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 PDF

Info

Publication number: OA11213A
Authority: OA; OAPI
Prior art keywords: cox; carprofen; inhibitors; inhibitor; inhibition
Prior art date: 1997-05-05

Application number

OA9900242A

Other languages

English (en)

Inventor

Kristin Marie Lundy

Anthony Paul Ricketts

Original Assignee

Pfizer

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

1999-11-02

Publication date

2003-07-14

1999-11-02 Application filed by Pfizer filed Critical Pfizer

2003-07-14 Publication of OA11213A publication Critical patent/OA11213A/en

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

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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)

OA9900242A 1997-05-05 1999-11-02 Cox-2 selective carprofen for treating pain and inflammation in dogs OA11213A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US4563597P	1997-05-05	1997-05-05

Publications (1)

Publication Number	Publication Date
OA11213A true OA11213A (en)	2003-07-14

Family

ID=21939053

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900242A OA11213A (en)	1997-05-05	1999-11-02	Cox-2 selective carprofen for treating pain and inflammation in dogs

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
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 (fr) *	1998-10-23	2000-05-04	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
NZ513965A (en) *	1999-03-10	2004-04-30	G	Method and composition for administering a cyclooxygenase-2 inhibitor
AU1592901A (en) *	1999-11-11	2001-06-06	Eli Lilly And Company	Oncolytic combinations for the treatment of cancer
US20020016342A1 (en) *	2000-05-15	2002-02-07	Edward Scolnick	Combination therapy using COX-2 selective inhibitor and thromboxane inhibitor and compositions therefor
EA011309B1 (ru)	2000-06-13	2009-02-27	Вайет	Составы для ослабления боли, содержащие целекоксиб
DE10032132A1 (de) *	2000-07-01	2002-01-17	Lohmann Therapie Syst Lts	Dermales Therapeutisches System enthaltend nichtsteroidale Antiphlogistika mit selektiver COX-2-Hemmung
AU8475301A (en)	2000-08-07	2002-02-18	Univ Vanderbilt	Detection of cox-2 activity and anandamide metabolites
WO2003007875A2 (fr) *	2001-07-16	2003-01-30	Hoegestaett Edward	Substances organoleptiques d'acetaminophene et composes associes utilises comme substrats pour conjugaison d'acides gras et utilisation de ces substances dans le traitement de la douleur, de la fievre et des inflammations
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.
CA2533101A1 (fr) *	2003-07-31	2005-02-03	Pharmacia & Upjohn Company Llc	Formulation dispersable d'un agent anti-inflammatoire
EP1940380A2 (fr) *	2005-05-20	2008-07-09	Pfizer Limited	Combinaisons synergiques des medicaments anti-inflammatoires non steroidiens avec des ligands alpha-2 delta
EP2061440A2 (fr) *	2007-04-04	2009-05-27	Sigmoid Pharma Limited	Composition pharmaceutique à base de tacrolimus
ES2963291T3 (es)	2007-04-26	2024-03-26	Sublimity Therapeutics Ltd	Fabricación de múltiples minicápsulas
ES2530049T3 (es)	2009-05-18	2015-02-26	Sigmoid Pharma Limited	Composición que comprende gotas de aceite
BR112012002963A2 (pt)	2009-08-12	2017-10-24	Sigmoid Pharma Ltd	composições imunomoduladoras compreendendo uma matriz de polímero e uma fase oleosa
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
CN105939713A (zh) *	2014-03-06	2016-09-14	阿莱塔纳治疗学股份有限公司	格拉匹纶组合物及其使用方法
EA036036B1 (ru)	2014-11-07	2020-09-16	Сигмойд Фарма Лимитед	Композиции, содержащие циклоспорин
WO2016112312A1 (fr) *	2015-01-09	2016-07-14	Jaguar Animal Health	Méthodes de traitement de la diarrhée chez des animaux de compagnie
JP2023520367A (ja) *	2020-03-25	2023-05-17	エスアールアイインターナショナル	リポキシゲナーゼ阻害剤
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 HU HU0001286A patent/HUP0001286A3/hu unknown
- 1998-05-01 YU YU55899A patent/YU55899A/sh unknown
- 1998-05-01 SK SK1481-99A patent/SK148199A3/sk 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 IL IL13257098A patent/IL132570A0/xx unknown
- 1998-05-01 CA CA002288759A patent/CA2288759A1/fr not_active Abandoned
- 1998-05-01 KR KR1019997010252A patent/KR20010012300A/ko not_active Ceased
- 1998-05-01 EA EA199900895A patent/EA003696B1/ru 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 EP EP98915041A patent/EP0988034A1/fr not_active Withdrawn
- 1998-05-01 BR BR9808720-7A patent/BR9808720A/pt not_active IP Right Cessation
- 1998-05-01 ID IDP980651A patent/ID21311A/id unknown
- 1998-05-01 CN CN98804845A patent/CN1255059A/zh active Pending
- 1998-05-01 NZ NZ500183A patent/NZ500183A/en unknown
- 1998-05-01 PL PL98337003A patent/PL337003A1/xx unknown
- 1998-05-04 TN TNTNSN98059A patent/TNSN98059A1/fr unknown
- 1998-05-04 MA MA25059A patent/MA26491A1/fr unknown
- 1998-05-04 GT GT199800063A patent/GT199800063A/es unknown
- 1998-05-04 ZA ZA9803722A patent/ZA983722B/xx unknown
- 1998-05-04 PE PE1998000335A patent/PE72599A1/es not_active Application Discontinuation
- 1998-05-04 UY UY24989A patent/UY24989A1/es not_active Application Discontinuation
- 1998-05-04 AP APAP/P/1998/001234A patent/AP9801234A0/en unknown
- 1998-05-05 AR ARP980102089A patent/AR011726A1/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
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
AU6932198A (en)	1998-11-27
IL132570A0 (en)	2001-03-19
PE72599A1 (es)	1999-08-12
HUP0001286A3 (en)	2000-12-28
BG103852A (en)	2000-06-30
HRP980244A2 (en)	1999-02-28
EA003696B1 (ru)	2003-08-28
WO1998050033A1 (fr)	1998-11-12
JP2000513020A (ja)	2000-10-03
DZ2479A1 (fr)	2003-02-01
GT199800063A (es)	1999-10-26
EP0988034A1 (fr)	2000-03-29
EA199900895A1 (ru)	2000-06-26
UY24989A1 (es)	2001-10-25
ID21311A (id)	1999-05-20
AR039628A2 (es)	2005-03-02
SK148199A3 (en)	2001-09-11
AR011726A1 (es)	2000-08-30
PL337003A1 (en)	2000-07-31
NZ500183A (en)	2002-04-26
TW590773B (en)	2004-06-11
MA26491A1 (fr)	2004-12-20
BR9808720A (pt)	2000-07-11
YU55899A (sh)	2003-08-29
NO995389D0 (no)	1999-11-04
AP9801234A0 (en)	1999-11-04
NO995389L (no)	2000-01-04
CA2288759A1 (fr)	1998-11-12
KR20010012300A (ko)	2001-02-15
TNSN98059A1 (fr)	2005-03-15
HUP0001286A2 (hu)	2000-11-28
CN1255059A (zh)	2000-05-31
IS5220A (is)	1999-10-19
PA8450601A1 (es)	2000-05-24
KR20040004406A (ko)	2004-01-13
ZA983722B (en)	1999-11-04

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