JP2007502327A - 椎間板変性症の治療法 - Google Patents
椎間板変性症の治療法 Download PDFInfo
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- JP2007502327A JP2007502327A JP2006533113A JP2006533113A JP2007502327A JP 2007502327 A JP2007502327 A JP 2007502327A JP 2006533113 A JP2006533113 A JP 2006533113A JP 2006533113 A JP2006533113 A JP 2006533113A JP 2007502327 A JP2007502327 A JP 2007502327A
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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
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- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47009803P | 2003-05-13 | 2003-05-13 | |
| US10/456,948 US7344716B2 (en) | 2003-05-13 | 2003-06-06 | Transdiscal administration of specific inhibitors of pro-inflammatory cytokines |
| US10/610,355 US7429378B2 (en) | 2003-05-13 | 2003-06-30 | Transdiscal administration of high affinity anti-MMP inhibitors |
| US10/631,487 US20040229878A1 (en) | 2003-05-13 | 2003-07-31 | Transdiscal administration of specific inhibitors of P38 kinase |
| US10/640,412 US7553827B2 (en) | 2003-08-13 | 2003-08-13 | Transdiscal administration of cycline compounds |
| PCT/US2004/015285 WO2005000283A2 (en) | 2003-05-13 | 2004-05-13 | A method of treating degenerative disc disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007502327A true JP2007502327A (ja) | 2007-02-08 |
| JP2007502327A5 JP2007502327A5 (enExample) | 2007-06-28 |
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Family Applications (1)
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|---|---|---|---|
| JP2006533113A Pending JP2007502327A (ja) | 2003-05-13 | 2004-05-13 | 椎間板変性症の治療法 |
Country Status (8)
| Country | Link |
|---|---|
| EP (2) | EP2286804A1 (enExample) |
| JP (1) | JP2007502327A (enExample) |
| KR (1) | KR20060014048A (enExample) |
| AU (1) | AU2004251042A1 (enExample) |
| BR (1) | BRPI0410331A (enExample) |
| CA (1) | CA2525928A1 (enExample) |
| MX (1) | MXPA05012275A (enExample) |
| WO (1) | WO2005000283A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019513823A (ja) * | 2016-04-04 | 2019-05-30 | ゲーウー・ベンチャーズ・アーベー | 椎間板ヘルニアの治療のための方法及び組成物 |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7744651B2 (en) | 2002-09-18 | 2010-06-29 | Warsaw Orthopedic, Inc | Compositions and methods for treating intervertebral discs with collagen-based materials |
| US20040054414A1 (en) | 2002-09-18 | 2004-03-18 | Trieu Hai H. | Collagen-based materials and methods for augmenting intervertebral discs |
| JP2006515765A (ja) | 2002-11-15 | 2006-06-08 | エスディージーアイ・ホールディングス・インコーポレーテッド | 滑膜性関節を治療するためのコラーゲンベース材料および方法 |
| US7344716B2 (en) | 2003-05-13 | 2008-03-18 | Depuy Spine, Inc. | Transdiscal administration of specific inhibitors of pro-inflammatory cytokines |
| US7553827B2 (en) | 2003-08-13 | 2009-06-30 | Depuy Spine, Inc. | Transdiscal administration of cycline compounds |
| US8273347B2 (en) | 2003-05-13 | 2012-09-25 | Depuy Spine, Inc. | Autologous treatment of degenerated disc with cells |
| US7429378B2 (en) | 2003-05-13 | 2008-09-30 | Depuy Spine, Inc. | Transdiscal administration of high affinity anti-MMP inhibitors |
| US8361467B2 (en) | 2003-07-30 | 2013-01-29 | Depuy Spine, Inc. | Trans-capsular administration of high specificity cytokine inhibitors into orthopedic joints |
| US20050100538A1 (en) * | 2003-07-31 | 2005-05-12 | Attawia Mohamed | Intradiscal injection of anti-oxidants |
| US8895540B2 (en) | 2003-11-26 | 2014-11-25 | DePuy Synthes Products, LLC | Local intraosseous administration of bone forming agents and anti-resorptive agents, and devices therefor |
| US20070043118A1 (en) * | 2005-08-16 | 2007-02-22 | Discogen, Llc | Method of treating a subject suffering from degenerative disc disease using a nitric oxide synthase inhibitor |
| CA2623648C (en) | 2005-09-21 | 2018-05-22 | The Regents Of The University Of California | Systems, compositions, and methods for local imaging and treatment of pain |
| WO2007098099A2 (en) * | 2006-02-16 | 2007-08-30 | Discogen, Llc | Method of treating a subject suffering from degenerative disc disease using a matrix metalloprotease inhibitor |
| US8118779B2 (en) | 2006-06-30 | 2012-02-21 | Warsaw Orthopedic, Inc. | Collagen delivery device |
| US8399619B2 (en) | 2006-06-30 | 2013-03-19 | Warsaw Orthopedic, Inc. | Injectable collagen material |
| US7928111B2 (en) * | 2007-06-08 | 2011-04-19 | Senomyx, Inc. | Compounds including substituted thienopyrimidinone derivatives as ligands for modulating chemosensory receptors |
| US8986696B2 (en) | 2007-12-21 | 2015-03-24 | Depuy Mitek, Inc. | Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints |
| EP3085699B1 (en) | 2008-07-31 | 2022-03-02 | Firmenich Incorporated | Processes for making sweet taste enhancers |
| WO2019060869A1 (en) * | 2017-09-25 | 2019-03-28 | Discitisdx, Inc. | METHODS FOR TREATING DEGENERATIVE DISC DISEASE AND CHRONIC LOMBALGIA |
| US11911504B2 (en) * | 2018-02-02 | 2024-02-27 | Galen Therapeutics Llc | Apparatus and method for protecting neurons and reducing inflammation and scarring |
| WO2020033420A1 (en) | 2018-08-07 | 2020-02-13 | Firmenich Incorporated | 5-substituted 4-amino-1h-benzo[c][1,2,6]thiadiazine 2,2-dioxides and formulations and uses thereof |
| CN110613837A (zh) * | 2019-10-24 | 2019-12-27 | 内蒙古医科大学第二附属医院 | TGF-β在制备预防或治疗腰椎间盘突出药物中的应用 |
| CN117106900A (zh) * | 2023-09-27 | 2023-11-24 | 上海长征医院 | 一种适用于椎间盘退变预防和诊疗的分子标志物ace2及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010006948A1 (en) * | 1998-11-25 | 2001-07-05 | James D. Kang | Gene transfer to intervertebral disc cells |
| JP2002525331A (ja) * | 1998-09-25 | 2002-08-13 | エイプラス サイエンス インベスト アーベー | 神経根障害を処置するための所定薬剤の使用 |
| JP2002537356A (ja) * | 1999-02-24 | 2002-11-05 | トビニク、エドワード、エル． | 神経障害治療のための腫瘍壊死因子拮抗薬 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870163A (en) | 1985-08-29 | 1989-09-26 | New York Blood Center, Inc. | Preparation of pure human tumor necrosis factor and hybridomas producing monoclonal antibodies to human tumor necrosis factor |
| DE3631229A1 (de) | 1986-09-13 | 1988-03-24 | Basf Ag | Monoklonale antikoerper gegen humanen tumornekrosefaktor (tnf) und deren verwendung |
| EP0288088B1 (en) | 1987-04-24 | 1994-03-09 | Teijin Limited | Detection of tumor necrosis factor; monoclonal antibody and kit |
| US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| EP0486526B2 (en) | 1989-08-07 | 2001-03-07 | Peptech Limited | Tumour necrosis factor binding ligands |
| GB9022648D0 (en) | 1990-10-18 | 1990-11-28 | Charing Cross Sunley Research | Polypeptide and its use |
| US6277969B1 (en) | 1991-03-18 | 2001-08-21 | New York University | Anti-TNF antibodies and peptides of human tumor necrosis factor |
| US5270300A (en) | 1991-09-06 | 1993-12-14 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone |
| US5447851B1 (en) | 1992-04-02 | 1999-07-06 | Univ Texas System Board Of | Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells |
| DE69720190T2 (de) | 1996-02-02 | 2003-12-11 | Alza Corp | Implantierbares system mit verzögerter freisetzung von leuprolid |
| US7115557B2 (en) | 1998-09-25 | 2006-10-03 | Sciaticon Ab | Use of certain drugs for treating nerve root injury |
| US6537549B2 (en) * | 1999-02-24 | 2003-03-25 | Edward L. Tobinick | Cytokine antagonists for the treatment of localized disorders |
| US6982089B2 (en) | 1999-02-24 | 2006-01-03 | Tact Ip, Llc | Cytokine antagonists for neurological and neuropsychiatric disorders |
| US6419944B2 (en) | 1999-02-24 | 2002-07-16 | Edward L. Tobinick | Cytokine antagonists for the treatment of localized disorders |
| US6428576B1 (en) * | 1999-04-16 | 2002-08-06 | Endospine, Ltd. | System for repairing inter-vertebral discs |
| US6352557B1 (en) | 1999-08-13 | 2002-03-05 | Bret A. Ferree | Treating degenerative disc disease through transplantion of extracellular nucleus pulposus matrix and autograft nucleus pulposus cells |
| US6541477B2 (en) | 1999-08-27 | 2003-04-01 | Scios, Inc. | Inhibitors of p38-a kinase |
| US20020032155A1 (en) * | 2000-06-30 | 2002-03-14 | Ferree Bret A. | Method of treating disc herniation and disc degeneration with concentrated growth and differentiation factors |
| US20020026244A1 (en) | 2000-08-30 | 2002-02-28 | Trieu Hai H. | Intervertebral disc nucleus implants and methods |
| NZ526624A (en) | 2000-12-22 | 2005-07-29 | Ortho Mcneil Pharm Inc | Substituted triazole diamine derivatives as kinase inhibitors |
| SE0102067D0 (sv) | 2001-06-11 | 2001-06-11 | A & Science Invest Ab | Prevention of neovascularization of intervertebral discs and/or of tissues with local inflammation |
| JP2004535434A (ja) | 2001-06-25 | 2004-11-25 | デピユイ | 関節炎にかかった関節の処置のためのグリコサミノグリカン類のリポソームカプセル化 |
-
2004
- 2004-05-13 JP JP2006533113A patent/JP2007502327A/ja active Pending
- 2004-05-13 EP EP20100183305 patent/EP2286804A1/en not_active Withdrawn
- 2004-05-13 BR BRPI0410331-9A patent/BRPI0410331A/pt not_active Application Discontinuation
- 2004-05-13 EP EP04776014A patent/EP1631266B1/en not_active Expired - Lifetime
- 2004-05-13 WO PCT/US2004/015285 patent/WO2005000283A2/en not_active Ceased
- 2004-05-13 CA CA002525928A patent/CA2525928A1/en not_active Abandoned
- 2004-05-13 KR KR1020057021572A patent/KR20060014048A/ko not_active Withdrawn
- 2004-05-13 AU AU2004251042A patent/AU2004251042A1/en not_active Abandoned
- 2004-05-13 MX MXPA05012275A patent/MXPA05012275A/es not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002525331A (ja) * | 1998-09-25 | 2002-08-13 | エイプラス サイエンス インベスト アーベー | 神経根障害を処置するための所定薬剤の使用 |
| US20010006948A1 (en) * | 1998-11-25 | 2001-07-05 | James D. Kang | Gene transfer to intervertebral disc cells |
| JP2002537356A (ja) * | 1999-02-24 | 2002-11-05 | トビニク、エドワード、エル． | 神経障害治療のための腫瘍壊死因子拮抗薬 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019513823A (ja) * | 2016-04-04 | 2019-05-30 | ゲーウー・ベンチャーズ・アーベー | 椎間板ヘルニアの治療のための方法及び組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2525928A1 (en) | 2005-01-06 |
| EP1631266B1 (en) | 2011-03-16 |
| EP1631266A2 (en) | 2006-03-08 |
| BRPI0410331A (pt) | 2006-05-30 |
| WO2005000283A3 (en) | 2005-08-11 |
| EP2286804A1 (en) | 2011-02-23 |
| WO2005000283A2 (en) | 2005-01-06 |
| AU2004251042A1 (en) | 2005-01-06 |
| MXPA05012275A (es) | 2006-02-10 |
| AU2004251042A2 (en) | 2005-01-06 |
| KR20060014048A (ko) | 2006-02-14 |
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