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Composition and device for in vivo cartilage repair comprising nanocapsules with osteoinductive and/or chondroinductive factors

Assignee: Sulzer Markets and Technology AG
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Filing: 1997-08-14
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Granted: —
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Expires: 2017-08-14
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Abstract

Abstract The composition as described serves for in vivo cartilage repair. It basically consists of a naturally derived osteoinductive and/or chondroinductive mixture of factors (e.g. derived from bone) or of a synthetic mimic of such a mixture combined with a nanosphere delivery system. A preferred mixture of factors is the combination of factors isolated from bone, known as BP and described by Poser and Benedict (WO 95/13767). The nanosphere delivery system consists of nanospheres defined as polymer particles of less than 1000 nm in diameter (whereby the majority of particles preferably ranges between 200-400 nm) in which nanospheres the combination of factors is encapsulated. The nanospheres are loaded with the mixture of factors in a weight ratio of 0.001 to 17% (w/w), preferably of 1 to 4% (w/w) and have a release profile with an initial burst of 10 to 20% of the total load over the first 24 hours and a long time release of at least 0.1 per day during at least seven following days. The nanospheres are composed of e.g. ((D,L)-lactic acid / glycolic acid)-copolymer (PLGA). The loaded nanospheres are e.g. made by phase inversion. The composition is advantageously utilized as a device comprising any biodegradable matrix in which the nanospheres loaded with the factor combination is contained.

Inventors

  • 👤 Brent A. Atkinson
  • 👤 John Ranieri
  • 👤 Pedro Bittmann
  • 👤 Marsha Lynn Whitney
  • 👤 James John Benedict
  • 👤 Donald Chickering

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-08 06:11
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/51; A61K9/5107; A61K9/513; A61K9/5146; A61K9/5153; A61F; A61F2/00; A61F2/02; A61F2/30; A61F2/30756; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61L27/24; A61L27/26; A61L27/40; A61L27/44; A61L27/48; A61L27/50; A61L27/54; A61P; A61P19/00; B; B82; B82Y; B82Y5/00; A61B; A61B17/00; A61B17/04; A61B17/06; A61B17/06166; A61F2/28; A61F2002/2817; A61F2002/30001; A61F2002/30003; A61F2002/30004; A61F2002/30036; A61F2002/3006; A61F2002/30062; A61F2002/30667; A61F2002/30677; A61F2210/00; A61F2210/0004; A61F2250/00; A61F2250/0014; A61F2250/0035; A61F2310/00; A61F2310/00005; A61F2310/00365; A61L2300/00; A61L2300/20; A61L2300/252; A61L2300/30; A61L2300/60; A61L2300/62; A61L2300/624; A61L2400/00; A61L2400/12; A61L2430/00; A61L2430/06; Y; Y10; Y10S; Y10S977/00; Y10S977/902; Y10S977/904; Y10S977/908; Y10S977/91; Y10S977/914

Claims Analysis

Total Claims: 23
Claim 1
Independent Claim 106 words
Composition for inducing in vivo cartilage repair comprising an osteoinductive and/or chondroinductive mixture of factors derived from natural tissue or a sythetic mimic of such a mixture encapsulated in nanospheres, whereby the nanospheres are polymer particles having a size of less than 1000 nm and an in vitro analytically determined release rate profile with an initial burst of 10 to 20% of the total load over the first 24 hours and a long time release of at least 0.1 % per day during at least seven following days and whereby the nanospheres are loaded with between 0.001 and 17% weight percent of the mixture of factors.
Claim 2
Dependent Claim 31 words
Composition according to claim 1, characterized in that the long term release is between 0. 1 and 1 % of the total load per day over between 40 and 70 days.
Claim 3
Dependent Claim 26 words
Composition according to claim 1 or 2, characterized in that the osteoinductive and/or chondroinductive mixture of factors is derived from bone, cartilage, tendon, meniscus or ligament.
Claim 4
Dependent Claim 33 words
Composition according to claim 1 or 2, characterized in that the osteoinductive and/or chondroinductive mixture of factors is the mixture known as BP (bone protein) derived from bovine long bones and partly purified.
Claim 5
Dependent Claim 22 words
Composition according to claim 4, characterized , in that the nanospheres are loaded with between 1 and 4% weight percent of BP.
Claim 6
Dependent Claim 35 words
Composition according to one of claims 1 to 5, characterized in that the nanospheres consist of ((D,L)lactic acid / glycolic acid)copolymer containing 20 to 80% of lactic acid and 80 to 20% of glycolic acid.
Claim 7
Dependent Claim 28 words
Composition according to one of claims 1 to 5, characterized in that the ((D,L)lactic acid / glycolic acid)-copolymer contains 50% of lactic acid and 50% of glycolic acid.
Claim 8
Dependent Claim 19 words
Composition according to one of claims 1 to 7, characterized in that the nanospheres are made by phase inversion.
Claim 9
Dependent Claim 19 words
Device containing the composition according to one of claims 1 to 8 and further comprising a porous biodegradable matrix.
Claim 10
Dependent Claim 18 words
Device according to claim 9, characterized in that it contains at least 2µg of loaded nanospheres per ml.
Claim 11
Dependent Claim 23 words
Device according to claim 9, characterized in that it contains at least 20ng of the osteoinductive and/or chondroinductive mixture of factors per ml.
Claim 12
Dependent Claim 24 words
Device according to one of claims 9 to 11, characterized in that the matrix has the form of a sponge, membrane, film or gel.
Claim 13
Dependent Claim 25 words
Device according to one of claims 9 to 12, characterized in that the matrix consists of collagen type I, collagen type II or hyaluronic acid.
Claim 14
Dependent Claim 21 words
Use of the composition according to one of claims 1 to 8 for preparing a device for in vivo cartilage repair.
Claim 15
Dependent Claim 16 words
Use according to claim 14, characterized in that the cartilage is articular cartilage or meniscus cartilage.
Claim 16
Dependent Claim 22 words
Use of the composition according to one of claims 1 to 8 for cartilage repair on an animal with a degenerative disease.
Claim 17
Dependent Claim 22 words
Use of the device according to one of claims 9 to 13 for cartilage repair on an animal with a degenerative disease.
Claim 18
Dependent Claim 25 words
Method for in vivo cartilage repair comprising the step of filling a cartilage defect with a device according to one of claims 9 to 13.
Claim 19
Dependent Claim 14 words
Method according to claim 18, characterized in that the defect is dressed before filling.
Claim 20
Dependent Claim 25 words
Method for in vitro cartilage repair comprising the step of applying to the cartilage defect a composition according to one of claims 1 to 8.
Claim 21
Dependent Claim 14 words
Method according to claim 20, characterized in that the composition is applied by injection.
Claim 22
Dependent Claim 25 words
Method according to claim 20 or 21, characterized in that the composition is applied in an amount of at least 2µg per ml defect size.
Claim 23
Dependent Claim 40 words
Method according to claim 20 or 21, characterized in that the composition is applied in an amount such that the osteoinductive and/or chondroinductive mixture is present in the defect in an amount of at least 20ng per ml defect size.

References Cited (Backward Citations)

US4620327A Cited
US5368858A Cited
US5595722A Cited

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