| PATENT ASSIGNEE'S COUNTRY | Korea |
| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | 17.10.2000 |
| PATENT TITLE |
Method for preventing or treating elevated blood lipid level-related diseases by administering natural phenolic compounds |
| PATENT ABSTRACT |
A method for treating or preventing an elevated blood lipid level-related diseases such as hyperlipidemia, arteriosclerosis, angina pectoris, stroke and hepatic diseases in a mammal, which comprises administering thereto an effective amount of tannin, gallic acid or ellagic acid. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | September 15, 1999 |
| PATENT FOREIGN APPLICATION PRIORITY DATA | This data is not available for free |
| PATENT REFERENCES CITED |
CA 112:97139, Zhou et al., Jan. 1988. CA 99:98818, Okuda et al., Jan. 1988. |
| PATENT CLAIMS |
What is claimed is: 1. A method for treating or preventing an elevated blood lipid level-related disease in a mammal, which comprises administering thereto an effective amount of tannin, gallic acid, ellagic acid or a mixture thereof. 2. The method of claim 1, wherein the disease is hyperlipidemia, arteriosclerosis, angina pectoris, stroke or fatty liver. 3. The method of claim 1, wherein the mammal is human. 4. The method of claim 1, wherein the tannin, gallic acid, ellagic acid or mixture thereof is administered in the form of a pharmaceutical composition containing an effective amount of tannin, gallic acid, ellagic acid or a mixture thereof and pharmaceutically acceptable excipients, carriers or diluents. 5. The method of claim 4, wherein the effective amount of the tannin, gallic acid, ellagic acid or a mixture thereof ranges from 0.1 to 500 mg/kg of body weight/day. 6. The method of claim 1, wherein the tannin, gallic acid, ellagic acid or a mixture thereof is administered in the form of a health-improving food composition containing the tannin, gallic acid, ellagic acid or a mixture thereof in an amount ranging from 0.01 to 20 wt %. 7. The method of claim 6, wherein the food is meat, chocolate, snack, confectionery, pizza, a health food product or a food product made from cereal flour, gums, dairy products, soups, broths, pastes, ketchups, sauces or vitamin complexes. 8. The method of claim 7, wherein the food product made from cereal flour is bread, cake, cracker, cookie, biscuit or noodle. 9. The method of claim 7, wherein the dairy product is milk, ice cream, cheese or yogurt. 10. The method of claim 1, wherein the tannin, gallic acid, ellagic acid or a mixture thereof is administered in the form of a health-improving beverage composition containing the tannin, gallic acid, ellagic acid or a mixture thereof in an amount ranging from 0.01 to 20 wt %. 11. The method of claim 10, wherein the beverage is a vegetable juice, fruit juice, tea, alcoholic beverage or carbonated beverage. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
FIELD OF THE INVENTION The present invention relates to a method for treating or preventing elevated blood lipid level-related diseases such as hyperlipidemia, arteriosclerosis, angina pectoris, stroke and hepatic diseases in a mammal, which comprises administering thereto an effective amount of tannin, gallic acid or ellagic acid. BACKGROUND OF THE INVENTION It has been reported that blood lipids, especially cholesterol and triglycerides, are closely related to various kind of diseases such as coronary cardio-circulatory diseases, e.g., arteriosclerosis and hypercholesterolemia, and fatty liver. Cholesterol, a fatty steroid alcohol, is a blood lipid produced from saturated fat in the liver. Triglycerides are another type of blood lipids which are known to increase the risk of various diseases. It has also been reported that an elevated blood or plasma cholesterol level causes the deposition of fat, macrophages and foam cells on the wall of blood vessels, such deposit leading to plaque formation and then to arteriosclerosis (see Ross, R., Nature, 362, 801-809 (1993)). One of the methods for decreasing the plasma cholesterol level is alimentotherapy to reduce the ingestion of cholesterol and lipids. Another method is to inhibit the absorption of cholesterol by inhibiting enzymes involved therein. Acyl CoA-cholesterol-o-acyltransferase (ACAT) promotes the esterification of cholesterol in blood. Foam cells are formed by the action of ACAT and contain a large amount of cholesterol ester carried by low density lipoprotein (LDL) in the blood. The formation of foam cells on the wall of artery increases with the ACAT activity, and, accordingly, an inhibitor of ACAT may also be an agent for preventing arteriosclerosis. Further, it has been reported that the blood level of LDL-cholesterol can be reduced by inhibiting the ACAT activity (see Witiak, D. T. and D. R. Feller (eds.), Anti-Lipidemic Drugs: Medicinal, Chemical and Biochemical Aspects, Elsevier, pp159-195 (1991)). Further, it has been reported that hypercholesterolemia can be treated effectively by reducing the rate of cholesterol biosynthesis through the inhibition of cholesterol ester transfer protein (CETP) which mediates the cholesterol transfers between the lipoproteins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which mediates the synthesis of mevalonic acid, an intermediate in the biosynthesis of sterols or isoprenoids (see Cardiovascular Pharmacoloqy, William W. Parmley and Kanu Chatterjee Ed., Wolfe Publishing, pages 8.6-8.7, 1994). Therefore, numerous efforts have been made to develop medicines to inhibit HMG-COA reductase; and, as a result, several compounds derived from Penicillium sp. and Aspergillus sp. have been commercialized. Specifically, Lovastatin.RTM. and Simvastatin.RTM. developed by Merck Co., U.S.A., and Pravastatin.RTM. developed by Sankyo Co., Japan, have been commercialized (see C. D. R. Dunn, Stroke: Trends, Treatment and Markets, SCRIPT Report, PJB Publications Ltd., 1995). However, these medicines are very expensive and a long-term administration thereof is known to induce an adverse side effect in the central nervous system. Further, although Lovastatin.RTM. and Simvastatin.RTM. may reduce the plasma LDL cholesterol level by enhancing the activity of LDL receptor in the liver, they cause side effects such as increase in creatine kinase in the liver and rhabdomyolysis (see Farmer, J. A., et al., Baillers-clin. Endocrinol. Metal., 9, 825-847 (1995)). Accordingly, there has continued to exist a need to develop an inexpensive and non-toxic inhibitor of HMG-COA reductase. Another example of the elevated blood-lipid level-related disease is fatty liver which is causes by excessive intake of fat-containing foods and alcohol. When afflicted by fatty liver, a large amount of lipids is deposited in the liver tissue and the levels of serum GOT (glutamate-oxaloacetate transaminase), GPT (glutamate-pyruvate transaminase) and .gamma.-GTP (.gamma.-glutamyl transpeptidase) become elevated (see T. Banciu et al., Med. Interne., 20, 69-71 (1982); and A. Par et al., Acta. Med. Acad. Sci. Hunq., 33, 309-319 (1976)). In the process of developing fatty liver, fat accumulates in the liver mainly in the form of triglycerides and fatty acids, and also to a minor extent, in the form of cholesterol. Further, it has been reported that one of the major signs of fatty liver is high blood cholesterol and/or triglyceride contents. Therefore, fatty liver is closely related to the level of cholesterol and/or triglycerides in the blood. Hayashi et al. has reported that an extract from green tea improved liver function in a rat by preventing the elevation of serum GOT and GPT (M. Hayashi et al., Nippon Yakuri gaku Zasshi, 100, 391-399 (1992)). It has been reported that the phenolic compounds which exist in the natural world, especially in vegetables and fruits exhibit various useful pharmacological activities against anti-cancer, virus and lipid oxidation and also in preventing circulatory diseases. The present inventors have endeavored to develop a novel pharmacological use of phenolic compounds which are abundantly present in vegetables and fruits. As a result, it has been discovered that tannin, gallic acid and ellagic acid are effective in treating or preventing elevated blood lipid level-related diseases. Specifically, it can greatly reduce plasma cholesterol level; prevent the activities of HMG-COA reductase and ACAT; inhibit the accumulation of macrophage-lipid complex on the endothelial wall of an artery; and prevent hepatic dysfunctions in a mammal. SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a method of administering tannin, gallic acid or ellagic acid for treating or preventing an elevated blood lipid level-related disease. In accordance with one aspect of the present invention, there is provided a method for treating or preventing an elevated blood lipid level-related disease in a mammal, which comprises administering thereto an effective amount of tannin, gallic acid or ellagic acid. BRIEF DESCRIPTION OF THE DRAWINGS The above and other objects and features of the present invention will become apparent from the following description of the invention, when taken in conjunction with the accompanying drawings, in which: FIGS. 1A, 1B and 1C show the arterial endothelium of the rabbits administered with 1% cholesterol; 1% cholesterol plus 1 mg/kg Lovastatin.RTM.; and 1% cholesterol plus 0.1% ellagic acid, respectively; and FIGS. 2A, 2B and 2C present the microscopic features of the livers of the rabbits administered with 1% cholesterol; 1% cholesterol plus 1 mg/kg Lovastatin.RTM.; and 1% cholesterol plus 0.1% ellagic acid, respectively. DETAILED DESCRIPTION OF THE INVENTION Throughout the specification, the term "blood lipid" designates a lipid present in the blood. The blood lipid is represented by cholesterol and triglycerides carried in the blood. The term "high or elevated level" of a blood lipid means higher than normal level, the normal level varying with specific conditions of a patient, such as age, gender and body weight. A high level of blood lipid is ordinarily considered to be harmful to health. The term "elevated blood lipid level-related disease" means a disease which is caused by a high or elevated level of blood lipid, and/or a disease whose symptoms include a high or elevated level of blood lipid. Examples of such a disease include hyperlipidemia, arteriosclerosis, angina pectoris, stroke, hepatic diseases such as fatty liver and the like. Tannin (C.sub.76 H.sub.52 O.sub.46) can be easily extracted from plants, e.g., acorn, persimmon and walnut shell, while gallic acid (C.sub.7 H.sub.6 O.sub.5) and ellagic acid (C.sub.14 H.sub.6 O.sub.8) can be synthesized from tannin in accordance with known methods. Tannin, gallic acid and ellagic acid exert inhibitory as well as therapeutic effects on elevated blood lipid level-related diseases, e.g., hyperlipidemia, arteriosclerosis, angina pectoris, stroke and hepatic diseases. Further, in spite of their potent efficacies, tannin, gallic acid and ellagic acid exhibit no toxicity when they are orally administered to a mouse at a dose of 5,000 mg/kg. Moreover, they do not adversely affect on the liver function. The present invention provides a pharmaceutical composition for treating or preventing elevated blood lipid level-related diseases which comprises tannin, gallic acid or ellagic acid in an effective amount together with a pharmaceutically acceptable excipients, carriers or diluents. A pharmaceutical formulation may be prepared in accordance with any of the conventional procedures. In preparing the formulation, the active ingredient is preferably admixed or diluted with a carrier, or enclosed within a carrier which may be in the form of a capsule, sachet or other container. When the carrier serves as a diluent, it may be a solid, semi-solid or liquid material acting as a vehicle, excipient or medium for the active ingredient. Thus, the formulations may be in the form of a tablet, pill, powder, sachet, elixir, suspension, emulsion, solution, syrup, aerosol, soft and hard gelatin capsule, sterile injectable solution, sterile packaged powder and the like. Examples of suitable carriers, excipients, and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxy-benzoates, propylhydroxybenzoates, talc, magnesium stearate and mineral oil. The formulations may additionally include fillers, anti-agglutinating agents, lubricating agents, wetting agents, flavoring agents, emulsifiers, preservatives and the like. The compositions of the invention may be formulated so as to provide quick, sustained or delayed release of the active ingredient after their administration to a mammal by employing any of the procedures well known in the art. Further, the pharmaceutical composition of the present invention can be administered via various routes including oral, transdermal, subcutaneous, intravenous and intramuscular introduction. In case of human, a typical daily dose of tannin, gallic acid or ellagic acid may range from about 0.1 to 500 mg/kg body weight, preferably 1 to 100 mg/kg body weight, and can be administered in a single dose or in divided doses. However, it should be understood that the amount of the active ingredient actually administered ought to be determined in light of various relevant factors including the condition to be treated, the chosen route of administration, the age, sex and body weight of the individual patient, and the severity of the patient's symptom; and, therefore, the above dose should not be intended to limit the scope of the invention in any way. Moreover, tannin, gallic acid or ellagic acid can be advantageously incorporated in foods or beverages for the purpose of treating or preventing elevated blood lipid level-related diseases. The foods or beverages may include meats; juices such as a vegetable juice (e.g., carrot juice and tomato juice) and a fruit juice (e.g., orange juice, grape juice, pineapple juice, apple juice and banana juice); chocolates; snacks; confectionery; pizza; food products made from cereal flour such as breads, cakes, crackers, cookies, biscuits, noodles and the likes; gums; dairy products such as milk, cheese, yogurt and ice creams; soups; broths; pastes, ketchups and sauces; teas; alcoholic beverages; carbonated beverages; vitamin complexes; and various health foods. The content of the tannin, gallic acid and ellagic acid in a food or beverage may range from 0.01 to 20 wt %, preferably, from 0.1 to 5 wt %. As described above, tannin, gallic acid and ellagic acid can be used as an effective, non-toxic pharmaceutical agent for treating or preventing elevated blood lipid level-related diseases, e.g., hyperlipidemia, arteriosclerosis and hepatic diseases. The following Examples are intended to further illustrate the present invention without limiting its scope. Further, percentages given below for solid in solid mixture, liquid in liquid, and solid in liquid are on a wt/wt, vol/vol and wt/vol basis, respectively, and all the reactions were carried out at room temperature, unless specifically indicated otherwise. |
| PATENT EXAMPLES | This data is not available for free |
| PATENT PHOTOCOPY | Available on request |
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