Traditional Chinese medicine composition for preventing and / or treating coronary heart disease as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating and / or preventing coronary heart disease as well as a preparation method and application thereof. Specifically, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 8-13 parts of herba artemisiae scopariae, 8-12 parts of rhizoma atractylodis, 8-12 parts of rhizoma alismatis, 8-14 parts of rhizoma curcumae longae, 10-20 parts of radix salviae miltiorrhizae, 8-14 parts of radix curcumae, 1-5 parts of pseudo-ginseng powder, 5-10 parts of rhizoma corydalis, 8-12 parts of pinellia ternate, 5-10 parts of coptis chinensis, 4-10 parts of ginseng, 5-12 parts of pericarpium citri reticulatae and 4-10 parts of liquorice. The invention also provides a method for preparing the traditional Chinese medicine composition and application of the traditional Chinese medicine composition in preparation of medicines for treating and / or preventing coronary atherosclerotic heart disease. The traditional Chinese medicine composition can reduce the blood viscosity, improve the heart function, reduce the myocardial infarction area, inhibit atherosclerotic plaque formation, regulate the blood fat level or reduce the myocardial injury marker level in serum.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology. Specifically, this invention relates to a traditional Chinese medicine composition for treating and / or preventing coronary heart disease, its preparation method, and its application. Background Technology

[0002] Coronary artery disease (CAD) is a chronic inflammatory disease caused by the combined effects of genetic and environmental factors. It involves multiple intertwined pathological processes, including lipid metabolism disorders, vascular endothelial damage, inflammatory cell infiltration, oxidative stress, platelet aggregation, and thrombus formation. CAD is prevalent in adults over 40 years of age, but has recently shown a trend towards affecting younger individuals. Common symptoms include chest tightness, chest pain, and palpitations, and it can even lead to myocardial infarction and sudden death. In Western medicine, current treatment primarily relies on antiplatelet drugs, statins, vasodilators, and surgical procedures such as percutaneous coronary intervention and coronary artery bypass grafting. While these methods can alleviate symptoms or restore blood flow to some extent, they still have many limitations: long-term use of Western medicine may be accompanied by risks such as bleeding, liver damage, myopathy, elevated blood sugar, and drug resistance; while interventional and surgical procedures have complications such as trauma, restenosis, and thrombosis, and their applicability to multivessel diffuse lesions or elderly and frail patients is limited. Overall, although existing Western medicine methods can control risk factors or locally improve blood supply, they are still insufficient in systematically regulating the overall pathological process of atherosclerosis and reversing plaques, and their long-term safety and patient tolerability need to be improved.

[0003] In Traditional Chinese Medicine (TCM) theory, coronary heart disease falls under the categories of "chest pain" and "heart pain." Its pathogenesis has a long history, with relevant discussions appearing as early as the *Huangdi Neijing* and *Jinkui Yaolue*. The basic pathogenesis is described as "deficient Yang and taut Yin." Modern TCM considers this disease to be mostly "deficiency of the root and excess of the branch," with the root deficiency primarily being Qi deficiency and Yang deficiency, while the branch excess focuses on blood stasis and phlegm turbidity. Among these, "the mutual binding of phlegm and blood stasis" is considered a crucial core pathogenesis throughout the development of coronary heart disease. Internal accumulation of phlegm turbidity obstructs Qi flow and affects blood circulation, potentially leading to internal blood stasis; conversely, blood stasis obstructs the collaterals, hindering the distribution of body fluids and contributing to the generation of phlegm turbidity. These two factors are mutually causal, intertwined, and entangled in the chest Yang area and the heart vessels, resulting in obstruction of the heart vessels and the manifestation of chest pain and heart pain. Current traditional Chinese medicine (TCM) compound prescriptions and prepared medicines used clinically for coronary heart disease, such as Danshen preparations and blood-activating and stasis-removing formulas, focus more on the treatment of phlegm and blood stasis. However, they still lack a comprehensive and systematic approach to synergistic intervention and treatment of the complex pathogenesis of "phlegm and blood stasis." Furthermore, existing TCM preparations generally suffer from relatively slow onset of action, insufficient control of acute symptoms, inconsistent manufacturing processes and quality control levels, and low bioavailability of some drugs, limiting their widespread clinical application and stable efficacy.

[0004] Therefore, combining the modern pathological mechanisms of coronary heart disease with the traditional Chinese medicine understanding of the "phlegm-blood stasis" pathogenesis, there is an urgent need to construct a traditional Chinese medicine compound that can target multiple pathological links in atherosclerosis while closely addressing the characteristics of the phlegm-blood stasis pathogenesis, achieving a holistic treatment of both phlegm and blood stasis, addressing both the root cause and the symptoms. Through rational component selection and preparation processes, its comprehensive efficacy in regulating blood lipids, inhibiting inflammation, protecting vascular endothelium, and reducing myocardial damage can be enhanced. This would provide a new traditional Chinese medicine treatment option for coronary heart disease, especially the phlegm-blood stasis type, with relatively stable onset of action, comprehensive target points, and suitability for long-term use. Summary of the Invention

[0005] To address the above problems, the purpose of this invention is to provide a traditional Chinese medicine composition for treating coronary atherosclerotic heart disease, especially for treating coronary atherosclerotic heart disease of the phlegm-blood stasis type.

[0006] The traditional Chinese medicine composition involved in this invention originates from Academician Zhang Boli's clinical experience formula for coronary heart disease of the "phlegm-blood stasis" type. Based on long-term clinical practice, Academician Zhang discovered that the proportion of patients with phlegm-blood stasis syndrome in coronary heart disease is increasing, while the existing selection of proprietary Chinese medicines for this syndrome is relatively limited. Therefore, he summarized the empirical formula "Phlegm-Blood Stasis Relief Formula." This formula primarily uses the methods of dispelling dampness and relieving pain, promoting blood circulation and alleviating pain, while also regulating the spleen and stomach, using pungent and bitter herbs to open and descend, and combining tonification and purgation. By strengthening the middle jiao (middle burner) to reduce the generation of phlegm and dampness, it aligns with the pathogenesis characteristics of phlegm-blood stasis type coronary heart disease, embodying the principle of treating both the root cause and the symptoms.

[0007] The traditional Chinese medicine composition provided by this invention is derived from the above-mentioned clinical practice and embodies the treatment strategy of treating both phlegm and blood stasis. It can reduce heart and arterial damage related to coronary heart disease by lowering blood lipids and regulating blood rheology, providing another option for the clinical treatment of coronary heart disease with phlegm and blood stasis.

[0008] Another object of the present invention is to provide a method for preparing the traditional Chinese medicine composition of the present invention, which is simple and easy to industrialize.

[0009] The above-mentioned objective of the present invention is achieved by providing the following technical solution.

[0010] In a first aspect, the present invention provides a traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease, which is prepared from raw materials comprising the following components:

[0011] Artemisia capillaris 8-13 parts, Atractylodes lancea 8-12 parts, Alisma plantago-aquatica 8-12 parts, Curcuma longa 8-14 parts, Salvia miltiorrhiza 10-20 parts, Curcuma longa 8-14 parts, Panax notoginseng powder 1-5 parts, Corydalis yanhusuo 5-10 parts, Pinellia ternata 8-12 parts, Coptis chinensis 5-10 parts, Panax ginseng 4-10 parts, Citrus reticulata peel 5-12 parts, Glycyrrhiza uralensis 4-10 parts.

[0012] Preferably, the traditional Chinese medicine composition of the present invention is prepared from raw materials comprising the following components:

[0013] Artemisia capillaris 10-13 parts, Atractylodes lancea 9-11 parts, Alisma plantago-aquatica 9-11 parts, Curcuma longa 10-13 parts, Salvia miltiorrhiza 12-18 parts, Curcuma longa 10-13 parts, Panax notoginseng powder 1-3 parts, Corydalis yanhusuo 5-9 parts, Pinellia ternata 9-11 parts, Coptis chinensis 5-8 parts, Panax ginseng 4-8 parts, Citrus reticulata peel 6-11 parts, Glycyrrhiza uralensis 4-8 parts.

[0014] Preferably, the traditional Chinese medicine composition of the present invention is prepared from raw materials comprising the following components:

[0015] Artemisia capillaris 12 parts, Atractylodes lancea 10 parts, Alisma plantago-aquatica 10 parts, Curcuma longa 12 parts, Salvia miltiorrhiza 15 parts, Curcuma longa 12 parts, Panax notoginseng powder 2 parts, Corydalis yanhusuo 6 parts, Pinellia ternata 10 parts, Coptis chinensis 6 parts, Panax ginseng 5 parts, Citrus reticulata peel 10 parts, Glycyrrhiza uralensis 5 parts.

[0016] The traditional Chinese medicine composition provided by this invention is designed for chest pain and heart pain caused by phlegm and blood stasis. It uses the method of dispelling dampness and unblocking the meridians to eliminate dampness, relieve pain, promote blood circulation, and alleviate pain. The formula uses Artemisia capillaris and Atractylodes lancea as the principal herbs. Artemisia capillaris is good at clearing damp heat and guiding dampness out through urination; Atractylodes lancea is good at drying dampness and strengthening the spleen, helping the spleen to transport and transform water and dampness. The two herbs work together to eliminate dampness and turbidity, directly targeting the root cause of phlegm and dampness obstruction, which is the foundation for eliminating dampness and relieving pain. The assistant herb Alisma plantago-aquatica assists Artemisia capillaris in promoting diuresis and eliminating dampness, giving the pathogenic factors an outlet; Curcuma longa breaks up blood stasis, promotes qi circulation, unblocks the meridians, and relieves pain; Salvia miltiorrhiza promotes blood circulation, removes blood stasis, unblocks the meridians, and activates the collaterals; Curcuma longa promotes blood circulation, promotes qi circulation, and relieves liver depression. The three herbs work together to promote blood circulation, unblock the meridians, promote qi circulation, and relieve pain, assisting the principal herbs in relieving pain and alleviating pain. Pinellia ternata, an adjuvant herb, dries dampness and resolves phlegm, while Atractylodes lancea strengthens the spleen and eliminates dampness, thus resolving phlegm and removing blood stasis. Coptis chinensis clears heat and dries dampness, clearing both damp heat and, together with Pinellia ternata, promotes the opening and descending of dampness, thus dispersing blood stasis. Ginseng greatly replenishes vital energy, and when the energy is strong, blood circulation is powerful, preventing the dampness-removing and blood-activating effects from damaging the body's vital energy. Citrus reticulata peel regulates qi and strengthens the spleen, dries dampness and resolves phlegm, and assists the spleen and stomach in their digestive functions, preventing the generation of dampness. Corydalis yanhusuo activates blood circulation, promotes qi circulation, and relieves pain, while Panax notoginseng disperses blood stasis, stops bleeding, and relieves pain, working together with the principal herbs to unblock the meridians and relieve pain.

[0017] Preferably, in the traditional Chinese medicine composition of the present invention, the components other than Panax notoginseng powder are selected from medicinal decoction pieces, water extracts of medicinal materials, and alcohol-water mixed solvent extracts of medicinal materials.

[0018] Preferably, in the traditional Chinese medicine composition of the present invention, the volume concentration of ethanol in the alcohol-water mixed solvent is 20%-90%.

[0019] Preferably, in the traditional Chinese medicine composition of the present invention, the aqueous extract of the medicinal materials is prepared by a method comprising the following steps: taking the medicinal materials (excluding Panax notoginseng powder) and decocting them with water at least once, filtering the decoction to obtain the aqueous extract; and / or

[0020] The medicinal material alcohol-water mixed solvent extract is prepared by a method including the following steps: taking the medicinal material slices except for Panax notoginseng powder, and heating and extracting them with an alcohol-water mixed solvent with an ethanol volume concentration of 20%-90% to obtain the medicinal material alcohol-water mixed solvent extract.

[0021] Secondly, the present invention provides a method for preparing the traditional Chinese medicine composition of the present invention, comprising the following steps:

[0022] (1) Take the medicinal materials other than Panax notoginseng powder, decoct them with water at least once, filter the decoction, and obtain the water extract;

[0023] (2) Concentrate the water extract, and then dry the concentrate to make a dry powder;

[0024] (3) The dry powder is mixed with Panax notoginseng powder to obtain the traditional Chinese medicine composition.

[0025] Preferably, in the method described in this invention, step (1) includes the following steps:

[0026] (i) Take all medicinal materials except Panax notoginseng powder, add 8-14 times the amount of water and soak for 20-40 minutes;

[0027] (ii) Perform the first decoction: bring to a boil over high heat, then reduce to a simmer and maintain for 40-80 minutes. Filter to obtain the first decoction.

[0028] (iii) Add 6-10 times the amount of water to the dregs and decoct for the second time. After boiling over high heat, reduce to low heat and maintain for 30-50 minutes. Filter to obtain the second decoction.

[0029] (iv) Combine the first decoction and the second decoction to obtain an aqueous extract.

[0030] Preferably, in the method of the present invention, the concentration of the water extract in step (2) includes the following steps: concentrating the water extract at 50-70°C to a relative density of 1.020-1.090 g / ml.

[0031] Preferably, in the method described in this invention, the drying of the concentrate in step (2) includes the following steps: spray drying the concentrate at an air inlet temperature of 150°C-180°C.

[0032] Thirdly, the present invention provides a pharmaceutical preparation for the prevention and / or treatment of coronary heart disease, comprising a preventive and / or therapeutically effective amount of the traditional Chinese medicine composition of the present invention, and pharmaceutically acceptable excipients.

[0033] Preferably, in the pharmaceutical formulation of the present invention, the pharmaceutically acceptable excipient is selected from one or more of diluents, excipients, binders, preservatives and flavoring agents.

[0034] The pharmaceutical preparations described in this invention can be oral preparations, preferably tablets, capsules, pills, granules, powders, oral liquids, or drop pills; or the pharmaceutical preparations described in this invention can be non-oral preparations, preferably injections, patches, or sprays.

[0035] Fourthly, the present invention provides the use of the traditional Chinese medicine composition of the present invention in the preparation of a medicament for treating and / or preventing coronary atherosclerotic heart disease.

[0036] Preferably, in the use described in this invention, the coronary atherosclerotic heart disease is a phlegm-blood stasis type of coronary atherosclerotic heart disease.

[0037] Preferably, in the uses described in this invention, the drug is used for one or more of the following purposes: reducing blood viscosity, improving cardiac function, reducing myocardial infarction area, inhibiting the formation of atherosclerotic plaques, regulating blood lipid levels, or reducing the level of myocardial injury markers in serum.

[0038] In clinical observation, patients diagnosed with stable angina pectoris due to phlegm-stasis syndrome were treated with the aforementioned Phlegm-Stasis-Clearing and Pain-Relieving Formula (i.e., the traditional Chinese medicine composition of this invention), one dose daily, decocted in water to 300 ml, divided into two administrations of 150 ml each time, for a course of 4 weeks. All patients maintained their original routine Western medicine treatments such as antihypertensive and hypoglycemic agents, without the addition of other antianginal drugs. During the treatment period, patients were instructed to maintain emotional stability, engage in 30 minutes of gentle exercise daily (such as slow walking), avoid spicy and greasy foods, quit smoking and limit alcohol consumption, and maintain regular sleep patterns. Post-treatment results showed that 83.7% of patients experienced significant improvement in chest pain and chest tightness symptoms. The Seattle Angina Scale was used for assessment, and patients' scores in all five dimensions—physical activity limitation (PL), angina stability (AS), angina attack frequency (AF), treatment satisfaction (TS), and disease awareness (DP)—were significantly improved compared to before treatment. In terms of TCM syndromes, the patient's purplish-dark tongue color lessened, the thick, greasy coating mostly turned into a thin, white coating, and the pulse, which was hesitant and wiry, became milder. The overall syndrome improvement rate was 87.5%.

[0039] The present invention has at least the following beneficial effects:

[0040] This invention, based on the traditional Chinese medicine theory of "treating phlegm and blood stasis together," targets the core pathogenesis of coronary heart disease caused by the mutual binding of phlegm and blood stasis, and provides a traditional Chinese medicine composition with clearly defined components and synergistic effects. Animal experiments have demonstrated that this composition can exert comprehensive therapeutic effects through multiple pathways and multiple targets.

[0041] 1. Improves cardiac structure and function: Significantly reduces myocardial ischemia-induced damage, reduces myocardial infarction area, improves cardiac function indicators such as ejection fraction (EF) and fractional shortening (FS), and inhibits undesirable left ventricular remodeling.

[0042] 2. Regulates blood lipids and inhibits atherosclerosis: Effectively reduces serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels, increases high-density lipoprotein cholesterol (HDL-C), reduces lipid deposition in the aorta, and inhibits the formation and development of atherosclerotic plaques.

[0043] 3. Reduces myocardial cell damage: Significantly downregulates the release of myocardial injury markers lactate dehydrogenase (LDH), creatine kinase (CK), and its isoenzyme (CK-MB), indicating a clear protective effect on ischemic myocardium.

[0044] 4. Improves blood rheology: Reduces whole blood viscosity and plasma viscosity, decreases fibrinogen content, helps improve microcirculation, and alleviates "blood stasis" state.

[0045] In summary, the traditional Chinese medicine composition of the present invention achieves holistic intervention on key pathological links of coronary heart disease (especially the phlegm-blood stasis type) by "treating phlegm and blood stasis simultaneously". It has the comprehensive characteristics of definite curative effect, multi-target synergy and relatively safe action, providing a new treatment option for clinical practice. Attached Figure Description

[0046] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings, wherein:

[0047] Figure 1 The graph shows the results of detecting the effects of the drug composition on the viability of HepG2 cells, HUVEC cells, and THP-1 cells, as well as its effect on lipid metabolism in HepG2 cells; among them Figure 1 A is a statistical graph of HepG2 cell viability; Figure 1 B is a statistical graph of HUVEC cell viability; Figure 1 C represents the statistical graph of THP-1 cell viability; Figure 1 D is a graph showing the TC content in the supernatant of HepG2 cells; Figure 1 E represents the TG content in the supernatant of HepG2 cells; Figure 1 F shows the LDL content in the supernatant of HepG2 cells. Compared with the control group, ****P<0.0001; compared with the model group, ## P < 0.01, ### P < 0.001, #### P < 0.0001.

[0048] Figure 2 This is a diagram showing the results of co-culturing HUVEC and THP-1 cells;Figure 2 A shows the results of co-culture staining (×100). Figure 2 B is a statistical graph showing the migration results of THP-1 cells. Compared with the control group, ****P<0.0001; compared with the model group, #### P < 0.0001.

[0049] Figure 3 This is a graph showing the detection and statistical analysis of rat electrocardiogram signals; among which... Figure 3 A is the electrocardiogram of a rat. Figure 3 B is a statistical graph of the ST segment height in rats. Compared with the control group, ****P<0.0001; compared with the model group, # P < 0.05 #### P < 0.0001.

[0050] Figure 4 The graph shows the echocardiographic findings and statistical analysis of rat hearts; among which... Figure 4 A is a rat cardiac ultrasound image. Figure 4 B is a statistical graph of the ejection fraction of the rat heart. Figure 4 C is a graph showing the fractional shortening of the minor axis. Figure 4 D is a statistical chart of stroke volume. Figure 4 E represents the statistical graph of left ventricular end-diastolic diameter. Compared with the control group, ****P < 0.0001; compared with the model group, # P < 0.05 ## P < 0.01, ### P < 0.001, #### P < 0.0001.

[0051] Figure 5 This is an ultrasound image of the aortic arch in a rat.

[0052] Figure 6 Image of rat heart stained with HE (×200).

[0053] Figure 7 Image of rat aortic arch stained with HE (×200).

[0054] Figure 8 Oil Red O staining image of rat liver (×200).

[0055] Figure 9 This is a Masson staining image of a rat heart.

[0056] Figure 10 This is a statistical chart of four lipid tests in rats, among which... Figure 10 A shows the serum TC content in rats. Figure 10 B is a graph showing the serum TG content in rats. Figure 10 C represents the serum LDL-C content in rats. Figure 10D represents the serum HDL-C content in rats. Compared with the control group, ****P < 0.0001; compared with the model group, # P < 0.05 ## P < 0.01, #### P < 0.0001.

[0057] Figure 11 This is a statistical chart of rat myocardial injury indicators, in which... Figure 11 A shows the serum lactate dehydrogenase content in rats. Figure 11 B is a graph showing the serum creatine kinase content in rats. Figure 11 C represents the serum creatine kinase isoenzyme levels in rats. Compared with the control group, ****P < 0.0001; compared with the model group, # P < 0.05 ### P < 0.001, #### P < 0.0001.

[0058] Figure 12 This is a statistical graph of whole blood viscosity analysis in rats, where... Figure 12 A is a low-cut plot of whole blood viscosity in rats. Figure 12 B is a high-cut image of whole blood viscosity in rats. Figure 12 C represents the fibrinogen content in rats. Figure 12 D represents the rat plasma viscosity map. Compared with the control group, *P<0.05, ****P<0.0001; compared with the model group, # P < 0.05 ## P < 0.01, ### P < 0.001, #### P < 0.0001.

[0059] Figure 13 This is a statistical graph showing the changes in the body weight of rats. Detailed Implementation

[0060] The present invention will be further described in detail below with reference to specific embodiments. The embodiments given are only for illustrating the present invention and are not intended to limit the scope of the present invention.

[0061] Example 1

[0062] Weigh the following components by weight: 12 parts Artemisia capillaris, 10 parts Atractylodes lancea, 10 parts Alisma plantago-aquatica, 12 parts Curcuma longa, 15 parts Salvia miltiorrhiza, 12 parts Curcuma longa, 2 parts Panax notoginseng powder, 6 parts Corydalis yanhusuo, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Panax ginseng, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0063] The traditional Chinese medicine composition was prepared according to the following method:

[0064] (1) Decoction steps: Place all medicinal materials except Panax notoginseng powder into a decoction pot, add 12 times the amount of water and soak for 30 minutes. For the first decoction, bring to a boil over high heat, then simmer over low heat for 60 minutes; filter the extract through a 100-mesh filter. For the second decoction, add 8 times the amount of water, bring to a boil over high heat, then simmer over low heat for 40 minutes; filter the extract through a 100-mesh filter.

[0065] (2) Concentration step: Concentrate at 60°C until the density is 1.050 mg / ml.

[0066] (3) Drying steps: Spray drying is carried out at an air inlet temperature of 165℃, and finally Panax notoginseng powder is added to obtain the traditional Chinese medicine composition.

[0067] Example 2

[0068] Weigh the following components by weight: 8 parts Artemisia capillaris, 12 parts Atractylodes lancea, 12 parts Alisma plantago-aquatica, 9 parts Curcuma longa, 10 parts Salvia miltiorrhiza, 14 parts Curcuma longa, 4 parts Panax notoginseng powder, 10 parts Corydalis yanhusuo, 12 parts Pinellia ternata, 9 parts Coptis chinensis, 10 parts Panax ginseng, 12 parts Citrus reticulata peel, and 10 parts Glycyrrhiza uralensis.

[0069] The traditional Chinese medicine composition was prepared according to the method in Example 1.

[0070] Example 3

[0071] Weigh the following components by weight: 13 parts Artemisia capillaris, 8 parts Atractylodes lancea, 8 parts Alisma plantago-aquatica, 14 parts Curcuma longa, 20 parts Salvia miltiorrhiza, 8 parts Curcuma longa, 1 part Panax notoginseng powder, 5 parts Corydalis yanhusuo, 8 parts Pinellia ternata, 5 parts Coptis chinensis, 4 parts Panax ginseng, 5 parts Citrus reticulata peel, and 4 parts Glycyrrhiza uralensis.

[0072] The traditional Chinese medicine composition was prepared according to the method in Example 1.

[0073] Comparative Example 1

[0074] Weigh the following components by weight: 10 parts Atractylodes lancea, 10 parts Alisma plantago-aquatica, 12 parts Curcuma longa, 15 parts Salvia miltiorrhiza, 12 parts Curcuma longa, 2 parts Panax notoginseng powder, 6 parts Corydalis yanhusuo, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Panax ginseng, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0075] The traditional Chinese medicine composition was prepared according to the method of Example 1 (the only difference being that it did not contain Artemisia capillaris).

[0076] Comparative Example 2

[0077] Weigh the following components by weight: 12 parts Artemisia capillaris, 10 parts Atractylodes lancea, 10 parts Alisma plantago-aquatica, 15 parts Salvia miltiorrhiza, 12 parts Curcuma longa, 2 parts Panax notoginseng powder, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Panax ginseng, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0078] The traditional Chinese medicine composition was prepared according to the method of Example 1 (the only difference being that it did not contain turmeric and corydalis).

[0079] Comparative Example 3

[0080] Weigh the following components by weight: 12 parts Artemisia capillaris, 10 parts Alisma plantago-aquatica, 12 parts Curcuma longa, 15 parts Salvia miltiorrhiza, 2 parts Panax notoginseng powder, 6 parts Corydalis yanhusuo, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Panax ginseng, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0081] The traditional Chinese medicine composition was prepared according to the method of Example 1 (the only difference being that it did not contain Atractylodes lancea and Curcuma longa).

[0082] Comparative Example 4

[0083] Weigh the following components by weight: 12 parts Artemisia capillaris, 10 parts Atractylodes lancea, 10 parts Alisma plantago-aquatica, 12 parts Ligusticum chuanxiong, 15 parts Salvia miltiorrhiza, 12 parts Curcuma longa, 2 parts Panax notoginseng powder, 6 parts Corydalis yanhusuo, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Panax ginseng, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0084] The traditional Chinese medicine composition was prepared according to the method of Example 1 (the only difference being that Chuanxiong was used instead of turmeric).

[0085] Comparative Example 5

[0086] Weigh the following components by weight: 12 parts Artemisia capillaris, 10 parts Atractylodes lancea, 10 parts Alisma plantago-aquatica, 12 parts Curcuma longa, 15 parts Salvia miltiorrhiza, 12 parts Curcuma longa, 2 parts Panax notoginseng powder, 6 parts Corydalis yanhusuo, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Astragalus membranaceus, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0087] The traditional Chinese medicine composition was prepared according to the method of Example 1 (the only difference being that Astragalus membranaceus was used instead of ginseng).

[0088] Comparative Example 6

[0089] Weigh the following components by weight: 6 parts Artemisia capillaris, 10 parts Atractylodes lancea, 10 parts Alisma plantago-aquatica, 12 parts Curcuma longa, 15 parts Salvia miltiorrhiza, 12 parts Curcuma longa, 2 parts Panax notoginseng powder, 6 parts Corydalis yanhusuo, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Panax ginseng, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0090] The traditional Chinese medicine composition was prepared according to the method in Example 1 (the only difference being the reduced dosage of Artemisia capillaris).

[0091] Comparative Example 7

[0092] Weigh the following components by weight: 16 parts Artemisia capillaris, 10 parts Atractylodes lancea, 10 parts Alisma plantago-aquatica, 12 parts Curcuma longa, 15 parts Salvia miltiorrhiza, 12 parts Curcuma longa, 2 parts Panax notoginseng powder, 6 parts Corydalis yanhusuo, 10 parts Pinellia ternata, 6 parts Coptis chinensis, 5 parts Panax ginseng, 10 parts Citrus reticulata peel, and 5 parts Glycyrrhiza uralensis.

[0093] The traditional Chinese medicine composition was prepared according to the method of Example 1 (the only difference being the increased dosage of Artemisia capillaris).

[0094] Comparative Example 8

[0095] Weigh the following components by parts by weight: 12 parts of Artemisia capillaris, 10 parts of Atractylodes lancea, 10 parts of Alisma orientale, 12 parts of Curcuma longa, 15 parts of Salvia miltiorrhiza, 12 parts of Curcuma aromatica, 2 parts of Panax notoginseng powder, 6 parts of Corydalis yanhusuo, 10 parts of Pinellia ternata, 14 parts of Coptis chinensis, 5 parts of Panax ginseng, 10 parts of Citrus reticulata Blanco, and 5 parts of Glycyrrhiza uralensis Fisch.

[0096] Prepare the traditional Chinese medicine composition according to the method of Example 1 (only the difference is that the dosage of Coptis chinensis is increased).

[0097] Pharmacodynamic evaluation

[0098] The present inventors evaluated the therapeutic effect of the traditional Chinese medicine compositions prepared in the above Examples 1-3 and Comparative Examples 1-8 on coronary heart disease, and found that the traditional Chinese medicine compositions prepared in Examples 1-3 had a good therapeutic effect on coronary heart disease. The following are the specific protocols and test results of the pharmacodynamic evaluation.

[0099] 1. Test materials

[0100] Test animals: SPF female SD rats, weighing 180-220 g, provided by Vital River (Beijing) Laboratory Animal Technology Co., Ltd. and raised in Tianjin Jinke Biotechnology Co., Ltd. SPF (22±2°C, natural light-dark cycle, relative humidity 50±10%), normal diet. Animal license number SYXK (Jin) 2020-0007. This study was approved by the Laboratory Animal Ethics Committee (Ethical batch number GENINK-20240033).

[0101] Experimental cells: Human umbilical vein endothelial cells (HUVEC), human hepatoma cells (HepG2) and human monocytes (THP-1) cells were all purchased from Shanghai iCell Bioscience Co., Ltd.

[0102] Test reagents and drugs: High-fat feed (Xiaoshu Youtai Biotechnology Co., Ltd.); Wulai sugar (Sinopharm Chemical Reagent Co., Ltd.); Physiological saline (self-made); Cholesterol assay kit, Triglyceride assay kit, High-density lipoprotein cholesterol assay kit, Low-density lipoprotein cholesterol assay kit, Creatine kinase assay kit, Creatine kinase isoenzyme assay kit, Lactate dehydrogenase assay kit (Shenzhen Mindray Animal Medical Technology Co., Ltd.); Danlou tablets (Jilin Kangnai'er Pharmaceutical Co., Ltd.); Lovastatin tablets (Shandong Luoxin Pharmaceutical Group Co., Ltd.); Vitamin D3 injection (Zhejiang Xinhecheng Co., Ltd.); Palmitic acid (PA) and phorbol-12-myristate-13-acetate (PMA) were purchased from Sigma-Aldrich, USA; Fetal bovine serum (FBS), DMEM, MEM and 1640 medium were purchased from Gibco, USA; Hematoxylin staining solution and Cell Counting Kit-8 (CCK-8) were purchased from Servicebio, China.

[0103] 2. Experimental methods and results

[0104] 2.1 Pharmacodynamic Evaluation in Cellular Experiments

[0105] 2.1.1 Test Methods

[0106] 2.1.1.1 Cell Culture

[0107] HUVEC cells were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin, and 1% streptomycin; THP-1 cells were cultured in 1640 medium supplemented with the same additives (10% FBS, 1% penicillin, and 1% streptomycin); and HepG2 cells were cultured in MEM medium supplemented with the same additives (10% FBS, 1% penicillin, and 1% streptomycin). All cells were incubated at 37°C in a CO2 incubator containing 5% CO2, and passaged when cell confluence reached 80%-90%. All cells used in the experiments were passaged to within 50 generations; unless otherwise specified, the standard seeding density was 4 × 10⁶ cells / year. 5 / ml.

[0108] 2.1.1.2 Cell viability assay

[0109] Cells in the logarithmic growth phase were seeded into 96-well plates. After incubation at 37°C and 5% CO2 for 24 hours, cells were treated with different concentrations of drugs for 24 hours. Cell viability was assessed using a CCK-8 assay, and absorbance at 450 nm was measured using a microplate reader.

[0110] 2.1.1.3 Cell migration detection

[0111] THP-1 cells were seeded in 6-well plates and induced to differentiate into macrophages by adding 200 ng / mL PMA for 48 hours. After differentiation, they were incubated with 15 μg / mL PA for 24 hours to induce lipid accumulation, and drug treatment was added simultaneously. For HUVECs, 1×10 6 Cells were seeded at a density of 100 cells / well in 6-well plates and cultured to 80% confluence. A model was established by inducing the induction of the cell line with 100 μg / mL PA for 24 hours. After discarding the culture medium, the cells were washed with PBS, fixed with 4% paraformaldehyde, and stained with hematoxylin for 5 minutes. The staining intensity was observed using an inverted microscope, and the area of ​​lipid droplet-positive regions was quantitatively analyzed using Image-ProPlus 6.0 software.

[0112] 2.1.1.4 Detection of cellular lipid metabolism factors

[0113] The cell modeling method is the same as in 2.1.1.1. After the model is established, the cell supernatant is taken and the contents of TC, TG and LDL are detected according to the instructions of each kit.

[0114] 2.1.1.5 Data Statistics

[0115] All data obtained in this experiment were analyzed using GraphPad Prism 8.0. The analysis method was one-way ANOVA, and the statistical results are shown as mean ± standard deviation (SD). P < 0.05 was considered statistically significant.

[0116] 2.1.2 Test Results

[0117] 2.1.2.1 Cytotoxicity Detection

[0118] like Figure 1 As shown in A, 1B, and 1C, the pharmaceutical composition prepared in Example 1 showed no significant toxicity to HepG2, HUVEC, and THP-1 cells at concentrations up to 2000 μg crude drug / ml. Figure 1 (The horizontal axes A, 1B, and 1C represent the concentrations of the pharmaceutical composition prepared in Example 1). Since Comparative Examples 4 and 5 only changed one component, separate cytotoxicity tests were not performed. Based on the cytotoxicity experiments, the dosage for the cell administration groups was determined according to Table 1.

[0119] Table 1 Cell drug delivery regimen

[0120] Group Dosing concentration (μg drug / ml) Control group 0 Model group 0 Lovastatin group 10 Example 1 2000 Comparative Example 4 2000 Comparative Example 5 2000

[0121] 2.1.2.2 Detection of cellular lipid metabolism indicators

[0122] like Figure 1As shown in D, 1E, and 1F, this invention used HepG2 cells to detect the lipid clearance ability of different drug compositions according to the dosing regimens shown in Table 1. The results showed that the intracellular TC, TG, and LDL contents of the Example 1 group were significantly reduced, and its effect was better than that of Comparative Examples 4 and 5. This indicates that the efficacy of the comparative examples (Comparative Examples 4 and 5) was reduced when Chuanxiong replaced turmeric and astragalus replaced ginseng.

[0123] 2.1.2.3 Cell migration ability detection

[0124] like Figure 2 As shown, after co-culturing HUVEC and THP-1 cells, only a small number of THP-1 cells migrated to the HUVEC cell layer in the control group, while a large number of THP-1 cells migrated to the HUVEC cell layer in the model group. After administering each composition according to the dosing regimens shown in Table 1, the cell migration amount was significantly reduced. Figure 2 B shows that Example 1 is more effective than Comparative Examples 4 and 5 in reducing migration rate. The comparative examples (Comparative Examples 4 and 5) that replaced turmeric with chuanxiong and ginseng with astragalus showed insufficient efficacy.

[0125] 2.2 Pharmacodynamic evaluation in animal experiments

[0126] 2.2.1 Test Methods

[0127] 2.2.1.1 Dosing regimen

[0128] The administration regimen during rat modeling is shown in the table below.

[0129] Table 2. Dosing regimen for rats

[0130] Group Dosing volume (ml) Daily dosing amount (g / kg) Control group 0 0 Model group 0 0 Danlou tablet group 4 0.473 Lovastatin group 4 0.002 Test group 1 (Chinese medicine composition prepared in Example 1) 4 12.075 Test group 2 (Chinese medicine composition prepared in Example 1) 4 24.15 Test group 3 (Chinese medicine composition prepared in Example 2) 4 13.86 Test group 4 (Chinese medicine composition prepared in Example 3) 4 10.815 Comparative Example 1 (Chinese medicine composition prepared in Comparative Example 1) 4 10.815 Comparative Example 2 (Chinese medicine composition prepared in Comparative Example 2) 4 10.815 Comparative Example 3 (Chinese medicine composition prepared in Comparative Example 3) 4 9.765 Comparative Example 4 (Chinese medicine composition prepared in Comparative Example 4) 4 12.075 Comparative Example 5 (Chinese medicine composition prepared in Comparative Example 5) 4 12.075 Comparative Example 6 (Chinese medicine composition prepared in Comparative Example 6) 4 11.445 Comparative Example 7 (Chinese medicine composition prepared in Comparative Example 7) 4 12.495 Comparative Example 8 (Chinese medicine composition prepared in Comparative Example 8) 4 12.915

[0131] The human body weight is calculated as 60 kg, the human-to-rat equivalent dose ratio is 6.3, the Danlou tablets are calculated based on a human daily dose of 4.5 g, and the Lovastatin tablets are calculated based on a human daily dose of 20 mg.

[0132] 2.2.1.2 Model Establishment

[0133] Rats in both the model and treatment groups were fed a high-fat diet. Starting from week 2, they were intraperitoneally injected with vitamin D3 (600,000 IU / kg) once every week for a total of 2 weeks. Blood lipid levels were measured at week 5, and rats with normal blood lipid levels were culled. The left anterior descending artery was then ligated. Drug administration began after the rats regained mobility. Rats in both the model and control groups were administered pure water by gavage. All rats in each group received the drug via gastric administration for 6 consecutive weeks. Electrocardiogram and echocardiogram tests were performed on the rats at the end of the treatment period.

[0134] Sample collection: Rats were anesthetized with 20% ursotose, and blood was collected from the abdominal aorta. The rat heart, aortic arch, and aorta were then separated for further testing.

[0135] 2.2.1.3 Electrocardiogram (ECG) testing

[0136] Electrodes were inserted subcutaneously into the left upper limb, right upper limb, and right lower limb of the rat in sequence to set up the original channel for electrocardiogram signal acquisition and standard lead II electrocardiogram.

[0137] 2.2.1.4 Echocardiography

[0138] Under isoflurane anesthesia, chest hair was shaved, and a high-frequency matrix probe was used. The probe was perpendicular to the left chest wall to examine the long and short axis images of the left ventricle along the mitral valve orifice to the apex. The probe was also aligned with the right side of the sternum to examine the aortic arch image. The main ultrasound parameters were: left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), stroke volume (SV), and left ventricular end-systolic diameter (LVIDd).

[0139] 2.2.1.5 Liver Oil Red O Staining

[0140] Liver tissues from three rats in each group were randomly selected, fixed with 4% paraformaldehyde for 30 min, and washed thoroughly with double-distilled water. The tissues were then incubated with Oil Red O working solution at room temperature for 30 min, differentiated with 60% isopropanol until normal liver tissue regained its color, and photographed for observation.

[0141] 2.2.1.6 Histopathology of the heart and aortic arch

[0142] Heart and aortic arch tissues were collected, fixed in 4% paraformaldehyde solution for 24 hours, dehydrated in 95% ethanol, embedded in paraffin, and serially sectioned on a paraffin microtome to a thickness of 5 μm. Hematoxylin and eosin (HE) staining was used to stain the sections, and pathological changes were observed under a microscope. Oil Red O staining of the aortic arch was used to observe lipid deposition. Heart sections were incubated in 1% TTC staining solution at 37°C for 15 min, then fixed in 10% formalin, and the TTC staining was observed.

[0143] 2.2.1.7 Masson staining of the heart

[0144] Paraffin sections were dewaxed to water (xylene I and II for 5 minutes each, followed by sequential dehydration with ethanol and then rinsed with distilled water), stained with hematoxylin for 5-8 minutes, rinsed with tap water, differentiated with 1% hydrochloric acid ethanol for 30 seconds, rinsed with running water to regain blue color, then stained with Ponceau S-Acid Fuchsin for 10-15 minutes and rinsed quickly with distilled water, then treated with phosphomolybdic acid solution for 5 minutes, then stained directly with aniline blue solution for 5 minutes, finally dehydrated quickly with 70% ethanol, dehydrated with sequential ethanol, cleared with xylene, mounted with neutral resin and observed under a microscope.

[0145] 2.2.1.8 Detection of four blood lipid parameters and myocardial injury markers

[0146] 3 ml of blood was collected from rats, and the whole blood was placed in EP tubes and centrifuged (3000 rpm, 15 min). The supernatant was aspirated with a pipette and aliquoted into 1.5 mL centrifuge tubes. The four lipid parameters (serum TC, TG, LDL, HDL) and myocardial injury markers (LDH, CK, CK-MB) were measured using a fully automated biochemical analyzer.

[0147] 2.2.1.9 Hemorheological Detection

[0148] Collect 2 mL of whole blood using a lancet and slowly inject it into the anticoagulant tube. Gently invert and mix 5-8 times to avoid hemolysis from vigorous shaking. Place the anticoagulant whole blood in a 37°C constant temperature water bath for 10 minutes to preheat. Simultaneously, start and preheat the blood rheology analyzer to 37°C and calibrate the instrument for later use. Take the preheated whole blood sample and inject it into the detection channel to measure the high shear viscosity, low shear viscosity, and fibrinogen content of the whole blood. Centrifuge the remaining whole blood sample at 3000 r / min for 15 minutes to separate the upper plasma layer. Take the plasma and inject it into the corresponding channel of the instrument to measure the plasma viscosity index.

[0149] 2.2.1.10 Data Statistics

[0150] All data obtained in this experiment were analyzed using GraphPad Prism 8.0. The analysis method was one-way ANOVA, and the statistical results are shown as mean ± standard deviation (SD). P < 0.05 was considered statistically significant.

[0151] 2.2.2 Test Results

[0152] 2.2.2.1 Electrocardiogram (ECG) test results

[0153] Figure 3 A is the T-wave electrocardiogram of the experimental animal after modeling. For example... Figure 3 As shown in B, this study constructed a rat model of myocardial ischemia and, after grouping and intervening the model rats, detected the ST segment height on electrocardiogram (ECG), a characteristic indicator of myocardial ischemia. The results showed that compared with the normal control group, the ST segment height on the ECG of rats in the myocardial ischemia model group was significantly increased, indicating the successful establishment of the myocardial ischemia model. Compared with the model group, the ST segment height on the ECG of rats in each treatment group was significantly reduced. The improvement effects of test groups 1 and 2 provided by this invention were particularly outstanding, with test group 2 showing a significantly greater reduction in ST segment height than test group 1. Test group 1, in turn, showed a significantly better effect in alleviating ST segment elevation than the other test groups. Furthermore, the treatment effect of comparative group 1 was significantly reduced due to the absence of the principal herb; the treatment effects of comparative groups 2, 3, and 6 were significantly lower than those of test groups 1 and 2 due to the absence of some herbs or reduced dosages; and in comparative group 5, astragalus was used instead of ginseng, resulting in a decrease in efficacy.

[0154] 2.2.2.2 Echocardiography Results

[0155] Rat cardiac ultrasound images showed Figure 4 In section A, this invention further assesses the improvement in cardiac function by detecting cardiac function in rats using echocardiography: compared with the normal control group, the left ventricular ejection fraction (LVEF) of rats in the myocardial ischemia model group was significantly improved. Figure 4 B) Left ventricular fractional shortening rate ( Figure 4 C) Stroke volume ( Figure 4 D) were all significantly reduced, while the left ventricular diameter at end-systole ( Figure 4 E) was significantly elevated, indicating significant impairment of cardiac function in the model rats; compared with the model group, the above-mentioned cardiac function indicators in each treatment group were significantly improved; however, the test groups 1 and 2 provided by this invention showed a more advantageous effect on improving cardiac function: in left ventricular ejection fraction (LEF) Figure 4 B) Left ventricular fractional shortening rate ( Figure 4 C) Stroke volume ( Figure 4 D) In ​​terms of indicators, the improvement in test group 2 was significantly better than that in test group 1, and the improvement effect of test group 1 was significantly better than that of the other test groups and each comparative group. Regarding the corresponding end-systolic left ventricular diameter, the reduction in test group 2 was better than that in test group 1, and the reduction effect of test group 1 was also better than that of the other test groups and each comparative group. The effects of each comparative group were inferior to those of test groups 1 and 2: the therapeutic effect of comparative group 1 was significantly reduced due to the absence of the principal drug; the efficacy of comparative groups 2, 3, and 6 was greatly reduced due to missing ingredients or dosage adjustments in the formulation; the comparative group (comparative group 5) using Astragalus to replace ginseng showed insufficient efficacy. In summary, the test group compositions of this invention can effectively improve cardiac function in rats with myocardial ischemia, and the activity levels are clearly defined, with test group 2 showing the best improvement effect.

[0156] Aortic ultrasound imaging results showed ( Figure 5 Significant differences were observed in the morphology of the aortic arch, intimal thickness, and hemodynamic parameters among the rat groups. In the model group, the intimal thickness of the aortic arch was significantly increased, with prominent atherosclerotic plaques and varying degrees of stenosis in the vascular lumen at the plaque sites. In test group 1, the intimal thickness of the aortic arch was significantly thinner than in the model group, and the protrusion of local atherosclerotic plaques was significantly reduced. In test group 2, no atherosclerotic plaques were observed throughout the aortic arch, and the vessel wall remained smooth and flat without significant protrusions. Test groups 3 and 4 also showed significant therapeutic improvement, but their effects were weaker than those in test groups 1 and 2. In comparative group 1, the pathological improvement effect on the aortic arch was significantly reduced due to the absence of the principal drug in the formula. In comparative groups 2, 3, and 6, the protective efficacy against the aortic arch was significantly weakened due to incomplete formulation or dosage adjustments.

[0157] 2.2.2.3 Pathological section results

[0158] Figure 6 The image shows HE staining of rat hearts. HE staining results revealed significant pathological damage in the model group rats. Normally parallel myocardial fibers showed signs of twisting and breakage, and the intercellular spaces were significantly widened, filled with pale pink matrix components, indicating interstitial edema and early fibrosis. Scattered, deeply stained small cells were also visible in local intercellular spaces, showing signs of inflammatory cell infiltration. Some myocardial cells were enlarged, with loose, vacuolated cytoplasm, and the originally clear striations became blurred or even disappeared. Significant differences in myocardial tissue morphology were observed among the drug-treated groups. Test group 2 and test group 1, which involved intervention with high and low doses of the drug combination, showed superior myocardial protective effects and exhibited a clear dose-dependent characteristic. In test group 2 rats, the myocardial fibers were neatly and tightly arranged with clearly distinguishable striations. The myocardial cells were regularly shaped with uniform cytoplasm and only occasionally showed a small amount of inflammatory cell infiltration. No obvious pathological changes such as myocardial cell edema, necrosis, or interstitial fibrosis were observed. The myocardial tissue morphology of test group 1 rats was slightly inferior to that of test group 2. The myocardial fibers were basically neatly arranged with relatively clear striations. A small amount of mild edema of myocardial cells was visible locally, accompanied by a very small amount of inflammatory cell infiltration, but no obvious necrotic foci were formed. The degree of pathological damage was significantly milder than that of the other groups. In Comparative Groups 1, 2, and 3, the lack of a key active ingredient in the formula resulted in significantly aggravated myocardial tissue pathological damage, manifested as disordered and broken myocardial fibers, blurred or absent striations, significant swelling and vacuolar degeneration of myocardial cells, extensive inflammatory cell infiltration and collagen fiber proliferation in the interstitium, and even focal myocardial cell necrosis in some areas, suggesting that this key component plays an indispensable role in improving myocardial pathological damage. In Comparative Group 5, where ginseng was replaced with astragalus in the formula, the myocardial protective effect was significantly weakened, with moderate edema in the myocardial tissue, irregular arrangement of myocardial fibers, decreased striation clarity, and higher levels of interstitial inflammatory cell infiltration and fibrosis than in Test Groups 1 and 2.

[0159] The pathological section results of the aortic arch showed ( Figure 7In the control group, the aortic intima was intact, the vascular smooth muscle cells in the tunica media had normal morphology and structure, clear boundaries, and regular arrangement, and the adventitia was rich in collagen fibers with no obvious inflammatory changes. Compared with the control group, the model group showed endothelial loss in the aortic arch intima and widespread vascular smooth muscle cell necrosis and calcification in the tunica media; the drug-treated group showed endothelial loss in the aortic arch intima; a small number of vascular smooth muscle cells showed necrosis and calcification in the tunica media, with localized water-like degeneration of vascular smooth muscle cells, cell swelling, and loose, lightly stained cytoplasm; the adventitia was rich in collagen fibers with no obvious inflammatory changes. The experimental effect of test group 2 was better than that of test group 1 and each comparative group. The protective effects of each comparative group were not as good as those of test groups 1 and 2: the pathological improvement effect of comparative group 1 was significantly weakened due to the absence of the principal drug; the protective efficacy of comparative groups 2 and 3 was greatly reduced due to the absence of key medicinal ingredients in the formula; the comparative group (comparative group 5) in which Astragalus replaced ginseng did not achieve the ideal protective effect.

[0160] Liver oil red O staining results showed ( Figure 8 The lipid deposition in the liver tissue of rats in each group showed significant differences. In the model group, numerous red lipid droplets of varying sizes were widely distributed in the liver tissue, merging into patches and diffusely filling the hepatocyte cytoplasm, indicating severe lipid deposition. In test group 1, the number of red lipid droplets in the liver tissue was significantly reduced compared to the model group, with no obvious merging, and the degree of lipid deposition was significantly alleviated. In test group 2, only a few scattered small lipid droplets were observed in the liver tissue, and the hepatocytes remained intact, showing the most significant improvement in lipid deposition. Test groups 3 and 4 also showed significant improvement in lipid deposition in the liver tissue, with fewer and less distributed lipid droplets than the model group, but more residual lipid droplets than in test groups 1 and 2, indicating a slightly weaker improvement. In comparative group 1, due to the absence of the principal drug in the formula, a large number of red lipid droplets were still observed in the liver tissue, significantly weakening the lipid deposition improvement effect. In comparative groups 2, 3, and 6, due to missing ingredients or dosage adjustments in the formula, the lipid clearance effect in the liver tissue was greatly reduced, with more lipid droplets distributed in the range and number than in the test groups, showing only slight improvement compared to the model group.

[0161] Cardiac TTC staining results showed ( Figure 9In the control group, myocardial tissue stained with TTC showed a uniform bright red color with few bluish-white infarct areas. In the model group, obvious discolored infarct foci were visible in the myocardium, with clear boundaries, indicating severe myocardial ischemia and necrosis. In the drug-treated groups, the area of ​​blue infarct foci was significantly smaller than in the model group, with the smallest infarct area observed in test group 2, showing only a few scattered ischemic areas and a significantly increased proportion of red viable myocardium. Compared to test groups 1 and 2, the vascular pathological protective effects of each comparative group showed significant differences: Comparative group 1 lacked the core principal drug, resulting in a significant decrease in the improvement of aortic arch pathological damage; comparative groups 2 and 3 had limited protective efficacy due to incomplete key ingredients in their formulations; and the comparative group (comparative group 5) using Astragalus to replace Ginseng ultimately failed to achieve the expected protective effect.

[0162] 2.2.2.4 Blood lipid test results

[0163] Figure 10 The statistical chart shows the results of four lipid tests in rats. In the control group, all four lipid indicators (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) were within normal levels, with no significant abnormalities. In the model group, the levels of TC, TG, and LDL-C were significantly higher than those in the control group, while the HDL-C level showed no significant change. In the treatment groups, the levels of TC, TG, and LDL-C were all lower than those in the model group to varying degrees. The lipid indicators in test group 2 were closest to those in the control group, indicating that the traditional Chinese medicine composition can effectively regulate lipid metabolism and correct lipid disorders. Compared with test groups 1 and 2, there were significant differences in the lipid-lowering effects of each comparative group. The shortcomings in efficacy of each comparative group were directly related to the defects in the formulation: Comparative Group 1, due to the absence of the core principal drug Artemisia capillaris, not only had its lipid-lowering effect impaired, but also its improvement effect on aortic arch pathological damage was significantly reduced; Comparative Groups 2, 3 and 6, due to the incomplete or insufficient dosage of key medicinal ingredients in the formulation, not only affected the lipid-lowering effect, but also significantly restricted the protective effect on blood vessels.

[0164] 2.2.2.5 Results of myocardial injury marker detection and analysis

[0165] Figure 11This is a statistical chart showing the results of myocardial injury marker detection in experimental animals. The results showed that in the control group, myocardial enzyme levels (lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase isoenzyme (CK-MB)) remained at normal physiological levels, indicating no myocardial tissue damage. In the model group, LDH, CK, and CK-MB levels were significantly higher than in the control group, indicating that myocardial cells ruptured and died due to ischemia, releasing large amounts of intracellular enzymes into the bloodstream. Serum LDH, CK, and CK-MB levels in all treatment groups were lower than in the model group, with the most significant decrease in all three indicators in test group 2. This indicates that the traditional Chinese medicine composition can effectively alleviate cell damage caused by myocardial ischemia, inhibit myocardial enzyme release, and protect ischemic myocardium. The therapeutic effect of comparative group 1 was significantly reduced, primarily due to the absence of a key principal herb in the formula. Comparative groups (comparative groups 4 and 5), where chuanxiong replaced turmeric and astragalus replaced ginseng, showed insufficient efficacy.

[0166] 2.2.2.6 Results of hemorheological analysis

[0167] This invention assesses blood circulation status by detecting core hemorheological indicators such as low-shear whole blood viscosity, high-shear whole blood viscosity, fibrinogen, and plasma viscosity in rats: Compared with the normal control group, the myocardial ischemia model group showed low-shear whole blood viscosity (… Figure 12 A) High-viscosity whole blood ( Figure 12 B), fibrinogen ( Figure 12 C) Plasma viscosity ( Figure 12 D) All were significantly elevated, indicating increased blood viscosity and deterioration of blood circulation in the model rats. Compared with the model group, the above indicators in each treatment group were significantly reduced, while the test group provided by this invention showed a greater advantage in improving blood rheology: in terms of whole blood viscosity at low and high shear rates, fibrinogen, and plasma viscosity, test group 2 showed significantly better reductions in each indicator than test group 1. The blood rheology improvement effects of each comparative group were significantly worse than those of test group 1 and test group 2. The specific shortcomings were directly related to the defects in the formulation: the treatment effect of comparative group 1 was significantly reduced due to the lack of the core principal drug; the efficacy of comparative groups 2, 3, and 6 was significantly limited due to the lack of ingredients or dosage adjustments in the formulation; the relevant indicators of comparative group 4 were significantly lower than those of the control group, suggesting that the excessive blood-breaking effect of Chuanxiong may have caused excessively low blood viscosity, and its improvement effect was far inferior to that of the series of treatments in the test group. The above results confirm that the compositions corresponding to the test groups of the present invention can effectively improve the blood viscosity state of rats with myocardial ischemia, and there are clear activity levels among the various schemes. Among them, test group 2 is the scheme with the best blood rheology improvement activity in this series of compositions.

[0168] 2.2.2.7 Clinical observation results in rats

[0169] Figure 13The graph shows the statistical changes in rat body weight. During the drug administration process, rats in Comparative Groups 7 and 8 exhibited significant diarrhea, yellowing of fur, and decreased body weight and food intake with increasing intervention time. Their body weight changes were significantly less pronounced compared to the test group. In accordance with animal ethics requirements, these two groups of rats were euthanized.

[0170] This experiment verified the intervention effect of the traditional Chinese medicine composition of the present invention from multiple dimensions: compared with the model group, the traditional Chinese medicine composition of the present invention significantly improved myocardial ischemia-related T-wave abnormalities in rats, improved cardiac function in rats, reduced pathological damage and lipid deposition in aortic atherosclerosis, reduced myocardial infarction area, corrected dyslipidemia (reduced TC, TG, and LDL-C), and inhibited the release of LDH, CK, and CK-MB, while also reducing blood viscosity. Overall, the traditional Chinese medicine composition of the present invention has a good protective effect against atherosclerosis and myocardial ischemia in rats.

Claims

1. A traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease, characterized in that, The traditional Chinese medicine composition is prepared from raw materials containing the following components: Artemisia capillaris 8-13 parts, Atractylodes lancea 8-12 parts, Alisma plantago-aquatica 8-12 parts, Curcuma longa 8-14 parts, Salvia miltiorrhiza 10-20 parts, Curcuma longa 8-14 parts, Panax notoginseng powder 1-5 parts, Corydalis yanhusuo 5-10 parts, Pinellia ternata 8-12 parts, Coptis chinensis 5-10 parts, Panax ginseng 4-10 parts, Citrus reticulata peel 5-12 parts, Glycyrrhiza uralensis 4-10 parts.

2. The traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease according to claim 1, characterized in that, The traditional Chinese medicine composition is prepared from raw materials containing the following components: Artemisia capillaris 10-13 parts, Atractylodes lancea 9-11 parts, Alisma plantago-aquatica 9-11 parts, Curcuma longa 10-13 parts, Salvia miltiorrhiza 12-18 parts, Curcuma longa 10-13 parts, Panax notoginseng powder 1-3 parts, Corydalis yanhusuo 5-9 parts, Pinellia ternata 9-11 parts, Coptis chinensis 5-8 parts, Panax ginseng 4-8 parts, Citrus reticulata peel 6-11 parts, Glycyrrhiza uralensis 4-8 parts.

3. The traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease according to claim 1, characterized in that, The traditional Chinese medicine composition is prepared from raw materials containing the following components: Artemisia capillaris 12 parts, Atractylodes lancea 10 parts, Alisma plantago-aquatica 10 parts, Curcuma longa 12 parts, Salvia miltiorrhiza 15 parts, Curcuma longa 12 parts, Panax notoginseng powder 2 parts, Corydalis yanhusuo 6 parts, Pinellia ternata 10 parts, Coptis chinensis 6 parts, Panax ginseng 5 parts, Citrus reticulata peel 10 parts, Glycyrrhiza uralensis 5 parts.

4. The traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease according to claim 1, characterized in that, The components other than Panax notoginseng powder are selected from processed medicinal materials, aqueous extracts of medicinal materials, and alcohol-water mixed solvent extracts of medicinal materials.

5. The traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease according to claim 4, characterized in that, The volume concentration of ethanol in the alcohol-water mixed solvent is 20%-90%.

6. The traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease according to claim 4, characterized in that, The aqueous extract of the medicinal materials is prepared by a method comprising the following steps: taking slices of each medicinal material except for Panax notoginseng powder, decocting them in water at least once, filtering the decoction to obtain the aqueous extract of the medicinal materials; and / or The medicinal material alcohol-water mixed solvent extract is prepared by a method including the following steps: taking the medicinal material slices except for Panax notoginseng powder, and heating and extracting them with an alcohol-water mixed solvent with an ethanol volume concentration of 20%-90% to obtain the medicinal material alcohol-water mixed solvent extract.

7. A method for preparing a traditional Chinese medicine composition for the prevention and / or treatment of coronary heart disease as described in any one of claims 1-6, characterized in that, The method includes the following steps: (1) Take the medicinal materials other than Panax notoginseng powder, decoct them with water at least once, filter the decoction, and obtain the water extract; (2) Concentrate the water extract, and then dry the concentrate to make a dry powder; (3) The dry powder is mixed with Panax notoginseng powder to obtain the traditional Chinese medicine composition.

8. The method according to claim 7, characterized in that, Step (1) includes the following steps: (i) Take all medicinal materials except Panax notoginseng powder, add 8-14 times the amount of water and soak for 20-40 minutes; (ii) Perform the first decoction: bring to a boil over high heat, then reduce to a simmer and maintain for 40-80 minutes. Filter to obtain the first decoction. (iii) Add 6-10 times the amount of water to the dregs and decoct for the second time. After boiling over high heat, reduce to low heat and maintain for 30-50 minutes. Filter to obtain the second decoction. (iv) Combine the first decoction and the second decoction to obtain an aqueous extract.

9. The method according to claim 7, characterized in that, The concentration of the water extract in step (2) includes the following steps: concentrating the water extract at 50-70°C to a relative density of 1.020-1.090 mg / ml.

10. The method according to claim 7, characterized in that, The drying of the concentrate in step (2) includes the following steps: spray drying the concentrate at an inlet air temperature of 150℃-180℃.

11. A pharmaceutical preparation for the prevention and / or treatment of coronary heart disease, characterized in that, The pharmaceutical preparation comprises a therapeutically effective amount of the traditional Chinese medicine composition according to any one of claims 1-6, and pharmaceutically acceptable excipients.

12. The pharmaceutical preparation for the prevention and / or treatment of coronary heart disease according to claim 11, characterized in that, The pharmaceutically acceptable excipients are selected from one or more of diluents, excipients, binders, preservatives, and flavoring agents.

13. The pharmaceutical preparation for the prevention and / or treatment of coronary heart disease according to claim 11, characterized in that, The pharmaceutical preparation may be in the form of an oral preparation or a non-oral preparation.

14. The pharmaceutical preparation for the prevention and / or treatment of coronary heart disease according to claim 13, characterized in that, The oral preparations are tablets, capsules, pills, granules, powders, oral liquids, or drop pills; the non-oral preparations are injections, patches, or sprays.

15. Use of the traditional Chinese medicine composition according to any one of claims 1-6 in the preparation of a medicament for treating and / or preventing coronary atherosclerotic heart disease.

16. The use according to claim 15, characterized in that, The coronary atherosclerotic heart disease mentioned is the phlegm-blood stasis type.

17. The use according to claim 15, characterized in that, The drug is used for one or more of the following purposes: reducing blood viscosity, improving cardiac function, reducing myocardial infarction area, inhibiting the formation of atherosclerotic plaques, regulating blood lipid levels, or reducing the level of myocardial injury markers in serum.

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