Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-08-15
1997-01-07
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
549401, 549408, A61K 31355, C07D31122, C07D31172
Patent
active
055917720
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION
The present invention relates to novel tocotrienols and tocotrienol-like compounds displaying biological activity. The tocotrienols and tocotrienol-like compounds of this invention may be conveniently obtained from biological sources or by chemical synthesis and may be used in pharmaceutical compositions, foodstuffs and dietary supplements. This invention also relates to the use of tocotrienols, tocotrienol-like compounds, and mixtures thereof, as hypocholesterolemic, antithrombotic, antioxidizing, antiatherogenic, antiinflammatory and immunoregulatory agents, or as agents useful to decrease lipoprotein (a) concentration in the blood or to increase feed conversion efficiency.
BACKGROUND OF THE INVENTION
Plant constituents have been proven useful in the prevention and treatment of a wide variety of diseases and conditions. For example, barley has been shown to be particularly effective in lowering lipid levels in animal models (A. A. Qureshi et al., "Suppression Of Cholesterogenesis By Plant Constituents", Lipids, 20, pp. 817-24 (1985)). More specifically, .alpha.-tocotrienol, a chromanol isolated from barley extract, has been identified as a therapeutic agent for hypercholesterolemia (A. A. Qureshi et al., "The Structure Of An Inhibitor Of Cholesterol Biosynthesis Isolated From Barley", J. Biol. Chem., 261, pp. 10544-50 (1986)). In addition, tocotrienol, .gamma.-tocotrienol and .delta.-tocotrienol have also been shown to reduce hypercholesterolemia in mammals (European patent application 421,419).
Hypercholesterolemia involves high serum cholesterol levels and is a causative agent of diseases including arteriosclerosis, atherosclerosis, cardiovascular disease and xanthomatosis. In addition, high serum cholesterol levels are seen in patients suffering from diseases including diabetes mellitus, familial hypercholesterolemia, acute intermittent prothyria, anorexia nervosa, nephrotic syndrome, primary cirrhosis and various liver disorders, such as hepatitis and obstructive jaundice. Improvement of lipoprotein profiles and a decrease in total serum and low density lipoprotein cholesterol have been shown to retard the progression of such diseases, as well as to induce regression of clinically significant lesions in hypercholesterolemic patients.
Although the relationship between hypercholesterolemia and its many associated diseases, most notably cardiovascular disease, has been extensively studied, no clear answer to this world-wide problem has yet been found. As a result, coronary artery disease remains the leading cause of death in the United States and other developed countries. Coronary artery disease is the result of complex interactions between a large number of different processes, including lipoprotein metabolism, aggregation of blood platelets, blood coagulation and fibrinolysis. Accordingly, the cardiovascular risk profile of a given patient is dependent on these interactions.
In addition to lowering cholesterol levels, the cardiovascular risk profile of a patient may also be reduced by decreasing the levels of other factors in the serum and the blood. For example, reduction of thromboxane A.sub.2 generation (measured by the levels of thromboxane B.sub.2, a stable metabolite of thromboxane A.sub.2) and platelet factor 4 levels in the serum lessens the risk of cardiovascular disease because of decreased thrombogenic activity.
Thromboxane A.sub.2 and platelet factor 4 levels are also associated with other biological activities. For example, when reduction of these factors is accompanied by a reduction in macrophage cell count, lower tumor necrosis factor (TNF) levels and lower arachidonic acid levels in bodily tissues, reduced levels of prostaglandins, leukotrienes and interleukins are implicated. Reduction of these factors, therefore, leads to a decrease in the inflammation accompanying a wide variety of diseases. In addition, since prostaglandins inhibit glucose-induced insulin release and increase glucagon secretion, an increased insulin to glucagon ratio may also
REFERENCES:
patent: 3064012 (1962-11-01), Folkers et al.
patent: 3122565 (1964-02-01), Kijima et al.
patent: 4603143 (1986-07-01), Schmidt
patent: 4788304 (1988-11-01), Marshall et al.
patent: 5034420 (1991-07-01), Wang
patent: 5138075 (1992-08-01), Ohgaki et al.
patent: 5204373 (1993-04-01), Pearce
patent: 5217992 (1993-06-01), Wright et al.
patent: 5296508 (1994-03-01), Pearce
patent: 5348974 (1994-09-01), Wright et al.
patent: 5393776 (1995-02-01), Pearce
Qureshi et al, Journal of Biological Chemistry, vol. 261, No. 23 (1986) pp. 10544-10550.
Schudel et al, Helvetica Chimica Acta, vol. 46, No. 7 (1963) pp. 2517-2526.
Patent Abstracts of Japan, vol. 9, No. 91 (C-277)(1814) 19 Apr. 1958 of JP,A, 59 222 414 (Kuraray) 12 Dec. 1984).
Lane Ronald H.
Qureshi Asaf A.
Salser Winston A.
LipoGenics, Inc.
Raymond Richard L.
LandOfFree
Tocotrienols and tocotrienol-like compounds and methods for thei does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Tocotrienols and tocotrienol-like compounds and methods for thei, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Tocotrienols and tocotrienol-like compounds and methods for thei will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1764732