Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
1999-02-18
2001-08-14
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S461000, C424S462000, C514S772300, C514S781000, C514S782000
Reexamination Certificate
active
06274170
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to compounds for the prevention and treatment of diseases such as atherosclerotic cardiovascular disease (ASCVD). More particularly, the present invention encompasses a comprehensive approach including the use of anti-platelet aggregating agents in conjunction with certain vitamins and minerals which, in combination, have a positive effect on normalizing elevated homocysteine levels in vivo, and which impact free radicals with the use of anti-oxidants implicated in the initiation of atherosclerotic cardiovascular disease.
BACKGROUND INFORMATION
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in most industrial countries. This disease involves large, medium and small arteries throughout the body. In addition to family history, the atherogenic risk factors are known to include smoking, hypertension, diabetes mellitus, cholesterol abnormalities and homocysteinuria. The presence of each additional risk factor markedly aggravates the potential for development of the disease. Although seemingly diverse, the risk factors all damage the artery wall and effect formation of thrombosis.
In the aorta, the largest artery, the artery wall damage may lead to aortic aneurysm or embolism. ASCVD in medium and small arteries can result in sudden occlusion of the vessel or progressive narrowing of the arterial lumen. The symptoms of persons with this disease are dictated by the organs supplied by the effected arteries. Lumenal narrowing of the arteries supplying the heart with blood is called coronary artery disease (CAD). The symptoms include angina, unstable angina, myocardial infarction (MI) and sudden death. Cerebral vascular disease (CVD) symptoms include progressive neural deterioration, transient ischemic attack (TIA), seizures, and cerebral vascular accident (CVA), i.e., stroke. Kidney effects include hypertension, renal infarction and renal failure. Abdominal vascular insufficiency results in abdominal angina and bowel infarction. Peripheral vascular disease (PVD) symptoms include intermittent claudication, gangrene and amputation.
Because atherosclerosis greatly increases the risk of peripheral vascular disease, angina, stroke, some causes of neural degeneration, and heart attacks—the number one cause of death in the USA, a comprehensive approach is needed to address this problem. Despite the broad use of lipid lowering agents, individuals with elevated homocysteine levels are about four times more likely to die of cardiovascular disease than those with normal levels.
Currently accepted clinical treatment of ASCVD includes prescription medications such as beta blockers, angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers, and cholesterol lowering medication. In addition, aspirin is prescribed by cardiologists in many ASCVD conditions. For example, in atherosclerotic heart disease (ASHD), there is evidence of protection from a second MI, if aspirin is used after the sentinel event. Risk of MI is decreased by approximately 50 percent. Vitamins are also currently prescribed by many cardiologists and endocrinologists with intent of preventing both primary (first event), and secondary events.
The affect of arterial thrombus formation contributes to vascular wall damage and acts as the terminal event in a condition like MI. Thrombus formation is a complex interaction of platelets, coagulation factors, and damage to the intima and endothelial layer of the artery wall. Certain risk factors and thrombosis on the vascular wall contribute to damage the inner vascular wall and expose vascular endothelium. Circulating platelets adhere to the exposed subendothelium collagen. The Von Willebrand factor binds platelets causing adhesion. This initiates a series of progressive events stimulating platelet aggregation, and includes prostaglandin H2 and thromboxane A2. Circulating fibrinogen converts to fibrin with the formation of fibrin strands which secure the platelet mass to the arterial wall. If the reaction ceases at this juncture, the artery wall has been weakened and can deteriorate again at any time, and the lumen of the vessel has been diminished to some degree. If the event is self propagating the vessel can occlude and result in infarction of the affected organ. In this overview of the intravascular process of clotting, it must be remembered that this is a delicate balance of the tendency of blood to lyse or clot based on relative amounts of chemicals and enzymes present in the artery wall and platelets. For example, platelet aggregation is mediated by prostacyclin. Prostacyclin is also a vasodilator and is thought to render the vessel lining inert to platelets. Thromboxane causes platelet aggregation and smooth muscle spasm in the arterial wall. Thus, TxA2 and prostacyclin have opposing effects on platelet aggregation and the regulation of thrombus formation is determined by their quantitative balance.
The compounds of the present invention contain a combination of vitamins to help decrease homocysteine levels and modify the oxidation of LDL cholesterol in the initiation of ASCVD. Even mild and moderate elevation of homocysteine levels have been demonstrated to induce cerebrovascular and CAD. Several mechanisms have been proposed including direct toxic effects of homocysteine levels on the vascular endothelium and in proliferation of arterial wall smooth muscle cells. Folate and B6 are required for the degradation of homocysteine to methionine. There is an inverse relation between serum folate and homocysteine levels. It has also been demonstrated that administering folate and B6 will lower homocysteine levels. Fatal CAD incidence is increased as folate level decreases. In one study approximately 28 percent of people had depressed serum folate levels.
Lipid peroxidation, oxidative modification of LDL cholesterol and free radicals are implicated in the initiation of atherosclerosis. LDL undergoes oxidative modification, giving origin to foam cells, a very early sate of atherosclerosis. Macrophages, the precursors of foam cells, can only take up the LDL if it has been oxidized. Oxidized LDL is highly toxic to cells and may be responsible for endothelial damage and destruction of smooth muscle cells. Fatty streaks, an accumulation of foam cells just beneath the arterial endothelium, are precursors of more significant lesions or blockage. The atherosclerotic process also shows an accumulation of lipid peroxidation in the blood and the arterial wall. Interventions that block oxidative modifications of LDL are the subject of multiple studies. If oxidative modification of LDL results in enhanced macrophage uptake, use of an appropriate antioxidant should protect LDL from oxidation, thereby decreasing fatty streaks in the artery wall.
U.S. Pat. No. 5,770,215 to Moshyedi discloses compositions consisting of aspirin and many different types of vitamins and minerals for use in inhibiting vascular occlusion.
Despite the above-noted approaches, a need still exists for an effective compound for treating ASCVD. This invention addresses such problems by lowering artery damaging amino acids while at the same time inhibiting cyclo-oxygenase to block platelet aggregation associated with thrombus formation. Furthermore, a need exists for such a compound which is stable and possesses long shelf life. The present invention has been developed in view of the foregoing, and to address other deficiencies of the prior art.
SUMMARY OF THE INVENTION
An aspect of the present invention is to provide a compound in dosage form which is effective in the treatment of ASCVD. The compound comprises an anti-platelet aggregating agent such as aspirin in combination with multiple vitamins including ascorbic acid, folic acid, vitamin E, vitamin B6 and vitamin B12. The compound further comprises zinc.
Another aspect of the present invention is to provide a compound for the treatment of ASCVD comprising an anti-platelet aggregating agent, zinc, and at least two vitamins selected from the group comprising ascorbic acid, folic acid, vit
Abbott John J.
Heibel Richard
Eckert Seamans Cherin & Mellott , LLC
Spear James M.
Towner Alan G.
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