OA11213A - Cox-2 selective carprofen for treating pain and inflammation in dogs - Google Patents
Cox-2 selective carprofen for treating pain and inflammation in dogs Download PDFInfo
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- OA11213A OA11213A OA9900242A OA9900242A OA11213A OA 11213 A OA11213 A OA 11213A OA 9900242 A OA9900242 A OA 9900242A OA 9900242 A OA9900242 A OA 9900242A OA 11213 A OA11213 A OA 11213A
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- cox
- carprofen
- inhibitors
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Classifications
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4563597P | 1997-05-05 | 1997-05-05 |
Publications (1)
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|---|---|
| OA11213A true OA11213A (en) | 2003-07-14 |
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|---|---|---|---|
| OA9900242A OA11213A (en) | 1997-05-05 | 1999-11-02 | Cox-2 selective carprofen for treating pain and inflammation in dogs |
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| EP (1) | EP0988034A1 (is) |
| JP (1) | JP2000513020A (is) |
| KR (2) | KR20040004406A (is) |
| CN (1) | CN1255059A (is) |
| AP (1) | AP9801234A0 (is) |
| AR (2) | AR011726A1 (is) |
| AU (1) | AU6932198A (is) |
| BG (1) | BG103852A (is) |
| BR (1) | BR9808720A (is) |
| CA (1) | CA2288759A1 (is) |
| DZ (1) | DZ2479A1 (is) |
| EA (1) | EA003696B1 (is) |
| GT (1) | GT199800063A (is) |
| HR (1) | HRP980244A2 (is) |
| HU (1) | HUP0001286A3 (is) |
| ID (1) | ID21311A (is) |
| IL (1) | IL132570A0 (is) |
| IS (1) | IS5220A (is) |
| MA (1) | MA26491A1 (is) |
| NO (1) | NO995389L (is) |
| NZ (1) | NZ500183A (is) |
| OA (1) | OA11213A (is) |
| PA (1) | PA8450601A1 (is) |
| PE (1) | PE72599A1 (is) |
| PL (1) | PL337003A1 (is) |
| SK (1) | SK148199A3 (is) |
| TN (1) | TNSN98059A1 (is) |
| TW (1) | TW590773B (is) |
| UY (1) | UY24989A1 (is) |
| WO (1) | WO1998050033A1 (is) |
| YU (1) | YU55899A (is) |
| ZA (1) | ZA983722B (is) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6245797B1 (en) | 1997-10-22 | 2001-06-12 | Merck & Co., Inc. | Combination therapy for reducing the risks associated with cardio-and-cerebrovascular disease |
| AU2003204888B2 (en) * | 1998-05-22 | 2005-07-28 | Pfizer Products Inc. | Treating or Preventing the Early Stages of Degeneration of Articular Cartilage or Subchondral Bone in Mammals Using Carprofen and Derivatives |
| US6506785B2 (en) | 1998-05-22 | 2003-01-14 | Pfizer, Inc. | Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in mammals using carprofen and derivatives |
| CA2347365A1 (en) * | 1998-10-23 | 2000-05-04 | Merck Frosst Canada & Co. | Combination product comprising an e-type prostaglandin ligand and a cox-2 selective inhibitor and methods of use |
| DE60023119T2 (de) * | 1999-03-10 | 2006-07-20 | G.D. Searle Llc | Zusammensetzungen zur verabreichung eines cyclooxygenase-2-hemmers an tiere |
| WO2001034204A1 (en) * | 1999-11-11 | 2001-05-17 | Eli Lilly And Company | Oncolytic combinations for the treatment of cancer |
| JP2004521856A (ja) * | 2000-05-15 | 2004-07-22 | メルク フロスト カナダ アンド カンパニー | Cox−2選択的阻害剤およびトロンボキサン阻害剤を用いる併用療法ならびにそのための組成物 |
| ATE511844T1 (de) | 2000-06-13 | 2011-06-15 | Wyeth Llc | Analgetische und entzündungshemmende zusammensetzungen enthaltend celecoxib und ibuprofen |
| DE10032132A1 (de) * | 2000-07-01 | 2002-01-17 | Lohmann Therapie Syst Lts | Dermales Therapeutisches System enthaltend nichtsteroidale Antiphlogistika mit selektiver COX-2-Hemmung |
| CA2422803A1 (en) | 2000-08-07 | 2002-02-14 | Vanderbilt University | Detection of cox-2 activity and anandamide metabolites |
| WO2003007875A2 (en) * | 2001-07-16 | 2003-01-30 | Hoegestaett Edward | Compounds with analgesic, antipyretic and/or anti-inflammatory activity |
| ATE342722T1 (de) | 2003-05-07 | 2006-11-15 | Osteologix As | Behandlung von knorpel/knochen-erkrankungen mit wasserlöslichen strontiumsalzen |
| CN1829510A (zh) * | 2003-07-31 | 2006-09-06 | 法马西亚和厄普乔恩公司 | 抗炎剂的可分散性制剂 |
| KR20080003429A (ko) * | 2005-05-20 | 2008-01-07 | 화이자 리미티드 | 비스테로이드 소염 약물 및 알파-델타-리간드의 상승작용적조합물 |
| WO2008122965A2 (en) | 2007-04-04 | 2008-10-16 | Sigmoid Pharma Limited | Pharmaceutical cyclosporin compositions |
| EP2061587A1 (en) | 2007-04-26 | 2009-05-27 | Sigmoid Pharma Limited | Manufacture of multiple minicapsules |
| ES2530049T3 (es) | 2009-05-18 | 2015-02-26 | Sigmoid Pharma Limited | Composición que comprende gotas de aceite |
| EP2464341B1 (en) | 2009-08-12 | 2022-07-06 | Sublimity Therapeutics Limited | Immunomodulatory compositions comprising a polymer matrix and an oil phase |
| GB201020032D0 (en) | 2010-11-25 | 2011-01-12 | Sigmoid Pharma Ltd | Composition |
| GB201212010D0 (en) | 2012-07-05 | 2012-08-22 | Sigmoid Pharma Ltd | Formulations |
| GB201319791D0 (en) | 2013-11-08 | 2013-12-25 | Sigmoid Pharma Ltd | Formulations |
| US12109218B2 (en) | 2014-12-09 | 2024-10-08 | Aratana Therapeutics, Inc. | Compositions of grapiprant and methods for using the same |
| WO2015134792A1 (en) | 2014-03-06 | 2015-09-11 | Aratana Therapeutics, Inc. | Compositions of grapiprant and methods for using the same |
| HUE053624T2 (hu) | 2014-11-07 | 2021-07-28 | Sublimity Therapeutics Ltd | Ciklosporint tartalmazó készítmények |
| MX2017009011A (es) * | 2015-01-09 | 2017-10-02 | Jaguar Animal Health | Metodos para tratar la diarrea en animales de compañia. |
| EP4125874A4 (en) * | 2020-03-25 | 2024-05-01 | SRI International | LIPOXYGENASE INHIBITORS |
| US11116737B1 (en) | 2020-04-10 | 2021-09-14 | University Of Georgia Research Foundation, Inc. | Methods of using probenecid for treatment of coronavirus infections |
| KR102404883B1 (ko) | 2020-11-30 | 2022-06-07 | (주)이노보테라퓨틱스 | 벤즈브로마론을 포함하는 켈로이드 또는 비대흉터 예방 또는 치료용 약학 조성물 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3896145A (en) * | 1972-07-24 | 1975-07-22 | Hoffmann La Roche | Carbazoles |
| CA1319886C (en) * | 1987-02-03 | 1993-07-06 | Alberto Ferro | Mixed micelle solutions |
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1998
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- 1998-05-01 YU YU55899A patent/YU55899A/sh unknown
- 1998-05-01 ID IDP980651A patent/ID21311A/id unknown
- 1998-05-01 CA CA002288759A patent/CA2288759A1/en not_active Abandoned
- 1998-05-01 AU AU69321/98A patent/AU6932198A/en not_active Abandoned
- 1998-05-01 EP EP98915041A patent/EP0988034A1/en not_active Withdrawn
- 1998-05-01 WO PCT/IB1998/000662 patent/WO1998050033A1/en not_active Ceased
- 1998-05-01 EA EA199900895A patent/EA003696B1/ru not_active IP Right Cessation
- 1998-05-01 NZ NZ500183A patent/NZ500183A/en unknown
- 1998-05-01 BR BR9808720-7A patent/BR9808720A/pt not_active IP Right Cessation
- 1998-05-01 JP JP10547869A patent/JP2000513020A/ja active Pending
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- 1998-05-01 KR KR10-2003-7005258A patent/KR20040004406A/ko not_active Ceased
- 1998-05-01 CN CN98804845A patent/CN1255059A/zh active Pending
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