Medicine composition for treating coronary heart disease as well as preparation method and application thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to a medicine composition for treating coronary heart disease and a preparation method and application thereof.The medicine composition is prepared from, by mass, 10-15 parts of radix salviae miltiorrhizae, 10-15 parts of pseudo-ginseng, 10-15 parts of the root of kudzu vine and 4-12 parts of saffron crocus. All the medicine raw materials in the formula play a comprehensive synergistic effect to prevent and treat coronary heart disease angina pectoris and cerebrovascular sclerosis, and the traditional Chinese medicine composition is mild in medicine property and does not cause medicine dependence; meanwhile, aiming at syndromes of blood stasis, collateral obstruction and the like, the medicine composition can achieve a good treatment effect of preventing and treating the coronary heart disease by adopting a treatment method of activating blood and stimulating the menstrual flow, and the medicine composition adopts radix salviae miltiorrhizae for composition, and has a remarkable curative effect through in-vitro and clinical verification. And the traditional compound salvia tablets for promoting blood circulation to remove blood stasis are better than the traditional compound salvia tablets for preventing and treating myocardial ischemia, coronary artery obstruction and vascular restenosis after angioplasty.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a pharmaceutical composition for treating coronary heart disease, and a preparation method and application thereof. Background Art

[0002] Coronary heart disease is a common disease that seriously endangers human health. Angina pectoris, one of its five types, is very common. Moreover, patients with coronary heart disease often have cerebral arteriosclerosis, making them a high-risk group for stroke. This type of disease belongs to the category of blood stasis syndrome in traditional Chinese medicine. The clinical treatment of angina pectoris and cerebral arteriosclerosis of coronary heart disease through Chinese medicine formulas for promoting blood circulation and removing blood stasis can relieve symptoms and improve coronary artery blood supply. It can also be used for treatment in the remission period and prevention and treatment of reperfusion injury, as well as prevention of restenosis after interventional treatment, and inhibition of the growth, proliferation and collagen synthesis of scar fibroblasts. For example, the Chinese invention patent with document number CN102362971B discloses a Chinese medicine for treating coronary heart disease. The Chinese medicine is composed of ginseng, ophiopogon japonicus, Panax notoginseng, ligusticum chuanxiong, salvia miltiorrhiza and kudzu root. The formula is concise and has certain efficacy on coronary heart disease, but the overall efficacy of the formula is not significant. Then, the inventor of the patent continued to improve on the above formula and obtained a Chinese medicine preparation for treating coronary heart disease as described in the Chinese invention patent with document number CN104225217A, which is composed of the following weights: The prescription is composed of 20-150 parts of salvia miltiorrhiza, 20-100 parts of kudzu root, 10-100 parts of chuanxiong, 1-50 parts of ophiopogon, 1-50 parts of ginseng, 1-50 parts of panax notoginseng, 1-30 parts of hawthorn, 1-30 parts of trichosanthes, 1-30 parts of allium macrostemon, and 1-30 parts of safflower. The above-mentioned medicines are used together to significantly relieve the symptoms of angina pectoris and improve myocardial ischemia. Although this prescription is more effective than the previous one, its components are complex, the medicinal flavors are various, the chemical components are complex and it is easy to cause waste of traditional Chinese medicine resources, and further improvement is still needed. Summary of the invention

[0003] In order to solve the above technical problems, the purpose of the present invention is to provide a pharmaceutical composition for treating coronary heart disease, and a preparation method and application thereof. The pharmaceutical composition can significantly reduce the formation of restenosis after interventional treatment and reduce the recurrence of angina pectoris, fundamentally achieving the purpose of correcting myocardial and cerebral ischemia and hypoxia. It is safe and reliable to use and can provide a new choice for the clinical treatment of related diseases with traditional Chinese medicine.

[0004] In order to achieve the above technical effects, the present invention adopts the following technical solutions:

[0005] Firstly, the present invention provides a pharmaceutical composition for treating coronary heart disease, comprising the following medicinal raw materials: salvia miltiorrhiza, notoginseng, kudzu root and saffron.

[0006] Furthermore, the pharmaceutical composition comprises the following raw materials in parts by mass: 10-15 parts of Salvia miltiorrhiza, 10-15 parts of Panax notoginseng, 10-15 parts of Pueraria root and 4-12 parts of Saffron.

[0007] Preferably, the pharmaceutical composition is made of the following pharmaceutical raw materials in parts by mass: 10-15 parts of Salvia miltiorrhiza, 10-15 parts of Panax notoginseng, 10-15 parts of Pueraria lobata and 4-12 parts of Saffron.

[0008] Furthermore, the pharmaceutical composition comprises the following medicinal raw materials in parts by mass: 15 parts of Salvia miltiorrhiza, 15 parts of Panax notoginseng, 15 parts of Pueraria lobata and 6 parts of Saffron.

[0009] Preferably, the pharmaceutical composition is made of the following medicinal raw materials in parts by mass: 15 parts of Salvia miltiorrhiza, 15 parts of Panax notoginseng, 15 parts of Pueraria lobata and 6 parts of Saffron.

[0010] Preferably, the pharmaceutical composition further comprises clinically or pharmaceutically acceptable excipients.

[0011] Preferably, the pharmaceutical composition is prepared as any one of capsules, pills, tablets, granules or oral liquid preparations.

[0012] Preferably, the pharmaceutical composition is prepared as any one of a rapid-release preparation or a sustained-release preparation.

[0013] In a second aspect, the present invention further provides a method for preparing a pharmaceutical composition for treating coronary heart disease, comprising the steps of:

[0014] S1: Grind Panax notoginseng into coarse powder, and prepare a paste or nearly paste Panax notoginseng extract by alcohol extraction and water precipitation method;

[0015] S2: extracting salvia miltiorrhiza and saffron with ethanol solution, and separating the ethanol extract and the extraction residue after extraction;

[0016] The extraction residue and Pueraria root are mixed and boiled in water, filtered and a decoction is obtained after boiling, and the decoction is concentrated into a paste-like or nearly paste-like mixed extract;

[0017] S3: further mixing and dispersing the paste or nearly paste-like Panax notoginseng extract obtained in S1 and the paste or nearly paste-like mixed extract obtained in S2, and adding pharmaceutically acceptable excipients to prepare them into a pharmaceutical composition.

[0018] In a third aspect, the present invention also provides a pharmaceutical composition for treating coronary heart disease for use in the preparation of a drug for preventing, treating or improving any aspect of coronary heart disease, angina pectoris, cerebral arteriosclerosis, myocardial infarction, coronary atherosclerotic heart disease, and chronic heart failure. The pharmaceutical composition is the pharmaceutical composition provided in the first aspect above.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The invention provides a pharmaceutical composition for treating coronary heart disease. The pharmaceutical composition uses Chinese medicine as raw materials and is formulated according to the theory of traditional Chinese medicine so that the various raw materials in the prescription can exert a comprehensive synergistic effect to prevent and treat angina pectoris of coronary heart disease and cerebral vascular sclerosis. The pharmaceutical composition has mild medicinal properties and does not cause drug dependence. At the same time, the pharmaceutical composition adopts the method of promoting blood circulation and unblocking menstruation for symptoms such as blood stasis and obstruction of collaterals, so as to achieve a good therapeutic effect of preventing and treating coronary heart disease. In the prescription, purple salvia miltiorrhiza removes blood stasis and relieves pain, promotes blood circulation and unblocks menstruation; Panax notoginseng unblocks blood vessels and activates collaterals, promotes blood circulation and removes blood stasis; Pueraria root relieves spasm and relieves pain, activates collaterals and unblocks menstruation; saffron promotes blood circulation and unblocks menstruation, removes blood stasis and relieves pain. The combination of the drugs can further enhance the effects of promoting blood circulation and unblocking collaterals, and the effects of one dissolving and one dispersing can effectively relieve the symptoms of angina pectoris. The pharmaceutical composition adopts purple salvia miltiorrhiza to formulate the prescription. It has been verified in vitro and clinically that the drug composition is superior to the traditional compound salvia miltiorrhiza tablet, a blood circulation and stasis-removing drug, in preventing and treating myocardial ischemia, coronary artery obstruction and restenosis after angioplasty. DETAILED DESCRIPTION

[0021] The following examples are only used to more clearly illustrate the technical solutions of the present invention, and are therefore only used as examples, and cannot be used to limit the scope of protection of the present invention. The specific embodiments listed in the present invention are only examples of the present invention, and the present invention is not limited to the specific embodiments described below. For those skilled in the art, any equivalent modifications and substitutions made to the embodiments described below are also within the scope of the present invention. Therefore, the equalization changes and modifications made without departing from the spirit and scope of the present invention should be included in the scope of the present invention.

[0022] In order to better illustrate the present invention, numerous specific details are given in the specific embodiments below. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In other embodiments, methods, means, equipment and steps well known to those skilled in the art are not described in detail to highlight the gist of the present invention. And those who do not specify specific conditions in the embodiments are carried out according to conventional conditions or conditions recommended by the manufacturer. Those who do not specify the manufacturer of all reagents or instruments are conventional products that can be purchased commercially.

[0023] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. Unless otherwise specified, the units used in this specification are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0024] It should be noted that the purple salvia used in the present invention is the dried root of Yunnan sage of the Labiatae family, a Yi medicine, bitter, slightly cold, and enters the heart and liver meridians; Panax notoginseng is the dried root of Panax notoginseng (Burk.) FHChen of the Araliaceae family, sweet, slightly bitter, warm, enters the liver and stomach meridians, and has the effects of dispersing blood stasis, stopping bleeding, and relieving swelling and pain; Pueraria root is the dried root of Pueraria lobata of the Leguminosae family, commonly known as Pueraria lobata, sweet, pungent, cool, enters the spleen, stomach, and lung meridians; Saffron is the upper part and stigma of the crocus style of the Iridaceae family, sweet, flat, enters the heart and liver meridians.

[0025] Example 1

[0026] This embodiment provides a pharmaceutical composition for treating coronary heart disease and a preparation method thereof. The pharmaceutical composition is prepared from the following pharmaceutical raw materials in parts by weight:

[0027] Red salvia miltiorrhiza 15g, Panax notoginseng 15g, Pueraria root 15g and saffron 9g;

[0028] The above-mentioned pharmaceutical composition is prepared according to the following method:

[0029] S1: Grind Panax notoginseng into coarse powder, extract it with 6 times the amount of 70% ethanol under reflux for 3 times, each time for 2 hours, combine the ethanol extracts and concentrate them to a paste, add 1 times the amount of water for water precipitation, filter, take the filtrate and apply it to a macroporous resin column, elute it with 20 times 80% ethanol, concentrate the eluate, and obtain a paste or nearly paste Panax notoginseng extract;

[0030] S2: Extract purple salvia miltiorrhiza and saffron with 10 times the amount of 70% ethanol for 2 times, each time for 1 hour, and perform solid-liquid separation after extraction to obtain ethanol extract for standby use, and obtain purple salvia miltiorrhiza and saffron extract residues;

[0031] The above-mentioned salvia miltiorrhiza and saffron extract residues and kudzu root are decocted twice with about 10 times the amount of water, each time for 2 hours, and filtered to obtain a decoction after decocting, and the decoction is concentrated into a paste or nearly paste mixed extract;

[0032] S3: Combine the paste or nearly paste-like Panax notoginseng extract obtained in S1 and the paste or nearly paste-like mixed extract obtained in S2, add conventional excipients and prepare them into capsules according to conventional processes.

[0033] Example 2

[0034] This embodiment provides a pharmaceutical composition for treating coronary heart disease and a preparation method thereof. The pharmaceutical composition is prepared from the following pharmaceutical raw materials in parts by weight:

[0035] Red salvia miltiorrhiza 15g, Panax notoginseng 10g, Pueraria root 15g and saffron 6g;

[0036] The above-mentioned pharmaceutical composition is prepared according to the following method:

[0037] S1: Grind Panax notoginseng into coarse powder, extract with 5 times the volume of 70% ethanol under reflux for 3 times, 2 hours each time, combine the ethanol extracts and concentrate them to a paste, add 1 times the volume of water of the product for water precipitation, filter, take the filtrate and apply it to a macroporous resin column, elute with 20 times the volume of 80% ethanol, concentrate the eluate, and obtain a paste or nearly paste Panax notoginseng extract;

[0038] S2: Extract purple salvia miltiorrhiza and saffron with 10 times the amount of 70% ethanol for 2 times, each time for 1 hour, and perform solid-liquid separation after extraction to obtain ethanol extract for standby use, and obtain purple salvia miltiorrhiza and saffron extract residues;

[0039] The above-mentioned salvia miltiorrhiza and saffron extract residues and kudzu root are decocted twice with about 10 times the amount of water, each time for 2 hours, and filtered to obtain a decoction after decocting, and the decoction is precipitated with 70% ethanol, and the supernatant is taken and concentrated into a paste or nearly paste mixed extract;

[0040] S3: Combine the pasty or nearly pasty Panax notoginseng extract obtained in S1 and the pasty or nearly pasty mixed extract obtained in S2, add conventional excipients and prepare tablets according to conventional processes.

[0041] Example 3

[0042] This embodiment provides a pharmaceutical composition for treating coronary heart disease and a preparation method thereof. The pharmaceutical composition is prepared from the following pharmaceutical raw materials in parts by weight:

[0043] Red salvia miltiorrhiza 10g, Panax notoginseng 10g, Pueraria root 10g and saffron 7g;

[0044] The above-mentioned pharmaceutical composition is prepared according to the following method:

[0045] S1: Grind Panax notoginseng into coarse powder, extract with 5 times the volume of 70% ethanol under reflux for 3 times, 2 hours each time, combine the ethanol extracts and concentrate them to a paste, add 1 times the volume of water of the product for water precipitation, filter, take the filtrate and apply it to a macroporous resin column, elute with 20 times the volume of 80% ethanol, concentrate the eluate, and obtain a paste or nearly paste Panax notoginseng extract;

[0046] S2: Extract purple salvia miltiorrhiza and saffron with 10 times the amount of 70% ethanol for 2 times, each time for 1 hour, and perform solid-liquid separation after extraction to obtain ethanol extract for standby use, and obtain purple salvia miltiorrhiza and saffron extract residues;

[0047] The above-mentioned salvia miltiorrhiza and saffron extract residues and kudzu root are decocted twice with about 10 times the amount of water, each time for 2 hours, and filtered to obtain a decoction after decocting, and the decoction is precipitated with 70% ethanol, and the supernatant is taken and concentrated into a paste or nearly paste mixed extract;

[0048] S3: Combine the pasty or nearly pasty Panax notoginseng extract obtained in S1 and the pasty or nearly pasty mixed extract obtained in S2, add conventional excipients and prepare drop pills according to conventional processes.

[0049] Example 4

[0050] This example is an in vitro test example of the pharmaceutical composition provided in the above-mentioned Example 1, specifically, comprising:

[0051] 4.1 Effect of the pharmaceutical composition of the present invention on the survival rate of H9c2 cells damaged by hypoxia

[0052] 4.1.1 Experimental group settings

[0053] This embodiment sets up a blank control group, an experimental group, a positive control group 1, a positive control group 2, a positive control group 3 and a positive control group 4, specifically:

[0054] The blank control group was treated with normal saline;

[0055] The experimental group was treated with the pharmaceutical composition prepared in Example 1;

[0056] The positive control group 1 was prepared with the following drug raw materials: 15 g of salvia miltiorrhiza, 15 g of Panax notoginseng, 15 g of Pueraria root and 9 g of saffron. The specific preparation method was as described in Example 1. The product was recorded as positive control drug composition 1.

[0057] Positive control group 2 uses the drug raw materials in Example 1 and is directly prepared by water decoction, and then concentrated after water decoction to obtain positive control drug composition 2;

[0058] The positive control group 3 was prepared with the following drug raw materials: 15 g of Panax notoginseng, 15 g of Pueraria root and 9 g of Saffron. The specific preparation method was as described in Example 1. The product was recorded as positive control drug composition 3.

[0059] The positive control group 4 was prepared with the following raw materials: 15 g of Salvia miltiorrhiza, 15 g of Panax notoginseng, and 15 g of Pueraria root. The specific preparation method was as described in Example 1. The product was recorded as positive control pharmaceutical composition 3.

[0060] 4.1.2 Experimental methods

[0061] H9c2 cells in the logarithmic growth phase were cultured in DMEM containing 10% calf serum and 1% penicillin-streptomycin double antibody solution, and the cell concentration was adjusted to 5×10 4 / mL, inoculated into 96-well culture plates, replaced with new sugar-free and serum-free fresh culture medium after about 24 hours, and added with test samples of each group respectively, and placed in an anaerobic workstation for hypoxia damage for 1 hour (except the blank control group). After being taken out, sugar and serum were added and cultured for another 24 hours. After 24 hours, the cell survival rate of each well was detected by MTT staining method. Three replicates were set for each group of experiments.

[0062] 4.1.3 Experimental Results

[0063] According to the test results of the MTT method, the effects of each drug composition on the survival rate of H9c2 cells injured by ischemia-reperfusion were calculated and the results are shown in Table 1.

[0064] Table 1 Effects of test samples on the survival rate of H9c2 cells with ischemia-reperfusion injury

[0065]

[0066]

[0067] The above experimental results show that compared with the model group, different concentrations of the pharmaceutical composition for preventing and treating coronary heart disease prepared in Example 1 can significantly increase the survival rate of myocardial cells after treatment, indicating that the composition of the present invention can effectively protect H9c2 myocardial cells from damage caused by hypoxia / reoxygenation, and can be used as an active ingredient for treating any aspect of myocardial infarction, coronary atherosclerotic heart disease, and chronic heart failure.

[0068] Compared with positive control group 1, positive control group 2, positive control group 3 and positive control group 4, the pharmaceutical composition for preventing and treating coronary heart disease prepared in Example 1 acts on H9c2 cardiomyocytes, and the cell survival rate is significantly higher. It can be seen that the composition of the present invention is significantly superior to the pharmaceutical composition prepared by the Danshen prescription and the traditional water decoction process.

[0069] 4.2 Effect of the pharmaceutical composition of the present invention on whole blood viscosity and plasma viscosity in rats with qi stagnation and blood stasis

[0070] 4.2.1 Modeling of Qi stagnation and blood stasis syndrome

[0071] This experiment set up a blank control group, a model group, an experimental group, a positive control group 1, a positive control group 2, a positive control group 3 and a positive control group 4. The treatment methods of each group are as follows:

[0072] Blank control group: no modeling steps were performed and the mice were treated with normal saline;

[0073] Model group: modeling and treatment with normal saline;

[0074] Experimental group: the pharmaceutical composition prepared in Example 1 was administered;

[0075] Positive control group 1: prepared with reference to the positive control pharmaceutical composition 1 in 4.1.1;

[0076] Positive control group 2: prepared with reference to the positive control pharmaceutical composition 2 in 4.1.1;

[0077] Positive control group 3: prepared with reference to the positive control pharmaceutical composition 3 in 4.1.1;

[0078] Positive control group 4: prepared with reference to the positive control pharmaceutical composition 3 in 4.1.1.

[0079] 4.2.2 Experimental methods

[0080] Rats were randomly divided into blank control group, model group, experimental group, positive control group 1, positive control group 2, positive control group 3 and positive control group 4, 8 rats in each group, half of them were male and half were female. Rats in blank control group and model group were given normal saline by gavage, and rats in experimental group, positive control group 1, positive control group 2, positive control group 3 and positive control group 4 were given corresponding drug solution (all prepared by dissolving with normal saline as solvent) by gavage once a day for 4 weeks.

[0081] Starting from the 8th day of drug administration, except for the blank control group, the rats in the other groups were subjected to electrical stimulation to establish models. The specific method was as follows:

[0082] After daily medication, acupuncture needles were inserted under the ears of each group of rats, and then connected to the G-6805 electroacupuncture instrument with wires. Intermittent waves were used, and the voltage was 30-35V, and the power was turned on for 0.3s every 2s, and the stimulation was 5min every 2h, 5 times a day, for 3 consecutive weeks. The model of Qi stagnation and blood stasis syndrome was established. 24 hours after the model was established, blood was collected from the abdominal artery of the rats and sent for blood rheology detection to confirm whether the model was successful. The specific method was as follows:

[0083] The rats in each group were fasted for 14 h and anesthetized with 25% urethane (4 ml / kg -1 ), to measure microcirculation indexes, blood flow velocity and blood rheology indexes.

[0084] 4.2.3 Experimental Results

[0085] Microcirculation index blood flow rate determination: Anesthetized rats were cut open, the blind mesentery was gently pulled out and placed on a plexiglass observation platform, and Tyrode's solution (constant temperature 37°C) was dripped into it. The BI-2000 medical image analysis system was used to select blood vessels with similar diameters under a microscope to measure the blood flow rate. The experimental results are shown in Table 2:

[0086] Table 2 Effects of electrical stimulation modeling on mesenteric microcirculation indices of rats in each group

[0087]

[0088] The above experimental results show that compared with the blank control group, the mesenteric blood flow velocity of each group after electrical stimulation decreased, and compared with the model group, the mesenteric blood flow velocity of the rats in the positive control group 1, the positive control group 2, the positive control group 3, the positive control group 4 and the experimental group was significantly increased; compared with the positive control group 1, the positive control group 2, the positive control group 3 and the positive control group 4, the mesenteric venous blood flow velocity and the arterial blood flow velocity of the rats in the experimental group were faster. It can be seen that the pharmaceutical composition of the present invention is significantly superior to the Danshen prescription, the traditional water decoction preparation and the prescription preparation without Danshen / purple Danshen.

[0089] Determination of blood rheology indexes: Blood was collected from the abdominal aorta, 4 ml of blood was collected in a heparin sodium vacuum blood collection tube, and the South990btt fully automatic blood viscosity dynamic analyzer was used to detect blood rheology related indexes. The experimental results are shown in Table 3:

[0090] Table 3 Effects of electrical stimulation on blood rheology indexes of rats in each group

[0091]

[0092] The above experimental results show that compared with the blank control group, the blood rheology indicators of each group after electrical stimulation were increased; compared with the model group, the blood rheology indicators of the positive control group 1, the positive control group 2, the positive control group 3, the positive control group 4 and the experimental group were significantly changed, specifically manifested as an increase in whole blood viscosity and plasma viscosity; compared with the positive control group 1, the positive control group 2, the positive control group 3 and the positive control group 4, the whole blood high, medium and low shear viscosities and plasma viscosity in the blood rheology indicators of the experimental group administered with the pharmaceutical composition prepared in Example 1 were significantly lower, which shows that the composition of the present invention is significantly better than the other groups.

[0093] 4.3 Effect of the pharmaceutical composition of the present invention on thrombosis in rats

[0094] In this embodiment, a model group, an experimental group and a positive control group 1 are set to conduct experiments, specifically:

[0095] 4.3.1 Experimental sample preparation:

[0096] Model group: administration of normal saline;

[0097] Experimental group low-dose group: according to the Danshen prescription (Danshen 15g, Panax notoginseng 15g, Pueraria lobata 15g and Crocus 9g), the preparation prepared by the method of Example 1 was administered at a dosage of 10g / kg;

[0098] Experimental group: medium dose group: the preparation prepared by the method of Example 1 according to the prescription of Example 1 (15 g of Salvia miltiorrhiza, 15 g of Panax notoginseng, 15 g of Pueraria root and 9 g of Crocus sativus), the dosage was 20 g / kg;

[0099] Experimental group high dose group: according to the prescription of Example 1 (15g of Salvia miltiorrhiza, 15g of Panax notoginseng, 15g of Pueraria root and 9g of Crocus sativus), the preparation prepared by the method of Example 1 was administered at a dosage of 40g / kg;

[0100] Positive control group 1: prepared with reference to the positive control pharmaceutical composition 1 in 4.1.1.

[0101] 4.3.2 Experimental methods and results

[0102] Animal modeling: Rats were randomly divided into model group, positive control group 1, positive control group 2, experimental group low-dose group, experimental group medium-dose group and experimental group high-dose group. There were 8 rats in each group, half of them were male and half were female. According to the groups, the rats in each group were gavaged with the corresponding drug solution (all dissolved in physiological saline as the solvent) once a day for 21 days and weighed twice a week.

[0103] After the last administration, the rats in each group were anesthetized with isoflurane, and then quickly fixed on the small animal thrombosis instrument, the common carotid artery was isolated, and a direct current of 0.8 mA was used to stimulate for 1 minute, and the thrombosis-related conditions within 3 minutes were detected. The detection indicators were the maximum occlusion rate, the time point at which the maximum occlusion rate was reached, and the average occlusion rate after stimulation. The experimental results are shown in Table 4:

[0104] Table 4 Effect of the pharmaceutical composition of the present invention on thrombosis

[0105]

[0106] The above experimental results show that the four groups of rats did not die after continuous administration for 21 days, and their weight gain was normal. Compared with the model group, each control group significantly reduced the maximum blockage rate and average blockage rate of the blood vessels after stimulation (P < 0.05), indicating that the pharmaceutical composition of the present invention has an inhibitory effect on thrombosis in rats; compared with the positive control group 1, the average blockage rate, maximum blockage rate, maximum blockage time, etc. of the high, medium and low dose groups of the experimental group prepared by this embodiment 1 were significantly smaller.

[0107] 4.4 Clinical effect verification

[0108] 4.4.1 Experimental methods

[0109] A retrospective study was conducted using the method of follow-up and data collection, and 256 patients with coronary heart disease who visited the hospital consecutively from 2019 to 2022 were studied, including 152 males and 104 females, aged 52-72 years old, with a treatment duration of 12-18 months and an average treatment duration of 16±0.4 months.

[0110] According to different treatment schemes, the patients were divided into a control group (administered with compound danshen tablets, the drug raw materials consisted of danshen, borneol and notoginseng) with 120 cases (72 males and 48 females) and an observation group (administered with the drug composition capsules prepared in Example 1) with 136 cases (82 males and 56 females).

[0111] 4.4.2 Observation methods and clinical results

[0112] (1) Diagnostic criteria

[0113] a. Formulated with reference to the "Guiding Principles for Clinical Research of New Chinese Medicines" and "Standards for Diagnosis and Efficacy of Heart Diseases and Regulations on Medication Use in Traditional Chinese Medicine";

[0114] b. TCM syndrome diagnostic criteria:

[0115] Main symptoms: chest tightness, stabbing or dull pain in the heart and chest, shortness of breath, fatigue, fullness in the chest and diaphragm, palpitations, sticky mouth with phlegm;

[0116] Secondary symptoms: heavy head and body fatigue, sticky and tasteless mouth, poor appetite and abdominal distension, fatigue and spontaneous sweating, dark complexion, nausea and vomiting, dry hair and skin, aversion to cold, etc.

[0117] Tongue: Pale or dark purple tongue, with petechiae and ecchymoses on the sides, dark purple and tortuous veins under the tongue, and greasy or white and slippery tongue coating;

[0118] Pulse condition: The pulse is sluggish, or knotted and intermittent, or stringy and sluggish, or the pulse is thin and smooth, or deep and thin.

[0119] (2) Criteria for determining efficacy

[0120] a. Clinical symptom efficacy criteria:

[0121] Marked effect: Major symptoms such as angina pectoris disappeared or reached the mark of marked effect, and the electrocardiogram returned to normal or became approximately normal.

[0122] Effective: Major symptoms such as angina pectoris are alleviated or reach effective standards, and electrocardiogram improvement reaches effective standards.

[0123] Ineffective: There was no improvement in the main symptoms such as angina pectoris, and the electrocardiogram was basically the same as before treatment.

[0124] In comprehensive diagnosis and treatment judgment, if the efficacy of major symptoms such as angina pectoris is inconsistent with the efficacy of electrocardiogram, the lower efficacy result shall be regarded as the comprehensive efficacy.

[0125] b. TCM syndrome score evaluation criteria for efficacy:

[0126] Therapeutic index (n) = (total score before treatment - total score after treatment) / total score before treatment × 100%

[0127] Markedly effective: clinical symptoms and signs are significantly improved, and the syndrome score is reduced by ≥70%;

[0128] Effective: Clinical symptoms and signs have improved, and the syndrome score has decreased by ≥30%

[0129] Ineffective: clinical symptoms and signs have no significant improvement or even worsen, and the symptom score decreases by <30%;

[0130] (3) Results analysis

[0131] The efficacy of the observation group and the control group was compared before and after treatment. The results are shown in Tables 5 to 7:

[0132] Table 5 Comparison of electrocardiogram efficacy of patients with angina pectoris after treatment

[0133]

[0134] The results show that the electrocardiogram efficacy of the drug of the present invention is significantly better than that of the control group of drugs in patients with angina pectoris due to coronary heart disease after treatment.

[0135] Table 6 Comparison of adverse reactions after treatment in patients with angina pectoris due to coronary heart disease

[0136]

[0137] The results showed that no serious adverse reactions such as liver and kidney dysfunction occurred in the two groups of patients with angina pectoris due to coronary heart disease during and after the treatment, and the total incidence of adverse reactions was significantly better than that of the drug of the control group.

[0138] Table 8 Comparison of clinical efficacy of patients with angina pectoris after treatment [cases (%)]

[0139]

[0140] The results show that the clinical efficacy of the drug of the present invention in treating angina pectoris due to coronary heart disease is better than that of the drug of the control group.

[0141] In summary, after treatment, the total clinical efficacy and total electrocardiogram efficacy of the observation group were significantly higher than those of the control group, and the difference was statistically significant (P < 0.05). No serious adverse reactions occurred in the two groups during and after the treatment, and the clinical efficacy of the pharmaceutical composition of the present invention in treating angina pectoris of coronary heart disease was better than that of the control drug, and the safety and effectiveness were greatly improved compared with the prior art.

[0142] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the purpose and scope of the technical solutions of the present invention, which should be included in the scope of the claims of the present invention. The techniques, shapes, and structural parts not described in detail in the present invention are all known technologies.

Claims

1. A pharmaceutical composition for treating coronary heart disease, characterized in that: The invention comprises the following medicinal raw materials: salvia miltiorrhiza, notoginseng, kudzu root and saffron.

2. A pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: The invention comprises the following medicinal raw materials in parts by weight: 10 to 15 parts of salvia miltiorrhiza, 10 to 15 parts of panax notoginseng, 10 to 15 parts of kudzu root and 4 to 12 parts of saffron.

3. A pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: The pharmaceutical composition is prepared from the following pharmaceutical raw materials in parts by mass: 10-15 parts of salvia miltiorrhiza, 10-15 parts of panax notoginseng, 10-15 parts of kudzu root and 4-12 parts of saffron.

4. A pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: The invention comprises the following medicinal raw materials in parts by weight: 15 parts of salvia miltiorrhiza, 15 parts of panax notoginseng, 15 parts of kudzu root and 6 parts of saffron.

5. A pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: The pharmaceutical composition is prepared from the following pharmaceutical raw materials in parts by mass: 15 parts of salvia miltiorrhiza, 15 parts of notoginseng, 15 parts of kudzu root and 6 parts of saffron.

6. A pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: The pharmaceutical composition also includes clinically or pharmaceutically acceptable excipients.

7. A pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: The pharmaceutical composition is prepared as any one of capsules, pills, tablets, granules or oral liquid preparations.

8. A pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: The pharmaceutical composition is prepared as either a rapid-release preparation or a sustained-release preparation.

9. The method for preparing a pharmaceutical composition for treating coronary heart disease according to claim 1, characterized in that: Includes steps: S1: Grind Panax notoginseng into coarse powder, and prepare a paste or nearly paste Panax notoginseng extract by alcohol extraction and water precipitation method; S2: extracting salvia miltiorrhiza and saffron with an ethanol solution, separating the ethanol extract and the extraction residue after the extraction; mixing the extraction residue and kudzu root and decocting them with water, filtering and obtaining a decoction after the decoction, and concentrating the decoction into a paste-like or nearly paste-like mixed extract; S3: further mixing and dispersing the paste or nearly paste-like Panax notoginseng extract obtained in S1 and the paste or nearly paste-like mixed extract obtained in S2, and adding pharmaceutically acceptable excipients to prepare them into a pharmaceutical composition.

10. Use of a pharmaceutical composition for treating coronary heart disease as claimed in claim 1 in the preparation of a drug for preventing, treating or improving any aspect of coronary heart disease, angina pectoris, cerebral arteriosclerosis, myocardial infarction, coronary atherosclerotic heart disease, and chronic heart failure.

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