Traditional Chinese medicine composition for preventing and treating myocardial ischemia reperfusion injury, preparation and preparation method

Abstract

The invention relates to the technical field of traditional Chinese medicine preparation, in particular to a traditional Chinese medicine composition for preventing and treating myocardial ischemia reperfusion injury, a preparation and a preparation method. The traditional Chinese medicine composition is prepared from the following raw medicinal materials in parts by weight: 15-25 parts of radix salviae miltiorrhizae, 15-25 parts of radix astragali, 10-15 parts of ground beetles, 10-15 parts of cornu bubali, 10-20 parts of poria cocos, 10-20 parts of semen plantaginis, 10-15 parts of honeysuckle stems, 10-20 parts of radix polygonati officinalis, 10-20 parts of radix asparagi, 10-15 parts of herba asari, 10-20 parts of gypsum, 10-20 parts of rhizoma anemarrhenae, 10-15 parts of allium macrostemon, 10-15 parts of geranium wilfordii and 10-15 parts of silybum marianum seeds. The preparation method comprises the following steps: weighing the traditional Chinese medicine composition according to the formula dosage, and then adding water for decoction to obtain a traditional Chinese medicine decoction; combining the traditional Chinese medicine decoction, filtering and concentrating to obtain traditional Chinese medicine extract; and adding auxiliary materials into the traditional Chinese medicine extract, and preparing by adopting a conventional preparation mode. Combined use of monarch, minister, assistant and guide drugs can fully relieve myocardial ischemia reperfusion injury.

Description

Technical field:

[0001] The present invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition, a preparation and a preparation method for preventing and treating myocardial ischemia-reperfusion injury. Background technology:

[0002] Cardiovascular disease (CVD) remains one of the leading causes of mortality worldwide. Restoration of blood flow after myocardial ischemia can alleviate ischemic symptoms but may exacerbate myocardial damage caused by myocardial ischemia-reperfusion injury (MIRI). Myocardial ischemia damage is caused by myocardial hypoxia and nutrient deprivation, leading to myocardial cell necrosis or temporary functional impairment. Conduction block often occurs in some areas, and inferior myocardial infarction may lead to complete right bundle branch block. IRI is caused by the reaction of oxygen in the blood HbO2 with dissolved substances in damaged or necrotic myocardial cells to form oxygen free radicals, which damage parts of the myocardium.

[0003] Mechanisms such as oxidative stress and inflammatory response during myocardial ischemia-reperfusion injury cause serious heart diseases such as cardiac dysfunction and arrhythmias, and can also cause myocardial cell necrosis. In addition, severe reperfusion injury can affect the blood circulation of the lungs, reduce blood flow to the kidneys, liver, and brain, and then cause acute lung, kidney, liver, and brain damage. Currently, the prevention and treatment of myocardial ischemia-reperfusion injury has become a hot topic in current research. The name of "myocardial ischemia-reperfusion injury" has never been mentioned in traditional Chinese medicine classics. Modern Chinese medicine doctors have different views on the etiology and pathogenesis of myocardial ischemia-reperfusion injury. Some traditional Chinese medicine theories believe that the pathogenesis of MIRI is coronary microcirculatory perfusion disorder. However, the Chinese medicine formulas designed only for this pathogenesis are not ideal for treatment. Therefore, it is necessary to develop new targeted Chinese medicine formulas. Summary of the invention:

[0004] In view of the deficiencies in the prior art, the present invention provides a Chinese medicine composition, a preparation and a preparation method for preventing and treating myocardial ischemia-reperfusion injury.

[0005] Specifically, the first aspect of the present invention provides a traditional Chinese medicine composition for preventing and treating myocardial ischemia-reperfusion injury, which is composed of the following raw medicinal materials: Salvia miltiorrhiza, Astragalus membranaceus, Eupolyphaga sinensis, Buffalo horn, Poria cocos, Plantago seed, Honeysuckle vine, Polygonatum odoratum, Asparagus cochinchinensis, Asarum sieboldii, Gypsum, Anemarrhena asphodeloides, Allium macrostemon, Geranium herb, and Milk thistle seed.

[0006] As a further illustration of the present invention, the traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15-25 parts of Salvia miltiorrhiza, 15-25 parts of Astragalus membranaceus, 10-15 parts of Eupolyphaga sinensis, 10-15 parts of buffalo horn, 10-20 parts of Poria rubra, 10-20 parts of Plantago asiatica, 10-15 parts of Lonicera japonica stem, 10-20 parts of Polygonatum odoratum, 10-20 parts of Asparagus cochinchinensis, 10-15 parts of Asarum sieboldii, 10-20 parts of Gypsum fibrosum, 10-20 parts of Anemarrhena asphodeloides, 10-15 parts of Allium macrostemon, 10-15 parts of Geranium wilfordii, 10-15 parts of Silybum marianum seeds.

[0007] As a further illustration of the present invention, the traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 20 parts of Salvia miltiorrhiza, 20 parts of Astragalus membranaceus, 13 parts of Eupolyphaga sinensis, 13 parts of buffalo horn, 15 parts of Poria rubra, 15 parts of Plantago asiatica, 13 parts of Lonicera japonica stem, 15 parts of Polygonatum odoratum, 15 parts of Asparagus cochinchinensis, 13 parts of Asarum sieboldii, 15 parts of Gypsum fibrosum, 15 parts of Anemarrhena asphodeloides, 13 parts of Allium macrostemon, 13 parts of Geranium wilfordii, 13 parts of Silybum marianum seeds.

[0008] The second aspect of the present invention provides the use of the traditional Chinese medicine composition described in any one of the above in the preparation of a drug for preventing and treating myocardial ischemia-reperfusion injury.

[0009] As a further illustration of the present invention, the dosage form of the drug for preventing and treating myocardial ischemia-reperfusion injury is an oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

[0010] The third aspect of the present invention provides a preparation method of an oral preparation for preventing and treating myocardial ischemia-reperfusion injury, comprising the following steps: S1. Weigh the traditional Chinese medicine composition provided above according to the formula dosage, and then decoct it three times with water 5-20 times the total weight of the traditional Chinese medicine composition to obtain a traditional Chinese medicine decoction. S2. Combine, filter and concentrate the traditional Chinese medicine decoction obtained from the three decoctions in step S1 to a relative density of 1-1.2 to obtain a traditional Chinese medicine extract. S3. Add clinically acceptable excipients to the traditional Chinese medicine extract obtained in step S2, and carry out preparation by a conventional preparation method to prepare any one of clinically acceptable granules, tablets, capsules, powders, decoctions or pills.

[0011] As a further illustration of the present invention, when preparing granules, step S3 specifically includes: Step S31. Add 5-10% of dextrin based on the total weight of the traditional Chinese medicine composition to the traditional Chinese medicine extract obtained in step S2, and spray-dry to obtain a spray-dried powder. Step S32. Add 15-20% of dextrin based on the total weight of the granule preparation to be prepared to the dried powder obtained in step S3 and mix evenly to prepare the final granules.

[0012] Salvia miltiorrhiza: Bitter in taste and slightly cold in nature, it pertains to the heart and liver meridians. It has the effects of promoting blood circulation to remove blood stasis, clearing heart fire, cooling blood to reduce swelling, dredging channels to relieve pain, nourishing blood and calming the mind, etc. It can be used to treat chest and hypochondriac pain, rheumatic arthralgia, mass accumulation, sores and ulcers, traumatic injury, irregular menstruation, amenorrhea and dysmenorrhea, postpartum stasis pain, etc. It is used to treat chest and hypochondriac pain, mass accumulation, etc.

[0013] Astragalus membranaceus: Sweet in taste and slightly warm in nature, it pertains to the lung and spleen meridians. It has the functions of strengthening the spleen and replenishing qi, promoting diuresis to reduce swelling, benefiting the defensive qi and consolidating the exterior, promoting granulation for sore healing; it can be used for lassitude, limb fatigue, abdominal distension after eating, loose stools caused by spleen qi deficiency, and also for middle qi sinking and visceral prolapse caused by the further development of spleen qi deficiency. Entering the lung meridian, it has the effect of benefiting the defensive qi and consolidating the exterior, and can be used for spontaneous sweating caused by lung qi deficiency and insecurity of the lung defense.

[0014] Eupolyphaga seu Steleophaga: Salty in taste and cold in nature, slightly poisonous, mainly pertains to the liver meridian. It has a relatively strong effect of breaking blood stasis and removing blood stasis in terms of promoting blood circulation, and has good effects in treating amenorrhea in women, postpartum abdominal pain, mass accumulation and abdominal mass.

[0015] Buffalo horn: Bitter in taste and cold in nature, it pertains to the heart and liver meridians. It has the effects of clearing heat and cooling blood, calming the mind and detoxifying, and can be used to treat high fever, unconsciousness, convulsions, blood heat bleeding, hematemesis, carbuncles and sores, sore throat, etc. It can also treat macules and epistaxis caused by blood heat running amok.

[0016] Poria rubra: Sweet, light and neutral in nature, it pertains to the heart, spleen and bladder meridians. It has the effects of promoting diuresis, clearing away damp-heat, benefiting the heart and moistening the lungs, and can be used to treat dysuria, edema, gonorrhea, diarrhea.

[0017] Plantago asiatica: Sweet and cold in nature, it pertains to the liver meridian, kidney meridian, lung meridian and small intestine meridian. It has the effects of clearing heat and promoting diuresis, resolving phlegm and relieving cough, clearing the eyes and purging the liver, moistening the intestine and promoting defecation, antioxidant and anti-inflammatory. It has the functions of promoting diuresis and relieving swelling, relieving asthma and resolving dampness, relieving eye diseases, improving constipation, regulating immunity, and is mainly used to treat urinary system diseases, exogenous wind-cold or dryness pathogen invasion, liver fire disturbing upward, constipation, etc.

[0018] Honeysuckle stem: Cold in nature and sweet in taste. It pertains to the lung meridian and stomach meridian. It has the functions of clearing heat and detoxifying, dispersing wind and dredging collaterals, and can be used to treat febrile diseases, heat-toxic dysentery, sores and ulcers, rheumatic heat arthralgia, red, swollen, hot and painful joints, etc.

[0019] Polygonatum odoratum: Neutral in nature and sweet in taste, it pertains to the lung meridian and stomach meridian. It has the effects of nourishing yin and moistening dryness, nourishing the stomach and promoting fluid production, and can be used to treat dry cough with little phlegm, hemoptysis, hoarseness caused by yin deficiency of the lung, and symptoms such as dry tongue and thirst, anorexia despite hunger, red tip of the tongue, less body fluid caused by dryness injuring the stomach yin.

[0020] Asparagus: It is cold in nature and bitter in taste, and belongs to the lung meridian, kidney meridian and stomach meridian. It has the effects of nourishing yin and moistening dryness, clearing the lung and promoting the production of body fluid, and can nourish yin fluid, being suitable for treating dry cough, dry throat and other symptoms caused by yin deficiency. Clearing the lung and reducing fire: It can effectively clear the heat and dryness in the lungs, and is helpful for relieving cough caused by excessive lung fire.

[0021] Asarum: The nature and flavor of asarum are pungent and warm, and it belongs to the lung, kidney and heart meridians. It has the effects of expelling wind and cold, opening orifices and relieving pain, warming the lung and resolving fluid-retention. Because asarum is pungent and warm, it can treat wind-cold cold, headache, nasal congestion and runny nose caused by wind-cold cold.

[0022] Gypsum: Its nature and flavor are sweet, pungent and extremely cold, and it belongs to the lung meridian and stomach meridian. It has the effects of clearing heat and purging fire, removing vexation and relieving cough, and can be used for exogenous febrile diseases, high fever and restlessness, cough due to lung heat, excessive stomach fire, headache and toothache.

[0023] Anemarrhena rhizome: It is bitter, sweet and cold in nature. It belongs to the lung, stomach and kidney meridians. It has the effects of clearing heat and purging fire, nourishing yin and moistening dryness. Its main effects are clearing heat, purging fire and detoxifying, nourishing yin and moistening dryness, promoting defecation, draining water and dampness. It is mainly used to treat fever and restlessness, dry cough due to yin deficiency, steaming bone and tidal fever, night sweats, internal heat and polydipsia, restlessness and irritability, constipation, cough with yellow sticky phlegm, sore throat and hoarseness.

[0024] Geranium herb: Its nature and flavor are pungent, bitter and flat, and it belongs to the liver meridian, kidney meridian and spleen meridian. It can dredge and benefit the muscles and bones, expel wind, remove dampness and dredge collaterals, and has the effects of antioxidant, increasing microcirculation, enhancing immunity and reducing disease infection.

[0025] Allium macrostemon bunge: Its nature and flavor are pungent, bitter and warm in nature, and it enters the heart, lung, stomach and large intestine meridians. It has the effects of promoting yang circulation and dispersing stagnation, promoting qi movement and relieving stagnation, and can be used to treat chest impediment and heart pain, fullness and distension in the epigastric and abdominal regions, tenesmus after diarrhea and dysentery, sore throat and other symptoms. Modern pharmacological research shows that it also has the effects of reducing blood lipid, anticoagulation, bacteriostasis and relieving pain.

[0026] Silybum marianum seeds: Its nature and flavor are bitter and cool, and it belongs to the liver and gallbladder meridians. It has the effects of anti-inflammatory, lipid-lowering, protecting the liver and antioxidant. Specifically, it can eliminate free radicals in the body, inhibit abnormal immune responses, and is beneficial to relieving chronic liver diseases and liver function damage.

[0027] The core pathogenesis of traditional Chinese medicine for myocardial ischemia-reperfusion injury is coronary microcirculation perfusion disorder. On this basis, the present invention combines the main symptoms of myocardial ischemia-reperfusion injury, such as qi deficiency and blood stasis, internal toxin attacking the heart, collateral stasis obstruction, oxidative stress, etc., and designs the above traditional Chinese medicine composition. In the formula: Salvia miltiorrhiza, Astragalus membranaceus, and Eupolyphaga sinensis are the monarch drugs. The combination of Salvia miltiorrhiza and Eupolyphaga sinensis in them can activate blood circulation and remove blood stasis. Coupled with Astragalus membranaceus benefiting the heart qi to assist blood circulation, it can achieve the effect of fully promoting blood circulation and removing blood stasis; Buffalo horn, Polyporus rubescens, Plantago asiatica, and Lonicera japonica stem are the ministerial drugs. The combination of buffalo horn and Lonicera japonica stem in them can clear heat, detoxify, and cool the blood. Coupled with Polyporus rubescens and Plantago asiatica benefiting the heart, anti-inflammatory, and promoting diuresis and clearing damp-heat, it can remove the pathogenic factors of toxin attacking the heart; Polygonatum odoratum, Asparagus cochinchinensis, Asarum sieboldii, Gypsum fibrosum, and Anemarrhena asphodeloides are the adjuvant drugs. The combination of Polygonatum odoratum and Asparagus cochinchinensis in them can warm and dredge the meridians of the pericardium. Together with Asarum sieboldii promoting the flow of liver qi and facilitating the transportation of the liver meridian, and coupled with Gypsum fibrosum and Anemarrhena asphodeloides clearing the heat of the lung and stomach and regulating the damp-heat in the yangming meridian caused by the blood of the heart yang, it can achieve the purpose of dredging the heart and liver collaterals and regulating the blood of the heart yang; Allium macrostemon, Geranium wilfordii, and Silybum marianum seeds are the envoy drugs, which can dredge the meridians and relieve pain, scavenge free radicals, resist oxidation, and relieve the oxidative stress symptoms during the reperfusion injury process. The combination of all parties in the traditional Chinese medicine composition provided by the present invention can effectively relieve myocardial ischemia-reperfusion injury.

[0028] Compared with the prior art, the present invention has the following beneficial technical effects: In the formula of the present invention: Salvia miltiorrhiza, Astragalus membranaceus, and Eupolyphaga sinensis are the monarch drugs. The combination of Salvia miltiorrhiza and Eupolyphaga sinensis in them can activate blood circulation and remove blood stasis. Coupled with Astragalus membranaceus benefiting the heart qi to assist blood circulation, it can achieve the effect of fully promoting blood circulation and removing blood stasis; Buffalo horn, Polyporus rubescens, Plantago asiatica, and Lonicera japonica stem are the ministerial drugs. The combination of buffalo horn and Lonicera japonica stem in them can clear heat, detoxify, and cool the blood. Coupled with Polyporus rubescens and Plantago asiatica benefiting the heart, anti-inflammatory, and promoting diuresis and clearing damp-heat, it can remove the pathogenic factors of toxin attacking the heart; Polygonatum odoratum, Asparagus cochinchinensis, Asarum sieboldii, Gypsum fibrosum, and Anemarrhena asphodeloides are the adjuvant drugs. The combination of Polygonatum odoratum and Asparagus cochinchinensis in them can warm and dredge the meridians of the pericardium. Together with Asarum sieboldii promoting the flow of liver qi and facilitating the transportation of the liver meridian, and coupled with Gypsum fibrosum and Anemarrhena asphodeloides clearing the heat of the lung and stomach and regulating the damp-heat in the yangming meridian caused by the blood of the heart yang, it can achieve the purpose of dredging the heart and liver collaterals and regulating the blood of the heart yang; Allium macrostemon, Geranium wilfordii, and Silybum marianum seeds are the envoy drugs, which can dredge the meridians and relieve pain, scavenge free radicals, resist oxidation, and relieve the oxidative stress symptoms during the reperfusion injury process. The combination of all parties in the traditional Chinese medicine composition provided by the present invention can effectively relieve myocardial ischemia-reperfusion injury. Description of the drawings:

[0029] Figure 1 It is the result of HE staining of the myocardium of mice provided by the present invention. Among them, (a) is the staining result of the sham operation group of mice, (b) is the staining result of the model group of mice, (c) is the staining result of the low-dose group of Example 1 of mice, (d) is the staining result of the medium-dose group of Example 1 of mice, and (e) is the staining result of the high-dose group of Example 1 of mice. Detailed implementation manners:

[0030] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0031] Example 1 A traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 20 parts of Salvia miltiorrhiza, 20 parts of Astragalus membranaceus, 13 parts of Eupolyphaga sinensis, 13 parts of Buffalo horn, 15 parts of Red Poria, 15 parts of Plantago asiatica, 13 parts of Lonicera japonica stem, 15 parts of Polygonatum odoratum, 15 parts of Asparagus cochinchinensis, 13 parts of Asarum sieboldii, 15 parts of Gypsum fibrosum, 15 parts of Anemarrhena asphodeloides, 13 parts of Allium macrostemon, 13 parts of Geranium wilfordii, and 13 parts of Silybum marianum seeds.

[0032] Example 2 A traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15 parts of Salvia miltiorrhiza, 15 parts of Astragalus membranaceus, 10 parts of Eupolyphaga sinensis, 10 parts of Buffalo horn, 10 parts of Red Poria, 10 parts of Plantago asiatica, 10 parts of Lonicera japonica stem, 10 parts of Polygonatum odoratum, 10 parts of Asparagus cochinchinensis, 10 parts of Asarum sieboldii, 10 parts of Gypsum fibrosum, 10 parts of Anemarrhena asphodeloides, 10 parts of Allium macrostemon, 10 parts of Geranium wilfordii, and 10 parts of Silybum marianum seeds.

[0033] Example 3 A traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 25 parts of Salvia miltiorrhiza, 25 parts of Astragalus membranaceus, 15 parts of Eupolyphaga sinensis, 15 parts of Buffalo horn, 20 parts of Red Poria, 20 parts of Plantago asiatica, 15 parts of Lonicera japonica stem, 20 parts of Polygonatum odoratum, 20 parts of Asparagus cochinchinensis, 15 parts of Asarum sieboldii, 20 parts of Gypsum fibrosum, 20 parts of Anemarrhena asphodeloides, 15 parts of Allium macrostemon, 15 parts of Geranium wilfordii, and 15 parts of Silybum marianum seeds.

[0034] Comparative Examples 1-7 all provide a traditional Chinese medicine composition, and the specific raw medicinal materials and their dosages of the traditional Chinese medicine compositions in Comparative Examples 1-7 are shown in Table 1 below.

[0035] Table 1 Raw Medicinal Materials and Their Dosage Table

[0036] In the table, (Ginseng) and (Angelica sinensis) in the comparative examples respectively indicate that the traditional Chinese medicine components at this place are replaced with the same amount of ginseng and angelica sinensis. For example, 20 in Comparative Example 2 (人参) indicates that 20 parts of Astragalus membranaceus are replaced with 20 parts of ginseng, and 13 (当归) indicates that 13 parts of Eupolyphaga sinensis are replaced with 13 parts of angelica sinensis; "-" indicates that the corresponding traditional Chinese medicine component is not added to the traditional Chinese medicine composition.

[0037] The raw medicinal materials in the above examples and comparative examples were all commercially available Chinese herbal pieces.

[0038] The traditional Chinese medicine compositions provided in the above examples and comparative examples were made into granule preparations for preventing and treating myocardial ischemia-reperfusion injury. The specific preparation process was as follows: S1. Weigh the traditional Chinese medicine compositions provided in the above examples and comparative examples according to the formula dosage, and then decoct them three times with 10 times the total weight of the above traditional Chinese medicine compositions in water to obtain a traditional Chinese medicine decoction. S2. Combine, filter and concentrate the traditional Chinese medicine decoctions obtained from the three decoctions in step S1 to a relative density of 1.1 (60 °C) to obtain a traditional Chinese medicine extract. S3. Add 7% of dextrin based on the total weight of the traditional Chinese medicine composition to the traditional Chinese medicine extract obtained in step S2, and spray-dry to obtain a spray-dried powder. S4. Add 18% of dextrin based on the total weight of the granule preparation to be prepared to the dried powder obtained in step S3 and mix evenly to prepare the final granule preparation.

[0039] Experimental example: 1. Animal experiment: 1.1 Experimental drugs: Compound Danshen Granules, Zhuhai Jinhong Pharmaceutical Co., Ltd.; Granule preparations made from the traditional Chinese medicine formulas provided in Example 1 and Comparative Examples 1-7 above.

[0040] 1.2 Experimental animals: 155 SPF-grade male Wistar mice (body weight: 25 ± 3 g) were purchased from the Experimental Animal Center of Heilongjiang University of Chinese Medicine. After the mice were bought, they were placed under SPF-grade conditions and adaptively raised for 3 days before the experiment.

[0041] 1.3 Drug administration and model establishment: Grouping: The 155 SPF-grade male mice were randomly divided into the low-dose group of Example 1 (5 μmol / L), the medium-dose group of Example 1 (10 μmol / L), the high-dose group of Example 1 (20 μmol / L), the high-dose groups of Comparative Examples 1-7, the positive control group, the sham operation group and the model group. Among them, there were 15 mice in each of the low, medium and high-dose groups of Example 1, the sham operation group and the model group, and 10 mice in each of the other groups.

[0042] Modeling: After anesthetizing the mice in each group except the sham operation group, a myocardial ischemia-reperfusion injury model was prepared by ligating the left anterior descending coronary artery with reference to the method in the literature (Yang Liu, Yuan Yajing, Wu Yue. Paridis Saponin I alleviates myocardial ischemia / reperfusion injury in rats by inhibiting the NF-κB signaling pathway [J]. Chinese Critical Care Medicine, 2019(6): 746-749) (ischemia for 30 min, reperfusion for 2 h, with the increase in QRS wave and ST elevation in electrocardiogram as the criteria for successful modeling). The mice in the sham operation group were treated the same except without ligation.

[0043] Drug administration: The drug administration doses for the mice in each group were as follows: Low-dose group of Example 1: 0.25 g / kg of the Chinese medicine granules of Example 1 were dissolved in 0.4 mL of normal saline and administered by gavage once a day for 7 consecutive days.

[0044] Medium-dose group of Example 1: 0.5 g / kg of the Chinese medicine granules of Example 1 were dissolved in 0.4 mL of normal saline and administered by gavage once a day for 7 consecutive days.

[0045] High-dose group of Example 1: 1 g / kg of the Chinese medicine granules of Example 1 were dissolved in 0.4 mL of normal saline and administered by gavage once a day for 7 consecutive days.

[0046] High-dose groups of Comparative Examples 1-7: 1 g / kg of the Chinese medicine granules of Comparative Examples 1-7 were dissolved in 0.4 mL of normal saline and administered by gavage once a day for 7 consecutive days.

[0047] Sham operation group and model group: 0.4 mL of normal saline was administered by gavage once a day for 7 consecutive days.

[0048] After the last drug administration, the mice were fasted and anesthetized, and then connected to an electrocardiogram. After tracheostomy was completed, a ventilator was connected. The left coronary artery of the mice was ligated for 30 min, and then reperfused for 120 min.

[0049] 2. Animal experiment results 2.1 Detection experiment: Randomly select 5 mice from the sham operation group, model group, and low-, medium-, and high-dose groups of Example 1. Open the chest to take out the heart, dry the moisture and bloodstains with filter paper, cut off a part of the myocardial tissue (about 0.5 cm thick) and fix it in 4% paraformaldehyde for 72 h. After dehydration, clearing, paraffin embedding, and sectioning (4 μm thick), HE staining was performed. After dehydration with ethanol, clearing with xylene, and sealing with neutral tree gum slices, the myocardial pathological changes were observed under a microscope.

[0050] The remaining 130 mice were subjected to the following experiments: The left ventricular ejection fraction (LVEF), heart rate (HR), and left ventricular systolic pressure (LVSP) levels of mice in each group were examined by echocardiography.

[0051] Arterial blood was collected from mice in each group, and the levels of Mb (myoglobin), CK-MB (creatine kinase isoenzyme MB), and cTnI (cardiac troponin I) were detected by ELISA; the activity of SOD (superoxide dismutase) was detected by the WST-1 method, and the content of MDA (malondialdehyde) was detected by the TBA method.

[0052] After 24 h of reperfusion, rats were anesthetized with 4% sodium amobarbital, and 2 ml of blood was collected from the common carotid artery and placed in an EDTA-2K anticoagulant tube. The blood was centrifuged at 3000 r / min for 15 min to separate the plasma, which was stored at -20 °C for further testing. The chest cavity was opened, the heart was removed, rinsed thoroughly with physiological saline, frozen in a -20 °C refrigerator for 30 min, and 2-mm myocardial tissue was excised below the ligation line. The tissue was stained in 0.05% NBT staining solution at 37 °C for 20 min and then scanned. The infarct rate of the rat heart was calculated using Image-Pro Plus image analysis software, and the infarct rate = infarct area / total area × 100%.

[0053] 2.2 Statistical methods: The measurement data were analyzed by t-test, and the count data were analyzed by χ 2 test. All measurement data were expressed as ( ), and the data were processed using SPSS 17.0 statistical software.

[0054] 2.3 Experimental results: 2.3.1 Changes in myocardial tissue It can be seen from Figure 1 that there was no obvious infiltration of inflammatory cells in the myocardial interstitium and no swelling of myocardial cells in the sham operation group. The myocardial structure of the model group mice was disordered, and a large number of inflammatory cells infiltrated the myocardial interstitium. The myocardial structures of the low, medium, and high dose groups of Example 1 were significantly improved compared with those of the model group mice, and the infiltration of inflammatory cells was alleviated; moreover, both the myocardial structure and the inflammatory cells showed gradually obvious improvement with the increase in the dosage of the drug. Until the myocardial structure and the degree of infiltration of inflammatory cells in the high dose group mice were close to those of the sham operation group, indicating that the traditional Chinese medicine composition provided by the present invention can significantly improve the myocardial tissue of mice.

[0055] 2.3.2 Comparison of left heart function index levels in each group of mice.

[0056] Table 2 Left heart function index levels in each group of mice

[0057] Note: Compared with the sham operation group, # P < 0.05, ##P < 0.01 and ### P < 0.001; compared with the model group, * P < 0.05, ** P < 0.01 and *** P < 0.001 (n = 10).

[0058] As shown in Table 2, compared with the model group of mice, the left ventricular function indexes of the positive group and the low, medium and high dose groups of Example 1 were significantly increased, indicating that the traditional Chinese medicine composition provided by the present invention can effectively improve the cardiac function indexes of mice.

[0059] 2.3.3 Changes in the levels of Mb, CK-MB and cTnI in the sera of mice in each group are shown in Table 3 Table 3 Changes in the levels of Mb, CK-MB and cTnI in the sera of mice in each group

[0060] Note, compared with the sham operation group, # P < 0.05, ## P < 0.01 and ### P < 0.001; compared with the model group, * P < 0.05, ** P < 0.01 and *** P < 0.001; compared with the high dose group of Example 1, 、 and 。

[0061] As shown in Table 3, compared with the model group of mice, the levels of Mb, CK-MB and cTnI in the sera of mice in the positive group and the low, medium and high dose groups of Example 1 were significantly decreased, indicating that the traditional Chinese medicine composition provided by the present invention can effectively improve myocardial injury in mice. In addition, compared with the high doses of Comparative Examples 1-7, the improvement effect of the levels of Mb, CK-MB and cTnI in the sera of mice in the high dose group of Example 1 of the present application was more obvious, indicating that the curative effect of the traditional Chinese medicine composition provided by the present application is better than that of the traditional Chinese medicine preparations provided by Comparative Examples 1-7.

[0062] 2.3.4 Changes in the SOD activity and MDA content in the plasma of mice in each group are shown in Table 4.

[0063] Table 4 Changes in the SOD activity and MDA content in the plasma of mice in each group

[0064] Note, compared with the sham operation group, # P < 0.05, ## P < 0.01 and ### P < 0.001; compared with the model group, *P < 0.05, ** P < 0.01 and *** P < 0.001; Compared with the high-dose group of Example 1, 、 and 。

[0065] It can be seen from Table 4 that compared with the sham operation group, the SOD activity in the plasma of the model group decreased significantly, and the MDA content increased significantly. Compared with the model group, the SOD activity of the positive group, the low, medium and high-dose groups of Example 1, and the high-dose groups of Comparative Examples 1-7 increased significantly, and the MDA content decreased significantly, indicating that the traditional Chinese medicine preparations provided by the positive group, Example 1 and Comparative Examples 1-7 can significantly improve the antioxidant stress ability of mice. In addition, compared with the high-dose groups of Comparative Examples 1-7, the improvement effects of the SOD activity and MDA content indexes in the high-dose group of Example 1 of the present application are more obvious, indicating that the curative effect of the traditional Chinese medicine composition provided by the present application is better than that of the traditional Chinese medicine preparations provided by Comparative Examples 1-7.

[0066] 2.3.5 Changes in the heart infarction rate of mice in each group are shown in Table 5.

[0067] Table 5 Changes in the heart infarction rate of rats in each group

[0068] Note, compared with the sham operation group, # P < 0.05, ## P < 0.01 and ### P < 0.001; Compared with the model group, * P < 0.05, ** P < 0.01 and *** P < 0.001; Compared with the high-dose group of Example 1, 、 and 。

[0069] It can be seen from Table 5 that compared with the sham operation group, the heart infarction rate of the model group increased significantly. Compared with the model group, the heart infarction rates of the positive group, the low, medium and high-dose groups of Example 1, and the high-dose groups of Comparative Examples 1-7 were significantly improved, indicating that the traditional Chinese medicine preparations provided by the positive group, Example 1 and Comparative Examples 1-7 can significantly improve the heart infarction situation of mice. In addition, compared with the high-dose groups of Comparative Examples 1-7, the improvement effect of the heart infarction rate in the high-dose group of Example 1 of the present application is more obvious, indicating that the curative effect of the traditional Chinese medicine composition provided by the present application is better than that of the traditional Chinese medicine preparations provided by Comparative Examples 1-7.

[0070] In summary, compared with Comparative Examples 1-7, whether replacing or removing the two components of Astragalus membranaceus and Eupolyphaga sinensis in the monarch drug, and Asarum and Gypsum in the adjuvant drug of this application, the efficacy of the traditional Chinese medicine composition will be significantly reduced. In addition, removing some of the ministerial drugs or envoy drugs with synergistic effects will also reduce the efficacy of the traditional Chinese medicine composition. Therefore, it can be seen that the monarch, ministerial, adjuvant, and envoy drugs in this application complement each other and are all indispensable parts of this traditional Chinese medicine formula. Lacking or replacing some of the traditional Chinese medicine prescriptions cannot achieve the best effect of improving myocardial injury in mice.

[0071] 3. Clinical Trials 3.1 Case Source The cases were all from the outpatients and inpatients of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from June 1, 2024 to December 31, 2024. 80 patients diagnosed with acute ST-segment elevation myocardial infarction were collected. Using the stratified randomization method, an appropriate segment length was selected and divided into a treatment group and a control group according to a 1:1 ratio. There were 40 cases in the treatment group, including 25 males and 15 females, with an average age of (53.2 ± 4.4) years. There were 40 cases in the control group, including 26 males and 14 females, with an average age of (51.3 ± 5.1) years. The distribution of the general data of the two groups of patients was not significantly different after statistical test (P > 0.05), and they were comparable.

[0072] 3.2 Diagnostic Criteria Refer to the diagnostic criteria of "2019 Acute ST-segment Elevation Myocardial Infarction Diagnosis and Treatment Guidelines": (1) Severe myocardial ischemia symptoms lasting more than 20 minutes; (2) Electrocardiogram showing ST-segment elevation with or without pathological Q waves and their dynamic changes, or complete left bundle branch block; (3) Acute elevation or dynamic changes of troponin. Two of the above three conditions are required for a definite diagnosis.

[0073] Inclusion criteria for cases: (1) Meeting the above diagnostic criteria; (2) The onset time is within 12 hours; (3) ST-segment elevation in two consecutive limb leads on the electrocardiogram ≥ 0.1 mV or ST-segment elevation in chest leads ≥ 0.2 mV; (4) Age over 18 years old.

[0074] Exclusion criteria for cases: (1) Presence of cardiogenic shock at admission; (2) Having received thrombolytic therapy at admission; (3) Combining with digestive tract ulcers and other conditions that cannot undergo anticoagulant and antiplatelet therapy; (4) Severe liver and kidney function damage; (5) Presence of other situations inappropriate for percutaneous coronary intervention (PCI).

[0075] 3.3 Treatment Methods Take the formula of the traditional Chinese medicine composition provided in the above Example 1, and refer to the production method of traditional Chinese medicine granules in the Chinese Pharmacopoeia (2020 Edition). The traditional Chinese medicine bagged granules are prepared by the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, with each bag containing 10 g of crude drug, constituting the granules for taking traditional Chinese medicine in the treatment group.

[0076] Both groups were given PCI treatment. On this basis, the control group was treated with Compound Danshen Granules in combination, while the treatment group was treated with the granule preparation made by the above method in combination. The dosage for both groups was 3 times a day, taken before meals, 1 bag each time (containing 10 g of crude drug), and 6 weeks was taken as 1 course of treatment.

[0077] 3.4 Efficacy evaluation criteria The electrocardiogram STR efficacy was used for evaluation. Marked effect: STR≥70%; Effective: 70%>STR≥30%; Ineffective: STR<30%, and the elevation of the electrocardiogram ST segment was basically the same as that before treatment. The total effective rate of electrocardiogram (STR) (%) = (number of marked effect cases + number of effective cases) / total number of cases × 100%.

[0078] 3.5 Statistical methods For measurement data, the t-test was used, and for count data, the χ 2 test was used. All measurement data were expressed in ( ), and the statistical software SPSS 17.0 was used for data processing.

[0079] 3.6 Experimental results Table 6 Comparison of electrocardiogram STR efficacy between two groups of patients

[0080] Note: Compared with the control group, * P<0.05.

[0081] It can be seen from Table 6 that the total effective rate of the treatment group was 87.5%, and that of the control group was 67.5%. Moreover, the clinical efficacy of the treatment group was significantly better than that of the control group ( * P<0.05), indicating that the efficacy of the traditional Chinese medicine composition provided in this application is better than that of the traditional Compound Danshen Granules, with certain clinical advantages.

[0082] It should be noted that in this article, terms such as "including", "comprising" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements not only includes those elements, but also includes other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0083] Although embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for preventing and treating myocardial ischemia-reperfusion injury, characterized in that, The traditional Chinese medicine composition is composed of the following raw medicinal materials: Salvia miltiorrhiza, Astragalus membranaceus, Eupolyphaga sinensis, Cornu Bubali, Poria rubra, Plantago asiatica, Lonicera japonica Thunb., Polygonatum odoratum, Asparagus cochinchinensis, Asarum sieboldii, Gypsum fibrosum, Anemarrhena asphodeloides, Allium macrostemon, Geranium wilfordii, Silybum marianum seeds.

2. The traditional Chinese medicine composition for preventing and treating myocardial ischemia-reperfusion injury according to claim 1, wherein The traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15 - 25 parts of Salvia miltiorrhiza, 15 - 25 parts of Astragalus membranaceus, 10 - 15 parts of Eupolyphaga sinensis, 10 - 15 parts of Cornu Bubali, 10 - 20 parts of Poria rubra, 10 - 20 parts of Plantago asiatica, 10 - 15 parts of Lonicera japonica Thunb., 10 - 20 parts of Polygonatum odoratum, 10 - 20 parts of Asparagus cochinchinensis, 10 - 15 parts of Asarum sieboldii, 10 - 20 parts of Gypsum fibrosum, 10 - 20 parts of Anemarrhena asphodeloides, 10 - 15 parts of Allium macrostemon, 10 - 15 parts of Geranium wilfordii, 10 - 15 parts of Silybum marianum seeds.

3. The traditional Chinese medicine composition for preventing and treating myocardial ischemia-reperfusion injury according to claim 1, wherein The traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 20 parts of Salvia miltiorrhiza, 20 parts of Astragalus membranaceus, 13 parts of Eupolyphaga sinensis, 13 parts of Cornu Bubali, 15 parts of Poria rubra, 15 parts of Plantago asiatica, 13 parts of Lonicera japonica Thunb., 15 parts of Polygonatum odoratum, 15 parts of Asparagus cochinchinensis, 13 parts of Asarum sieboldii, 15 parts of Gypsum fibrosum, 15 parts of Anemarrhena asphodeloides, 13 parts of Allium macrostemon, 13 parts of Geranium wilfordii, 13 parts of Silybum marianum seeds.

4. Use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for preventing and treating myocardial ischemia - reperfusion injury.

5. The application according to claim 4, characterized in that, The dosage form of the drug for preventing and treating myocardial ischemia - reperfusion injury is an oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

6. A preparation method of an oral preparation for preventing and treating myocardial ischemia-reperfusion injury, characterized in that, It includes the following steps: S1. Weigh the traditional Chinese medicine composition provided in claim 2 or 3 according to the formula dosage, and then decoct it three times with water 5 - 20 times the total weight of the above traditional Chinese medicine composition to obtain a traditional Chinese medicine decoction. S2. Combine, filter and concentrate the traditional Chinese medicine decoction obtained from the three - time decoction in step S1 to a relative density of 1 - 1.2 to obtain a traditional Chinese medicine extract. S3. Add clinically acceptable excipients to the traditional Chinese medicine extract obtained in step S2, and carry out formulation by conventional formulation methods to prepare any one of clinically acceptable granules, tablets, capsules, powders, decoctions or pills.

7. The preparation method of the oral preparation for preventing and treating myocardial ischemia-reperfusion injury according to claim 6, wherein When preparing granules, step S3 specifically includes: Step S31. Add 5 - 10% of dextrin based on the total weight of the traditional Chinese medicine composition to the traditional Chinese medicine extract obtained in step S2, and spray - dry to obtain a spray - dried powder. Step S32. Add 15 - 20% of dextrin based on the total weight of the granules to be prepared to the dried powder obtained in step S31 and mix evenly to prepare the final granules.

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