Traditional Chinese medicine composition for qi deficiency, blood stasis and phlegm stagnation type coronary heart disease as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of cardiovascular disease treatment medicines, and particularly relates to a traditional Chinese medicine composition for qi deficiency, blood stasis and phlegm stagnation type coronary heart disease as well as a preparation method and application thereof. The traditional Chinese medicine composition comprises codonopsis pilosula, astragalus membranaceus, dogwood, rhizoma anemarrhenae, platycodon grandiflorum, radix bupleuri, rhizoma cimicifugae, rhizoma sparganii, curcuma zedoary, cassia twig, trichosanthes kirilowii maxim, allium macrostemon, rhizoma pinelliae preparata, Chinese yam and honey-fried licorice root. The traditional Chinese medicine composition can tonify qi, activate blood, eliminate phlegm and resolve turbidity, can be used for treating qi deficiency, blood stasis and phlegm stagnation type coronary heart disease, and can treat both symptoms and root causes. Experiments prove that for a mouse with coronary heart disease, the traditional Chinese medicine composition can obviously improve the heart function of the mouse, and has the effects of inhibiting atherosclerosis and regulating lipid metabolism; for patients with qi deficiency, blood stasis and phlegm stagnation type coronary heart disease, the traditional Chinese medicine composition can improve the symptoms of chest pain and chest distress of the patients. Therefore, the traditional Chinese medicine composition can be used for preparing a medicine for treating qi deficiency, blood stasis and phlegm stagnation type coronary heart disease, and can also be used for preparing a medicine for regulating blood fat.

Description

Technical Field

[0001] The present invention belongs to the technical field of drugs for treating cardiovascular diseases, and particularly relates to a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type, and a preparation method and application thereof. Background Art

[0002] Coronary atherosclerotic heart disease (hereinafter referred to as coronary heart disease) is a heart disease caused by atherosclerotic lesions of the coronary arteries, resulting in lumen stenosis or occlusion, and triggering myocardial ischemia, hypoxia or necrosis. The pathological core is lipid deposition, inflammatory reaction and fibrous plaque formation in the arterial wall, ultimately causing vascular dysfunction, and the clinical manifestations are angina pectoris, myocardial infarction, heart failure, etc. Coronary heart disease shows a trend of getting younger and has become one of the main diseases threatening human life and health.

[0003] The existing treatment methods for coronary heart disease are mainly surgical treatment and drug treatment. Surgical treatment is an important means to improve myocardial blood supply and save patients' lives. Currently, the mainstream surgical methods include percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). However, the former has limitations such as the risk of restenosis and thrombosis after surgery and low success rate in opening severely calcified or completely occluded blood vessels, and the latter has defects such as low long-term patency rate of venous bridges, inapplicability to patients with distal blood vessel diameter < 1.0 mm or diffuse stenosis, and great difficulty in secondary surgery. Moreover, surgical treatment cannot reverse the atherosclerotic process. Among the drug treatment methods for coronary heart disease, chemical drugs generally use anticoagulants, lipid-lowering drugs, β-blockers, etc. Although anticoagulants can reduce the risk of thrombosis, long-term use can lead to gastrointestinal bleeding; lipid-lowering drugs can delay the progression of plaques, but cannot reverse the already formed plaques, and have side effects such as muscle damage and abnormal liver function; β-blockers can relieve angina pectoris, but are prone to drug resistance and have limited effect on improving prognosis. Traditional Chinese medicine has advantages such as multi-target intervention, small adverse reactions and high economy in the treatment of coronary heart disease, but there are also some problems, such as: traditional Chinese medicine lacks pertinence in eliminating atherosclerotic plaques; clinically, methods such as "promoting blood circulation to remove blood stasis" are commonly used, but atherosclerosis involves multiple links such as abnormal lipid metabolism and endothelial injury, and simple stasis removal is difficult to achieve "treating both the symptoms and the root cause". Summary of the Invention

[0004] In view of the above technical problems, the present invention provides a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type, and a preparation method and application thereof. This traditional Chinese medicine composition can replenish qi and activate blood circulation, resolve phlegm and remove turbidity, not only improve heart function and blood lipid, but also effectively eliminate atherosclerotic plaques, can be used for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type, and can achieve the treatment of both the symptoms and the root cause.

[0005] To achieve the above invention purpose, the present invention adopts the following technical solutions: In the first aspect of the present invention, a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type is provided. The raw materials are proportioned by mass fraction and include 25 - 35 parts of Codonopsis pilosula, 25 - 35 parts of Astragalus membranaceus, 12 - 18 parts of Cornus officinalis, 12 - 18 parts of Anemarrhena asphodeloides, 5 - 7 parts of Platycodon grandiflorum, 5 - 7 parts of Bupleurum chinense, 5 - 7 parts of Cimicifuga foetida, 12 - 18 parts of Sparganium stoloniferum, 12 - 18 parts of Curcuma zedoaria, 8 - 12 parts of Cinnamomum cassia, 16 - 24 parts of Trichosanthes kirilowii, 16 - 24 parts of Allium macrostemon, 12 - 18 parts of Pinellia ternata, 25 - 35 parts of Dioscorea opposita and 8 - 12 parts of honey-fried licorice root.

[0006] This traditional Chinese medicine composition has the effects of supplementing qi and activating blood circulation, resolving phlegm and removing turbidity, and can be used for the treatment of coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type.

[0007] Codonopsis pilosula is sweet in taste and neutral in nature, and belongs to the spleen and lung meridians. It has the effects of replenishing middle qi, strengthening the spleen and nourishing the lung, and nourishing blood and promoting fluid production; Astragalus membranaceus is sweet in taste and slightly warm in nature, and belongs to the spleen and lung meridians. It has the effects of strengthening the spleen and replenishing middle qi, lifting yang and raising prolapse, benefiting the defensive qi and consolidating the exterior, inducing diuresis and reducing swelling, and expelling toxins and promoting granulation; Cornus officinalis is sour and astringent in taste and slightly warm in nature, and belongs to the liver and kidney meridians. It has the effects of tonifying the liver and kidney, and arresting sweating and preventing leakage; Anemarrhena asphodeloides is bitter and sweet in taste and cold in nature, and belongs to the lung, stomach and kidney meridians. It has the effects of clearing heat and purging fire, and nourishing yin and moistening dryness; Platycodon grandiflorum is bitter and pungent in taste and neutral in nature, and belongs to the lung meridian. It has the effects of dispersing the lung qi and relieving sore throat, resolving phlegm and discharging pus, and can also promote defecation and urination, dredge intestinal stagnation, and open up obstruction; Bupleurum chinense is bitter and pungent in taste and slightly cold in nature, and belongs to the liver, gallbladder and lung meridians. It has the effects of inducing sweating and relieving fever, soothing the liver and relieving depression, and lifting yang qi; Cimicifuga foetida is pungent and sweet in taste and slightly cold in nature, and belongs to the lung, spleen, large intestine and stomach meridians. It has the effects of inducing eruption, clearing heat and detoxifying, and lifting yang qi; Sparganium stoloniferum is bitter in taste and neutral in nature, and belongs to the liver and spleen meridians. It has the effects of promoting blood circulation to remove blood stasis, promoting qi movement and relieving pain, and reducing accumulation; Curcuma zedoaria is pungent and bitter in taste and warm in nature, and belongs to the liver and spleen meridians. It has the effects of promoting qi movement and breaking blood stasis, promoting qi movement and relieving pain, and reducing accumulation; Cinnamomum cassia is pungent and sweet in taste and warm in nature, and belongs to the heart and lung meridians. It has the effects of inducing sweating and releasing the muscles, warming the channels and promoting blood circulation, assisting yang to transform qi, and calming the mind; Trichosanthes kirilowii is sweet and slightly bitter in taste and cold in nature, and belongs to the lung, stomach and large intestine meridians. It has the effects of clearing heat and resolving phlegm, widening the chest and dissipating binds, and moistening the intestine and promoting defecation; Allium macrostemon is pungent and bitter in taste and warm in nature, and belongs to the heart, lung, stomach and large intestine meridians. It has the effects of promoting yang qi to disperse binds, promoting qi movement and guiding qi stagnation; Pinellia ternata is pungent in taste and warm in nature, and belongs to the spleen, stomach and lung meridians. It has the effects of drying dampness and resolving phlegm, lowering adverse qi and stopping vomiting, and dissipating binds and resolving masses; Dioscorea opposita is sweet in taste and neutral in nature, and belongs to the spleen, lung and kidney meridians. It has the effects of strengthening the spleen and nourishing the stomach, promoting fluid production and nourishing the lung, and tonifying the kidney and arresting seminal emission; Zhigancao is sweet in taste and neutral in nature, and it pertains to the heart, lung, spleen, and stomach meridians. It has the effects of tonifying the spleen and stomach, replenishing qi and restoring the pulse, relieving spasm and pain, moistening the lungs and relieving cough, and harmonizing various medicinal herbs.

[0008] The pathogenesis of coronary heart disease of the qi deficiency, blood stasis, and phlegm obstruction type is as follows: Deficiency in origin and excess in superficiality. The deficiency in origin is mainly qi deficiency, and the excess in superficiality is mainly blood stasis and phlegm turbidity. In the formula of this medicine, Astragalus membranaceus is used as the monarch drug to tonify qi. It is good at tonifying qi and ascending qi, and can raise the zong qi that has sunken. Codonopsis pilosula and Dioscorea opposita are used as ministerial drugs to tonify the spleen qi and benefit the source of qi and blood generation in the acquired constitution. Cornus officinalis can both astringe the dissipation of qi aspect and tonify the congenital primordial qi of the kidney. The combination of these three drugs enables the sunken and deficient zong qi to be raised and filled. At the same time, Sparganium stoloniferum and Curcuma zedoaria are used as ministerial drugs to promote blood circulation and dredge collaterals, and Cinnamomum cassia, Trichosanthes kirilowii, Allium macrostemon, and Pinellia ternata are used to promote yang and disperse stagnation, resolve phlegm and dissipate turbidity. Bupleurum chinense and Cimicifuga foetida are used as adjuvant drugs, which can both raise the sunken qi and relieve depression. Anemarrhena asphodeloides is cool in nature and can restrict the warm nature of Astragalus membranaceus. Platycodon grandiflorum is used as the guiding drug to direct the medicine to reach the chest. Zhigancao tonifies the spleen and qi, and can also harmonize various medicinal herbs. The combination of all these drugs can not only tonify qi and raise the sunken, promote blood circulation and dredge collaterals, but also resolve phlegm and relieve depression, enabling the vital qi to be filled, the sunken qi to be lifted, the chest yang to be extended, the qi and blood to circulate smoothly, and treating both the root cause and the symptoms simultaneously.

[0009] Experiments have shown that this traditional Chinese medicine composition can significantly increase the ejection fraction and shortening fraction of the left ventricular minor axis in mice with coronary heart disease, reduce the serum proBNP level, significantly reduce myocardial fibrosis, improve the morphology of myocardial cells, and can also significantly reduce the area of arterial plaques and the area of plaque necrotic cores, reduce total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increase high-density lipoprotein cholesterol. Clinical trials have shown that for patients with coronary heart disease of the qi deficiency, blood stasis, and phlegm obstruction type, this traditional Chinese medicine composition can improve the symptoms of chest pain and chest tightness in patients.

[0010] Preferably, the raw materials of the traditional Chinese medicine composition are proportioned by mass fraction to include 27 - 33 parts of Codonopsis pilosula, 27 - 33 parts of Astragalus membranaceus, 13.5 - 16.5 parts of Cornus officinalis, 13.5 - 16.5 parts of Anemarrhena asphodeloides, 5.5 - 6.5 parts of Platycodon grandiflorum, 5.5 - 6.5 parts of Bupleurum chinense, 5.5 - 6.5 parts of Cimicifuga foetida, 13.5 - 16.5 parts of Sparganium stoloniferum, 13.5 - 16.5 parts of Curcuma zedoaria, 9 - 11 parts of Cinnamomum cassia, 18 - 22 parts of Trichosanthes kirilowii, 18 - 22 parts of Allium macrostemon, 13.5 - 16.5 parts of Pinellia ternata, 27 - 33 parts of Dioscorea opposita, and 9 - 11 parts of Zhigancao; or, it includes 27 - 33 parts of Codonopsis pilosula, 27 - 33 parts of Astragalus membranaceus, 13.5 - 16.5 parts of Cornus officinalis, 13.5 - 16.5 parts of Anemarrhena asphodeloides, 5.5 - 6.5 parts of Platycodon grandiflorum, 9.5 - 10.5 parts of Bupleurum chinense, 9.5 - 10.5 parts of Cimicifuga foetida, 13.5 - 16.5 parts of Sparganium stoloniferum, 13.5 - 16.5 parts of Curcuma zedoaria, 9 - 11 parts of Cinnamomum cassia, 28 - 32 parts of Trichosanthes kirilowii, 18 - 22 parts of Allium macrostemon, 13.5 - 16.5 parts of Pinellia ternata, 27 - 33 parts of Dioscorea opposita, and 9 - 11 parts of Zhigancao.

[0011] Preferably, the raw materials of the traditional Chinese medicine composition include 30 parts of Codonopsis pilosula, 30 parts of Astragalus, 15 parts of Cornus officinalis, 15 parts of Anemarrhena asphodeloides, 6 parts of Platycodon grandiflorum, 6 parts of Bupleurum chinense, 6 parts of Cimicifuga heracleifolia, 15 parts of Sparganium wilfordii, 15 parts of Curcuma zedoaria, 10 parts of Cinnamon twig, 20 parts of Trichosanthes kirilowii, 20 parts of Allium macrostemon, 15 parts of Pinellia ternata, 30 parts of Yam and 10 parts of Radix Glycyrrhizae uralensis; or, include 30 parts of Codonopsis pilosula, 30 parts of Astragalus, 15 parts of Cornus officinalis, 15 parts of Anemarrhena asphodeloides, 6 parts of Platycodon grandiflorum, 10 parts of Bupleurum chinense, 10 parts of Cimicifuga heracleifolia, 15 parts of Sparganium wilfordii, 15 parts of Curcuma zedoaria, 10 parts of Cinnamon twig, 30 parts of Trichosanthes kirilowii, 20 parts of Allium macrostemon, 15 parts of Pinellia ternata, 30 parts of Yam and 10 parts of Glycyrrhiza uralensis.

[0012] Preferably, the Cornus officinalis is Fructus Corni.

[0013] Preferably, the Bupleurum is Bupleurum chinense.

[0014] Preferably, the Tripterygium wilfordii is Tripterygium wilfordii.

[0015] Preferably, the Curcuma zedoaria is vinegar Curcuma zedoaria.

[0016] In clinical application of the Chinese medicine composition, the corresponding weight of each portion in each dose of the Chinese medicine composition is 0.8-1.2 g.

[0017] The second aspect of the present invention provides a method for preparing the above-mentioned Chinese medicine composition, comprising: extracting the raw material with water. The obtained extract can be taken directly, or can be stored after being concentrated and dried and taken with water before use, or can be made into a concentrated solution or a clear paste and then mixed with a pharmaceutically acceptable excipient to prepare a common preparation for use.

[0018] Preferably, the extraction method is decoction extraction.

[0019] Further preferably, the extraction is performed 2 to 3 times, the mass of the water in each extraction is 6 to 8 times the mass of the raw material, the extraction time is 50 to 70 minutes, and the extracts obtained from each extraction are combined.

[0020] More preferably, the extraction is performed twice, each time for 1 hour.

[0021] Preferably, the preparation method further comprises concentrating the water extract obtained by extraction.

[0022] Optionally, it can be concentrated to a relative density of 1.10 to 1.20 (70°C).

[0023] The third aspect of the present invention provides the use of the above-mentioned Chinese medicine composition or the Chinese medicine composition prepared by the above-mentioned preparation method, comprising: Application in the preparation of medicines for treating qi deficiency, blood stasis and phlegm stagnation type coronary heart disease; Application in the preparation of drugs for regulating blood lipids.

[0024] Preferably, the drug is an oral preparation, including but not limited to granules, capsules, tablets, powders, oral liquids, etc.

[0025] Preferably, the drug further comprises a pharmaceutically acceptable excipient. After the above traditional Chinese medicine is subjected to steps such as extraction and concentration to prepare a concentrated solution or clear extract, it is then made into the above dosage form together with the excipient to obtain the product.

[0026] The beneficial effects of the present invention are as follows: The traditional Chinese medicine composition provided by the present invention can replenish qi and activate blood circulation, eliminate phlegm and remove turbidity. For coronary heart disease mice, it can significantly increase their ejection fraction and shortening fraction of the minor axis, reduce the serum proBNP level, significantly reduce myocardial fibrosis, improve the morphology of myocardial cells, and can also significantly reduce their arterial plaque area and plaque necrotic core area, reduce total cholesterol, triglyceride and low-density lipoprotein cholesterol, and increase high-density lipoprotein cholesterol; for patients with coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type, the traditional Chinese medicine composition can improve the symptoms of chest pain and chest tightness of the patients. Therefore, the traditional Chinese medicine composition can be used to prepare drugs for treating coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type, and can also be used to prepare drugs for regulating blood lipid, and has good clinical application value. Description of the Drawings

[0027] Figure 1 It is the echocardiogram of each group of mice in Example 12; Figure 2 It is the LVEF value of each group of mice in Example 12 ( n =6) and FS value ( n =6); **, compared with the Control group, P < 0.01; ##, compared with the Model group, P < 0.01; Figure 3 It is the serum proBNP level of each group of mice in Example 12 ( n =6); **, compared with the Control group, P < 0.01; ##, compared with the Model group, P < 0.01; Figure 4 It is the representative diagram of H&E staining and Masson staining of each group of mice in Example 12; Figure 5 It is the plaque and necrosis conditions of the aorta and root of each group of mice in Example 12; Figure A is the representative diagram of oil red O staining of the aorta and root and H&E staining of the aortic root; Figure B is the aortic plaque area of each group of mice ( n =8); Figure C is the aortic root plaque area of each group of mice ( n =8); Figure D is the aortic root plaque necrotic core area of each group of mice ( n =8); Figure 6 For the contents of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the blood of mice in each group in Example 12 ( n n = 6); **, compared with the Control group, P  < 0.01; ##, compared with the Model group, P  < 0.01; &&, compared with the L-SXHZ group, P  < 0.01; &, compared with the L-SXHZ group, P  < 0.05. Specific Embodiments

[0028] In order to make the objectives, technical solutions, and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts fall within the protection scope of the present invention.

[0029] In the following embodiments, Codonopsis pilosula, Astragalus membranaceus, Fructus Corni preparata (under Fructus Corni), Anemarrhena asphodeloides, Platycodon grandiflorus, Bupleurum chinense (under Bupleurum), Cimicifuga foetida, Sparganii Rhizoma vinegar-processed (under Sparganii), Rhizoma Curcumae vinegar-processed (under Curcumae), Cinnamomum cassia, Trichosanthes kirilowii, Allium macrostemon, Pinellia ternata, Dioscorea opposita, and Radix Glycyrrhizae preparata all comply with the relevant regulations under each medicinal material item in Part I of the Chinese Pharmacopoeia (2020 Edition).

[0030] In the following embodiments, the raw materials, reagents, etc. used, unless otherwise specified, are all obtained through commercial channels.

[0031] Example 1 The embodiment of the present invention provides a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis, and phlegm obstruction type. The raw materials for each dose are 30 g of Codonopsis pilosula, 30 g of Astragalus membranaceus, 15 g of Fructus Corni preparata, 15 g of Anemarrhena asphodeloides, 6 g of Platycodon grandiflorus, 6 g of Bupleurum chinense, 6 g of Cimicifuga foetida, 15 g of Sparganii Rhizoma vinegar-processed, 15 g of Rhizoma Curcumae vinegar-processed, 10 g of Cinnamomum cassia, 20 g of Trichosanthes kirilowii, 20 g of Allium macrostemon, 15 g of Pinellia ternata, 30 g of Dioscorea opposita, and 10 g of Radix Glycyrrhizae preparata.

[0032] The preparation method is as follows: Take the above-mentioned traditional Chinese medicine decoction pieces, first decoct with 8 times the amount of water for 1 hour, filter the extract, then decoct the medicinal residues with 7 times the amount of water for 1 hour, filter the extract, combine the filtrates, and concentrate to a clear paste with a relative density of 1.10 - 1.20 (70 °C) at 70 °C to obtain.

[0033] Example 2 An embodiment of the present invention provides a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The raw materials per dose are 30 g of Codonopsis pilosula, 30 g of Astragalus membranaceus, 15 g of Fructus Corni preparata, 15 g of Anemarrhena asphodeloides, 6 g of Platycodon grandiflorum, 10 g of Bupleurum chinense, 10 g of Cimicifuga foetida, 15 g of Sparganii rhizoma praeparatum with vinegar, 15 g of Curcumae rhizoma praeparatum with vinegar, 10 g of Ramulus Cinnamomi, 30 g of Trichosanthes kirilowii, 20 g of Allium macrostemon, 15 g of Pinellia ternata, 30 g of Dioscorea opposita and 10 g of Radix Glycyrrhizae preparata.

[0034] The preparation method is the same as that in Example 1.

[0035] Example 3 An embodiment of the present invention provides a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The raw materials per dose are 27 g of Codonopsis pilosula, 27 g of Astragalus membranaceus, 13.5 g of Fructus Corni preparata, 13.5 g of Anemarrhena asphodeloides, 5.5 g of Platycodon grandiflorum, 5.5 g of Bupleurum chinense, 5.5 g of Cimicifuga foetida, 13.5 g of Sparganii rhizoma praeparatum with vinegar, 13.5 g of Curcumae rhizoma praeparatum with vinegar, 9 g of Ramulus Cinnamomi, 18 g of Trichosanthes kirilowii, 18 g of Allium macrostemon, 13.5 g of Pinellia ternata, 27 g of Dioscorea opposita and 9 g of Radix Glycyrrhizae preparata.

[0036] The preparation method is as follows: Take the above-mentioned traditional Chinese medicine pieces, first decoct with 8 times the amount of water for 1 hour, filter the extract, then decoct the medicinal residues with 7 times the amount of water for 1 hour, filter the extract, combine the filtrates, and concentrate at 70 °C to obtain a clear paste with a relative density of 1.10 - 1.20 (70 °C).

[0037] Example 4 An embodiment of the present invention provides a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The raw materials per dose are 33 g of Codonopsis pilosula, 33 g of Astragalus membranaceus, 16.5 g of Fructus Corni preparata, 16.5 g of Anemarrhena asphodeloides, 6.5 g of Platycodon grandiflorum, 6.5 g of Bupleurum chinense, 6.5 g of Cimicifuga foetida, 16.5 g of Sparganii rhizoma praeparatum with vinegar, 16.5 g of Curcumae rhizoma praeparatum with vinegar, 11 g of Ramulus Cinnamomi, 22 g of Trichosanthes kirilowii, 22 g of Allium macrostemon, 16.5 g of Pinellia ternata, 33 g of Dioscorea opposita and 11 g of Radix Glycyrrhizae preparata.

[0038] The preparation method is as follows: Take the above-mentioned traditional Chinese medicine pieces, first decoct with 8 times the amount of water for 1 hour, filter the extract, then decoct the medicinal residues with 7 times the amount of water for 1 hour, filter the extract, combine the filtrates, and concentrate at 70 °C to obtain a clear paste with a relative density of 1.10 - 1.20 (70 °C).

[0039] Example 5 An embodiment of the present invention provides a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The raw materials per dose are 25 g of Codonopsis pilosula, 25 g of Astragalus membranaceus, 12 g of Fructus Corni preparata, 12 g of Anemarrhena asphodeloides, 5 g of Platycodon grandiflorum, 5 g of Bupleurum chinense, 5 g of Cimicifuga foetida, 12 g of Sparganii rhizoma praeparatum with vinegar, 12 g of Curcumae rhizoma praeparatum with vinegar, 8 g of Ramulus Cinnamomi, 16 g of Trichosanthes kirilowii, 16 g of Allium macrostemon, 12 g of Pinellia ternata, 25 g of Dioscorea opposita and 8 g of Radix Glycyrrhizae preparata.

[0040] The preparation method is as follows: Take the above-mentioned traditional Chinese medicine pieces, first decoct with 7 times the amount of water for 50 minutes, filter the extract, then decoct the medicinal residues with 6 times the amount of water twice, each time for 50 minutes, filter the extract, combine all the filtrates, and concentrate at 70°C to obtain a clear paste with a relative density of 1.10 - 1.20 (70°C), then you will get it.

[0041] Example 6 An embodiment of the present invention provides a traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The raw materials for each dose are 35 g of Codonopsis pilosula, 35 g of Astragalus membranaceus, 18 g of Fructus Corni praeparata, 18 g of Anemarrhena asphodeloides, 7 g of Platycodon grandiflorum, 7 g of Bupleurum chinense, 7 g of Cimicifuga foetida, 18 g of Sparganii Rhizoma vinegar-processed, 18 g of Curcumae Rhizoma vinegar-processed, 12 g of Ramulus Cinnamomi, 24 g of Trichosanthes kirilowii Maxim., 24 g of Allium macrostemon Bunge, 18 g of Pinellia ternata, 35 g of Dioscorea opposita Thunb. and 12 g of Glycyrrhiza uralensis Fisch. preparata.

[0042] The preparation method is as follows: Take the above-mentioned traditional Chinese medicine pieces, first decoct with 8 times the amount of water for 70 minutes, filter the extract, then decoct the medicinal residues with 6 times the amount of water for 50 minutes, filter the extract, combine the filtrates, and concentrate at 70°C to obtain a clear paste with a relative density of 1.10 - 1.20 (70°C), then you will get it.

[0043] Example 7 An embodiment of the present invention provides a traditional Chinese medicine powder for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The preparation method is as follows: Mix the traditional Chinese medicine composition in any one of Examples 1 - 6 with dextrin, dry at 40 - 50°C and then pulverize, mix with stevioside or aspartame and then subpackage, then you will get it.

[0044] Stevioside and aspartame can be replaced with other pharmaceutically acceptable flavoring agents.

[0045] Example 8 An embodiment of the present invention provides a traditional Chinese medicine granule for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The preparation method is as follows: Mix the clear paste of the traditional Chinese medicine composition in any one of Examples 1 - 6 with an appropriate amount of dextrin, dry at 40 - 50°C and then pulverize, add an appropriate amount of dextrin again, mix evenly, add water to make a soft material, granulate through a 18 - 20 mesh sieve, dry at 40 - 50°C and then screen with a 20 - 22 mesh sieve, and subpackage, then you will get it.

[0046] Dextrin can be replaced with other pharmaceutically acceptable granule excipients. Flavoring agents and other excipients can also be added to the granule according to clinical needs.

[0047] Example 9 An embodiment of the present invention provides a traditional Chinese medicine hard capsule for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The preparation method is as follows: Mix the traditional Chinese medicine composition in any one of Examples 1 - 6 with dextrin, dry at 40 - 50°C and then pulverize, add 1% magnesium stearate, mix and then fill into hard capsule shells, then you will get it.

[0048] The dextrin can be replaced with other pharmaceutically acceptable fillers, and the magnesium stearate can be replaced with other pharmaceutically acceptable glidants.

[0049] Example 10 An embodiment of the present invention provides a traditional Chinese medicine tablet for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The preparation method is as follows: mix the traditional Chinese medicine composition in any one of Examples 1 to 6 with dextrin, dry and crush at 40 - 50 °C, then mix with microcrystalline cellulose and crospovidone, add water to prepare soft materials, granulate through 18 - 20 meshes, dry at 40 - 50 °C and then screen through 20 - 22 meshes, add 1% magnesium stearate and 0.5% silicon dioxide, mix and then press into tablets to obtain the tablets.

[0050] The dextrin and microcrystalline cellulose can be replaced with other pharmaceutically acceptable fillers, the crospovidone can be replaced with other pharmaceutically acceptable disintegrants, and the magnesium stearate and silicon dioxide can be replaced with other pharmaceutically acceptable lubricants and glidants. The tablets can also be film-coated or sugar-coated according to clinical needs.

[0051] Example 11 An embodiment of the present invention provides a traditional Chinese medicine oral liquid for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type. The preparation method is as follows: dissolve the traditional Chinese medicine composition in any one of Examples 1 to 6 in water, add sucralose, ascorbic acid and sodium benzoate, and then fill into bottles to obtain the oral liquid.

[0052] The sucralose can be replaced with other pharmaceutically acceptable flavoring agents, the ascorbic acid can be replaced with other pharmaceutically acceptable antioxidants, and the sodium benzoate can be replaced with other pharmaceutically acceptable preservatives.

[0053] Example 12 An embodiment of the present invention provides the effects of the traditional Chinese medicine composition obtained in Example 1 on the cardiac function, arterial plaques and blood lipid levels of coronary heart disease mice.

[0054] 1. Modeling method and grouping 8-week-old SPF-grade ApoE- / - mice were raised in a pathogen-free barrier system at a room temperature of 20-25°C and a relative humidity of 40%-60%. The light and dark environments alternated for 12 hours each. They were randomly divided into a control group (Control group), a model group (Model group), and a drug administration group (low-dose traditional Chinese medicine group (L-SXHZ group), medium-dose traditional Chinese medicine group (Z-SXHZ group), high-dose traditional Chinese medicine group (H-SXHZ group)), with 8 mice in each group. Except for the control group, the mice in the model group and the drug administration group were fed with a high-fat diet (Xiaoshu Youtai (Beijing) Biotechnology Co., Ltd., D12492) for 16 weeks, and a left anterior descending coronary artery ligation surgery was performed at the 11th week to establish a mouse model of coronary heart disease; the control group was given a basal diet (Xiaoshu Youtai (Beijing) Biotechnology Co., Ltd., D12450B) for 16 weeks and a sham operation was performed at the 11th week. The mice in each group were continuously intragastrically administered for 6 weeks at a volume of 0.2 mL per 10 g, once a day. The L-SXHZ group, Z-SXHZ group, and H-SXHZ group were respectively given the aqueous solution of the traditional Chinese medicine composition in Example 1. The administration dose of the L-SXHZ group was 31.59 g / kg / d (equivalent dose calculated by the crude drug amount), the administration dose of the Z-SXHZ group was 63.18 g / kg / d (2 equivalent doses calculated by the crude drug amount), and the administration dose of the H-SXHZ group was 94.77 g / kg / d (3 equivalent doses calculated by the crude drug amount) for intragastric treatment. The Control group and the Model group were given an equal volume of normal saline.

[0055] 2. Detection indicators 2.1 Echocardiogram detection 24 hours after the last administration, after the mice in each group were anesthetized by inhaling isoflurane, the abdominal hair was removed, and the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (FS) values were recorded.

[0056] 2.2 Serum B-type natriuretic peptide precursor (proBNP) detection Blood was drawn from the mice in each group, and plasma and serum were separated. The serum proBNP level was detected by ELISA.

[0057] 2.3 Four lipid parameters The levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in the plasma of the mice in each group were detected.

[0058] 2.4 H&E staining The heart tissue was separated, fixed with 4% paraformaldehyde, embedded in paraffin, and cut into 5-μm-thick sections. After dewaxing and permeabilization, H&E staining and Masson staining were performed to detect the structure and cell morphology of the heart.

[0059] 2.5 Oil Red O staining of the aorta and root Separate each group of mice, fix the aorta with paraformaldehyde, and prepare pathological sections of the aortic root. In the Oil Red O working solution, stain in the dark at 37 °C for 60 minutes. After staining, use 60% isopropanol to differentiate the specimen until the fat plaques in the aorta show bright red. Take pictures and record on a black background board, and calculate the plaque area.

[0060] 2.6 H&E staining of aortic root Separate the aorta of each group of mice, select the aortic root for fixation with 4% paraformaldehyde, embed in paraffin, and cut into 5-μm-thick sections. After dewaxing and permeabilization, perform H&E staining to detect the area of the necrotic core.

[0061] 3. Results As Figures 1 to 4 shown: The traditional Chinese medicine composition of Example 1 can significantly increase the left ventricular ejection fraction (LVEF%) and fractional shortening (FS%) of coronary heart disease mice ( Figure 1 and Figure 2 ), and reduce the serum proBNP level ( Figure 3 ); The pathological results show that the traditional Chinese medicine composition of Example 1 can significantly reduce myocardial fibrosis and improve the morphology of myocardial cells in coronary heart disease mice ( Figure 4 ). The above results show that the traditional Chinese medicine composition of Example 1 can improve the cardiac function of coronary heart disease mice.

[0062] As Figures 5 to 6 shown: The traditional Chinese medicine composition of Example 1 can significantly reduce the arterial plaque area and plaque necrotic core area of coronary heart disease mice ( Figure 5 ); The detection results of serum blood lipid levels show that the traditional Chinese medicine composition of Example 1 has the effects of reducing total cholesterol, triglyceride and low-density lipoprotein cholesterol, and increasing high-density lipoprotein cholesterol ( Figure 6 ). The above results show that the traditional Chinese medicine composition of Example 1 can inhibit atherosclerosis and regulate lipid metabolism in coronary heart disease mice.

[0063] Example 13 The embodiments of the present invention provide specific cases of the traditional Chinese medicine compositions obtained in Example 1 and Example 2 in clinical applications.

[0064] Case 1: I. Medical history 1. General information Patient Zhu, female, 82 years old, first diagnosed on January 12, 2025.

[0065] 2. Medical history Chief complaint: Occasional chest tightness and chest pain for more than 1 month.

[0066] Present medical history: Chest tightness and pain occurred more than 10 years ago. After stent implantation in a local hospital, restenosis occurred again. During that period, balloon and stent procedures were performed several times (specific details are unknown). On March 15, 2022, coronary artery bypass grafting was performed in a local hospital, and the symptoms improved. Chest tightness, chest pain, and shortness of breath recurred 1 month ago. On November 30, 2024, percutaneous subclavian artery stent implantation + left subclavian artery angiography + percutaneous selective arterial catheterization were performed in a local hospital. After the operation, there were still discomforts such as chest tightness, shortness of breath, and chest pain, so the patient came to the First Affiliated Hospital of Henan University of Traditional Chinese Medicine for treatment. Current medications: Rosuvastatin 10mg, Isosorbide Dinitrate Tablets, Ticagrelor Tablets, Metoprolol.

[0067] Current symptoms: Conscious, in good spirits, with chest tightness, shortness of breath, chest pain, and dry mouth. The tongue is dull and dark, the tongue coating is white and greasy, and the pulse is string-like.

[0068] Past medical history: No special history.

[0069] Personal history and allergy history: No smoking or alcohol addiction, deny drug and food allergies.

[0070] Family history: No family history of genetic diseases.

[0071] II. Auxiliary examinations Lipid levels checked in a local hospital (unit: mmol / L): Triglyceride: 1.63; Total cholesterol: 3.27; HDL-C: 1.32, LDL-C: 1.71.

[0072] III. Chinese and Western medicine diagnoses 1. Chinese medicine diagnosis: Chest Bi syndrome: Syndrome of qi deficiency, blood stasis, and phlegm obstruction.

[0073] 2. Western medicine diagnosis: 1. Coronary atherosclerotic heart disease; 2. Status after coronary artery stent implantation; 3. Status after coronary artery bypass grafting.

[0074] IV. Intervention measures Based on the original medications, add the following herbal formula: Prescription: The same as in Example 2.

[0075] Total of 14 doses. Usage: Decoct in water for oral administration; Frequency: 1 dose per day, warm it and take it in two divided doses after meals.

[0076] V. Condition changes and prognosis Follow-up visit on February 11, 2025. The patient's chest tightness and chest pain were significantly improved, and there were no other obvious discomforts. Continue to take the same prescription for a total of 14 doses.

[0077] Case 2: I. Medical history data 1. General information Patient Pan, male, 68 years old, first diagnosed on February 8, 2025.

[0078] 2. Medical history Chief complaint: Palpitations and chest tightness for more than 3 years.

[0079] Current medical history: 3 years ago, when working, he felt a tightness in the throat and went to the local hospital. He was diagnosed with coronary heart disease and underwent PCI surgery. After the symptoms improved, he was discharged. He has not had regular follow-up examinations in the past 3 years. Now, in order to adjust the medication, he came to the First Affiliated Hospital of Henan University of Chinese Medicine.

[0080] Current symptoms: Conscious, in good spirits. After getting up at night to urinate, he feels palpitations and discomfort, blurred vision, normal appetite and sleep, and normal bowel and bladder movements. The tongue is dull, the tongue coating is white and greasy, the sublingual collaterals are tortuous, and the pulse is deep, string-like and thready.

[0081] Past medical history: Coronary heart disease for more than 3 years, more than 3 years after PCI surgery; diabetes for more than 3 years. Currently taking metformin hydrochloride sustained-release tablets, dapagliflozin, and glimepiride, with blood sugar controlled at 7; heart failure for more than 3 years.

[0082] Personal history and allergy history: No smoking or alcohol addiction, denying drug and food allergies.

[0083] Family history: No family history of genetic diseases.

[0084] II. Auxiliary examinations On July 26, 2021, at the local hospital: Electrocardiogram examination showed: 1. Sinus tachycardia; 2. Subacute inferior wall myocardial infarction; 3. Subacute anterior septal myocardial infarction; On April 29, 2024, at the local hospital: High-density lipoprotein: 1.13 mmol / L, low-density lipoprotein: 2.1 mmol / L, glucose: 7.49 mmol / L; On February 8, 2025, at the local hospital: Echocardiogram showed abnormal segmental motion amplitude of the left ventricular wall; aortic valve calcification: mild regurgitation of the mitral, tricuspid and aortic valves; low left heart function.

[0085] III. Chinese and Western medicine diagnoses 1. Chinese medicine diagnosis: Chest impediment: Syndrome of qi deficiency, blood stasis and phlegm obstruction.

[0086] 2. Western medicine diagnosis: Coronary atherosclerotic heart disease.

[0087] IV. Intervention measures On the basis of the original medications, add the following formula: Prescription: The same as in Example 1.

[0088] Total of 14 doses. Usage: Decoct in water; Frequency: 1 dose per day, taken warm in 2 divided doses after meals.

[0089] V. Condition Changes and Prognosis On February 25, 2025, the patient came for a follow-up visit. The palpitations and chest tightness had improved significantly, and there were no other obvious discomforts. The original prescription was continued for a total of 14 doses.

[0090] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type, characterized in that, The raw materials of the traditional Chinese medicine composition are proportioned by mass fraction and include 25-35 parts of Codonopsis pilosula, 25-35 parts of Astragalus membranaceus, 12-18 parts of Cornus officinalis, 12-18 parts of Anemarrhena asphodeloides, 5-7 parts of Platycodon grandiflorum, 5-11 parts of Bupleurum chinense, 5-11 parts of Cimicifuga foetida, 12-18 parts of Sparganium stoloniferum, 12-18 parts of Curcuma zedoaria, 8-12 parts of Cinnamomum cassia, 16-34 parts of Trichosanthes kirilowii, 16-24 parts of Allium macrostemon, 12-18 parts of Pinellia ternata, 25-35 parts of Dioscorea opposita, and 8-12 parts of honey-fried licorice root.

2. The traditional Chinese medicine composition according to claim 1, wherein The raw materials of the traditional Chinese medicine composition are proportioned by mass fraction and include 27-33 parts of Codonopsis pilosula, 27-33 parts of Astragalus membranaceus, 13.5-16.5 parts of Cornus officinalis, 13.5-16.5 parts of Anemarrhena asphodeloides, 5.5-6.5 parts of Platycodon grandiflorum, 5.5-6.5 parts of Bupleurum chinense, 5.5-6.5 parts of Cimicifuga foetida, 13.5-16.5 parts of Sparganium stoloniferum, 13.5-16.5 parts of Curcuma zedoaria, 9-11 parts of Cinnamomum cassia, 18-22 parts of Trichosanthes kirilowii, 18-22 parts of Allium macrostemon, 13.5-16.5 parts of Pinellia ternata, 27-33 parts of Dioscorea opposita, and 9-11 parts of honey-fried licorice root; or, it includes 27-33 parts of Codonopsis pilosula, 27-33 parts of Astragalus membranaceus, 13.5-16.5 parts of Cornus officinalis, 13.5-16.5 parts of Anemarrhena asphodeloides, 5.5-6.5 parts of Platycodon grandiflorum, 9.5-10.5 parts of Bupleurum chinense, 9.5-10.5 parts of Cimicifuga foetida, 13.5-16.5 parts of Sparganium stoloniferum, 13.5-16.5 parts of Curcuma zedoaria, 9-11 parts of Cinnamomum cassia, 28-32 parts of Trichosanthes kirilowii, 18-22 parts of Allium macrostemon, 13.5-16.5 parts of Pinellia ternata, 27-33 parts of Dioscorea opposita, and 9-11 parts of honey-fried licorice root.

3. The Chinese medicine composition according to claim 2, wherein, The raw materials of the traditional Chinese medicine composition are proportioned by mass fraction and include 30 parts of Codonopsis pilosula, 30 parts of Astragalus membranaceus, 15 parts of Cornus officinalis, 15 parts of Anemarrhena asphodeloides, 6 parts of Platycodon grandiflorum, 6 parts of Bupleurum chinense, 6 parts of Cimicifuga foetida, 15 parts of Sparganium stoloniferum, 15 parts of Curcuma zedoaria, 10 parts of Cinnamomum cassia, 20 parts of Trichosanthes kirilowii, 20 parts of Allium macrostemon, 15 parts of Pinellia ternata, 30 parts of Dioscorea opposita, and 10 parts of honey-fried licorice root; or, it includes 30 parts of Codonopsis pilosula, 30 parts of Astragalus membranaceus, 15 parts of Cornus officinalis, 15 parts of Anemarrhena asphodeloides, 6 parts of Platycodon grandiflorum, 10 parts of Bupleurum chinense, 10 parts of Cimicifuga foetida, 15 parts of Sparganium stoloniferum, 15 parts of Curcuma zedoaria, 10 parts of Cinnamomum cassia, 30 parts of Trichosanthes kirilowii, 20 parts of Allium macrostemon, 15 parts of Pinellia ternata, 30 parts of Dioscorea opposita, and 10 parts of honey-fried licorice root.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The Cornus officinalis is Cornus officinalis processed with wine; and / or The Bupleurum chinense is Bupleurum chinense DC.; and / or The Sparganium stoloniferum is Sparganium stoloniferum processed with vinegar; and / or The Curcuma zedoaria is Curcuma zedoaria processed with vinegar.

5. The preparation method of the traditional Chinese medicine composition according to any one of claims 1 to 4, characterized in that, The raw materials are extracted with water.

6. The preparation method according to claim 5, characterized in that, The extraction method is decoction extraction.

7. The preparation method according to claim 6, characterized in that, Extract 2-3 times. Each time, the mass of the water is 6-8 times the mass of the raw materials, and the extraction time is 50-70 minutes. Combine the extraction solutions obtained each time.

8. The preparation method according to claim 7, characterized in that, Extract 2 times, 1 hour each time.

9. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4 or the traditional Chinese medicine composition prepared by the preparation method according to any one of claims 5 to 8, characterized in that, It includes: Application in the preparation of a drug for treating coronary heart disease of qi deficiency, blood stasis and phlegm obstruction type; Application in the preparation of a drug for regulating blood lipid.

10. The application according to claim 8, characterized in that, The drug is an oral preparation; and / or The drug also includes a pharmaceutically acceptable excipient.

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