Traditional Chinese medicine composition and application thereof in preparation of medicine for treating atherosclerosis

Abstract

The invention discloses an application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia. The traditional Chinese medicine composition comprises the following components: ginseng, lucid ganoderma, safflower, musk, calculus bovis, bear gall, pearl, venenum bufonis, radix aconiti carmichaeli and borneol. According to the traditional Chinese medicine composition disclosed by the invention, through reasonable compatibility of all the components, at least one of indexes such as aorta plaque area, vasomotor inner diameter difference, intima-media thickness, blood fat level, homocysteine content and the like in atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia can be effectively improved; the symptoms of atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia are relieved from multiple aspects, and the progress of the disease course is blocked. The traditional Chinese medicine composition is controllable in quality, convenient for standardized production, safe and reliable in prescription and free of toxic and side effects on human bodies.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a Chinese medicine composition and its application in preparing a medicine for treating atherosclerosis, in particular to preparing a medicine for treating atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia. Background Art

[0002] Atherosclerotic cardiovascular disease (ASCVD) includes ischemic heart disease (IHD) and ischemic stroke (IS); its main pathophysiological factor is to prevent atherosclerosis (AS). Therefore, targeting ASCVD should be regarded as the top priority for CVD prevention in China.

[0003] The etiology of AS is complex and the disease is lingering. In clinical practice, TCM can establish a theory based on phlegm and blood stasis, and use the method of promoting blood circulation and resolving phlegm to treat AS. However, TCM diagnosis and treatment of diseases is based on the root cause. Deficiency of vital energy is the basis of AS, which mainly involves deficiency of the heart, spleen, and kidney. The phlegm and blood stasis caused by deficiency of vital energy and the obstruction of the meridians are the key to the pathogenesis of AS. Therefore, in clinical treatment, while paying equal attention to phlegm and blood stasis, we must also pay attention to tonifying deficiency; it is necessary to clarify the pathogenesis of AS "deficiency-phlegm and blood stasis" from multiple pathways and multiple targets. At the same time, we can try to integrate the TCM idea of ​​"prevention before illness" into the prevention of the disease from the perspective of tonifying deficiency, and provide new ideas for the prevention and treatment of AS. TCM theory believes that spleen dysfunction is the prerequisite for the onset of AS, spleen deficiency produces phlegm, phlegm causes blood stasis, and phlegm and blood stasis are important pathogenesis of AS, and proposes a theoretical system for AS treatment of "treatment based on phlegm and blood stasis, and strengthening the spleen is the key". Invigorating qi and strengthening the spleen (ginseng) and removing phlegm and removing blood stasis (calculus gall) are good methods for treating AS. Professor Lei Zhongyi, a master of traditional Chinese medicine, believes that if phlegm and blood stasis are not removed for a long time, they will easily turn into heat and poison. On this basis, we should add heat-clearing and detoxifying products (such as bezoar) as appropriate to treat the syndrome of phlegm, blood stasis and toxicity caused by internal accumulation of heat and toxic evil by the method of clearing phlegm and turbidity, promoting blood circulation and removing blood stasis, clearing heat and detoxifying.

[0004] Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular and cerebrovascular diseases and has received increasing attention from the medical community in recent years. Currently, a large number of epidemiological studies have shown that HHcy is an independent risk factor for atherosclerosis, which can promote the occurrence and progression of atherosclerosis by promoting the production of inflammatory factors and mediating inflammatory responses. Studies have shown that HHcy patients may have obvious atherosclerotic lesions before inducing cardiovascular and cerebrovascular diseases, and drug intervention in patients during the period of atherosclerosis can effectively prevent the occurrence of cardiovascular and cerebrovascular diseases.

[0005] Therefore, in view of the above pathogenesis or molecular mechanisms, replenishing qi and strengthening the spleen (ginseng), resolving phlegm, removing stasis, clearing heat and detoxifying (cow-bezoar) are important strategies in the treatment of AS with traditional Chinese medicine. If hyperhomocysteinemia in patients can be improved simultaneously, it will be more beneficial to control the progression of atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia. Summary of the Invention

[0006] The present invention aims to solve at least one of the above technical problems in the prior art. To this end, the object of the present invention is to provide a traditional Chinese medicine composition and its application in the preparation of a drug for treating atherosclerosis, especially its application in the preparation of a drug for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia.

[0007] The first aspect of the present invention provides a traditional Chinese medicine composition, which contains the following raw materials in parts by weight: 400 - 600 parts of ginseng, 150 - 300 parts of cow-bezoar, 50 - 150 parts of ganoderma lucidum, 15 - 50 parts of pearl, 2 - 10 parts of aconite, 20 - 100 parts of safflower, 2 - 20 parts of musk, 5 - 15 parts of bear bile, 4 - 20 parts of bufotoxin, 2 - 10 parts of borneol;

[0008] Or the traditional Chinese medicine composition contains extracts of the following raw materials in parts by weight: 400 - 600 parts of ginseng, 150 - 300 parts of cow-bezoar, 50 - 150 parts of ganoderma lucidum, 15 - 50 parts of pearl, 2 - 10 parts of aconite, 20 - 100 parts of safflower, 2 - 20 parts of musk, 5 - 15 parts of bear bile, 4 - 20 parts of bufotoxin, 2 - 10 parts of borneol.

[0009] In some embodiments, the traditional Chinese medicine composition contains the following raw materials in parts by weight: 450 - 600 parts of ginseng, 150 - 280 parts of cow-bezoar, 70 - 150 parts of ganoderma lucidum, 15 - 45 parts of pearl, 2 - 8 parts of aconite, 20 - 80 parts of safflower, 2 - 18 parts of musk, 5 - 12 parts of bear bile, 4 - 15 parts of bufotoxin, 2 - 8 parts of borneol;

[0010] Or the traditional Chinese medicine composition contains extracts of the following raw materials in parts by weight: 450 - 600 parts of ginseng, 150 - 280 parts of cow-bezoar, 70 - 150 parts of ganoderma lucidum, 15 - 45 parts of pearl, 2 - 8 parts of aconite, 20 - 80 parts of safflower, 2 - 18 parts of musk, 5 - 12 parts of bear bile, 4 - 15 parts of bufotoxin, 2 - 8 parts of borneol.

[0011] In some embodiments, the traditional Chinese medicine composition contains the following raw materials in parts by weight: 450 parts of ginseng, 150 parts of cow-bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotoxin, 5 parts of borneol;

[0012] Or the traditional Chinese medicine composition contains extracts of the following raw medicinal materials in parts by weight: 450 parts of ginseng, 150 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol.

[0013] In some embodiments, the traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 500 parts of ginseng, 200 parts of bezoar, 100 parts of ganoderma lucidum, 30 parts of pearl, 8 parts of aconite, 60 parts of safflower, 18 parts of musk, 5 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol;

[0014] Or the traditional Chinese medicine composition contains extracts of the following raw medicinal materials in parts by weight: 500 parts of ginseng, 200 parts of bezoar, 100 parts of ganoderma lucidum, 30 parts of pearl, 8 parts of aconite, 60 parts of safflower, 18 parts of musk, 5 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol.

[0015] In some embodiments, the traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 600 parts of ginseng, 280 parts of bezoar, 150 parts of ganoderma lucidum, 45 parts of pearl, 2 parts of aconite, 20 parts of safflower, 3 parts of musk, 5 parts of bear bile, 10 parts of bufotalin, and 2 parts of borneol;

[0016] Or the traditional Chinese medicine composition contains extracts of the following raw medicinal materials in parts by weight: 600 parts of ginseng, 280 parts of bezoar, 150 parts of ganoderma lucidum, 45 parts of pearl, 2 parts of aconite, 20 parts of safflower, 3 parts of musk, 5 parts of bear bile, 10 parts of bufotalin, and 2 parts of borneol.

[0017] In some embodiments, the raw medicinal materials include any one form of dried medicinal materials, fresh medicinal materials, raw medicinal materials, cooked medicinal materials, and processed medicinal materials.

[0018] In some embodiments, the raw medicinal materials include any one of natural medicinal materials and natural medicinal material equivalent substitutes.

[0019] In some embodiments, the traditional Chinese medicine composition further includes pharmaceutically acceptable excipients.

[0020] In some embodiments, the pharmaceutically acceptable excipients include at least one of fillers, disintegrants, diluents, lubricants, binders, wetting agents, flavoring agents, suspending agents, solvents, sustained release agents, emulsifiers, absorption promoters, surfactants, or preservatives.

[0021] In some embodiments, the dosage form of the traditional Chinese medicine composition includes any one of decoctions, tablets, capsules, granules, pills, oral liquids, powders, or ointments.

[0022] The second aspect of the present invention provides the application of the traditional Chinese medicine composition provided in the first aspect in the preparation of a drug for treating atherosclerosis.

[0023] In some embodiments, there is provided an application of the traditional Chinese medicine composition provided in the first aspect in the preparation of a medicament for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia.

[0024] In some embodiments, the medicament for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia can improve atherosclerosis, including at least one efficacy index among aortic plaque area, vasomotor inner diameter difference, and intima-media thickness.

[0025] In some embodiments, the medicament for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia can improve hyperlipidemia, including at least one efficacy index among serum triglyceride, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol contents.

[0026] In some embodiments, the medicament for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia can improve hyperhomocysteinemia, including the efficacy index of homocysteine content in blood.

[0027] The beneficial effects of the present invention are as follows:

[0028] Through the reasonable compatibility of each component, the traditional Chinese medicine composition of the present invention can effectively improve at least one of the indexes such as aortic plaque area, vasomotor inner diameter difference, intima-media thickness, blood lipid level, and homocysteine content in atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia, relieve the symptoms of atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia from multiple aspects, and block the progression of the disease course. The traditional Chinese medicine composition of the present invention has controllable quality, is convenient for standardized production, has a safe and reliable prescription, and has no toxic and side effects on the human body. Description of the Drawings

[0029] Figure 1 The staining ratio of oil red O area in rats of each group (x±s, n = 10). Among them, compared with the Control group, #, p < 0.05. Compared with the ASCH group, *, p < 0.05; **, p < 0.01; compared with the original formula group, Δ, p < 0.05; ΔΔ, p < 0.01. Detailed Embodiments

[0030] The following further elaborates on the content of the present invention through specific examples. The raw materials, reagents, or devices used in the examples and comparative examples can be obtained from conventional commercial channels or by existing technical methods without special instructions. Unless otherwise specified, the test or measurement methods are all conventional methods in the art.

[0031] In the first aspect of the present invention, a traditional Chinese medicine composition is provided. The traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 400 - 600 parts of ginseng, 150 - 300 parts of bezoar, 50 - 150 parts of ganoderma lucidum, 15 - 50 parts of pearl, 2 - 10 parts of aconite root, 20 - 100 parts of safflower, 2 - 20 parts of musk, 5 - 15 parts of bear bile, 4 - 20 parts of bufotoxin, and 2 - 10 parts of borneol;

[0032] Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 400 - 600 parts of ginseng, 150 - 300 parts of bezoar, 50 - 150 parts of ganoderma lucidum, 15 - 50 parts of pearl, 2 - 10 parts of aconite root, 20 - 100 parts of safflower, 2 - 20 parts of musk, 5 - 15 parts of bear bile, 4 - 20 parts of bufotoxin, and 2 - 10 parts of borneol.

[0033] Chinese invention patent CN108057066A discloses a traditional Chinese medicine composition for preventing and treating unstable angina pectoris, which is composed of ginseng, aconite, ganoderma lucidum, safflower, artificial musk, bear bile, pearl, toad venom, borneol and bezoar. The inventor surprisingly found that after greatly adjusting the compatibility combination ratio of this formula, its original characteristic of mainly invigorating qi and promoting blood circulation, warming the meridians and dredging collaterals was transformed into mainly invigorating qi and strengthening the spleen, resolving phlegm and removing stasis. This transformation led to diseases that could not be treated by the original formula showing good curative effects in the new formula, such as atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia. The newly formed traditional Chinese medicine composition (i.e., the traditional Chinese medicine composition in the present invention) showed good therapeutic effects on atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia. A large amount of experimental data proved that the traditional Chinese medicine composition in the present invention, through the reasonable compatibility of each component, could effectively improve indicators such as the aortic plaque area, the difference in vasomotor inner diameter, the intima-media thickness, serum triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol content, and homocysteine content in the blood of atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia, relieve the symptoms of atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia from multiple aspects, and block the progression of the disease course. The prescription is safe and reliable and has no toxic and side effects on the human body. Heat toxin is the key to the lingering and progressive aggravation of coronary heart disease, which promotes the growth and rupture of atherosclerotic plaques. In view of this situation, "treating heat with cold" comes from "Plain Questions: Treatise on the Most Important Pathogenic Factors", which belongs to the correct treatment method in traditional Chinese medicine. Its meaning is "using cold and cool prescriptions to treat heat diseases". Since the transformation of phlegm and stasis into heat and heat transformation run through the whole process of the disease, and rise to the main contradiction during the unstable period of the disease fluctuation and deterioration. For the initial stage of heat pathogen, whose pathogenesis is not yet complex, and the stage of phlegm and stasis transforming into heat mainly manifested by simple fever or traditional Chinese medicine fire symptoms, its symptom manifestations and the nature of the internal pathogenic factors are relatively consistent. At this time, according to the correct treatment principle of traditional Chinese medicine, namely "treating heat with cold", it is sufficient, and at this time, the main focus should be on clearing heat. Since heat belongs to an intangible pathogen and must attach to something. In the pathogenesis of phlegm and stasis binding, heat pathogen often binds with tangible pathogens such as water, dampness, phlegm and stasis. According to the nature of the middle pathogen heat and its different attachments to body fluids, nutrient qi and blood, generally, methods such as clearing heat with sweet and cold herbs, purging fire with bitter and cold herbs or detoxifying are used. Therefore, in the present invention, emphasis is placed on increasing the effects of invigorating qi and strengthening the spleen, promoting blood circulation and removing stasis, and clearing heat and resolving phlegm. From the perspective of modern pharmacology, traditional Chinese medicine clinical applications and pre-clinical studies have shown that ginseng has the effect of invigorating qi and strengthening the spleen, safflower has the effect of promoting blood circulation and removing stasis, and bezoar has the effect of resolving phlegm.

[0034] In the present invention, parts by weight can be any fixed weight expressed in milligrams, grams or kilograms (such as 1 mg, 1 g, 2 g or 1 kg, etc.). For example, a traditional Chinese medicine composition composed of 1 part by weight of component a and 9 parts by weight of component b can be a traditional Chinese medicine composition composed of 1 g of component a + 9 g of component b, or 10 g of component a + 90 g of component b, etc. In the said traditional Chinese medicine composition, the percentage content of a certain component = (the number of parts by weight of this component / the sum of the number of parts by weight of all components) × 100%. Therefore, in the traditional Chinese medicine composition composed of 1 part by weight of component a and 9 parts by weight of component b, the content of component a is 10%, and the content of component b is 90%.

[0035] In some embodiments, the extract of the raw medicinal materials refers to the extract obtained by extracting the mixed raw medicinal materials, and / or the extract obtained by separately extracting the raw medicinal materials of each component and then mixing them. Optionally, the extract is further refined and purified. Among them, the said extraction methods include decoction extraction, reflux extraction, maceration extraction, ultrasonic extraction, percolation extraction, microwave extraction, etc.: the said refining and purification methods include water extraction and alcohol precipitation, alkali dissolution and acid precipitation, and / or various column chromatography purification methods, such as macroporous resin column, silica gel column, gel column, reverse phase column, etc.

[0036] In some embodiments, the traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 450 - 600 parts of ginseng, 150 - 280 parts of bezoar, 70 - 150 parts of ganoderma lucidum, 15 - 45 parts of pearl, 2 - 8 parts of aconite root, 20 - 80 parts of safflower, 2 - 18 parts of musk, 5 - 12 parts of bear bile, 4 - 15 parts of bufotalin, 2 - 8 parts of borneol;

[0037] or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 450 - 600 parts of ginseng, 150 - 280 parts of bezoar, 70 - 150 parts of ganoderma lucidum, 15 - 45 parts of pearl, 2 - 8 parts of aconite root, 20 - 80 parts of safflower, 2 - 18 parts of musk, 5 - 12 parts of bear bile, 4 - 15 parts of bufotalin, 2 - 8 parts of borneol.

[0038] In some embodiments, the traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 450 parts of ginseng, 150 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite root, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotalin, 5 parts of borneol;

[0039] or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 450 parts of ginseng, 150 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite root, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotalin, 5 parts of borneol.

[0040] In some embodiments, the traditional Chinese medicine composition contains the following raw medicinal materials by weight: 500 parts of ginseng, 200 parts of bezoar, 100 parts of ganoderma lucidum, 30 parts of pearl, 8 parts of aconite root, 60 parts of safflower, 18 parts of musk, 5 parts of bear bile, 10 parts of toad venom, and 5 parts of borneol;

[0041] Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials by weight: 500 parts of ginseng, 200 parts of bezoar, 100 parts of ganoderma lucidum, 30 parts of pearl, 8 parts of aconite root, 60 parts of safflower, 18 parts of musk, 5 parts of bear bile, 10 parts of toad venom, and 5 parts of borneol.

[0042] In some embodiments, the traditional Chinese medicine composition contains the following raw medicinal materials by weight: 600 parts of ginseng, 280 parts of bezoar, 150 parts of ganoderma lucidum, 45 parts of pearl, 2 parts of aconite root, 20 parts of safflower, 3 parts of musk, 5 parts of bear bile, 10 parts of toad venom, and 2 parts of borneol;

[0043] Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials by weight: 600 parts of ginseng, 280 parts of bezoar, 150 parts of ganoderma lucidum, 45 parts of pearl, 2 parts of aconite root, 20 parts of safflower, 3 parts of musk, 5 parts of bear bile, 10 parts of toad venom, and 2 parts of borneol.

[0044] In the present invention, the raw medicinal materials refer to the Chinese medicinal materials used as active ingredients in the traditional Chinese medicine composition of the present invention. The Chinese medicinal materials may include various forms. For example, the Chinese medicinal materials include (but are not limited to) dried medicinal materials, fresh medicinal materials, raw medicinal materials, cooked medicinal materials, processed medicinal materials, or combinations thereof.

[0045] The raw medicinal materials in the present invention can be Chinese medicinal materials of natural origin or equivalent substitutes of Chinese medicinal materials of natural origin. For example, the bezoar can be selected from at least one of natural bezoar, cultivated bezoar, in vitro cultivated bezoar, and artificial bezoar. The musk can be selected from at least one of natural musk and artificial musk.

[0046] In some embodiments, the traditional Chinese medicine composition further includes pharmaceutically acceptable excipients.

[0047] In some embodiments, the pharmaceutically acceptable excipients include at least one of fillers, disintegrants, diluents, lubricants, binders, wetting agents, flavoring agents, suspending agents, solvents, sustained-release agents, emulsifiers, absorption promoters, surfactants, or preservatives.

[0048] In some embodiments of the present invention, the filler is selected from at least one of starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose; the disintegrant is selected from at least one of corn starch, potato starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, carboxymethyl cellulose, cross-linked carboxymethyl cellulose sodium, calcium carboxymethyl cellulose and alginic acid; the diluent is selected from at least one of lactose, sucrose, mannitol, corn starch, potato starch, calcium phosphate, calcium citrate and crystalline cellulose; the lubricant is selected from at least one of stearic acid, polyethylene glycol, calcium carbonate, sodium bicarbonate, colloidal silica, talc, anhydrous silica and magnesium stearate; the binder is selected from at least one of cellulose derivatives, alginates, starch, water, dextrin, gelatin, hydroxypropyl cellulose, methyl cellulose or polyvinylpyrrolidone; the wetting agent is selected from at least one of glycerol, Tween-80, oxyhydrogenated castor oil, sodium dodecyl sulfate and lecithin; the flavoring agent is selected from at least one of aspartame, sucralose, essence, steviol glycosides, acesulfame potassium, citric acid and sodium saccharin; the suspending agent is selected from at least one of colloidal silica, beeswax, cellulose, sodium carboxymethyl cellulose and solid polyethylene glycol; the solvent is selected from at least one of water, ethanol, liquid polyethylene glycol, isopropanol, Tween-80, glycerol, propylene glycol and vegetable oil, wherein the vegetable oil is selected from at least one of rapeseed oil, beeswax, soybean oil, castor oil, peanut oil and blended oil; the sustained-release agent is selected from at least one of ethyl cellulose, cellulose acetate, polyethylene, polypropylene, polylactic acid, polyglycolic acid, polylactic acid-polyglycolic acid copolymer, polyvinyl chloride, polycarbonate, epoxy resin, polyamide, acetal polymer, polyester, polyurethane, polyimide and polystyrene derivatives, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, gelatin, peach gum, polyvinylpyrrolidone; the emulsifier is selected from at least one of anionic surfactants (such as sodium stearate, potassium stearate, sodium oleate, potassium oleate, calcium stearate, sodium dodecyl sulfate, sulfated castor oil hexadecyl), zwitterionic surfactants (such as lecithin and soya lecithin), non-ionic surfactants (such as polysorbates, sorbitan fatty acid esters, poloxamer, glycerol monostearate, glyceryl tristearate, sucrose stearate, polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers), gum arabic, gelatin, tragacanth, oil-in-water (O / W) emulsifiers (such as magnesium hydroxide, aluminum hydroxide, silica, bentonite), water-in-oil (W / O) emulsifiers (calcium hydroxide, zinc hydroxide, magnesium stearate); the absorption enhancer is selected from at least one of sodium caprylate and its derivatives, sodium caprate and its derivatives, alkyl glycosides, EDTA, chitosan and its derivatives, polyamidoamine dendrimers (PAMAM).The surfactant is selected from at least one of sodium dodecylbenzenesulfonate, stearic acid, polyoxyethylene-polyoxypropylene (PEO-PPO) block polyether, sorbitan fatty acid ester, and polysorbate; the preservative is selected from at least one of methyl paraben or propyl paraben.;

[0049] In some embodiments, the dosage form of the traditional Chinese medicine composition includes any one of decoction, tablet, capsule, granule, pill, oral liquid, powder, or ointment.

[0050] The second aspect of the present invention provides the use of the traditional Chinese medicine composition provided in the first aspect in the preparation of a drug for treating atherosclerosis.

[0051] Treatment in the present invention includes delaying and terminating the progression of the disease, or eliminating the disease, and does not require 100% inhibition, elimination, and reversal.

[0052] In some embodiments, there is provided the use of the traditional Chinese medicine composition provided in the first aspect in the preparation of a drug for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia.

[0053] Atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia refers to any one of atherosclerosis complicated with hyperhomocysteinemia, atherosclerosis complicated with hyperlipidemia, and atherosclerosis complicated with hyperhomocysteinemia and hyperlipidemia.

[0054] In some embodiments, the drug for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia can improve atherosclerosis including at least one efficacy index among aortic plaque area, difference in vasomotor inner diameter, and intima-media thickness.

[0055] In some embodiments, the drug for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia can improve hyperlipidemia including at least one efficacy index among serum triglyceride, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol contents.

[0056] In some embodiments, the drug for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia can improve hyperhomocysteinemia including the efficacy index of homocysteine content in the blood.

[0057] Example 1

[0058] In this example, a traditional Chinese medicine composition was prepared, and the traditional Chinese medicine composition was composed of the following raw materials in parts by weight: 450 parts of ginseng, 150 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol.

[0059] Process preparation:

[0060] All medicinal materials are separately powdered and then mixed; the coating pan is equipped with an internal water spraying device. The medicinal powder is scattered in the coating pan. First, add a small amount of medicinal powder, turn on the water spraying for 2 minutes and rotate the coating pan; stop the water spraying, continue to roll the coating pan, repeatedly spray water and scatter powder until the particles are firm, forming firm and dense particles. Subsequently, use a 1mm aperture pill mold for screening, and collect the pills with a diameter of 1mm, which are the finished products.

[0061] Example 2

[0062] In this example, a traditional Chinese medicine composition was prepared. The traditional Chinese medicine composition was composed of the following raw materials in parts by weight: 500 parts of ginseng, 200 parts of bezoar, 100 parts of ganoderma lucidum, 30 parts of pearl, 8 parts of aconite, 60 parts of safflower, 18 parts of musk, 5 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol.

[0063] Process preparation:

[0064] All medicinal materials are separately powdered and then mixed; the coating pan is equipped with an internal water spraying device. The medicinal powder is scattered in the coating pan. First, add a small amount of medicinal powder, turn on the water spraying for 2 minutes and rotate the coating pan; stop the water spraying, continue to roll the coating pan, repeatedly spray water and scatter powder until the particles are firm, forming firm and dense particles. Subsequently, use a 1mm aperture pill mold for screening, and collect the pills with a diameter of 1mm, which are the finished products.

[0065] Example 3

[0066] In this example, a traditional Chinese medicine composition was prepared. The traditional Chinese medicine composition was composed of the following raw materials in parts by weight: 600 parts of ginseng, 280 parts of bezoar, 150 parts of ganoderma lucidum, 45 parts of pearl, 2 parts of aconite, 20 parts of safflower, 3 parts of musk, 5 parts of bear bile, 10 parts of bufotalin, and 2 parts of borneol.

[0067] Process preparation:

[0068] All medicinal materials are separately powdered and then mixed; the coating pan is equipped with an internal water spraying device. The medicinal powder is scattered in the coating pan. First, add a small amount of medicinal powder, turn on the water spraying for 2 minutes and rotate the coating pan; stop the water spraying, continue to roll the coating pan, repeatedly spray water and scatter powder until the particles are firm, forming firm and dense particles. Subsequently, use a 1mm aperture pill mold for screening, and collect the pills with a diameter of 1mm, which are the finished products.

[0069] Comparative Example 1

[0070] In this example, a traditional Chinese medicine composition was prepared. The traditional Chinese medicine composition was composed of the following raw materials in parts by weight: 80 parts of ginseng, 150 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol;

[0071] Process preparation:

[0072] All the medicinal materials are separately powdered and then mixed; an internal water spraying device is installed in the coating pan. The medicinal powder is scattered into the coating pan. First, add a small amount of medicinal powder, turn on the water spray for 2 minutes and rotate the coating pan; stop the water spray and continue to roll the coating pan. Repeatedly spray water and scatter powder until the granules are firm, forming firm and dense granules. Subsequently, use a pill mold with a 1 mm aperture to screen, and collect the pills with a diameter of 1 mm, which are the finished products.

[0073] Comparative Example 2

[0074] In this example, a traditional Chinese medicine composition was prepared. The traditional Chinese medicine composition was composed of the following raw medicinal materials in parts by weight: 450 parts of ginseng, 50 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol.

[0075] Process preparation:

[0076] All the medicinal materials are separately powdered and then mixed; an internal water spraying device is installed in the coating pan. The medicinal powder is scattered into the coating pan. First, add a small amount of medicinal powder, turn on the water spray for 2 minutes and rotate the coating pan; stop the water spray and continue to roll the coating pan. Repeatedly spray water and scatter powder until the granules are firm, forming firm and dense granules. Subsequently, use a pill mold with a 1 mm aperture to screen, and collect the pills with a diameter of 1 mm, which are the finished products.

[0077] Comparative Example 3

[0078] In this example, a traditional Chinese medicine composition was prepared. The traditional Chinese medicine composition was composed of the following raw medicinal materials in parts by weight: 80 parts of ginseng, 50 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite, 50 parts of safflower, 10 parts of musk, 10 parts of bear bile, 10 parts of bufotalin, and 5 parts of borneol.

[0079] Process preparation:

[0080] All the medicinal materials are separately powdered and then mixed; an internal water spraying device is installed in the coating pan. The medicinal powder is scattered into the coating pan. First, add a small amount of medicinal powder, turn on the water spray for 2 minutes and rotate the coating pan; stop the water spray and continue to roll the coating pan. Repeatedly spray water and scatter powder until the granules are firm, forming firm and dense granules. Subsequently, use a pill mold with a 1 mm aperture to screen, and collect the pills with a diameter of 1 mm, which are the finished products.

[0081] Pharmacological research

[0082] 1 Experimental method

[0083] 1.1 Model establishment

[0084] Combined with multiple literatures 1,2, Establish an atherosclerotic model combined with hyperhomocysteinemia and / or hyperlipidemia: Feed 80 SD rats with a high-methionine and high-fat diet containing 3% methionine for 6 weeks, and then intraperitoneally inject vitamin D3 (600,000 IU / kg) once every 2 weeks. At the same time, a group of 20 SD rats were fed a normal diet.

[0085] 1.2 Grouping and administration

[0086] Nine weeks after modeling, randomly select 3 rats from the modeled rats and the rats fed a normal diet, collect blood from the abdominal aorta to detect the serum levels of TG, TC, LDL-C, HDL-C and homocysteine, and take the thoracic aorta tissue for Oil Red O staining to determine whether the model is successful.

[0087] The successfully modeled rats were randomly divided into an atherosclerotic group combined with hyperhomocysteinemia and / or hyperlipidemia (ASCH group, 10 rats), the original formula group (OHP group, 10 rats), the new formula group (NHP group, 10 rats), the atorvastatin group (At group, 10 rats) and control groups 1-3 (10 rats in each group). Randomly select 10 rats from the normal diet group as the blank group (control group, 10 rats). Atorvastatin is a commercially available product.

[0088] Rats in the normal group and the ASCH group were respectively intragastrically administered and intraperitoneally injected with an equal amount of normal saline. After modeling, the original formula group, the new formula group and the At group were respectively administered the traditional Chinese medicine composition in the original formula (the traditional Chinese medicine composition in CN108057066A), the traditional Chinese medicine composition in Example 1, the positive drug atorvastatin and the traditional Chinese medicine compositions in control groups 1-3, and continuously administered for 14 days. Using the oral gavage mode, the administration concentrations of the original formula group, the new formula group and control groups 1-3 were 150 mg·kg -1 ·d -1 , After atorvastatin was ground and formed a suspension with the solvent normal saline, the suspension concentration was 0.003 g·mL -1 , Calculated by the weight of atorvastatin, the dose was 8.4 mg·kg -1 , The ASCH group and the blank group were gavaged with normal saline, 2 mL was gavaged once a day, and continuously administered for 12 weeks. During the administration process, the blank group was normally fed, and the other groups were fed with a high-methionine and high-fat diet containing 3% methionine.

[0089] 1.3 Echocardiogram detection method

[0090] The VE95 echocardiograph and a cardiac probe with a frequency of (5-12) MHz were used to evaluate the cardiac ultrasound structure and function, including collecting static and dynamic images at the parasternal (long-axis and short-axis sections) and apical four-chamber views (4, 5, 2, and 3 chambers). A preset condition for maintaining stable clarity of rat images: frequency (5-10) MHz, depth 2.5 cm, frame rate 125 fps, Doppler sampling 1.0 mm, and color Doppler mixing velocity 40 cm / s. At least 3 cardiac cycles were recorded.

[0091] 1.4 Determination of the contents of TG, TC, HDL-C, LDL-C, and homocysteine in rat serum by ELISA

[0092] After 12 weeks of administration in each group, the rats were fasted overnight. After weighing the rats, they were anesthetized, blood was collected by eye enucleation, and the rats were randomly sacrificed to obtain the whole aorta. The blood was allowed to stand at 4°C for 12 h, centrifuged at 12,000 r / min for 15 min, the supernatant was taken, and stored at -80°C for later use.

[0093] An enzyme-linked immunosorbent assay kit was used to detect the contents of TG, TC, HDL-C, LDL-C, and homocysteine in the serum. The specific detection method referred to the instruction manual of the kit.

[0094] 1.5 Oil red O staining of the aorta

[0095] The whole aorta was placed in 4% paraformaldehyde and fixed for more than 24 h. Then it was taken out, washed 3 times with PBS for 5 min each time. The excess connective tissue was dissected under a stereomicroscope and placed in an oil red O staining solution at 45°C for 15 min, differentiated with 75% ethanol, placed on a black rubber pad, and photographed. After the heart was fixed and embedded in paraffin, the section thickness was 3 μm. After dewaxing to water, HE staining was performed: hematoxylin staining for 8 min, differentiation solution for 2 s, bluing with tap water for 3 min, eosin staining for 45 s. Masson staining: hematoxylin for 3 min, acidic differentiation solution for 2 s, bluing with distilled water for 10 min, ponceau fuchsin for 8 min, rinsed with weak acid working solution, phosphomolybdic acid for 6 min, aniline blue for 5 min. All were sealed with neutral gum, observed and photographed under an optical microscope, and HE and Masson staining analysis was performed using the ImageJ software.

[0096] 2. Experimental results

[0097] 2.1 Evaluation of atherosclerotic-related aortic indexes, intima-media thickness (IMT), and difference in vasomotor inner diameter (Dimers-Dimerd, Ds-Dd)

[0098] The ultrasonic echocardiogram-detected changes in the IMT of the rat aorta and Ds-Dd ultrasound are shown in Table 1. The results show that compared with the Control group, the IMT of the atrial aorta and Ds-Dd in the ASCH group were significantly increased, and the difference was statistically significant (P<0.01). Compared with the ASCH group, the original formula group (OHP group) in the drug administration group failed to improve the atherosclerotic indicators such as the IMT of the rat aorta and Ds-Dd, while the atorvastatin group (At group) and the new formula group (NHP) significantly improved the aortic-related indicators (P<0.01), and the results were statistically significant; there was no therapeutic effect in Comparative Example groups 1-3.

[0099] Table 1 Ultrasonic changes in the IMT of the aorta and Ds-Dd in rats of each group (x±s, n=10)

[0100]

[0101] Note: Compared with the Control group, #, p<0.05. Compared with the ASCH group, *, p<0.05; **, p<0.01; compared with the original formula group, Δ, p<0.05; ΔΔ, p<0.01.

[0102] 2.2 Evaluation of rat blood lipids

[0103] Compared with the Control group, the TC, TG, and LDL-C of the rats in the ASCH group were all increased (Table 2, P<0.01), and the HDL-C decreased (Table 2, P<0.01), indicating that the ASCH model rats showed symptoms of elevated blood lipids. Compared with the ASCH group, the TC, TG, and LDL-C of the rats in the NHP group decreased (P<0.01), and the HDL-C increased (P<0.01); however, the OHP group failed to improve the above indicators, and the atorvastatin group only had an effect on reducing LDL-C; there was no therapeutic effect in Comparative Example groups 1-3.

[0104] Table 2 Changes in blood lipids of rats in each group (x±s, n=10)

[0105]

[0106]

[0107] Note: Compared with the Control group, #, p<0.05. Compared with the ASCH group, *, p<0.05; **, p<0.01; compared with the original formula group, Δ, p<0.05; ΔΔ, p<0.01.

[0108] 2.3 Evaluation of homocysteine content

[0109] Compared with the Control group, the homocysteine content in the ASCH group of rats was significantly increased (P<0.01). Compared with the ASCH group, the homocysteine in the NHP group of rats decreased significantly, while there was no difference between the OHP group and the atorvastatin group and the ASCH group (P<0.05, P<0.01); there was no therapeutic effect in Comparative Example groups 1-3.

[0110] Table 3 Changes in blood lipids of rats in each group (x±s, n=10)

[0111]

[0112] 2.4 Aortic Oil Red O staining

[0113] As Figure 1 shown, compared with the Control group, the Oil Red staining area in the ASCH group of rats was significantly increased (P<0.01). Compared with the ASCH group, the homocysteine in the NHP group of rats decreased significantly, while there was no difference between the OHP group and the atorvastatin group and the ASCH group (P<0.05, P<0.01); there was no therapeutic effect in Comparative Example groups 1-3.

[0114] The results of this study indicate that there are significant differences between the original formula and the new formula in the direction of treating atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia. The new formula can improve various indicators of atherosclerosis combined with hyperhomocysteinemia and / or hyperlipidemia.

[0115] It was verified that the therapeutic effects of the traditional Chinese medicine compositions in Example 2 and Example 3 were similar to those of Prescription 1.

[0116] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

[0117] References:

[0118] [1] Dai Yuan, Wei Jiangping, Pan Ting, et al. Study on the preparation of a rat model of hyperhomocysteinemia by intragastric administration of methionine [J]. Chinese Journal of Basic Medicine in Traditional Chinese Medicine, 2017, 23(12): 1697-1700. DOI: 10.19945 / j.cnki.issn.1006-3250.2017.12.019.

[0119] [2] Chen Zhuoming, Liu Xiaoling, Huang Na, et al. Study on the effect of Wenyang Huoxue Jiedu Prescription in regulating RIPK1 / NLRP3 / Caspase-1 to stabilize vulnerable atherosclerotic plaques [J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2024, 33(22): 3067-3072+3087.

Claims

1. A traditional Chinese medicine composition, characterized in that, The traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 400 - 600 parts of ginseng, 150 - 300 parts of bezoar, 50 - 150 parts of ganoderma lucidum, 15 - 50 parts of pearl, 2 - 10 parts of aconite root, 20 - 100 parts of safflower, 2 - 20 parts of moschus, 5 - 15 parts of bear bile, 4 - 20 parts of bufotalin, 2 - 10 parts of borneol; Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 400 - 600 parts of ginseng, 150 - 300 parts of bezoar, 50 - 150 parts of ganoderma lucidum, 15 - 50 parts of pearl, 2 - 10 parts of aconite root, 20 - 100 parts of safflower, 2 - 20 parts of moschus, 5 - 15 parts of bear bile, 4 - 20 parts of bufotalin, 2 - 10 parts of borneol.

2. The traditional Chinese medicine composition according to claim 1, wherein The traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 450 - 600 parts of ginseng, 150 - 280 parts of bezoar, 70 - 150 parts of ganoderma lucidum, 15 - 45 parts of pearl, 2 - 8 parts of aconite root, 20 - 80 parts of safflower, 2 - 18 parts of moschus, 5 - 12 parts of bear bile, 4 - 15 parts of bufotalin, 2 - 8 parts of borneol; Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 450 - 600 parts of ginseng, 150 - 280 parts of bezoar, 70 - 150 parts of ganoderma lucidum, 15 - 45 parts of pearl, 2 - 8 parts of aconite root, 20 - 80 parts of safflower, 2 - 18 parts of moschus, 5 - 12 parts of bear bile, 4 - 15 parts of bufotalin, 2 - 8 parts of borneol.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 450 parts of ginseng, 150 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite root, 50 parts of safflower, 10 parts of moschus, 10 parts of bear bile, 10 parts of bufotalin, 5 parts of borneol; Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 450 parts of ginseng, 150 parts of bezoar, 70 parts of ganoderma lucidum, 30 parts of pearl, 5 parts of aconite root, 50 parts of safflower, 10 parts of moschus, 10 parts of bear bile, 10 parts of bufotalin, 5 parts of borneol.

4. The traditional Chinese medicine composition according to claim 1, wherein, The traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 500 parts of ginseng, 200 parts of bezoar, 100 parts of ganoderma lucidum, 30 parts of pearl, 8 parts of aconite root, 60 parts of safflower, 18 parts of moschus, 5 parts of bear bile, 10 parts of bufotalin, 5 parts of borneol; Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 500 parts of ginseng, 200 parts of bezoar, 100 parts of ganoderma lucidum, 30 parts of pearl, 8 parts of aconite root, 60 parts of safflower, 18 parts of moschus, 5 parts of bear bile, 10 parts of bufotalin, 5 parts of borneol.

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition contains the following raw medicinal materials in parts by weight: 600 parts of ginseng, 280 parts of bezoar, 150 parts of ganoderma lucidum, 45 parts of pearl, 2 parts of aconite root, 20 parts of safflower, 3 parts of moschus, 5 parts of bear bile, 10 parts of bufotalin, 2 parts of borneol; Or the traditional Chinese medicine composition contains the extracts of the following raw medicinal materials in parts by weight: 600 parts of ginseng, 280 parts of bezoar, 150 parts of ganoderma lucidum, 45 parts of pearl, 2 parts of aconite root, 20 parts of safflower, 3 parts of moschus, 5 parts of bear bile, 10 parts of bufotalin, 2 parts of borneol.

6. The traditional Chinese medicine composition according to claim 1, characterized in that The raw medicinal materials include any one form of dried medicinal materials, fresh medicinal materials, raw medicinal materials, cooked medicinal materials, and processed medicinal materials.

7. The traditional Chinese medicine composition according to claim 1, wherein The raw medicinal materials include any one of natural medicinal materials and natural medicinal material equivalent substitutes.

8. The traditional Chinese medicine composition according to claim 1, wherein The traditional Chinese medicine composition further comprises a pharmaceutically acceptable excipient.

9. The traditional Chinese medicine composition according to claim 1, wherein: The dosage form of the traditional Chinese medicine composition includes any one of decoction, tablets, capsules, granules, pills, oral liquids, powders or ointments.

10. Use of the traditional Chinese medicine composition according to any one of claims 1-9 in the preparation of a medicament for treating atherosclerosis; Preferably, use in the preparation of a medicament for treating atherosclerosis complicated with hyperhomocysteinemia and / or hyperlipidemia.

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