WO2005084684A1 - Verwendung eines gemisches für die herstellung eines mittels zur behandlung von defektem oder degeneriertem knorpel in vivo und bei der herstellung von natürlichem knorpelerszy in vitro - Google Patents
Verwendung eines gemisches für die herstellung eines mittels zur behandlung von defektem oder degeneriertem knorpel in vivo und bei der herstellung von natürlichem knorpelerszy in vitro Download PDFInfo
- Publication number
- WO2005084684A1 WO2005084684A1 PCT/CH2004/000131 CH2004000131W WO2005084684A1 WO 2005084684 A1 WO2005084684 A1 WO 2005084684A1 CH 2004000131 W CH2004000131 W CH 2004000131W WO 2005084684 A1 WO2005084684 A1 WO 2005084684A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- substances
- group
- cartilage
- solvent
- mixture
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
Definitions
- the invention relates to the use of a mixture for the production of an agent for the treatment of defective or degenerated cartilage in vivo according to the preamble of claim 1 and to the use of this mixture in the production of natural cartilage replacement in vitro according to claim 9.
- scaffolds made of polymer materials which are colonized with chondrocytes. They serve as a carrier material for the chondrocytes and are available as resorbable or non-resorbable material.
- scaffolds made from natural and synthetically resorbable carrier materials have been developed and tested. It was found that these in vitro grown cartilage-like constructions do not achieve the biochemical or biomechanical properties of in vivo tissues.
- osteochondral grafts are inserted into the cartilage defect and anchored in the subchondral bone.
- organ donor and host are one and the same person
- in the second case they are different, but from the same species.
- cylindrical cartilage pins are removed from the donor region together with the subchondral bone and anchored in the defect zone using a pre-made press fit.
- a pin or several pins are used to close the damaged surface.
- Chondrocyte transplantation removes chondrocytes from regions of the knee that are less stressed.
- the removed cells are grown in nutrient solution within 14 to 21 days. After culturing, the cells are injected into the region of the defect and covered with a piece of periosteum or perichondrium. After 2 years, a biopsy can show that hyaline cartilage has formed. In one study, the clinical outcome of 14 out of 16 patients was described as good to very good. A study in Sweden with 400 patients showed comparable results.
- articular cartilage consists on the one hand in the absorption and distribution of forces which occur when the joint is loaded and on the other hand in the provision of a lubricating surface which prevents the abrasion and degradation of the joint.
- the first function is ensured by a unique composition and structure of the extracellular matrix, the second Function, however, depends on a functional cartilage-synovial interface. These functions are disrupted, particularly in patients with degeneratively altered or otherwise affected cartilage surfaces.
- the invention seeks to remedy this.
- the invention is based, on the one hand, to provide an agent for treating defective or degenerated cartilage in vivo and, on the other hand, to provide an improved production of natural cartilage replacement in vitro, in particular for cartilage defects in the joint area.
- the invention achieves the stated object with a means which has the features of claim 1 and a use of this means which has the features of claim 9.
- the lubricin is the lubricating glycoprotein-1 (LGP-1), which is produced from the same gene as the megakaryocyte stimulation factor (MSF) by alternative splicing.
- Lubricin has a molecular weight of approximately 230 kDa (purified form in human synovial fluid) and is highly glycosylated.
- Proteoglycan 4 is the name of the surface zone protein (SZP), which is obtained from the MSF gene by alternative splicing. It has a molecular weight of approximately 340 kDa (from human articular cartilage) and carries several oligosaccharide residues and glycosaminoglycan chains. It has been shown that the use of SZP and similar substances (group A) in the mixture according to the invention not only shows a strong lubricating effect, but also acts as a chondroprotective molecule, which provides protection for the deep-lying cartilage cells.
- SZP surface zone protein
- SZP was originally isolated and purified from culture fluids from explants that originated from the surface zone of bovine cartilage. SZP can be synthesized by chondrocytes in the surface zone, but not from the middle and lower zones.
- the hyaluronic acid consists of glucuronic acid and acetylglucosamine, which build up the disaccharide hyalubironic acid. Due to its filiform, unbranched molecular structure, hyaluronic acid forms highly viscous solutions. Although hyaluronic acid has no direct lubricating properties, it is important for the theological behavior of the synovial fluid by setting a suitable viscosity level, which prevents the synovial fluid from flowing out during the stress phase of the joint.
- the improved lubrication can be expected to reduce cartilage degeneration and reduce abrasion of the artificial joint. This increases the lifespan of the implant and revision can be prevented or delayed.
- the phospholipids used are surface-active in nature.
- the resulting interface lubrication causes less severe cartilage damage in the further course.
- the hyaluronic acid to be used advantageously has a molecular weight of at least 1x10 6 Da.
- the weight ratio A / B between the substances of group A [Lubricin, Proteoglycan 4 (PRG4) and phospholipids (SAPL)] and of group B [hyaluronic acid, glycosaminoglycan and derivatives of these substances] is advantageously in the range from 0.05 and 0.40 , preferably in the range of 0.08 and 0.25.
- the solvent to be used is advantageously a Ringer's solution, preferably a physiological saline solution.
- the concentration of the group A substances in the solvent is preferably in the range from 0.02 to 0.05% by weight and that of the group B substances in the range from 0.2 to 0.4% by weight.
- B) hyaluronic acid, glycosaminoglycan and derivatives of these substances; dissolved in a solvent, can also be used to make natural cartilage replacements in vitro.
- Such a mixture can also be used for a method for producing a cartilage replacement material for cartilage defects in the joint area, wherein an open-pore, elastic cell carrier body is populated with chondrocytes in its pores and this mixture is dissolved in a physiologically acceptable solvent and brought into contact with the chondrocytes.
- the solvent is preferably moved over the cell carrier body in a laminar flow.
- an axial and a rotary force are simultaneously applied to the cell carrier body by means of a joint ball-like device.
- the rotation of the joint ball-like device is preferably carried out about two axes orthogonal to one another.
- a patient was injected with a solution containing 6 mg lubricin and 45 mg hyaluronic acid into the closed joint capsule.
- the solvent consisted of 25 ml of physiological saline (Ringer's solution), to which 5% human serum from the same patient was added.
- the endoscopic examination after physiotherapeutic therapy of the joint showed an improved healing of the cut surfaces between the host and the donor tissue.
- the patient was free of pain and was able to carry out his usual activities.
- Chondrocytes were isolated from the weightless region of the defect surface of the knee joint and implanted directly into an open pore, elastic cell support body.
- the cell carrier body consisted of a cylindrical, porous, biodegradable polyurethane frame with an identical size of 8 mm x 4 mm to the defect. The cell density was 25-30 x 10 6 .
- the cell carrier body which is populated with chondrocytes in its pores, was modified in “Dulbecco's Eagles medium "(DMEM), which 5% human serum (the same
- L-alanine (0.89 mg / L), L-asparagine (1.32 mg / L), L-aspartic acid (1.33 mg / L), L-
- the mechanical load on the cell carrier body was carried out in a so-called
- Bioreactor system in which the cell carrier body was exposed to the action of a sphere, so that both rotational and axial forces on the
- Cell carrier body could be applied. A mechanical stress of this type was applied to the cell carrier body twice a day. In a
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP04717539A EP1740190A1 (de) | 2004-03-05 | 2004-03-05 | Verwendung eines gemisches für die herstellung eines mittels zur behandlung von defektem oder degeneriertem knorpel in vivo und bei der herstellung von natürlichem knorpelersatz in vitro |
US10/591,833 US20070275032A1 (en) | 2004-03-05 | 2004-03-05 | Use Of A Mixture For The Production Of An Agent For Treating Defective Or Degenerated Cartilage In The Production Of Natural Cartilage Replacement In Vitro |
PCT/CH2004/000131 WO2005084684A1 (de) | 2004-03-05 | 2004-03-05 | Verwendung eines gemisches für die herstellung eines mittels zur behandlung von defektem oder degeneriertem knorpel in vivo und bei der herstellung von natürlichem knorpelerszy in vitro |
CA002558497A CA2558497A1 (en) | 2004-03-05 | 2004-03-05 | Use of a mixture for the production of an agent for treating defective or degenerated cartilage in the production of natural cartilage replacement in vitro |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CH2004/000131 WO2005084684A1 (de) | 2004-03-05 | 2004-03-05 | Verwendung eines gemisches für die herstellung eines mittels zur behandlung von defektem oder degeneriertem knorpel in vivo und bei der herstellung von natürlichem knorpelerszy in vitro |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005084684A1 true WO2005084684A1 (de) | 2005-09-15 |
Family
ID=34916964
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CH2004/000131 WO2005084684A1 (de) | 2004-03-05 | 2004-03-05 | Verwendung eines gemisches für die herstellung eines mittels zur behandlung von defektem oder degeneriertem knorpel in vivo und bei der herstellung von natürlichem knorpelerszy in vitro |
Country Status (4)
Country | Link |
---|---|
US (1) | US20070275032A1 (de) |
EP (1) | EP1740190A1 (de) |
CA (1) | CA2558497A1 (de) |
WO (1) | WO2005084684A1 (de) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006012492A2 (en) * | 2004-07-23 | 2006-02-02 | Mucosal Therapeutics Llc | Compositions and methods for viscosupplementation |
FR2922219A1 (fr) * | 2007-10-10 | 2009-04-17 | Maco Pharma Sa | Methode pour stimuler la proliferation de cellules differenciees appartenant au lignage chondrogenique |
US7618941B2 (en) | 1999-04-23 | 2009-11-17 | Rhode Island Hospital | Treating degenerative joint disorders with tribonectins |
WO2013068014A1 (en) * | 2011-11-08 | 2013-05-16 | Danmarks Tekniske Universitet | Pharmaceutical compositions comprising lubricants for preventing or reducing aseptic loosening in a subject |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE59903490D1 (de) | 1998-09-11 | 2003-01-02 | Schmidmaier Gerhard | Biologisch aktive implantate |
US8506944B2 (en) | 2008-05-07 | 2013-08-13 | The Regents Of The University Of California | Replenishment and enrichment of ocular surface lubrication |
PT2285364E (pt) * | 2008-05-07 | 2015-02-24 | Univ California | Reposição e enriquecimento terapêutico de lubrificação da superficie ocular |
US8980840B2 (en) | 2009-01-13 | 2015-03-17 | Schepens Eye Research Institute | Therapeutic modulation of vaginal epithelium boundary lubrication |
US9730865B2 (en) | 2009-05-22 | 2017-08-15 | Lubris, Llc | Application and uses of PRG4 and therapeutic modulation thereof |
WO2011005493A2 (en) * | 2009-06-22 | 2011-01-13 | Mayo Foundation For Medical Education And Research | Methods and materials for tissue repair |
EP2464375B1 (de) | 2009-08-13 | 2017-06-14 | Lubris LLC | Prg4-behandlung für interstitielle zystitis |
US11213566B2 (en) | 2010-01-19 | 2022-01-04 | Lubris Llc | Oral care compositions and methods |
US8617240B2 (en) | 2010-11-17 | 2013-12-31 | Charles D. Hightower | Moldable cushion for implants |
CN102552996A (zh) * | 2010-12-07 | 2012-07-11 | 宁小静 | 人体润滑剂 |
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WO2001068800A1 (en) * | 2000-03-11 | 2001-09-20 | The Trustees Of Columbia University In The City Of New York | Bioreactor for generating functional cartilaginous tissue |
WO2002062847A2 (en) * | 2000-12-29 | 2002-08-15 | Glaxo Group Limited | Superficial zone protein and methods of making and using same |
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2004
- 2004-03-05 US US10/591,833 patent/US20070275032A1/en not_active Abandoned
- 2004-03-05 CA CA002558497A patent/CA2558497A1/en not_active Abandoned
- 2004-03-05 EP EP04717539A patent/EP1740190A1/de not_active Withdrawn
- 2004-03-05 WO PCT/CH2004/000131 patent/WO2005084684A1/de not_active Application Discontinuation
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WO2002062847A2 (en) * | 2000-12-29 | 2002-08-15 | Glaxo Group Limited | Superficial zone protein and methods of making and using same |
JP2002348243A (ja) * | 2001-05-28 | 2002-12-04 | Denki Kagaku Kogyo Kk | 関節症治療用注入剤 |
WO2003007784A2 (en) * | 2001-07-16 | 2003-01-30 | Depuy Products, Inc. | Meniscus regeneration device and method |
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GRAD SIBYLLE ET AL: "Chondrocyte SZP/lubricin expression is mediated by applied surface motion.", TISSUE ENGINEERING, vol. 9, no. 4, August 2003 (2003-08-01), & SECOND MEETING OF THE EUROPEAN TISSUE ENGINEERING SOCIETY; GENOA, ITALY; SEPTEMBER 03-06, 2003, pages 797 - 798, XP002301693, ISSN: 1076-3279 * |
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KAWANO TSUTOMU ET AL: "Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis.", ARTHRITIS AND RHEUMATISM. JUL 2003, vol. 48, no. 7, July 2003 (2003-07-01), pages 1923 - 1929, XP002301692, ISSN: 0004-3591 * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7618941B2 (en) | 1999-04-23 | 2009-11-17 | Rhode Island Hospital | Treating degenerative joint disorders with tribonectins |
US8026346B2 (en) * | 1999-04-23 | 2011-09-27 | Rhode Island Hospital | Tribonectins |
US8680057B2 (en) | 1999-04-23 | 2014-03-25 | Rhode Island Hospital | Tribonectins |
WO2006012492A2 (en) * | 2004-07-23 | 2006-02-02 | Mucosal Therapeutics Llc | Compositions and methods for viscosupplementation |
WO2006012492A3 (en) * | 2004-07-23 | 2006-09-14 | Mucosal Therapeutics Llc | Compositions and methods for viscosupplementation |
FR2922219A1 (fr) * | 2007-10-10 | 2009-04-17 | Maco Pharma Sa | Methode pour stimuler la proliferation de cellules differenciees appartenant au lignage chondrogenique |
WO2009080914A2 (fr) * | 2007-10-10 | 2009-07-02 | Maco Pharma | Méthode pour stimuler la prolifération de cellules différenciées appartenant au lignage chondrogénique |
WO2009080914A3 (fr) * | 2007-10-10 | 2009-12-23 | Maco Pharma | Méthode pour stimuler la prolifération de cellules différenciées appartenant au lignage chondrogénique |
US8383406B2 (en) | 2007-10-10 | 2013-02-26 | Maco Parma | Method for stimulating the proliferation of differentiated cells belonging to the chondrogenic lineage |
WO2013068014A1 (en) * | 2011-11-08 | 2013-05-16 | Danmarks Tekniske Universitet | Pharmaceutical compositions comprising lubricants for preventing or reducing aseptic loosening in a subject |
Also Published As
Publication number | Publication date |
---|---|
CA2558497A1 (en) | 2005-09-15 |
EP1740190A1 (de) | 2007-01-10 |
US20070275032A1 (en) | 2007-11-29 |
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