Methods of treating mixed dyslipidemia

• US 10,220,013 B2
• Filed: 09/22/2016
• Issued: 03/05/2019
• Est. Priority Date: 04/29/2009
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Osterloh, Ian, Wicker, Pierre, Braeckman, Rene, Soni, Paresh, Manku, Mehar
• Primary Examiner(s): Weddington, Kevin E
• Application Number:
  US15/273,430
• Publication Number:
  US 20170014366A1
• Time in Patent Office: 894 Days
• Field of Search: 514558, 514559, 514560
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/222 with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/12 : Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

The present disclosure relates to, inter alia, methods of treating mixed dyslipidemia with ethyl eicosapentaenoate.

Claims

1. A pharmaceutical composition comprising (a) an omega-3 polyunsaturated fatty acid (PUFA) comprising eicosapentaenoic acid (EPA) or a derivative of EPA, docosahexaenoic acid (DHA) or a derivative of DHA, and (b) at least one polyoxyethylene-polyoxypropylene block copolymer.

2. The pharmaceutical composition of claim 1 further comprising at least one additional fatty acid selected from the group consisting of linolenic acid (LA), derivative of LA, arachidonic acid (AA), derivative of AA, alpha-linolenic acid (ALA), derivative of ALA, stearadonic acid (STA), derivative of STA, eicosatrienoic acid (ETA), derivative of ETA, docosapentaenoic acid (DPA), derivative of DPA, or combinations thereof.

3. The pharmaceutical composition of claim 1 wherein the derivative of EPA is ethyl-EPA.

4. The pharmaceutical composition of claim 1 wherein the derivative of DHA is ethyl-DHA.

5. The pharmaceutical composition of claim 1 comprising a mixture of EPA or a derivative of EPA and DHA or a derivative of DHA, in a ratio of EPA or a derivative of EPA to DHA or a derivative of DHA from greater than about 2:

1 to about 19;

1, wherein the EPA or a derivative of EPA and DHA or a derivative of DHA in combination comprise more than about 50% by weight of total fatty acids present in the pharmaceutical composition.

6. The pharmaceutical composition of claim 1 comprising a mixture of EPA or a derivative of EPA and DHA or a derivative of DHA, wherein the EPA or a derivative of EPA comprises about 50% by weight of total fatty acids present in the pharmaceutical composition and the DHA or a derivative of DHA comprises about 20% by weight of total fatty acids present in the pharmaceutical composition.

7. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition further comprises at least one surfactant selected from the group consisting—

a polysorbate, a poloxamer, or combinations thereof.

8. The pharmaceutical composition of claim 7 wherein the at least one polysorbate is present in an amount from about 0.25% to about 15% by weight of the pharmaceutical composition.

9. The pharmaceutical composition of claim 8 wherein the at least one polysorbate is Polysorbate 80.

10. The pharmaceutical composition of claim 9 wherein the at least one poloxamer is present in an amount from about 0.25% to about 15% by weight of the composition.

11. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition comprises a mixture of Polysorbate 80 and the polyoxyethylene-polyoxypropylene block copolymer.

12. The pharmaceutical composition of claim 1 further comprising at least one antioxidant.

13. The pharmaceutical composition of claim 12 wherein the at least one antioxidant is selected from the group consisting of tocopherol, lecithin, citric acid, and ascorbic acid.

14. The pharmaceutical composition of claim 13 wherein the tocopherol comprises from about 0.0001% to about 5% of the total weight of the pharmaceutical composition.

15. The composition of claim 1, wherein the omega PUFA is in an amount between about 50% and about 95%, by weight.

16. The composition of claim 1, wherein the omega-3 PUFA is present in an amount of about 50 mg to about 5000 mg.

17. The composition of claim 1, wherein the composition is administered to provide a daily dose of omega-3 PUFA in an amount of about 1 mg to about 10,000 mg.

18. The composition of claim 7, wherein the at least one surfactant comprises polyoxyethylene fatty acid glyceride and/or polyoxyethylene fatty acid oil.

19. The composition of claim 7, wherein the at least one surfactant comprises polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan esters, or combinations thereof.

20. The composition of claim 7, wherein the surfactant is in an amount between about 0.25% and about 15%, by weight.