Traditional Chinese medicine composition for preventing and treating atherosclerosis as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for preventing and treating atherosclerosis as well as a preparation method and application thereof. The traditional Chinese medicine composition comprises the following components: kudzuvine root, hawthorn, lotus seed and poria cocos. The traditional Chinese medicines in the traditional Chinese medicine composition provided by the invention respectively have unique pharmacological actions, and can synergistically play the roles of regulating blood fat, improving vascular functions, resisting inflammation and oxidation, protecting cardiovascular and the like after being combined. The radix puerariae, the hawthorn, the lotus seed and the poria cocos are all medicinal and edible traditional Chinese medicinal materials, are high in safety, have few side effects and are suitable for long-term administration. The composition is mild in effect and suitable for early prevention and long-term conditioning of atherosclerosis. And meanwhile, the medicine is suitable for adjuvant therapy and prevention of atherosclerosis.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly to a traditional Chinese medicine composition for preventing and treating atherosclerosis, a preparation method thereof, and an application thereof. Background Art

[0002] Atherosclerosis (AS) is a chronic non-controllable inflammatory disease of the blood vessel wall and is the common pathological basis of cardiovascular and cerebrovascular diseases. AS can lead to cardiovascular and cerebrovascular diseases such as hypertension, coronary atherosclerotic heart disease, stroke, etc., and seriously threatens human health due to its high incidence, disability rate, and fatality rate.

[0003] At present, the Western medicine treatment of AS mainly includes drugs for controlling risk factors, including controlling blood sugar, blood pressure, blood lipid levels, antiplatelet and anticoagulation, etc.; among them, the clinically more mature treatment plan is to reduce blood lipids, especially reduce LDL-C. Commonly used drugs include HMG-CoA reductase inhibitors, namely statins (such as atorvastatin calcium) and intestinal cholesterol transporter inhibitors (such as ezetimibe), or fibrate drugs (such as bezafibrate) that mainly reduce triglycerides, which reduce the entry of triglycerides into the blood by inhibiting adipose tissue hydrolysis. Although statins are effective inhibitors of cholesterol biosynthesis, muscle and skeletal related symptoms and related biochemical disturbances are common adverse reactions that occur when using statins.

[0004] The treatment of AS with traditional Chinese medicine has a history of thousands of years. In recent years, with the development of relevant clinical trials, the mechanism of action of traditional Chinese medicine in treating AS has been preliminarily explored. Currently, the literature shows that many traditional Chinese medicines or active ingredients of traditional Chinese medicine have obvious curative effects in anti-atherosclerosis and are widely used in clinical practice. Traditional Chinese medicine has many advantages such as multi-pathway, multi-effect, and multi-target intervention, and is more effective in controlling the progression of AS. Summary of the Invention

[0005] In order to solve the above problems, the present invention provides a traditional Chinese medicine composition for preventing and treating atherosclerosis, a preparation method thereof, and an application thereof. The traditional Chinese medicine composition provided by the present invention has a mild effect, is suitable for the early prevention and long-term conditioning of atherosclerosis, and is also suitable as an adjuvant treatment and preventive drug for atherosclerosis.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention provides a traditional Chinese medicine composition for preventing and treating atherosclerosis, which is prepared from the following components in parts by weight: 20 parts of Pueraria lobata, 10 parts of Crataegus pinnatifida, 10 parts of Nelumbo nucifera Gaertn. seeds, and 15 parts of Poria cocos.

[0008] The present invention also provides a preparation method of the above-mentioned traditional Chinese medicine composition, which includes the following steps:

[0009] 1) Mix the kudzu root, hawthorn, lotus seeds, Poria cocos and water, and soak them to obtain a soaked material;

[0010] 2) Decoct the soaked material obtained in step 1), and dry the obtained decoction to obtain a traditional Chinese medicine composition.

[0011] Preferably, the mass ratio of the total mass of the four components of kudzu root, hawthorn, lotus seeds and Poria cocos to the mass of water in step 1) is 1:10.

[0012] Preferably, the soaking time in step 1) is 2 h.

[0013] Preferably, the decocting conditions in step 2) include: the number of decocting times is 2 times, and each time is 30 min.

[0014] Preferably, the drying conditions in step 2) include: combine the decoctions obtained by decocting twice, filter, remove most of the water from the filtrate with a rotary evaporator, and dry it in an oven at 80 °C until it becomes a powder.

[0015] The present invention also provides the application of the traditional Chinese medicine composition described in the above technical solution in the preparation of a drug for preventing and treating atherosclerosis.

[0016] Preferably, the traditional Chinese medicine composition reduces the area of atherosclerotic arterial plaques and / or lipid deposition.

[0017] Preferably, the traditional Chinese medicine composition reduces the contents of cholesterol, total triglyceride and low-density lipoprotein cholesterol in the serum of atherosclerosis, and increases the content of high-density lipoprotein cholesterol.

[0018] Preferably, the traditional Chinese medicine composition reduces the content of TNF-a in the serum of atherosclerosis.

[0019] Kudzu root has the effects of dredging meridians and activating collaterals, and promoting the production of body fluid, and is the monarch drug; hawthorn promotes qi circulation and removes stasis, reduces turbidity and lipid, and strengthens the stomach and promotes digestion, assisting kudzu root to disperse stasis and activate collaterals, and is the minister drug; Poria cocos promotes diuresis and dampness elimination, strengthens the spleen and soothes the mind, lotus seeds tonify the kidney and strengthen the spleen, nourish the heart and soothe the mind, and can also neutralize the cold nature of kudzu root to avoid damaging the spleen yang, and the two are the assistant drug and the envoy drug respectively. All the drugs together play the roles of promoting blood circulation and removing stasis, tonifying the heart, spleen and kidney, and have a certain improvement effect on the characteristics of deficiency in origin and excess in superficiality of atherosclerosis. The beneficial effects of the present invention:

[0020] The traditional Chinese medicine composition provided by the present invention has the functions of regulating the immune system, reducing anti-inflammatory occurrence, improving cardiac blood supply and myocardial hypoxia, protecting cardiac function, improving blood lipid metabolism, and inhibiting the formation of arterial plaques. The specific prevention and treatment effects are embodied in the following examples. Pueraria lobata, hawthorn, lotus seeds, and poria cocos are all traditional Chinese medicinal materials that are both edible and medicinal, with high safety and few side effects, and are suitable for long-term use. The composition has a mild effect and is suitable for the early prevention and long-term conditioning of atherosclerosis. At the same time, it is suitable as an adjuvant treatment and preventive drug for atherosclerosis. Description of the Drawings

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments.

[0022] Figure 1 For the body weights of four groups of mice and the progress of atherosclerosis, (A) Oil Red O positive staining of the entire aorta; (B) Changes in the body weights of mice during modeling and treatment for 12 weeks; (C) Quantitative analysis of the Oil Red O staining area of the entire aorta;

[0023] Figure 2 For the HE staining images of the aortic roots of four groups of mice, (A) HE staining of the aortic roots; (B) Quantitative analysis of the damaged area of HE staining of the aortic roots;

[0024] Figure 3 For the Oil Red O staining images of the aortic roots of four groups of mice; (A) Oil Red O staining of the aortic roots; (B) Quantitative analysis of lipid deposition in Oil Red O staining of the aortic roots;

[0025] Figure 4 For the Masson staining images of the aortic roots of four groups of mice, (A) Masson staining of the aortic roots; (B) Quantitative analysis of the collagen content in Masson staining of the aortic roots;

[0026] Figure 5 For the blood lipid contents of four groups of mice, (A) Serum total triglyceride (TG); (B) Serum total cholesterol (TC); (C) High-density lipoprotein (HDL-C); (D) Low-density lipoprotein (LDL-C);

[0027] Figure 6 For the comparison of the levels of inflammatory factors IL-6 and TNF-α in mice, (A) Serum IL-6 level in mice; (B) Serum TNF-α level in mice. Detailed Embodiments

[0028] The present invention provides a traditional Chinese medicine composition for preventing and treating atherosclerosis, which is prepared from the following components in parts by weight: 20 parts of Pueraria lobata, 10 parts of hawthorn, 10 parts of lotus seeds, and 15 parts of poria cocos. The present invention has no special limitation on the sources of the Pueraria lobata, hawthorn, lotus seeds, and poria cocos, and conventional commercially available products can be used.

[0029] The present invention also provides a preparation method of the traditional Chinese medicine composition described in the above technical solution, including the following steps:

[0030] 1) Mix the kudzu root, hawthorn, lotus seeds, Poria cocos and water, and soak them to obtain a soaked material;

[0031] 2) Decoct the soaked material obtained in step 1), and dry the obtained decoction to obtain the traditional Chinese medicine composition.

[0032] In the present invention, the kudzu root, hawthorn, lotus seeds and Poria cocos are mixed with water and soaked to obtain a soaked material. In the present invention, the mass ratio of the total mass of the four components of kudzu root, hawthorn, lotus seeds and Poria cocos to the mass of water is preferably 1:10. In the present invention, the soaking time is preferably 2 h.

[0033] In the present invention, the obtained soaked material is decocted, and the obtained decoction is dried to obtain the traditional Chinese medicine composition. In the present invention, the decocting conditions preferably include: the number of decocting times is 2 times, 30 min each time. In the present invention, the drying conditions preferably include: combining the decoctions obtained by decocting twice, filtering, removing most of the water from the filtrate by a rotary evaporator, and drying in an oven at 80 °C until it becomes a powder.

[0034] The present invention also provides the application of the traditional Chinese medicine composition described in the above technical solution in the preparation of drugs for preventing and treating atherosclerosis. In the present invention, the traditional Chinese medicine composition preferably reduces the area of atherosclerotic arterial plaques and / or lipid deposition. In the present invention, the traditional Chinese medicine composition preferably reduces the contents of cholesterol, total triglyceride and low-density lipoprotein cholesterol in the serum of atherosclerosis, and increases the content of high-density lipoprotein cholesterol. In the present invention, the traditional Chinese medicine composition preferably reduces the content of TNF-α in the serum of atherosclerosis. In the present invention, the dosage form of the drug is preferably decoction, granules, pills or capsules. The present invention has no special limitation on the preparation methods of the above-mentioned decoction, granules, pills or capsules, and they can be prepared by conventional preparation methods.

[0035] In order to further illustrate the present invention, the following examples are used to describe the present invention in detail, but they should not be construed as limiting the protection scope of the present invention.

[0036] Example 1

[0037] A preparation method of a traditional Chinese medicine composition for preventing and treating atherosclerosis is as follows:

[0038] 1) Mix 20 g of kudzu root, 10 g of hawthorn, 10 g of lotus seeds and 15 g of Poria cocos according to a mass ratio of 1:10 with water, and soak for 2 h to obtain a soaked material;

[0039] 2) Decoct the soaked material obtained in step 1), dry the obtained decoction to obtain a traditional Chinese medicine composition; wherein, the number of decocting times is 2 times, 30 minutes each time; combine the decoctions obtained from the two decoctings, filter, and remove most of the water from the filtrate with a rotary evaporator, and dry it in an oven at 80 °C until it becomes a powder.

[0040] Pharmacodynamic examples

[0041] Pharmacodynamic evaluation:

[0042] Preparation of experimental drugs:

[0043] The powder of the traditional Chinese medicine composition prepared in Example 1 (composed of Pueraria lobata, Hawthorn, Lotus seed, and Poria cocos) was formulated with purified water into a solution with a concentration of 0.21 g / mL;

[0044] Atorvastatin calcium tablets, with a specification of 10 mg / tablet, were formulated with purified water into a solution with a concentration of 0.13 mg / mL.

[0045] High-fat diet D12492 [60% fat and 20% carbohydrate (kcal / 100 g), D12492] (Nanjing Xietong).

[0046] Establishment, grouping, and administration of ApoE- / - mouse AS model

[0047] Forty-five SPF-grade healthy male ApoE- / - mice, with a body weight of (20 ± 5) g and 7 - 8 weeks old. The above mice were housed in independent ventilated cages in a sterilized environment. After 1 week of adaptive feeding, they were fed with a high-fat diet to establish an AS model. During the high-fat diet feeding, mice were randomly selected, and their aortas were taken for Oil Red O staining to observe the growth of plaques and determine the success of model establishment. The successfully established AS mice were randomly grouped, with 15 mice in each group. The control group was C57BL / 6 mice, drinking normal water, and intragastrically administered with the same volume of 0.5% CMC-Na solution as the atorvastatin group every day. The specific grouping is as follows:

[0048] Model group (Model): Successfully established ApoE- / - mice, fed with a high-fat diet, drinking normal water, and intragastrically administered with the same volume of 0.5% CMC-Na solution as the atorvastatin group every day;

[0049] Traditional Chinese medicine composition group (TMJZW): Successfully established ApoE- / - mice, fed with a high-fat diet, drinking normal water, and intragastrically administered with 0.2 mL / mouse of TMJZW solution every day

[0050] Atorvastatin group (Ato): Successfully established ApoE- / - mice, fed with a high-fat diet, drinking normal water, and intragastrically administered with 0.2 mL / mouse of Ato solution every day;

[0051] After continuous intragastric administration for 14 weeks, at the end of the 14th week, after the last intragastric administration, the mice were fasted overnight, weighed, blood was collected by eye socket puncture, and the mouse serum and aorta were collected and stored at -80 °C for subsequent detection and analysis.

[0052] Specimen collection:

[0053] (1) Serum: Whole blood was taken into a centrifuge tube and left to stand at room temperature for 30 min. After the blood had coagulated, it was centrifuged at 3000 r·min-1 for 10 min, and the upper layer of serum was carefully aspirated, aliquoted, and stored in a -80 °C refrigerator for testing.

[0054] (2) Aorta: The abdominal and thoracic cavities were opened along the midline of the abdomen, other organs were removed, the heart, thoracic aorta, and abdominal aorta were exposed, and the aorta was carefully removed using ophthalmic forceps and placed in ice-cold physiological saline; under a stereomicroscope, the fat and connective tissue were slowly dissected using micro forceps and micro scissors, and after cleaning, the whole aorta was stained with Oil Red O, the aortic arch paraffin sections were stained with HE, and the frozen sections were stained with Oil Red O.

[0055] Statistical analysis

[0056] All data were processed using SPSS 26.0 statistical software. Measurement data that conformed to a normal distribution were expressed as mean ± standard deviation, those that did not conform to a normal distribution were expressed as median M (P25, P75), and count data were expressed as percentages. For measurement data that conformed to a normal distribution, a t-test was used, and for those that did not follow a normal distribution, a rank sum test was used. For comparison of count data, a x2 test was used. P < 0.05 indicated that the difference was statistically significant.

[0057] Experimental results:

[0058] Detection of indicators:

[0059] (1) Improvement effect of TMJZW on body weight and atherosclerotic progression in atherosclerotic model mice

[0060] After animal model establishment and drug intervention, in terms of body weight, the body weight of the mice after model establishment was significantly increased compared with the blank control group. After drug administration, different degrees of body weight reduction were observed in the Ato group and the traditional Chinese medicine composition group (see Figure 1 Figure B), indicating that TMJZW may regulate body weight through lipid metabolism.

[0061] As shown in Figure 1 Figure A, after artery exposure, compared with the blank group, the plaque area of Model increased. After drug treatment, the arterial plaque areas of the atorvastatin group and the TMJZW group of mice were significantly reduced (P < 0.001).

[0062] According to Figure 1As can be seen from C, the average area of total aortic plaques in the TMJJW group and the Ato group was significantly reduced compared with the Model group. The above results indicate that the traditional Chinese medicine composition has a certain inhibitory effect on plaque formation.

[0063] (2) Improvement effect of TMJJW on HE staining of mouse aorta

[0064] As Figure 2 shown in A of [Figure / Chart / Diagram] [X], in the blank group of mice, the endothelium of the aortic blood vessels was continuous and intact, with clear structure, no stenosis of the blood vessel lumen, no atherosclerotic plaque formation, and no obvious inflammatory cell infiltration. In the Model group of mice, the aortic endothelium was locally torn and the structure was damaged, obvious plaque formation was visible, the lumen was narrowed, and there were a large number of cholesterol crystals and inflammatory cell infiltration inside the plaque. Compared with the Model group, in the Ato group of mice, obvious collagen hyperplasia was seen in the aortic endothelium, and the plaque area was significantly reduced, with statistical significance (P < 0.05). Compared with the Model group, in the TMJJW group, the vascular endothelium was thickened, but the structure was still intact, and the plaque area was significantly reduced as seen Figure 2 in B of [Figure / Chart / Diagram] [X] (P < 0.01). Through the analysis of the HE staining results of the mouse aorta, it was found that there was no inflammatory cell infiltration and obvious reduction of plaques in the TMJJW group, indicating that TMJJW has anti-inflammatory effects and an inhibitory effect on plaque formation.

[0065] (3) Improvement effect of TMJJW on oil red staining of mouse aorta

[0066] As Figure 3 shown in A of [Figure / Chart / Diagram] [X], in the blank group of mice, the aortic structure was intact and no obvious lesion area was seen. In the Model group of mice, the aortic structure was damaged, obvious lesion area and a large amount of lipid deposition were visible. Figure 3 As shown in B of [Figure / Chart / Diagram] [X], compared with the Model group, the lesion area and lipid deposition in the aortic blood vessels of the Ato group and the TMJJW group of mice were significantly reduced (P < 0.05). From this analysis, it can be seen that TMJJW has the effect of improving blood lipid metabolism and protecting blood vessels.

[0067] (4) Improvement effect of TMJJW on Masson staining of mouse aorta

[0068] As Figure 4 shown in A of [Figure / Chart / Diagram] [X], in the blank group of mice, the aortic structure was intact and no obvious increase in collagen content was seen. In the Model group of mice, the aortic structure was damaged and obvious increase in collagen content was visible. Compared with the Model group, the collagen content in the aorta of the Ato group and the TMJJW group of mice was significantly reduced as seen Figure 4 in B of [Figure / Chart / Diagram] [X] (P < 0.05), suggesting that TMJJW may inhibit the formation of arterial plaques by reducing the collagen content in the aorta.

[0069] (5) Improvement effect of TMJJW on blood lipids in atherosclerotic model mice

[0070] According to Figure 5 It can be seen that the contents of total cholesterol (TC), total triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of model mice were significantly increased, while the content of high-density lipoprotein cholesterol (HDL-C) was significantly decreased. The comparison showed obvious differences and statistical significance (P<0.05, P<0.01). Compared with the Model group, the levels of serum TC, TG, and LDL-C in the Ato group and TMJJW group mice were significantly decreased (P<0.05); the level of serum HDL-C was significantly increased (P<0.05). From the above results, it can be known that TMJJW has the effect of improving blood lipid.

[0071] (6) Improvement effect of TMJJW on inflammatory factors in atherosclerotic model mice

[0072] From Figure 6 the changes of inflammatory factors among different groups, compared with the blank group, the contents of serum IL-6 and TNF-a in Model mice were significantly increased, and there were obvious statistical significances in the comparison (P<0.05, P<0.01);

[0073] compared with the Model group, the level of serum IL-6 in the Ato group and TMJJW group mice decreased, but the difference was not obvious; the level of TNF-a was significantly decreased (P<0.05), indicating that TMJJW can regulate the immune system and reduce the occurrence of inflammation.

[0074] In summary, TMJJW can prevent and treat atherosclerosis by regulating the immune system, reducing the occurrence of anti-inflammation, improving blood lipid metabolism, and inhibiting the formation of arterial plaques.

[0075] Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, not all embodiments. People can also obtain other embodiments according to this embodiment without creative efforts, and these embodiments all belong to the protection scope of the present invention.

Claims

1. A Chinese medicine composition for preventing and treating atherosclerosis, characterized in that: The invention is prepared from the following components in parts by weight: 20 parts of kudzu root, 10 parts of hawthorn, 10 parts of lotus seeds and 15 parts of tuckahoe.

2. A method for preparing the Chinese medicine composition according to claim 1, characterized in that: The following steps are involved: 1) mixing the kudzu root, hawthorn, lotus seeds, and poria with water and soaking them to obtain a soaking material; 2) decocting the soaking material obtained in step 1), and drying the obtained decoction to obtain a traditional Chinese medicine composition.

3. The preparation method according to claim 2, characterized in that: In the step 1), the mass ratio of the total mass of the four ingredients of Pueraria root, hawthorn, lotus seed and Poria cocos to water is 1:

10.

4. The preparation method according to claim 2, characterized in that: The soaking time in step 1) is 2 hours.

5. The preparation method according to claim 2, characterized in that: The conditions for decoction in step 2) include: decoction is performed twice, each time for 30 minutes.

6. The preparation method according to claim 2, characterized in that: The drying conditions of step 2) include: combining the decoctions obtained by decoction twice and filtering them, removing most of the water from the filtrate by a rotary evaporator, and drying in an oven at 80° C. until they are dried into powder.

7. Use of the Chinese medicine composition according to claim 1 in preparing a medicine for preventing and treating atherosclerosis.

8. The use according to claim 7, characterized in that: The Chinese medicine composition reduces the arterial plaque area and / or lipid deposition of atherosclerosis.

9. The use according to claim 7, characterized in that: The traditional Chinese medicine composition reduces the content of cholesterol, total triglyceride and low-density lipoprotein cholesterol in the serum of patients with atherosclerosis, and increases the content of high-density lipoprotein cholesterol.

10. The use according to claim 7, characterized in that: The traditional Chinese medicine composition reduces the TNF-a content in the serum of patients with atherosclerosis.

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