Application of composition in preparation of synergist of medicine for treating atherosclerosis

Abstract

The invention discloses an application of a composition in preparation of a synergist of a medicine for treating atherosclerosis, the composition can effectively enhance the treatment effect of the medicine for treating atherosclerosis through reasonable compatibility of all components, improve the effect of the medicine for treating atherosclerosis in multiple aspects, block the progress of the disease course, reduce the treatment cost and improve the treatment effect of the medicine for treating atherosclerosis. Comprising the following steps: improving indexes such as aorta plaque area, vasomotor inner diameter difference, intima-media thickness, serum triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol content, homocysteine content in blood and the like in atherosclerosis, and reducing the dosage of medicines for treating atherosclerosis; the prescription is safe and reliable without toxic and side effects on human bodies.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to the use of a composition in the preparation of a drug potentiator for treating atherosclerosis. Background Technology

[0002] Atherosclerosis (AS) is one of the most common cardiovascular diseases, characterized by thickening of the arterial walls, atherosclerosis, lipid accumulation, and inflammation. Epidemiological studies show that risk factors for AS include hypertension, smoking, diabetes, and hyperlipidemia. With improved living standards, the incidence of AS is increasing year by year, and the affected population is becoming younger. As AS progresses, it can eventually lead to clinical complications such as myocardial infarction and stroke. Therefore, actively controlling atherosclerosis is crucial for preventing cardiovascular disease.

[0003] Asthenia gravis (AS) has a complex etiology and a protracted course. Traditional Chinese medicine (TCM) can treat AS by addressing phlegm and blood stasis, using methods to invigorate blood and resolve phlegm. However, TCM emphasizes addressing the root cause of disease. Deficiency of vital energy (Qi) is the underlying basis for AS, primarily involving deficiencies in the heart, spleen, and kidneys. The mutual binding of phlegm and blood stasis caused by Qi deficiency, obstructing the blood vessels, is the key pathogenesis of AS. Therefore, in clinical treatment, while addressing both phlegm and blood stasis, it is crucial to focus on tonifying the deficiency. The pathogenesis of AS involving "deficiency-phlegm and blood stasis" needs to be elucidated from multiple perspectives and targets. Furthermore, the TCM concept of "prevention before disease" can be integrated into the prevention of AS from the perspective of tonifying the deficiency, providing new insights for the prevention and treatment of AS. TCM theory holds that spleen dysfunction is a prerequisite for the onset of AS. Spleen deficiency leads to phlegm production, which in turn causes blood stasis. The mutual binding of phlegm and blood stasis is a significant pathogenesis of AS, leading to the TCM treatment theory system of "treating phlegm and blood stasis, with strengthening the spleen as the key." First, lipids (phlegm and turbidity) in the blood deposit on the blood vessel walls, infiltrate the damaged intima, and combine with the matrix to form lipid streaks. Blood stasis obstructing the collaterals leads to slowed local blood flow and activated inflammation, promoting fibrin deposition and accelerating plaque progression. The accumulation of phlegm and turbidity provides the material basis for plaques, while blood stasis exacerbates the local inflammatory microenvironment, ultimately leading to atherosclerotic plaques and arterial stenosis. Invigorating Qi and strengthening the spleen (ginseng) and resolving phlegm and removing blood stasis (bezoar) are good methods for treating AS. Professor Lei Zhongyi, a master of traditional Chinese medicine, believes that persistent phlegm and blood stasis easily transform into heat and toxins. Therefore, on this basis, heat-clearing and detoxifying herbs (such as bezoar) should be added to treat the syndrome of phlegm, blood stasis, and toxin accumulation caused by internal heat and toxins through methods of resolving phlegm and turbidity, promoting blood circulation and removing blood stasis, and clearing heat and detoxifying.

[0004] In addition, the occurrence of AS is closely related to "heat toxin" in vivo. The so-called "heat toxin" refers to a pathological state that the body's yin fluid is damaged and the vital qi is consumed due to the accumulation of fire-heat evil, which disturbs the running of qi and blood, and eventually leads to the stagnation of qi and blood and the endogenous of toxic stasis. The heat toxin theory believes that improper diet, excessive fatigue, emotional disorders and other external factors induce fire-heat evil in the body, further causing the disorder of qi and blood running, and the endogenous of phlegm turbidity due to the failure of body fluid distribution. Phlegm turbidity and heat toxin adhere to each other, which is an important factor for the formation of AS plaque. At the same time, factors such as qi deficiency, blood stasis, and imbalance of yin and yang can also affect the generation and development of heat toxin. If the heat toxin persists, it can cause vascular endothelial dysfunction, damage the blood vessel wall, promote inflammatory and oxidative stress reactions, and thus lead to the occurrence and progression of AS. Traditional Chinese medicine believes that "heat toxin theory" or stasis heat toxin is an important factor for the occurrence and development of AS: first, toxic evil has acute onset, and similarly, AS progresses to the late stage, which can lead to acute conditions such as coronary artery disease and cerebral hemorrhage, which seriously threaten life. Second, toxic evil is easy to mix with other evils. Dr. He Xiushan once pointed out that "fire is accompanied by poison". When toxic evil is accumulated inside, phlegm is accumulated and heat is abundant, which promotes the deeper penetration of toxic evil into the body and the more severe stasis heat adhesion. Heat toxin can be converted into fire, and fire is easy to be accompanied by toxic evil. Toxic evil has the characteristics of virtual and real mixture, stubbornness and difficult cure. Toxic evil is contained in the body, and toxic stasis phlegm and fire stagnation make the pathogenic factors deeply rooted, enter the blood and collaterals, and are difficult to cure. At the same time, fire and toxin consume qi and blood, burn body fluid, and damage viscera. The virtual and real mixture is stubborn and difficult to cure. AS is a chronic disease that is not easy to cure, and the disease is long and recurrent. The heat toxin theory also emphasizes the systemic and complex nature of AS, and the lesion is not only limited to local blood vessels, but also affects the microenvironment and metabolic state of the whole body. SUMMARY

[0005] The present application aims at at least one of the above-mentioned technical problems existing in the prior art. To this end, the purpose of the present application is to provide a composition for treating atherosclerosis.

[0006] In order to achieve the above-mentioned purpose, the technical solution adopted by the present application is: The first aspect of the present application provides use of a composition in preparation of a medicine synergist for treating atherosclerosis, wherein the composition is prepared from raw medicinal materials including: 50-450 parts of Huangqi, 50-450 parts of Xuanshen, 25-265 parts of Niu Bangzi, 100-350 parts of Bohe, 10-60 parts of Lianqiao, 5-80 parts of Jiegeng, 10-85 parts of Gancao, 20-160 parts of Banlangen, 2-75 parts of Mabu, 10-80 parts of Jiangcan, 5-40 parts of Chenpi, 5-20 parts of Chaihu, and 2-20 parts of Shengma.

[0007] In some embodiments, the composition is prepared from raw medicinal materials including: 200-450 parts of Huangqi, 200-425 parts of Xuanshen, 100-200 parts of Niu Bangzi, 100-200 parts of Bohe, 10-50 parts of Lianqiao, 5-75 parts of Jiegeng, 10-80 parts of Gancao, 20-80 parts of Banlangen, 5-60 parts of Mabu, 10-60 parts of Jiangcan, 10-40 parts of Chenpi, 5-20 parts of Chaihu, and 5-20 parts of Shengma.

[0008] In some embodiments, the medicine for treating atherosclerosis is prepared from raw medicinal materials including: 450-600 parts of Renshen, 150-280 parts of Niuhuang, 70-150 parts of Lingzhi, 15-45 parts of Zhenzhu, 2-8 parts of Fuzi, 20-80 parts of Honghua, 2-18 parts of Mosmann, 5-12 parts of Xiongdan, 4-15 parts of Chancaosu, and 2-8 parts of Bingpian.

[0009] The second aspect of the present application provides a medicine composition including an active component and a synergist, wherein the synergist is prepared from raw medicinal materials including: 50-450 parts of Huangqi, 50-450 parts of Xuanshen, 25-265 parts of Niu Bangzi, 100-350 parts of Bohe, 10-60 parts of Lianqiao, 5-80 parts of Jiegeng, 10-85 parts of Gancao, 20-160 parts of Banlangen, 2-75 parts of Mabu, 10-80 parts of Jiangcan, 5-40 parts of Chenpi, 5-20 parts of Chaihu, and 2-20 parts of Shengma. The active component is prepared from raw medicinal materials including: 400-600 parts of Renshen, 150-300 parts of Niuhuang, 50-150 parts of Lingzhi, 15-50 parts of Zhenzhu, 2-10 parts of Fuzi, 20-100 parts of Honghua, 2-20 parts of Mosmann, 5-15 parts of Xiongdan, 4-20 parts of Chancaosu, and 2-10 parts of Bingpian.

[0010] In some embodiments, the synergist is made of raw medicinal materials in parts by weight as follows: Scutellaria 200-450 parts, Figwort 200-425 parts, Burdock 100-200 parts, Mint 100-200 parts, Forsythia 10-50 parts, Platycodon 5-75 parts, Licorice 10-80 parts, Isatidis Root 20-80 parts, Calvatia 5-60 parts, Scolithus 10-60 parts, Tangerine Peel 10-40 parts, Bupleurum 5-20 parts, Cimicifuga 5-20 parts.

[0011] In some embodiments, the active component is made of raw medicinal materials in parts by weight as follows: Ginseng 450-600 parts, Ox Gallstone 150-280 parts, Ganoderma 70-150 parts, Pearl 15-45 parts, Aconitum 2-8 parts, Safflower 20-80 parts, Musk 2-18 parts, Bear Gall 5-12 parts, Toad Venom 4-15 parts, Borneol 2-8 parts.

[0012] In some embodiments, the active component and the synergist are in the same formulation unit or in different formulation units.

[0013] In some embodiments, the active component and the synergist are administered simultaneously, separately or sequentially.

[0014] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0015] The third aspect of the present application provides use of the pharmaceutical composition of the second aspect in the preparation of a medicament for treating atherosclerosis.

[0016] The present application has the following advantages: the composition provided by the present application as a synergist for treating atherosclerosis can effectively enhance the therapeutic effect of the atherosclerosis treatment drug, improve the effect of the atherosclerosis treatment drug from multiple aspects, block the progression of the disease, including improving the aortic plaque area, the difference between the vasomotor inner diameter, the intima-media thickness, the serum triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol content, homocysteine content in blood and other indicators in atherosclerosis, and reducing the dosage of the atherosclerosis treatment drug. The prescription is safe and reliable, has no toxic and side effects on the human body. DETAILED DESCRIPTION

[0017] The content of the present application is further described in detail through specific examples. The raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial channels or can be obtained by existing technical methods, unless otherwise specified. Unless otherwise specified, the test or test method is a conventional method in the art.

[0018] The application provides the use of a composition in the preparation of a drug potentiator for treating atherosclerosis, wherein the composition is prepared from raw medicinal materials including Scutellaria 50-450 parts, Figwort 50-450 parts, Burdock 25-265 parts, Mint 100-350 parts, Forsythia 10-60 parts, Platycodon 5-80 parts, Licorice 10-85 parts, Isatidis Root 20-160 parts, Calvatia 2-75 parts, Strychindendrum 10-80 parts, Tangerine Peel 5-40 parts, Bupleurum 5-20 parts, Cimicifuga 2-20 parts, and the drug for treating atherosclerosis is prepared from raw medicinal materials including Ginseng 400-600 parts, Ox Gallstone 150-300 parts, Ganoderma 50-150 parts, Pearl 15-50 parts, Aconite 2-10 parts, Safflower 20-100 parts, Musk 2-20 parts, Bear Gall 5-15 parts, Toad Venom 4-20 parts, and Borneol 2-10 parts.

[0019] CN 120241852 A discloses a drug for treating atherosclerosis, which is composed of Ginseng, Aconite, Ganoderma, Safflower, artificial Musk, Bear Gall, Pearl, Toad Venom, Borneol and Ox Gallstone. Based on the pathogenesis or molecular mechanism of AS, the application provides the use of a composition with heat-clearing and detoxifying effect in the preparation of a drug potentiator for treating atherosclerosis, which can clear away heat and toxic materials, cool blood, reduce swelling, regulate immune function and resist inflammation and oxidation. Phlegm-removing and blood-stasis-removing (Ox Gallstone), Qi-reinforcing and blood-activating (Ginseng / Safflower) and heat-clearing and detoxifying (Scutellaria / Giant Knotweed / Figwort) can enhance the efficacy of resisting atherosclerosis and reduce the dosage, which is more conducive to controlling the progression of atherosclerosis. A large amount of experimental data prove that the composition can effectively enhance the therapeutic effect of the drug for treating atherosclerosis by reasonable matching of components, improve the effect of the drug for treating atherosclerosis from multiple aspects, block the progression of the disease, including improving the aortic plaque area, the difference between the systolic and diastolic diameters of blood vessels, the intima-media thickness, the contents of serum triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and homocysteine in blood, and reducing the dosage of the drug for treating atherosclerosis, which is safe and reliable and has no toxic and side effects on human bodies.

[0020] In some embodiments, the composition and the drug for treating atherosclerosis are in the same formulation unit or different formulation units.

[0021] In some embodiments, the composition and the drug for treating atherosclerosis are in different formulation units.

[0022] In some embodiments, the composition is a mixture of each raw material after being pulverized; or an extract obtained by mixing each raw material after being extracted; or an extract obtained by mixing each raw material after being extracted separately. Optionally, the extract is further refined and purified. The extraction method includes decoction extraction, reflux extraction, immersion extraction, ultrasonic extraction, percolation extraction, microwave extraction, etc.; and the refining and purifying method includes 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.

[0023] In some embodiments, the dosage form of the composition includes any one of decoction, tablet, capsule, granule, pill, oral liquid, powder or paste.

[0024] In some embodiments, the composition further comprises a pharmaceutically acceptable excipient.

[0025] In some embodiments, the composition is a mixture of each raw material after being pulverized; or an extract obtained by mixing each raw material after being extracted; or an extract obtained by mixing each raw material after being extracted separately. Optionally, the extract is further refined and purified. The extraction method includes decoction extraction, reflux extraction, immersion extraction, ultrasonic extraction, percolation extraction, microwave extraction, etc.; and the refining and purifying method includes 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.

[0026] In some embodiments, the dosage form of the composition includes any one of decoction, tablet, capsule, granule, pill, oral liquid, powder or paste.

[0027] In some embodiments, the composition further comprises a pharmaceutically acceptable excipient.

[0028] In some embodiments, the composition and the therapeutic drug for treating atherosclerosis are administered simultaneously, separately or sequentially.

[0029] In some embodiments, the composition is made of raw materials including, by weight, 200-450 parts of Huangqi, 200-425 parts of Xuan- shen, 100-200 parts of Niu Bang- zi, 100-200 parts of Bo- he, 10-50 parts of Lian- qiao, 5-75 parts of Jie- geng, 10-80 parts of Gan- cao, 20-80 parts of Ban- lang- gen, 5-60 parts of Ma- bo, 10-60 parts of Jang- can, 10-40 parts of Chen- pi, 5-20 parts of Chai- hu, 5-20 parts of Sheng- ma.

[0030] In some embodiments, the composition is made from raw medicinal materials including the following weight parts: Huangqi 200 parts, Xuanshen 150 parts, Niu Bangzi 100 parts, Bohe 150 parts, Lianqiao 15 parts, Jiegeng 20 parts, Gancao 15 parts, Banlangen 40 parts, Mabu 10 parts, Jiangcan 30 parts, Chenpi 20 parts, Chaihu 10 parts, Shengma 10 parts.

[0031] In some embodiments, the composition is made from raw medicinal materials including the following weight parts: Huangqi 300 parts, Xuanshen 200 parts, Niu Bangzi 150 parts, Bohe 200 parts, Lianqiao 30 parts, Jiegeng 40 parts, Gancao 40 parts, Banlangen 70 parts, Mabu 30 parts, Jiangcan 50 parts, Chenpi 25 parts, Chaihu 15 parts, Shengma 10 parts.

[0032] In some embodiments, the composition is made from raw medicinal materials including the following weight parts: Huangqi 400 parts, Xuanshen 375 parts, Niu Bangzi 225 parts, Bohe 250 parts, Lianqiao 45 parts, Jiegeng 30 parts, Gancao 25 parts, Banlangen 55 parts, Mabu 50 parts, Jiangcan 45 parts, Chenpi 35 parts, Chaihu 20 parts, Shengma 20 parts.

[0033] In some embodiments, the medicine for treating atherosclerosis is made from raw medicinal materials including the following weight parts: Renshen 450-600 parts, Niuhuang 150-280 parts, Lingzhi 70-150 parts, Zhenzhu 15-45 parts, Fuzi 2-8 parts, Honghua 20-80 parts, Mosha 2-18 parts, Xiongdan 5-12 parts, Chansu 4-15 parts, Bingpian 2-8 parts.

[0034] In some embodiments, the medicine for treating atherosclerosis is made from raw medicinal materials including the following weight parts: Renshen 450 parts, Niuhuang 150 parts, Lingzhi 70 parts, Zhenzhu 30 parts, Fuzi 5 parts, Honghua 50 parts, Mosha 10 parts, Xiongdan 10 parts, Chansu 10 parts, Bingpian 5 parts.

[0035] The second aspect of the present application provides a pharmaceutical composition including an active component and a synergist, the synergist being made from raw medicinal materials including the following weight parts: Huangqi 50-450 parts, Xuanshen 50-450 parts, Niu Bangzi 25-265 parts, Bohe 100-350 parts, Lianqiao 10-60 parts, Jiegeng 5-80 parts, Gancao 10-85 parts, Banlangen 20-160 parts, Mabu 2-75 parts, Jiangcan 10-80 parts, Chenpi 5-40 parts, Chaihu 5-20 parts, Shengma 2-20 parts; The active component is made from raw medicinal materials including the following weight parts: Renshen 400-600 parts, Niuhuang 150-300 parts, Lingzhi 50-150 parts, Zhenzhu 15-50 parts, Fuzi 2-10 parts, Honghua 20-100 parts, Mosha 2-20 parts, Xiongdan 5-15 parts, Chansu 4-20 parts, Bingpian 2-10 parts.

[0036] In some embodiments, the synergist is made from raw medicinal materials comprising the following parts by weight: Scutellaria 200-450 parts, Figwort 200-425 parts, Burdock 100-200 parts, Mint 100-200 parts, Forsythia 10-50 parts, Platycodon 5-75 parts, Licorice 10-80 parts, Radix Isatidis 20-80 parts, Calvatia 5-60 parts, Scolithus 10-60 parts, Tangerine Peel 10-40 parts, Bupleurum 5-20 parts, Cimicifuga 5-20 parts.

[0037] In some embodiments, the synergist is made from raw medicinal materials comprising the following parts by weight: Scutellaria 200 parts, Figwort 150 parts, Burdock 100 parts, Mint 150 parts, Forsythia 15 parts, Platycodon 20 parts, Licorice 15 parts, Radix Isatidis 40 parts, Calvatia 10 parts, Scolithus 30 parts, Tangerine Peel 20 parts, Bupleurum 10 parts, Cimicifuga 10 parts.

[0038] In some embodiments, the synergist is made from raw medicinal materials comprising the following parts by weight: Scutellaria 300 parts, Figwort 200 parts, Burdock 150 parts, Mint 200 parts, Forsythia 30 parts, Platycodon 40 parts, Licorice 40 parts, Radix Isatidis 70 parts, Calvatia 30 parts, Scolithus 50 parts, Tangerine Peel 25 parts, Bupleurum 15 parts, Cimicifuga 10 parts.

[0039] In some embodiments, the synergist is made from raw medicinal materials comprising the following parts by weight: Scutellaria 400 parts, Figwort 375 parts, Burdock 225 parts, Mint 250 parts, Forsythia 45 parts, Platycodon 30 parts, Licorice 25 parts, Radix Isatidis 55 parts, Calvatia 50 parts, Scolithus 45 parts, Tangerine Peel 35 parts, Bupleurum 20 parts, Cimicifuga 20 parts.

[0040] In some embodiments, the active component is made from raw medicinal materials comprising the following parts by weight: Ginseng 450-600 parts, Ox Gallstone 150-280 parts, Ganoderma 70-150 parts, Pearl 15-45 parts, Aconitum 2-8 parts, Safflower 20-80 parts, Musk 2-18 parts, Bear Gall 5-12 parts, Toad Venom 4-15 parts, Borneol 2-8 parts.

[0041] In some embodiments, the active component is made from raw medicinal materials comprising the following parts by weight: Ginseng 450 parts, Ox Gallstone 150 parts, Ganoderma 70 parts, Pearl 30 parts, Aconitum 5 parts, Safflower 50 parts, Musk 10 parts, Bear Gall 10 parts, Toad Venom 10 parts, Borneol 5 parts.

[0042] In some embodiments, the active component and the synergist are in the same formulation unit or in different formulation units.

[0043] In some embodiments, the active component and the synergist are in different formulation units.

[0044] In some embodiments, the synergistic agent is a composition of each raw material mixed after being pulverized; or an extract of each raw material mixed after being extracted; or an extract of each raw material mixed after being extracted separately. Optionally, the extract is further refined and purified. The extraction method includes decoction extraction, reflux extraction, immersion extraction, ultrasonic extraction, percolation extraction, microwave extraction, etc. The refining and purifying method includes 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.

[0045] In some embodiments, the dosage form of the synergistic agent includes any one of decoction, tablet, capsule, granule, pill, oral liquid, powder or paste.

[0046] In some embodiments, the synergistic agent further comprises a pharmaceutically acceptable excipient.

[0047] In some embodiments, the active component is a composition of each raw material mixed after being pulverized; or an extract of each raw material mixed after being extracted; or an extract of each raw material mixed after being extracted separately. Optionally, the extract is further refined and purified. The extraction method includes decoction extraction, reflux extraction, immersion extraction, ultrasonic extraction, percolation extraction, microwave extraction, etc. The refining and purifying method includes 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.

[0048] In some embodiments, the dosage form of the active component includes any one of decoction, tablet, capsule, granule, pill, oral liquid, powder or paste.

[0049] In some embodiments, the active component further comprises a pharmaceutically acceptable excipient.

[0050] In some embodiments, the active component and the synergistic agent are administered simultaneously, separately or sequentially.

[0051] The third aspect of the present application provides use of the pharmaceutical composition of the second aspect in the preparation of a medicament for treating atherosclerosis.

[0052] In some embodiments, the medicament for treating atherosclerosis can improve at least one of the following efficacy indicators: aortic plaque area, blood vessel diastolic inner diameter difference, intima-media thickness, serum triglyceride content, cholesterol content, high-density lipoprotein cholesterol content, low-density lipoprotein cholesterol content and homocysteine content in blood.

[0053] Terminology In the present application, "parts by weight" can be any one of the 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 1 g of component a + 9 g of component b, or 10 g of component a + 90 g of component b, etc. In the traditional Chinese medicine composition, the percentage content of a certain component = (the weight fraction of the component / the sum of the weight fractions of all components) x 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%.

[0054] In the present application, "raw material medicine" refers to traditional Chinese medicinal materials as active medicinal materials in the traditional Chinese medicine composition of the present application. The traditional Chinese medicinal materials can include various forms, for example, the traditional 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. The raw material medicine in the present application can be a natural source of traditional Chinese medicinal materials, or an equivalent substitute of a natural source of traditional Chinese medicinal materials. For example, the calculus bovis can be selected from at least one of natural calculus bovis, cultivated calculus bovis, in vitro cultivated calculus bovis and artificial calculus bovis. The musk can be selected from at least one of natural musk and artificial musk.

[0055] The "pharmaceutically acceptable excipient" in the present invention includes at least one of a filler, a disintegrant, a diluent, a lubricant, a binder, a humectant, a flavoring agent, a suspending agent, a solvent, a sustained release agent, an emulsifying agent, an absorption enhancer, a surfactant, or a preservative. 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 sodium carboxymethyl cellulose, 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, microfine silica, talc, anhydrous silica gel, and magnesium stearate; the binder is selected from at least one of a cellulose derivative, an alginate, starch, water, dextrin, gelatin, hydroxypropyl cellulose, methyl cellulose, or polyvinylpyrrolidone; the humectant is selected from at least one of glycerin, Tween-80, oxyhydrogenated castor oil, sodium lauryl sulfate, and lecithin; the flavoring agent is selected from at least one of aspartame, sucralose, essence, stevioside, acesulfame potassium, citric acid, and sodium saccharin; the suspending agent is selected from at least one of microfine silica, beeswax, cellulose, sodium carboxymethyl cellulose, and solid polyethylene glycol; the solvent is selected from at least one of water, ethanol, liquid polyethylene glycol, isopropyl alcohol, Tween-80, glycerin, 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, polyhydroethylene, polycarbonate, epoxy resin, polyamide, acetal polymer, polyester, polyurethane, polyimide, and polystyrene derivative, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, gelatin, peach gum, polyvinylpyrrolidone; the emulsifying agent is selected from at least one of an anionic surfactant (such as sodium stearate, potassium stearate, sodium oleate, potassium oleate, calcium stearate, sodium dodecyl sulfate, cetyl sulfate castor oil), a zwitterionic surfactant (such as lecithin and soybean phospholipid), a nonionic surfactant (such as polysorbate, sorbitan fatty acid ester, poloxamer, glycerol monostearate, glycerol tristearate, sucrose stearate, polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether), gum arabic, gelatin, xanthan gum, oil-in-water (O / W) emulsifier (such as magnesium hydroxide, aluminum hydroxide, silicon dioxide, bentonite), water-in-oil (W / O) emulsifier (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 glycoside, EDTA, chitosan and its derivatives, polyamidoamine dendrimer (PAMAM); and the preservative is selected from at least one of methyl paraben, propyl paraben, chlorobutanol, benzalkonium chloride, benzyl alcohol, phenylethyl alcohol, and sorbic acid.The surfactant is selected from at least one of sodium dodecyl benzene sulfonate, stearic acid, polyoxyethylene-polyoxypropylene (PEO-PPO) block polyether, fatty acid sorbitan and polysorbate; and the preservative is selected from at least one of methyl or propyl p-hydroxybenzoate.

[0056] Example 1 The traditional Chinese medicine composition is prepared from the following raw medicinal materials: 200 parts of Huangqi, 150 parts of Xuanshen, 100 parts of Niu Bangzi, 150 parts of Bohe, 15 parts of Lianqiao, 20 parts of Jiegeng, 15 parts of Gancao, 40 parts of Banlangen, 10 parts of Mabu, 30 parts of Jiangcan, 20 parts of Chenpi, 10 parts of Chaihu, and 10 parts of Shengma.

[0057] Process preparation: The cleaned, washed and dried medicinal materials are weighed according to the prescription, crushed into fine segments with a length of less than 10 mm, and mixed uniformly for use. Water vapor distillation extraction is used to collect the emulsion containing volatile oil, and the extract is prepared. The residues are extracted with water (the ratio of medicinal materials to water is 1:3), and the extract is filtered. The combined extract is subjected to alcohol precipitation process, and the extract after alcohol precipitation is concentrated to obtain a concentrated liquid with a relative density of 1.05-1.20 at 65°C. More than 85% ethanol is added to the extract, mixed uniformly to make the alcohol content reach 70%, and then placed for 4 hours. The supernatant is filtered, and the alcohol is recovered under reduced pressure and concentrated to 65°C, and the relative density is 1.20-1.30. Volatile oil inclusion treatment: the collected volatile oil emulsion is subjected to preliminary ultrasonic inclusion treatment with water-soluble cyclodextrin, and then colloidal silicon dioxide is added for auxiliary gel inclusion to obtain a volatile oil inclusion compound. The volatile oil inclusion compound is mixed with the concentrated liquid, and then appropriate amounts of honey and sucrose are added. The pH value is adjusted to 5.0-5.5 with 10% sodium hydroxide solution, and then the volume is adjusted with purified water, filtered, sealed, sterilized, and obtained.

[0058] Example 2 The traditional Chinese medicine composition is prepared from the following raw medicinal materials: 300 parts of Huangqi, 200 parts of Xuanshen, 150 parts of Niu Bangzi, 200 parts of Bohe, 30 parts of Lianqiao, 40 parts of Jiegeng, 40 parts of Gancao, 70 parts of Banlangen, 30 parts of Mabu, 50 parts of Jiangcan, 25 parts of Chenpi, 15 parts of Chaihu, and 10 parts of Shengma.

[0059] Process preparation: The cleaned, washed and dried medicinal materials are weighed according to the prescription, crushed into fine segments with a length less than 10 mm, and mixed uniformly for use; water vapor distillation extraction is adopted, and the emulsion containing volatile oil is collected, and the extract is prepared; the residue is extracted with water again (the ratio of medicinal materials to water is 1:3), and the extract is filtered; the combined extract is subjected to alcohol precipitation process, the extract after alcohol precipitation is concentrated to obtain a concentrated solution with a relative density of 1.05-1.20 measured at 65℃; more than 85% of ethanol is added to the extract, mixed uniformly to make the alcohol content reach 70%, and then left to stand for 4 hours; the supernatant is filtered, and the alcohol is returned under reduced pressure and concentrated to 65℃, and the relative density is 1.20-1.30; volatile oil inclusion treatment: the collected volatile oil emulsion is subjected to preliminary ultrasonic inclusion treatment with water-soluble cyclodextrin, and then colloidal silicon dioxide is added for auxiliary gel inclusion to obtain a volatile oil inclusion compound; the volatile oil inclusion compound is mixed with the concentrated solution, and then an appropriate amount of honey and sucrose is added, and the pH value is adjusted to 5.0-5.5 with 10% sodium hydroxide solution, and then the volume is adjusted with purified water, filtered, filled and sealed, sterilized, and then the Chinese medicine composition is obtained.

[0060] Example 3 In this example, a traditional Chinese medicine composition is prepared, which is composed of the following raw medicinal materials by weight: Huangqi 400 parts, Xuan- shen 375 parts, Niu Bangzi 225 parts, Bohe 250 parts, Lianqiao 45 parts, Jiegeng 30 parts, Gancao 25 parts, Banlangen 55 parts, Mabu 50 parts, Jiangcan 45 parts, Chenpi 35 parts, Chaihu 20 parts, Shengma 20 parts.

[0061] Process preparation: The cleaned, washed and dried medicinal materials are weighed according to the prescription, crushed into fine segments with a length less than 10 mm, and mixed uniformly for use; water vapor distillation extraction is adopted, and the emulsion containing volatile oil is collected, and the extract is prepared; the residue is extracted with water again (the ratio of medicinal materials to water is 1:3), and the extract is filtered; the combined extract is subjected to alcohol precipitation process, the extract after alcohol precipitation is concentrated to obtain a concentrated solution with a relative density of 1.05-1.20 measured at 65℃; more than 85% of ethanol is added to the extract, mixed uniformly to make the alcohol content reach 70%, and then left to stand for 4 hours; the supernatant is filtered, and the alcohol is returned under reduced pressure and concentrated to 65℃, and the relative density is 1.20-1.30; volatile oil inclusion treatment: the collected volatile oil emulsion is subjected to preliminary ultrasonic inclusion treatment with water-soluble cyclodextrin, and then colloidal silicon dioxide is added for auxiliary gel inclusion to obtain a volatile oil inclusion compound; the volatile oil inclusion compound is mixed with the concentrated solution, and then an appropriate amount of honey and sucrose is added, and the pH value is adjusted to 5.0-5.5 with 10% sodium hydroxide solution, and then the volume is adjusted with purified water, filtered, filled and sealed, sterilized, and then the Chinese medicine composition is obtained.

[0062] Comparative Example 1 The present embodiment prepares a traditional Chinese medicine composition, which is composed of the following raw medicinal materials: 40 parts of Huangqi, 30 parts of Xuan- shen, 20 parts of Niu Bangzi, 50 parts of Bohe, 20 parts of Lianqiao, 5 parts of Rengeng, 5 parts of Gancao, 15 parts of Banlangen, 30 parts of Mabu, 20 parts of Jiangcan, 5 parts of Chenpi, 2 parts of Chaihu, and 2 parts of Shengma.

[0063] Process preparation: The prescription is weighed after cleaning, drying, and grinding into fine segments with a length of less than 10 mm, and then mixed uniformly for use; water vapor distillation extraction is used to collect the emulsion containing volatile oil, and the extract is prepared; the residue is extracted with water (the ratio of medicinal materials to water is 1:3), and the extract is filtered; the combined extract is subjected to alcohol precipitation process, and the extract after alcohol precipitation is concentrated to obtain a concentrated liquid with a relative density of 1.05-1.20 at 65°C; more than 85% ethanol is added to the extract, mixed uniformly to make the alcohol content reach 70%, and then placed for 4 hours; the supernatant is obtained by filtration, and the alcohol is recovered under reduced pressure and concentrated to 65°C, and the relative density is 1.20-1.30; volatile oil inclusion treatment: the collected volatile oil emulsion is subjected to preliminary ultrasonic inclusion treatment with water-soluble cyclodextrin, and then colloidal silicon dioxide is added for auxiliary gel inclusion to obtain a volatile oil inclusion compound; the volatile oil inclusion compound is mixed with the concentrated liquid, and then an appropriate amount of honey and sucrose is added, and the pH value is adjusted to 5.0-5.5 with 10% sodium hydroxide solution, and then the volume is adjusted with purified water, filtered, sealed, sterilized, and obtained.

[0064] Comparative Example 2 A commercially available antiviral oral solution has the following prescription: Banlangen 128.57 g, Shigao 57.14 g, Lugen 60.71 g, Dihuang 32.14 g, Yujin 25 g, Zhimu 25 g, Shichangpu 25 g, Guanghuoxiang 28.57 g, and Lianqiao 46.43 g. According to the Chinese Pharmacopoeia, the product contains not less than 25 μg of forsythiaside (C 27 H 34 O 11 ) per 1 ml of Lianqiao.

[0065] Comparative Example 3 The present embodiment prepares a traditional Chinese medicine composition, which has the effect of treating atherosclerosis, and is composed of the following raw medicinal materials: 450 parts of Renshen, 150 parts of Niu Huang, 70 parts of Lingzhi, 30 parts of Zhenzhu, 5 parts of Fuzi, 50 parts of Honghua, 10 parts of Mosha, 10 parts of Xiongdan, 10 parts of Can- su, and 5 parts of Bingpian.

[0066] Process preparation: Radix ginseng, calculus bovis, lucid ganoderma, pearl, aconite, safflower, bear gall, toad venom are decocted twice with water, and the filtrates are combined and concentrated to a thick extract with a relative density of 1.25-1.30 at 60°C; musk and borneol are separately powdered. The extract is vacuum-dried, mixed with the musk and borneol powders, and then ground to obtain a composite powder. A coating pan is provided with a built-in water spraying device, and the extract ethanol solution and the composite powder are alternately sprayed into the pan. After spraying the liquid, the pan is rolled for 5 minutes, and after sprinkling the powder, the pan is rolled for 10 minutes. The process is repeated until solid and slightly dense granules are formed. Then, a 1mm aperture pill die is used for screening, and the pills with a diameter of 1mm are collected as the finished product.

[0067] Pharmacological studies 1 Experimental methods 1.1 Modeling Combined with multiple literatures 1,2 , an atherosclerosis model was constructed: 80 SD rats were fed with high-methionine and high-fat feed containing 3% methionine for 6 weeks, and then injected intraperitoneally with vitamin D3 (6 million IU / kg) once every 2 weeks. At the same time, a group of SD rats (20) were fed with normal diet.

[0068] 1.2 Grouping and administration After 9 weeks of modeling, 3 rats were randomly selected from the modeling rats and the rats fed with normal diet, and the abdominal aorta was taken for blood test to detect the contents of serum TG, TC, LDL-C, HDL-C and homocysteine, and the thoracic aorta tissue was taken for oil red O staining to determine whether the model was successful.

[0069] The successfully modeled rats were randomly divided into a blank control group (control group, 10), a negative control group (AS group, 10), and experimental groups 1-4 (10 rats in each group). After modeling, the rats were administered as follows: Table 1 Grouping and administration scheme:

[0070] During the administration process, the blank control group was normally bred and fed, and the other groups were fed with high-methionine and high-fat feed containing 3% methionine.

[0071] 1.3 Echocardiography detection method A VE95 echocardiograph and a frequency (5-12) MHZ heart probe were used for heart structure and function evaluation, including collecting still images and dynamic images at the parasternal (long and short axis sections) and apical four-chamber (4, 5, 2 and 3 chambers). A preset condition was used to maintain the clarity and stability of the rat images: frequency (5-10) MHz, depth 2.5 cm, frame rate 125 fps, Doppler sampling 1.0 mm, and color Doppler mixing speed 40 cm / s. At least 3 cardiac cycles were recorded.

[0072] 1.4 Determination of TG, TC, HDL-c, LDL-c and homocysteine content in rat serum by ELISA method After 12 weeks of administration in each group, the rats were fasted overnight. After weighing, the rats were anesthetized, blood was taken by enucleation, and the rats were sacrificed to take the whole aorta. The blood was allowed to stand at 4°C for 12 h, centrifuged at 12 000 r / min for 15 min, and the supernatant was taken and stored at -80°C.

[0073] The TG, TC, HDL-c, LDL-c and homocysteine content in serum was detected by enzyme-linked immunoassay kit, and the specific detection method was described in the instruction manual of the kit.

[0074] 1.5 Oil red O staining of aorta The whole aorta was placed in 4% paraformaldehyde for fixation for more than 24 hours, taken out, washed with PBS for 3 times, 5 minutes each time, the excess connective tissue was stripped under a stereomicroscope, placed in oil red O staining solution at 45°C for 15 minutes, differentiated with 75% ethanol, and placed on a black rubber pad for photography. After the heart was fixed and paraffin-embedded, the section thickness was 3 μm, and after dewaxing to water, HE staining was performed: hematoxylin staining for 8 minutes, differentiation solution for 2 seconds, tap water for 3 minutes, and eosin staining for 45 seconds. Masson staining: hematoxylin for 3 minutes, acidic differentiation solution for 2 seconds, distilled water for 10 minutes, ponceau red for 8 minutes, weak acid working solution for washing, phosphomolybdate for 6 minutes, and aniline blue for 5 minutes. All were sealed with neutral gum, observed and photographed under an optical microscope, and analyzed by HE and Masson staining using ImageJ software.

[0075] 2. Experimental results 2.1 Evaluation of atherosclerosis-related aortic indicators intima-media thickness (IMT) and dimers-dimerd (Ds-Dd) The changes in IMT and Ds-Dd of rat aorta detected by echocardiography are shown in Table 2. The results showed that compared with the Control group, the IMT and Ds-Dd of the aorta of the AS group were significantly increased, and the difference was statistically significant (P<0.01). Compared with the AS group, the experimental group 2 significantly improved the atherosclerosis indicators such as IMT and Ds-Dd of the rat aorta (P<0.05, P<0.01), and was better than the experimental group 1. There was no statistically significant difference in the improvement effect between the experimental group 3-4 and the experimental group 1.

[0076] Table 2 Changes in IMT and Ds-Dd of rat aorta (x±s, n=10):

[0077] Note: compared with Control group, ##, P<0.01. Compared with negative control group, *, P<0.05; **, P<0.01. Compared with experimental group 1, P<0.05. P<0.01.

[0078] 2.2 Evaluation of blood lipid in rats Compared with Control group, the TC, TG and LDL-C of negative control rats were increased (Table 3, P<0.01), and the HDL-C was decreased (Table 3, P<0.01), indicating that the AS model rats showed symptoms of hyperlipidemia. Compared with negative control group, the TC, TG and LDL-C of experimental group 2 rats were decreased (P<0.01), and the HDL-C was increased (P<0.01), and the improvement effect of the above indexes was more significant compared with experimental group 1 (P<0.05); the treatment effect of experimental groups 3-4 was equivalent to that of experimental group 1.

[0079] Table 3 Changes of blood lipid in rats of each group (x±s, n=10):

[0080] Note: compared with Control group, #, P<0.05; ##, P<0.01. Compared with negative control group, *, P<0.05; **, P<0.01. Compared with experimental group 1, P<0.05. P<0.01.

[0081] 2.3 Evaluation of homocysteine content The results are shown in Table 4. Compared with Control group, the homocysteine content of negative control rats was significantly increased (P<0.01). Compared with negative control group, the homocysteine of experimental group 2 rats was significantly decreased, and the treatment effect was better than that of experimental group 1, and there was no statistically significant difference between experimental groups 3-4 and experimental group 1.

[0082] Table 4 Changes of homocysteine content in blood of rats of each group (x±s, n=10):

[0083] Note: compared with Control group, ##, P<0.01. Compared with negative control group, *, P<0.05; **, P<0.01. Compared with experimental group 1, P<0.05. P<0.01.

[0084] 2.4 Aortic oil red O staining As shown in Table 5, compared with the Control group, the oil red staining area ratio of the negative control rats was significantly increased (P<0.01). Compared with the negative control, the oil red staining area ratio of the aorta of the rats in the experimental group 2 was significantly decreased, and there was no difference between the experimental groups 3-4 and the experimental group 1.

[0085] Table 5 Percentage of oil red staining area of aorta of rats in each group (x±s, n=10):

[0086] Note: compared with the Control group, ###, p<0.001. Compared with the negative control, *, p<0.05; **, p<0.01; compared with the experimental group 1, , p<0.05; , p<0.01.

[0087] The above results show that the traditional Chinese medicine composition in Example 1 can significantly improve the therapeutic effect of the traditional Chinese medicine composition for treating atherosclerosis and reduce the dosage.

[0088] It has been verified that the traditional Chinese medicine composition in Example 2 and Example 3 has similar effects to the traditional Chinese medicine composition in Example 1 in improving the therapeutic effect of the traditional Chinese medicine composition for treating atherosclerosis.

[0089] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application shall be equivalent replacement methods, and all shall be included in the protection scope of the present application.

[0090] References: [1] Dai Y, Wei JP, Pan T, et al. Study on preparation of high homocysteine rat model by intragastric administration of methionine [J]. Chinese Journal of Basic and Clinical Medicine, 2017, 23(12): 1697-1700. DOI:10.19945 / j.cnki.issn.1006-3250.2017.12.019.

[0091] [2] Chen Z M, Liu XL, Huang N, et al. Study on the effect of Wenyang Huoxue Jiedu recipe on regulating RIPK1 / NLRP3 / Caspase-1 and stabilizing vulnerable atherosclerotic plaque [J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2024, 33(22): 3067-3072+3087.

Claims

1. Use of a composition in the preparation of a medicine synergist for treating atherosclerosis, the composition being made of raw medicinal materials including: Scutellaria 50-450 parts, Figwort 50-450 parts, Burdock 25-265 parts, Mint 100-350 parts, Forsythia 10-60 parts, Platycodon 5-80 parts, Licorice 10-85 parts, Indigo 20-160 parts, Calvatia 2-75 parts, Silkworm 10-80 parts, Orange Peel 5-40 parts, Bupleurum 5-20 parts, Cimicifuga 2-20 parts, the medicine for treating atherosclerosis being made of raw medicinal materials including: Ginseng 400-600 parts, Ox Gallstone 150-300 parts, Ganoderma 50-150 parts, Pearl 15-50 parts, Aconite 2-10 parts, Safflower 20-100 parts, Musk 2-20 parts, Bear Gall 5-15 parts, Toad Venom 4-20 parts, Borneol 2-10 parts.

2. Use according to claim 1, characterized in that, The composition is made of raw medicinal materials including: Scutellaria 200-450 parts, Figwort 200-425 parts, Burdock 100-200 parts, Mint 100-200 parts, Forsythia 10-50 parts, Platycodon 5-75 parts, Licorice 10-80 parts, Indigo 20-80 parts, Calvatia 5-60 parts, Silkworm 10-60 parts, Orange Peel 10-40 parts, Bupleurum 5-20 parts, Cimicifuga 5-20 parts.

3. Use according to claim 1, characterized in that, The medicine for treating atherosclerosis is made of raw medicinal materials including: Ginseng 450-600 parts, Ox Gallstone 150-280 parts, Ganoderma 70-150 parts, Pearl 15-45 parts, Aconite 2-8 parts, Safflower 20-80 parts, Musk 2-18 parts, Bear Gall 5-12 parts, Toad Venom 4-15 parts, Borneol 2-8 parts.

4. A pharmaceutical composition including an active component and a synergist, the synergist being made of raw medicinal materials including: Scutellaria 50-450 parts, Figwort 50-450 parts, Burdock 25-265 parts, Mint 100-350 parts, Forsythia 10-60 parts, Platycodon 5-80 parts, Licorice 10-85 parts, Indigo 20-160 parts, Calvatia 2-75 parts, Silkworm 10-80 parts, Orange Peel 5-40 parts, Bupleurum 5-20 parts, Cimicifuga 2-20 parts; The active component is made of raw medicinal materials including: Ginseng 400-600 parts, Ox Gallstone 150-300 parts, Ganoderma 50-150 parts, Pearl 15-50 parts, Aconite 2-10 parts, Safflower 20-100 parts, Musk 2-20 parts, Bear Gall 5-15 parts, Toad Venom 4-20 parts, Borneol 2-10 parts.

5. The pharmaceutical composition of claim 4, wherein, The synergist is made of raw medicinal materials including: Scutellaria 200-450 parts, Figwort 200-425 parts, Burdock 100-200 parts, Mint 100-200 parts, Forsythia 10-50 parts, Platycodon 5-75 parts, Licorice 10-80 parts, Indigo 20-80 parts, Calvatia 5-60 parts, Silkworm 10-60 parts, Orange Peel 10-40 parts, Bupleurum 5-20 parts, Cimicifuga 5-20 parts.

6. The pharmaceutical composition of claim 4, wherein, The active ingredient is made of raw medicinal materials including ginseng 450-600 parts, ox gall 150-280 parts, lucid ganoderma 70-150 parts, pearl 15-45 parts, monkshood 2-8 parts, safflower 20-80 parts, musk 2-18 parts, bear gall 5-12 parts, toad venom 4-15 parts, and borneol 2-8 parts.

7. The pharmaceutical composition of claim 4, wherein, The active ingredient and the synergist are in the same formulation unit or in different formulation units.

8. The pharmaceutical composition of claim 4, wherein, The active ingredient and the synergist are administered simultaneously, separately or sequentially.

9. The pharmaceutical composition of claim 4, wherein, The pharmaceutical composition further comprises pharmaceutically acceptable adjuvants.

10. Use of the pharmaceutical composition of any one of claims 4-9 in the preparation of a medicament for treating atherosclerosis.

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