EP1740190A1 - Utilisation d'un melange pour produire un agent servant a traiter un cartilage defectueux ou degenere in vivo et pour produire un substitut de cartilage naturel in vitro - Google Patents
Utilisation d'un melange pour produire un agent servant a traiter un cartilage defectueux ou degenere in vivo et pour produire un substitut de cartilage naturel in vitroInfo
- Publication number
- EP1740190A1 EP1740190A1 EP04717539A EP04717539A EP1740190A1 EP 1740190 A1 EP1740190 A1 EP 1740190A1 EP 04717539 A EP04717539 A EP 04717539A EP 04717539 A EP04717539 A EP 04717539A EP 1740190 A1 EP1740190 A1 EP 1740190A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- substances
- group
- cartilage
- solvent
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 210000000845 cartilage Anatomy 0.000 title claims abstract description 37
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 12
- 238000000338 in vitro Methods 0.000 title claims abstract description 8
- 230000002950 deficient Effects 0.000 title claims abstract description 7
- 102100028965 Proteoglycan 4 Human genes 0.000 claims abstract description 26
- 239000000126 substance Substances 0.000 claims abstract description 24
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 15
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 14
- 108010009030 lubricin Proteins 0.000 claims abstract description 14
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 13
- 101710127913 Proteoglycan 4 Proteins 0.000 claims abstract description 12
- 229920002683 Glycosaminoglycan Polymers 0.000 claims abstract description 7
- 238000001727 in vivo Methods 0.000 claims abstract description 6
- 101000991410 Homo sapiens Nucleolar and spindle-associated protein 1 Proteins 0.000 claims abstract description 5
- 101001095380 Homo sapiens Serine/threonine-protein phosphatase 6 regulatory subunit 3 Proteins 0.000 claims abstract description 5
- 102100030991 Nucleolar and spindle-associated protein 1 Human genes 0.000 claims abstract description 5
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 4
- 210000004027 cell Anatomy 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 15
- 230000007547 defect Effects 0.000 claims description 13
- 210000001612 chondrocyte Anatomy 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 239000002504 physiological saline solution Substances 0.000 claims description 6
- 239000011148 porous material Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 3
- 238000005461 lubrication Methods 0.000 description 7
- 201000008482 osteoarthritis Diseases 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 5
- 230000035876 healing Effects 0.000 description 4
- 230000001050 lubricating effect Effects 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 210000001503 joint Anatomy 0.000 description 3
- 210000000629 knee joint Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 210000001179 synovial fluid Anatomy 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- 229930182821 L-proline Natural products 0.000 description 2
- 208000006735 Periostitis Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000005299 abrasion Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 210000001145 finger joint Anatomy 0.000 description 2
- 210000004394 hip joint Anatomy 0.000 description 2
- 210000003035 hyaline cartilage Anatomy 0.000 description 2
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 2
- 229940099552 hyaluronan Drugs 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 210000003460 periosteum Anatomy 0.000 description 2
- 229960002429 proline Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000005065 subchondral bone plate Anatomy 0.000 description 2
- 238000011477 surgical intervention Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 1
- 206010007710 Cartilage injury Diseases 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010060820 Joint injury Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- DUKURNFHYQXCJG-UHFFFAOYSA-N Lewis A pentasaccharide Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(NC(C)=O)C(OC2C(C(OC3C(OC(O)C(O)C3O)CO)OC(CO)C2O)O)OC1CO DUKURNFHYQXCJG-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 238000011882 arthroplasty Methods 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000003321 cartilage cell Anatomy 0.000 description 1
- 230000008355 cartilage degradation Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003011 chondroprotective effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 210000004276 hyalin Anatomy 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 210000000281 joint capsule Anatomy 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000010363 phase shift Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Rheumatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
L'invention concerne un mélange comprenant une ou plusieurs substances du groupe A) qui rassemble lubricine, protéoglycane 4 (PRG4) et phospholipide (SAPL), et une ou plusieurs substances du groupe B) qui rassemble acide hyaluronique, glycosaminoglycane et des dérivés de ces substances, en dissolution dans un solvant, et servant à produire un agent pour traiter un cartilage défectueux ou dégénéré in vivo. Le mélange selon l'invention peut également être utilisé pour produire un substitut de cartilage naturel in vitro.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CH2004/000131 WO2005084684A1 (fr) | 2004-03-05 | 2004-03-05 | Utilisation d'un melange pour produire un agent servant a traiter un cartilage defectueux ou degenere in vivo et pour produire un substitut de cartilage naturel in vitro |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1740190A1 true EP1740190A1 (fr) | 2007-01-10 |
Family
ID=34916964
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP04717539A Withdrawn EP1740190A1 (fr) | 2004-03-05 | 2004-03-05 | Utilisation d'un melange pour produire un agent servant a traiter un cartilage defectueux ou degenere in vivo et pour produire un substitut de cartilage naturel in vitro |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20070275032A1 (fr) |
| EP (1) | EP1740190A1 (fr) |
| CA (1) | CA2558497A1 (fr) |
| WO (1) | WO2005084684A1 (fr) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4854114B2 (ja) | 1998-09-11 | 2012-01-18 | シュミドマイヤー，ゲルハルド | 生物学的に活性なインプラント |
| US6743774B1 (en) | 1999-04-23 | 2004-06-01 | Rhode Island Hospital | Tribonectins |
| EP1778360A2 (fr) * | 2004-07-23 | 2007-05-02 | Mucosal Therapeutics LLC | Compositions et procedes de viscosupplementation |
| FR2922219B1 (fr) | 2007-10-10 | 2009-12-04 | Maco Pharma Sa | Methode pour stimuler la proliferation de cellules differenciees appartenant au lignage chondrogenique |
| US8506944B2 (en) * | 2008-05-07 | 2013-08-13 | The Regents Of The University Of California | Replenishment and enrichment of ocular surface lubrication |
| HUE024146T2 (en) * | 2008-05-07 | 2016-02-29 | Univ California | Medical filling and enrichment of eye surface lubrication |
| US8980840B2 (en) | 2009-01-13 | 2015-03-17 | Schepens Eye Research Institute | Therapeutic modulation of vaginal epithelium boundary lubrication |
| CA2762989C (fr) | 2009-05-22 | 2021-04-13 | Benjamin Sullivan | Prg4 pour traitement des troubles de lubrification des limites de la cavite buccale |
| WO2011005493A2 (fr) * | 2009-06-22 | 2011-01-13 | Mayo Foundation For Medical Education And Research | Procédés et matériels pour réparation de tissu |
| WO2011019963A2 (fr) * | 2009-08-13 | 2011-02-17 | Singularis, Inc. | Traitement de prg4 pour cystite interstitielle |
| WO2011091000A2 (fr) * | 2010-01-19 | 2011-07-28 | Singularis, Inc. | Compositions et procédés destinés à l'hygiène buccale |
| 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 |
| EP2776044A1 (fr) * | 2011-11-08 | 2014-09-17 | Danmarks Tekniske Universitet | Compositions pharmaceutiques comprenant des lubrifiants pour prévenir ou réduire le descellement aseptique chez un sujet |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5036056A (en) * | 1987-07-08 | 1991-07-30 | Martin Kludas | Methods for treating damaged corneal, uterine, or cartilage tissue |
| US5403592A (en) * | 1987-08-25 | 1995-04-04 | Macnaught Pty Limited | Lubricant composition for rheumatism |
| US5171273A (en) * | 1989-01-13 | 1992-12-15 | University Of Medicine And Dentistry Of New Jersey | Synthetic collagen orthopaedic structures such as grafts, tendons and other structures |
| JP3714683B2 (ja) * | 1992-07-30 | 2005-11-09 | 生化学工業株式会社 | 抗リウマチ剤 |
| US5515590A (en) * | 1994-07-19 | 1996-05-14 | University Of Kentucky Research Foundation | Method for reducing the generation of wear particulates from an implant |
| US5891558A (en) * | 1994-11-22 | 1999-04-06 | Tissue Engineering, Inc. | Biopolymer foams for use in tissue repair and reconstruction |
| AU3203599A (en) * | 1998-04-01 | 1999-10-18 | Parallax Medical, Inc. | Pressure applicator for hard tissue implant placement |
| WO2001068800A1 (fr) * | 2000-03-11 | 2001-09-20 | The Trustees Of Columbia University In The City Of New York | Bioreacteur destine a la production de tissu cartilagineux fonctionnel |
| WO2001087323A2 (fr) * | 2000-05-16 | 2001-11-22 | Genentech, Inc. | Procede de traitement des lesions du cartilage |
| EP1347993A2 (fr) * | 2000-12-29 | 2003-10-01 | Glaxo Group Limited | Proteine szp et procedes de production et d'utilisation de cette proteine |
| JP4990446B2 (ja) * | 2001-05-28 | 2012-08-01 | 電気化学工業株式会社 | 関節症治療用注入剤 |
| AU2002354911B2 (en) * | 2001-07-16 | 2007-08-30 | Depuy Products, Inc. | Meniscus regeneration device and method |
-
2004
- 2004-03-05 CA CA002558497A patent/CA2558497A1/fr not_active Abandoned
- 2004-03-05 WO PCT/CH2004/000131 patent/WO2005084684A1/fr not_active Ceased
- 2004-03-05 US US10/591,833 patent/US20070275032A1/en not_active Abandoned
- 2004-03-05 EP EP04717539A patent/EP1740190A1/fr not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2005084684A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2558497A1 (fr) | 2005-09-15 |
| WO2005084684A1 (fr) | 2005-09-15 |
| US20070275032A1 (en) | 2007-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69531779T2 (de) | Herstllung von autogenen körperersatzteilen | |
| DE69333556T2 (de) | Injizierbare keramische Zusammensetzungen sowie Verfahren für ihre Herstellung und Verwendung | |
| DE69021204T2 (de) | Meniskus-prothese. | |
| DE60020807T2 (de) | Verformbare Paste zum Füllen von Knochendefekten | |
| DE69927512T2 (de) | Verwendung von op-1 zur herstellung einer pharmazeutischen zusammensetzung zur reparatur von nicht-gelenksknorpeldefekten eines säugers | |
| DE69518042T2 (de) | Biomaterialszusammensetzung und verfahren zu seiner herstellung | |
| DE69434122T2 (de) | Osteogenisches produkt und verwendung | |
| DE69633197T2 (de) | Osteogene vorrichtungen und methode zur herstellung derselben | |
| DE69126971T2 (de) | Bandscheibenprothese | |
| DE69534038T2 (de) | Vorrichtung und verfahren zum in-vivo-züchten von verschiedenen gewebezellen | |
| DE60023754T2 (de) | Künstlicher kalciumphosphatknochen als osteokonduktives und biologisch abbauba res knochenersatzmaterial | |
| DE69835810T2 (de) | OSTEOGENE VORRICHTUNGEN UND VERFAHREN ZU IHRER VERWENDUNG ZUR FöRDERUNG DER KNOCHENHEILUNG | |
| EP0605799B1 (fr) | Endoprothèse creuse avec un remplissage favorisant la croissance osseuse | |
| EP0520237B1 (fr) | Matériau de prothèse osseuse contenant des facteurs de croissance de fibroblastes | |
| DE69621612T2 (de) | Gewebetransplantat aus der submucosa der harnblase | |
| KR940007920B1 (ko) | 온혈 동물에서 뼈 골절 및 골절술의 치료와 치유증진을 위한 방법 | |
| EP2272467B1 (fr) | Implant surélevé pour la reconstruction de défauts du ménisque ou de défauts partiels du ménisque | |
| EP1740190A1 (fr) | Utilisation d'un melange pour produire un agent servant a traiter un cartilage defectueux ou degenere in vivo et pour produire un substitut de cartilage naturel in vitro | |
| JP5739894B2 (ja) | 軟骨組織修復用組成物及びその製造方法 | |
| EP3733198B1 (fr) | Composition pour la régénération de cartilage fibreux ou de cartilage élastique humain | |
| DE112016001386B4 (de) | Kohlenstoffpartikel und Komposite derselben für die Regeneration von Skelettmuskelgewebe und Weichgewebe | |
| EP1732618A1 (fr) | Procede pour realiser un materiau d'implant osseux | |
| KR20120007513A (ko) | 연골 복구 | |
| DE102009032216B4 (de) | Spacer-Implantat zur Behandlung von menschlichen oder tierischen Gelenkknorpelschäden | |
| EP1846055B1 (fr) | Procede de production d'un revetement d'implant osteoinductif-antiseptique |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20060721 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): CH DE FR GB LI |
|
| DAX | Request for extension of the european patent (deleted) | ||
| RBV | Designated contracting states (corrected) |
Designated state(s): CH DE FR GB LI |
|
| 17Q | First examination report despatched |
Effective date: 20070529 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 20071009 |