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EP0530804A1
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Kits and compositions for the treatment and repair of defects or lesions in cartilage or bone
Assignee: SHAW, ROBERT FRANCIS
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Filing: 1992-09-03
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Granted: —
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Expires: 2012-09-03
Abstract
Abstract Kits and compositions are provided for the treatment and repair of defects in the cartilage or bone of humans and other animals as in full-thickness defects in joints. A matrix having pores large enough to allow cells to populate the matrix and to form blood vessels is used to fill the defect in bone. The matrix filling the bone defect contains an angiogenic factor and also contains an osteogenic factor in an appropriate delivery system. A matrix having pores sufficiently large to allow cartilage repair cells to populate the matrix is used to fill a defect in cartilage to induce cartilage formation. The matrix filling the defect in cartilage contains a proliferation agent and also contains a transforming factor in an appropriate delivery system. The matrix may also contain a chemotactic agent to attract cartilage repair cells. In a full-thickness defect, a membrane is used to separate the defect sites in bone and cartilage, which is sealed to the cartilage-bone-junction and which prevents blood vessels and associated cells from penetrating from one site to the other.
Inventors
- 👤 Ernst B. Hunziker
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 10:38
CPC Classifications
A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1825; A61F; A61F2/00; A61F2/02; A61F2/28; A61F2/30; A61F2/30756; A61K38/1841; A61L; A61L24/00; A61L24/001; A61L24/0015; A61L24/04; A61L24/10; A61L24/106; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61L27/50; A61L27/54; A61P; A61P19/00; A61P19/04; A61P19/08; A61P43/00; A61F2/2846; A61F2002/2817; A61F2002/30001; A61F2002/30003; A61F2002/3006; A61F2002/30062; A61F2002/30667; A61F2002/30677; A61F2210/00; A61F2210/0004; A61F2310/00; A61F2310/00005; A61F2310/00365; A61L2300/00; A61L2300/20; A61L2300/252; A61L2300/254; A61L2300/40; A61L2300/412; A61L2300/414; A61L2300/45; A61L2300/60; A61L2300/62; A61L2300/626; A61L2430/00; A61L2430/02; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/84
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
88 words
A composition for the treatment of defects in bone comprising: a matrix or matrix-forming material used to fill a defect in bone; an angiogenic factor at an appropriate concentration to stimulate the formation and ingrowth of blood vessels and associated cells in the matrix and the area of the defect; and an osteogenic factor associated with a delivery system and at an appropriate concentration such that upon delivery of the osteogenic factor to cells in the matrix and defect, the cells develop into bone cells which form bone.
Claim 2
Dependent Claim
33 words
The composition according to claim 1, wherein the angiogenic factor is selected from the group consisting of bFGF, a mixture of bFGF and heparin sulfate, TGF-β, PDGF, TNF-α, angiogenin, angiotropin or combinations thereof.
Claim 3
Dependent Claim
32 words
The composition according to claim 1 or 2, wherein the osteogenic factor is selected from the group consisting of TGF-β, a mixture of a TGF-β and EGF, osteogenin, BMP and combinations thereof.
Claim 4
Dependent Claim
38 words
The composition according to any one of claims 1 to 3, wherein the matrix used to fill the defect area is selected from the group consisting of fibrin, collagen, gelatin, agarose, calcium phosphate containing compounds and combinations thereof.
Claim 5
Dependent Claim
51 words
The composition according to any one of claims 1 to 3, wherein the angiogenic factor is bFGF present at a concentration of 5-10 ng/ml in the matrix and the osteogenic factor is TGF-β associated with an appropriate delivery system which provides a concentration of TGF-β of 100 ng/ml of matrix solution.
Claim 6
Dependent Claim
38 words
The composition according to any one of claims 1 to 3, wherein the delivery system is selected from the group consisting of liposomes, bioerodible polymers, collagen fibers chemically linked to heparin sulfate proteoglycans, carbohydrate-based corpuscles, and water-oil emulsions.
Claim 7
Dependent Claim
42 words
A composition for the treatment of defects in bone comprising; a collagenous matrix solution; basic FGF present at a concentration of 5-10 ng/ml of matrix solution; and TGF-β encapsulated in liposomes and present at a concentration of 100 ng/ml of matrix solution.
Claim 8
Dependent Claim
33 words
The composition according to claims 1 to 7 for the induction of bone formation at a selected site in bone tissue of an animal wherein the composition is used to fill the site.
Claim 9
Dependent Claim
194 words
A kit for treating full-thickness defects in joints in animals which comprises: a first matrix containing an effective amount of an angiogenic factor to stimulate formation and ingrowth of blood vessels with associated cells and containing an osteogenic factor associated with a delivery system that releases the osteogenic factor at a concentration sufficient to induce differentiation of bone repair cells into bone cells which form bone, which is used for filling the bone portion of the full-thickness defect; a membrane which prevents migration of cells from the bone defect side to the cartilage defect side, which is used for covering the matrix-filled bone portion of the full-thickness defect and may be sealed to the perimeter of the defect in the region of the cartilage-bone junction; and a second matrix containing an effective amount of a proliferation agent to stimulate proliferation of repair cells, an effective amount of a chemotactic agent to attract repair cells, and an effective amount of a transforming factor associated with a delivery system that releases the transforming factor at a concentration sufficient to transform repair cells into chondrocytes, which is used for filling the cartilage portion of the full-thickness defect.
Claim 10
Dependent Claim
36 words
The kit according to claim 9 further comprising transglutaminase which may be used for covering the surface of the cartilage portion of the full-thickness defect prior to dressing the defect or lesion with the second matrix.
Claim 11
Dependent Claim
24 words
The kit according to any one of claims 9 to 10 wherein the osteogenic factor, the proliferation agent, and the transforming factor, are TGF-β.
Claim 12
Dependent Claim
50 words
The kit according to any one of claims 9 to 11 in which the delivery system for the delivery of the transforming factor and the osteogenic factor is selected from the group consisting of liposomes, bioerodible polymers, collagen fibers chemically linked to heparin sulfate proteoglycans, carbohydrate-based corpuscles, and water-oil emulsions.
Claim 13
Dependent Claim
35 words
The kit according to any one of claims 9 to 12 in which the first matrix is selected from the group consisting of fibrin, collagen, gelatin, agarose, and calcium phosphate containing compounds or combinations thereof.
Claim 14
Dependent Claim
30 words
The kit according to any one of claims 9 to 13 in which the second matrix is selected from the group consisting of fibrin, collagen, gelatin, agarose, and combinations thereof.
Claim 15
Dependent Claim
43 words
The kit according to any one of claims 9 to 14, wherein the first and the second matrix is fibrin which is formed by addition of thrombin to a solution of fibrinogen immediately before filling the defect or lesion with the fibrinogen solution.
Claim 16
Dependent Claim
92 words
The kit according to any one of claims 9 to 15 wherein the angiogenic factor is bFGF present at a concentration of 5-10 ng/ml of the first matrix; the osteogenic factor is TGF-β encapsulated in liposomes and present at a concentration of 100 ng/ml of the first biodegradable matrix; the proliferation agent and the chemotactic agent are TGF-β present at a concentration of 2-10 ng/ml of the second matrix; and the transforming factor is TGF-β encapsulated in liposomes and present at a concentration of greater than 200 ng/ml of the second matrix.
Claim 17
Dependent Claim
28 words
The kit according to any one of claims 9 to 16, wherein the first and second matrices further contain a cell adhesion promoting factor comprising the tripeptide Arg-Gly-Asp.
Claim 18
Dependent Claim
152 words
A kit for treating full-thickness defects in joints of animals which comprises: a first collagenous matrix containing bFGF present at a concentration of 5-10 ng/ml of the first collagenous matrix, and containing TGF-β in liposomes at a concentration of 100 ng/ml of the first collagenous matrix, which may be used for filling the bone portion of the full-thickness defect; a membrane, which is impermeable to blood vessels and cells, which may be used for covering the first collagenous matrix-filled bone portion of the full-thickness defect and may be sealed at its perimeter to the edges of the defect in the region of the cartilage-bone junction; a second collagenous matrix containing TGF-β at a concentration of 2-10 ng/ml of the second collagenous matrix, and containing TGF-β in liposomes at a concentration of greater than 200 ng/ml of the second collagenous matrix, which is used for filling the cartilage portion of the full-thickness defect.
Claim 19
Dependent Claim
34 words
The kit according to claim 18 further comprising the step of covering the surface of the cartilage portion of the full-thickness defect with transglutaminase prior to filling the defect with the second collagenous matrix.
Claim 20
Dependent Claim
24 words
The composition according to claim 5 or 7 further comprising an amount of heparin sulfate sufficient to enhance the angiogenic activity of the bFGF.
Claim 21
Dependent Claim
28 words
The kit according to claim 16 or 18 wherein the first matrix also contains an amount of heparin sulfate sufficient to enhance the angiogenic activity of the bFGF.
Claim 22
Dependent Claim
12 words
The kit according to claim 11 wherein the angiogenic factor is bFGF.
Claim 23
Dependent Claim
22 words
The use of the composition in any one of claims 1-8 to prepare a medicament for the treatment of defects in bone.
Claim 24
Independent Claim
85 words
A method of preparing a composition for the treatment of defects in bone comprising: adding to a matrix or matrix-forming material useful for filling a defect in bone an amount of an angiogenic factor sufficient to stimulate the formation and ingrowth of blood vessels and associated cells in the matrix and area of the bone defect, and an amount of an osteogenic factor associated with an appropriate delivery system which can provide a sufficient concentration of osteogenic factor to stimulate the formation of bone cells.
Claim 25
Independent Claim
245 words
A method for making a kit for treating full-thickness defects in joints in animals comprising: combining a first matrix or matrix-forming material useful to fill a defect in a bone with an angiogenic factor at a concentration sufficient to stimulate the formation and ingrowth of blood vessels and associated cells in the matrix and area of the bone defect and an osteogenic factor associated with an appropriate delivery system which can provide a sufficient concentration of osteogenic factor to blood vessels and associated cells in the matrix and defect, to stimulate the formation of bone cells; providing a membrane which can be sealed to the perimeter of the cartilage-bone junction of the full-thickness defect to cover the matrix-filled bone portion of the full-thickness defect and prevent the migration of cells from the bone defect side to the cartilage defect side of the full-thickness defect; and combining a second matrix or matrix-forming material useful to fill the cartilage portion of the full-thickness defect with a proliferation agent at a sufficient concentration to stimulate proliferation of repair cells in the cartilage portion of the full-thickness defect, and a chemotactic agent at a sufficient concentration to attract repair cells to the matrix in the cartilage portion of the full-thickness, and a transforming factor associated with an appropriate delivery system which can provide a sufficient concentration of the transforming factor to stimulate the formation of cartilage from the repair cells in the matrix-filled cartilage portion of the full-thickness defect.
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