WO1999044563A2

WO1999044563A2 - Composition for treatment and prevention of coronary artery disease

Info

Publication number: WO1999044563A2
Application number: PCT/US1999/004945
Authority: WO
Inventors: Charles L. Brown, Iii
Original assignee: Individual
Current assignee: Individual
Priority date: 1998-03-06
Filing date: 1999-03-05
Publication date: 1999-09-10
Anticipated expiration: 2000-09-06
Also published as: AU2899099A

Abstract

The present invention is a single tablet or capsule composition that combines many of the antioxidant and/or anti-platelet compounds that can be taken by the patient on a desirably daily basis. The composition is a compilation of anti-platelet therapy provided by aspirin in addition to a range of antioxidant agents. Depending upon the conditions to be treated, additional agents such as cobalamin may be added for hyperhomocysteinemia protection.

Description

COMPOSITION FOR TREATMENT AND

PREVENTION OF CORONARY ARTERY DISEASE

Field of the Invention

The present invention is directed to a dietary composition that is effective in preventing coronary disease.

Background of the Invention

Coronaiy artery disease continues to be the leading cause of mortality in industrial nations. Ischemic heart disease affects more than a million people a year in the U.S. alone. The first symptom in up to a third of these patients is sudden cardiac death.

Peripheral atherosclerotic vascular disease also contributes greatly to the morbidity and mortality of these same patients. Multiple risk factors for the development of vascular disease have been identified over years, and modification of these have shown to be beneficial in reducing morbidity and mortality from cardiovascular disease. These traditional risk factors include cholesterol abnormalities, obesity, diabetes, hypertension and cigarette usage.

The role of oxidized LDL in generating atherosclerosis has recently received widespread attention as an additional risk factor in the development of vascular disease. There is an increasing body of evidence that treatment with antioxidants will have a beneficial affect not only on the development of vascular disease but also on preventing the clinical events, such as myocardial infarction.

Hyperhomocysteinemia has also been recently identified as another potential risk factor for vascular disease. This is especially true in young individuals who have few other risk factors at play. In individuals who are prone to hyperhomocysteinemia, simple folate supplementation has also been shown to retard progression of vascular disease.

Aspirin has been unequivocally shown to have a benefit in preventing heart attack and also reduce potential thrombotic events in several disease states that are related to cardiovascular disease. Regular intake of aspirin is now standard therapy as a primary prevention agent in patients with either heart disease risk factors, or documented coronary artery disease.

Frequently, patients with cardiovascular disease are faced with taking many prescriptions medications in addition to aspirin. Multiple supplements are now routinely being added to provide the potential benefits which are briefly outlined above.

There are many theoretical mechanisms by which oxidized LDL can promote atherosclerosis. These include the recruitment of macrophages into areas of damaged endothelium, the enhancement of endothelium damage by oxidized LDL, and inhabitation of vasodilatation by oxidized LDL. It is felt that antioxidants such as Vitamin E, C and Beta Carotene may help prevent this first step of atherogenesis. There are several studies which have looked at the proposed mechanisms by which antioxidants may prevent atherosclerosis. These include actual demonstrations of decreased rates of plaque formation, and increased rates of atherosclerotic regression. These studies are included in the associated bibliography. There have been four large prospective studies that have looked at individuals consuming high levels of antioxidant vitamins and whether or not they had lower risks of subsequent cardiovascular disease events. These are the NURSES HEALTH STUDIES, HEALTH PROFESSIONALS FOLLOW UP

STUDIES, MASSACHUSETTES HEALTHCARE PANEL STUDY, and THE FIRST NATIONAL HEALTH NUTRITION EXAMINATION SURVEY. These references are again listed in the bibliography. The summary of these studies demonstrated that individuals with high intake of beta carotene, alphatocopherol or

Vitamin C, had lower rates of cardiovascular disease. It should be recognized that these studies cannot be controlled for factors which may influence beneficial outcomes in patients that consume large amounts of antioxidants.

Early trials of Vitamin E therapy have shown a benefit in controlling symptoms of cardiovascular disease. The CHAOS Trial, published in Lancet in March, 1996, showed a reduction in the rate of non-fatal MI in patients treated with Vitamin E, who had demonstrated angiographically proven symptomatic coronary atherosclerosis. Stephens, N.G., et al., Randomised controlled trial of Vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS), The Lancet, Vol. 347, No. 9004, p. 781-786. The effect of Vitamin E therapy on cardiovascular death rate was not defined in this study and warrants further investigation.

The effect of Vitamin E therapy on cardiovascular death rate was not defined in this study and warrants further investigation.

There are numerous ongoing trials of antioxidant therapy and its role in primary and secondary prevention of cardiovascular disease. These include the Physicians' Health

Study, The Women's Health Study and The Supplementation

EnVitamines It Mineraux Antioxydants Trial (SU.VI.MAX). These are all primary prevention trials. The secondary prevention trials which are ongoing include the Women's Antioxidant Cardiovascular Study, Heart Protection Study and The Heart Outcomes Prevention Evaluation Study. These all examine the use of Beta Carotene, Vitamin E, Aspirin, Selenium, Zinc in the use of primary and secondary prevention.

There have been several trials to indicate the benefits of aspirin therapy, particularly in secondary prevention of cardiovascular and cerebral vascular events. Over the last decade, aspirin therapy has evolved into the cornerstone of treatment for patients with known coronary artery disease. The results of a mete analysis of 18,000 patients revealed that aspirin alone was as effective as a combination of aspirin and dipyridamole and more effective than sulfinpyrazone in reducing cardiovascular mortality, non-fatal reinfarction and non-fatal stroke.

Two studies have examined the use of aspirin in primary prevention. The United States Physicians Health Study examining more than 22,000 physicians between the ages of 40 and 84, demonstrated a 44% reduction in acute myocardial infarction (MI) in the aspirin treated group. This effect was limited to those patients greater than 50 years of age. The cardiovascular death rates in the two groups did not differ. The British Primary Prevention Trial did not show a significant difference although sample size was smaller, at approximately 5,000 patients. As a result of these studies, benefits associated with the use of aspirin for primary prevention, were considered to be limited.

Mild to moderate hyperhomocysteinemia has been linked to both cerebrovascular and coronary artery disease. In patients with elevated homocysteine, supplementation with folate has been shown to reduce homocysteine levels by enhancing the conversion of homocysteine to methionine. Folate consumption and low serum folate levels have been linked with an increased rate of fatal coronary artery disease. In appropriate individuals with abnormal homocysteine levels, folate supplementation may provide benefit by normalizing these serum levels.

What is needed is a single composition that combines the various antioxidant and anti-platelet therapies. Such a composition would decrease the risk of coronary disease and would greatly increase patient compliance with recommend therapeutic and preventative regimens.

Summary of the invention

The present invention is a single tablet or capsule composition that combines many of the antioxidant and/or anti- platelet compounds that can be taken by the patient on a desirably daily basis. The composition is a compilation of anti-platelet therapy provided by aspirin in addition to a range of antioxidant agents. Depending upon the condition to be treated, additional agents such as cobalamin and folate are added for hyperhomocysteinemia protection.

The present invention provides a composition which streamlines the administration of many commonly advised non- prescription agents. These are already in widespread use in cardiovascular disease patients. The present invention also includes standard doses of aspirin in addition to a series of antioxidants, all of which have similar effects on the vasculature. In certain individuals who have demonstrated hyperhomocysteinemia, folate and cobalamin could be included in the composition.

Thus, the present invention is effective in protecting patients who have suffered a cardiac event from suffering another event, and is effective in preventing a cardiac event in healthy individuals.

Accordingly, it is an object of the present invention to provide compositions and methods that will protect individuals from coronary disease. It is another object of the present invention to provide compositions that can be taken orally.

It is another object of the present invention to provide compositions and methods for treating and preventing coronary disease that will result in high compliance in the majority of patients.

Another object of the present invention is to ease administration of multiple supplements for patients already on numerous medications.

It is yet another object of the present invention, to provide formulations and methods for preventing and treating coronary disease wherein the formulations comprise Vitamin E, Vitamin C, beta carotene, selenium, cobalamin, folate and aspirin.

These and other objects, features and advantages of the present invention will become apparent after a review of the following detailed description of the disclosed embodiments and the appended claims.

Detailed Description

The present invention is a composition that is useful for patients suffering from coronary artery disease or for healthy patients to prevent coronary artery disease. The composition of the present invention may be manufactured to include either in one pill or one tablet, or alternatively in a preset combination of pills or tablets the compounds provided in table 1 below:

TABLE 1

Optionally, the compounds listed in Table 2 can be added to the composition for certain patients, i.e., those patients in need of hyperhomocysteinemia protection:

TABLE 2

The compounds listed in Tables 1 and 2 are commercially available from pharmaceutical suppliers (i.e. Sigma-Aldrich, St. Louis, MO) familiar to those skilled in the art.

The use of a composition according to the present invention is for individuals interested in the potential benefits of both primary and secondary prevention of coronary disease or peripheral vascular disease. Primary prevention would be for those individuals who have not manifested signs of either peripheral or coronary artery disease. Secondary prevention would be for those individuals who have had signs or symptoms related to documented peripheral or coronary disease.

The composition of the present invention is desirably administered on a daily basis, but the composition of the present invention can be administered more or less often. For example, the composition of the present invention can be administered up to four times daily or can be administered once every two days depending upon the needs of the patient.

The use would be as a daily supplement, either alone or in combination with prescription medications. For those patients on prescription medications, the composition would be used under the direction of the patient's physician. The composition of the present invention can be administered as a pill or a tablet or as a combination of pills and/or tablets. It is to be understood that excipients may be added to the composition to aid in the manufacture of the pill or tablet. The terms "pill" and "tablet" are used herein interchangeably.

Manufacture of such a pill or tablet is well know to those of ordinary skill in the art.

It should be understood, of course, that the foregoing relates only to preferred embodiments of the present invention and that numerous modifications or alterations may be made therein without departing from the spirit and the scope of the invention as set forth in the appended claims.

Claims

Claims:

1. A composition comprising an effective amount of vitamin E, vitamin C, aspirin, beta carotene, and selenium.

2. The composition of Claim 1, further containing cobalamin.

3. The composition of Claim 1, further containing folate.

4. The composition of Claim 1 wherein the composition is administered in the form of a tablet.

5. A method of preventing coronary artery diseas'e comprising the administration to a human or animal a composition containing an effective amount of vitamin E, vitamin C, aspirin, beta carotene, and selenium.

6. The method of Claim 5, wherein the composition further contains cobalamin.

7. The method of Claim 5, wherein the composition further contains folate.

8. The method of Claim 5, wherein the composition is administered in the form of a tablet.