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Title:
USE OF TRIMETAZIDINE TO INHIBIT ACYL-COA ACETYL TRANSFERASE
Document Type and Number:
WIPO Patent Application WO/2001/064220
Kind Code:
A1
Abstract:
The invention concerns the use of trimetazidine or one of it addition salts to a pharmaceutically acceptable acid to obtain pharmaceutical compositions designed to inhibit acyl-CoA transferase, which can be used for various cardiac and coronary pathologies, for treating angiopathies, intermittent claudication, orientation and equilibrium disorders, age-related maculopathy, diabetic retinopathy or any other pathology related to energy cellular metabolism.

Inventors:
LOPASCHUK GARY (CA)
LUCIEN ARNAUD (FR)
Application Number:
PCT/FR2001/000535
Publication Date:
September 07, 2001
Filing Date:
February 23, 2001
Export Citation:
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Assignee:
ADIR (FR)
LOPASCHUK GARY (CA)
LUCIEN ARNAUD (FR)
International Classes:
A61K31/495; A61P3/00; A61P9/00; A61P9/04; A61P9/08; A61P9/10; A61P25/00; A61P27/02; A61P27/16; A61P39/00; A61P39/06; (IPC1-7): A61K31/495; A61P39/00; A61P39/06; A61P9/10; A61P9/04; A61P9/08; A61P27/16; A61P27/02
Domestic Patent References:
WO1997000678A11997-01-09
Foreign References:
FR2490963A11982-04-02
US3262852A1966-07-26
FR805M1961-09-01
EP0533579A11993-03-24
Other References:
LUCIEN A ET AL: "THE ANTI-ANGINAL ACTIONS OF TRIMETAZIDINE ARE A RESULT OF A DECREASE IN CARDIAC FATTY ACID OXIDATION RATES DUE TO INHIBITION OFLONG CHAIN 3-KETO ACYL COA THIOLASE", JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,XX,XX, vol. 32, no. 5, 10 May 2000 (2000-05-10), pages A42, XP000978197, ISSN: 0022-2828
DATABASE MEDLINE XP002158323
LOPASCHUK G D ET AL: "TRIMETAZIDINE INHIBITS FATTY ACID OXIDATION IN THE HEART", TELETRAFFIC ANALYSIS AND COMPUTER PERFORMANCE EVALUATION, PROCEEDINGS OF THE INTERNATIONAL SEMINAR,ELSEVIER SCIENCE PUBLISHERS B.V,NL, vol. 30, no. 6, June 1998 (1998-06-01), pages A112, XP000978199
SPEDDING M ET AL: "MEDICAMENTS INTERAGISSANT AVEC LES MITOCHONDRIES: EFFETS ANTI-ISCHEMIQUES DE LA TRIMETAZIDINE", THERAPIE,DOIN, PARIS,FR, vol. 54, no. 5, September 1999 (1999-09-01), pages 627 - 635, XP000978190, ISSN: 0040-5957
LOPASCHUK: "Optimizaing cardiac energy metabolism: a new approach to treating ischemic heart disease", EUROPEAN HEART JOURNAL, SUPPL., vol. 1, no. 0, - 1999, pages 032 - 039, XP000978353
DI GIROLAMO ET AL.: "Trimetazidine inhibits fatty acid beta -oxidation, resulting in less production and accumulation of lactate and H+ during ischemia", CARDIOVASC. DRUGS THER., vol. 13, no. 1, 1999, pages 18, XP000978472
KANTOR ET AL.: "Fatty acid oxidation in the reperfused ischemic heart", AM. J. MED. SCI., vol. 318, no. 1, 1999, pages 3 - 14, XP000978354
STANLEY ET AL.: "Regulation of myocardial carbohydrate metabolism under normal and ischemic conditions. Potential for pharmacological interventions", CARDIOVASCULAR RESEARCH, vol. 33, no. 2, February 1997 (1997-02-01), pages 243 - 257, XP000978213
JACKSON: "Clinical benefits of a metabolic approach to the menegement of coronary patients", EUROPEAN HEART JOURNAL, vol. 1, no. suppl., 1999, pages O28 - O31, XP000978351
CARGNONI A ET AL: "INSIGHT INTO CYTOPROTECTION WITH METABOLIC AGENTS", EUROPEAN HEART JOURNAL, THE EUROPEAN SOCIETY OF CARDIOLOGY, XX, vol. 1, no. SUPPL O, August 1999 (1999-08-01), pages O40 - O48, XP000978352, ISSN: 0195-668X
DEMAISON L ET AL: "INFLUENCE OF THE ANTI-ISCHEMIC TRIMETAZIDINE ON CARDIAC ENERGY METABOLISM", JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, XX, XX, vol. 25, no. SUPPL 4, 1993, pages S15, XP000978201, ISSN: 0022-2828
Attorney, Agent or Firm:
Adir, Compagnie ET. (1 rue Carle Hébert Courbevoie Cedex, FR)
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Claims:
REVENDICATIONS
1. Utilisation de la trimetazidine ou d'un de ses sels d'addition à un acide pharmaceutiquement acceptable pour l'obtention de compositions pharmaceutiques destinées à inhiber l'acylCoA acétyltransférase.
2. Utilisation selon la revendication 1 caractérisée en ce que les compositions pharmaceutiques sont destinées au traitement des cardiomyopathies ischémiques, des cardiopathies diabétiques, de l'insuffisance coronarienne, de l'insuffisance cardiaque, des angiopathies, de la claudication intermittente, des troubles de l'orientation et de l'équilibre, de la dégénérescence maculaire liée à l'âge, de la rétinopathie diabétique ou de toute pathologie où l'amélioration du métabolisme énergétique cellulaire est impliquée.
3. Utilisation selon l'une quelconque des revendications 1 ou 2 caractérisée en ce que la trimetazidine est sous forme de dichlorhydrate.
4. Composition pharmaceutique utilisable selon l'une quelconque des revendications 1,2 ou 3 contenant comme principe actif la trimetazidine ou l'un de ses sels d'addition à un acide pharmaceutiquement acceptable ainsi qu'un ou plusieurs excipients pharmaceutiquement acceptables.
5. Composition pharmaceutique selon la revendication 4 caractérisée en ce que le principe actif est la trimetazidine sous forme de dichlorhydrate.