EP1474125A1 - Utilisation d'esters ethyliques d'acides polyinsatures omega 3 chez des patients atteints d'une insuffisance cardiaque - Google Patents

Utilisation d'esters ethyliques d'acides polyinsatures omega 3 chez des patients atteints d'une insuffisance cardiaque

Info

Publication number
EP1474125A1
EP1474125A1 EP03739455A EP03739455A EP1474125A1 EP 1474125 A1 EP1474125 A1 EP 1474125A1 EP 03739455 A EP03739455 A EP 03739455A EP 03739455 A EP03739455 A EP 03739455A EP 1474125 A1 EP1474125 A1 EP 1474125A1
Authority
EP
European Patent Office
Prior art keywords
epa
heart failure
ethyl esters
patients suffering
medicament
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Withdrawn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
EP03739455A
Other languages
German (de)
English (en)
Inventor
Jadranka Rogan
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.)
Victorix Assets Ltd
Original Assignee
Victorix Assets Ltd
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 Victorix Assets Ltd filed Critical Victorix Assets Ltd
Publication of EP1474125A1 publication Critical patent/EP1474125A1/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Withdrawn legal-status Critical Current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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Definitions

  • the present invention relates to the use of ethyl esters of polyunsaturated acids in the ⁇ -3 series obtained from fish oil, and in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters at high concentrations, alone or mixed, to prepare pharmaceutical compositions useful in reducing the risk of mortality, caused by sudden death, in patients suffering from heart failure.
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • Heart failure is a clinical symptom caused by the inability of the heart to pump a quantity of blood sufficient for venous return and metabolic needs, leading to congestion of the pulmonary and systemic circulation.
  • the polyunsaturated fatty acids in the ⁇ -3 series in particular EPA and DHA, are known for their potential usefulness in the treatment of cardiovascular diseases and their risk factors.
  • EP 0,409,903-Bl, patent IT 1,235,978 and others disclose their efficacy in the treatment of hyperlipaemia, hypercholesterolaemia and hypertension.
  • the usefulness of this treatment is independent of the etiopathogenesis of the heart failure, and in particular of the presence or absence of a prior ischaemic coronary event.
  • heart failure was experimentally induced in dogs by injecting latex microspheres at coronary level to induce a malfunction of the left ventricle, which was evaluated in terms of reduction in the ejection fraction accompanied by dilatation and hypertrophy of the ventricle, reduction in cardiac output and other characteristic signs of heart failure in man.
  • One group of animals was then treated orally with one 0.5/1 g capsule of EPA and DHA ethyl esters a day for 8 weeks, and a second comparison group was treated with placebo capsules. Any mortality which occurred during that period was recorded. The survival rate was significantly higher in the treated group than the placebo group.
  • the experimental model proved to be applicable both to healthy animals and to those which had suffered prior experimentally induced heart attacks.
  • compositions of ⁇ -3 polyunsaturated acids ethyl esters of the invention mainly represented by EPA and/or DHA ethyl esters at a high concentration, can easily be obtained by procedures well known to experts in the art, such as those described in WO 89/11521, US 5130061, IT 1,235,879, US 4,377,526, US 4,554,107 and others, which are incorporated herein as regards the production processes.
  • the content of EPA and/or DHA ethyl esters generally exceeds 25%; in particular it ranges between approx. 50% and approx. 100%, and preferably between 80% and 90% (approx. 85%).
  • the percentage of EPA ethyl ester is preferably 40 to 60%, and the percentage of DHA ethyl ester is preferably in the 25-50% range; in any event the ratio between the EPA and DHA ethyl esters should be between 0.9 and 1.5.
  • said oily compositions comprising high concentrations of EPA and/or DHA ethyl esters are used to make a medicament useful in reducing the risk of mortality caused by sudden death in patients suffering from heart failure.
  • the medicament is preferably administered orally, in particular using a pharmaceutical formulation of soft gelatin capsules.
  • the preparation process of said capsules, which are particularly suitable to carry oily active ingredients, is well known to those skilled in the art.
  • the unit dose of the capsules is usually 0.5-1 g, and preferably 1 g, while the daily dose is between 0.5 and 2 g, depending on the severity of the disorder and the physician's opinion, and preferably around 1 g/day.
  • oral formulations may also be suitable, such as hard capsules, tablets and granulates in which the oily composition can be adsorbed on a solid medium, or drops, syrups, etc., as known in pharmaceutical technology.
  • Other pharmaceutical forms include parenteral formulations such as sterile emulsions and the like.
  • the medicament according to the invention may also include other active ingredients with synergistic or complementary activity; as well as diluents, thickeners, surfactants, dyes, flavouring agents, stabilisers and antioxidants, according to the usual practice.
  • Particularly preferred antioxidants are vitamin E (tocopherol) and p-oxybenzoates.
  • the model used is the one described by H.N. Sabbat et al. (Am. J. Physiol., 260, 1379, 1991) in which the incidence, frequency and complexity of the spontaneous or inducible tachyarrhythmias agrees with the observations made in patients suffering from heart failure.
  • heart failure was induced by coronary microembolisations with latex microspheres, repeated until a loss of contractile myocardium was angiographically recorded, this being defined as a left ventricle ejection fraction equal to or less than 35%.
  • composition of soft gelatin capsules containing 1 g of a mixture of EPA and DHA ethyl esters with a titre of approx. 85%
  • composition of soft gelatm capsules containing 1 g of a mixture of EPA and DHA ethyl esters with a titre of approx. 85%

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention se rapporte à l'utilisation d'ester éthylique d'acides polyinsaturés dans une série O-3 provenant d'huile de poisson. L'invention se rapporte en particulier à des esters éthyliques d'acide eicosapentanoïque (EPA) et d'acide docosahexaenoïque (DHA) à forte concentration, seuls ou mélangés utilisés dans la préparation de compositions pharmaceutiques permettant de réduire le risque de mort subite chez des patients atteints d'une insuffisance cardiaque.
EP03739455A 2002-02-12 2003-02-05 Utilisation d'esters ethyliques d'acides polyinsatures omega 3 chez des patients atteints d'une insuffisance cardiaque Withdrawn EP1474125A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IT2002MI000269A ITMI20020269A1 (it) 2002-02-12 2002-02-12 Uso di steri etilici di acidi poliinsaturi omega-3 in pazienti con insufficienza cardiaca
ITMI20020269 2002-12-19
PCT/EP2003/001108 WO2003068216A1 (fr) 2002-02-12 2003-02-05 Utilisation d'esters ethyliques d'acides polyinsatures omega 3 chez des patients atteints d'une insuffisance cardiaque

Publications (1)

Publication Number Publication Date
EP1474125A1 true EP1474125A1 (fr) 2004-11-10

Family

ID=11449201

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03739455A Withdrawn EP1474125A1 (fr) 2002-02-12 2003-02-05 Utilisation d'esters ethyliques d'acides polyinsatures omega 3 chez des patients atteints d'une insuffisance cardiaque

Country Status (4)

Country Link
EP (1) EP1474125A1 (fr)
AU (1) AU2003210210A1 (fr)
IT (1) ITMI20020269A1 (fr)
WO (1) WO2003068216A1 (fr)

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GB9901809D0 (en) 1999-01-27 1999-03-17 Scarista Limited Highly purified ethgyl epa and other epa derivatives for psychiatric and neurological disorderes
ITMI20022511A1 (it) * 2002-11-26 2004-05-27 Victorix Assets Ltd Uso di composizioni farmaceutiche contenenti esteri etilici di acidi poliinsaturi omega-3 nella orevenzione della fibrillazione atriale.
GB0403247D0 (en) 2004-02-13 2004-03-17 Tillotts Pharma Ag A pharmaceutical composition
RU2437583C2 (ru) * 2005-12-21 2011-12-27 Бруди Текнолоджи, С.Л. Применение дгк (dha), эпк (epa) или эпк, полученных из дгк, для лечения патологии, связанной с окислительным повреждением клетки, a также их нетерапевтические применения
ES2277557B1 (es) 2005-12-21 2008-07-01 Proyecto Empresarial Brudy, S.L. Utilizacion de acido docosahexaenoico para el tratamiento del daño celular oxidativo.
EP3578177A1 (fr) 2008-09-02 2019-12-11 Amarin Pharmaceuticals Ireland Limited Composition pharmaceutique contenant de l'acide eicosapentaénoïque et leurs procédés d'utilisation
EP2596786B1 (fr) 2009-02-10 2019-11-27 Amarin Pharmaceuticals Ireland Limited Utilisation de l'ester ethylique de l'acide eicosapentaenoique pour le traitement de l'hypertriglycéridémie
CN110538148A (zh) 2009-03-09 2019-12-06 巴斯夫股份公司 含有脂肪酸油混合物和表面活性剂的组合物及其方法和用途
EP3563842A1 (fr) 2009-04-29 2019-11-06 Amarin Pharmaceuticals Ireland Limited Compositions pharmaceutiques comprenant de l'epa et un agent cardiovasculaire et leurs procédés d'utilisation
RU2538691C2 (ru) 2009-04-29 2015-01-10 Амарин Фарма, Инк. Стабильные фармацевтические композиции и способы их применения
LT3318255T (lt) 2009-06-15 2021-05-25 Amarin Pharmaceuticals Ireland Limited Kompozicijos ir būdai, skirti insulto gydymui pacientui kartu su statinų terapija
CA2775339C (fr) 2009-09-23 2017-03-28 Amarin Corporation Plc Composition pharmaceutique comportant de l'acide gras omega-3 et derive hydroxy d'une statine et procedes d'utilisation de ceux-ci
NZ744990A (en) 2010-11-29 2019-10-25 Amarin Pharmaceuticals Ie Ltd Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity
US11712429B2 (en) 2010-11-29 2023-08-01 Amarin Pharmaceuticals Ireland Limited Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity
CA2826663A1 (fr) 2011-02-07 2012-08-16 Mochida Pharmaceutical Co., Ltd. Agent therapeutique pour l'insuffisance cardiaque congestive diastolique
EP2775837A4 (fr) 2011-11-07 2015-10-28 Amarin Pharmaceuticals Ie Ltd Méthodes de traitement de l'hypertriglycéridémie
US11291643B2 (en) 2011-11-07 2022-04-05 Amarin Pharmaceuticals Ireland Limited Methods of treating hypertriglyceridemia
EP2800469B1 (fr) 2012-01-06 2021-08-25 Amarin Pharmaceuticals Ireland Limited Compositions et procédés pour abaisser les taux de crp à haute sensibilité (hs-crp) chez un sujet
EP4342546A3 (fr) 2012-06-29 2024-05-22 Amarin Pharmaceuticals Ireland Limited Procédés de réduction du risque d'un événement cardiovasculaire chez un sujet soumis à un traitement par une statine
US20150265566A1 (en) 2012-11-06 2015-09-24 Amarin Pharmaceuticals Ireland Limited Compositions and Methods for Lowering Triglycerides without Raising LDL-C Levels in a Subject on Concomitant Statin Therapy
US20140187633A1 (en) 2012-12-31 2014-07-03 Amarin Pharmaceuticals Ireland Limited Methods of treating or preventing nonalcoholic steatohepatitis and/or primary biliary cirrhosis
US9814733B2 (en) 2012-12-31 2017-11-14 A,arin Pharmaceuticals Ireland Limited Compositions comprising EPA and obeticholic acid and methods of use thereof
US9452151B2 (en) 2013-02-06 2016-09-27 Amarin Pharmaceuticals Ireland Limited Methods of reducing apolipoprotein C-III
US9624492B2 (en) 2013-02-13 2017-04-18 Amarin Pharmaceuticals Ireland Limited Compositions comprising eicosapentaenoic acid and mipomersen and methods of use thereof
US9662307B2 (en) 2013-02-19 2017-05-30 The Regents Of The University Of Colorado Compositions comprising eicosapentaenoic acid and a hydroxyl compound and methods of use thereof
US9283201B2 (en) 2013-03-14 2016-03-15 Amarin Pharmaceuticals Ireland Limited Compositions and methods for treating or preventing obesity in a subject in need thereof
US20140271841A1 (en) 2013-03-15 2014-09-18 Amarin Pharmaceuticals Ireland Limited Pharmaceutical composition comprising eicosapentaenoic acid and derivatives thereof and a statin
US10966968B2 (en) 2013-06-06 2021-04-06 Amarin Pharmaceuticals Ireland Limited Co-administration of rosiglitazone and eicosapentaenoic acid or a derivative thereof
US20150065572A1 (en) 2013-09-04 2015-03-05 Amarin Pharmaceuticals Ireland Limited Methods of treating or preventing prostate cancer
US9585859B2 (en) 2013-10-10 2017-03-07 Amarin Pharmaceuticals Ireland Limited Compositions and methods for lowering triglycerides without raising LDL-C levels in a subject on concomitant statin therapy
US10561631B2 (en) 2014-06-11 2020-02-18 Amarin Pharmaceuticals Ireland Limited Methods of reducing RLP-C
WO2015195662A1 (fr) 2014-06-16 2015-12-23 Amarin Pharmaceuticals Ireland Limited Procédés de réduction ou de prévention de l'oxydation des ldl petites et denses ou des acides gras polyinsaturés membranaires
US10406130B2 (en) 2016-03-15 2019-09-10 Amarin Pharmaceuticals Ireland Limited Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids
TW201900160A (zh) 2017-05-19 2019-01-01 愛爾蘭商艾瑪琳製藥愛爾蘭有限公司 用於降低腎功能下降之個體中的三酸甘油酯之組合物及方法
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FI4056176T3 (fi) 2018-09-24 2024-05-30 Amarin Pharmaceuticals Ie Ltd Menetelmät kardiovaskulaaristen tapahtumien riskin pienentämiseksi tutkittavassa
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ATE305810T1 (de) * 2000-05-22 2005-10-15 Pro Aparts Investimentos E Con Fettsäure enthaltende pharmazeutische zusammensetzung die wenigstens 80 gew. epa und dha enthält
ITMI20010129A1 (it) * 2001-01-25 2002-07-25 Pharmacia & Upjohn Spa Acidi grassi essenziali nella terapia di insufficienza cardiaca e scompenso cardiaco

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Also Published As

Publication number Publication date
ITMI20020269A1 (it) 2003-08-12
WO2003068216A1 (fr) 2003-08-21
ITMI20020269A0 (it) 2002-02-12
AU2003210210A1 (en) 2003-09-04

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