A traditional Chinese medicine composition for preventing and treating metabolic cardiovascular diseases, a preparation method and application thereof

Abstract

The application belongs to the field of traditional Chinese medicines, and particularly discloses a traditional Chinese medicine composition for preventing and treating metabolic cardiovascular diseases, a preparation method and application. The traditional Chinese medicine composition is composed of 10-20g of Huangqi, 10-20g of Chishao, 5-15g of Zexie, 5-15g of Lingzhi, 5-10g of Chenpi and 5-10g of Huanglian. The traditional Chinese medicine composition can benefit qi and activate blood, resolve turbidity and detoxify, regulate blood lipid, blood sugar and other AS metabolic risk factors, mediate anti-inflammatory, lipid-lowering, blood sugar-lowering, weight loss, inhibit AS plaque formation, increase AS plaque stability, delay AS progression, and can be used for effectively treating CMD.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a traditional Chinese medicine composition for the prevention and treatment of metabolic cardiovascular diseases, its preparation method, and its application. Background Technology

[0002] Metabolic cardiovascular disease (CMD) refers to cardiovascular diseases caused by metabolic risk factors, excluding other cardiovascular causes such as structural heart disease, arrhythmia, and cardiomyopathy. With the accelerating aging of the population, the incidence and mortality rates of CMD are rising year by year. It frequently triggers cardiovascular events, seriously endangering public health and affecting patients' quality of life, and has become a significant burden on global public health.

[0003] Patients with chronic cardiovascular disease (CMD) often have long-term metabolic risk factors such as dyslipidemia, hypertension, obesity, and glucose metabolism disorders. These factors synergistically promote vascular endothelial damage, activate inflammatory responses, and accelerate lipid accumulation, ultimately leading to the development and progression of atherosclerosis (AS). Therefore, CMD not only manifests as metabolic disorders but also involves AS lesions. Its pathological basis includes glucose and lipid metabolism disorders and the resulting damage to vascular structure and function. Atherosclerotic cardiovascular disease (ASCVD) is one of the main clinical manifestations of CMD and a key cause of cardiovascular events and death caused by CMD. Studies have shown that effective management of metabolic risk factors can effectively delay the progression of AS, significantly reduce the occurrence of cardiovascular events, and improve patient clinical outcomes. However, there is currently a lack of clinical guidelines for the diagnosis and treatment of CMD, and large-scale, standardized clinical studies have not yet been conducted. Therefore, there is an urgent need to develop effective drugs that synergistically regulate metabolic disorders and delay the progression of AS to meet the needs of CMD prevention and treatment.

[0004] According to traditional Chinese medicine theory, CMD's fundamental pathogenesis is blood turbidity. The *Ling Shu* (Spiritual Pivot), in its chapter on *Jing Shui* (Classic of Water), states, "The clarity and turbidity of blood...all have a great number," meaning that blood components exceeding normal levels constitute blood turbidity. Due to disordered glucose and lipid metabolism, CMD leads to the accumulation of large amounts of metabolic products within the blood vessels, obstructing the blood vessels and forming blood turbidity, which can ultimately induce chest pain and angina. The pathological processes that occur during the progression of CMD, such as endothelial damage, lipid deposition, platelet activation and aggregation, and inflammatory reactions, correspond to deficiencies in the blood vessels, phlegm turbidity and blood stasis, and the accumulation of toxins. CMD patients often have a fondness for rich and fatty foods, easily damaging the spleen and stomach. Disruption of the spleen and stomach's ascending and descending functions, disordered metabolism of food essence, and insufficient distribution of body fluids lead to the formation of phlegm turbidity. Phlegm turbidity can affect blood circulation, and prolonged blood stasis leads to internal blood stasis. The accumulation of phlegm turbidity and blood stasis in the body, over time, transforms into toxins. Furthermore, in CMD patients, metabolic byproducts such as glucose and lipid toxins accumulate in the blood vessels, causing poor blood circulation and leading to blood stasis. Over time, this can further damage Qi and Yin. Qi deficiency weakens blood circulation, while Yin deficiency and internal heat deplete body fluids, resulting in stagnation and blood stasis. Over time, this stagnation transforms into heat and toxins, forming a complex pathogenesis of "deficiency, stasis, turbidity, and toxins." This pathological process is similar to the mechanism of plaque progression and rupture in modern medicine, where the mutual binding of blood stasis and toxins obstructs the heart vessels, which is the core pathological link in triggering cardiovascular events. Therefore, treating CMD from the perspective of deficiency, stasis, turbidity, and toxins, with "tonifying Qi and activating blood circulation, resolving turbidity and detoxifying" as the basic treatment principle, may achieve better clinical efficacy.

[0005] Chinese invention patent application CN120189462A discloses a traditional Chinese medicine composition with the function of regulating glucose and lipid metabolism. The key technical points of the composition are: the composition consists of Cirsium japonicum, Phyllanthus emblica, Citrus medica, and Cassia tora. This invention's traditional Chinese medicine compound has the effects of regulating blood lipids, reducing inflammation, and treating hepatic steatosis. Although this invention has similar effects on regulating metabolic-related indicators to the present invention, it does not show any anti-atherosclerotic effects.

[0006] Chinese invention patent application CN116966252A discloses a traditional Chinese medicine composition for treating menopausal ankylosing spondylitis (AS). The key technical points are: the composition consists of 10-20g of *Dioscorea nipponica*, 5-15g of *Curcuma zedoaria*, 5-15g of *Paeonia lactiflora*, and 3-7g of *Coptis chinensis*. This composition has the effects of dispelling wind and promoting blood circulation, removing blood stasis and eliminating masses. Although both this invention and the present invention contain *Paeonia lactiflora* and *Coptis chinensis*, and have similar effects in lowering lipids, anti-inflammation, and anti-AS, the traditional Chinese medicine components and preparation techniques used in this invention differ significantly. Furthermore, this invention mainly targets menopausal women, thus its applicability is somewhat limited. In addition, this invention does not formulate its prescription from the perspective of invigorating qi and promoting blood circulation, and resolving turbidity and detoxifying, so its therapeutic effect on CMD may be somewhat insufficient. Summary of the Invention

[0007] Based on the shortcomings of existing technologies, this invention proposes to incorporate qi-tonifying and turbidity-reducing drugs into the existing "blood-activating and detoxifying" approach for treating CMD, aiming to achieve better results. Therefore, this invention aims to provide a traditional Chinese medicine composition with therapeutic effects on CMD, capable of tonifying qi and activating blood circulation, eliminating turbidity and detoxifying, regulating metabolic risk factors of ankylosing spondylitis (AS) such as blood lipids and blood sugar, mediating anti-inflammatory, lipid-lowering, blood sugar-lowering, weight-loss, inhibition of AS plaque formation, increase of AS plaque stability, and delay of AS progression, and can be used to treat CMD.

[0008] Based on the above objectives, the present invention first provides a traditional Chinese medicine composition for treating CMD, characterized in that: the traditional Chinese medicine composition is composed of Astragalus membranaceus, Paeonia lactiflora, Alisma plantago-aquatica, Ganoderma lucidum, Citrus reticulata peel and Coptis chinensis.

[0009] Specifically, the formula consists of: 10-20g Astragalus membranaceus, 10-20g Paeonia lactiflora, 5-15g Alisma plantago-aquatica, 5-15g Ganoderma lucidum, 5-10g Citrus reticulata peel, and 5-10g Coptis chinensis.

[0010] Preferably, the weight ratio of Astragalus membranaceus, Paeonia lactiflora, Alisma plantago-aquatica, Ganoderma lucidum, Citrus reticulata peel and Coptis chinensis in the traditional Chinese medicine composition is 3:3:2:2:1.2:1.2.

[0011] More preferably, the formula is as follows: Astragalus membranaceus 15g, Paeonia lactiflora 15g, Alisma plantago-aquatica 10g, Ganoderma lucidum 10g, Citrus reticulata 6g, and Coptis chinensis 6g.

[0012] Specifically, it is a mixture of various drugs, or a decoction obtained by decocting a mixture of various drugs.

[0013] The present invention also provides a method for preparing the traditional Chinese medicine composition, which involves mixing the various medicinal ingredients in proportion to obtain a mixture; further, soaking the mixture in water, decocting the soaked medicinal ingredients, mixing the decocted decoction, and filtering it with gauze to obtain the final product.

[0014] Specifically, the ratio of the total weight of each drug to the amount of water is 1g:3-8mL, preferably 1g:4-6mL, for example 1g:5mL.

[0015] More specifically, the soaking time is 0.5-4 hours, preferably 1-3 hours, for example 3 hours.

[0016] In a specific implementation, the decoction is performed 1-3 times, for example 2 times, each time for 20-40 minutes, for example 25-35 minutes, and the decoction obtained from each decoction is mixed together.

[0017] The present invention also provides the use of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for treating CMD.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0019] (1) The inventors believe that the key pathogenesis of CMD is blood turbidity. Blood turbidity accumulates in the blood vessels, causing poor blood circulation and stagnation, which can further damage Qi and Yin over time. Qi deficiency leads to weak blood circulation, while Yin deficiency and internal heat deplete body fluids, resulting in stagnation and blood stasis. Over time, this stagnation transforms into heat and toxins, ultimately forming a complex pathogenesis of "deficiency, stasis, turbidity, and toxins" coexisting. Therefore, the key to the treatment of CMD in this invention lies in invigorating Qi and promoting blood circulation, as well as resolving turbidity and detoxifying. This invention is designed and verified based on this principle.

[0020] (2) The traditional Chinese medicine composition of the present invention contains Astragalus membranaceus, Paeonia lactiflora, Alisma plantago-aquatica, Ganoderma lucidum, Citrus reticulata, and Coptis chinensis. Astragalus membranaceus is the principal ingredient, which invigorates qi and strengthens the exterior, replenishes qi and raises yang, and warms and unblocks the heart vessels. Ganoderma lucidum is used as an adjuvant to replenish qi and calm the mind, detoxify and support the body's resistance, and regulate the heart vessels. Paeonia lactiflora clears heat and cools the blood, invigorates blood and removes blood stasis. Coptis chinensis clears and transforms the heat and toxins accumulated in the blood vessels, and at the same time can guide the medicine into the heart meridian and blood vessels. Citrus reticulata regulates qi and resolves phlegm, strengthens the spleen and dries dampness. Alisma plantago-aquatica promotes diuresis and eliminates dampness, clears heat and transforms turbidity, and together they achieve the effect of strengthening the spleen and transforming turbidity. The present invention creatively combines the above-mentioned traditional Chinese medicine composition to achieve the effects of invigorating blood and removing blood stasis, strengthening the spleen and transforming turbidity, invigorating qi and detoxifying, and clearing blood vessels, thereby having a better effect in preventing and treating CMD.

[0021] (3) The herbal composition of this invention is simple in formulation yet highly effective. Pharmacological experiments revealed that the herbal composition of this invention can reduce body weight, regulate blood lipid levels, decrease serum TC, TG, and LDL levels while increasing HDL levels. It can significantly reduce the levels of inflammatory factors IL-1β, IL-6, TNF-α, and MCP-1, lower blood glucose levels, reduce aortic AS plaque area, increase plaque stability, and delay AS progression, thus exhibiting significant protective and preventative effects against CMD and CMD-induced ASCVD. Compared with most existing formulations whose main function is to invigorate blood and detoxify, experimental results show that the herbal composition of this invention has better preventative and therapeutic effects. Attached Figure Description

[0022] Figure 1 The values ​​represent the serum lipid levels in mice studied in this invention (**Compared with the normal group, P<0.01; #Compared with the model group, P<0.05; ##Compared with the model group, P<0.01; Compared with the low-dose group in the example, P<0.05).

[0023] Figure 2 Image A is a representative HE-stained image (150X) of the aortic root of mice in the experimental study of this invention; Image B is a semi-quantitative analysis of the plaque area of ​​the aortic root of mice in the experimental study of this invention (**P<0.01 compared with the normal group; ##P<0.01 compared with the model group; ▼P<0.05 compared with the high-dose group).

[0024] Figure 3Image A is a representative image (150X) of Masson staining of the aortic root of mice in the experimental study of this invention; Image B is a semi-quantitative analysis of collagen content in the aortic root of mice in the experimental study of this invention (**P<0.01 compared with the normal group; #P<0.05 compared with the model group; ##P<0.01 compared with the model group; ▼▼P<0.01 compared with the high-dose group).

[0025] Figure 4 The values ​​represent the mouse body weight levels in the experimental study of this invention (*P<0.05 compared to the normal group; **P<0.01 compared to the normal group; #P<0.05 compared to the model group; ##P<0.01 compared to the model group).

[0026] Figure 5 The values ​​represent the serum inflammatory factor levels in mice during the experimental study of this invention (**P<0.01 compared with the normal group; ##P<0.01 compared with the model group).

[0027] Figure 6 The fasting blood glucose level of mice in the experimental study of this invention is shown in the figure (**P<0.01 compared with the normal group; #P<0.05 compared with the model group). Detailed Implementation

[0028] The present invention will be described below through specific embodiments in order to better understand the present invention, but this does not constitute a limitation on the present invention.

[0029] Example 1: Preparation of a Traditional Chinese Medicine Composition for Treating CMD

[0030] The weight ratio of Astragalus membranaceus, Paeonia lactiflora, Alisma plantago-aquatica, Ganoderma lucidum, Citrus reticulata peel, and Coptis chinensis in the traditional Chinese medicine composition is 3:3:2:2:1.2:1.2. The specific proportions of the traditional Chinese medicine composition are: Astragalus membranaceus 15g, Paeonia lactiflora 15g, Alisma plantago-aquatica 10g, Ganoderma lucidum 10g, Citrus reticulata peel 6g, and Coptis chinensis 6g.

[0031] The traditional Chinese medicine composition was prepared according to the following method:

[0032] (1) Weigh out the prescribed amounts of Astragalus membranaceus, Paeonia lactiflora, Alisma plantago-aquatica, Ganoderma lucidum, Citrus reticulata and Coptis chinensis respectively, mix the above drugs, add water to soak, the ratio of drug weight to water volume is 1g:5mL, soak for 2h;

[0033] (2) The soaked medicine was decocted twice, each time for 30 minutes. The decoctions obtained from the two decoctions were mixed and filtered through gauze to obtain 300 ml of Chinese medicine mixture.

[0034] Comparative Example 1

[0035] The formula is as follows: Angelica sinensis 15g, Salvia miltiorrhiza 15g, Curcuma zedoaria 10g, Paeonia lactiflora 10g, Ligusticum chuanxiong 10g, Coptis chinensis 5g.

[0036] Both Comparative Example 1 and the present invention contain ingredients such as Paeonia lactiflora and Coptis chinensis, and have the effect of "activating blood circulation and detoxifying," showing some similarity to the present invention in terms of formulation and efficacy. However, the formulation of Comparative Example 1 focuses on simply activating blood circulation and detoxifying, failing to systematically design a holistic approach targeting the "deficiency, stasis, phlegm, and toxin" pathogenesis of CMD. It lacks ingredients for tonifying the middle energizer and replenishing qi, as well as strengthening the spleen and resolving turbidity, resulting in limited efficacy in improving metabolic disorders and regulating blood lipids.

[0037] The comparative example of traditional Chinese medicine composition was prepared according to the following preparation method:

[0038] (1) Weigh out the prescribed amounts of Angelica sinensis, Curcuma zedoaria, Paeonia lactiflora, Salvia miltiorrhiza, Ligusticum chuanxiong, and Coptis chinensis respectively, mix the above drugs, add them to water for soaking, the ratio of drug weight to water volume is 1g:5mL, soak for 2h;

[0039] (2) The soaked medicine was decocted twice, each time for 30 minutes. The decoctions obtained from the two decoctions were mixed and filtered through gauze to obtain 300 ml of Chinese medicine mixture.

[0040] Comparative Example 2

[0041] The formula is as follows: Astragalus membranaceus 15g, Paeonia lactiflora 10g, Alisma plantago-aquatica 10g, Ganoderma lucidum 10g, Citrus reticulata 6g, Coptis chinensis 10g.

[0042] The Chinese medicine composition in Comparative Example 2 also follows the formulation principle of "activating blood circulation and removing blood stasis, strengthening the spleen and removing turbidity, replenishing qi and detoxifying, and clearing blood vessels". However, the ratio of blood-activating drugs to detoxifying drugs is adjusted to 1:1, and the ratio of all drugs is 3:2:2:2:1.2:2.

[0043] The comparative example of traditional Chinese medicine composition was prepared according to the following preparation method:

[0044] (1) Weigh out the prescribed amounts of Astragalus membranaceus, Paeonia lactiflora, Alisma plantago-aquatica, Ganoderma lucidum, Citrus reticulata and Coptis chinensis respectively, mix the above drugs, add water to soak, the ratio of drug weight to water volume is 1g:5mL, soak for 2h;

[0045] (2) The soaked medicine was decocted twice, each time for 30 minutes. The decoctions obtained from the two decoctions were mixed and filtered through gauze to obtain 300 ml of Chinese medicine mixture.

[0046] Test case

[0047] The following test experiments demonstrate that the traditional Chinese medicine composition of the present invention can be used to prepare a drug for treating CMD.

[0048] 1. Experimental Materials

[0049] 1.1 Laboratory Animals

[0050] The control group consisted of male C57BL / 6J mice at 6 - 7 weeks of age, and the experimental group consisted of male ApoE mice at 6 - 7 weeks of age with the same genetic background. - / - The mice weighed 20 ± 2 g and were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Experimental Animal Production License Number: SCKX (Beijing) 2021 - 0006).

[0051] 1.2 Feed

[0052] High - sugar and high - fat diet for mice (fat 21.2%, carbohydrate 49.1%, protein 19.8%, cholesterol 0.2%): provided by Xiaoshu Youtai Biotechnology Co., Ltd., product number D12079B.

[0053] 1.3 Experimental drugs

[0054] Positive control drug: Atorvastatin was purchased from Pfizer Pharmaceuticals Ltd. (USA), national drug approval number: H20051407. According to the equivalent dose ratio table of human and animal body surface area, the dose for mice was calculated to be 10 mg / kg / d of atorvastatin by gavage.

[0055] Research drugs: Traditional Chinese medicine compositions prepared in Example 1, Comparative Example 1, and Comparative Example 2.

[0056] The traditional Chinese medicine composition in Example 1 consisted of 15 g of Astragalus membranaceus, 15 g of Paeonia lactiflora, 10 g of Alisma orientale, 10 g of Ganoderma lucidum, 6 g of Citrus reticulata, and 6 g of Coptis chinensis. The Chinese herbal pieces were purchased from Beijing Kangrentang Pharmaceutical Co., Ltd. Astragalus membranaceus, Paeonia lactiflora, Alisma orientale, Ganoderma lucidum, Citrus reticulata, and Coptis chinensis were mixed, soaked in water, and the ratio of the weight of the drug to the amount of water was 1 g:5 mL. After soaking for 2 h, the drug was decocted twice, each time for 30 min. The decoctions obtained from the two decoctions were mixed and filtered through gauze to obtain 300 ml of traditional Chinese medicine mixture, which was the high - dose concentration liquid medicine in the experiment. The high - dose concentration liquid medicine was diluted 2 times to obtain the low - dose concentration liquid medicine.

[0057] The traditional Chinese medicine composition in Comparative Example 1 consisted of 15 g of Angelica sinensis, 15 g of Salvia miltiorrhiza, 10 g of Curcuma zedoaria, 10 g of Paeonia lactiflora, 10 g of Ligusticum chuanxiong, and 5 g of Coptis chinensis. The Chinese herbal pieces were purchased from Beijing Kangrentang Pharmaceutical Co., Ltd. The decoction method was the same as that in Example 1.

[0058] The traditional Chinese medicine composition in Comparative Example 2 consisted of 15 g of Astragalus membranaceus, 10 g of Paeonia lactiflora, 10 g of Alisma orientale, 10 g of Ganoderma lucidum, 6 g of Citrus reticulata, and 10 g of Coptis chinensis. The Chinese herbal pieces were purchased from Beijing Kangrentang Pharmaceutical Co., Ltd. The decoction method was the same as that in Example 1.

[0059] 2 Experimental methods

[0060] 2.1 Grouping and administration

[0061] A total of 10 C57BL / 6J mice were used as the normal group, and the experimental group ApoE- / - Mice were randomly divided into five groups: model group, low-dose group of the example, high-dose group of the example, positive control group, and comparative group, with 10 mice in each group. The experimental groups were administered the corresponding drug by gavage, while the normal control group was administered an equal volume of physiological saline by gavage, once daily at a volume of 0.1 ml / 10g, for 8 weeks. Specific grouping and intervention measures are shown in Table 1.

[0062] Table 1 Grouping and Intervention Methods

[0063]

[0064] 2.2 Specimen Collection

[0065] Mice were acclimatized for one week and then fed a high-sugar, high-fat diet for eight weeks. Once the high-sugar, high-fat model was confirmed, the mice were given the drug, with an eight-week administration period. Samples were collected eight weeks after gavage administration, with mice fasted for 12 hours but allowed free access to water before sample collection. Mice were anesthetized with 0.1% sodium pentobarbital, and blood was collected via enucleation. The blood was allowed to stand at room temperature for 2 hours until stratification occurred, then centrifuged at 3000 rpm for 15 minutes at 4°C. The supernatant serum was collected and frozen at -80°C. After blood collection, the heart was exposed by opening the chest with sterile scissors. The connective tissue near the heart was grasped with forceps, the heart was lifted, and the dorsal vessels of the heart were severed. Finally, the diaphragm and abdominal viscera were carefully removed to expose the complete abdominal aorta. The aorta was severed below the bifurcation of the iliac artery, and small branches of the aorta were cut upwards along the spine to free them. The three branches of the aorta were then severed distally in the neck. In pre-cooled physiological saline, the connective tissue around the aorta was quickly dissected. The cleaned aorta was placed in a cryovial and fixed in 4% paraformaldehyde solution for relevant index testing.

[0066] 2.3 Experimental Testing

[0067] 2.3.1 Blood lipid level testing

[0068] The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) in mouse serum were measured using a fully automated biochemical analyzer.

[0069] 2.3.2 Aortic tissue examination

[0070] After fixing, dehydrating, and paraffin-impregnated aortic tissue, it was embedded in paraffin to prepare paraffin sections, which were then stored at room temperature for later use. HE and Masson staining were performed to observe the area and structure of plaques at the aortic root.

[0071] HE staining: After dewaxing and pretreating the paraffin sections to water, the sections were placed in high-resolution constant staining pretreatment solution and stained with hematoxylin and eosin respectively. Finally, the sections were dehydrated and mounted.

[0072] Masson staining: After dewaxing the paraffin sections to water, immerse the sections in Masson's solution, rinse the differentiated sections with 1% acetic acid, then immerse them in anhydrous ethanol for dehydration, and finally perform clearing and mounting.

[0073] 2.3.3 Serum inflammatory factor detection

[0074] The serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) in mice were detected by ELISA.

[0075] 2.3.4 Blood glucose testing

[0076] Mice were fasted for 12 hours before collection. They were then removed, fixed, and their tail tips were cut off. Blood glucose levels were measured using a glucometer.

[0077] 2.4 Statistical Analysis

[0078] Experimental results are expressed as mean ± standard deviation or mean ± standard error. For comparisons between groups, if the data conform to a normal distribution and have homogeneous variances, one-way ANOVA is used; if they do not conform to a normal distribution, nonparametric tests are used. A two-sided p-value < 0.05 is considered statistically significant.

[0079] 3 Experimental Results

[0080] 3.1 Blood lipid level testing (Comparative Example 1)

[0081] Changes in blood lipids in mice as follows Figure 1As shown in the figure. Compared with the normal group, the levels of TG, TC, and LDL in the model group mice were significantly increased (P < 0.01), and the level of HDL was significantly decreased (P < 0.01). Compared with the model group, the low- and high-dose traditional Chinese medicine composition in the examples, the positive control drug atorvastatin, and the traditional Chinese medicine composition in Comparative Example 1 all significantly reduced the levels of TG, TC, and LDL in mice (P < 0.01). Compared with the model group, the low- and high-dose traditional Chinese medicine composition in the examples and the positive control drug atorvastatin all significantly increased the level of HDL in mice (P < 0.01; P < 0.01; P < 0.05). Compared with the model group, there was no statistically significant difference in HDL level in the traditional Chinese medicine composition group in Comparative Example 1. The serum TC, TG, and LDL levels in the low-dose group of the traditional Chinese medicine composition in the examples were significantly lower than those in the traditional Chinese medicine composition group in Comparative Example 1 (P < 0.05). These results indicate that the traditional Chinese medicine composition in Example 1 is superior to the traditional Chinese medicine composition in Comparative Example 1 in regulating blood lipids.

[0082] Based on the above results, this invention subsequently conducted a series of pharmacodynamic experiments, including those on weight reduction, anti-inflammation, blood sugar reduction, and inhibition of AS progression, aiming to systematically evaluate the comprehensive therapeutic value of this traditional Chinese medicine composition. Since it has been confirmed that this invention has an advantage over the traditional Chinese medicine composition of Comparative Example 1 in regulating blood lipids, the subsequent experiments did not include a group containing the traditional Chinese medicine composition of Comparative Example 1.

[0083] 3.2 HE staining of atherosclerotic plaques in mice (Comparative Example 2)

[0084] To determine the optimal ratio of the traditional Chinese medicine composition, HE and Masson staining were performed on AS plaques in the aortic root. The experimental results are as follows:

[0085] like Figure 2 As shown, A is a representative HE-stained image (150X) of the aortic root of mice in the experimental study of this invention; B is a semi-quantitative analysis of the plaque area in the aortic root of mice in the experimental study of this invention. It can be seen from the figures that there are no plaques in the aortic lumen of the normal group mice. Compared with the normal group, the model group mice have obvious AS plaques in the aortic wall, and the arterial lumen is narrowed. Compared with the model group, administration of atorvastatin significantly reduced the plaque area (P < 0.01). Compared with the model group, both low and high doses of the herbal composition in the examples significantly reduced ApoE. - / - The aortic root plaque area in mice was measured (P < 0.01). The high dose showed a more significant effect in reducing plaque. Compared to the high dose of the herbal composition in the examples, the low dose of the herbal composition in the examples and the herbal composition in Comparative Example 2 resulted in significantly higher aortic root plaque areas in mice (P < 0.05). The high dose of the herbal composition in the examples did not show a significant difference in plaque reduction effect compared to the positive control drug atorvastatin.

[0086] In summary, the HE staining results indicate that the herbal composition in this example significantly inhibits the progression of AS and reduces pathological damage to the aorta. Furthermore, the high-dose herbal composition in this example demonstrates a significantly better plaque-reducing effect than the herbal composition in Comparative Example 2.

[0087] 3.3 Masson staining of atherosclerotic plaques in mice (Comparative Example 2)

[0088] like Figure 3 As shown in the figure, A is a representative image (150X) of Masson staining of the aortic root of mice in the experimental study of this invention; B is a semi-quantitative analysis of collagen content in the aortic root of mice in the experimental study of this invention. As can be seen from the figure, no obvious plaques were observed in the aortic lumen of the normal group mice, and the collagen in the vessel wall was neatly arranged. However, different degrees of plaques were observed in the aortic lumen of the model group, the low- and high-dose groups of the traditional Chinese medicine composition in the examples, and the positive control group mice. These plaques contained loosely arranged, blue-stained, and broken collagen. Compared with the normal group, the collagen content in the aortic plaques of the model group was significantly reduced (P<0.01). Compared with the model group, administration of the positive control drug atorvastatin significantly increased collagen content (P<0.01). Compared with the model group, the low- and high-dose groups of the traditional Chinese medicine composition in the examples significantly increased the collagen content in the aortic plaques of mice and improved the collagen breakage in the aorta. The high-dose group of the traditional Chinese medicine composition in the examples showed a more significant effect (P<0.05; P<0.01). Compared with the high-dose group of the traditional Chinese medicine composition in the examples, the proportion of collagen content in the aortic root plaque of mice with the low-dose group of the traditional Chinese medicine composition in the examples and the traditional Chinese medicine composition in Comparative Example 2 was significantly lower (P < 0.01). The high-dose group of the traditional Chinese medicine composition in the examples and the positive control drug atorvastatin had no significant difference in the effect of increasing the collagen content in the plaque.

[0089] In summary, the Masson staining results further validated the positive effect of the traditional Chinese medicine composition in improving the collagen fiber structure within AS plaques. These results indicate that the traditional Chinese medicine composition in this example can not only inhibit AS plaque formation but also repair arterial damage, increase collagen content, enhance the structural integrity and function of the vessel wall, and stabilize AS plaques. Furthermore, the high-dose traditional Chinese medicine composition in this example showed a significantly better effect than the traditional Chinese medicine composition in Comparative Example 2 in increasing collagen content within plaques.

[0090] Therefore, based on the experimental results of HE staining of mouse atherosclerotic plaques (3.2 above) and Masson staining of mouse atherosclerotic plaques (3.3 above), the drug ratio of the herbal composition in the subsequent examples was selected as the final ratio. The drug ratio of 3:3:2:2:1.2:1.2 used in this invention reflects the principle of orderly primary and secondary components and synergistic consideration in traditional Chinese medicine formulation. Since it has been confirmed that this invention has advantages over the herbal composition of Comparative Example 2 in reducing the area of ​​AS plaques, increasing the collagen content in AS plaques, and stabilizing AS plaques, the herbal composition group of Comparative Example 2 was not included in subsequent experiments.

[0091] 3.4 Changes in mouse body weight

[0092] Week 0 was defined as the start of a high-sugar, high-fat diet. Mouse body weight was recorded weekly. Mouse body weight changes were as follows: Figure 4 As shown in the figure. In the initial stage of high-sugar, high-fat feeding, there was no significant difference in body weight among the groups (P > 0.05), while the body weight of the model group mice increased rapidly over time. After 10 weeks of high-sugar, high-fat diet, the body weight of the model group mice began to show a significant difference compared to the normal group (P < 0.05). After 12 weeks of high-sugar, high-fat diet, the difference in body weight between the model group and the normal group further increased (P < 0.01), a classic manifestation of CMD. After 4 weeks of drug intervention, the body weight difference between the high-dose group of the traditional Chinese medicine composition and the model group began to be significant (P < 0.05), and the difference further increased after 7 weeks of drug intervention (P < 0.01). Compared to the normal group, the body weight of mice treated with the low-dose group of the traditional Chinese medicine composition and the positive control drug atorvastatin for 8 weeks showed a significant difference (P < 0.05).

[0093] 3.5 Changes in serum inflammatory factor levels in mice

[0094] Changes in the levels of inflammatory factors in mice, such as Figure 5 As shown in the figure. Compared with the normal group, the serum levels of inflammatory factors IL-1β, IL-6, MCP-1, and TNF-α in the model group were significantly increased (P < 0.01); compared with the model group, the positive control drug atorvastatin significantly reduced the levels of IL-1β, IL-6, MCP-1, and TNF-α in mice (P < 0.01); compared with the model group mice, both low- and high-dose intervention with the drug composition in the examples significantly reduced the levels of IL-1β, IL-6, MCP-1, and TNF-α in mice after 8 weeks (P < 0.01).

[0095] 3.6 Changes in blood glucose levels in mice

[0096] Changes in blood glucose in mice as follows Figure 6As shown in the figure. Compared with the normal group, the blood glucose level of mice in the model group was significantly increased (P < 0.01), indicating that a high-sugar, high-fat diet can induce glucose and lipid metabolism disorders in mice. Compared with the model group, the blood glucose level of mice decreased after 8 weeks of gavage administration of the low-dose traditional Chinese medicine composition and the positive control drug atorvastatin, but the difference was not significant. Compared with the model group, the high-dose traditional Chinese medicine composition significantly reduced the blood glucose level of mice after 8 weeks of gavage administration (P < 0.05).

Claims

1. A traditional Chinese medicine composition for treating CMD, characterized in that: The traditional Chinese medicine composition is composed of Huangqi, Chishao, Zexie, Lingzhi, Chenpi and Huanglian, and the proportion is: Huangqi 10-20g, Chishao 10-20g, Zexie 5-15g, Lingzhi 5-15g, Chenpi 5-10g and Huanglian 5-10g.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: The weight ratio of Huangqi, Chishao, Zexie, Lingzhi, Chenpi and Huanglian in the traditional Chinese medicine composition is 3:3:2:2:1.2:1.

2.

3. The traditional Chinese medicine composition according to claim 2, characterized in that: The proportion is: Huangqi 15g, Chishao 15g, Zexie 10g, Lingzhi 10g, Chenpi 6g and Huanglian 6g.

4. The traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that: It is a mixture of the drugs, or a decoction obtained by decocting the mixture of the drugs.

5. The preparation method of the traditional Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The drugs are mixed in proportion, soaked in water, and then decocted to obtain the decoction.

6. The production method according to claim 5, characterized by: The ratio of the total weight of the drugs to the amount of water is 1g:3-8mL.

7. The production method according to claim 6, characterized by: The ratio of the total weight of the drugs to the amount of water is 1g:4-6mL.

8. The production method according to claim 5, wherein: The soaking time is 0.5-4h.

9. The production method according to claim 8, characterized by: The soaking time is 1-3h.

10. The production method according to claim 5, wherein: The decoction is performed 1-3 times, each time for 20-40min, and the decoctions obtained by filtering each time are mixed to obtain the traditional Chinese medicine composition.

11. The production method according to claim 10, wherein: The decoction is performed 2 times, each time for 25-35min, and the decoctions obtained by filtering each time are mixed to obtain the traditional Chinese medicine composition.

12. The use of the traditional Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for treating CMD.

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