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

Abstract

The present application relates to the technical field of Chinese medicine preparation, and particularly relates to a Chinese medicine composition for preventing and treating myocardial ischemia-reperfusion injury, a preparation and a preparation method, the Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15-25 parts of Danshen, 15-25 parts of Huangqi, 10-15 parts of Di Bie Chong, 10-15 parts of Shui Niu Jiao, 10-20 parts of Chi Fuling, 10-20 parts of Che Qian Zi, 10-15 parts of Rengdong Teng, 10-20 parts of Yu Zhu, 10-20 parts of Tian Dou, 10-15 parts of Xi Xing, 10-20 parts of Shi Gao, 10-20 parts of Zhi Mu, 10-15 parts of Xie Bai, 10-15 parts of Lao Gan Cao, and 10-15 parts of Shui Fei Ji Zi. The preparation method comprises the following steps: weighing the above Chinese medicine composition according to the formula amount, then adding water to decoct to obtain Chinese medicine decoction; combining, filtering and concentrating the Chinese medicine decoction to obtain Chinese medicine extract; adding excipients to the Chinese medicine extract, and preparing the preparation by using a conventional preparation method. The combined use of monarch, minister, assistant and guide drugs in the present application can fully relieve myocardial ischemia-reperfusion injury.

Description

TECHNICAL FIELD

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

[0002] Cardiovascular diseases (CVD) are still one of the highest mortality diseases in the world. Blood flow recovery after myocardial ischemia can relieve ischemic symptoms, but can aggravate myocardial injury caused by myocardial ischemia-reperfusion injury (MIRI). The injury of myocardial ischemia is caused by myocardial anoxia, lack of nutrient components, and necrosis or temporary functional impairment of myocardial cells, and most parts will have conduction block lower wall myocardial infarction which can cause complete right bundle branch block. The ischemia-reperfusion injury is caused by the reaction of oxygen in blood HbO2 and the dissolved substances of damaged myocardial cells or necrotic myocardial cells to form oxygen free radicals which have damaging effects on part of the myocardium.

[0003] Oxidative stress, inflammatory response and other mechanisms in the process of myocardial ischemia-reperfusion injury cause serious heart diseases such as heart dysfunction and arrhythmia, and can also cause myocardial cell necrosis. In addition, severe reperfusion injury can affect blood circulation in the lungs, kidneys, liver and brain, and further cause acute lung, kidney, liver and brain injury. At present, the prevention and treatment of myocardial ischemia-reperfusion injury has become a hot research issue. The disease name of "myocardial ischemia-reperfusion injury" is not mentioned in the traditional Chinese medicine classics, and modern Chinese medicine doctors have different views on the pathogenesis of myocardial ischemia-reperfusion injury. Some Chinese medicine theories believe that the pathogenesis of MIRI is coronary microcirculation perfusion disorder, but the treatment effect of traditional Chinese medicine formula designed only for this pathogenesis is not ideal, so it is necessary to develop a new targeted traditional Chinese medicine formula. SUMMARY

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

[0005] Specifically, the present application provides a traditional Chinese medicine composition for preventing and treating myocardial ischemia-reperfusion injury in the first aspect, which is composed of the following raw medicinal materials: Danshen, Huangqi, Dibunose, Shui Niu Jiao, Chizhuyin, Cheqianzi, Rendongteng, Yuzhu, Tian Dou, Xi Xing, Shigao, Zhimu, Xiebai, Laoguanteng, Shuifeijizi.

[0006] As a further illustration of the present application, the traditional Chinese medicine composition is composed of the following raw medicinal materials by weight: Danshen 15-25 parts, Huangqi 15-25 parts, Dibunose 10-15 parts, Shui Niu Jiao 10-15 parts, Chi Fu Ling 10-20 parts, Che Qian Zi 10-20 parts, Rengdong Teng 10-15 parts, Yu Zhu 10-20 parts, Tian Dou 10-20 parts, Xi Xing 10-15 parts, Shi Gao 10-20 parts, Zhi Mu 10-20 parts, Xie Bai 10-15, Lao Gan Cao 10-15 parts, Shui Fei Ji Zi 10-15 parts.

[0007] As a further illustration of the present application, the traditional Chinese medicine composition is composed of the following raw medicinal materials by weight: Danshen 15-25 parts, Huangqi 15-25 parts, Dibunose 10-15 parts, Shui Niu Jiao 10-15 parts, Chi Fu Ling 10-20 parts, Che Qian Zi 10-20 parts, Rengdong Teng 10-15 parts, Yu Zhu 10-20 parts, Tian Dou 10-20 parts, Xi Xing 10-15 parts, Shi Gao 10-20 parts, Zhi Mu 10-20 parts, Xie Bai 10-15, Lao Gan Cao 10-15 parts, Shui Fei Ji Zi 10-15 parts.

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

[0009] As a further illustration of the present application, the dosage form of the medicament 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 application provides a preparation method of an oral preparation for preventing and treating myocardial ischemia-reperfusion injury, comprising the following steps:

[0011] S1, the traditional Chinese medicine composition provided above is weighed according to the formula dosage, and then decocted with water for 3 times at 5-20 times the total weight of the traditional Chinese medicine composition to obtain a traditional Chinese medicine decoction;

[0012] S2, the traditional Chinese medicine decoction obtained by three times of decoction in step S1 is combined, filtered and concentrated to a relative density of 1-1.2 to obtain a traditional Chinese medicine extract;

[0013] S3, a clinically acceptable excipient is added to the traditional Chinese medicine extract obtained in step S2, and a conventional preparation method is used to prepare a clinically acceptable granule, tablet, capsule, powder, decoction or pill.

[0014] As a further illustration of the present application, when preparing a granule, step S3 specifically comprises:

[0015] Step S31, 5-10% of dextrin of the total weight of the traditional Chinese medicine composition is added to the traditional Chinese medicine extract obtained in step S2, and spray drying is performed to obtain a spray dried powder;

[0016] Step S32, to the dry powder obtained in step S3, add 15-20% of the total weight of the granular preparation to be prepared of dextrin and mix evenly to make the final granules.

[0017] Salvia miltiorrhiza: bitter, slightly cold, heart, liver, blood circulation, clear heart, blood swelling, pain, pain, blood, blood, etc. Can be used for treatment of chest and rib pain, rheumatism, symptoms, lumps, sores, swelling, pain, pain, dysmenorrhea, dysmenorrhea, postpartum pain, etc. Treatment of chest pain, symptoms, lumps, etc.

[0018] Radix Astragali: sweet, slightly warm, lung and spleen, spleen and qi, water and swelling, Wei and solid, sores and muscle regeneration; can be used for spleen deficiency caused by fatigue, limbs, postprandial abdominal distension, loose stool, and further development of spleen deficiency caused by qi and organ prolapse. Huangqi enters the lung, has the effect of benefiting Wei and solidifying the surface, and can be used for lung qi deficiency and lung Wei deficiency caused by spontaneous sweating.

[0019] Eupolyphaga: salty, cold, with small poison, mainly liver. It has a strong effect of breaking blood and removing blood stasis in blood circulation, and can be used for treating women with amenorrhea, postpartum abdominal pain, and symptoms.

[0020] Buffalo horn: bitter, cold, heart, liver, heat, blood, detoxification, can be used for high fever, delirium, convulsions, blood heat, hematemesis, carbuncle, sore, sore throat, etc. Also can be used for blood heat and rash and vomiting.

[0021] Red Indian bread: sweet, mild, flat, heart, spleen, bladder, with water, heat, heart, lung, can be used for the treatment of dysuria, edema, leucorrhea, diarrhea.

[0022] Plantago: sweet, cold, liver, kidney, lung and small intestine. It has the effects of clearing heat and diuresis, relieving phlegm and cough, clearing liver and eyes, moistening the intestines and relieving constipation, and can be used for urinary system diseases, external wind and cold or dryness invasion, liver fire, constipation, etc.

[0023] Honeysuckle: cold, sweet. Lung and stomach. It has the effects of clearing heat and resolving toxins, and relieving wind and dredging collaterals, and can be used for treating warm fever, blood dysentery, carbuncle, sore, rheumatic arthritis, joint redness and pain, etc.

[0024] Polygonatum: flat, sweet, lung and stomach. It has the effects of nourishing yin and moistening dryness, nourishing stomach and generating saliva, and can be used for treating dry cough, hemoptysis, hoarseness, and symptoms such as dry mouth, thirst, tongue, and tongue.

[0025] Asparagus : cold in nature, bitter in taste, and belongs to the lung, kidney and stomach channels. It has the effects of nourishing yin and moistening dryness, clearing the lungs and producing saliva, and can be used to treat dry cough, dry throat and other symptoms caused by yin deficiency. Clearing the lungs and reducing fire: can effectively remove dry heat from the lungs, and help relieve cough caused by excessive lung fire.

[0026] Asarum : Asarum is pungent and warm, and belongs to the lung, kidney and heart channels. It has the effects of dispelling wind and cold, relieving pain, and warming the lungs and reducing phlegm. Asarum can be used to treat wind-cold syndrome, headache, nasal congestion, and runny nose caused by wind-cold syndrome.

[0027] Gypsum : sweet and pungent in nature, extremely cold, and belongs to the lung and stomach channels. It has the effects of clearing heat and reducing fire, relieving cough and headache, and can be used to treat external heat disease, high fever, dry cough, stomach fire, headache, and toothache.

[0028] Anemarrhena : bitter and sweet in nature, cold in nature, and belongs to the lung, stomach and kidney channels. It has the effects of clearing heat and reducing fire, nourishing yin and moistening dryness. Its main functions are clearing heat and reducing fire, nourishing yin and moistening dryness, promoting bowel movement, and reducing water and dampness. It is used to treat heat disease, dry cough, bone fever, night sweats, internal heat, dry cough, constipation, yellow phlegm, sore throat, hoarseness, and other symptoms.

[0029] Old Crane Grass : pungent, bitter and neutral in nature, and belongs to the liver, kidney and spleen channels. It can dredge the joints and bones, dispel wind and dampness, and unblock the collaterals, and has the effects of antioxidant, increasing microcirculation, enhancing immunity, and reducing disease infection.

[0030] Allium : pungent and bitter in nature, warm in nature, and enters the heart, lung, stomach and large intestine channels. It has the effects of unblocking and resolving, and can be used to treat chest pain, abdominal distension, diarrhea, sore throat and other symptoms. Modern pharmacological research shows that it also has the effects of lowering blood lipids, anticoagulation, bacteriostasis and analgesia.

[0031] Silybum Seed : bitter and cold in nature, and belongs to the liver and gallbladder channels. It has the effects of anti-inflammatory, lipid-lowering, liver protection, and antioxidant. It can eliminate free radicals in the body, inhibit abnormal immune responses, and help relieve chronic liver disease and liver function damage.

[0032] The core pathogenesis of myocardial ischemia-reperfusion injury in traditional Chinese medicine is coronary microcirculation perfusion disorder, and the application is designed based on the main symptoms of myocardial ischemia-reperfusion injury, such as qi deficiency and blood stasis, internal toxin attacking heart, collateral stasis, oxidative stress and the like, and the above traditional Chinese medicine composition is designed, wherein: Danshen, Huangqi and Dibuchong are the monarch drug, wherein Danshen and Dibuchong are combined to activate blood and remove stasis, and Huangqi is added to benefit heart qi to help blood flow, so as to achieve the effect of fully activating blood and removing stasis; Shui-niujiao, Chizhiling, Cheqianzi and Nindongteng are the ministerial drug, wherein Shui-niujiao and Nindongteng are combined to clear heat, detoxify and cool blood, and Chizhiling and Cheqianzi are added to benefit heart, resist inflammation and benefit damp heat, so as to eliminate the symptoms of attacking heart toxin; Yuzhu, Tian-dong, Xixi, Shigao and Zhimu are the auxiliary drug, wherein Yuzhu and Tian-dong are combined to warm and pass through meridians of pericardium, Xixi is added to run liver qi, promote the transportation of liver meridian, and Shigao and Zhimu are added to clear heat of lung and stomach, and harmonize damp heat of yangming caused by heart yang and blood, so as to achieve the purpose of dredging heart and liver collaterals and harmonizing heart yang and blood; Xiebai, Laogancao and Shuifeijizi are the ministerial drug, which can dredge channels and relieve pain, remove free radicals and resist oxidation, and relieve oxidative stress in the process of reperfusion injury. The combination of each party in the traditional Chinese medicine composition provided by the application can effectively relieve myocardial ischemia-reperfusion injury.

[0033] Compared with the prior art, the application has the following beneficial technical effects:

[0034] The application is provided: Danshen, Huangqi and Dibuchong are the monarch drug, wherein Danshen and Dibuchong are combined to activate blood and remove stasis, and Huangqi is added to benefit heart qi to help blood flow, so as to achieve the effect of fully activating blood and removing stasis; Shui-niujiao, Chizhiling, Cheqianzi and Nindongteng are the ministerial drug, wherein Shui-niujiao and Nindongteng are combined to clear heat, detoxify and cool blood, and Chizhiling and Cheqianzi are added to benefit heart, resist inflammation and benefit damp heat, so as to eliminate the symptoms of attacking heart toxin; Yuzhu, Tian-dong, Xixi, Shigao and Zhimu are the auxiliary drug, wherein Yuzhu and Tian-dong are combined to warm and pass through meridians of pericardium, Xixi is added to run liver qi, promote the transportation of liver meridian, and Shigao and Zhimu are added to clear heat of lung and stomach, and harmonize damp heat of yangming caused by heart yang and blood, so as to achieve the purpose of dredging heart and liver collaterals and harmonizing heart yang and blood; Xiebai, Laogancao and Shuifeijizi are the ministerial drug, which can dredge channels and relieve pain, remove free radicals and resist oxidation, and relieve oxidative stress in the process of reperfusion injury. The combination of each party in the traditional Chinese medicine composition provided by the application can effectively relieve myocardial ischemia-reperfusion injury. BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 The mouse myocardial pathological HE staining results provided by the application are shown in the table, wherein (a) is the staining result of the sham operation group mice, (b) is the staining result of the model group mice, (c) is the staining result of the low-dose group mice in Example 1, (d) is the staining result of the medium-dose group mice in Example 1, and (e) is the staining result of the high-dose group mice in Example 1. DETAILED DESCRIPTION:

[0036] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative effort belong to the scope of protection of the present application.

[0037] Embodiment 1

[0038] A traditional Chinese medicine composition, which is composed of the following raw medicinal materials in parts by weight: 20 parts of Danshen, 20 parts of Huangqi, 13 parts of Di Bie Chong, 13 parts of Shui Niu Jiao, 15 parts of Chi Fu Ling, 15 parts of Che Qian Zi, 13 parts of Ren Dong Teng, 15 parts of Yu Zhu, 15 parts of Tian Dou, 13 parts of Xi Xing, 15 parts of Zhi Mu, 13 parts of Xie Bai, 13 parts of Lao Gan Cao, and 13 parts of Shui Fei Ji Zi.

[0039] Embodiment 2

[0040] A traditional Chinese medicine composition, which is composed of the following raw medicinal materials in parts by weight: 15 parts of Danshen, 15 parts of Huangqi, 10 parts of Di Bie Chong, 10 parts of Shui Niu Jiao, 10 parts of Chi Fu Ling, 10 parts of Che Qian Zi, 10 parts of Ren Dong Teng, 10 parts of Yu Zhu, 10 parts of Tian Dou, 10 parts of Xi Xing, 10 parts of Zhi Mu, 10 parts of Xie Bai, 10 parts of Lao Gan Cao, and 10 parts of Shui Fei Ji Zi.

[0041] Embodiment 3

[0042] A traditional Chinese medicine composition, which is composed of the following raw medicinal materials in parts by weight: 25 parts of Danshen, 25 parts of Huangqi, 15 parts of Di Bie Chong, 15 parts of Shui Niu Jiao, 20 parts of Chi Fu Ling, 20 parts of Che Qian Zi, 15 parts of Ren Dong Teng, 20 parts of Yu Zhu, 20 parts of Tian Dou, 15 parts of Xi Xing, 20 parts of Zhi Mu, 15 parts of Xie Bai, 15 parts of Lao Gan Cao, and 15 parts of Shui Fei Ji Zi.

[0043] Comparative Examples 1-7 each provide a traditional Chinese medicine composition, and the specific raw medicinal materials and their amounts of the traditional Chinese medicine compositions of Comparative Examples 1-7 are shown in Table 1 below.

[0044] Table 1: Raw medicinal materials and their amounts

[0045]

[0046] In the table, (Renshen) and (Danggui) in the comparative examples respectively represent that the traditional Chinese medicine component at the place is replaced by the same amount of Renshen and Danggui, for example, 20 (人参) in Comparative Example 2 represents that 20 parts of Huangqi is replaced by 20 parts of Renshen, 13 (当归)"---" indicates that the corresponding traditional Chinese medicine component is not added in the traditional Chinese medicine composition.

[0047] The raw medicinal materials in the above examples and comparative examples are all commercially available traditional Chinese medicine decoction pieces.

[0048] The traditional Chinese medicine composition provided in the above examples and comparative examples is made into a granular preparation for preventing and treating myocardial ischemia-reperfusion injury, and the specific preparation process is as follows:

[0049] S1, the traditional Chinese medicine composition provided in the above examples and comparative examples is weighed according to the formula amount, and then boiled three times with water 10 times the total weight of the traditional Chinese medicine composition to obtain a traditional Chinese medicine decoction;

[0050] S2, the traditional Chinese medicine decoction obtained by three times of boiling in step S1 is combined, filtered and concentrated to a relative density of 1.1 (60°C) to obtain a traditional Chinese medicine extract;

[0051] S3, 7% of dextrin of the total weight of the traditional Chinese medicine composition is added to the traditional Chinese medicine extract obtained in step S2, and spray dried to obtain a spray dried powder;

[0052] S4, 18% of dextrin of the total weight of the granular preparation to be prepared is added to the dried powder obtained in step S3 and mixed uniformly to prepare the final granular preparation.

[0053] Experimental example:

[0054] 1. Animal experiment:

[0055] 1.1 Experimental drugs: Compound Danshen Granules, Zhuhai Jinhong Pharmaceutical Co., Ltd.; granular preparations prepared from the traditional Chinese medicine formulations provided in the above example 1 and comparative examples 1-7.

[0056] 1.2 Experimental animals: 155 SPF Wistar male mice (body weight: 25±3g) were purchased from Heilongjiang University of Chinese Medicine Experimental Animal Center. After the mice were bought, they were placed in SPF conditions for adaptive test for 3 days before the experiment.

[0057] 1.3 Drug administration and modeling:

[0058] Grouping: 155 SPF male mice were randomly divided into example 1 low dose group (5 μmol / L), example 1 medium dose group (10 μmol / L), example 1 high dose group (20 μmol / L), comparative examples 1-7 high dose group, positive control group, sham operation group and model group, wherein the example 1 low, medium and high dose groups, sham operation group and model group each have 15 mice, and the rest groups each have 10 mice.

[0059] Modeling: After the mice in each group except the sham operation group were injected with anesthesia, the left anterior descending branch of the coronary artery was ligated to prepare a myocardial ischemia-reperfusion injury model (ischemia for 30 min and reperfusion for 2 h) according to the literature method (Yang Liu, Yuan Yajing, Wu Yue. Gastrodia elata Blume saponin I reduces rat myocardial ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway [J]. Chinese Journal of Critical Care Medicine, 2019(6):746-749). The sham operation group was treated in the same way except that the left anterior descending branch of the coronary artery was not ligated.

[0060] Dosing: The dosing of mice in each group was as follows:

[0061] Example 1 low-dose group: 0.25 g / kg of Example 1 traditional Chinese medicine granules were dissolved in 0.4 mL of normal saline and administered by gavage, once a day for 7 consecutive days.

[0062] Example 1 medium-dose group: 0.5 g / kg of Example 1 traditional Chinese medicine granules were dissolved in 0.4 mL of normal saline and administered by gavage, once a day for 7 consecutive days.

[0063] Example 1 high-dose group: 1 g / kg of Example 1 traditional Chinese medicine granules were dissolved in 0.4 mL of normal saline and administered by gavage, once a day for 7 consecutive days.

[0064] Comparative Example 1 to Comparative Example 7 high-dose group: 1 g / kg of traditional Chinese medicine granules of Comparative Example 1 to Comparative Example 7 were dissolved in 0.4 mL of normal saline and administered by gavage, once a day for 7 consecutive days.

[0065] Sham operation group and model group: 0.4 mL of normal saline was administered by gavage, once a day for 7 consecutive days.

[0066] After the last administration, the mice were fasted and anesthetized, and then connected to an electrocardiogram. After tracheal intubation was completed, a respirator was connected. The left coronary artery of the mice was ligated for 30 min, and then reperfused for 120 min.

[0067] 2. Animal experiment results

[0068] 2.1 Detection experiment:

[0069] Five mice each from the sham operation group, model group, and Example 1 low-, medium-, and high-dose groups were randomly selected, the hearts were removed by thoracotomy, the water and blood stains were absorbed with filter paper, and part of the myocardial tissue (thickness about 0.5 cm) was fixed in 4% paraformaldehyde for 72 h. After dehydration, transparency, paraffin embedding, sectioning (thickness 4 μm), HE staining, ethanol dehydration, xylene transparency, and neutral resin mounting, the myocardial pathological changes were observed under a microscope.

[0070] The remaining 130 mice were subjected to the following experiments:

[0071] Echocardiography was used to examine the left ventricular ejection fraction (LVEF), heart rate (HR) and left ventricular systolic pressure (LVSP) of the mice in each group.

[0072] The arterial blood of the mice in each group was taken, and the levels of Mb (myoglobin), CK-MB (creatine kinase isoenzyme MB) and cTnI (cardiac troponin I) were detected by ELISA; the SOD (superoxide dismutase) activity was detected by WST-1 method, and the MDA (malondialdehyde) content was detected by TBA method.

[0073] After 24 hours of reperfusion, the rats were anesthetized with 4% sodium barbital, 2ml of blood was taken from the common carotid artery and placed in an EDTA-2K anticoagulant tube, centrifuged at 3000r / min for 15min, the plasma was separated and stored at-20℃ for testing. The chest was opened, the heart was removed and washed with normal saline, and the myocardial tissue was cut under the ligation line after being frozen in a refrigerator at-20℃ for 30min. The heart was dyed in 0.05% NBT dye solution in a 37℃ incubator for 20min, and then scanned. The infarction rate of the rat heart was calculated by using Image-Pro Plus image analysis processing software, and the infarction rate = infarction area / total area x 100%.

[0074] 2.2 Statistical method:

[0075] The measurement data were analyzed by t test, and the count data were analyzed by χ 2 test. All measurement data were represented by ( ), and the statistical software was SPSS 17.0 version for data processing.

[0076] 2.3 Experimental results:

[0077] 2.3.1 Myocardial tissue changes

[0078] As can be seen from Figure 1 , no obvious inflammatory cell infiltration was observed in the myocardial interstitium of the sham operation group, and the myocardial cells were not swollen. The myocardial structure of the model group mice was disordered, and a large number of inflammatory cells infiltrated the myocardial interstitium. The myocardial structure of the low, medium and high dose groups of Example 1 was obviously improved compared with that of the model group mice, and the inflammatory cell infiltration was slowed down; and whether it was the myocardial structure or the inflammatory cells, the improvement effect was gradually obvious with the increase of the dose, and the myocardial structure and the degree of inflammatory cell infiltration of the mice in the high dose group were close to those of the sham operation group, indicating that the traditional Chinese medicine composition provided by the application can obviously improve the myocardial tissue of the mice.

[0079] 2.3.2 Comparison of the levels of left heart function indexes of the mice in each group

[0080] Table 2 Levels of left heart function indexes of the mice in each group

[0081]

[0082] 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).

[0083] As shown in Table 2, compared with the model group of mice, the left heart 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 application can effectively improve the heart function indexes of mice.

[0084] 2.3.3 Changes in the levels of Mb, CK-MB and cTnI in the serum of mice in each group, see Table 3

[0085] Table 3 Changes in the levels of Mb, CK-MB and cTnI in the serum of mice in each group

[0086]

[0087] 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 .

[0088] As shown in Table 3, compared with the model group of mice, the levels of Mb, CK-MB and cTnI in the serum of mice in the positive group and the low, medium and high dose groups of Example 1 were significantly reduced, indicating that the traditional Chinese medicine composition provided by the application can effectively improve myocardial injury in mice. In addition, compared with the high dose of Comparative Examples 1-7, the improvement effect of the levels of Mb, CK-MB and cTnI in the serum of mice in the high dose group of Example 1 was more obvious, indicating that the therapeutic effect of the traditional Chinese medicine composition provided by the application is superior to that of the traditional Chinese medicine preparation provided by Comparative Examples 1-7.

[0089] 2.3.4 Changes in the SOD activity and MDA content in the plasma of mice in each group, see Table 4.

[0090] Table 4 Changes in the SOD activity and MDA content in the plasma of mice in each group

[0091]

[0092] 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 .

[0093] As can be seen from Table 4, compared with the sham operation group, the SOD activity in the plasma of the model group was greatly reduced, and the MDA content was significantly increased. 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 was greatly increased, and the MDA content was significantly reduced, indicating that the traditional Chinese medicine preparation provided by the positive group, Example 1 and Comparative Examples 1-7 can significantly improve the ability of mice to resist oxidative stress. In addition, compared with the high-dose of Comparative Examples 1-7, the SOD activity and MDA content of the high-dose group of Example 1 improved more obviously, indicating that the therapeutic effect of the traditional Chinese medicine composition provided by the present application is superior to that of the traditional Chinese medicine preparation provided by Comparative Examples 1-7.

[0094] 2.3.5 Changes in myocardial infarction rate of mice in each group, see Table 5.

[0095] Table 5 Changes in myocardial infarction rate of rats in each group

[0096]

[0097] 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 .

[0098] As can be seen from Table 5, compared with the sham operation group, the heart infarction rate of the model group is greatly increased, and compared with the model group, the heart infarction rate of the positive group, the low, medium and high dose groups of Example 1 and the high dose group of Comparative Examples 1-7 is obviously improved, indicating that the traditional Chinese medicine preparation provided by the positive group, Example 1 and Comparative Examples 1-7 can obviously improve the heart infarction of mice. In addition, compared with the high dose of Comparative Examples 1-7, the heart infarction rate of the high dose group of Example 1 is more obviously improved, 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 preparation provided by Comparative Examples 1-7.

[0099] In summary, compared with Comparative Examples 1-7, whether replacing or removing two components of the monarch drug in the present application, Astragalus and Eupolyphaga, and the assistant drug, Asarum and Gypsum, will obviously reduce the effect of the traditional Chinese medicine composition. In addition, removing part of the ministerial drug or auxiliary drug will also reduce the effect of the traditional Chinese medicine composition, so it can be seen that the monarch, minister and assistant in the present application complement each other, and are an indispensable part of the traditional Chinese medicine formula. The absence or replacement of part of the traditional Chinese medicine formula cannot achieve the best effect of improving myocardial injury in mice.

[0100] 3. Clinical experiment

[0101] 3.1 Case source

[0102] The cases all come 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. A stratified randomization method was used to select appropriate segment length, and the patients were divided into a treatment group and a control group at a ratio of 1:1. 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 general data distribution of the patients in the two groups had no significant difference (P>0.05) and were comparable.

[0103] 3.2 Diagnostic criteria

[0104] According to the diagnostic criteria in the "2019 Acute ST Segment Elevation Myocardial Infarction Diagnosis and Treatment Guidelines": (1) symptoms of severe myocardial ischemia lasting more than 20 minutes; (2) electrocardiogram showing ST segment elevation with or without pathological Q wave and dynamic changes, or complete left bundle branch block; (3) acute elevation or dynamic changes of troponin. The above three conditions meet two of them to be diagnosed.

[0105] Inclusion criteria: (1) meet the diagnostic criteria; (2) onset time within 12 h; (3) ST segment elevation of 2 consecutive limb leads ≥0.1 mV or ST segment elevation of chest leads ≥0.2 mV on electrocardiogram; (4) age over 18 years old.

[0106] Exclusion criteria: (1) cardiogenic shock at admission; (2) thrombolytic therapy at admission; (3) combined with gastrointestinal ulcer and other conditions that cannot be treated with anticoagulation and antiplatelet therapy; (4) severe liver and kidney dysfunction; (5) other conditions that are not suitable for percutaneous coronary intervention (PCI).

[0107] 3.3 Treatment method

[0108] The above-mentioned traditional Chinese medicine composition formula provided in Example 1 was used to prepare traditional Chinese medicine bagged granules by the First Affiliated Hospital of Heilongjiang University of Chinese Medicine Pharmaceutical Factory, each bag containing 10 g of crude drug, to constitute the traditional Chinese medicine taking granules in the treatment group.

[0109] Both groups were given PCI treatment. The control group was given compound Danshen granules on this basis, and the treatment group was given the granule preparation prepared by the above-mentioned method on this basis. The dosage of the two groups was 1 bag (containing 10 g of crude drug) per time, 3 times a day, taken before meals, and 6 weeks as a course of treatment.

[0110] 3.4 Efficacy evaluation criteria

[0111] The efficacy of electrocardiogram STR was evaluated. Markedly effective: STR≥70%; effective: 70%>STR≥30%; ineffective: STR<30% electrocardiogram ST segment elevation was basically similar to that before treatment. The total effective rate of electrocardiogram (STR) treatment (%)=(number of markedly effective cases+number of effective cases) / total number of cases x 100%.

[0112] 3.5 Statistical method

[0113] Measurement data were analyzed by t test, and count data were analyzed by χ 2 test. All measurement data were represented by ( ), and statistical software SPSS17.0 was used for data processing.

[0114] 3.6 Experimental results

[0115] Table 6 Comparison of electrocardiogram STR efficacy between the two groups of patients

[0116]

[0117] Note: compared with the control group, * P<0.05.

[0118] As can be seen from Table 6, the total effective rate of the treatment group was 87.5%, and the total effective rate of the control group was 67.5%, and the clinical effect of the treatment group was obviously better than that of the control group (P<0.05), indicating that the effect of the traditional Chinese medicine composition provided in the application is better than that of the traditional compound Danshen granules, and has certain clinical advantages. * P<0.05), indicating that the effect of the traditional Chinese medicine composition provided in the application is better than that of the traditional compound Danshen granules, and has certain clinical advantages.

[0119] It should be noted that in this text, terms such as "including", "containing" 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 inherent to such a process, method, article or device.

[0120] Although the embodiments of the present application 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 the embodiments without departing from the principles and spirit of the present application, and the scope of the present application 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 in parts by weight: 20 parts of Danshen, 20 parts of Huangqi, 13 parts of Eupolyphaga, 13 parts of water buffalo horn, 15 parts of Red Fuling, 15 parts of Plantago seed, 13 parts of Lonicera, 15 parts of Yuzhu, 15 parts of Tian Dong, 13 parts of Coptis, 15 parts of Gypsum Fibrosum, 15 parts of Anemarrhena, 13 parts of Baiji, 13 parts of Old Crane Grass, and 13 parts of Silybum seed.

2. Use of the traditional Chinese medicine composition of claim 1 in the preparation of a medicament for preventing and treating myocardial ischemia-reperfusion injury.

3. Use according to claim 2, characterized in that, The medicament for preventing and treating myocardial ischemia-reperfusion injury is in the form of oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, decoction or pills.

4. A method for preparing an oral preparation for preventing and treating myocardial ischemia-reperfusion injury, characterized by, The method comprises the following steps: S1. The traditional Chinese medicine composition provided in claim 1 is weighed according to the formula dosage, and then boiled three times with water in an amount of 5-20 times the total weight of the traditional Chinese medicine composition to obtain a traditional Chinese medicine decoction; S2. The traditional Chinese medicine decoction obtained by three times of boiling in step S1 is combined, filtered and concentrated to a relative density of 1-1.2 to obtain a traditional Chinese medicine extract; S3. The traditional Chinese medicine extract obtained in step S2 is added with clinically acceptable excipients, and prepared into a clinically acceptable granules, tablets, capsules, powders, decoction or pills by a conventional preparation method.

5. The method for preparing the oral formulation for preventing myocardial ischemia-reperfusion injury as described in claim 4, characterized in that, When preparing granules, step S3 specifically comprises: Step S31. 5-10% of dextrin based on the total weight of the traditional Chinese medicine composition is added to the traditional Chinese medicine extract obtained in step S2, and then spray-dried to obtain a spray-dried powder; Step S32. The spray-dried powder obtained in step S31 is mixed with 15-20% of dextrin based on the total weight of the granules to be prepared, and then prepared into the final granules.

Images