Application of thymol isobutyrate in preparation of blood fat reducing medicine
阅读说明：本技术 百里香酚异丁酸酯在制备降血脂药物中的应用 (Application of thymol isobutyrate in preparation of blood fat reducing medicine ) 是由 成向荣 董文乐 赵蔚 孙进 乐国伟 于 2019-10-18 设计创作，主要内容包括：本发明公开了百里香酚异丁酸酯在制备降血脂药物中的应用,属于降血脂药物技术领域。本发明提供了一种百里香酚异丁酸酯在制备降血脂药物中的应用,所述百里香酚异丁酸酯为8,9-环氧-10-异丁氧基百里香酚异丁酸酯,具有安全性高、降脂作用好的性能,可应用于预防和辅助治疗肥胖、酒精性脂肪肝、非酒精性脂肪肝、2型糖尿病、代谢综合征、冠心病、动脉粥样硬化疾病的药品、食品或功能食品。(The invention discloses an application of thymol isobutyrate in preparation of a blood fat reducing drug, belonging to the technical field of blood fat reducing drugs. The invention provides an application of thymol isobutyrate in preparing a blood fat reducing medicine, wherein the thymol isobutyrate is 8, 9-epoxy-10-isobutoxy thymol isobutyrate, has high safety and good lipid reducing effect, and can be applied to medicines, foods or functional foods for preventing and assisting in treating obesity, alcoholic fatty liver, non-alcoholic fatty liver, type 2 diabetes, metabolic syndrome, coronary heart disease and atherosclerosis.)
1. The application of thymol isobutyrate in preparing the blood fat reducing medicine is characterized in that the thymol isobutyrate is 8, 9-epoxy-10-isobutoxy thymol isobutyrate, and the structural formula of the thymol isobutyrate is as follows:
2. the use according to claim 1, characterized in that it comprises the use for the prevention and adjuvant treatment of obesity, alcoholic fatty liver, non-alcoholic fatty liver, type 2 diabetes, metabolic syndrome, coronary heart disease, atherosclerotic diseases.
3. Use according to claim 1 or 2, for modulating lipid metabolism in cells, oxidative stress.
4. A pharmaceutical composition for reducing blood lipid, wherein the pharmaceutical composition comprises 8, 9-epoxy-10-isobutoxy thymol isobutyrate, and the structural formula is as follows:
5. the pharmaceutical composition of claim 4, further comprising a pharmaceutical carrier and/or a pharmaceutical excipient.
6. The pharmaceutical composition of claim 4 or 5, wherein the pharmaceutical composition is in any pharmaceutically acceptable form.
7. A pharmaceutical formulation for reducing blood lipid, comprising 8, 9-epoxy-10-isobutoxy thymol isobutyrate having the formula:
8. the pharmaceutical formulation of claim 7, wherein the formulation comprises a powder, an injection, a capsule, a tablet, an oral liquid.
9. The health-care product or food or feed for assisting in regulating blood fat is characterized in that the formula of the health-care product or food or feed comprises 8, 9-epoxy-10-isobutoxy thymol isobutyrate, and the structural formula of the health-care product or food or feed is as follows:
10. the blood fat regulator is characterized in that the formula of the blood fat regulator comprises 8, 9-epoxy-10-isobutoxy thymol isobutyrate, and the structural formula of the blood fat regulator is as follows:
Technical Field
The invention relates to an application of thymol isobutyrate in preparation of a blood fat reducing drug, belonging to the technical field of blood fat reducing drugs.
Background
Hyperlipidemia is a systemic disease in which one or more lipids in plasma or serum are higher than in a normal range due to abnormal fat transportation or metabolism, and is particularly characterized by abnormally increased triglyceride, total cholesterol and low-density lipoprotein cholesterol, and is a common chronic disease. The existing research shows that the hyperlipemia can cause diseases such as fatty liver, cirrhosis, pancreatitis, fundus hemorrhage, peripheral vascular diseases, hyperuricemia and the like. In addition, hyperlipidemia is also an important risk factor for the development and progression of coronary heart disease, stroke, myocardial infarction, cerebral infarction, hypertension, impaired glucose tolerance, DIABETES, atherosclerosis (McFarlane SI, Jacober S J, Winer N, et al. control of cardiovascular disorders with DIABETES and hypertension in neurological clinical sites [ J ]. DIABETES CARE,2002,25(4): 718-. Therefore, prevention and treatment of hyperlipidemia is an important link for prevention of related chronic diseases.
At present, the treatment of hyperlipemia comprises four aspects of medicament treatment, operation treatment, gene immunotherapy, health-care product blood fat reduction treatment and the like. The drug therapy of hyperlipemia is the main clinical treatment means at present, the curative effect is definite, the applicability is wide, the commonly used chemical drugs are statins, fibrates, nicotinic acids, resins and the like, however, there are some side effects (Ballantyne C M, Blazing M A, King T R, et al. Effect and safety of ezetimibe-supplemented with simvastatin compounded with atorvastatin [ J ]. The American Journal of medicine, 2004,93(12):1487-1494.), for example, statin drugs may cause myopathies including myalgia, myositis, rhabdomyolysis, etc., niacin may cause nausea, vomiting, in severe cases may induce ulcers and liver damage, and may also aggravate gout and diabetes (The research on main biological properties of Antarctic krill oil and its lipid-lowering mechanism [ D ] in China university, 2019.). Although partial curative effect is achieved by the operation and the gene immunotherapy, the operation and the gene immunotherapy are still in the exploration test stage.
Excessive fat deposits in a plurality of tissues and organs in ectopic way, induces oxidative stress, inflammatory reaction and damages cell morphology and function, and is an important factor for the occurrence and development of lipid metabolism abnormal chronic diseases, such as obesity, alcoholic fatty liver, non-alcoholic fatty liver, type 2 diabetes, metabolic syndrome, coronary heart disease, atherosclerosis and other diseases. The current life style intervention and the resistance treatment aiming at disease symptoms have poor long-term curative effect and are difficult to reverse the development of diseases, and the importance of developing a novel intervention strategy and a prevention and treatment medicine is highlighted. The method searches safe components with good lipid-lowering effect from traditional medicine-food dual-purpose resources, and is one of important directions for developing intervention strategies of lipid metabolism disorder chronic diseases.
The research of the inventor discovers for the first time that 8, 9-epoxy-10-isobutoxy thymol isobutyrate is the main functional component of a plant small black medicine (Inula nervosa wall) which can be used as both medicine and food, and mainly exists in the low-polarity part of the alcohol extract of the small black medicine. The research shows that the small black drug has higher safety, when male and female rats are fed with the pulse-developing inula flower dry powder feed with the dosage of 2000, 4000, 8000mg/kg & BW for 90 days, the result shows that the growth and activity conditions of the rats are normal, indexes such as hematology, hematochemistry, organ coefficients and the like are not obviously abnormal, and pathological damage to the rats is not found in pathological histological examination (Liumin, Hujia Xiang, Xuanjing, Lihui, Qinhui, Jingxiao, pulse-developing inula flower rat chronic toxicity research [ J ] toxicology journal, 2012,26(02): 156-. Research shows that the inula flower with obvious vein is rich in phenols and volatile oil components, wherein thymol and thymol isobutyrate are main components in the volatile oil, and the yunweiling oil soft capsule developed by the volatile oil is used for treating rheumatism and arthralgia (lithocarpus, smithji, chendan, huyibingbing, luoluofang, plum exists and prunus lucidus. HPLC is used for measuring the content of thymol and thymol isobutyrate in the inula flower with different medicinal parts, production areas and collection periods [ J ]. Hunan university of medicine, 2013,33(07): 41-44). However, no report on the blood fat reducing activity of 8, 9-epoxy-10-isobutoxy thymol isobutyrate exists at present. Our studies found for the first time that 8, 9-epoxy-10-isobutoxy thymol isobutyrate has hypolipidemic activity.
Disclosure of Invention
In order to solve the problems, the invention provides the application of thymol isobutyrate in preparing the blood fat reducing medicine, has the properties of high safety and good blood fat reducing effect, can be applied to medicines, foods or functional foods for preventing and assisting in treating obesity, alcoholic fatty liver, non-alcoholic fatty liver, type 2 diabetes, metabolic syndrome, coronary heart disease and atherosclerotic diseases, and has wide economic benefit and social benefit.
The first purpose of the invention is to provide an application of thymol isobutyrate in preparing a blood fat reducing medicine, wherein the thymol isobutyrate is 8, 9-epoxy-10-isobutoxy thymol isobutyrate, and the structural formula of the 8, 9-epoxy-10-isobutoxy thymol isobutyrate is as follows:
in one embodiment of the invention, the application comprises the application in prevention and adjuvant therapy of obesity, alcoholic fatty liver, non-alcoholic fatty liver, type 2 diabetes, metabolic syndrome, coronary heart disease and atherosclerosis.
In one embodiment of the invention, the application is the application of regulating lipid metabolism and oxidative stress of cells.
The second object of the invention is to provide a blood fat reducing pharmaceutical composition, which comprises 8, 9-epoxy-10-isobutoxy thymol isobutyrate, wherein the structural formula of the 8, 9-epoxy-10-isobutoxy thymol isobutyrate is as follows:
in one embodiment of the present invention, the pharmaceutical composition further comprises a pharmaceutical carrier and/or a pharmaceutical excipient.
In one embodiment of the present invention, the dosage form of the pharmaceutical composition is any pharmaceutically acceptable dosage form.
The third purpose of the invention is to provide a blood fat reducing pharmaceutical preparation, which comprises 8, 9-epoxy-10-isobutoxy thymol isobutyrate, wherein the structural formula of the 8, 9-epoxy-10-isobutoxy thymol isobutyrate is as follows:
in one embodiment of the invention, the preparation comprises powder, injection, capsule, tablet and oral liquid.
The fourth purpose of the invention is to provide a dietary supplement or health care product or food or feed for assisting in regulating blood fat, wherein the formulation of the dietary supplement or health care product or food or feed comprises 8, 9-epoxy-10-isobutoxy thymol isobutyrate, and the structural formula is as follows:
the fifth purpose of the invention is to provide a blood lipid regulator, wherein the formula of the blood lipid regulator comprises 8, 9-epoxy-10-isobutoxy thymol isobutyrate, and the formula is as follows:
the invention has the beneficial effects that:
compared with the prior art, the thyme ester composition with the small black medicine and the lipid-lowering effect has the advantages of high safety and good lipid-lowering effect, and can be applied to medicines, foods or functional foods for preventing and assisting in treating obesity, alcoholic fatty liver, non-alcoholic fatty liver, type 2 diabetes, metabolic syndrome, coronary heart disease and atherosclerosis. By administering 20mg/
Drawings
FIG. 18, chemical structural formula of 9-epoxy-10-isobutoxy thymol isobutyrate.
FIG. 28, nuclear magnetic resonance hydrogen spectrum (400MHz) of 9-epoxy-10-isobutoxy thymol isobutyrate.
FIG. 38, effect of 9-epoxy-10-isobutoxy thymol isobutyrate on free fatty acid-induced intracellular lipid accumulation (A) and intracellular reactive oxygen species production (B) of HepG 2.
Detailed Description
The following description of the preferred embodiments of the present invention is provided for the purpose of better illustrating the invention and is not intended to limit the invention thereto.