阅读说明：本技术 雷公藤内酯酮的应用 (Application of triptonide ) 是由 周泉生 曹志飞 于 2018-06-15 设计创作，主要内容包括：本发明涉及医药技术领域,公开了雷公藤内酯酮的应用。本发明发现中草药单体雷公藤内酯酮能显著地降低高脂饮食小鼠胸主动脉粥样斑块的形成、三尖瓣脂肪的堆积和胶原纤维的形成,并显著地降低高脂饮食小鼠的体重和脂肪堆积。此外,雷公藤内酯酮还能明显地降低高脂饮食肥胖小鼠血液中的低密度脂蛋白和胆固醇的含量。这表明雷公藤内酯酮对动脉粥样硬化具有治疗作用,因而可以应用在相关药物的制备中,又因动脉粥样硬化是冠心病、脑梗死、外周血管病的主要原因,其也可应用在冠心病、脑梗死、外周血管病的相关药物制备中。(The invention relates to the technical field of medicines, and discloses application of triptonide. The invention finds that Chinese herbal medicine monomer triptolide ketone can remarkably reduce the formation of thoracic aortic atherosclerotic plaques, the accumulation of tricuspid valve fat and the formation of collagen fibers of high-fat diet mice, and remarkably reduce the weight and fat accumulation of the high-fat diet mice. In addition, triptolide can also significantly reduce the content of low-density lipoprotein and cholesterol in the blood of high-fat diet obese mice. The triptolide ketone has a treatment effect on atherosclerosis, so that the triptolide ketone can be applied to preparation of related medicines, and can also be applied to preparation of related medicines for coronary heart disease, cerebral infarction and peripheral vascular disease because the atherosclerosis is the main reason of the coronary heart disease, the cerebral infarction and the peripheral vascular disease.)

1. Application of triptonide or pharmaceutically acceptable salt thereof in preparing medicines for preventing and/or treating atherosclerosis is provided.

2. The use according to claim 1, wherein the medicament is a capsule, a microcapsule, a tablet, a granule, a pill, a dispersion powder, an injection, a liposome or an oral liquid.

3. A medicament for preventing and/or treating atherosclerosis, coronary heart disease, cerebral infarction or peripheral vascular disease is characterized by comprising effective amount of triptonide or pharmaceutically acceptable salt thereof and pharmaceutically acceptable medicinal auxiliary materials.

4. The drug according to claim 3, wherein the drug adjuvant is one or more selected from the group consisting of solvents, propellants, solubilizers, solubilizing agents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, tonicity adjusting agents, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integration agents, penetration enhancers, pH adjusting agents, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, encapsulation agents, humectants, absorbents, diluents, flocculants, deflocculants, filter aids, and release retardants.

5. The medicament of claim 3, wherein the triptonide or the pharmaceutically acceptable salt thereof accounts for 0.05 wt% to 90 wt% of the total weight of the medicament.

6. The medicament of claim 3 or 5, wherein the triptonide or the pharmaceutically acceptable salt thereof accounts for 15 wt% to 60 wt% of the total weight of the medicament.

7. Application of triptonide or pharmaceutically acceptable salt thereof in preparing medicine for preventing and/or treating coronary heart disease, cerebral infarction or peripheral vascular disease is provided.

Technical Field

The invention relates to the technical field of medicines, in particular to application of triptonide.

Background

Atherosclerosis is the leading cause of coronary heart disease, cerebral infarction, peripheral vascular disease. Atherosclerosis (atherosclerosis) is a common disease that seriously endangers human health. In recent years, the incidence of the disease is obviously increased in China. According to autopsy results, the detection rates of coronary artery and aortic atherosclerotic lesions are 58.36% and 88.31% respectively in the population of 40-49 years old, and gradually increase with the age. Atherosclerosis generally refers to a group of arteriosclerotic diseases including: atherosclerosis,Medial calcification of arteries and arteriosclerotic. Risk factors for atherosclerosis hyperlipidemia is well known and hyperlipidemia (hyperlipemia) is an important risk factor for atherosclerosis. Hyperlipidemia may actually be considered as hyperlipoproteinemia, and is generally characterized by 12-14 hours fasting by adults with blood triglyceride over 160mg/dl (1.81mmol/L) and cholesterol over 260mg/dl (6.76 mmol/L). Numerous epidemiological investigations have demonstrated that sustained elevated levels of plasma Cholesterol (CHO), Low Density Lipoprotein (LDL) and Very Low Density Lipoprotein (VLDL) are positively correlated with the incidence of atherosclerosis.

In recent years, scholars at home and abroad have more deep understanding on the pathogenesis of atherosclerosis, and the pathogenesis of atherosclerosis is not completely clear at present, and the theories mainly include a lipid infiltration theory, a smooth muscle cell clone theory, a thrombosis theory, an endothelial injury reaction theory and an inflammatory reaction theory. Therefore, the prevention and treatment of the disease comprises drug treatment and operation treatment. The drug therapy only aims at blood fat adjusting drugs such as statins, antiplatelet drugs such as aspirin, and thrombolytic and anticoagulant drugs; vasodilators and the like are applied in the corresponding treatment aiming at ischemic symptoms such as angina pectoris; surgical treatment includes surgical procedures such as recanalization or reconstruction or bypass grafting of stenotic or occluded coronary, renal and limb arteries to restore blood supply to the arteries. The literature reports that the Huangshi pulse-activating decoction has obvious effect on preventing and treating atherosclerosis. Currently, the epidemiology of atherosclerosis has made great progress, but it is still a weak link in China. Therefore, an ideal medicament for treating atherosclerosis is not available at present. Therefore, there is an urgent need to develop a novel anti-atherosclerotic effect against cardiovascular and cerebrovascular diseases caused by atherosclerosis.

Disclosure of Invention

In view of the above, the present invention aims to provide an application of Triptonide (TN) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for preventing and/or treating atherosclerosis.

Tripterygium wilfordii lactone (TN) is a monomer substance extracted from the whole plant or peeled xylem of Tripterygium wilfordii hook F.H. Chen et S.F. Chen of Celastraceae, with purity up to 98%, and has the following structure:

research reports that triptolide ketone has the effects of male antifertility, leukemia resistance and malignant tumor resistance, but the triptolide ketone has not been reported at home and abroad in the aspect of resisting atherosclerosis.

The invention researches the effect of triptolide on mice on high-fat and high-cholesterol diet, and proves that the triptolide can remarkably reduce the weight, fat accumulation, thoracic aortic atherosclerotic plaque formation, tricuspid valve fat accumulation and collagen fiber formation of the mice on high-fat and high-cholesterol diet after treatment, and reduce the contents of LDL and CHO1 in the blood of the mice on high-fat diet and obesity. The experimental results show that the triptonide has a treatment effect on atherosclerosis. Since atherosclerosis is the main cause of coronary heart disease, cerebral infarction and peripheral vascular disease, triptonide or pharmaceutically acceptable salt thereof can be used for preventing and/or treating coronary heart disease, cerebral infarction and peripheral vascular disease, and can be applied to the preparation of drugs for the diseases.

The triptonide can be an artificial extract, such as an extract obtained by extracting the whole plant or peeled xylem part of tripterygium wilfordii; or artificial chemical synthesis substances, such as synthesis according to the existing chemical synthesis process.

The invention provides application of triptolide or pharmaceutically acceptable salts thereof in preparing medicaments for preventing and/or treating atherosclerosis, coronary heart disease, cerebral infarction or peripheral vascular diseases, wherein the medicaments can be any suitable dosage form in the field of medicaments, such as capsules, microcapsules, tablets, granules, pills, dispersion powder, injections, liposomes or oral liquids.

According to the related application, the invention also provides a medicament for preventing and/or treating atherosclerosis, coronary heart disease, cerebral infarction or peripheral vascular disease, which comprises effective amount of triptolide or pharmaceutically acceptable salt thereof and pharmaceutically acceptable medicinal auxiliary materials; or consists of effective dose of triptolide or pharmaceutically acceptable salt thereof and pharmaceutically acceptable pharmaceutical excipients.

Preferably, the pharmaceutical excipients are selected from the pharmaceutical excipients generally used in the art according to the dosage form to be prepared, such as one or more selected from solvents, propellants, solubilizers, solubilizing agents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, tonicity adjusting agents, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integration agents, permeation enhancers, pH adjusting agents, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, encapsulation agents, humectants, absorbents, diluents, flocculants, deflocculants, filter aids, and release retardants.

Preferably, the triptonide or the pharmaceutically acceptable salt thereof accounts for 0.05-90 wt% of the total weight of the medicine; further, the triptonide or the pharmaceutically acceptable salt thereof accounts for 15 wt% -60 wt% of the total weight of the medicine.

The medicament of the present invention may be administered by any suitable means of: oral, rectal, nasal, topical, buccal, sublingual, parenteral such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal or intracranial injection or infusion, or via an explanted reservoir.

The dosage and method of administration of the drug of the present invention will depend on a variety of factors including the age, weight, sex, physical condition, nutritional status, the activity intensity of the compound, time of administration, metabolic rate, severity of the course of disease, and the subjective judgment of the treating physician. The dosage and method of use can be readily determined by one skilled in the art based on the factors described above.

According to the technical scheme, the Chinese herbal medicine monomer triptolide ketone is found to be capable of remarkably reducing the formation of thoracic aortic atherosclerotic plaques, the accumulation of tricuspid valve fat and the formation of collagen fibers of high-fat diet mice, and remarkably reducing the weight and fat accumulation of the high-fat diet mice. In addition, triptolide can also significantly reduce the content of low-density lipoprotein and cholesterol in the blood of high-fat diet obese mice. The triptolide ketone has a treatment effect on atherosclerosis, so that the triptolide ketone can be applied to preparation of related medicines, and can also be applied to preparation of related medicines for coronary heart disease, cerebral infarction and peripheral vascular disease because the atherosclerosis is the main reason of the coronary heart disease, the cerebral infarction and the peripheral vascular disease.

Drawings

FIG. 1 shows the effect of triptonide on the formation of atherosclerotic plaque of thoracic aorta in mice on a high-fat and high-cholesterol diet (FIG. 1-A) and the statistical result (FIG. 1-B); wherein, the high fat diet group (HFD-TN), the normal diet group (ND), and the triptonide treatment group (HFD + TN);

FIG. 2 shows the results of oil red O staining (200X) of the effect of triptonide on tricuspid fat accumulation in mice on a high-fat high-cholesterol diet; wherein, the high fat diet group (HFD-TN), the normal diet group (ND), and the triptonide treatment group (HFD + TN);

FIG. 3 shows the results of Masson staining of triptonide on tricuspid tissue collagen deposition in mice on a high-fat high-cholesterol diet (200X); among them, high fat diet group (HFD-TN), normal diet group (ND), and triptonide treatment group.

Detailed Description

The invention discloses application of triptonide, and can be realized by appropriately improving process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the invention has been described in terms of embodiments, it will be apparent to those skilled in the art that the technology can be practiced and applied by modifying or appropriately combining the embodiments described herein without departing from the spirit and scope of the invention.

In the specific embodiment of the invention, the comparison test is involved, and the test environment, the raw materials and the like are consistent except for the difference of each test group.

The triptolide provided by the present invention is further described below.