Traditional Chinese medicine compound and preparation for treating coronary heart disease as well as preparation method and application of traditional Chinese medicine compound and preparation

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a traditional Chinese medicine compound and preparation for treating coronary heart disease and a preparation method and application of the traditional Chinese medicine compound and preparation. The traditional Chinese medicine composition is prepared from the following medicinal materials in parts by weight: 10-30 parts of astragalus membranaceus, 5-15 parts of rhodiola rosea, 10-30 parts of salvia miltiorrhiza, 5-15 parts of ligusticum wallichii, 10-30 parts of trichosanthes kirilowii maxim, 5-15 parts of allium macrostemon, 5-15 parts of folium ginkgo, 10-30 parts of radix puerariae, 10-30 parts of radix ophiopogonis, 3-10 parts of schisandra chinensis, 15-30 parts of oyster, 5-15 parts of cassia twig and 3-10 parts of liquorice. Animal experiment results show that the traditional Chinese medicine composition provided by the invention has remarkable and multi-aspect curative effect advantages in the aspect of treating a coronary heart disease rat model. The traditional Chinese medicine composition not only can enhance myocardial contractility and recover heart blood pumping function, but also can inhibit inflammatory response, relieve myocardial damage, effectively relieve myocardial structure damage and protect myocardial tissue integrity. In addition, a proportional experiment result shows that the effect of the composition provided by the invention can be obviously weakened by losing any medicine pair, so that all the medicines in the formula cannot be absent.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a traditional Chinese medicine compound for treating coronary heart disease, its preparation method and application. Background Technology

[0002] Coronary artery disease (CAD) is a common cardiovascular disease caused by atherosclerosis, leading to narrowing or blockage of the coronary arteries and subsequently causing myocardial ischemia and hypoxia. With rising socioeconomic levels and changing lifestyles, its prevalence is increasing year by year. The "China Cardiovascular Health and Disease Report 2024" shows that there are over 11.3 million adult CAD patients in my country, and the disease burden continues to worsen. Currently, CAD not only ranks second in global disease burden but is also the third leading cause of death, seriously threatening human health.

[0003] Modern medicine primarily treats coronary heart disease using medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). While these methods can alleviate myocardial ischemia symptoms to some extent, they cannot completely eliminate the risk of postoperative cardiovascular events, and some patients still face problems such as restenosis and drug side effects.

[0004] In Traditional Chinese Medicine (TCM) theory, coronary heart disease falls under the categories of "chest pain" and "heart pain," with the disease location in the heart. It is a condition of deficiency in the root and excess in the branch, and treatment emphasizes "tonifying deficiency and purging excess, unblocking the meridians and resolving blood stasis." In recent years, with the deepening integration of evidence-based medicine and TCM research, the mechanism of action of TCM in the prevention and treatment of coronary heart disease has gradually become clear, especially demonstrating unique advantages in holistic regulation and multi-target intervention. Studies have shown that TCM compound prescriptions not only invigorate blood circulation and remove blood stasis, and promote yang and dissipate nodules, but also have the effects of tonifying qi and nourishing yin, calming the mind and soothing the nerves. Their effects are not limited to improvement at the vascular level, but also focus on the overall harmony of qi and blood and the restoration of organ function. Compared to Western medicine, which mainly focuses on revascularization and symptom control, TCM emphasizes the fundamental regulation of the etiology and pathogenesis, reflecting the characteristics of multi-component, multi-pathway, and systemic intervention.

[0005] Traditional Chinese medicine (TCM) demonstrates a unique approach to holistic regulation and multi-target intervention in the treatment of coronary heart disease (CHD). It possesses potential advantages in improving long-term prognosis, enhancing quality of life, and reducing adverse reactions, providing important insights and scientific basis for the integration of TCM and Western medicine in prevention and treatment, as well as the development of new TCM drugs. However, the existing TCM formulas available for clinical reference in treating CHD remain relatively limited, necessitating further research and development of more TCM formulas for clinical application to address the increasingly severe needs in CHD prevention and treatment. Summary of the Invention

[0006] In Traditional Chinese Medicine (TCM), coronary heart disease (CHD) is often categorized under "chest pain" or "heart pain," with its core pathogenesis typically involving qi deficiency and blood stasis, phlegm obstruction, and impaired heart vessels, sometimes accompanied by qi and yin deficiency and restlessness. The compound formula provided in this invention utilizes multi-target combinations, encompassing the effects of tonifying qi, promoting blood circulation, resolving phlegm, warming yang, nourishing yin, and calming the mind. This aligns with the TCM treatment principles for CHD and is particularly suitable for complex CHD patterns identified in TCM, such as qi deficiency and blood stasis with phlegm obstruction or qi and yin deficiency with blood stasis and phlegm obstruction. Furthermore, this compound formula combines traditional classical formulas with modern pharmacological evidence. For example, Trichosanthes kirilowii and Allium macrostemon originate from the Trichosanthes kirilowii and Allium macrostemon decoction in the *Synopsis of Prescriptions of the Golden Chamber*, specifically for treating chest pain. Simultaneously, the addition of Ginkgo biloba and Pueraria lobata, a herb pair, has been supported by modern research for its blood-activating and meridian-clearing effects. Furthermore, this compound formula employs a strategy of combining cold and warm properties (such as combining the cooling properties of Ophiopogon japonicus with the warming properties of Cinnamomum cassia), avoiding side effects caused by excessive dryness or coolness, making it suitable for long-term conditioning in patients with coronary heart disease. In summary, this compound formula integrates traditional theory with modern science, achieving comprehensive regulation of the physiological, psychological, and multiple pathogenesis mechanisms of coronary heart disease. Compared with Western medicine, it has unique advantages in long-term safety and overall efficacy, providing new ideas for the research and development and clinical practice of new Chinese medicine drugs.

[0007] The first aspect of this invention provides a traditional Chinese medicine composition for treating coronary heart disease, which is made from the following medicinal materials: Astragalus membranaceus, Rhodiola rosea, Salvia miltiorrhiza, Ligusticum chuanxiong, Trichosanthes kirilowii, Allium macrostemon, Ginkgo biloba leaf, Pueraria lobata, Ophiopogon japonicus, Schisandra chinensis, Ostrea gigas, Cinnamomum cassia twig, and Glycyrrhiza uralensis. The compatibility of this compound is based on the theory of "principal, assistant, adjuvant, and guide" in traditional Chinese medicine, emphasizing the synergistic effect and overall balance of the drug pairs. Specifically, Astragalus membranaceus and Salvia miltiorrhiza are the principal drugs in the formula, and they complement each other to form the core of invigorating qi and promoting blood circulation. Astragalus membranaceus is more inclined to tonify deficiency, while Salvia miltiorrhiza is more inclined to purge excess. One tonifies and the other promotes circulation, working together to correct the qi deficiency and blood stasis of coronary heart disease. Rhodiola rosea, Ligusticum chuanxiong, Trichosanthes kirilowii, and Allium macrostemon are the assistant herbs. Rhodiola rosea and Ligusticum chuanxiong enhance the qi-tonifying and blood-activating effects of the principal herb, while Trichosanthes kirilowii and Allium macrostemon target the common concurrent symptom of phlegm turbidity, forming a secondary core for resolving phlegm and promoting yang. The assistant herbs and the principal herb work together to address the interactive pathogenesis of qi deficiency, blood stasis, and phlegm turbidity, making the formula more comprehensive. Ophiopogon japonicus, Schisandra chinensis, oyster shell, ginkgo biloba leaf, kudzu root, and cinnamon twig are used as adjuvant herbs. Oyster shell has a calming and sedative effect, and can suppress yang and consolidate the body. It is effective for coronary heart disease accompanied by restlessness and palpitations. It can calm the mind and soothe the nerves. It works synergistically with Ophiopogon japonicus and Schisandra chinensis to form a combination of nourishing yin and calming the mind, balancing the dispersing properties of the formula. Ginkgo biloba leaf can assist Salvia miltiorrhiza and Ligusticum chuanxiong in enhancing the ability to unblock the meridians. Kudzu root works synergistically with ginkgo biloba leaf to improve blood circulation in the head and neck. Cinnamon twig can balance cold and heat, promote the flow of yang qi, and restrain the coldness of Ophiopogon japonicus. The heavy nature of oyster shell can also prevent the dispersing effect of Ligusticum chuanxiong, making the formula more balanced. Licorice is used as the guiding herb. It not only harmonizes the whole formula, but also relieves acute chest pain through its sweet and soothing properties, and works synergistically with the principal, assistant, and adjuvant herbs.

[0008] The sources, properties, channels, effects, and modern pharmacological effects of each herb in this formula are as follows: Astragalus: Derived from the dried root of *Astragalus mongholicus* or *Astragalus membranaceus*, both belonging to the legume family. Properties and Channels Entered: Sweet, slightly warm. Enters the spleen and lung channels. Astragalus greatly replenishes vital energy and promotes blood circulation. Targeting the pathogenesis of coronary heart disease involving qi deficiency and blood stasis, it can enhance cardiac function and improve symptoms such as shortness of breath and fatigue. When combined with Rhodiola rosea, it invigorates qi and blood, preventing blood stasis from worsening qi deficiency. Modern pharmacological evidence: It has immune-enhancing, anti-inflammatory, and antioxidant effects; it can improve myocardial metabolism, reduce myocardial ischemia-reperfusion injury, and promote the recovery of vascular endothelial function.

[0009] Rhodiola rosea: Derived from the dried root and rhizome of the Crassulaceae plant Rhodiola rosea. Properties and Channels Entered: Sweet, bitter, neutral. Enters the Lung and Heart channels. Rhodiola rosea invigorates Qi and blood circulation, clears the meridians and relieves asthma. When combined with Astragalus membranaceus, it enhances the Qi-tonifying effect, jointly targeting Qi deficiency and blood stasis, relieving chest pain and asthma. Modern pharmacological evidence: Studies have shown that Rhodiola rosea has anti-fatigue, antioxidant, and anti-hypoxia effects, can improve cardiovascular function, lower blood pressure and blood lipids, and inhibit platelet aggregation, reducing thrombus formation.

[0010] Danshen (Salvia miltiorrhiza): Derived from the dried root and rhizome of the plant *Salvia miltiorrhiza*, belonging to the Lamiaceae family. Properties and Channels Entered: Bitter, slightly cold. Enters the Heart and Liver channels. Danshen invigorates blood circulation, removes blood stasis, clears the heart and relieves irritability, targeting blood stasis in the heart vessels, and alleviating chest pain and palpitations. Modern Pharmacological Evidence: Modern research shows that Danshen can improve microcirculation, inhibit platelet aggregation, has antioxidant properties, protect cardiomyocytes, and reduce ischemic damage. Its active ingredients (such as tanshinone) have anti-inflammatory and anti-fibrotic effects.

[0011] Chuanxiong (Ligusticum striatum): Derived from the dried rhizome of Ligusticum striatum, a plant in the Apiaceae family. Properties and Channels Entered: Pungent, warm. Enters the Liver, Gallbladder, and Pericardium channels. Chuanxiong invigorates blood circulation, promotes qi flow, dispels wind, and relieves pain. It assists Danshen (Salvia miltiorrhiza) in strengthening blood circulation and removing blood stasis, alleviating chest pain caused by qi stagnation and blood stasis. Modern pharmacological evidence: It has the effects of dilating coronary arteries, improving cerebral blood flow, inhibiting platelet aggregation, and anti-inflammatory effects. It can reduce myocardial oxygen consumption and prevent arteriosclerosis.

[0012] Trichosanthes kirilowii: Derived from the dried, mature fruit of *Trichosanthes kirilowii* or *Trichosanthes spp.*, belonging to the Cucurbitaceae family. Properties and Channels Entered: Sweet, slightly bitter, cold. Enters the Lung, Stomach, and Large Intestine channels. Trichosanthes kirilowii clears heat and resolves phlegm, relieves chest tightness and dissipates nodules. For chest pain caused by phlegm obstructing the channels, it is combined with *Allium macrostemon* to resolve phlegm and restore chest yang. Modern pharmacological evidence: Studies have shown that Trichosanthes kirilowii has expectorant, antibacterial, and anti-inflammatory effects; it can lower blood lipids, inhibit platelet aggregation, and improve coronary artery blood flow.

[0013] Allium macrostemon: Derived from the dried bulbs of Allium macrostemon or Allium chinense, both belonging to the Liliaceae family. Properties and Channels Entered: Pungent, bitter, warm. Enters the Lung, Stomach, and Large Intestine channels. Allium macrostemon promotes Yang, disperses stagnation, regulates Qi, and relieves chest tightness and pain. Combined with Trichosanthes kirilowii, it is specifically used to treat chest pain. Modern Pharmacological Evidence: Modern pharmacology shows that Allium macrostemon has anti-platelet aggregation, antioxidant, and anti-inflammatory effects; it can dilate blood vessels, improve myocardial blood supply, and lower cholesterol levels.

[0014] Ginkgo leaf: Derived from the dried leaves of the ginkgo plant (Ginkgo biloba). Properties and channels: Sweet, bitter, astringent, neutral. Enters the heart and lung channels. Ginkgo leaf invigorates blood circulation, removes blood stasis, unblocks channels, and relieves pain. For blood stasis syndrome, it works synergistically with kudzu root to improve circulation and alleviate chest pain. Modern pharmacological evidence: Studies have confirmed that ginkgo leaf extract can improve blood circulation, has antioxidant and anti-platelet aggregation effects, protects the nervous and cardiovascular systems, and lowers blood lipids and blood pressure.

[0015] Kudzu root: Derived from the dried root of the legume plant *Pueraria lobata* or *Pueraria truncata*. Properties and channels: Sweet, pungent, cool. Enters the spleen and stomach channels. Kudzu root relieves muscle tension, raises yang energy, improves circulation, and assists ginkgo leaves in promoting blood circulation and clearing the meridians, targeting qi stagnation and blood stasis in coronary heart disease. Modern pharmacological evidence: Kudzu root has the effects of dilating coronary arteries, improving myocardial ischemia, lowering blood pressure, and anti-inflammatory properties. Its flavonoid components can have antioxidant effects and reduce the risk of atherosclerosis.

[0016] Ophiopogon japonicus: Derived from the dried tuberous root of the plant Ophiopogon japonicus (Liliaceae family). Properties and Channels Entered: Sweet, slightly bitter, slightly cold. Enters the Heart, Lung, and Stomach channels. Ophiopogon japonicus nourishes Yin and generates fluids, clears the heart and relieves irritability, and is effective for palpitations and dry mouth caused by deficiency of both Qi and Yin, preventing damage to Yin from warming and drying herbs. Modern pharmacological evidence: Studies have shown that Ophiopogon japonicus has anti-myocardial ischemia, antioxidant, and immunomodulatory effects, and can improve cardiac function and reduce inflammatory responses.

[0017] Schisandra chinensis: Derived from the dried, mature fruit of *Schisandra chinensis* or *Schisandra sibirica*, both belonging to the Magnoliaceae family. Properties and Channels Entered: Sour, sweet, warm. Enters the Lung, Heart, and Kidney channels. Schisandra chinensis has astringent and consolidating properties, replenishes qi and generates fluids, and works synergistically with *Ophiopogon japonicus* to nourish yin and calm the mind, improving palpitations and fatigue. Modern Pharmacological Evidence: Modern research shows that Schisandra chinensis has antioxidant, anti-fatigue, and sedative effects, can protect myocardial cells, regulate heart rate, and enhance immunity.

[0018] Oyster: Derived from the dried shells of oysters such as the Pacific oyster and the Dalian Bay oyster. Properties and Channels Entered: Salty, slightly cold. Enters the Liver, Gallbladder, and Kidney channels. Oyster has a strong calming and sedative effect, softens hard masses and dissipates nodules, and can soothe the mind, relieve anxiety and insomnia. Modern Pharmacological Evidence: Modern research shows that oysters have sedative, anti-ulcer, and calcium-supplementing effects, can regulate blood pressure and heart rate, and have antioxidant properties.

[0019] Cinnamon twig: Derived from the dried tender twigs of the cinnamon tree (Cinnamomum cassia), a plant in the Lauraceae family. Properties and Channels Entered: Pungent, sweet, warm. Enters the Heart, Lung, and Bladder channels. Cinnamon twig warms and unblocks the channels, assists Yang and promotes Qi circulation. When combined with Allium macrostemon (Allium tuberosum), it enhances the Yang-clearing and Qi-dispersing effects, relieving chest Yang deficiency. Modern pharmacological evidence: Studies have shown that cinnamon twig has vasodilatory, anti-inflammatory, and antipyretic effects, can improve coronary artery blood flow, and reduce myocardial ischemia.

[0020] Licorice: Derived from the dried root and rhizome of the legume plant *Glycyrrhiza uralensis*. Properties and Channels Entered: Sweet, neutral. Enters the Heart, Lung, Spleen, and Stomach channels. Licorice harmonizes the effects of other herbs, tonifies the spleen and replenishes qi, relieves spasms and pain, moderates the overall properties of the formula, ensures synergistic effects of the drugs, and prevents blood-activating herbs from harming the spleen and stomach. Modern pharmacological evidence: It has anti-inflammatory and immunomodulatory effects, can alleviate drug toxicity, protect the gastric mucosa, and relieve smooth muscle spasms, contributing to the safety of long-term medication use in patients with coronary heart disease.

[0021] As a further explanation of the present invention, the composition is made from the following medicinal materials in parts by weight: Astragalus membranaceus 10-30 parts, Rhodiola rosea 5-15 parts, Salvia miltiorrhiza 10-30 parts, Ligusticum chuanxiong 5-15 parts, Trichosanthes kirilowii 10-30 parts, Allium macrostemon 5-15 parts, Ginkgo biloba 5-15 parts, Pueraria lobata 10-30 parts, Ophiopogon japonicus 10-30 parts, Schisandra chinensis 3-10 parts, Ostrea gigas 15-30 parts, Cinnamomum cassia 5-15 parts, Glycyrrhiza uralensis 3-10 parts.

[0022] As a further explanation of the present invention, the composition is made from the following medicinal materials in parts by weight: 15 parts Astragalus membranaceus, 10 parts Rhodiola rosea, 15 parts Salvia miltiorrhiza, 10 parts Ligusticum chuanxiong, 15 parts Trichosanthes kirilowii, 10 parts Allium macrostemon, 10 parts Ginkgo biloba, 15 parts Pueraria lobata, 15 parts Ophiopogon japonicus, 6 parts Schisandra chinensis, 20 parts Ostrea gigas, 10 parts Cinnamomum cassia, and 6 parts Glycyrrhiza uralensis.

[0023] A second aspect of the present invention provides a traditional Chinese medicine preparation for treating coronary heart disease, which is made from the traditional Chinese medicine composition and excipients described in any one of the above-mentioned methods.

[0024] As a further explanation of the present invention, the dosage form of the traditional Chinese medicine preparation is any one of decoction, pill, powder, paste, wine, capsule, tablet, granule and oral liquid.

[0025] A third aspect of this invention provides a method for preparing a freeze-dried powder of traditional Chinese medicine for treating coronary heart disease, comprising the following steps: S1. Grind each of the Chinese herbs in the Chinese herbal composition described above into coarse powder for later use; S2. Soak the crude Chinese medicine powder obtained in S1 in water for 20-60 minutes, then decoct it 1-3 times, each time for 20-60 minutes. Filter the liquid after each decoction and combine the liquids from all decoctions to obtain the total decoction. S3. The total decoction obtained in S2 is concentrated to obtain a Chinese herbal extract. Then, the Chinese herbal extract is freeze-dried to obtain freeze-dried Chinese herbal powder.

[0026] As a further explanation of the present invention, the concentration process in S3 is as follows: vacuum concentration is carried out using a rotary evaporator at 50-60°C.

[0027] As a further explanation of the present invention, the relative density of the Chinese herbal extract obtained in S3 is 1.10-1.20.

[0028] As a further explanation of the present invention, the freeze-drying process in S3 specifically includes: The Chinese herbal extract was placed in a liquid nitrogen environment and rapidly frozen for 2-4 hours until it was completely solidified. The solidified solids were quickly transferred to a freeze dryer and subjected to vacuum freeze drying for 24-36 hours until the moisture content of the sample was <5%.

[0029] The fourth aspect of the present invention provides the use of the traditional Chinese medicine composition, the traditional Chinese medicine preparation, or the traditional Chinese medicine freeze-dried powder prepared by the preparation method described in any one of the above-mentioned methods in the preparation of a drug for treating coronary heart disease.

[0030] Compared with the prior art, the present invention has the following beneficial technical effects: The compound formula provided by this invention, through multi-target compatibility, encompasses the effects of invigorating qi, promoting blood circulation, resolving phlegm, tonifying yang, nourishing yin, and calming the mind, aligning with the principles of traditional Chinese medicine treatment for coronary heart disease. Furthermore, this compound combines traditional classical formulas with modern pharmacological evidence; for example, the addition of ginkgo biloba and kudzu root, whose blood-activating and meridian-clearing effects are supported by modern research. In addition, this compound employs a combination of warming and cooling herbs, avoiding side effects caused by excessive dryness or coolness, making it suitable for long-term conditioning in patients with coronary heart disease. In summary, this compound formula integrates traditional theory with modern science, achieving comprehensive regulation of the physiological, psychological, and multiple pathogenesis mechanisms of coronary heart disease. Compared to Western medicine, it has unique advantages in long-term safety and overall efficacy, providing new ideas for the research and development and clinical practice of new traditional Chinese medicine drugs.

[0031] Animal experiments demonstrate that the traditional Chinese medicine composition provided by this invention exhibits significant and multifaceted therapeutic advantages in treating a rat model of coronary heart disease. This composition effectively increases left ventricular ejection fraction (LVEF) and fractional shortening (FS), significantly enhances myocardial contractility, and restores cardiac pumping function, thus demonstrating a clear protective effect on cardiac function. The composition significantly reduces the levels of pro-inflammatory factors IL-6, IL-1β, and TNF-α in myocardial tissue, inhibits inflammatory responses, and alleviates myocardial damage, indicating that it may indirectly improve cardiac function through an anti-inflammatory mechanism. Pathological evaluation shows that the composition significantly reduces myocardial pathological scores, effectively alleviates myocardial structural damage, and protects the integrity of myocardial tissue. Furthermore, comparative experiments show that the absence of any drug pair significantly weakens the effects of the composition provided by this invention in improving cardiac function, inhibiting inflammation, and alleviating pathological damage, thus confirming a close synergistic relationship between the drug pairs and the fact that each drug in the formula is indispensable. Attached Figure Description

[0032] Figure 1 The results of cardiac function tests in rats of each group are shown in the figure. The significance marker # indicates that the difference between the rats and the normal group is P<0.01. This indicates that the p-value is less than 0.01 compared to the model group. This indicates that compared with Example 1 group, P < 0.05. This indicates that compared with Example 1 group, P < 0.01, n = 12.

[0033] Figure 2 The myocardial tissue pathology scores for each group are shown in the figure. The significance marker # indicates that the score is significantly different from that of the normal group (P < 0.01). This indicates that the p-value is less than 0.01 compared to the model group. This indicates that compared with Example 1 group, P < 0.05. This indicates that compared with Example 1 group, P < 0.01, n = 12. Detailed Implementation

[0034] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] Example 1 This embodiment provides a traditional Chinese medicine composition for treating coronary heart disease, which is made from the following medicinal materials in parts by weight: Astragalus membranaceus 15g, Rhodiola rosea 10g, Salvia miltiorrhiza 15g, Ligusticum chuanxiong 10g, Trichosanthes kirilowii 15g, Allium macrostemon 10g, Ginkgo biloba 10g, Pueraria lobata 15g, Ophiopogon japonicus 15g, Schisandra chinensis 6g, Ostrea gigas 20g, Cinnamomum cassia 10g, Glycyrrhiza uralensis 6g.

[0036] Comparative Example 1 This comparative example provides a traditional Chinese medicine composition for treating coronary heart disease. The difference between this composition and Example 1 is that Astragalus membranaceus and Salvia miltiorrhiza are omitted.

[0037] Comparative Example 2 This comparative example provides a traditional Chinese medicine composition for treating coronary heart disease. The difference between this composition and Example 1 is that the two herbs, Chuanxiong and Rhodiola rosea, are omitted.

[0038] Comparative Example 3 This comparative example provides a traditional Chinese medicine composition for treating coronary heart disease. The difference between this composition and Example 1 is that the two herbs, Trichosanthes kirilowii and Allium macrostemon, are omitted.

[0039] Comparative Example 4 This comparative example provides a traditional Chinese medicine composition for treating coronary heart disease. The difference between this composition and Example 1 is that the two herbs, ginkgo leaves and kudzu root, are omitted.

[0040] Comparative Example 5 This comparative example provides a traditional Chinese medicine composition for treating coronary heart disease. The difference between this composition and Example 1 is that Ophiopogon japonicus and Schisandra chinensis are omitted.

[0041] Comparative Example 6 This comparative example provides a traditional Chinese medicine composition for treating coronary heart disease. The difference between this composition and Example 1 is that the ingredients of oyster shell and cinnamon twig are omitted.

[0042] The following animal experiments were used to verify the therapeutic effect of the traditional Chinese medicine composition provided in the embodiments and comparative examples of the present invention on a rat model of coronary heart disease.

[0043] 1. Experimental materials: 1.1 Laboratory Animals All animals used in the following animal experiments were healthy male SD rats purchased from the Animal Experiment Center of Heilongjiang University of Traditional Chinese Medicine. The rats were 8-12 weeks old and weighed 220±30 g. Before the formal experiments began, all animals underwent a week of acclimatization feeding under laboratory conditions.

[0044] 1.2 Experimental reagents: Positive control drug: Compound Danshen Tablets, specification: 0.32g 200 tablets, National Drug Approval Number Z22022342, Manufacturer: Shanghai Kaiherong Tumen Pharmaceutical Co., Ltd.

[0045] The traditional Chinese medicine composition provided in the above embodiments and comparative examples is used to prepare freeze-dried powder of traditional Chinese medicine.

[0046] The specific preparation process of the freeze-dried traditional Chinese medicine powder obtained from the traditional Chinese medicine composition provided in Example 1 above is as follows: S1. Crush each herb in the herbal composition provided in Example 1 into coarse powder, and then weigh each herb coarse powder according to the corresponding weight parts for later use.

[0047] S2. Soak the crude Chinese medicine powder obtained in S1 in water for 30 minutes. The first decoction time is 40 minutes. After the decoction is finished, filter to obtain filtrate and dregs. Add water to the dregs and decoct once more for 20 minutes. Filter to obtain filtrate after the second decoction. Combine the two filtrates to obtain the total decoction. Filter the total decoction twice with gauze to obtain the total Chinese medicine filtrate.

[0048] S3. Transfer the total filtrate of the Chinese herbal medicine to a rotary evaporator and concentrate it under reduced pressure in a 55°C water bath until it becomes an extract with a relative density of 1.10 (measured at 50°C).

[0049] S4. Pour the extract obtained in S3 into a freeze-drying pan and place it in a liquid nitrogen environment for rapid freezing for 2 hours until it is completely solidified.

[0050] S5. Quickly transfer the solidified solid to a freeze dryer for vacuum freeze drying for 24 hours until the moisture content of the sample is <5%, and obtain the freeze-dried powder of traditional Chinese medicine.

[0051] The preparation process of the freeze-dried Chinese medicine powders in the above comparative examples is the same as that in Example 1, except that specific Chinese medicine components are omitted in the corresponding steps.

[0052] 2. Experimental methods: 2.1 Animal model establishment and drug administration The process of establishing a rat model of coronary heart disease: Each rat was fed 30 g of high-fat diet daily (composition: basal diet + 10% egg yolk powder + 2% cholesterol + 10% lard + 0.2% propylthiouracil + 0.5% sodium cholate) for 10 weeks. Forty-eight hours before the end of the 10-week feeding period, posterior pituitary extract was injected intraperitoneally at a dose of 30 U / kg, once daily for two consecutive days. Electrocardiogram (ECG) recordings were performed within 24 hours of the last injection, with ST segment elevation and / or abnormal T wave elevation (peak value ≥0.1 mV) as the marker of successful model establishment.

[0053] Grouping: The successfully modeled rats were randomly divided into 9 groups of 12 rats each: model group, positive control group, Example 1 group, comparative example 1 group, comparative example 2 group, comparative example 3 group, comparative example 4 group, comparative example 5 group, and comparative example 6 group. An additional 12 healthy rats were used as the normal control group.

[0054] Administration: After successful modeling, rats in all groups began receiving oral administration. Specifically, rats in Example 1 group were administered the lyophilized powder of the traditional Chinese medicine composition provided in Example 1 via oral administration at a dose of 2.5 g / kg / day; rats in Comparative Examples 1 to 6 were administered the lyophilized powder of the traditional Chinese medicine composition provided in their respective comparative examples via oral administration at a dose of 2.5 g / kg / day; rats in the positive control group were administered Compound Danshen Tablets via oral administration at a dose of 200 mg / kg / day; while rats in the model group and normal group were administered the same volume of sterile saline via oral administration as in the Example groups. All rats in all groups received oral administration for 4 consecutive weeks.

[0055] 2.2 Evaluation Indicators Four weeks after administration, the following indicators were evaluated in each group of rats.

[0056] 2.2.1 Cardiac function testing Echocardiography of rats was performed using a small animal ultrasound imaging system and a high-frequency probe. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (FS) were analyzed and calculated.

[0057] 2.2.2 Detection of pro-inflammatory factors in myocardial tissue The levels of IL-6, IL-1β, and TNF-α in myocardial tissue were determined using ELISA. The specific steps were as follows: First, myocardial tissue was homogenized, and then the supernatant was collected by centrifugation. Subsequently, the concentrations of IL-6, IL-1β, and TNF-α were measured according to the instructions of the IL-6, IL-1β, and TNF-α kits.

[0058] 2.2.3 Histopathological examination HE staining method for observing myocardial tissue pathology: Myocardial tissue was fixed in 4% paraformaldehyde, routinely dehydrated, embedded in paraffin, sectioned (5 μm) using a paraffin microtome, stained with hematoxylin and eosin, and mounted with neutral resin. Pathological changes in myocardial tissue were observed under an optical microscope. A blinded histopathological scoring method was used: each observer randomly selected 10 non-overlapping fields of view from each slide, scored each field of view according to the scoring criteria, and calculated the average score of all fields of view for each slide as the final histological damage score for that rat. The specific scoring criteria are as follows: 0 points: Normal myocardial tissue morphology, neatly arranged muscle fibers, normal cell nucleus morphology, and virtually no inflammatory cell infiltration. 1 point: Swollen cardiomyocytes with blurred borders, accompanied by mild interstitial edema or focal inflammatory cell infiltration (<25% of visual field area). 2 points: Obvious granular or vacuolar degeneration of cardiomyocytes, accompanied by significant inflammatory cell infiltration and interstitial edema (25% - 50% of visual field area). 3 points: Extensive necrosis of cardiomyocytes, extensive inflammatory cell infiltration, and muscle fiber rupture (50% - 75% of visual field area). 4 points: Large areas of myocardial necrosis, accompanied by extensive inflammatory cell infiltration and hemorrhage, with severe destruction of normal myocardial structure (>75% of visual field area).

[0059] 3. Statistical Analysis Statistical analysis was performed using SPSS 25.0 software. Quantitative data were expressed as mean ± standard deviation. The comparison between the two groups was performed using an independent samples t-test, with P < 0.05 or P < 0.01 as the criteria for statistical significance.

[0060] 4. Experimental Results 4.1 Results of cardiac function tests in each group of rats.

[0061] according to Figure 1The results of the rat cardiac function tests shown indicate that the left ventricular ejection fraction (LVEF) and fractional shortening (FS) of the model group rats were significantly lower than those of the normal group (P<0.01), indicating that the coronary heart disease model successfully induced cardiac dysfunction, specifically manifested as decreased myocardial contractility and impaired cardiac pumping function. In contrast, the LVEF and FS of the rats in Example 1 group and the positive group were significantly increased, and the improvement effect of Example 1 group was significantly better than that of the positive group (P<0.05). This fully demonstrates that the traditional Chinese medicine composition provided by this invention can effectively enhance myocardial contractility and has a clear therapeutic advantage in the recovery of cardiac function in rats with coronary heart disease. Further analysis showed that the LVEF and FS of rats in Comparative Examples 1 to 6 (each lacking different drug pairs) were lower than those in Example 1 group (P<0.05), indicating that the absence of any drug pair in the traditional Chinese medicine composition significantly weakens its effect on improving myocardial function. This demonstrates that the synergistic effect between the drug pairs in the traditional Chinese medicine composition provided by this invention is crucial, and further confirms the unique efficacy and rational formulation of the traditional Chinese medicine composition in improving cardiac function.

[0062] 4.2 Results of detection of pro-inflammatory factors in myocardial tissue of rats in each group.

[0063] Table 1 shows the results of pro-inflammatory factor detection in the myocardial tissue of rats in each group.

[0064] According to the results of pro-inflammatory factor detection in rat myocardial tissue shown in Table 1, the levels of pro-inflammatory factors IL-6, IL-1β, and TNF-α in the myocardial tissue of the model group rats were significantly higher than those in the normal group, indicating that there is a significant inflammatory response in the myocardial tissue of the coronary heart disease model rats, which may be an important inducing factor for cardiac dysfunction. In contrast, the levels of IL-6, IL-1β, and TNF-α in the myocardial tissue of the positive control group and the Example 1 group rats were significantly reduced, and the reduction was more significant in the Example 1 group rats. This further confirms that the freeze-dried traditional Chinese medicine powder provided in Example 1 can effectively inhibit the inflammatory response in rat myocardial tissue and alleviate myocardial damage by reducing the levels of key pro-inflammatory factors. Through the above analysis, the traditional Chinese medicine composition provided by the present invention not only significantly inhibits inflammation, but may also indirectly improve cardiac function through an anti-inflammatory mechanism, thus showing its multiple therapeutic effects and clinical application potential in the treatment of coronary heart disease. In addition, compared with the positive control drug, the traditional Chinese medicine composition of the present invention performs better in inhibiting inflammation, further illustrating its unique value in inhibiting the inflammatory response of myocardial tissue caused by coronary heart disease.

[0065] 4.3 Histopathological evaluation results of rats in each group.

[0066] Figure 2The experimental results of myocardial tissue pathological scoring in rats are shown. Comparison revealed that the myocardial pathological score of the model group was significantly higher than that of the normal group (P<0.01), indicating that under the coronary heart disease model conditions, the rat myocardial tissue showed significant structural damage and pathological changes. In contrast, the myocardial pathological score of rats treated with the lyophilized powder of the traditional Chinese medicine in Example 1 was significantly lower than that of the model group (P<0.01), and the degree of improvement was better than that of the positive control group, indicating that the traditional Chinese medicine composition has a more prominent therapeutic effect in reducing myocardial tissue damage. Compared with the Example 1 group, the pathological scores of Comparative Examples 1 to 6 (each lacking different drug pairs) all showed a significant increase (P<0.05), reflecting that the protective effect of the traditional Chinese medicine composition on myocardial function was significantly weakened in the absence of certain key drug pairs. The above results fully demonstrate that there is a close synergistic effect among the drug pairs in the traditional Chinese medicine composition provided by this invention, and its overall efficacy depends on the integrity of the entire formula; each drug in the formula is indispensable.

[0067] Based on the above animal experimental results, the traditional Chinese medicine composition provided by this invention exhibits significant and multifaceted therapeutic advantages in treating a rat model of coronary heart disease. This composition effectively increases left ventricular ejection fraction (LVEF) and fractional shortening (FS), significantly enhances myocardial contractility, and restores cardiac pumping function, thus demonstrating its clear protective effect on cardiac function. The composition significantly reduces the levels of pro-inflammatory factors IL-6, IL-1β, and TNF-α in myocardial tissue, inhibits inflammatory responses, and alleviates myocardial damage, indicating that it may indirectly improve cardiac function through an anti-inflammatory mechanism. Pathological evaluation shows that the traditional Chinese medicine composition significantly reduces myocardial pathological scores, effectively alleviates myocardial structural damage, and protects the integrity of myocardial tissue. Furthermore, comparative experiments show that the absence of any drug pair significantly weakens the effects of the composition provided by this invention in improving cardiac function, inhibiting inflammation, and alleviating pathological damage, thus confirming a close synergistic relationship between the drug pairs, and that each drug in the formula is indispensable.

[0068] It should be noted that, in this document, terms such as “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0069] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for treating coronary heart disease, characterized in that, The composition is made from the following medicinal materials: Astragalus membranaceus, Rhodiola rosea, Salvia miltiorrhiza, Ligusticum chuanxiong, Trichosanthes kirilowii, Allium macrostemon, Ginkgo biloba leaf, Pueraria lobata, Ophiopogon japonicus, Schisandra chinensis, Ostrea gigas, Cinnamomum cassia and Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition for treating coronary heart disease as described in claim 1, characterized in that, The composition is made from the following medicinal materials in parts by weight: Astragalus membranaceus 10-30 parts, Rhodiola rosea 5-15 parts, Salvia miltiorrhiza 10-30 parts, Ligusticum chuanxiong 5-15 parts, Trichosanthes kirilowii 10-30 parts, Allium macrostemon 5-15 parts, Ginkgo biloba 5-15 parts, Pueraria lobata 10-30 parts, Ophiopogon japonicus 10-30 parts, Schisandra chinensis 3-10 parts, Ostrea gigas 15-30 parts, Cinnamomum cassia 5-15 parts, Glycyrrhiza uralensis 3-10 parts.

3. The traditional Chinese medicine composition for treating coronary heart disease as described in claim 1, characterized in that, The composition is made from the following medicinal materials in parts by weight: Astragalus membranaceus 15 parts, Rhodiola rosea 10 parts, Salvia miltiorrhiza 15 parts, Ligusticum chuanxiong 10 parts, Trichosanthes kirilowii 15 parts, Allium macrostemon 10 parts, Ginkgo biloba 10 parts, Pueraria lobata 15 parts, Ophiopogon japonicus 15 parts, Schisandra chinensis 6 parts, Ostrea gigas 20 parts, Cinnamomum cassia 10 parts, Glycyrrhiza uralensis 6 parts.

4. A traditional Chinese medicine preparation for treating coronary heart disease, characterized in that, It is made from the traditional Chinese medicine composition and excipients described in any one of claims 1-3.

5. The traditional Chinese medicine preparation for treating coronary heart disease as described in claim 4, characterized in that, The dosage form of the traditional Chinese medicine preparation is any one of the following: decoction, pill, powder, paste, medicated wine, capsule, tablet, granule, and oral liquid.

6. A method for preparing a freeze-dried powder of traditional Chinese medicine for treating coronary heart disease, characterized in that, Includes the following steps: S1. Each herb in the herbal composition according to any one of claims 1-3 is pulverized into coarse powder for later use; S2. Soak the crude Chinese medicine powder obtained in S1 in water for 20-60 minutes, then decoct it 1-3 times, each time for 20-60 minutes. Filter the liquid after each decoction and combine the liquids from all decoctions to obtain the total decoction. S3. The total decoction obtained in S2 is concentrated to obtain a Chinese herbal extract. Then, the Chinese herbal extract is freeze-dried to obtain freeze-dried Chinese herbal powder.

7. The method for preparing the freeze-dried powder of traditional Chinese medicine for treating coronary heart disease as described in claim 6, characterized in that, The concentration process in S3 is as follows: vacuum concentration is carried out using a rotary evaporator at 50-60℃.

8. The method for preparing the freeze-dried powder of traditional Chinese medicine for treating coronary heart disease as described in claim 6, characterized in that, The relative density of the herbal extract obtained in S3 is 1.10-1.

20.

9. The method for preparing the freeze-dried powder of traditional Chinese medicine for treating coronary heart disease as described in claim 6, characterized in that, The freeze-drying process in S3 specifically includes: The Chinese herbal extract was placed in a liquid nitrogen environment and rapidly frozen for 2-4 hours until it was completely solidified. The solidified solids were quickly transferred to a freeze dryer and subjected to vacuum freeze drying for 24-36 hours until the moisture content of the sample was <5%.

10. The use of the traditional Chinese medicine composition according to any one of claims 1-3, the traditional Chinese medicine preparation according to any one of claims 4-5, or the traditional Chinese medicine freeze-dried powder prepared by the preparation method according to any one of claims 6-9 in the preparation of a drug for treating coronary heart disease.

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