Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids

• US 10,172,818 B2
• Filed: 06/16/2015
• Issued: 01/08/2019
• Est. Priority Date: 06/16/2014
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Mason, Richard Preston
• Primary Examiner(s): Katakam, Sudhakar
• Application Number:
  US15/312,113
• Publication Number:
  US 20170087111A1
• Time in Patent Office: 1,302 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 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• 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: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• 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 methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of reducing or preventing small dense LDL (“sdLDL”) oxidation in a subject, the method comprising administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.

Claims

1. A method of reducing small dense LDL (“

sdLDL”

) oxidation in a subject in need thereof, the method comprising;

determining a baseline oxidized sdLDL level in the subject; and

administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof in an amount effective to provide 4 g of eicosapentaenoic acid or a derivative thereof to the subject daily, wherein the baseline oxidized sdLDL level is determined prior to administering the pharmaceutical composition to the subject.

2. The method of claim 1, wherein the pharmaceutical composition comprises eicosapentaenoic acid or a derivative thereof, wherein an amount of eicosapentaenoic acid present in the pharmaceutical composition is selected from the group consisting of at least at 80%, at least at 90%, at least at 95%, and at least at 96%, by weight of all fatty acids (and/or derivatives thereof) that are present in the composition.

3. The method of claim 1, wherein the pharmaceutical composition comprises no docosahexaenoic acid or esters thereof.

4. The method of claim 1, wherein the reduction occurs by a free radical chain-breaking mechanism.

5. The method of claim 1 further comprising determining a second oxidized sdLDL level in the subject after administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof in an amount effective to provide 4 g of eicosapentaenoic acid or a derivative thereof to the subject daily, wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level and/or wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has not received the pharmaceutical composition.

6. The method of claim 5, wherein the method further comprises administering o-hydroxyatorvastatin to the subject.

7. The method of claim 6, wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has received the o-hydroxyatorvastatin but not the pharmaceutical composition.

8. The method of claim 6, wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has received the pharmaceutical composition but not the o-hydroxyatorvastatin.

9. The method of claim 1, wherein the subject has a baseline triglyceride level of at least 500 mg/dL.

10. The method of claim 1, wherein the subject has a baseline triglyceride level of about 200 mg/dL to 499 mg/dL.

11. The method of claim 10, wherein the subject is on statin therapy, optionally stable statin therapy.

12. The method of claim 1, wherein the subject is hyperglycemic or is diabetic.