EP1505985A1 - Therapie de combinaison destinee a traiter des maladies a mediation par cyclooxygenase-2 chez des malades presentant un risque d'accident cardiovasculaire thrombotique - Google Patents

Therapie de combinaison destinee a traiter des maladies a mediation par cyclooxygenase-2 chez des malades presentant un risque d'accident cardiovasculaire thrombotique

Info

Publication number
EP1505985A1
EP1505985A1 EP03726785A EP03726785A EP1505985A1 EP 1505985 A1 EP1505985 A1 EP 1505985A1 EP 03726785 A EP03726785 A EP 03726785A EP 03726785 A EP03726785 A EP 03726785A EP 1505985 A1 EP1505985 A1 EP 1505985A1
Authority
EP
European Patent Office
Prior art keywords
cyclooxygenase
aspirin
administered
risk
nitric oxide
Prior art date
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.)
Withdrawn
Application number
EP03726785A
Other languages
German (de)
English (en)
Inventor
Richard H. Hunt
Thomas J. Simon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
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.)
Filing date
Publication date
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of EP1505985A1 publication Critical patent/EP1505985A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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

Definitions

  • the present invention encompasses a method for treating a chronic cyclooxygenase-2 mediated disease or condition and reducing the risk of a thrombotic cardiovascular event in a human patient in need of such treatment and at risk of a thrombotic cardiovascular event comprising orally concomitantly or sequentially administering to said patient a cyclooxygenase-2 selective inhibitor in an amount effective to treat the cyclooxygenase-2 mediated disease or condition and nitric oxide releasing aspirin in an amount effective to reduce the risk of the thrombotic cardiovascular event while maintaining a high level of upper gastrointestinal safety and tolerability.
  • treating a chronic cylcooxygenase-2 mediated disease or condition means treating or preventing any chronic disease or condition that is advantageously treated or prevented by inhibiting the cyclooxygenase-2 enzyme.
  • the term includes the relief of pain, fever and inflammation of a variety of conditions including rheumatic fever, symptoms associated with influenza or other viral infections, common cold, low back pain, neck pain, dysmenorrhea, headache, migraine, toothache, sprains and strains, myositis, neuralgia, synovitis, arthritis, including rheumatoid arthritis, degenerative joint diseases (osteoarthritis), gout, ankylosing spondylitis, bursitis, burns, injuries, and pain and inflammation following surgical procedures.
  • inhibitor of cyclooxygenase-2 means compounds which selectively inhibit cyclooxygenase-2 over cyclooxygenase-1.
  • nitric oxide releasing-cyclooxygenase-2 selective inhibitor means a modified version of a cycloxygenase-2 selective inhibitor as defined above linked to a NO releasing moiety by means of a linking group such as an ester linkage. Examples of such compounds are known in the art and disclosed, for example, in WO01/45703, published on June 28, 2001, which is hereby incorporated by reference in its entirety.
  • amounts that are effective to treat is intended to mean that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, a system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.
  • the term also encompasses the amount of a pharmaceutical drug that will prevent or reduce the risk of occurrence of the biological or medical event that is sought to be prevented in a tissue, a system, animal or human by a researcher, veterinarian, medical doctor or other clinician.
  • the inhibitor of cyclooxygenase-2 may be administered at a dosage level up to conventional dosage levels for NSAIDs.
  • Suitable dosage levels will depend upon the antiinflammatory effect of the chosen inhibitor of cyclooxygenase-2, but typically suitable levels will be about 0.001 to 50 mg/kg per day, preferably 0.005 to 30 mg/kg per day, and especially 0.05 to 10 mg/kg per day.
  • the compound may be administered on a regimen of once or twice per day.
  • amount effective to reduce the risk of means the amount of a pharmaceutical drug that will prevent or reduce the risk of occurrence of the biological or medical event that is sought to be prevented in a tissue, a system, animal or human by a researcher, veterinarian, medical doctor or other clinician.
  • Aspirin is administered at a dose of about 30 mg to about 1 g once daily, preferably at a dose of about 80 mg to about 650 mg.
  • a cyclooxygenase-2 selective inhibitor in an amount effective to treat the cyclooxygenase-2 mediated disease or condition and nitric oxide releasing aspirin in an amount effective to reduce the combined risk of death and nonfatal myocardial infarction, or
  • the medicament may be comprised of a nitric oxide releasing-COX-2 inhibitor in combination with about 30 mg to 1 g of aspirin, or more particularly about 80 mg to about 650 mg of aspirin.
  • the instant invention also encompasses the use of nitric oxide releasing-aspirin for the preparation of a medicament for the combined use with a cyclooxygenase-2 inhibitor for use as provided by the present invention; and the use of a cyclooxygenase-2 inhibitor for the preparation of a medicament for the combined use with nitric oxide releasing-aspirin for use as provided by the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé de traitement de maladies ou de troubles chroniques à médiation par cyclooxygénase-2, et de réduction du risque d'accident cardiovasculaire thrombotique chez un malade humain nécessitant un tel traitement et présentant un risque d'accident cardiovasculaire thrombotique. Ledit procédé consiste à administrer oralement au malade, de façon simultanée ou séquencée, un inhibiteur sélectif de cyclooxygénase-2 dans une quantité efficace pour le traitement des maladies ou troubles à médiation par cyclooxygénase-2, et de l'aspirine libérant de l'oxyde nitrique dans une quantité efficace pour réduire le risque d'accident cardiovasculaire thrombotique, tout en maintenant un taux élevé de fiabilité et de tolérabilité gastro-intestinale supérieure. L'invention concerne également un procédé de traitement de maladies ou de troubles chroniques à médiation par cyclooxygénase-2, et de réduction du risque d'accident cardiovasculaire thrombotique chez un malade humain nécessitant un tel traitement et présentant un risque d'accident cardiovasculaire thrombotique. Ledit procédé consiste à administrer oralement au malade, de façon simultanée ou séquencée, un inhibiteur sélectif de cyclooxygénase-2 libérant de l'oxyde nitrique, et de l'aspirine, dans une quantité efficace pour réduire le risque d'accident cardiovasculaire thrombotique, tout en maintenant un taux élevé de fiabilité et de tolérabilité gastro-intestinale supérieure. L'invention concerne par ailleurs des compositions pharmaceutiques.
EP03726785A 2002-05-10 2003-05-09 Therapie de combinaison destinee a traiter des maladies a mediation par cyclooxygenase-2 chez des malades presentant un risque d'accident cardiovasculaire thrombotique Withdrawn EP1505985A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US38866002P 2002-05-10 2002-05-10
US388660P 2002-05-10
PCT/US2003/014778 WO2003094924A1 (fr) 2002-05-10 2003-05-09 Therapie de combinaison destinee a traiter des maladies a mediation par cyclooxygenase-2 chez des malades presentant un risque d'accident cardiovasculaire thrombotique

Publications (1)

Publication Number Publication Date
EP1505985A1 true EP1505985A1 (fr) 2005-02-16

Family

ID=29420650

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03726785A Withdrawn EP1505985A1 (fr) 2002-05-10 2003-05-09 Therapie de combinaison destinee a traiter des maladies a mediation par cyclooxygenase-2 chez des malades presentant un risque d'accident cardiovasculaire thrombotique

Country Status (3)

Country Link
EP (1) EP1505985A1 (fr)
AU (1) AU2003229005A1 (fr)
WO (1) WO2003094924A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE419840T1 (de) 2002-04-09 2009-01-15 Flamel Tech Sa Orale wässrige suspension, mikrokapseln enthaltend, zur kontrollierten freisetzung von wirkstoffen
JP2006501161A (ja) 2002-06-11 2006-01-12 ニトロメッド インク． ニトロソ化および／またはニトロシル化シクロオキシゲナーゼ−２選択的阻害剤、組成物ならびに使用方法
EP1527045A1 (fr) 2002-07-26 2005-05-04 Merck Frosst Canada & Co. Promedicaments de diaryl-2-(5h)-furanones en tant qu'inhibiteurs de la cyclo-oxygenase-2 liberant de l'oxyde nitrique
WO2004058354A1 (fr) * 2002-12-20 2004-07-15 Pharmacia Corporation Compositions d'inhibiteurs selectifs de cyclooxygenase-2 et d'inhibiteurs selectifs de recaptage de serotonine dans le traitement ou dans la prevention d'un evenement vaso-occlusif
ATE432258T1 (de) 2003-03-05 2009-06-15 Merck Frosst Company Stickstoffmonoxid freisetzende prodrugs von diaryl-2-(5h)-furanonen als inhibitoren von cyclooxygenase-2
JP2007519641A (ja) * 2004-01-27 2007-07-19 メルク フロスト カンパニー 血栓性心血管イベントの危険がある患者におけるシクロオキシゲナーゼ−２に媒介される疾患又は病態を治療するための併用療法
WO2007016095A2 (fr) * 2005-07-27 2007-02-08 Nitromed, Inc. Composes d'inhibiteurs selectifs de cyclo-oxygenase-2 comprenant des groupes activant l'oxyde nitrique, compositions et procedes d'utilisation correspondants
CN104173359B (zh) * 2014-09-05 2017-05-03 罗国安 一种降低罗非考昔副作用的消炎镇痛复方药物及其应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1276071B1 (it) * 1995-10-31 1997-10-24 Nicox Ltd Compositi ad attivita' anti-infiammatoria
US6136804A (en) * 1998-03-13 2000-10-24 Merck & Co., Inc. Combination therapy for treating, preventing, or reducing the risks associated with acute coronary ischemic syndrome and related conditions

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03094924A1 *

Also Published As

Publication number Publication date
AU2003229005A1 (en) 2003-11-11
WO2003094924A1 (fr) 2003-11-20

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