EP1474125A1 - The use of omega-3 polyunsaturated acids ethyl esters in patients suffering from heart failure - Google Patents
The use of omega-3 polyunsaturated acids ethyl esters in patients suffering from heart failureInfo
- 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- Withdrawn
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
The invention discloses the use of ethyl esters of polyunsaturated acids in the ω-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 sudden death, in patients suffering from heart failure.
Description
THE USE OF OMEGA-3 POLYUNSATURATED ACIDS ETHYL ESTERS IN PATIENTS SUFFERING FROM HEART FAILURE
The present invention relates to the use of ethyl esters of polyunsaturated acids in the ω-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.
BASIS OF THE INVENTION
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.
Despite the progress made with pharmacological treatment, which now includes angiotensin-converting enzyme inhibitors (ACE) and beta-blockers in addition to the cardioactive glycosides and diuretics that have long been in use, mortality in patients with heart failure remains high, ranging between 7 and 11% per annum (S.G. Priori et al., European Heart Journal, 22, 1374, 2001). These mortality figures are independent of the original causes of heart failure such as ischaemic events, dilated cardiomyopathy, and the like. Sudden cardiac death accounts for 60% of deaths.
Current treatments are therefore insufficient to prevent mortality in patients suffering from heart failure. In particular, none of the drugs generally used, with the possible exception of beta-blockers, whose use is limited by their serious contraindications, has demonstrated specific preventive efficacy against the risk of sudden death.
The polyunsaturated fatty acids in the ω-3 series, in particular EPA and DHA, are known for their potential usefulness in the treatment of
cardiovascular diseases and their risk factors.
By way of example, EP 0,409,903-Bl, patent IT 1,235,978 and others disclose their efficacy in the treatment of hyperlipaemia, hypercholesterolaemia and hypertension.
A clinical trial conducted with formulations containing a high concentration of EPA and DHA ethyl esters on patients who had suffered prior myocardial infarctions demonstrated their efficacy in reducing mortality, and especially sudden death (Lancet, 354, 4476, 1999).
However, patients with manifest heart failure were excluded from that trial.
Patients with manifest heart failure were also excluded from other trials in which the administration of ω-3 polyunsaturated acid analogues to post-infarction patients by various procedures (diets and diet supplements) led to reductions in mortality or morbidity (Lancet ii, 257, 1989; Circulation, 99, 779, 1999; Cardiovascular Drugs and Therapy, 11, 485, 1997).
Even now, the literature regarding these polyunsaturated fatty acids, especially EPA and DHA esters, does not describe or suggest their use to reduce mortality in patients suffering from heart failure.
SUMMARY OF THE INVENTION
It has now been found that EPA and DHA ethyl esters can be used to reduce mortality caused by sudden death in patients suffering from heart failure.
The usefulness of this treatment, as clearly exemplified by the pharmacological data, is independent of the etiopathogenesis of the heart failure, and in particular of the presence or absence of a prior ischaemic coronary event.
DESCRIPTION OF THE INVENTION
The treatment method has been tested and verified, for ethical reasons,
on animal models reported in the literature and adapted for the particular use required. Briefly, 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.
The compositions of ω-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%). In the ambit of these EPA and DHA concentrations in a mixture, 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.
According to the invention, 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. For this clinical use, in accordance with the experimental findings, 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.
Other 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.
Typical pharmacological results of the therapeutic activity claimed are reported in Examples 1 and 2, and some compositions of soft gelatin capsule formulations are reported in Examples 3-6.
Example 1
Efficacy of EPA and DHA ethyl esters in dogs with heart failure following myocardial ischaemia
The effect of EPA and DHA ethyl esters in heart failure has been studied in a canine model developed by Adamson and Vanoli (Journal of the American College of Cardiology, 37, 1741, 2001).
Myocardial infarction was induced in mongrel dogs weighing between 20 and 35 kg by lengthy occlusion (20 min) of the left descending coronary artery during thoracotomy under general anaesthesia. In the animals in which transient ischaemia and physical exercise induced ventricular fibrillation after a suitable recovery period, heart failure was induced by injecting latex microspheres into the circumflex coronary artery, and the injections were repeated until a left ventricle ejection fraction of approx. 35% was recorded.
According to the findings reported in the above-mentioned study, these left ventricular malfunction conditions caused sudden death of all the animals within eight weeks; however, daily treatment of 10 animals with a capsule containing 0.5 g of EPA and DHA ethyl esters with a titre of 85%, as described in Example 5, kept 7 animals alive during the same period.
These results demonstrate that the compounds of the invention protect 70% of animals with heart failure consequent on myocardial ischaemia against sudden death.
Example 2
Efficacy of EPA and DHA ethyl esters in dogs with heart failure in the absence of prior ischaemic events
The effect of EPA and DHA ethyl esters has also been studied in an experimental model in mongrel dogs in which chronic malfunction of the left ventricle was induced in the absence of a prior myocardial infarction.
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. Once again, 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%.
Eighteen dogs which survived the operation in acceptable conditions were divided into two groups and treated daily for eight weeks with capsules containing 1 g of EPA and DHA ethyl esters with a titre of 85%, as described in Example 3, or with placebo capsules (olive oil). The programmed ventricular stimulation induced sustained ventricular tachycardia or ventricular fibrillation in seven of the nine dogs in the placebo group, which was terminated in all cases by direct-current cardioversion. In the group treated with the active ingredients, the electrophysiological test only induced ventricular fibrillation in two out of nine dogs.
These results demonstrate that even in the absence of prior myocardial ischaemia, EPA and DHA ethyl esters protect over 70% of animals with experimental heart failure against malignant tachyarrhythmias which would lead to sudden cardiac death in the absence of suitable defibrillation.
Example 3
Composition of soft gelatin capsules containing 1 g of a mixture of EPA and DHA ethyl esters with a titre of approx. 85%
EPA ethyl ester 525 mg
DHA ethyl ester 315 mg d-alpha tocopherol 4 IU gelatin 246 mg glycerol 118 mg red iron oxide 2.27 mg yellow iron oxide 1.27 mg
Example 4
Composition of soft gelatm capsules containing 1 g of a mixture of EPA and DHA ethyl esters with a titre of approx. 85%
Polyunsaturated fatty acids ethyl esters 1000 mg with an EPA ethyl ester and DHA ethyl ester content of 850 mg d-l-α tocopherol 0.3 mg gelatin succinate 233 mg glycerol 67 mg sodium p-oxybenzoate 1.09 mg sodium propyl p-oxybenzoate 0.54 mg Example 5
Composition of soft gelatin capsules containing 0.5 g of EPA and DHA ethyl esters with a titre of approx. 85%
Polyunsaturated fatty acids ethyl esters 500 mg with EPA ethyl ester and DHA ethyl ester content,
0.9-1.5 ratio, of 425 mg d-l-α tocopherol 0.15 mg gelatin succinate 139 mg glycerol 40 mg sodium ethyl p-oxybenzoate 0.66 mg sodium propyl p-hydroxybenzoate 0.32 mg
Example 6
Composition of soft gelatin capsules containing 0.5 g of polyunsaturated fatty acids ethyl esters
DHA ethyl ester > 400 mg d-l-α tocopherol 0.15 mg gelatin succinate 139 mg glycerol 40 mg sodium ethyl p-oxybenzoate 0.66 mg sodium propyl p-hydroxybenzoate 0.32 mg
Claims
1. Use of a composition of EPA and DHA ethyl esters for the preparation of a medicament useful in reducing mortality caused by "sudden death" in patients suffering from heart failure, wherein the EPA and DHA ethyl ester content exceeds 25%.
2. Use as claimed in claim 1, wherein the medicament is useful in reducing mortality in patients suffering from heart failure of any origin.
3. Use as claimed in claims 1-2, wherein the medicament is useful in reducing mortality in patients suffering from heart failure caused by dilated cardiomyopathy.
4. Use as claimed in claims 1-3, wherein the medicament is useful in reducing mortality in patients suffering from heart failure caused by ischaemic events.
5. Use as claimed in claims 1-4, wherein the EPA and DHA ethyl ester content is between 50 and 100%.
6. Use as claimed in claims 1-5, wherein the EPA and DHA ethyl ester content is between 80 and 90%.
7. Use as claimed in claims 1-6, wherein the medicament is administered orally.
8. Use as claimed in claims 1-7, wherein the medicament is used in soft gelatin capsules.
9. Use as claimed in claims 7 and 8, wherein the medicament is used at the dose of 0.5 - 2 g a day.
10. Use as claimed in claims 7-9, wherein the medicament is used at the dose of 1 g a day.
11. Use as claimed in claims 1-10, wherein the EPA ethyl ester content is between 40 and 60% and the DHA ethyl ester content is between 25 and 50%.
12. Use as claimed in claims 1-10, wherein the ratio of EPA to DHA ethyl ester contents is between 0.9 and 1.5.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT2002MI000269A ITMI20020269A1 (en) | 2002-02-12 | 2002-02-12 | USE OF OMEGA-3 POLYUNSATURATED ACID ETHYL STERES IN PATIENTS WITH HEART INSUFFICIENCY |
ITMI20020269 | 2002-12-19 | ||
PCT/EP2003/001108 WO2003068216A1 (en) | 2002-02-12 | 2003-02-05 | The use of omega-3 polyunsaturated acids ethyl esters in patients suffering from heart failure |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1474125A1 true EP1474125A1 (en) | 2004-11-10 |
Family
ID=11449201
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP03739455A Withdrawn EP1474125A1 (en) | 2002-02-12 | 2003-02-05 | The use of omega-3 polyunsaturated acids ethyl esters in patients suffering from heart failure |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1474125A1 (en) |
AU (1) | AU2003210210A1 (en) |
IT (1) | ITMI20020269A1 (en) |
WO (1) | WO2003068216A1 (en) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9901809D0 (en) | 1999-01-27 | 1999-03-17 | Scarista Limited | Highly purified ethgyl epa and other epa derivatives for psychiatric and neurological disorderes |
ITMI20022511A1 (en) * | 2002-11-26 | 2004-05-27 | Victorix Assets Ltd | USE OF PHARMACEUTICAL COMPOSITIONS CONTAINING ETHYL ESTERS OF OMEGA-3 POLYUNSATURATED ACIDS IN THE ORDER OF ATRIAL FIBRILLATION. |
GB0403247D0 (en) | 2004-02-13 | 2004-03-17 | Tillotts Pharma Ag | A pharmaceutical composition |
ES2277557B1 (en) | 2005-12-21 | 2008-07-01 | Proyecto Empresarial Brudy, S.L. | USE OF DOCOSAHEXAENOIC ACID FOR THE TREATMENT OF OXIDATIVE CELL DAMAGE. |
PL1962825T3 (en) * | 2005-12-21 | 2014-09-30 | Brudy Tech S L | Use of dha for treating a pathology associated with cellular oxidative damage |
EP2334295B1 (en) | 2008-09-02 | 2017-06-28 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical composition comprising eicosapentaenoic acid and nicotinic acid and methods of using same |
DK2596786T3 (en) | 2009-02-10 | 2020-02-24 | Amarin Pharmaceuticals Ie Ltd | Use of eicosapentaenoic acid ethyl ester for the treatment of hypertriglyceridemia |
WO2010119319A1 (en) | 2009-03-09 | 2010-10-21 | Pronova Biopharma Norge As | Compositions comprising a fatty acid oil mixture and a free fatty acid, and methods and uses thereof |
NZ624963A (en) | 2009-04-29 | 2016-07-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
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SG10201405994UA (en) | 2009-09-23 | 2014-10-30 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical Composition Comprising Omega-3 Fatty Acid And Hydroxy-derivative Of A Statin And Methods Of Using Same |
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 |
AU2011336856A1 (en) | 2010-11-29 | 2013-07-04 | Amarin Pharmaceuticals Ireland Limited | Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity |
CA2826663A1 (en) | 2011-02-07 | 2012-08-16 | Mochida Pharmaceutical Co., Ltd. | Therapeutic agent for diastolic congestive heart failure |
US11291643B2 (en) | 2011-11-07 | 2022-04-05 | Amarin Pharmaceuticals Ireland Limited | Methods of treating hypertriglyceridemia |
WO2013070735A1 (en) | 2011-11-07 | 2013-05-16 | Amarin Pharmaceuticals Ireland Limited | Methods of treating hypertriglyceridemia |
EP2800469B1 (en) | 2012-01-06 | 2021-08-25 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering levels of high-sensitivity (hs-crp) in a subject |
AU2013282394B2 (en) | 2012-06-29 | 2018-04-26 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing the risk of a cardiovascular event in a subject on statin therapy |
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 |
US9814733B2 (en) | 2012-12-31 | 2017-11-14 | A,arin Pharmaceuticals Ireland Limited | Compositions comprising EPA and obeticholic acid and methods of use thereof |
US20140187633A1 (en) | 2012-12-31 | 2014-07-03 | Amarin Pharmaceuticals Ireland Limited | Methods of treating or preventing nonalcoholic steatohepatitis and/or primary biliary cirrhosis |
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 |
US10172818B2 (en) | 2014-06-16 | 2019-01-08 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids |
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 (en) | 2017-05-19 | 2019-01-01 | 愛爾蘭商艾瑪琳製藥愛爾蘭有限公司 | Compositions and Methods for Lowering Triglycerides in a Subject Having Reduced Kidney Function |
US11058661B2 (en) | 2018-03-02 | 2021-07-13 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides in a subject on concomitant statin therapy and having hsCRP levels of at least about 2 mg/L |
KR102296068B1 (en) | 2018-09-24 | 2021-09-02 | 애머린 파마슈티칼스 아일랜드 리미티드 | Methods of Reducing the Risk of a Cardiovascular Event in a Subject |
KR20240012390A (en) | 2021-04-21 | 2024-01-29 | 애머린 파마슈티칼스 아일랜드 리미티드 | How to Reduce Your Risk of Heart Failure |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1308613B1 (en) * | 1999-02-17 | 2002-01-09 | Pharmacia & Upjohn Spa | ESSENTIAL FATTY ACIDS IN THE PREVENTION OF CARDIOVASCULAR EVENTS. |
DE60022987T2 (en) * | 2000-05-22 | 2006-10-19 | Pro Aparts - Investimentos E Consultoria Lda., Funchal | Fatty acid composition containing at least 80% by weight of EPA and DHA |
ITMI20010129A1 (en) * | 2001-01-25 | 2002-07-25 | Pharmacia & Upjohn Spa | ESSENTIAL FATTY ACIDS IN THE THERAPY OF HEART INSUFFICIENCY AND HEART FAILURE |
-
2002
- 2002-02-12 IT IT2002MI000269A patent/ITMI20020269A1/en unknown
-
2003
- 2003-02-05 EP EP03739455A patent/EP1474125A1/en not_active Withdrawn
- 2003-02-05 WO PCT/EP2003/001108 patent/WO2003068216A1/en not_active Application Discontinuation
- 2003-02-05 AU AU2003210210A patent/AU2003210210A1/en not_active Abandoned
Non-Patent Citations (2)
Title |
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None * |
See also references of WO03068216A1 * |
Also Published As
Publication number | Publication date |
---|---|
ITMI20020269A0 (en) | 2002-02-12 |
WO2003068216A1 (en) | 2003-08-21 |
AU2003210210A1 (en) | 2003-09-04 |
ITMI20020269A1 (en) | 2003-08-12 |
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