 200 microns, leaching the calcium and other divalent ions from the growing bone or cartilage with a buffered aqueous chelating solution at at a temperature less than 15° C. to produce a leached solid, extracting the leached solid with an acidic solution containing protease inhibitors at a temperature less than 15° C., and further extracting the extracted, leached solid with a 1M salt solution at a temperature of less than 15° C. to produce a demineralized organic matrix containing less than 2% by weight of phosphate and less than 100 mM calcium.
Claim 19
Dependent Claim
127 words
A demineralized organic matrix for correcting a tissue defect without creation of new tissue prepared by the method comprising grinding growing bone or cartilage to form particles having a diameter of between approximately 80 and 200 microns, leaching the calcium and other divalent ions from the growing bone or cartilage with a buffered aqueous chelating solution at at a temperature less than 15° C. to produce a leached solid, extracting the leached solid with an acidic solution containing protease inhibitors at a temperature less than 15° C., and further extracting the extracted, leached solid with a 1M salt solution at a temperature of less than 15° C. to produce a demineralized organic matrix containing less than 2% by weight of phosphate and less than 100 mM calcium.
Claim 20
Dependent Claim
32 words
The matrix of claim 16 wherein the method further comprises treating the demineralized matrix with acid phosphatase to decrease the phosphate content of the resulting material to less than 1% by weight.
Claim 21
Dependent Claim
12 words
The material of claim 16 wherein the matrix is prepared from cartilage.
Claim 22
Dependent Claim
12 words
The material of claim 16 wherein the matrix is prepared from bone.
References Cited (Backward Citations)
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1999-05-14 | 1999-11-13 | 2000-05-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-05-14 | 2003-11-13 | 2004-05-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-05-14 | 2007-11-13 | 2008-05-14 | $7700.00 | Window Closed / Lapsed |