WO1990004391A1 - Oral dosage forms of omega-3 polyunsaturated acids - Google Patents

Oral dosage forms of omega-3 polyunsaturated acids Download PDF

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Publication number
WO1990004391A1
WO1990004391A1 PCT/GB1989/001251 GB8901251W WO9004391A1 WO 1990004391 A1 WO1990004391 A1 WO 1990004391A1 GB 8901251 W GB8901251 W GB 8901251W WO 9004391 A1 WO9004391 A1 WO 9004391A1
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WO
WIPO (PCT)
Prior art keywords
enteric
acid
dosage form
claimε
enteric dosage
Prior art date
Application number
PCT/GB1989/001251
Other languages
French (fr)
Inventor
Roger Andre PLÜSS
Original Assignee
J.B. Tillott Limited
Tillotts Pharma Ag
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 J.B. Tillott Limited, Tillotts Pharma Ag filed Critical J.B. Tillott Limited
Publication of WO1990004391A1 publication Critical patent/WO1990004391A1/en

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    • 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
    • A61K9/4891—Coated capsules; Multilayered drug free capsule shells
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids

Definitions

  • the present invention relates to the oral administration of omega-3 polyunsaturated acids especially, but not exclusively, all-cis-5,8,11,14,17- eicosapentaenoic acid (i.e. all-cis-fatty acid 20:5 omega-3; EPA) and/or 22:6 omega-3-docosahexaenioc acid (DHA).
  • omega-3 polyunsaturated acids especially, but not exclusively, all-cis-5,8,11,14,17- eicosapentaenoic acid (i.e. all-cis-fatty acid 20:5 omega-3; EPA) and/or 22:6 omega-3-docosahexaenioc acid (DHA).
  • DHA omega-3-docosahexaenioc acid
  • US-A-4097602 disclosed the inhibition of blood platelet aggregation by administra ⁇ tion of EPA in its free acid form or a ⁇ a salt or lower alkyl ester. More recently, US-A-4526902 disclosed the prophlyaxis of thrombo-e bolic condition ⁇ by ⁇ imultan- eou ⁇ administration of EPA and/or DHA with one or more of linoleic, gamma-linolenic or dihomo-gamma-linolenic
  • SUBSTITUTE SHEET acid SUBSTITUTE SHEET acid.
  • the said acids can be pre ⁇ ent a ⁇ the free acid or a ⁇ pharmaceutically acceptable ⁇ alt ⁇ , or e ⁇ ters or amides thereof.
  • Formulations used or proposed for the administration of EPA and/or DHA include oral, rectal, topical, vaginal, intrapulmonary and parenteral formulations.
  • oral formulations have been employed, especially soft gelatine capsules.
  • a problem associated with such oral administration i ⁇ belching resulting in an unpleasant fishy smell and taste following disintegration or dissolution of the oral formulation in the stomach.
  • Such a problem previously wa ⁇ well established in the administration of cod liver oil capsules which, because of the vitamin A and D content of the oil, have been used for many decades a ⁇ a dietary supplement.
  • EPA and/or DHA When EPA and/or DHA are administered in the form of a derivative thereof, usually an alkyl ester or triglyceride, it must be converted into the free fatty acid before being absorbed by the body.
  • the conversion of ester is carried out in the stomach by the pancreatic enzyme Lipase.
  • Lipase the pancreatic enzyme Lipase.
  • the production of Lipase may be reduced, or even eliminated, as a result of disease or due to alcohol, smoking, stress etc. Accordingly, there is good rea ⁇ on to prefer to use EPA and/or DHA in the free acid form.
  • enteric do ⁇ age form i.e. a dosage form which, when taken orally, will pas ⁇ through the ⁇ tomach substantially without relea ⁇ e of the active principle but which will relea ⁇ e the active principle in the inte ⁇ tine.
  • enteric do ⁇ age form ⁇ are widely u ⁇ ed, there was, to the best of our knowledge, no previous proposal that omega-3 polyunsaturated free acids should be presented in enteric dosage form and it had not been appreciated that there was any reason or
  • the pre ⁇ ent invention re ⁇ ide ⁇ in the enteric pre ⁇ entation of omega-3 polyun ⁇ aturated free acid ⁇ a ⁇ distinct from enteric dosage form ⁇ in general.
  • the present invention provides an enteric dosage form containing as an active principle an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof. Further, the invention provides the use of said enteric dosage form ⁇ in the treatment or prophylaxi ⁇ of thrombo— embolic condition ⁇ . It also provides ⁇ aid enteric dosage forms for the treatment of other conditions for which omega-3 polyunsaturated acids in their free or precursor form, such a ⁇ their glyceride or alkyl esters, are indicated. Such conditions include rheumatoid arthritis, diabetes mellitu ⁇ , migraine, p ⁇ oria ⁇ is, cancer, and hyperchole ⁇ terolaemia and a ⁇ a dietetic.
  • omega-3 polyunsaturated acid is EPA, DHA or a mixture thereof. It i ⁇ pre ⁇ ent in free acid form or a ⁇ a pharmaceutically acceptable salt thereof and can be pre ⁇ ent as the ⁇ ole active principle or with other active principle ⁇ , e ⁇ pecially linoleic acid, gamma— linolenic acid and/or dihomo-gamma-linolenic acid in free acid or salt form. Omega-3 polyunsaturated acid ⁇ are readily oxidi ⁇ ed and hence an antioxidant u ⁇ ually will be pre ⁇ ent.
  • the pre ⁇ ently preferred antioxidant is gamma-tocopherol but other pharmacologically acceptable antioxidant ⁇ can be used, for example butylated hydroxy anisole, butylated hydroxy toluene, propyl gallate or a quinone.
  • the enteric dosage form may also contain one or more pharmaceutically acceptable excipients depending upon the precise nature of the do ⁇ age form.
  • the enteric dosage form can be an enterically coated tablets containing the omega-3 polyunsaturated acid in a microencapsulated form or loaded on a ⁇ uitable absorbent.
  • the enteric do ⁇ age form i ⁇ an enterically coated capsule, especially a soft or, more e ⁇ pecially, hard gelatine cap ⁇ ule.
  • Enteric coating ⁇ are widely used in the pharmaceutical indu ⁇ try and are formed of ⁇ ub ⁇ tance ⁇ which are relatively in ⁇ oluble in the acid medium of the ⁇ tomach but di ⁇ integrate in the medium of the ⁇ mall inte ⁇ tine.
  • Suitable enteric coating ⁇ include cellulo ⁇ e acetate phthalate and polymethacrylate.
  • the omega-3 polyunsaturated acid will be admini ⁇ tered in a daily do ⁇ age of 20 to 50 mg/kg, e ⁇ pecially 30-40 mg/kg.
  • the actual do ⁇ e will vary
  • each unit dose will contain 250 to 1000 mg especially 400 to 800 mg.
  • Example Transparent hard gelatine cap ⁇ ule ⁇ ( ⁇ ize 0), con ⁇ i ⁇ ting of 14% water and 86% gelatine were each filled with 500 mg of a fi ⁇ h oil concentrate (EPACHOL 600) . ⁇ upplied by Messrs. EPA Limited (Windsor, Ontario, Canada).
  • the concentrate contains about 32% by weight free EPA, about 28% by weight free DHA and 0.02% by weight gamma-tocopherol. It does not contain any chole ⁇ terol, cetoleic acid or saturated fatty acid ⁇ and i ⁇ an oily liquid of brown colour having a characteri ⁇ tic odour. It has the following phy ⁇ ico-chemical propertie ⁇ :- acid value 160 iodine value 340 peroxide value 3 saponification value 190 ⁇ aponifiable matter 1.25 relative density 0.935 refractive index 1.49
  • the filled gelatine cap ⁇ ule ⁇ were placed in a coating tower where they were carried in a heated (55 # C) air stream whilst being sprayed with an enteric coating ⁇ olution.
  • the coating solution had the following composition by weight:- cellulose acetate phthalate BPC 40 mg ethyl phthalate BPC 12 mg meth lene chloride 616 mg ethyl alcohol 95% I.B. 128 mg.

Abstract

Omega-3 polyunsaturated acids, especially EPA and/or DHA, in free acid form or as pharmaceutically acceptable salts are presented in enteric dosage forms to overcome the problems of belching and the risk of oxidation in the stomach associated with the oral administration of said acids. The acids can be used alone or with other active principles, especially linolenic acid, gamma-linolenic acid, and/or dihomo-gamma-linolenic acid. Preferably, the enteric dosage form is an enterically coated capsule such as a soft or, especially, hard gelatine capsule.

Description

ORAL DOSAGE FORMS OF OMEGA-3 POLYUNSATURATED ACIDS The present invention relates to the oral administration of omega-3 polyunsaturated acids especially, but not exclusively, all-cis-5,8,11,14,17- eicosapentaenoic acid (i.e. all-cis-fatty acid 20:5 omega-3; EPA) and/or 22:6 omega-3-docosahexaenioc acid (DHA). In particular, it provides enteric dosage forms of omega-3 polyunsaturated acids.
It has been known for many years that the low occurrence of aetherosclerotic cardiovascular diseases amongst Greenland Eskimos and the low mortality rate of cardiovascular patients in Scandinavia is attributable to the consumption of relatively high amounts of fish oil. The relevant active ingredients in fish oil have been identified as the omega-3 polyunsaturated acids EPA and DHA, which are present in their triglyceride and/or other eεterified forms. The use of EPA in free acid form or aε a pharmaceutically acceptable salt, ester or amide is disclosed in GB-A-1604554 and GB-A— 2033745. Further, US-A-4097602 disclosed the inhibition of blood platelet aggregation by administra¬ tion of EPA in its free acid form or aε a salt or lower alkyl ester. More recently, US-A-4526902 disclosed the prophlyaxis of thrombo-e bolic conditionε by εimultan- eouε administration of EPA and/or DHA with one or more of linoleic, gamma-linolenic or dihomo-gamma-linolenic
: SUBSTITUTE SHEET acid. The said acids can be preεent aε the free acid or aε pharmaceutically acceptable εaltε, or eεters or amides thereof.
Formulations used or proposed for the administration of EPA and/or DHA include oral, rectal, topical, vaginal, intrapulmonary and parenteral formulations. Usually, oral formulations have been employed, especially soft gelatine capsules. However, a problem associated with such oral administration iε belching resulting in an unpleasant fishy smell and taste following disintegration or dissolution of the oral formulation in the stomach. Such a problem previously waε well established in the administration of cod liver oil capsules which, because of the vitamin A and D content of the oil, have been used for many decades aε a dietary supplement.
When EPA and/or DHA are administered in the form of a derivative thereof, usually an alkyl ester or triglyceride, it must be converted into the free fatty acid before being absorbed by the body. The conversion of ester is carried out in the stomach by the pancreatic enzyme Lipase. However not all patients produce sufficient Lipase to properly convert the derivative into free fatty acid form. For example, the production of Lipase may be reduced, or even eliminated, as a result of disease or due to alcohol, smoking, stress etc. Accordingly, there is good reaεon to prefer to use EPA and/or DHA in the free acid form.
SUBSTITUTESHEET However, becauεe of their polyunεaturation the free fatty acidε are prone to rapid oxidation, which problem is not encountered with the eεterε. Although antioxidantε, e.g. gamma-tocopherol, are uεed to prevent or at leaεt reduce oxidation, the present Inventor suspectε that εignificant oxidation of the acid takes place in the stomach thereby reducing the availability of the fatty acidε.
The teaching and practice in the art to date has been that the free acid iε adminiεtered orally in the εame manner aε the esters.
The present Inventor has appreciated that the long standing problem of belching with the accompanying fishy smell and taste asεociated with the oral administration of EPA and/or DHA and the risk of oxidation in the εtomach can εimply and readily be overcome by uεe of an enteric doεage form (i.e. a dosage form which, when taken orally, will pasε through the εtomach substantially without releaεe of the active principle but which will releaεe the active principle in the inteεtine). Although enteric doεage formε are widely uεed, there was, to the best of our knowledge, no previous proposal that omega-3 polyunsaturated free acids should be presented in enteric dosage form and it had not been appreciated that there was any reason or
SUBSTITUTE SHEET advantage arising from the use of that form. Thuε, the preεent invention reεideε in the enteric preεentation of omega-3 polyunεaturated free acidε aε distinct from enteric dosage formε in general. The present invention provides an enteric dosage form containing as an active principle an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof. Further, the invention provides the use of said enteric dosage formε in the treatment or prophylaxiε of thrombo— embolic conditionε. It also provides εaid enteric dosage forms for the treatment of other conditions for which omega-3 polyunsaturated acids in their free or precursor form, such aε their glyceride or alkyl esters, are indicated. Such conditions include rheumatoid arthritis, diabetes mellituε, migraine, pεoriaεis, cancer, and hypercholeεterolaemia and aε a dietetic.
Aε indicated previouεly, it iε preferred that the omega-3 polyunsaturated acid is EPA, DHA or a mixture thereof. It iε preεent in free acid form or aε a pharmaceutically acceptable salt thereof and can be preεent as the εole active principle or with other active principleε, eεpecially linoleic acid, gamma— linolenic acid and/or dihomo-gamma-linolenic acid in free acid or salt form. Omega-3 polyunsaturated acidε are readily oxidiεed and hence an antioxidant uεually will be preεent. The preεently preferred antioxidant is gamma-tocopherol but other pharmacologically acceptable antioxidantε can be used, for example butylated hydroxy anisole, butylated hydroxy toluene, propyl gallate or a quinone.
The enteric dosage form may also contain one or more pharmaceutically acceptable excipients depending upon the precise nature of the doεage form. Suitably, the enteric dosage form can be an enterically coated tablets containing the omega-3 polyunsaturated acid in a microencapsulated form or loaded on a εuitable absorbent. However, it iε preferred that the enteric doεage form iε an enterically coated capsule, especially a soft or, more eεpecially, hard gelatine capεule.
Enteric coatingε are widely used in the pharmaceutical induεtry and are formed of εubεtanceε which are relatively inεoluble in the acid medium of the εtomach but diεintegrate in the medium of the εmall inteεtine. Suitable enteric coatingε include celluloεe acetate phthalate and polymethacrylate.
Uεually, the omega-3 polyunsaturated acid will be adminiεtered in a daily doεage of 20 to 50 mg/kg, eεpecially 30-40 mg/kg. The actual doεe will vary
SUBSTITUTESHEET depending inter alia on the identity of the omega-3 polyunsaturated acid and the nature and degree of the disorder being treated. Usually, each unit dose will contain 250 to 1000 mg especially 400 to 800 mg. The following iε a description, by way of example only, of a presently preferred embodiment of the invention.
Example Transparent hard gelatine capεuleε (εize 0), conεiεting of 14% water and 86% gelatine were each filled with 500 mg of a fiεh oil concentrate (EPACHOL 600) .εupplied by Messrs. EPA Limited (Windsor, Ontario, Canada). The concentrate contains about 32% by weight free EPA, about 28% by weight free DHA and 0.02% by weight gamma-tocopherol. It does not contain any choleεterol, cetoleic acid or saturated fatty acidε and iε an oily liquid of brown colour having a characteriεtic odour. It has the following phyεico-chemical propertieε:- acid value 160 iodine value 340 peroxide value 3 saponification value 190 εaponifiable matter 1.25 relative density 0.935 refractive index 1.49
The filled gelatine capεuleε were placed in a coating tower where they were carried in a heated (55#C) air stream whilst being sprayed with an enteric coating εolution. The coating solution had the following composition by weight:- cellulose acetate phthalate BPC 40 mg ethyl phthalate BPC 12 mg meth lene chloride 616 mg ethyl alcohol 95% I.B. 128 mg.
Sufficient coating solution was applied to provide a theoretical coating of 6 mg/2, which is an excesε of that theoretically required in order to allow for loεses during the coating process.
SUBSTITUTE SHEET

Claims

1. An enteric dosage form containing as an active principle an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof.
2. An enteric dosage form as claimed in Claim 1, wherein εaid acid iε EPA, DHA or a mixture thereof.
3. An enteric doεage form as claimed in Claim 1 or Claim 2, wherein εaid acid is present in free acid form 4 An enteric dosage form aε claimed in any one of the preceding claimε, wherein εaid acid or εalt iε preεent as the εole active principle.
5 An enteric doεage form aε claimed in any one of Claimε 1 to 4 wherein εaid acid or εalt iε preεent with another active principle εelected from linoleic acid, gamma-linolenic acid, and/or dihomo-gamma— linolenic acid in free acid form or aε a pharmaceutically acceptable εalt thereof.
6 An enteric doεage form aε claimed in any one of the preceding claimε containing an antioxidant amount of gamma-tocopherol.
7 An enteric doεage form aε claimed in any one of the preceding claimε which iε an enterically coated tablet containing the εaid acid or salt in a microencapsulated form or loaded on an abεorbent.
SUBSTITUTE SHEET 8 An enteric dosage form as claimed in any one of Claimε 1 to 6 which is an enterically coated capsule.
9 An enteric doεage form aε claimed in Claim 8, wherein the capεule is a soft gelatine capsule. 10 An enteric doεage form as claimed in Claim 8, wherein the capsule is a hard gelatine capsule. 11 An enteric dosage form aε claimed in any one of the preceding claims, wherein each unit dose contains 250 to 1000 mg of εaid omega-3 acid or salt. 12 An enteric dosage form as claimed in Claim 11, wherein each unit doεe containε 400 to 800 mg of εaid omega-3 acid or εalt.
13 An enteric dosage form substantially aε hereinbefore deεcribed in the Example. 14 The use of an enteric dosage form aε claimed in any one of the preceding claimε in the treatment or prophylaxiε of thro bo-embolic conditionε.
15 The use of an enteric dosage form aε claimed in any one of Claims 1 to 13 for the treatment of rheumatoid arthritis.
16 The use of an enteric dosage form as claimed in any one of Claimε 1 to 13 for the treatment of diabetes mellitus.
17 The use of an enteric doεage form aε claimed in any one of Claims 1 to 13 for the treatment of migraine . 18 The uεe of an enteric dosage form aε claimed in any one of Claimε 1 to 13 for the treatment of pεoriasiε.
19 The uεe of an enteric dosage form as claimed in any one of Claims 1 to 13 for the treatment of cancer.
20 The use of an enteric dosage form aε claimed in any one of Claimε 1 to 13 for the treatment of hypercholesterolaemla.
21 The uεe of an enteric dosage form aε claimed in any one of Claimε 1 to 13 aε a dietetic.
PCT/GB1989/001251 1988-10-21 1989-10-20 Oral dosage forms of omega-3 polyunsaturated acids WO1990004391A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8824709A GB2223943A (en) 1988-10-21 1988-10-21 Oral disage forms of omega-3 polyunsaturated acids
GB8824709.3 1988-10-21

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WO1990004391A1 true WO1990004391A1 (en) 1990-05-03

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CA (1) CA2000881A1 (en)
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Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5550156A (en) * 1991-01-24 1996-08-27 Martek Corporation Microbial oil mixtures and uses thereof
DE19930030A1 (en) * 1999-06-30 2001-01-11 Meduna Arzneimittel Gmbh Oral dosage form
US8188146B2 (en) 1999-01-27 2012-05-29 Amarin Corporation Plc. Highly purified ethyl EPA and other EPA derivatives
US8293727B2 (en) 2009-02-10 2012-10-23 Amarin Pharmaceuticals Ireland Limited Methods of treating hypertriglyceridemia
US8298554B2 (en) 2009-04-29 2012-10-30 Amarin Pharmaceuticals Ireland Limited Stable pharmaceutical composition and methods of using same
US8383678B2 (en) 2004-02-13 2013-02-26 Chrysalis Pharma Ag Type a gelatin capsule containing PUFA in free acid form
US8410086B2 (en) 2009-06-15 2013-04-02 Amarin Pharmaceuticals Ireland Limited Compositions and methods for lowering triglycerides
US8691871B2 (en) 2009-04-29 2014-04-08 Amarin Pharmaceuticals Ireland Limited Methods of treating mixed dyslipidemia
US9050309B2 (en) 2012-01-06 2015-06-09 Omthera Pharmaceuticals, Inc. DPA-enriched compositions of omega-3 polyunsaturated fatty acids in free acid form
US9259408B2 (en) 2005-12-21 2016-02-16 Brudy Technology S.L. Use of DHA, EPA or DHA-derived EPA for treating a pathology associated with cellular oxidative damage
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
US9452151B2 (en) 2013-02-06 2016-09-27 Amarin Pharmaceuticals Ireland Limited Methods of reducing apolipoprotein C-III
US9492545B2 (en) 2012-05-07 2016-11-15 Omthera Pharmaceuticals Inc. Compositions of statins and omega-3 fatty acids
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
US9603826B2 (en) 2012-06-29 2017-03-28 Amarin Pharmaceuticals Ireland Limited Methods of reducing the risk of a cardiovascular event in a subject on statin therapy
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
US9814733B2 (en) 2012-12-31 2017-11-14 A,arin Pharmaceuticals Ireland Limited Compositions comprising EPA and obeticholic acid and methods of use thereof
US9827219B2 (en) 2012-01-06 2017-11-28 Amarin Pharmaceuticals Ireland Limited Compositions and methods for lowering levels of high-sensitivity C-reactive protein (HS-CRP) in a subject
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
US10314803B2 (en) 2008-09-02 2019-06-11 Amarin Pharmaceuticals Ireland Limited Pharmaceutical composition comprising eicosapentaenoic acid and nicotinic acid and methods of using same
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
US10493008B2 (en) 2005-12-21 2019-12-03 Brudy Technology, S.L. Use of DHA, EPA or DHA-derived EPA for treating a pathology associated with cellular oxidative damage
US10493058B2 (en) 2009-09-23 2019-12-03 Amarin Pharmaceuticals Ireland Limited Pharmaceutical composition comprising omega-3 fatty acid and hydroxy-derivative of a statin and methods of using same
US10537544B2 (en) 2011-11-07 2020-01-21 Amarin Pharmaceuticals Ireland Limited Methods of treating hypertriglyceridemia
US10561631B2 (en) 2014-06-11 2020-02-18 Amarin Pharmaceuticals Ireland Limited Methods of reducing RLP-C
US10668042B2 (en) 2018-09-24 2020-06-02 Amarin Pharmaceuticals Ireland Limited Methods of reducing the risk of cardiovascular events in a subject
US10888539B2 (en) 2013-09-04 2021-01-12 Amarin Pharmaceuticals Ireland Limited Methods of treating or preventing prostate cancer
US10966968B2 (en) 2013-06-06 2021-04-06 Amarin Pharmaceuticals Ireland Limited Co-administration of rosiglitazone and eicosapentaenoic acid or a derivative thereof
US10966951B2 (en) 2017-05-19 2021-04-06 Amarin Pharmaceuticals Ireland Limited 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
US11141399B2 (en) 2012-12-31 2021-10-12 Amarin Pharmaceuticals Ireland Limited Methods of treating or preventing nonalcoholic steatohepatitis and/or primary biliary cirrhosis
US11179362B2 (en) 2012-11-06 2021-11-23 Amarin Pharmaceuticals Ireland Limited Compositions and methods for lowering triglycerides without raising LDL-C levels in a subject on concomitant statin therapy
US11291643B2 (en) 2011-11-07 2022-04-05 Amarin Pharmaceuticals Ireland Limited Methods of treating hypertriglyceridemia
US11547710B2 (en) 2013-03-15 2023-01-10 Amarin Pharmaceuticals Ireland Limited Pharmaceutical composition comprising eicosapentaenoic acid and derivatives thereof and a statin
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
US11712428B2 (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

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8906369D0 (en) * 1989-03-20 1989-05-04 Tisdale Michael J Eicosapentaenoic acid
US5457130A (en) * 1989-03-20 1995-10-10 Cancer Research Campaign Technology Limited Eicosapentaenoic acid used to treat cachexia
FR2663222A1 (en) * 1990-06-13 1991-12-20 Medgenix Group Sa OILY LIQUID MICROCAPSULE.
GB9509764D0 (en) * 1995-05-15 1995-07-05 Tillotts Pharma Ag Treatment of inflammatory bowel disease using oral dosage forms of omega-3 polyunsaturated acids
GB2300807B (en) * 1995-05-15 1999-08-18 Tillotts Pharma Ag Oral dosage forms of omega-3 polynunsaturated acids for the treatment of inflammatory bowel disease
US5840715A (en) * 1995-12-11 1998-11-24 Inholtra Investment Holdings & Trading, N.V. Dietary regimen of nutritional supplements for relief of symptoms of arthritis
EP0855908B1 (en) * 1995-12-11 2002-02-06 Omni Nutraceuticals, Inc. Dietary regimen of nutritional supplements for relief of symptoms of arthritis
US20070141181A1 (en) 1998-02-13 2007-06-21 Nutramax Laboratories, Inc. Use of anabolic agents, anti-catabolic agents, antioxidant agents, and analgesics for protection, treatment and repair of connective tissues in humans and animals
US6451771B1 (en) 1999-02-12 2002-09-17 Nutramax Laboratories, Inc. Use of anabolic agents anti-catabolic agents and antioxidant agents for protection treatment and repair of connective tissues in humans and animals
US6797289B2 (en) 1998-02-13 2004-09-28 Nutramax Laboratories, Inc. Use of anabolic agents, anti-catabolic agents, antioxidant agents, and analgesics for protection, treatment and repair of connective tissues in humans and animals
US20040176451A1 (en) * 2001-06-18 2004-09-09 Tadakazu Tamai Pparg agonistic medicinal compositions
WO2003043570A2 (en) * 2001-11-15 2003-05-30 Galileo Laboratories, Inc. Formulations and methods for treatment or amelioration of inflammatory conditions
CA2499501A1 (en) * 2002-09-27 2004-04-08 Martek Biosciences Corporation Prophylactic docosahexaenoic acid therapy for patients with subclinical inflammation
CA2515328A1 (en) * 2003-03-05 2004-09-16 Solvay Pharmaceuticals Gmbh Use of omega-3-fatty acids in the treatment of diabetic patients
US7759507B2 (en) 2003-09-05 2010-07-20 Abbott Laboratories Lipid system and methods of use
GB0428384D0 (en) * 2004-12-24 2005-02-02 Sla Pharma Ag Eicosapentaenoic acid
US20090214466A1 (en) * 2005-05-09 2009-08-27 Levin Bruce H Methods of Alleviating Disorders and Their Associated Pain
CN104288138A (en) * 2008-12-31 2015-01-21 尼特罗米加公司 Nutraceuticals containing nitro fatty acids
JP6018712B2 (en) * 2014-04-25 2016-11-02 株式会社山田養蜂場本社 Absorption accelerator for unsaturated fatty acids

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2090529A (en) * 1980-06-27 1982-07-14 Nippon Oils & Fats Co Ltd Thrombosis-prophylactic and curing agent
WO1988002221A1 (en) * 1986-09-29 1988-04-07 Kabivitrum Ab A granulate containing gamma linolenic acid, eicosapentaenoic acid and/or docosahexaenoic acid, the method for its manufacturing, its use in edible products, and a tablet containing it

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2090529A (en) * 1980-06-27 1982-07-14 Nippon Oils & Fats Co Ltd Thrombosis-prophylactic and curing agent
WO1988002221A1 (en) * 1986-09-29 1988-04-07 Kabivitrum Ab A granulate containing gamma linolenic acid, eicosapentaenoic acid and/or docosahexaenoic acid, the method for its manufacturing, its use in edible products, and a tablet containing it

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
STN Information Services, Data Base: CHEMICAL ABSTRACTS, Accession No.: 109(25):229174b,* see the Abstracts & JP-A-63216440 (Showa) 8 September 1988* *
STN International Information Services, Data Base: CHEMICAL ABSTRACTS, Accession No.: 102(16):137846z,* see the Abstract & JP-A-59225115 (Showa) 18 December 1984* *

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