Traditional Chinese medicine composition for treating coronary artery microcirculation diseases and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and provides a traditional Chinese medicine composition for treating coronary artery microcirculation diseases and a preparation method thereof, and the traditional Chinese medicine composition comprises the following components by weight: 25-35g of Radix Astragali, 25-35g of Salvia miltiorrhiza, 6-12g of lumbricus, 9-15g of Ligusticum wallichii, and 25-35g of Caulis Spatholobi. According to the whole formula, astragalus membranaceus is used for cultivating and tonifying primordial qi, earthworm is used for relieving spasm and dredging collaterals and is used for inducing waste, and various materials for activating blood and promoting qi circulation are used as auxiliary materials, so that a treatment pattern of consolidating foundation without forgetting to relieve arthralgia, removing blood stasis and especially protecting qi activity is finally formed, the training of dredging blood and qi and regulating the blood and qi through internal meridians is implied, qi yang is used as power, collaterals are used as a central machine, and the coronary artery microcirculation dysfunction is caused by deficiency in foundation and excess in superficies. And a three-dimensional intervention pattern of tonifying without stagnation and dredging without hurting the body is formed.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and relates to a traditional Chinese medicine composition for treating coronary microcirculation diseases, and a preparation method and application thereof. Background Art

[0002] Angina pectoris is the most common symptom of ischemic heart disease, affecting approximately 112 million patients worldwide. Coronary angiography (CAG) is currently a common diagnostic tool for coronary artery disease, but up to 70% of patients with angina do not have significant stenosis (less than 50%) detected on CAG. Clinically, this condition, characterized by symptoms of ischemic chest pain and objective evidence of myocardial ischemia but no obstructive coronary artery stenosis detected on CAG or coronary computer tomography angiography (CCTA), is defined as ischemia with non-obstructive coronary artery disease (INOCA). INOCA can be categorized into two subtypes based on their pathophysiological characteristics: microvascular angina and epicardial vasospasm. Year after year, studies have found that coronary microvascular dysfunction (CMD) is an important mechanism leading to myocardial ischemia. However, due to the current inability to visually assess coronary microvasculature, symptoms caused by its dysfunction are often mistakenly attributed to non-cardiac factors, resulting in inadequate diagnosis and treatment.

[0003] According to TCM theory, coronary microcirculatory dysfunction falls into the category of "chest pain" and "heart pain", with Qi deficiency and blood stasis as the core pathogenesis, and collateral congestion as the symptom. In clinical practice, Qi deficiency and blood stasis coexist with Yin and Yang imbalance, which manifests as paroxysmal chest pain, aggravated by cold, accompanied by shortness of breath, fatigue, cold hands and feet, etc. Existing TCM treatments mostly focus on promoting blood circulation and removing blood stasis (such as Danshen preparations) or warming Yang and unblocking meridians (such as Guizhi prescriptions). Although they can relieve acute symptoms, they fail to make overall adjustments to the core pathogenesis of "Qi deficiency and blood stasis-blood congestion", resulting in repeated attacks of the disease.

[0004] It should be noted that patients with coronary microcirculation dysfunction generally have the physical characteristics of "intermingling of deficiency and stasis". Long-term clinical observations have found that such patients are often accompanied by systemic changes such as autonomic nervous system dysfunction (such as reduced heart rate variability) and endocrine disorders (such as abnormal cortisol circadian rhythm), which highly coincide with the traditional Chinese medicine theory of "insufficient vital qi and disharmony between nutrient qi and defensive qi". Modern pharmacological studies have shown that qi-tonifying drugs can improve vascular endothelial function by regulating the NO / cGMP pathway, while the ingredients for promoting blood circulation and removing blood stasis can target and inhibit the RhoA / ROCK signaling pathway. The two work synergistically to effectively intervene in the molecular mechanism of vasospasm.

[0005] Chinese patent CN1171943A combines red ginseng, leech, earthworm, notoginseng, ophiopogon root, schisandra fruit, aconite, kudzu root, salvia miltiorrhiza, dalbergia odorifera, red peony root, and angelica sinensis for the treatment of heart diseases such as coronary heart disease and myocarditis. The formula of this group of drugs is complex.

[0006] In current clinical Chinese patent medicine preparations, there is no compound preparation specifically for coronary microcirculation dysfunction with the formula principle of "tonifying qi and dredging collaterals, promoting blood circulation and relieving spasm". Through innovative monarch-minister-assistant-servant compatibility, the present invention organically combines qi-tonifying and root-strengthening with promoting blood circulation and dredging collaterals, and at the same time is assisted by herbs for regulating yin and yang, forming a multi-target intervention strategy, providing a new traditional Chinese medicine solution for the prevention and treatment of coronary microcirculation dysfunction. Summary of the Invention

[0007] In view of the above-mentioned shortcomings of the prior art, the present invention provides a traditional Chinese medicine complex - Buqi Huoxue Decoction for treating coronary microcirculation dysfunction, which has definite curative effects. Aiming at the pathogenesis characteristics of "qi deficiency and blood stasis, and constriction of collaterals" in patients with coronary microcirculation dysfunction, it can effectively improve vascular endothelial function and prevent the recurrence of coronary microcirculation dysfunction. The traditional Chinese medicine composition of the present invention can significantly relieve chest pain symptoms and improve cardiac microcirculation, and is especially suitable for patients with coronary microcirculation dysfunction accompanied by the physical constitution of qi deficiency and blood stasis.

[0008] The present invention also provides a preparation method of the above-mentioned traditional Chinese medicine complex.

[0009] The present invention also provides the application of the above-mentioned traditional Chinese medicine complex in the preparation of drugs for treating coronary microcirculation dysfunction.

[0010] The technical solution adopted by the present invention to achieve the above object is as follows:

[0011] In the first aspect of the present invention, there is provided a traditional Chinese medicine complex (Buqi Huoxue Decoction) for treating coronary microcirculation dysfunction, which is prepared from raw materials of the following components, by weight: Astragalus membranaceus Fisch. var. mongholicus (Bunge) Hsiao 25 - 35 g, Salvia miltiorrhiza Bunge 25 - 35 g, Pheretima aspergillum (E. Perrier) 6 - 12 g, Ligusticum chuanxiong Hort. 9 - 15 g, Millettia reticulata Benth. 25 - 35 g.

[0012] As a preferred technical solution of the present invention, it is prepared from raw materials of the following components, by weight: 30 g of Astragalus membranaceus, 30 g of Salvia miltiorrhiza, 9 g of Pheretima aspergillum, 12 g of Ligusticum chuanxiong, and 30 g of Spatholobus suberectus.

[0013] As a preferred technical solution of the present invention, in the formula provided by the present invention, the raw medicinal materials may further include 6 - 12 g of Cinnamomum cassia by weight to assist in the effect of warming yang and dredging meridians.

[0014] As a preferred technical solution of the present invention, in the formula provided by the present invention, the raw medicinal materials may further include 9 - 15 g of Carthamus tinctorius and 6 - 12 g of Prunus persica by weight to strengthen the effect of promoting blood circulation and removing blood stasis.

[0015] As a preferred technical solution of the present invention, in the formula provided by the present invention, the raw medicinal materials may further include 6 - 12 g of Aurantii Fructus Immaturus and Cyperus rotundus by weight to promote qi movement and relieve chest tightness.

[0016] In the second aspect of the present invention, a preparation method of the above - mentioned traditional Chinese medicine complex is provided, including the following steps: Weigh the raw medicinal materials by weight, soak them in 1000 mL of pure water in a casserole for 60 minutes, bring to a boil over high heat and then simmer slowly over low heat for 1.5 hours until the medicinal juice is 400 mL.

[0017] Mix the above - prepared medicinal juice twice, divide it into two bags, each bag containing 200 mL, store it refrigerated, and take it warm half an hour after breakfast and dinner, one dose per day.

[0018] In the third aspect of the present invention, a traditional Chinese medicine preparation for treating coronary microcirculation diseases is provided, which is characterized in that the traditional Chinese medicine preparation is made from the above - mentioned traditional Chinese medicine composition as the raw material.

[0019] Furthermore, the traditional Chinese medicine preparation further includes pharmaceutically acceptable excipients. The dosage forms of the traditional Chinese medicine preparation include decoctions, infusions, granules, capsules, tablets, powders, pills or oral liquids. [[ID=2!3]]

[0020] In the fourth aspect of the present invention, the use of the above - mentioned traditional Chinese medicine composition for treating coronary microcirculation diseases in the preparation of drugs for preventing or treating coronary microcirculation diseases is provided.

[0021] In the fifth aspect of the present invention, the use of the above - mentioned traditional Chinese medicine composition for treating coronary microcirculation diseases in the preparation of drugs for preventing or treating myocardial infarction is provided.

[0022] Compared with the prior art, the present invention has significant advantages: After patients with coronary microcirculation dysfunction receive western medicines such as calcium channel blockers, although the symptoms can be temporarily relieved, long-term application is likely to cause adverse reactions such as hypotension and reflex tachycardia, and it cannot improve the core pathogenesis of "qi deficiency failing to promote transportation - blood vessel spasm". Most existing traditional Chinese patent medicines focus on promoting blood circulation to remove stasis (such as Compound Danshen Tablets) or warming yang and dredging collaterals (such as Shexiang Baoxin Pills), lacking an overall regulation plan for "intermingled deficiency and stasis".

[0023] For such patients, the inventor of the present invention believes that their pathological mechanism is: qi deficiency fails to promote transportation, resulting in weak propulsion, stagnant blood circulation, and collateral spasm. Therefore, in the treatment, it is necessary to take replenishing qi as the fundamental, promoting blood circulation and dredging collaterals as the secondary, and also taking into account relieving spasm and pain. The treatment plan follows the principle of "treating blood first by treating qi, and when qi moves, blood moves", and constructs a compatibility system of "mutual supplementation of dredging and tonifying": In the whole formula, Astragalus membranaceus is used as the monarch drug, taking on the heavy responsibility alone. It has the nature of ascending and developing, replenishing the middle-jiao to invigorate the qi source, and relying on its thick qi to penetrate the triple energizer and promote blood circulation. It directly enters to restore the function of qi movement; The earthworm and Salvia miltiorrhiza are used as the ministerial drugs in coordination. The earthworm is soft and good at moving, using the nature of insect drugs to search and dispel to relieve collateral spasm. Salvia miltiorrhiza is red in color and enters the nutrient aspect, using its function of promoting blood circulation and cooling and dispersing to transform the separated and stagnant stasis. The two, being rigid and soft in combination, jointly dredge the congestion in the channels; The Ligusticum wallichii and Spatholobus suberectus are used as the assistant and guiding drugs, wonderfully combining the principles of ascending and descending. Ligusticum wallichii is pungent, fragrant and running around, capable of promoting the stagnant qi in the blood, and Spatholobus suberectus is sweet, warm and moistening, good at dredging the tortuous collaterals. One ascending and one descending make the qi and blood flow smoothly without hindrance. The whole formula takes Astragalus membranaceus to cultivate and replenish the primordial qi as the fundamental, the earthworm to relieve spasm and dredge collaterals as the key to restoring the disabled, and is supplemented with various drugs for promoting blood circulation and regulating qi. Eventually, it forms a treatment pattern of "strengthening the root without forgetting to relieve arthralgia, and removing stasis while protecting the qi mechanism", secretly conforming to the teaching of "dredging its qi and blood to make it smooth and harmonious" in the Inner Canon of Huangdi. Taking qi and yang as the driving force and dredging collaterals as the pivot, aiming at the syndrome of "deficiency in the root and excess in the branch" of coronary microcirculation dysfunction, it forms a three-dimensional intervention pattern of "tonifying without stagnation and dredging without damaging the healthy qi".

[0024] Analysis of the formula composition:

[0025] 1. Monarch drugs: Astragalus membranaceus, Cinnamomum cassia

[0026] Astragalus membranaceus: Sweet and warm, entering the spleen and lung meridians, greatly replenishing the vital qi in the chest. It is said in "Medical Revelations with Integrated Chinese and Western Medicine" that it "can tonify qi and also promote qi ascending", just like a suspended bell hammer that can make a sound by itself. Its nature is ascending and lifting, like the spring breeze agitating, awakening the qi mechanism of the spleen and lung, enabling the clear yang to be sent upward, the ancestral qi to fill the chest, and the blood to move forward by the promotion of qi. Zhang Xichun even regarded Astragalus membranaceus as the "main drug for qi aspect", creating the Ascending and Sinking Decoction to treat the collapse of the vital qi. Its ascending and tonifying power is like the movement of clouds and rain, with the earth qi rising to form clouds and the sky qi descending to form rain. Zhang Zhongjing formulated the Astragalus and Cinnamon Twig Decoction for Five Ingredients in "Synopsis of the Golden Chamber", using Astragalus membranaceus as the monarch drug to treat blood stasis and "body numbness", taking its effect of strengthening the superficial resistance and promoting blood circulation to moisten the tendons. When combined with Cinnamomum cassia, it is like the sun shining brightly in the middle of the sky, and the haze will naturally disperse.

[0027] Cinnamon Twig: Pungent, sweet, and warm in nature, it is like the rising sun in the early morning, warming and nourishing the defensive yang, and reaching the acupoints of the twelve regular meridians. According to "Speculations on Materia Medica", it harmonizes the nutrient qi and defensive qi, dredges the meridians, and dispels cold pathogens; when used in combination with Astragalus membranaceus, one tonifies and the other dredges, like the bellows blowing the fire, invigorating qi and yang simultaneously, and stirring up the blood waves. In Zhang Zhongjing's Cinnamon Twig Decoction, Cinnamon Twig is combined with Paeonia lactiflora to harmonize the nutrient qi and defensive qi, while in Huangqi Guizhi Wuwu Decoction, Glycyrrhiza uralensis is removed and the amount of Zingiber officinale is doubled, specifically targeting blood stasis obstruction, especially emphasizing the power of Cinnamon Twig in warming and dredging, so that "when yang qi circulates smoothly, blood stasis obstruction is removed". Ye Tianshi also discussed in "Medical Records of Clinical Practice Guidelines" that Cinnamon Twig is pungent and warm, promoting yang and assisting the defensive qi. For those with stagnation in the meridians and failure of the defensive yang to circulate, only this herb can penetrate and reach.

[0028] 2. Ministerial herbs: Salvia miltiorrhiza, Pheretima

[0029] Salvia miltiorrhiza: Bitter and slightly cold in nature, it enters the blood aspects of the heart and liver, promoting blood circulation and removing blood stasis like unwinding silk cocoons. "On the Clear Understanding of Women's Diseases" praises it as "having the same efficacy as the Four Substances Decoction", but the Four Substances Decoction nourishes blood as its main function, while Salvia miltiorrhiza focuses on promoting blood circulation, and it can remove blood stasis without harming newly generated blood, especially excelling in dredging the stagnation of the heart meridian. Zhang Xichun said that "its nature is not fierce but its efficacy is very fast". For all stubborn diseases in the heart and abdomen, masses and accumulations, its clear and flexible nature can be used to dredge qi and blood. Although Salvia miltiorrhiza is not directly used in the various blood-activating prescriptions in Wang Qingren's "Corrections of Medical Errors", the principles and methods of its "Stasis-removing Decoction" and similar prescriptions are interlinked, all emphasizing promoting circulation as a form of tonification, which is in line with the use of Salvia miltiorrhiza in this prescription.

[0030] Pheretima: Salty, cold, and good at running through, it is good at searching for and removing the latent pathogens in the collaterals. According to "Seeking Truth from Materia Medica", its nature descends, and it can clear heat and promote diuresis, dredge collaterals and relieve spasm. Ye Tianshi created the method of "using insects and ants to dredge collaterals", stating that "for diseases that have persisted for a long time and entered the collaterals, only lively substances can search and remove". Pheretima is just right for this, like spring earthworms turning the soil, breaking the sticky binding of stasis heat and relieving the spasm of the meridians. In Wu Jutong's "Treatise on Febrile Diseases", when treating damp-heat arthralgia syndrome, Pheretima is also combined with Talcum and Stephania tetrandra to achieve the effect of "dredging collaterals and promoting diuresis", which is in line with the purpose of Pheretima in this prescription to relieve spasm and dredge collaterals.

[0031] 3. Assistant and guiding herbs: Ligusticum wallichii - Spatholobus suberectus

[0032] Ligusticum wallichii: Pungent, warm, and fragrant, it is a qi herb in the blood, like the surging waves hitting the shore, breaking the stasis in the blood. "Compendium of Materia Medica" states that "it ascends to the head, descends to regulate menstruation, and opens up stagnation in the middle". Its nature is ascending and dispersing, leading all the herbs to reach the top of the head, descend to the uterine cavity, and extend to the four extremities. Zhang Yuanxun in "Medical Origins" said that it disperses wind in the liver meridian and treats headache in the Shaoyang meridian. Li Dongyuan further combined Ligusticum wallichii with Astragalus membranaceus to treat qi deficiency and blood stasis. Therefore, Astragalus membranaceus becomes unobstructed with the assistance of Ligusticum wallichii, and Ligusticum wallichii is tonified with the assistance of Astragalus membranaceus. In Wang Qingren's Buyang Huanwu Decoction, Ligusticum wallichii complements Astragalus membranaceus and Pheretima to jointly achieve the effect of supplementing qi and promoting blood circulation, which is similar to the effect of Ligusticum wallichii in this prescription to lead the herbs to reach the top of the head and extend to the four extremities.

[0033] Spatholobus suberectus: Bitter, sweet, warm, and moist, it belongs to the category of vines. According to "New Materia Medica", it "enters the heart and spleen meridians, promoting blood circulation and relaxing tendons". Its shape is like a network, and its nature is unobstructed, like spring rain moistening the vines, nourishing blood and dredging collaterals, making the blood active and the tendons soft. Generally, most vine-like herbs have the ability to dredge collaterals, and Spatholobus suberectus is especially good at nourishing blood and promoting blood circulation. It is suitable for those with blood deficiency and collateral obstruction. Ye Tianshi emphasized "using pungent and moist herbs to dredge collaterals" in treating collateral diseases. Spatholobus suberectus nourishes blood and moistens tendons, combined with Salvia miltiorrhiza and Pheretima, jointly achieving the wonderful effect of "being moist without being greasy and unobstructed without causing harm".

[0034] Mystery of Compatibility:

[0035] Reinforcing and Promoting Circulation Complement Each Other: Astragalus membranaceus tonifies qi like building a dyke to store water, and Cinnamomum cassia promotes yang qi like opening a sluice to release water. One is static and the other is dynamic, enabling the qi mechanism to flow smoothly without obstruction, implicitly conforming to the profound principle of "when qi moves, blood moves". Combining Rigidity and Softness Harmoniously: Salvia miltiorrhiza is bitter and cold for clearing stasis, and Pheretima aspergillum is salty and cold for relieving spasm. Assisted by Ligusticum chuanxiong which is pungent, warm and dispersing, the combination of rigidity and softness restricts each other, enabling stasis removal without damaging healthy qi and spasm relief without causing stagnation. Regulating Form and Qi Simultaneously: Spatholobus suberectus treats the form with the form, taking the climbing image of the vine to dredge the meridians; Ligusticum chuanxiong promotes qi circulation with qi, borrowing its fragrant, ascending and dispersing nature to smooth the qi mechanism. Treating both form and qi together is like a strong wind sweeping away clouds, cleansing the turbid stasis in the collaterals.

[0036] Essence of the Whole Formula: Tonifying qi not only depends on the thick earth supporting things by Astragalus membranaceus, but also borrows the yang-promoting and qi-transforming effect of Cinnamomum cassia; promoting blood circulation not only relies on Salvia miltiorrhiza for breaking stasis, but also depends on Ligusticum chuanxiong for promoting qi circulation and guiding qi stagnation; relieving spasm not only depends on Pheretima aspergillum for searching and eliminating, but especially relies on Spatholobus suberectus for nourishing blood and softening tendons.

[0037] Modern Pharmacological Research:

[0038] (1) Astragalus membranaceus

[0039] Astragalus membranaceus is a perennial herb of the genus Astragalus in the legume family. Its medicinal properties are sweet and slightly warm, mainly entering the spleen and lung meridians. Its traditional effects include tonifying qi and lifting yang, securing the exterior and promoting diuresis, expelling toxins and promoting granulation, nourishing blood and dredging collaterals, etc. Modern research has further revealed its extensive pharmacological activities. Chemical composition analysis shows that Astragalus membranaceus mainly contains polysaccharides, saponins and flavonoids. Among them, Astragalus polysaccharide (APS) has become a research hotspot due to its high content and significant activity. Modern pharmacological research has confirmed that APS has anti-inflammatory, antioxidant and immunomodulatory effects, and has a protective effect on multiple organs. The research team led by Wu Jie found through diabetes models that APS can effectively inhibit oxidative stress response, increase the mitochondrial membrane potential level of the pancreas, reduce lipid accumulation in the liver, and at the same time reduce the apoptosis rate of pancreatic and liver cells, ultimately improving blood glucose levels. Tang Simeng et al. showed that APS can significantly reduce fasting blood glucose and lipid indexes in type 2 diabetic rats, improve insulin secretion ability, and delay the disease progression by repairing the pancreatic islet tissue structure and increasing the number of β cells. The flavonoid components of Astragalus membranaceus have unique value in regulating metabolism and organ protection. The experiments by Tang Yanyan et al. showed that total flavonoids of Astragalus membranaceus can reduce the degree of myocardial ischemia injury and the size of myocardial infarction. The saponin components show the characteristics of regulating metabolism and enhancing antioxidant capacity. The research team led by Wang Yumeng found that astragaloside IV can promote the release of vascular endothelial growth factor by endothelial progenitor cells, suggesting its role in promoting angiogenesis. Another study confirmed that total saponins and total flavonoids of Astragalus membranaceus have a synergistic protective effect on the heart, which can not only enhance myocardial contractile function but also improve the state of ischemic myocardium. The research by LIU et al. also found that astragaloside IV can inhibit the pathological structural changes in the cardiac hypertrophy model and improve cardiac function parameters.

[0040] (2) Pheretima aspergillum

[0041] Pheretima is salty and cold in nature, and belongs to the Liver, Spleen, and Bladder meridians. It has the effects of clearing heat and calming endogenous wind, dredging collaterals, relieving asthma, and promoting diuresis. In modern clinical practice of traditional Chinese medicine, it is widely used to treat various diseases such as high fever convulsions, qi stagnation and blood stasis, hemiplegia, arthralgia syndrome, pulmonary heat asthma, and dysuria, with good effects. Pheretima has multiple pharmacological effects. In terms of immune regulation, it enhances the phagocytic function of macrophages through active peptides and protein components, promotes lymphocyte transformation, and improves bone marrow hematopoiesis and immune protection functions. Its anticoagulant and antithrombotic mechanisms mainly stem from components such as lumbrokinase and plasmin, which can prolong the thrombus formation time, inhibit the intrinsic coagulation pathway, and dissolve fibrin thrombi. Its anti-tumor effect is manifested as multi-pathway synergy: by activating the immune system to enhance phagocytic activity, inducing apoptosis of tumor cells, using superoxide dismutase to inhibit the proliferation of cancer cells, and at the same time plasmin reducing the risk of tumor metastasis. Experiments have confirmed that it has a significant inhibitory effect on the growth and angiogenesis of solid tumors such as colon cancer. In terms of blood pressure reduction, earthworm polypeptides and platelet-activating factor-like substances achieve long-term blood pressure reduction by inhibiting the activity of angiotensin-converting enzyme (ACE) and dilating blood vessels. Animal experiments have shown significant effects on spontaneously hypertensive rats. The anti-asthmatic effect mainly depends on succinic acid and hypoxanthine to relax bronchial smooth muscle and relieve airway spasm through multiple targets. In addition, earthworm improves diabetic nephropathy by inhibiting glomerular mesangial cell proliferation and reducing the deposition of type IV collagen. A high-dose decoction can effectively reduce glomerulosclerosis and proteinuria symptoms. Comprehensive research shows that the pharmacological activities of earthworm involve multiple dimensions such as immune enhancement, blood system regulation, tumor inhibition, and circulatory system regulation. The multi-component synergistic action mechanism provides a scientific basis for its clinical application.

[0042] (3) Salvia miltiorrhiza

[0043] The chemical constituents of Salvia miltiorrhiza show high diversity, mainly including more than thirty lipophilic tanshinones and more than fifty water-soluble phenolic acids. Pharmacological studies have confirmed that its core active ingredient, tanshinone IIA, has a significant effect on anti-atherosclerosis (AS). The pathogenesis of AS involves vascular endothelial injury, intimal lipid deposition, smooth muscle cell proliferation and migration, platelet activation and aggregation, and is closely related to oxidative stress and chronic inflammation. Normal vascular endothelium plays a protective role by secreting various active substances, and endothelial dysfunction is an important initiating link in the occurrence of AS. Studies have revealed that tanshinone IIA exerts cardiovascular protection through multiple pathways: Yan et al. found that this ingredient can promote the generation of endogenous H2S by activating the ER / cAMP / CSE signaling pathway, thereby antagonizing acrolein-induced endothelial oxidative damage. He et al. confirmed that it enhances antioxidant capacity, maintains GSH homeostasis, and effectively inhibits ferroptosis-mediated coronary endothelial injury by promoting the nuclear translocation of Nrf2. Huang's research showed that this ingredient can upregulate the expression of TGF-β and VEGFA, enhancing the endothelial cell protection mechanism. In regulating smooth muscle cells, Sun Weiliang's team confirmed that tanshinone IIA inhibits phenotypic transformation by downregulating the expression of PCNA and p-YAP. Li et al. found that it blocks homocysteine-induced smooth muscle cell proliferation through the miR-145 / CD40 pathway, and Lou's research confirmed that it can antagonize PDGF-BB-mediated smooth muscle cell migration and activation. In addition to its direct anti-AS effect, tanshinone IIA also exhibits multi-dimensional cardiovascular protection characteristics: in a myocardial ischemia-reperfusion injury model, this ingredient inhibits miR-155-5p through the SIRT1-AMPK pathway to improve myocardial cell survival. LI's research further revealed that it reduces monocyte infiltration and promotes angiogenesis through the miR-223-5p / CCR2 axis. In addition, Salvia miltiorrhiza also has comprehensive pharmacological effects such as improving microcirculation disorders, inhibiting platelet activation, and regulating vascular tone, confirming its unique advantage of multi-target intervention in cardiovascular diseases.

[0044] (4) Ligusticum wallichii

[0045] Chuanxiong (Ligusticum chuanxiong), as a traditional and important drug for promoting blood circulation and removing blood stasis, its pharmacological mechanism of action has been systematically elucidated through modern research. In terms of blood circulation regulation, Chuanxiong improves the body's microenvironment through multi-dimensional interventions: ① inhibiting the expression of platelet CD62p gene and the activity of plasminogen activator inhibitor-1, and reducing blood viscosity; ② enhancing the adhesion of bone marrow stromal cells and hematopoietic cells, promoting the expression of hematopoietic markers such as CD31 / CD34, and stimulating the secretion of SCF to restore hematopoietic function; ③ bidirectionally regulating vasoactive factors, inhibiting the generation of ET-1 while increasing the level of NO, and achieving vasodilation by reducing inflammatory mediators such as TNF-α and hs-CRP; ④ improving glucose and lipid metabolism disorders, regulating the ratios of TC, TG and LDL-C / HDL-C, and restoring hemorheological indexes. Studies have confirmed that its active ingredient, senkyunolide I, promotes angiogenesis by upregulating PlGF and significantly improves microcirculation disorders. In terms of the analgesic mechanism, Chuanxiong plays a central regulatory role through multiple pathways: ① inhibiting the activation of microglial NF-κB and activating SIRT1, and reducing the release of inflammatory mediators such as TNF-α and IL-1β; ② regulating the CREB-BDNF pathway to promote nerve regeneration, and enhancing neuronal synaptic plasticity through the p38 MAPK signal; ③ inhibiting the excessive release of CGRP mediated by the TRPV1 channel, and at the same time exerting the agonist effect of the 5-HT1B receptor to regulate pain conduction in the periaqueductal gray area of the midbrain; ④ regulating the levels of glutamate metabolism and sphingolipid metabolites in the brain to maintain neurotransmitter homeostasis. Experiments have shown that its component, 2,3,5,6-tetramethylpyrazine, can reduce the level of reactive oxygen species by 42% and effectively relieve neuropathic pain. Studies on the anti-fibrotic effect have shown that the extract of Chuanxiong can significantly reduce serum markers such as HA and PCIII in the liver fibrosis model, and its phthalide components inhibit bile duct hyperplasia by regulating the H19 pathway. In terms of myocardial protection, Chuanxiong alkaloids reduce hydroxyproline deposition by increasing the activity of SOD and improve isoproterenol-induced myocardial fibrosis. Studies on bone injury repair have revealed that it regulates the proliferation and differentiation of chondrocytes through the PI3K / Akt pathway, and at the same time inhibits the Bax / caspase-3 pro-apoptotic pathway to promote the regeneration of the extracellular matrix of intervertebral disc nucleus pulposus cells. In addition, Chuanxiong also exhibits multi-organ protection characteristics: ① enhancing antioxidant capacity through the Nrf2 / HO-1 pathway and reducing ischemia-reperfusion injury; ② organic acid components regulate the TLR / TNF signaling pathway to exert a hepatoprotective effect, and Z-ligustilide improves fibrosis by inhibiting renal collagen deposition; ③ components such as chlorogenic acid inhibit inflammatory responses through the ERK pathway and enhance the body's immune response. These studies provide a modern pharmacological basis for the clinical application of Chuanxiong.

[0046] (5) Millettia reticulata

[0047] Spatholobus suberectus, a traditional herbal remedy for promoting blood circulation, possesses pharmacological effects such as antithrombotic and anticoagulant properties, lipid metabolism regulation, anti-inflammatory and analgesic properties, and anti-tumor effects. Modern research has confirmed these multifaceted pharmacological actions. In the antiviral field, its ethanol extract inhibits the activity of herpes simplex virus type 1 and influenza A virus, while its aqueous extract demonstrates protective effects against coxsackievirus-induced myocarditis, reducing mouse mortality by 38%. Its regulatory effects on the blood system are particularly prominent: ① Activating the MEK / Erk phosphorylation cascade, it promotes hematopoietic factor secretion and bone marrow cell proliferation; ② Ameliorating hematopoietic suppression through the JAK2 / STAT5a pathway, increasing white blood cell and platelet counts to 1.5 times normal levels; and ③ Total flavonoids inhibit ADP-induced platelet aggregation by 67%, significantly improving parameters in a blood deficiency model. Studies have shown that its flavonoid components can treat anemia through the IL-3 / EPO axis and regulate lipid metabolism (reducing TC by 21% and TG by 18%). Antioxidant studies revealed that flavonoids are key active components: ① The ethanol extract's ability to scavenge DPPH free radicals is comparable to that of vitamin C; ② Total flavonoids inhibited ROS production in LPS-stimulated RAW264.7 cells (by 52%) without significant cytotoxicity (at concentrations <100 μg / mL). Its antioxidant network involves inhibition of hepatic lipid peroxidation and mitochondrial protection. Regarding analgesia and anti-inflammatory properties, the aqueous extract contained higher concentrations of active ingredients than the ethanol extract: ① Catechins alleviated swelling in acute gouty arthritis by inhibiting MMP-1 expression (by 45%); ② Total flavonoids reduced glutamate content in the spinal dorsal horn (by 32%), improving mechanical allodynia; ③ Components such as angelica lactone reduced the frequency of writhing reactions by up to 60%. The mechanisms involved regulation of inflammatory mediators and maintenance of neurotransmitter homeostasis. Breakthroughs have been made in anti-tumor research: ① Total flavonoids induced apoptosis in HepG2 cells by 28%, arresting the cell cycle at the G0 / G1 phase; ② Luteolin inhibited Hela cell proliferation via the PI3K / Akt pathway (IC50 = 45 μM); and ③ Stigmasterol activated the caspase-3 pro-apoptotic pathway. Molecular docking revealed that the active ingredients have high affinity for tumor targets such as EGFR and VEGFR (binding energy < -8 kcal / mol). Existing research confirms that Millettia repens has achieved clinical translation through a multi-target mechanism of action. However, further analysis of the structure-activity relationship and metabolic pathways of its active ingredients is needed to provide theoretical support for the development of novel formulations.

[0048] The beneficial effects of the traditional Chinese medicine composition provided by the present invention for treating coronary microcirculatory dysfunction and preventing and treating weakness and disease attacks are as follows:

[0049] (1) It replenishes Qi and strengthens the body to restore the ability of Qi to mediate, activates blood circulation and relieves spasms to relieve the symptoms of spasms in the meridians. It is especially suitable for patients with coronary microcirculatory dysfunction due to Qi deficiency and blood stasis.

[0050] (2) Establish a trinity treatment system of "tonifying qi - dredging collaterals - relieving spasm" to effectively reduce the recurrence frequency of angina pectoris, improve myocardial microcirculation perfusion, enhance the quality of life, stabilize the condition, and achieve the goal of whole - process management of "preventing disease progression during illness and recurrence after recovery". BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 Comparison of LVEED levels in rats of each group. Different lowercase letters above the bar graph indicate significant differences between different groups (P < 0.05).

[0052] Figure 2 Comparison of LVESD levels in rats of each group. Different lowercase letters above the bar graph indicate significant differences between different groups (P < 0.05).

[0053] Figure 3 The traditional Chinese medicine composition of the present invention improves cardiac microvascular dysfunction and promotes angiogenesis after myocardial infarction in hyperhomocysteinemia mice.

[0054] (a) FITC - labeled tomato lectin was used to detect myocardial microvascular perfusion 2 weeks after myocardial infarction. Green fluorescence signals were observed under a fluorescence microscope (indicating immunostaining of microvascular endothelial cells). Scale bar: 50 μm (200×).

[0055] (b) Quantitative analysis of tomato lectin staining.

[0056] (c) CD31 immunofluorescence labeling showed cardiac vascular density. Green signals represented blood vessels, and blue were cell nuclei stained with DAPI. Representative confocal microscope images showed the co - localization of CD31 (green) in ventricular tissue. Scale bar: 50 μm (200×).

[0057] (d) Quantitative analysis of CD31. **P < 0.01. n = 6 for each group.

[0058] MI: Myocardial infarction; FITC: Fluorescein isothiocyanate; DAPI: 4',6 - diamidino - 2 - phenylindole. DETAILED DESCRIPTION OF THE INVENTION

[0059] To verify the efficacy of the traditional Chinese medicine composition of the present invention, the inventor carried out a pharmacodynamic experiment study. It should be noted that the drugs selected for the pharmacodynamic experiment study of the present invention are the drugs obtained from the representative formula of the present invention and its preparation method. The experiments and their results related to the drugs obtained from other formulas and preparation methods included in the present invention are not listed one by one here due to space limitations.

[0060] Example 1 A traditional Chinese medicine composition for treating coronary microcirculation diseases

[0061] Astragalus membranaceus 30g, Salvia miltiorrhiza 30g, Pheretima aspergillum 9g, Ligusticum wallichii 12g, Spatholobus suberectus 30g, Cinnamomum cassia 10g, Carthamus tinctorius 12g, Prunus persica 10g.

[0062] Weigh the raw materials by weight, soak them in 1000 mL of pure water in a casserole for 60 minutes, bring to a boil over high heat and then simmer gently for 1.5 hours until the medicinal juice is 400 mL.

[0063] Example 2 A traditional Chinese medicine composition for treating coronary microcirculation diseases

[0064] Astragalus membranaceus 30g, Salvia miltiorrhiza 30g, Pheretima aspergillum 9g, Ligusticum wallichii 12g, Spatholobus suberectus 30g.

[0065] The preparation method refers to Example 1.

[0066] Example 3 A traditional Chinese medicine composition for treating coronary microcirculation diseases

[0067] Astragalus membranaceus 35g, Salvia miltiorrhiza 25g, Pheretima aspergillum 12g, Ligusticum wallichii 9g, Spatholobus suberectus 35g, Cinnamomum cassia 6g, Carthamus tinctorius 9g, Prunus persica 12g. The preparation method refers to Example 1.

[0068] Example 4 A traditional Chinese medicine composition for treating coronary microcirculation diseases

[0069] Astragalus membranaceus 25g, Salvia miltiorrhiza 35g, Pheretima aspergillum 6g, Ligusticum wallichii 15g, Spatholobus suberectus 25g, Cinnamomum cassia 12g, Carthamus tinctorius 15g, Prunus persica 6g. The preparation method refers to Example 1.

[0070] Example 5 A traditional Chinese medicine composition for treating coronary microcirculation diseases

[0071] Astragalus membranaceus 25g, Salvia miltiorrhiza 35g, Pheretima aspergillum 12g, Ligusticum wallichii 9g, Spatholobus suberectus 35g.

[0072] The preparation method refers to Example 1.

[0073] Example 6 A traditional Chinese medicine composition for treating coronary microcirculation diseases

[0074] Astragalus membranaceus 35g, Salvia miltiorrhiza 25g, Pheretima aspergillum 6g, Ligusticum wallichii 15g, Spatholobus suberectus 25g.

[0075] The preparation method refers to Example 1.

[0076] Comparative Example 1

[0077] Salvia miltiorrhiza 30g, Pheretima aspergillum 9g, Ligusticum wallichii 12g, Spatholobus suberectus 30g, Carthamus tinctorius 12g, Prunus persica 10g.

[0078] Compared with Example 1, the difference is that it does not contain Astragalus membranaceus and Cinnamomum cassia, and the other components and dosages remain unchanged.

[0079] The preparation method refers to Example 1.

[0080] Comparative Example 2

[0081] Astragalus membranaceus 30 g, Pheretima aspergillum 9 g, Ligusticum wallichii 12 g, Spatholobus suberectus 30 g, Cinnamomum cassia 10 g, Prunus persica 10 g.

[0082] Compared with Example 1, the difference is that it does not contain Salvia miltiorrhiza and Carthamus tinctorius, and the other components and dosages remain unchanged.

[0083] The preparation method refers to Example 1.

[0084] Comparative Example 3

[0085] Salvia miltiorrhiza 30 g, Pheretima aspergillum 9 g, Ligusticum wallichii 12 g, Spatholobus suberectus 30 g.

[0086] Compared with Example 2, the difference is that it does not contain Astragalus membranaceus, and the other components and dosages remain unchanged.

[0087] The preparation method refers to Example 1.

[0088] Comparative Example 4

[0089] Astragalus membranaceus 35 g, Salvia miltiorrhiza 20 g, Pheretima aspergillum 5 g, Ligusticum wallichii 6 g, Spatholobus suberectus 20 g.

[0090] Compared with Example 2, the difference is that the dosages of the components are changed.

[0091] The preparation method refers to Example 1.

[0092] Study on the effect of the traditional Chinese medicine composition of the present invention on rats with coronary microcirculation disorder

[0093] 1. Experimental method

[0094] Forty-eight male SD rats, with a body weight of 160 - 200 g, were purchased and fed adaptively. After 1 week, 6 rats were randomly selected as the blank control group, and 42 rats were used as the model group.

[0095] The rats in the model group were anesthetized by intraperitoneal injection of sodium pentobarbital at 40 mg / kg, and assisted ventilation was performed using an animal ventilator. The chest cavity was longitudinally opened from the 3rd and 4th intercostal spaces on the left side of the sternum to expose the heart and the root of the aorta. A disposable 1 mL insulin needle was inserted into the left ventricle. When there was blood return, 1 mL / kg of sodium laurate with a concentration of 2 mg / mL was quickly injected, and at the same time, the connection between the ascending aorta and the aortic arch was clamped for 10 s. The chest cavity was closed. After the spontaneous breathing was stable, the tracheal intubation was removed, and a heating pad was used to maintain the body temperature, and the rats were returned to the cage for recovery. Sterile operation was carried out during the operation, and penicillin 800,000 U was intraperitoneally injected for 3 consecutive days after the operation to prevent infection.

[0096] After modeling, the rats were divided into a model control group, an experimental group 1, an experimental group 2, a control group 1, a control group 2, a control group 3, and a control group 4 according to the random number method, with 6 rats in each group.

[0097] The experimental grouping and gavage protocol are shown in Table 1.

[0098] Table 1 Gavage protocol for rats in each group

[0099] Group Dose Gavage dose Blank control group Normal saline - Model control group Normal saline - Experimental group 1 Traditional Chinese medicine composition of Example 1 14.5 g / kg Experimental group 2 Traditional Chinese medicine composition of Example 2 14.5 g / kg Control group 1 Traditional Chinese medicine composition of Comparative Example 1 14.5 g / kg Control group 2 Traditional Chinese medicine composition of Comparative Example 2 14.5 g / kg Control group 3 Traditional Chinese medicine composition of Comparative Example 3 14.5 g / kg Control group 4 Traditional Chinese medicine composition of Comparative Example 4 14.5 g / kg

[0100] Gavage was performed once a day. The dosage was adjusted according to body weight every week, and the administration lasted for 28 days.

[0101] After anesthesia, the chest area of the rats was shaved, coated with coupling agent, and the probe was aligned with the 3rd and 4th intercostal spaces on the left chest of the rats for scanning. After the standard two-dimensional left ventricular long-axis section appeared, the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were continuously measured for 3 different cardiac cycles with an ultrasonic diagnostic instrument, and the mean value was taken.

[0102] 2. Statistical methods

[0103] GraphPad Prism 8.0 software was used for data processing. Measurement data were expressed as mean ± standard deviation , one-way ANOVA was used for inter-group comparison, and LSD-t test was used for pairwise comparison between groups. P < 0.05 was considered statistically significant.

[0104] 3. Experimental results

[0105] 3.1 Effects on cardiac function indexes of rats

[0106] Compared with the blank control group, the LVEDD of rats in the model control group increased.

[0107] Compared with the model control group, the LVEDD of rats in experimental group 1 decreased, and there was a significant difference in reducing LVEDD of rats in experimental group 1 compared with control groups 1-4. The results are shown in Figure 1 .

[0108] Compared with the blank control group, the LVESD of rats in the model control group increased.

[0109] Compared with the model control group, the LVESD of rats in experimental group 1 decreased, and there was a significant difference in reducing LVESD of rats in experimental group 1 compared with control groups 1-4. The results are shown in Figure 2 .

[0110] Changing the components or compatibility ratios of the formula of the present invention will weaken the therapeutic effect of the traditional Chinese medicine composition on the coronary microcirculation disorder model, and the components of the present invention play a synergistic role.

[0111] After administering the traditional Chinese medicine composition of the present invention to rats with a coronary microcirculation disorder model, the LVEDD and LVESD of the rats were significantly reduced, suggesting that the traditional Chinese medicine composition of the present invention can improve the cardiac function of the coronary microcirculation disorder model with remarkable effects.

[0112] In addition, animal experiments have shown that the traditional Chinese medicine composition of the present invention - Buqi Huoxue Decoction can significantly improve the microvascular dysfunction and enhance the angiogenesis ability in mice with hyperhomocysteinemia (HHcy) complicated with myocardial infarction ( Figure 3 ), and promote the recovery of cardiac microvascular function by activating the STAT3 / KCa3.1 / eNOS signaling pathway. The eNOS inhibitor L-NAME can reverse the cardioprotective effect of Buqi Huoxue Decoction, indicating that eNOS plays a key role in the cardiovascular protection mediated by Buqi Huoxue Decoction. In addition, Buqi Huoxue Decoction reduces the cytotoxicity of homocysteine and hypoxia-induced human coronary artery endothelial cells (HCAECs) through this pathway, while inhibiting the STAT3 / KCa3.1 / eNOS pathway will block the protective effect of Buqi Huoxue Decoction.

[0113] Clinical trial part of the traditional Chinese medicine composition of the present invention: Efficacy observation of Buqi Huoxue Decoction in the treatment of qi deficiency and blood stasis syndrome of coronary microcirculation dysfunction diseases

[0114] The beneficial effects of the traditional Chinese medicine composition of the present invention will be further illustrated by the following clinical trial data.

[0115] I. Diagnostic criteria

[0116] (I) Traditional Chinese medicine diagnostic criteria: Refer to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" edited by the State Food and Drug Administration in 2002. The diagnostic criteria for chest pain and heartache with qi deficiency and blood stasis syndrome are as follows:

[0117] Main symptoms: Chest pain, chest tightness;

[0118] Secondary symptoms: Palpitation, shortness of breath, fatigue, and purplish complexion;

[0119] Tongue manifestation: Dark tongue or ecchymosis on the edge, thin white coating;

[0120] Pulse condition: Deep, thready and weak or unsmooth.

[0121] The main symptoms are essential, and at the same time, there are no less than two secondary symptoms. Combined with the tongue and pulse conditions, the diagnosis can be made.

[0122] (II) Western medicine diagnostic criteria

[0123] The diagnostic criteria for coronary microcirculation dysfunction diseases are formulated after referring to and modifying the "2020 EAPCI Expert Consensus on Non-Obstructive Coronary Ischemic Diseases". See Table 2 below for details.

[0124] Table 2 Diagnostic criteria for coronary microcirculation dysfunction diseases

[0125]

[0126] Note: Meeting the diagnostic criteria of items 1 to 4 can be diagnosed as CMVD without obstructive coronary artery disease. FFR is fractional flow reserve; SPECT is single photon emission computed tomography; CMR is cardiac magnetic resonance imaging.

[0127] II. Case Selection Criteria

[0128] (I) Inclusion Criteria

[0129] 1) Age: 18 - 80 years old (including 18 and 80 years old), both male and female are eligible;

[0130] 2) Patients who meet the diagnosis of non - obstructive coronary microvascular disease;

[0131] 3) Patients who meet the diagnosis of chest pain with qi deficiency and blood stasis syndrome;

[0132] 4) Voluntarily participate in this study and sign the informed consent form.

[0133] (II) Exclusion Criteria

[0134] 1) Patients with severe arrhythmia;

[0135] 2) Patients with bleeding tendency, active history of peptic ulcer, history of cerebral hemorrhage or subarachnoid hemorrhage, contraindications to anti - platelet agents and anticoagulant therapy, and unable to receive anticoagulant treatment;

[0136] 3) Patients with a history of severe drug or contrast agent allergy;

[0137] 4) Patients with severe hepatic and renal insufficiency;

[0138] 5) Patients with severe cardiopulmonary insufficiency;

[0139] 6) Patients with neuropsychiatric system diseases;

[0140] 7) Patients with malignant tumors;

[0141] 8) Pregnant or lactating women;

[0142] 9) Patients allergic to the drug components of this study;

[0143] 10) Patients who are currently participating in other clinical studies;

[0144] 11) Patients with other diseases not suitable for participating in clinical studies.

[0145] (III) Exclusion Criteria

[0146] 1) Cases misclassified as eligible but actually not meeting the inclusion criteria; 2) Cases with incomplete data that affect clinical evaluation; 3) Cases using prohibited drugs, making it impossible to evaluate the drug efficacy.

[0147] Treatment of excluded cases: The reasons for exclusion should be stated, and their case report forms should be retained. The final decision on whether to exclude a case will be made by the statistician and the principal investigator at the data review meeting.

[0148] (IV) Criteria for drop - out cases

[0149] 1) Patients who withdraw on their own for any reason;

[0150] 2) The principal investigator deems that the subject is not suitable to continue the study.

[0151] (V) Criteria for terminating the entire trial

[0152] 1) Serious safety events occur during the trial;

[0153] 2) Major mistakes are found in the clinical trial protocol during the trial, or although the protocol is good, serious deviations occur during implementation, making it difficult to evaluate the drug efficacy

[0154] 3) The therapeutic effect of the drug is found to be poor and has no clinical value during the trial, and the trial should be terminated;

[0155] 4) The administrative department in charge revokes the trial.

[0156] Treatment of cases with terminated trial: After the trial is terminated, the subjects should be transferred to normal clinical treatment; the doctors participating in the clinical trial should carefully record the reasons for terminating the trial, and all case report forms should be retained for future reference.

[0157] III. Research content and methods

[0158] (I) Grouping method

[0159] Patients meeting the inclusion criteria are randomly divided into a control group and a test group.

[0160] (II) Treatment method

[0161] 1 Control group

[0162] Symptomatic treatment is carried out according to the diagnosis and treatment plan in the "Chinese Expert Consensus on the Diagnosis and Treatment of Coronary Microvascular Diseases", and conventional Western medicine drugs for anti - angina and vasodilation are given. Oral aspirin enteric - coated tablets, 100 mg / time, 1 time / d; oral clopidogrel bisulfate tablets, 75 mg / time, 1 time / d.

[0163] 2 Test group

[0164] On the basis of the treatment in the control group, the traditional Chinese medicine composition of Example 2 of the present invention is added.

[0165] Qi - supplementing and Blood - harmonizing Decoction: Astragalus membranaceus 30g, Ligusticum wallichii 12g, Salvia miltiorrhiza 30g, Pheretima aspergillum 9g, Spatholobus suberectus 30g. All the above medicines are from the pharmacy of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The traditional Chinese medicines are decocted manually by the personnel with the qualification of traditional Chinese medicine processing in the decocting room. Decoction method: Soak 1000 mL of pure water in a casserole for 1 hour before each decoction. After bringing to a boil over high heat, simmer over low heat for 1.5 hours until the medicinal juice is 400 mL. Mix the two decoctions and divide them into two bags, each bag containing 200 mL. Refrigerate them, and warm them up and take orally half an hour after breakfast and dinner.

[0166] (3) Efficacy evaluation indicators

[0167] (1) Evaluation by Seattle Angina Questionnaire

[0168] The Seattle Angina Questionnaire consists of 19 questions, including 5 dimensions: degree of physical activity limitation, angina stability, angina attack situation, treatment satisfaction degree, and disease cognition degree. For the 5 major items and 19 sub - items, score item by item starting from 1 (indicating the score corresponding to the lowest level of this function), and perform positive transformation on each score, then convert the score into a standard score. The calculation method of the standard score is: subtract the lowest score of each major item from the actual score of each major item, then divide by the difference between the possible highest score and the lowest score of this major item, and finally multiply by 100. Since the 5 major items represent 5 different dimensions of the disease, there is no comparability and no need to sum between each major item. Therefore, each major item has a standard score, but there is no total score for the whole table.

[0169] (2) Evaluation by Duke Activity Status Index

[0170] The Duke Activity Status Index scale is divided into 5 dimensions and 12 items, including personal care, walking, housework, sexual function, and recreation. The answers of the scale are "binary". Each item is determined according to the METs of each activity. During the interview, each tester is asked whether he or she can complete each activity. Add up the affirmative answers, and the total score ranges from 0.0 - 58.2 points, corresponding to the range of 0.00 - 9.89 METs. The higher the score, the better the functional status.

[0171] (3) TCM syndrome integral

[0172] The TCM syndrome scoring refers to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines". The main symptoms are scored as severe (6 points), moderate (4 points), mild (2 points), and none (0 points), and the secondary symptoms are scored as severe (3 points), moderate (2 points), mild (1 point), and none (0 points). The higher the score, the more severe the symptoms.

[0173] Judgment criteria for TCM syndrome efficacy

[0174] Refer to the "Guiding Principles for Clinical Research of New Chinese Medicines" to determine the curative effect of traditional Chinese medicine syndromes by the heart failure integral method: curative effect index (N) = (pre-treatment integral - post-treatment integral) / pre-treatment integral * 100%

[0175] Marked effect: clinical symptoms and signs disappear or are significantly improved, N ≥ 70%;

[0176] Effective: clinical symptoms and signs are all improved, 30% ≤ N < 70%;

[0177] Ineffective: clinical symptoms and signs are not significantly improved, or even aggravated, N < 30%;

[0178] Aggravated: the original symptoms are aggravated after treatment, and the total integral increases by more than 10% compared with that before treatment.

[0179] (IV) Statistical methods

[0180] Use the statistical software SPSS 25.0 for analysis and processing. Measurement data are expressed as mean ± standard deviation (_X ± SD). If they conform to normal distribution and homogeneous variance, t-test is used. If they do not conform to normal distribution, rank sum test is used. Rank sum test is used for rank data, and x 2 test is used for count data. P < 0.05 indicates significant difference, and P < 0.01 indicates very significant difference.

[0181] IV. Curative effect analysis

[0182] (I) General information:

[0183] (1) Gender distribution and comparison

[0184] Among the subjects in the control group, there were 17 males and 13 females; among the subjects in the treatment group with the addition of Buqi Huoxue Decoction, there were 16 males and 14 females. After chi-square test, it is indicated that there is no statistical difference in gender between the two groups of subjects (χ 2 = 0.09, P = 0.956), and they are comparable, as shown in Table 3.

[0185] Table 3 Gender distribution and comparison of the two groups of subjects [case (%)]

[0186]

[0187] (2) Age structure distribution and comparison

[0188] The age of the control group was between 46 years old and 79 years old, and the median was 68 years old; the age of the treatment group with the addition of Buqi Huoxue Decoction was between 44 years old and 80 years old, and the median was 71.5 years old. The data did not conform to normal distribution. After non-parametric test, there was no statistical difference in age between the two groups (Z = 0.101, P = 0.951), and they were comparable, as shown in Table 4.

[0189] Table 4 Age distribution and comparison of two groups of subjects (cases)

[0190]

[0191] (3) Efficacy analysis

[0192] (1) Evaluation by Seattle Angina Questionnaire

[0193] The scores of the Seattle Angina Questionnaire for the two groups are shown in Table 5. It can be seen that before treatment, there were no statistically significant differences in the scores of the Seattle Angina Questionnaire between the two groups of patients in each dimension (P>0.05). When comparing the scores of the Seattle Angina Questionnaire before and after treatment in the experimental group and the control group, there were statistically significant differences in each dimension (P<0.05). When comparing the scores of the Seattle Angina Questionnaire after treatment between the experimental group and the control group, there were statistically significant differences in the degree of physical activity limitation PL, the stability of angina pectoris AS, the frequency of angina pectoris attacks AF, the degree of treatment satisfaction T, and the degree of disease awareness DP (P<0.05).

[0194] This indicates that the efficacy of the Seattle Angina Questionnaire in the experimental group is better than that in the control group.

[0195] Table 5 Seattle Angina Questionnaire for two groups

[0196]

[0197] Note: Compared with before treatment in the same group, ①P<0.05; compared with after treatment in the control group, ②P<0.05.

[0198] (2) Comparison of Duke Activity Status Index scores ( points)

[0199] The Duke Activity Status Index score sheets of the two groups of subjects before and after treatment were compared. It was found that when comparing within the group before and after treatment: the DASI of both groups increased significantly after treatment compared with before treatment (P<0.05); when comparing between groups: there were no significant differences in DASI between the two groups of subjects before treatment (P>0.05), and they were comparable; when comparing the control group and the Buqi Huoxue Decoction group, it was found that the DASI of the subjects increased significantly after treatment, and the difference was statistically significant (P<0.05), as shown in the following table, Table 6.

[0200] Table 6 Comparison of Duke Activity Status Index scores

[0201]

[0202] Note: ①Compared with before treatment in the same group, P<0.05; ②Compared with after treatment in the control group, P<0.05.

[0203] (3) Comparison of TCM syndrome scores

[0204] This study showed that after treatment, the total effective rate of the group treated with the Buqi Huoxue Decoction was 86.67%, significantly higher than 63.33% of the control group, and the difference was statistically significant (χ 2 = 6.533, P < 0.05), as shown in Table 7.

[0205] Table 7 Comparison of the curative effects of TCM syndrome scores between the two groups after treatment

[0206]

[0207] Note: ① Compared with the control group, P < 0.05

[0208] (4) Comparison of TCM symptom scores

[0209] The main TCM symptom scores of the two groups of subjects before and after treatment were compared. Intra-group comparison before and after treatment found that: the symptoms of chest tightness and chest pain in both groups of subjects were significantly reduced after treatment compared with before treatment, and the difference was statistically significant (P < 0.01). Inter-group comparison found that: there was no significant difference in the symptoms of chest tightness and chest pain in the control group before treatment compared with the Buqi Huoxue Decoction group (P > 0.05). The main symptoms of the subjects in the Buqi Huoxue Decoction group were significantly different from those of the control group after treatment (P < 0.05), as shown in Table 8.

[0210] The secondary TCM symptom scores of the two groups of subjects before and after treatment were compared. Intra-group comparison before and after treatment found that: the symptoms of palpitation and shortness of breath in the control group were significantly reduced after treatment compared with before treatment, and the difference was statistically significant (P < 0.05), while the symptoms of fatigue and purple complexion were not significantly reduced, and the difference was not statistically significant (P > 0.05); the symptoms of palpitation, shortness of breath, fatigue, and purple complexion in the Buqi Huoxue Decoction group were all significantly reduced (P < 0.05). Inter-group comparison found that: there was no significant difference in the secondary symptoms of the two groups of subjects before treatment (P > 0.05), and they were comparable; the symptoms of palpitation and purple complexion in the Buqi Huoxue Decoction group were significantly reduced compared with the control group after treatment (P < 0.05), while the symptoms of shortness of breath and fatigue were not significantly different (P > 0.05), as shown in Table 8.

[0211] Table 8 Comparison of TCM symptom scores of the two groups of subjects before and after treatment ( points)

[0212]

[0213]

[0214] From the above data, it can be seen that the traditional Chinese medicine composition of the present invention can effectively relieve the angina symptoms of patients, improve the TCM symptoms of patients, reduce the Seattle Angina Scale score, and at the same time can also improve the Duke Activity Status Index, improve the quality of life of patients, and reduce the occurrence of adverse cardiovascular events.

[0215] The above embodiments are not any formal limitations on the present invention. For those skilled in the art, any modifications, substitutions, etc. made within the scope of the technical solutions of the present invention based on the technical essence of the present invention still fall within the protection scope of the technical solutions of the present invention.

Claims

1. A traditional Chinese medicine composition for treating coronary microcirculation diseases, characterized in that, The traditional Chinese medicine composition comprises raw materials of the following components by weight: 25-35 parts of Astragalus membranaceus, 25-35 parts of Salvia miltiorrhiza, 6-12 parts of Pheretima aspergillum, 9-15 parts of Ligusticum chuanxiong, and 25-35 parts of Spatholobus suberectus.

2. The traditional Chinese medicine composition for treating coronary microcirculation diseases according to claim 1, wherein, The traditional Chinese medicine composition is made from the following components by weight: 30 parts of Astragalus membranaceus, 30 parts of Salvia miltiorrhiza, 9 parts of Pheretima aspergillum, 12 parts of Ligusticum chuanxiong, and 30 parts of Spatholobus suberectus.

3. The traditional Chinese medicine composition for treating coronary microcirculation diseases according to claim 1, wherein, The traditional Chinese medicine composition is made from the following raw materials by weight: 30 parts of Astragalus membranaceus, 30 parts of Salvia miltiorrhiza, 9 parts of Pheretima aspergillum, 12 parts of Ligusticum chuanxiong, 30 parts of Spatholobus suberectus, 10 parts of Cinnamomum cassia, 12 parts of Carthamus tinctorius, and 10 parts of Prunus persica.

4. The traditional Chinese medicine composition for treating coronary microcirculation diseases according to claim 1, wherein, The traditional Chinese medicine composition is made from the following raw materials by weight: 35 parts of Astragalus membranaceus, 25 parts of Salvia miltiorrhiza, 12 parts of Pheretima aspergillum, 9 parts of Ligusticum chuanxiong, 35 parts of Spatholobus suberectus, 6 parts of Cinnamomum cassia, 9 parts of Carthamus tinctorius, and 12 parts of Prunus persica.

5. The preparation method of the traditional Chinese medicine composition for treating coronary microcirculation diseases according to any one of claims 1-4, characterized in that, The preparation method comprises the following steps: Weigh the raw medicinal materials by weight, soak 1000 mL of purified water in a casserole for 60 minutes, bring to a boil over high heat and then simmer gently over low heat for 1.5 hours until the medicinal juice is 400 mL.

6. A traditional Chinese medicine preparation for treating coronary microcirculation diseases, characterized in that, The traditional Chinese medicine preparation is made from the traditional Chinese medicine composition according to any one of claims 1-4 as the raw material.

7. The traditional Chinese medicine preparation for treating coronary microcirculation diseases according to claim 6, characterized in that, The traditional Chinese medicine preparation further comprises pharmaceutically acceptable excipients.

8. The traditional Chinese medicine preparation for treating coronary microcirculation diseases according to claim 6 or 7, characterized in that, The dosage form of the traditional Chinese medicine preparation includes decoction, medicinal broth, granule, capsule, tablet, powder, pill or oral liquid.

9. Use of the traditional Chinese medicine composition for treating coronary microcirculation diseases according to any one of claims 1-4 in the preparation of a drug for preventing or treating coronary microcirculation diseases.

10. Use of the traditional Chinese medicine composition for treating coronary microcirculation diseases according to any one of claims 1-4 in the preparation of a drug for preventing or treating myocardial infarction.

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