Method of reducing the risk of oxidative stress

• US 20050065184A1
• Filed: 08/27/2004
• Published: 03/24/2005
• Est. Priority Date: 08/29/2003
• Status: Abandoned Application

• Current Assignee: aaiPharma, Inc.
• Original Assignee: aaiPharma, Inc.
• Inventors: Wolf, Gerald
• Application Number:
  US10/927,790
• Publication Number:
  US 20050065184A1
• Time in Patent Office: Days
• US Class Current: 514/323
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• 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 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 38/488 Aspartic endopeptidases (3.4.23), e.g. pepsin, chymosin, renin, cathepsin E
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

A method for ascertaining whether a subject has oxidative stress; evaluating the level of oxidative stress in a subject; reducing the risk of an adverse event, especially an adverse cardiovascular event, resulting from oxidative stress; treating oxidative stress; and evaluating the efficacy of treatment with at least one pharmaceutical composition for reducing oxidative stress is provided.

Claims

1. A method of treating a subject having oxidative stress, said method comprising administering to said subject an effective amount of at least one pharmaceutical composition for reducing or preventing an increase of the level of at least one biomarker for oxidative stress.

2. The method of claim 1 wherein the at least one pharmaceutical composition comprises an inhibitor of the renin-angiotensin-aldosterone system.

3. The method of claim 2 wherein the inhibitor of the renin-angiotensin-aldosterone system comprises an angiotensin converting enzyme inhibitor.

4. The method of claim 3 wherein the angiotensin converting enzyme inhibitor is selected from the group consisting of AB-103, ancovenin, benazeprilat, BRL-36378, BW-A575C, CGS13928C, CL242817, CV-5975, EU-4865, EU-4867, EU-5476, foroxymithine, FPL 66564, FR-900456, Hoe-065, 15B2, ketomethylureas, KRI-1177, KRI-1230, L681176, libenzapril, MDL-27088, MDL-27467A, moveltipril, MS-41, nicotianamine, phenacein, pivopril, rentiapril, RG-5975, RG-6134, RG-6207, RGH0399, ROO-911, RS-10085-197, RS-2039, RS 5139, RS-86127, RU-44403, S-8308, SA-291, spiraprilat, SQ26900, SQ-28084, SQ-28370, SQ-28940, SQ-31440, utibapril, WF-10129, Wy-44221, Wy-44655, Y23785, P-0154, zabicipril, Asahi Brewery AB-47, alatriopril, BMS 182657, Asahi Chemical C-111, Asahi Chemical C-112, Dainippon DU-1777, mixanpril, zofenoprilat, 1(-(I-carboxy-6-(4-piperidinyl)hexyl)amino)-1-oxopropyl octahydro-IH-indole-2-carboxylic acid, Bioproject BP1.137, Chiesi CHF 1514, Fisons FPL-66564, idrapril, perindoprilat, Servier S-5590, alacepril, cilazapril, delapril, enalapril, enalaprilat, fosinoprilat, imidapril, ramiprilat, saralasin acetate, temocapril, trandolapril, trandolaprilat, ceranapril, and uinaprilat.

5. The method of claim 2 wherein the inhibitor of the renin-angiotensin-aldosterone system comprises an angiotensin receptor blocker.

6. The method of claim 5 wherein the angiotensin receptor blocker is selected from the group consisting of saralasin, saralasin, candesartan, CGP-63170, EMD-66397, KT3-671, LRB/081, valsartan, A-81282, BIBR-363, BIBS-222, BMS-184698, CV11194, EXP-3174, KW-3433, L-161177, L-162154, LR-B/057, LY-235656, PD150304, U-96849, U-97018, UP-275-22, WAY-126227, WK-1492.2K, YM-31472, losartan, E-4177, EMD-73495, eprosartan, HN-65021, irbesartan, L-159282, ME-3221, SL-91.0102, tasosartan, telmisartan, UP-269-6, YM-358, CGP-49870, GA-0056, L-159689, L-162234, L-162441, L-163007, PD-123177, A81988, BMS-180560, CGP-38560A, CGP-48369, DA-2079, DE-3489, DuP-167, EXP-063, EXP-6155, EXP-6803, EXP-7711, EXP-9270, FK-739, HR-720, ICI D6888, ICI-D7155, ICI-D8731, isoteoline, KRI-1177, L-158809, L-158978, L-159874, LR B087, LY-285434, LY-302289, LY-315995, RG-13647, RWJ-38970, RWJ-46458, S-8307, S-8308, saprisartan, sarmesin, WK-1360, X-6803, ZD-6888, ZD-7155, ZD-8731, BIBS39, CI-996, DMP-811, DuP-532, EXP-929, L163017, LY-301875, XH-148, XR-510, zolasartan, and PD-123319.

7. The method of claim 2 wherein the inhibitor of the renin-angiotensin-aldosterone system comprises a renin inhibitor.

8. The method of claim 7 wherein the renin inhibitor is selected from the group consisting of renin antibodies, analogs of the prosegment of renin, analogs of pepstatin, and analogs of the renin analogs of the prosegment of renin, analogs of pepstatin, and analogs of the renin substrate angiotensinogen, remikiren (Ro 42-5892), A-72517, and A-74273.

9. The method of claim 1 wherein the at least one pharmaceutical composition comprises an inhibitor of the aldosterone system.

10. The method of claim 9 wherein the inhibitor of the aldosterone system is an aldosterone antagonist.

11. The method of claim 10 wherein the inhibitor is selected from the group consisting of spironolactones and eplerenones.

12. The method of claim 1 wherein the at least one pharmaceutical composition comprises a statin compound.

13. The method of claim 12 wherein the statin compound is selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, atorvastatin calcium, cerivastatin, mevastatin, fluindostatin, velostatin, compactin, dihydrocompactin, and dalvastatin.

14. The method of claim 1 wherein the at least one biomarker for oxidative stress is at least one member of the group selected CRP, IL-6, PAI-1, fibrinogen and urinary isoprostane.

15. The method of claim 1 wherein said administering occurs prior to treatment of at least one disease state associated with a surrogate for cardiovascular disease.

16. A method of treating a subject at risk of an adverse cardiovascular event as the result of having elevated oxidative stress, said method comprising administering to said subject an effective amount of at least one pharmaceutical composition for reducing or preventing the increase of the level of at least one biomarker for oxidative stress.

17. The method of claim 16 wherein said administering occurs prior to treatment of at least one disease state associated with a surrogate for cardiovascular disease.

18. The method of claim 16 wherein the at least one surrogate for cardiovascular disease is selected from the group consisting of hypertension, hypercholesterolemia, diabetes mellitus, and hyperhomocysteinemia.

19. A method of reducing the risk of an adverse cardiovascular event in a subject having elevated oxidative stress, said method comprising administering to said subject an effective amount of at least one pharmaceutical composition for reducing or preventing the increase of the level of at least one biomarker for oxidative stress.

20. The method of claim 19 wherein said administering occurs prior to treatment of at least one disease state associated with a surrogate for cardiovascular disease.

21. The method of claim 19 wherein the at least one surrogate for cardiovascular disease is selected from the group consisting of hypertension, hypercholesterolemia, diabetes mellitus, and hyperhomocysteinemia.

22. A method for treating a subject suspected of having oxidative stress, said method comprising:

measuring the oxidative stress of a subject by testing for at least one biomarker for oxidative stress from said subject;

determining whether the at least one tested biomarker is indicative of oxidative stress; and

wherein when the at least one tested biomarker is indicative of oxidative stress, treating said subject to reduce or prevent an increase of the level of the least one biomarker for oxidative stress.

23-69. -69. (Cancelled)