JP2000513020A - イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン - Google Patents

イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン

Info

Publication number: JP2000513020A
Authority: JP; Japan
Prior art keywords: cox; inhibitor; carprofen; inflammation; activity
Prior art date: 1997-05-05
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.): Pending

Application number

JP10547869A

Other languages

English (en)

Japanese (ja)

Inventor

ランディ，クリスティン，マリイ

リケッツ，アンソニー，ポール

Original Assignee

ファイザーインク．

Priority date (The priority date 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 date listed.)

1997-05-05

Filing date

1998-05-01

Publication date

2000-10-03

1998-05-01 Application filed by ファイザーインク． filed Critical ファイザーインク．

2000-10-03 Publication of JP2000513020A publication Critical patent/JP2000513020A/ja

Status Pending legal-status Critical Current

Links

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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
- A61K31/33—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)

JP10547869A 1997-05-05 1998-05-01 イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン Pending JP2000513020A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US4563597P	1997-05-05	1997-05-05
US60/045,635		1997-05-05
PCT/IB1998/000662 WO1998050033A1 (fr)	1997-05-05	1998-05-01	Carprofene inhibant selectivement cox-2 et utilise dans le traitement de la douleur et des inflammations chez les chiens

Publications (1)

Publication Number	Publication Date
JP2000513020A true JP2000513020A (ja)	2000-10-03

Family

ID=21939053

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP10547869A Pending JP2000513020A (ja)	1997-05-05	1998-05-01	イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン

Country Status (32)

Country	Link
EP (1)	EP0988034A1 (fr)
JP (1)	JP2000513020A (fr)
KR (2)	KR20040004406A (fr)
CN (1)	CN1255059A (fr)
AP (1)	AP9801234A0 (fr)
AR (2)	AR011726A1 (fr)
AU (1)	AU6932198A (fr)
BG (1)	BG103852A (fr)
BR (1)	BR9808720A (fr)
CA (1)	CA2288759A1 (fr)
DZ (1)	DZ2479A1 (fr)
EA (1)	EA003696B1 (fr)
GT (1)	GT199800063A (fr)
HR (1)	HRP980244A2 (fr)
HU (1)	HUP0001286A3 (fr)
ID (1)	ID21311A (fr)
IL (1)	IL132570A0 (fr)
IS (1)	IS5220A (fr)
MA (1)	MA26491A1 (fr)
NO (1)	NO995389L (fr)
NZ (1)	NZ500183A (fr)
OA (1)	OA11213A (fr)
PA (1)	PA8450601A1 (fr)
PE (1)	PE72599A1 (fr)
PL (1)	PL337003A1 (fr)
SK (1)	SK148199A3 (fr)
TN (1)	TNSN98059A1 (fr)
TW (1)	TW590773B (fr)
UY (1)	UY24989A1 (fr)
WO (1)	WO1998050033A1 (fr)
YU (1)	YU55899A (fr)
ZA (1)	ZA983722B (fr)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
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
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
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
EP1123091A1 (fr) *	1998-10-23	2001-08-16	Merck Frosst Canada & Co.	Produit de combinaison comprenant un ligand de prostaglandine de type e et un inhibiteur selectif de cox-2, et procedes d'utilisation dudit produit
ATE306263T1 (de) *	1999-03-10	2005-10-15	Searle Llc	Zusammensetzungen zur verabreichung eines cyclooxygenase-2-hemmers an tiere
AU1592901A (en) *	1999-11-11	2001-06-06	Eli Lilly And Company	Oncolytic combinations for the treatment of cancer
WO2001087343A2 (fr) *	2000-05-15	2001-11-22	Merck Frosst Canada & Co.	Polytherapie faisant appel a un inhibiteur selectif de cox-2 et a un inhibiteur de la thromboxane ainsi que des compositions contenant ceux-ci
MXPA02012344A (es)	2000-06-13	2004-02-26	Wyeth Corp	Composiciones y anti-inflamatorias que contienen inhibidores cox-2.
DE10032132A1 (de) *	2000-07-01	2002-01-17	Lohmann Therapie Syst Lts	Dermales Therapeutisches System enthaltend nichtsteroidale Antiphlogistika mit selektiver COX-2-Hemmung
WO2002012445A1 (fr)	2000-08-07	2002-02-14	Vanderbilt University	Detection de l'activite cox-2 et des metabolites d'anandamide
AU2002354901A1 (en) *	2001-07-16	2003-03-03	Edward Hogestatt	Compounds with analgesic, antipyretic and/or anti-inflammatory activity
ES2275218T3 (es)	2003-05-07	2007-06-01	Osteologix A/S	Sales de estroncio hidrosolubles para el tratamiento de afecciones de cartilagos y/o huesos.
JP2007500691A (ja) *	2003-07-31	2007-01-18	ファルマシア・アンド・アップジョン・カンパニー・エルエルシー	抗炎症剤の分散性製剤
BRPI0610316A2 (pt) *	2005-05-20	2010-06-15	Pfizer Ltd	combinações sinergìsticas de medicamentos atiinflamatórios não estereoidais com alfa-delta-ligantes
ES2393814T3 (es)	2007-04-04	2012-12-28	Sigmoid Pharma Limited	Una composición farmacéutica oral
CA2685118C (fr)	2007-04-26	2016-11-01	Sigmoid Pharma Limited	Fabrication de minicapsules multiples
ES2530049T3 (es)	2009-05-18	2015-02-26	Sigmoid Pharma Limited	Composición que comprende gotas de aceite
CN102573802A (zh)	2009-08-12	2012-07-11	希格默伊德药业有限公司	包含聚合物基质和油相的免疫调节组合物
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
PT3113774T (pt)	2014-03-06	2022-02-28	Elanco Animal Health Incorporated	Composições de grapiprant e métodos de utilização das mesmas
JP6716582B2 (ja)	2014-11-07	2020-07-01	サブリミティ・セラピューティクス・リミテッドＳｕｂｌｉｍｉｔｙＴｈｅｒａｐｅｕｔｉｃｓＬｉｍｉｔｅｄ	シクロスポリンを含む組成物
BR112017014750A2 (pt) *	2015-01-09	2018-06-19	Jaguar Animal Health	métodos para tratamento de diarreia em animais de estimação
CN115335046A (zh) *	2020-03-25	2022-11-11	思研（Sri）国际顾问与咨询公司	脂肪氧合酶抑制剂
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)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3896145A (en) *	1972-07-24	1975-07-22	Hoffmann La Roche	Carbazoles
CA1319886C (fr) *	1987-02-03	1993-07-06	Alberto Ferro	Solutions de micelles mixtes

1998
- 1998-03-02 DZ DZ980089A patent/DZ2479A1/fr active
- 1998-04-30 TW TW087106689A patent/TW590773B/zh not_active IP Right Cessation
- 1998-05-01 WO PCT/IB1998/000662 patent/WO1998050033A1/fr not_active Ceased
- 1998-05-01 JP JP10547869A patent/JP2000513020A/ja active Pending
- 1998-05-01 SK SK1481-99A patent/SK148199A3/sk unknown
- 1998-05-01 HU HU0001286A patent/HUP0001286A3/hu unknown
- 1998-05-01 KR KR10-2003-7005258A patent/KR20040004406A/ko not_active Ceased
- 1998-05-01 AU AU69321/98A patent/AU6932198A/en not_active Abandoned
- 1998-05-01 BR BR9808720-7A patent/BR9808720A/pt not_active IP Right Cessation
- 1998-05-01 YU YU55899A patent/YU55899A/sh unknown
- 1998-05-01 CA CA002288759A patent/CA2288759A1/fr not_active Abandoned
- 1998-05-01 EA EA199900895A patent/EA003696B1/ru not_active IP Right Cessation
- 1998-05-01 EP EP98915041A patent/EP0988034A1/fr not_active Withdrawn
- 1998-05-01 CN CN98804845A patent/CN1255059A/zh active Pending
- 1998-05-01 NZ NZ500183A patent/NZ500183A/en unknown
- 1998-05-01 IL IL13257098A patent/IL132570A0/xx unknown
- 1998-05-01 ID IDP980651A patent/ID21311A/id unknown
- 1998-05-01 KR KR1019997010252A patent/KR20010012300A/ko not_active Ceased
- 1998-05-01 PL PL98337003A patent/PL337003A1/xx unknown
- 1998-05-04 PE PE1998000335A patent/PE72599A1/es not_active Application Discontinuation
- 1998-05-04 TN TNTNSN98059A patent/TNSN98059A1/fr unknown
- 1998-05-04 UY UY24989A patent/UY24989A1/es not_active Application Discontinuation
- 1998-05-04 ZA ZA9803722A patent/ZA983722B/xx unknown
- 1998-05-04 AP APAP/P/1998/001234A patent/AP9801234A0/en unknown
- 1998-05-04 MA MA25059A patent/MA26491A1/fr unknown
- 1998-05-04 GT GT199800063A patent/GT199800063A/es unknown
- 1998-05-05 HR HR60/045,635A patent/HRP980244A2/hr not_active Application Discontinuation
- 1998-05-05 PA PA19988450601A patent/PA8450601A1/es unknown
- 1998-05-05 AR ARP980102089A patent/AR011726A1/es unknown
1999
- 1999-10-19 IS IS5220A patent/IS5220A/is unknown
- 1999-11-02 OA OA9900242A patent/OA11213A/en unknown
- 1999-11-03 BG BG103852A patent/BG103852A/xx unknown
- 1999-11-04 NO NO995389A patent/NO995389L/no not_active Application Discontinuation
2003
- 2003-04-09 AR ARP030101251A patent/AR039628A2/es unknown

Also Published As

Publication number	Publication date
NO995389D0 (no)	1999-11-04
CA2288759A1 (fr)	1998-11-12
PE72599A1 (es)	1999-08-12
EA199900895A1 (ru)	2000-06-26
CN1255059A (zh)	2000-05-31
PL337003A1 (en)	2000-07-31
KR20040004406A (ko)	2004-01-13
HUP0001286A2 (hu)	2000-11-28
NO995389L (no)	2000-01-04
AR011726A1 (es)	2000-08-30
ID21311A (id)	1999-05-20
IL132570A0 (en)	2001-03-19
AP9801234A0 (en)	1999-11-04
HRP980244A2 (en)	1999-02-28
WO1998050033A1 (fr)	1998-11-12
KR20010012300A (ko)	2001-02-15
OA11213A (en)	2003-07-14
PA8450601A1 (es)	2000-05-24
UY24989A1 (es)	2001-10-25
NZ500183A (en)	2002-04-26
BR9808720A (pt)	2000-07-11
EP0988034A1 (fr)	2000-03-29
GT199800063A (es)	1999-10-26
BG103852A (en)	2000-06-30
HUP0001286A3 (en)	2000-12-28
TNSN98059A1 (fr)	2005-03-15
EA003696B1 (ru)	2003-08-28
ZA983722B (en)	1999-11-04
YU55899A (sh)	2003-08-29
IS5220A (is)	1999-10-19
TW590773B (en)	2004-06-11
AU6932198A (en)	1998-11-27
MA26491A1 (fr)	2004-12-20
AR039628A2 (es)	2005-03-02
DZ2479A1 (fr)	2003-02-01
SK148199A3 (en)	2001-09-11

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