Pharmaceutical composition comprising omega-3 fatty acid and hydroxy-derivative of a statin and methods of using same

• US 10,493,058 B2
• Filed: 06/03/2015
• Issued: 12/03/2019
• Est. Priority Date: 09/23/2009
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Rowe, Jonathan
• Primary Examiner(s): Ramachandran, Umamaheswari
• Application Number:
  US14/729,615
• Publication Number:
  US 20150265574A1
• Time in Patent Office: 1,644 Days
• 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 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• 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 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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

Abstract

In various embodiments, the present invention provides compositions and methods for treating and/or preventing a cardiovascular-related disease in subject in need thereof.

Claims

1. A method of treating a cardiovascular-related disease in a subject in need thereof by lowering lipid hydroperoxide formation, comprising administering to the subject a composition comprising (a) about 0.1 mg to about 500 mg of a hydroxy-derivative of a statin or pharmaceutically acceptable salt thereof and (b) an oil comprising at least one omega-3 fatty acid, the omega-3 fatty acid comprising at least 95%, by weight, ethyl eicosapentaenoate or at least about 95%, by weight, ethyl docosahexaenoate wherein the subject has a baseline vLDL-C value of about 140 mg/dl to about 200 mg/dl and either (1) a baseline triglyceride level of about 200 mg/dl to about 500 mg/dl or (2) a baseline LDL-C level of about 30 mg/dl to about 300 mg/dl, wherein the hydroxy-derivative of a statin or pharmaceutically acceptable salt thereof is selected from ortho or para hydroxy atorvastatin and pharmaceutically acceptable salts thereof and wherein the cardiovascular-related disease is selected from hypertriglyceridemia, hypercholesterolemia, mixed dyslipidemia, coronary heart disease, vascular disease, stroke, atherosclerosis, arrhythmia, hypertension, and myocardial infarction.

2. The method of claim 1 wherein the omega-3 fatty acid comprises ethyl eicosapentaenoate.

3. The method of claim 1 wherein the oil further comprises ethyl docosahexaenoic acid.

4. The method of claim 1 wherein the hydroxy-derivative of a statin or pharmaceutically acceptable salt thereof is selected from o-hydroxy atorvastatin, p-hydroxy atorvastatin, p-hydroxy atorvastatin calcium, p-hydroxy atorvastatin disodium, o-hydroxy atorvastatin calcium, o-hydroxy atorvastatin lactone, o-hydroxy atorvastatin-d5 calcium, o-hydroxy atorvastatin-d5 disodium, o-hydroxy atorvastatin-d5 lactone, 2-hydroxy atorvastatin bisodium, p-hydroxy atorvastatin lactone, p-hydroxy atorvastatin-d5 calcium, p-hydroxy atorvastatin-d5 lactone, and 4-hydroxy atorvastatin bisodium.

5. The method of claim 1 wherein the cardiovascular-related disease is atherosclerosis.

6. The method of claim 1 wherein the subject also has a non-HDL-C value of about 200 mg/dl to about 400 mg/dl, a total cholesterol value of about 250 mg/dl to about 400 mg/dl, a HDL-C value of about 10 mg/dl to about 100 mg/dl, or a LDL-C value of about 40 mg/dl to about 100 mg/dl.

7. The method of claim 6 wherein the non-HDL-C value, the total cholesterol value, the vLDL-C value, the HDL-C value and the LDL-C value of the subject are mean values.

8. The method of claim 1 wherein the vLDL-C level, the baseline triglyceride level, and the LDL-C level of the subject are mean or median levels.

9. The method of claim 6 wherein the non-HDL-C value, the total cholesterol value, and the HDL-C value are baseline values.