Compositions containing natural lycopene and natural tocopherol

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C514S762000, C514S763000, C514S824000

Reexamination Certificate

active

06362221

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to the prevention or treatment of cardiovascular disease and more particularly to natural compositions which exert a protective action on the cardiovascular system against high levels of serum lipid and/or cholesterol. More particularly, the present invention relates to pharmaceutical compositions comprising a protective amount of natural lycopene, i.e., an amount of lycopene which protects the body against risks of high levels of cholesterol and/or lipid. The present invention is also directed to methods that prevent high serum lipid and cholesterol levels in a mammal, including humans, thereby lowering the risks of developing cardiovascular disease.
BACKGROUND OF THE INVENTION
Reduction of cholesterol greatly lowers the incidence of cardiovascular disease. Thus, it has been reported in
JAMA
1984; 251:351-64 that lowering of serum cholesterol levels with drugs prevents heart attacks. Coronary angiographic studies have also demonstrated the benefits of lower serum cholesterol in the prevention of coronary heart disease. See, for example, Levy et al,
Circulation,
69:32S-37 (1984). Other studies also reported the benefits of lower cholesterol in slowing the growth of atherosclerotic lesions. See, for example, Blankenhorn et al.,
JAMA,
257:3233-40 (1987).
The drugs which are being used in these studies are, for example, clofibrate, gemfibrozil, fenofibrate and bezafibrate or a combination of cholestyramine and niacin. These reports clearly support the theory that lowering of serum cholesterol level will retard coronary atherogenesis and therefore reduce the risk of cardiovascular disease.
One of the problems with the therapy described above is that they are all pharmaceutical compounds which tend to require a long course of therapy. Unfortunately, considerable undesirable side effects are experienced by a number of patients.
Several therapeutic approaches for using vitamin E have been proposed. One such approach is described in the articles, “Vitamin E Consumption And The Risk Of Coronary Disease In Women” by Stampfer et al.,
The New England Journal of Medicine,
328: 1444-9 (1993), and “Vitamin E Consumption And The Risk of Coronary Heart Disease In Men” by Rimm et al.,
The New England Journal of Medicine,
328: 1450-6 (1993), which disclose that oxidation of low-density lipoprotein (LDL) plays a role in atherosclerosis. It appears that the oxidation of LDL increases their incorporation into the arterial intima which is an essential step in atherogenesis.
Thus, in the foregoing articles, investigators have studied the effect of taking vitamin E and the risk of coronary disease and observed that the use of vitamin E supplements in middle-aged women is associated with a reduced risk of coronary heart disease. Similarly, an association between a high intake of vitamin E and a lower risk of coronary heart disease was also observed in men.
In another study reported in
Lancet,
342: 1379-84 (1993), it was observed that high beta-carotene intake reduced the risk of myocardial infarction. Beta-carotene has also been suggested as useful in reducing vascular events in patients with chronic stable angina. See, Gaziano et al., “Beta Carotene Therapy for Chronic Stable Angina,”
Circulation
82:III, Abstract No. 0796 (1990).
In spite of the foregoing attempts to develop a method for preventing or treating high levels of serum cholesterol and/or lipids, there still exists a need in the art for a composition and method for protecting a mammal, including humans, against high serum cholesterol and lipid levels without the disadvantages and side effects associated with conventional drug therapy.
SUMMARY OF THE INVENTION
Surprisingly, the present inventors have now found that a patient can be protected against the development of cardiovascular disease without the use of conventional drug therapy by the compositions and methods of the present invention. The compositions of the present invention comprise as an active ingredient an effective protective amount of natural lycopene in an inert pharmaceutically acceptable carrier. The composition comprises an amount of natural lycopene which protects the body against the risks of high levels of serum cholesterol and lipid.
Generally, the method comprises the step of administering to a mammal, including humans, in need of preventing or treating high levels of serum cholesterol or lipids, the composition of the present invention. The composition is preferably administered until the serum cholesterol is reduced and maintained at less than 200 mg per decaliter.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
According to the present invention, the inventors have discovered a composition in unit dosage form which protects the body against high serum cholesterol and lipid levels. These compositions comprise as an active ingredient an effective amount of natural lycopene to prevent or treat high levels of serum cholesterol and lipids.
Lycopene is a natural red carotinoid which occurs for example in tomatoes. It can also be produced synthetically. See for example U.S. Pat. No. 5,208,381. However, it is natural lycopene which is intended in the practice of the present invention.
Generally speaking to have the desired protective action a dose of approximately 1 mg to approximately 10 mg daily for a 70 kg adult is suggested until the cholesterol level is lowered to less than 200 mg per deciliter. The precise amount of natural lycopene administered to a patient, of course, depends on a wide variety of factors such as the age and overall health of the patient, whether other pharmaceuticals and nutritionals being administered, and the like. It will be realized that if the patient has been diagnosed for advanced stages of atherosclerosis, that is, treatment of an ongoing condition, dosages at the higher end of this range is suggested. However, if only for the protective or preventive action, dosage at the lower end may be sufficient.
To broaden and enhance the therapeutic spectrum of the compositions of the present invention, other known naturally occurring substances may be included. These include, for example, natural beta-carotene. Alternatively, lycopene can be combined with natural tocopherol, especially alpha-tocopherol, with or without natural beta-carotene. The natural beta-carotene is preferably obtained from natural sources, such as palm oil or algae.
Beta-carotene, provitamin A, is readily metabolized by the body into vitamin A when required. There is also increasing evidence which suggests that there is a therapeutic benefit to beta-carotene itself, independent of vitamin A activity.
The primary source of the beta-carotene is an algae named
Dunaliella salina.
The algal cell functions just like an ordinary plant cell. It is photosynthetic, converting carbon dioxide from the atmosphere into cell material and to provide energy. This is done by the green chlorophyll in the cell which is normally not visible as it is masked by the intense orange color of the beta-carotene.
Natural beta-carotene from the algae comprises an approximately equal mixture of cis and trans isomers with the cis form of beta carotene being more soluble in oil than synthetic trans beta carotene.
Synthetic beta-carotene is derived from synthetic organic chemicals and is a crystalline form of beta-carotene, primarily the trans isomer (a molecular configuration). The synthetic form is not the focus of the present invention which is directed to natural source products because of the advantages associated with their use.
The synthetic crystals of beta-carotene are difficult to dissolve in organic chemical solvents, implying that the human body would have similar, or greater, difficulties in assimilating the compound.
The natural carotenoids are mixture of compounds. Those include beta-carotene, alpha-carotene, lutein, cryptoxanthin, zeaxanthin and lycopen.
The natural carotinoids are a mixture of cis and trans isomers while the synthetic carotenoids are all trans isomers.
Betatene, natural mixed carotenoids, is

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