JP2002537022A - 軟骨病変を再生して修復する装置及び方法 - Google Patents
軟骨病変を再生して修復する装置及び方法Info
- Publication number
- JP2002537022A JP2002537022A JP2000599344A JP2000599344A JP2002537022A JP 2002537022 A JP2002537022 A JP 2002537022A JP 2000599344 A JP2000599344 A JP 2000599344A JP 2000599344 A JP2000599344 A JP 2000599344A JP 2002537022 A JP2002537022 A JP 2002537022A
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
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- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
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- A—HUMAN NECESSITIES
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- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00365—Proteins; Polypeptides; Degradation products thereof
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Prostheses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/250,370 US6514514B1 (en) | 1997-08-14 | 1999-02-16 | Device and method for regeneration and repair of cartilage lesions |
| US09/250,370 | 1999-02-16 | ||
| PCT/US2000/003972 WO2000048550A2 (en) | 1999-02-16 | 2000-02-16 | Device and method for regeneration and repair of cartilage lesions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002537022A true JP2002537022A (ja) | 2002-11-05 |
| JP2002537022A5 JP2002537022A5 (enExample) | 2007-04-05 |
Family
ID=22947449
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000599344A Pending JP2002537022A (ja) | 1999-02-16 | 2000-02-16 | 軟骨病変を再生して修復する装置及び方法 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1161201A4 (enExample) |
| JP (1) | JP2002537022A (enExample) |
| AU (1) | AU3699900A (enExample) |
| CA (1) | CA2362600A1 (enExample) |
| WO (1) | WO2000048550A2 (enExample) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005305162A (ja) * | 2004-04-20 | 2005-11-04 | Depuy Mitek Inc | 半月板修復スカフォールド |
| JP2006519782A (ja) * | 2003-01-30 | 2006-08-31 | ザ ユニバーシティ オブ チューリッヒ | 医薬組成物 |
| JP2007503852A (ja) * | 2003-08-20 | 2007-03-01 | ヒストジェニックス コーポレイション | 関節軟骨、骨、骨軟骨の欠損及び傷害を治療するための非細胞基質インプラント及びその使用方法 |
| JP2011041472A (ja) * | 2009-08-19 | 2011-03-03 | Tokai Univ | 細胞混合物からなる細胞移植治療用スフェロイド及びその作製方法 |
| JP4863868B2 (ja) * | 2003-03-28 | 2012-01-25 | バイオファーム・ゲゼルシャフト・ツア・バイオテクノロジシェン・エントヴィックルング・フォン・ファーマカ・ミット・ベシュレンクテル・ハフツング | 改良された骨誘導材料 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8545569B2 (en) | 2001-05-25 | 2013-10-01 | Conformis, Inc. | Patient selectable knee arthroplasty devices |
| US8556983B2 (en) | 2001-05-25 | 2013-10-15 | Conformis, Inc. | Patient-adapted and improved orthopedic implants, designs and related tools |
| US7468075B2 (en) | 2001-05-25 | 2008-12-23 | Conformis, Inc. | Methods and compositions for articular repair |
| US9603711B2 (en) | 2001-05-25 | 2017-03-28 | Conformis, Inc. | Patient-adapted and improved articular implants, designs and related guide tools |
| US8480754B2 (en) | 2001-05-25 | 2013-07-09 | Conformis, Inc. | Patient-adapted and improved articular implants, designs and related guide tools |
| US8083745B2 (en) | 2001-05-25 | 2011-12-27 | Conformis, Inc. | Surgical tools for arthroplasty |
| US8882847B2 (en) | 2001-05-25 | 2014-11-11 | Conformis, Inc. | Patient selectable knee joint arthroplasty devices |
| US7618451B2 (en) | 2001-05-25 | 2009-11-17 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools facilitating increased accuracy, speed and simplicity in performing total and partial joint arthroplasty |
| US7534263B2 (en) | 2001-05-25 | 2009-05-19 | Conformis, Inc. | Surgical tools facilitating increased accuracy, speed and simplicity in performing joint arthroplasty |
| DE69714035T2 (de) | 1997-08-14 | 2003-03-06 | Sulzer Innotec Ag, Winterthur | Zusammensetzung und Vorrichtung zur Reparatur von Knorpelgewebe in vivo bestehend aus Nanokapseln mit osteoinduktiven und/oder chondroinduktiven Faktoren |
| US7239908B1 (en) | 1998-09-14 | 2007-07-03 | The Board Of Trustees Of The Leland Stanford Junior University | Assessing the condition of a joint and devising treatment |
| ATE439806T1 (de) | 1998-09-14 | 2009-09-15 | Univ Leland Stanford Junior | Zustandsbestimmung eines gelenks und schadenvorsorge |
| US7067144B2 (en) | 1998-10-20 | 2006-06-27 | Omeros Corporation | Compositions and methods for systemic inhibition of cartilage degradation |
| US6458763B1 (en) | 1999-09-17 | 2002-10-01 | Depuy Orthopeadics | Bone sialoprotein-based compositions for enhancing connective tissue repair |
| WO2001036000A1 (en) | 1999-11-15 | 2001-05-25 | Bio Syntech Canada, Inc. | Temperature-controlled and ph-dependant self-gelling biopolymeric aqueous solution |
| EP1704866A3 (en) * | 2000-03-09 | 2006-10-04 | Zimmer Orthobiologics, Inc. | TGFbeta superfamily proteins for biological anchoring of connective tissue to bone |
| US6723335B1 (en) | 2000-04-07 | 2004-04-20 | Jeffrey William Moehlenbruck | Methods and compositions for treating intervertebral disc degeneration |
| US20020082220A1 (en) | 2000-06-29 | 2002-06-27 | Hoemann Caroline D. | Composition and method for the repair and regeneration of cartilage and other tissues |
| US6638312B2 (en) | 2000-08-04 | 2003-10-28 | Depuy Orthopaedics, Inc. | Reinforced small intestinal submucosa (SIS) |
| AU2001290887B2 (en) | 2000-09-14 | 2006-06-08 | The Board Of Trustees Of The Leland Stanford Junior University | Assessing condition of a joint and cartilage loss |
| EP1377661A4 (en) * | 2001-01-30 | 2009-10-21 | Orthogene Inc | COMPOSITIONS AND METHODS FOR TREATING OR REPAIRING DEFECTS OR LESIONS IN JOINT CARTILAGE USING SYNOVIAL LIQUID DERIVED TISSUE OR CELLS |
| CA2447694A1 (en) | 2001-05-25 | 2002-12-05 | Imaging Therapeutics, Inc. | Methods and compositions for articular resurfacing |
| US8439926B2 (en) | 2001-05-25 | 2013-05-14 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools |
| AU2002354913B2 (en) | 2001-07-16 | 2008-07-17 | Depuy Products, Inc. | Unitary surgical device and method |
| US7201917B2 (en) | 2001-07-16 | 2007-04-10 | Depuy Products, Inc. | Porous delivery scaffold and method |
| ATE499908T1 (de) | 2001-07-16 | 2011-03-15 | Depuy Products Inc | Gerät zur reparatur von knorpelmaterial |
| US7232802B2 (en) | 2001-12-21 | 2007-06-19 | Zimmer Orthobiologics, Inc. | Compositions and methods for promoting myocardial and peripheral angiogenesis |
| WO2004043305A1 (en) | 2002-11-07 | 2004-05-27 | Conformis, Inc. | Methods for determing meniscal size and shape and for devising treatment |
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| GB0421298D0 (en) | 2004-09-24 | 2004-10-27 | Univ Bristol | Cellular bandage |
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| US8623026B2 (en) | 2006-02-06 | 2014-01-07 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools incorporating anatomical relief |
| CN105030297A (zh) | 2006-02-06 | 2015-11-11 | 康复米斯公司 | 患者可选择的关节成形术装置和手术器具 |
| US9592125B2 (en) | 2006-12-22 | 2017-03-14 | Laboratoire Medidom S.A. | In situ system for intra-articular chondral and osseous tissue repair |
| EP2591756A1 (en) | 2007-02-14 | 2013-05-15 | Conformis, Inc. | Implant device and method for manufacture |
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| EP2405865B1 (en) | 2009-02-24 | 2019-04-17 | ConforMIS, Inc. | Automated systems for manufacturing patient-specific orthopedic implants and instrumentation |
| US8808303B2 (en) | 2009-02-24 | 2014-08-19 | Microport Orthopedics Holdings Inc. | Orthopedic surgical guide |
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| WO2012112694A2 (en) | 2011-02-15 | 2012-08-23 | Conformis, Inc. | Medeling, analyzing and using anatomical data for patient-adapted implants. designs, tools and surgical procedures |
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| JP2022531871A (ja) | 2019-05-29 | 2022-07-12 | ライト メディカル テクノロジー インコーポレイテッド | 置換足関節の脛骨インプラント部品を受容するための脛骨の準備 |
| WO2021146015A1 (en) | 2020-01-17 | 2021-07-22 | Wright Medical Technology, Inc. | Guidance tools, systems, and methods |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681353A (en) * | 1987-07-20 | 1997-10-28 | Regen Biologics, Inc. | Meniscal augmentation device |
| JP3356775B2 (ja) * | 1990-11-30 | 2002-12-16 | セルトリックス ファーマシューティカルズ, インコーポレイテッド | TGF―βとの共同的組合せによる骨修復のための骨形成タンパク質の使用 |
| US5206023A (en) * | 1991-01-31 | 1993-04-27 | Robert F. Shaw | Method and compositions for the treatment and repair of defects or lesions in cartilage |
| US5563124A (en) * | 1991-04-22 | 1996-10-08 | Intermedics Orthopedics/ Denver, Inc. | Osteogenic product and process |
| DE69714035T2 (de) * | 1997-08-14 | 2003-03-06 | Sulzer Innotec Ag, Winterthur | Zusammensetzung und Vorrichtung zur Reparatur von Knorpelgewebe in vivo bestehend aus Nanokapseln mit osteoinduktiven und/oder chondroinduktiven Faktoren |
-
2000
- 2000-02-16 JP JP2000599344A patent/JP2002537022A/ja active Pending
- 2000-02-16 EP EP00915782A patent/EP1161201A4/en not_active Withdrawn
- 2000-02-16 AU AU36999/00A patent/AU3699900A/en not_active Abandoned
- 2000-02-16 WO PCT/US2000/003972 patent/WO2000048550A2/en not_active Ceased
- 2000-02-16 CA CA002362600A patent/CA2362600A1/en not_active Abandoned
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006519782A (ja) * | 2003-01-30 | 2006-08-31 | ザ ユニバーシティ オブ チューリッヒ | 医薬組成物 |
| JP4863868B2 (ja) * | 2003-03-28 | 2012-01-25 | バイオファーム・ゲゼルシャフト・ツア・バイオテクノロジシェン・エントヴィックルング・フォン・ファーマカ・ミット・ベシュレンクテル・ハフツング | 改良された骨誘導材料 |
| JP2007503852A (ja) * | 2003-08-20 | 2007-03-01 | ヒストジェニックス コーポレイション | 関節軟骨、骨、骨軟骨の欠損及び傷害を治療するための非細胞基質インプラント及びその使用方法 |
| JP2005305162A (ja) * | 2004-04-20 | 2005-11-04 | Depuy Mitek Inc | 半月板修復スカフォールド |
| JP2011041472A (ja) * | 2009-08-19 | 2011-03-03 | Tokai Univ | 細胞混合物からなる細胞移植治療用スフェロイド及びその作製方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000048550A2 (en) | 2000-08-24 |
| WO2000048550A3 (en) | 2000-12-14 |
| EP1161201A4 (en) | 2006-07-19 |
| EP1161201A2 (en) | 2001-12-12 |
| AU3699900A (en) | 2000-09-04 |
| CA2362600A1 (en) | 2000-08-24 |
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