A traditional Chinese medicine composition for relieving or treating coronary heart disease

Abstract

The present application belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for relieving or treating coronary heart disease. The traditional Chinese medicine composition contains Astragalus, Salvia miltiorrhiza, Coix seed, orange kernel, Herba Patriniae, Curcuma, and Glycyrrhiza. The main purpose of the present application is to treat phlegm turbidity, blood stasis, qi stagnation, and cold coagulation of coronary heart disease by reasonable traditional Chinese medicine combination of activating blood and resolving stasis, regulating qi and resolving phlegm, warming meridians and dispelling cold, and supporting healthy qi and tonifying deficiency. Animal and clinical tests show that the traditional Chinese medicine composition can effectively relieve the clinical symptoms of coronary heart disease, and has great application and promotion value.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating coronary heart disease. BACKGROUND

[0002] Cardiovascular disease is a clinically common disease and also the first leading cause of death and disability worldwide. According to the latest data of China Cardiovascular Health and Disease Report 2021, the morbidity and mortality of cardiovascular disease in China have been at the top in recent years, with a morbidity rate of up to 23.4% of the total population, among which the morbidity rate of coronary heart disease is higher than 3.5%.

[0003] Coronary heart disease refers to a heart disease caused by stenosis of ≥50% of the lumen of blood vessels and coronary arteries due to coronary atherosclerosis, leading to insufficient blood supply and myocardial ischemia. It is generally believed that coronary atherosclerosis and thrombosis are the main causes of coronary heart disease. According to the clinical manifestations, coronary heart disease can be divided into asymptomatic coronary heart disease, angina pectoris, myocardial infarction, heart failure and arrhythmia type, primary cardiac arrest type (sudden death type) coronary heart disease and other types.

[0004] Western medicine believes that the degree of damage to vascular endothelial function, microcirculation disorder, inflammation, abnormal blood rheology, abnormal structure and function of platelets directly reflects the severity of coronary heart disease, so it is more common to use thrombolysis, anticoagulation and cardiotonic drugs to increase the amount of heart blood supply, reduce blood viscosity and improve microcirculation. Commonly used drugs include vasodilators and drugs that increase blood supply, such as nitrate ester drugs, calcium antagonists and beta blockers. In severe cases, coronary artery bypass surgery and stent placement surgery are also required. However, long-term use of drugs can easily cause liver and kidney toxicity, and surgery is expensive and patients have to bear more pain, and can only improve symptoms, not cure.

[0005] Traditional Chinese medicine has a long history and believes that coronary heart disease belongs to the category of “chest pain” and “heart pain”. The Treatise on the Eight Principles states: “Heart disease is chest pain, fullness in the lateral branch, pain in the lateral branch, pain between the clavicle and scapula, and pain in the two arms”. The Synopsis of Golden Chamber believes that “chest pain” is “chest pain through the back, back pain through the chest”, and believes that coronary heart disease is a deficiency in the root and excess in the branches. Among them, the root is deficiency of blood and the branches are phlegm, blood stasis, qi stagnation and cold. Therefore, the treatment should be to promote blood circulation, regulate qi and eliminate phlegm, warm the meridians and support the deficiency. Danqi tablets, compound Danshen dripping pills, Guanxin Suhe dripping pills and Xuesaitong granules are commonly used Chinese patent medicines, but in actual application, it is found that there are problems such as slower efficacy than western medicine, poor drug absorption due to individual differences in patients, bleeding caused by blood-activating and stasis-removing drugs, or worsening of the disease due to taking a large amount of warm and tonic drugs, and the curative effect is not significant.

[0006] Therefore, it is necessary to develop a drug that can significantly improve the clinical symptoms of patients and has high treatment efficiency and low toxicity. SUMMARY

[0007] In view of the above-mentioned technical problems, the present application aims to provide a new traditional Chinese medicine composition for treating or relieving coronary heart disease. Through years of clinical application, the traditional Chinese medicine composition has definite clinical effect, and pharmacodynamic experiments prove that the efficiency is high and side effects are small after medication.

[0008] Specifically, the present application adopts the technical solutions as follows:

[0009] The first object of the present application is to provide a traditional Chinese medicine composition for treating or relieving cardiovascular diseases, especially coronary heart disease, which is prepared from Huangqi, Danshen, Yiyiren, Juren, Baijiangcao, Yujin and Gancao.

[0010] Further, the traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight:

[0011] Huangqi 6.5-26 parts by weight, Danshen 10.8-17.5 parts by weight, Yiyiren 6.5-27.5 parts by weight

[0012] Juren 5-9.5 parts by weight

[0013] Gancao 1-18.5 parts by weight.

[0014] In a preferable embodiment, the traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight:

[0015] Baijiangcao 15 parts by weight, Yujin 8.5 parts by weight, Danshen 13.5 parts by weight

[0016] Yiyiren 20 parts by weight, Huangqi 22 parts by weight, Gancao 9 parts by weight

[0017] Juren 5.5 parts by weight.

[0018] Further, the Huangqi is a mixture of raw Huangqi and fried Huangqi in a weight ratio of 1:1, and the Gancao is a mixture of raw Gancao and fried Gancao in a weight ratio of 1:2.

[0019] Further, the Yujin is Wen Yujin.

[0020] The second object of the present application is to provide the pharmaceutical use of the above-mentioned traditional Chinese medicine composition. Specifically, the use of the above-mentioned traditional Chinese medicine composition in preparing a medicament for treating or relieving cardiovascular diseases is provided. Further, the cardiovascular diseases are coronary heart disease. Still further, the coronary heart disease is caused by phlegm turbidity and blood stasis, and still further, the use of the traditional Chinese medicine composition in preparing a medicament for treating or relieving coronary heart disease of phlegm turbidity and blood stasis type is provided. Pharmacodynamic experiments prove that the traditional Chinese medicine composition can tonify heart qi and activate blood and qi, and the effect is satisfactory.

[0021] The third object of the present application is to provide a dosage form of the Chinese medicine composition for the use. The Chinese medicine composition of the present application can be prepared with pharmaceutical excipients into oral preparations, preferably one or more of granules, tablets, pills, capsules or liquid oral preparations; further preferably into a mixture or granules.

[0022] Further, the pharmaceutical excipients are pharmaceutically acceptable pharmaceutical excipients, including but not limited to one or more of diluents, disintegrants, lubricants, flavoring agents, dispersants.

[0023] The fourth object of the present application is to provide a preparation method of the Chinese medicine composition described above, the preparation method of the Chinese medicine composition is:

[0024] (1) the Chinese medicinal materials are crushed into fine powder, sieved and prepared for use;

[0025] (2) the medicinal materials are first heated and refluxed with 55-75% ethanol for 120-180 minutes, the first clear extract is obtained at 60-70°C with a relative density of 1.05-1.12; the residues are added with water and secondly boiled for 120-240 minutes, the second clear extract is obtained at 50-60°C with a relative density of 1.15-1.20;

[0026] (3) the first clear extract and the second clear extract are mixed;

[0027] (4) pharmaceutical excipients are added and dried to prepare conventional oral preparations.

[0028] Further, the preparation method of the Chinese medicine composition further comprises a step of extracting volatile oil, and the volatile oil can be included with β-cyclodextrin, wherein the preparation method of the granules comprises the following steps:

[0029] (1) the Chinese medicinal materials are crushed into fine powder, sieved and prepared for use;

[0030] (2) 1 / 2 of Huangqin and Yujin and 1 / 4 of Baijiangcao are taken to extract volatile oil, the volatile oil is included with β-cyclodextrin, and the remaining residues are prepared for use;

[0031] (3) the residues of step (2) and the remaining medicinal materials are first heated and refluxed with 55-75% ethanol for 120-180 minutes, the first clear extract is obtained at 60-70°C with a relative density of 1.05-1.12; the residues are added with water and secondly boiled for 120-240 minutes, the second clear extract is obtained at 50-60°C with a relative density of 1.15-1.20;

[0032] (4) the first clear extract, the second clear extract and the volatile oil included with β-cyclodextrin are mixed;

[0033] (5) pharmaceutical excipients are added to prepare granules.

[0034] In specific embodiments, another preparation method of the traditional Chinese medicine composition of the present application is as follows:

[0035] (1) The traditional Chinese medicine materials are crushed into fine powder, sieved, and used;

[0036] (2) Half of the Huangqi and Yujin and one quarter of the Baojiangcao are taken, and the volatile oil is extracted, and the volatile oil is wrapped with β-cyclodextrin, and the remaining residue is reserved;

[0037] (3) The residue of step (2) and the remaining medicinal materials are first heated and refluxed with 55-75% ethanol for 120-180 minutes, the extract is concentrated at 60-70°C, and the relative density is 1.05-1.12 to obtain a first clear paste; the residue is added with water and secondly boiled for 120-240 minutes, and the second filtrate is collected and concentrated at 50-60°C, and the relative density is 1.15-1.20 to obtain a second clear paste;

[0038] (4) The first clear paste, the second clear paste, and the volatile oil wrapped with β-cyclodextrin are mixed;

[0039] (5) The medicinal adjuvant is added to prepare a mixture.

[0040] According to the traditional Chinese medicine, the treatment of coronary heart disease should activate blood and resolve stasis, regulate qi and resolve phlegm, warm the meridians and dispel cold, and support the healthy and supplement the deficiency. According to the clinical experience of the inventors for many years, the present application is based on the disease mechanism and the reasonable compatibility. Huangqi is a qi-tonifying medicinal material, and raw Huangqi is sweet and returns to the lung and spleen meridians, and can dredge stagnation and remove phlegm, and when used with Zhi Huangqi, it can tonify qi, raise yang, produce saliva, and nourish blood. Danshen is bitter and returns to the heart and liver meridians, and has the effects of activating blood and dredging channels, and cooling blood and relieving pain, and can treat chest pain and mass accumulation. Yiren is sweet and cool, and returns to the spleen, stomach, and lung meridians, and is good at tonifying the spleen and supplementing the lung, and can resolve phlegm, remove dampness, clear heat, and drain dampness. Juren is bitter and returns to the liver and kidney meridians, and can resolve phlegm and regulate qi, relieve pain and reduce swelling; Baojiangcao is pungent and bitter, and enters the stomach, large intestine, and liver meridians, and has the effects of clearing heat and resolving toxins, and removing pus and stasis; Yujin is pungent and bitter, and returns to the liver, heart, and lung meridians, and can regulate qi and resolve stagnation, activate blood and relieve pain. Gancao is sweet and returns to the heart, lung, spleen, and stomach meridians, and when used with Zhi Gancao, it can not only harmonize the medicinal materials, but also strengthen the effects of resolving toxins and phlegm, activating blood and dredging collaterals, regulating qi and dispelling cold, and supplementing the spleen and stomach. The present application can not only resolve phlegm and dampness, but also warm and supplement the heart qi, and is suitable for treating coronary heart disease with deficiency of heart qi and phlegm and stasis.

[0041] The beneficial effects of the present application mainly include:

[0042] (1) The traditional Chinese medicine composition of the present application has reasonable compatibility and definite curative effect.

[0043] (2) The traditional Chinese medicine composition has strong pertinence, and the pharmacodynamic experiment proves that the effect of treating coronary heart disease is remarkable, and compared with the prior art, the toxicity is smaller and the treatment effect is better.

[0044] (3) The present application particularly uses raw astragalus and fried astragalus, licorice and fried licorice, and produces a synergistic effect with other drug formulations, and has better curative effect.

[0045] Drawings

[0046] Figure 1 Influence of the traditional Chinese medicine composition on the TC value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0047] Figure 2 Influence of the traditional Chinese medicine composition on the TG value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0048] Figure 3 Influence of the traditional Chinese medicine composition on the LDL value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0049] Figure 4 Influence of the traditional Chinese medicine composition on the APTT value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0050] Figure 5 Influence of the traditional Chinese medicine composition on the PT value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0051] Figure 6 Influence of the traditional Chinese medicine composition on the Fib value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0052] Figure 7 Influence of the traditional Chinese medicine composition on the IL-8 value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0053] Figure 8 Influence of the traditional Chinese medicine composition on the TNF-α value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0054] Figure 9 Influence of the traditional Chinese medicine composition on the ET-1 value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome

[0055] Figure 10 Influence of the traditional Chinese medicine composition on the sVCAM-1 value of the rat with coronary heart disease and phlegm and blood stasis interlocking syndrome Specific embodiments

[0056] The technical solutions of the present application will be described below in conjunction with specific embodiments, but the described embodiments are only some of the embodiments of the present application, not all. All other embodiments obtained by those skilled in the art without creative labor fall within the scope of the present application.

[0057] Preparation of granules of Example 1

[0058]

[0059] (1) The above-mentioned Chinese medicinal materials are ground into fine powder, sieved and reserved;

[0060] (2) The first clear extract is obtained by heating and refluxing 55-75% of ethanol for 120-180 minutes, and the relative density of the extract is 1.05-1.12 at 60-70°C; the second clear extract is obtained by adding water to the residue and boiling for 120-240 minutes, and the relative density of the second filtrate is 1.15-1.20 at 50-60°C;

[0061] (3) The first clear extract and the second clear extract are mixed;

[0062] (4) The medicinal adjuvants are added to prepare tablets.

[0063] Preparation of granules of Example 2

[0064]

[0065] Preparation method: the same as that of Example 1.

[0066] Preparation of granules of Example 3

[0067]

[0068] Preparation method: the same as that of Example 1.

[0069] Preparation of granules of Example 4

[0070]

[0071] Preparation method:

[0072] (1) The above-mentioned Chinese medicinal materials are ground into fine powder, sieved and reserved;

[0073] (2) Half of Huangqin and Yujin and one quarter of Baijiangcao are taken to extract volatile oil, and the volatile oil is taken to be wrapped with β-cyclodextrin, and the remaining residue is reserved;

[0074] (3) The residue of step (2) and the remaining medicinal materials are taken to be heated and refluxed with 55-75% of ethanol for 120-180 minutes, and the first clear extract is obtained by heating and refluxing the extract at 60-70°C, and the relative density is 1.05-1.12; the second clear extract is obtained by adding water to the residue and boiling for 120-240 minutes, and the relative density of the second filtrate is 1.15-1.20 at 50-60°C;

[0075] (4) The first clear extract, the second clear extract and the volatile oil wrapped with β-cyclodextrin are mixed;

[0076] (5) Add pharmaceutical excipients to make granules.

[0077] Example 5 Preparation of a mixture

[0078]

[0079] Preparation method:

[0080] (1) The above traditional Chinese medicinal materials are ground into fine powder, sieved, and reserved for use;

[0081] (2) Take 1 / 2 of Huangqin and Yujin, and 1 / 4 of Baijiangcao, extract volatile oil, take the volatile oil to be wrapped with β-cyclodextrin, and reserve the remaining residue;

[0082] (3) Take the residue of step (2) and the remaining medicinal materials, heat and reflux with 55-75% ethanol for 120-180 minutes, collect the first filtrate with a relative density of 1.05-1.12 at 60-70°C to obtain the first clear extract; take the residue and add water to extract for the second time for 120-240 minutes, collect the second filtrate with a relative density of 1.15-1.20 at 50-60°C to obtain the second clear extract;

[0083] (4) Take the first clear extract, the second clear extract, and the volatile oil wrapped with β-cyclodextrin, and mix well;

[0084] (5) Add pharmaceutical excipients to make a mixture.

[0085] Example 6 Preparation of tablets

[0086]

[0087] Preparation method:

[0088] (1) The above traditional Chinese medicinal materials are ground into fine powder, sieved, and reserved for use;

[0089] (2) Take 1 / 2 of Huangqin and Yujin, and 1 / 4 of Baijiangcao, extract volatile oil, take the volatile oil to be wrapped with β-cyclodextrin, and reserve the remaining residue;

[0090] (3) Take the residue of step (2) and the remaining medicinal materials, heat and reflux with 55-75% ethanol for 120-180 minutes, collect the first filtrate with a relative density of 1.05-1.12 at 60-70°C to obtain the first clear extract; take the residue and add water to extract for the second time for 120-240 minutes, collect the second filtrate with a relative density of 1.15-1.20 at 50-60°C to obtain the second clear extract;

[0091] (4) Take the first clear extract, the second clear extract, and the volatile oil wrapped with β-cyclodextrin, and mix well;

[0092] (5) Add pharmaceutical excipients to make tablets.

[0093] Preparation of granules of Comparative Example 1

[0094]

[0095] Preparation method:

[0096] (1) The above Chinese medicinal materials are ground into fine powder, sieved, and reserved;

[0097] (2) One fourth of the Herba Patriniae is taken to extract volatile oil, and the volatile oil is wrapped with β-cyclodextrin, and the remaining residue is reserved;

[0098] (3) The residue of step (2) and the remaining medicinal materials are first heated and refluxed with 55-75% ethanol for 120-180 minutes, the first clear extract is collected at 60-70°C with a relative density of 1.05-1.12, the residue is added with water and secondly boiled for 120-240 minutes, the second filtrate is collected at 50-60°C with a relative density of 1.15-1.20, and concentrated to obtain the second clear extract;

[0099] (4) The first clear extract, the second clear extract, and the volatile oil wrapped with β-cyclodextrin are mixed;

[0100] (5) Pharmaceutical excipients are added to prepare tablets.

[0101] Preparation of granules of Comparative Example 2

[0102]

[0103]

[0104] Preparation method: same as Example 1.

[0105] Preparation method:

[0106] (1) The above Chinese medicinal materials are ground into fine powder, sieved, and reserved;

[0107] (2) The first clear extract is collected at 60-70°C with a relative density of 1.05-1.12, the residue is added with water and secondly boiled for 120-240 minutes, the second filtrate is collected at 50-60°C with a relative density of 1.15-1.20, and concentrated to obtain the second clear extract;

[0108] (3) The first clear extract, the second clear extract, and the volatile oil wrapped with β-cyclodextrin are mixed;

[0109] (4) Pharmaceutical excipients are added to prepare tablets.

[0110] Preparation of granules of Comparative Example 3

[0111] Composition:

[0112]

[0113] Preparation method:

[0114] (1) The above-mentioned Chinese medicinal materials are ground into fine powder, sieved, and reserved;

[0115] (2) The medicinal materials are decocted with water for 3-4 times, each time for 60-90 minutes, and the filtrates are combined and concentrated at 50-60°C to a clear extract with a relative density of 1.15-1.20;

[0116] (3) The medicinal adjuvants are added to prepare granules.

[0117] Preparation of granules in Comparative Example 4

[0118]

[0119] Preparation method:

[0120] (1) The above-mentioned Chinese medicinal materials are ground into fine powder, sieved, and reserved;

[0121] (2) The medicinal materials are first refluxed with 55-75% ethanol for 120-180 minutes, and the extract is concentrated at 60-70°C to a first clear extract with a relative density of 1.05-1.12; the residues are decocted with water for a second time for 120-240 minutes, and the second filtrate is concentrated at 50-60°C to a second clear extract with a relative density of 1.15-1.20;

[0122] (3) The first clear extract and the second clear extract are mixed;

[0123] (4) The medicinal adjuvants are added to prepare tablets.

[0124] Preparation of granules in Comparative Example 5

[0125]

[0126] (1) The above-mentioned Chinese medicinal materials are ground into fine powder, sieved, and reserved;

[0127] (2) The medicinal materials are decocted with water for 3-4 times, each time for 60-90 minutes, and the filtrates are combined and concentrated at 50-60°C to a clear extract with a relative density of 1.15-1.20;

[0128] (3) The medicinal adjuvants are added to prepare granules.

[0129] Pharmacodynamic test

[0130] To verify the efficacy of the traditional Chinese medicine composition of the present application, the inventors carried out pharmacodynamic test research. It should be noted that the drugs selected for the pharmacodynamic test of the present application are drugs obtained by the representative formula and preparation method of the present application. The tests and results of other formulas and drugs obtained by the preparation method included in the present application are similar to the technical effects achieved by the pharmacological and clinical tests of the traditional Chinese medicine composition of the present application in the treatment of coronary heart disease. Due to space limitations, they are not listed here.

[0131] I. The therapeutic effect of the traditional Chinese medicine composition of the present application on rats with coronary heart disease and phlegm and blood stasis

[0132] 1. Materials and methods

[0133] 1.1 Experimental animals

[0134] 2-3 month old SD rats, half male and half female, weighing (200±20) g, experimental animal qualification certificate number: SYXK(Lu)2020-0018.

[0135] The rats were adaptively fed for 1 week before the experiment, the room temperature was 20-28℃, the humidity was 40%-60%, the natural light was used, and the rats were allowed to drink and eat freely.

[0136] 1.2 Drugs and reagents

[0137] Example 3 granules; Example 4 granules; Example 5 mixture; Comparative Example 4 granules, Comparative Example 5 granules, Yixinshu granules (commercially available).

[0138] Preparation method: before use, the preparations prepared in Examples 3, 4, 5, Comparative Example 4, Comparative Example 5 and Yixinshu granules were weighed and dissolved in physiological saline to prepare suspensions of different concentrations for use. Among them:

[0139] Positive control drug group: Yixinshu granules, 1.08 g / kg;

[0140] Example 3 group: Example 3 granules, 46.8 g / kg in crude drug amount;

[0141] Example 4 low dose group: Example 4 granules, 46.8 g / kg in crude drug amount;

[0142] Example 4 high dose group: Example 4 granules, 93.5 g / kg in crude drug amount;

[0143] Example 5 group: Example 5 mixture, 46.8 g / kg in crude drug amount;

[0144] Comparative Example 4 group: Comparative Example 4 granules, 46.8 g / kg in crude drug amount;

[0145] Comparative Example 5 Group: Comparative Example 5 granules, 46.8 g / kg, based on the amount of crude drugs.

[0146] 1.3 Test Method

[0147] The rats were randomly divided into groups, with 10 rats in each group. The rats in each group were given a high-fat diet. After 4 weeks of feeding, the rats were anesthetized with 2% sodium pentobarbital (dose volume 2.3 mL / kg), a midline incision was made, and the heart was exposed by opening the chest at the 3rd and 4th intercostal spaces on the left margin of the sternum. The pericardium was opened, the fat pad was lifted, and the left atrial appendage was exposed. A 7-gauge needle was used to sew and ligate the left anterior descending branch of the coronary artery between the pulmonary artery conus and the left atrial appendage. The rats in each group were given oral administration, and the model group was given the same volume of normal saline, with an oral administration volume of 5 ml / Kg, 1 time / d, for 5 consecutive weeks. After the experiment, the animals were transferred to the animal management room for proper disposal.

[0148] 1.4 Detection Index and Method

[0149] (1) Serum three items and blood coagulation three items:

[0150] On the 2nd day after the end of the experiment, blood was taken from the jugular vein of each group of rats, and the content of TC, TG and LDL in serum was determined by automatic biochemical analyzer, and the values of APTT, PT and Fib in plasma were detected by automatic coagulation analyzer.

[0151] (2) Serum inflammatory mediator determination:

[0152] The serum was collected and the content of IL-8 and TNF-α in serum was detected according to the instructions of the Elisa kit.

[0153] (3) Serum endothelin (ET-1) and soluble vascular cell adhesion molecule (sVCAM-1) determination:

[0154] The serum was collected and the content of ET-1 and sVCAM-1 in serum was detected according to the instructions of the Elisa kit.

[0155] 2 Results

[0156] (1) Serum three items and blood coagulation three items:

[0157] After modeling, the content of TC, TG and LDL in serum of the model group of rats increased significantly, and the APTT and PT in plasma of the model group of rats were significantly shortened. After administration of different drugs, the content of TC, TG and LDL in serum of rats was reduced to different degrees, the values of APTT and PT were prolonged, and the value of Fib was reduced. Among them, the high-dose group had the largest degree of reduction in TC, TG and LDL values, the largest degree of increase in APTT and PT values, and the difference was significant (P<0.05). The specific values are shown in Table 1. Figures 1-6

[0158] ​(2) Serum inflammatory mediator determination:

[0159] After modeling, the model group rats TNF-α, IL-8 content was significantly higher than the normal control group, after administration of serum TNF-α and IL-8 content of rats in each group were decreased, including high dose group and low dose group in serum TNF-α were significantly reduced, the difference was significant (P<0.05). As shown in Table 2. Figures 7-8

[0160] (3) Serum endothelin (ET-1), soluble vascular cell adhesion molecule (sVCAM-1) determination:

[0161] The model group rats serum sVCAM-1, ET-1 content were significantly increased, after administration of rats in each group were reduced to varying degrees, including high dose group and low dose group in serum sVCAM-1, ET-1 content were significantly reduced, the difference was significant (P<0.05). As shown in Table 3. Figures 9-10

[0162] Second, the protective effect of the traditional Chinese medicine composition of the present application on isoprenaline hydrochloride-induced myocardial ischemia injury in rats

[0163] 1 Materials and methods

[0164] 1.1 Experimental animals

[0165] SD rats, female, body weight (200±20) g, experimental animal qualification certificate number: SYXK (Lu) 2020-0018.

[0166] Before the experiment, adapt to the conventional conditions for 1 week.

[0167] 1.2 Drugs and reagents

[0168] Example 3 granules were prepared; Example 4 granules were prepared; Comparative Example 2 granules were prepared, Comparative Example 5 granules were prepared, Xuesaitong granules (commercially available).

[0169] Preparation method: before use, the preparations prepared by Example 3, Example 4, Comparative Example 2, Comparative Example 5 and Xuesaitong granules are weighed, dissolved in physiological saline, and prepared into different concentrations of suspension for use. Among them:

[0170] Positive control drug group: Xuesaitong granules, 1.62 g / kg;

[0171] Example 3 group: Example 3 granules, 46.8 g / kg, in crude drug amount;

[0172] Example 4 group: Example 4 granules, 46.8 g / kg, in crude drug amount;

[0173] ​​Comparative Example 2 Group: Comparative Example 2 granules, 46.8 g / kg, based on crude drug content;

[0174] Comparative Example 5 Group: Comparative Example 5 granules, 46.8 g / kg, based on crude drug content.

[0175] 1.3 Test Method

[0176] Healthy rats were randomly divided into normal group, model group, positive control drug group, Example 3 group, Example 4 group, Comparative Example 2 group, and Comparative Example 5 group. The above groups were respectively given corresponding drugs by gavage according to the dosage, wherein the normal group and the model group were given the same amount of normal saline, and the gavage volume was 5 ml / Kg, 1 time / d, and the gavage was continuously performed for 7 days. 2 hours after the last administration, the rats were anesthetized by intraperitoneal injection of 20% urethane, and the electrocardiogram of the rats was recorded. After recording, the model group and each group of rats were subcutaneously injected with isopropyl hydrochloride 30 mg / kg, and the normal group was subcutaneously injected with the same volume of normal saline. The electrocardiogram was measured again. The J point change value (△J value = J point value at each time point after injection of ISO - J point value before injection) at each electrocardiogram time point was calculated. After the electrocardiogram measurement was completed, blood was taken from the jugular vein, and the serum was measured for the content of LDH and CK according to the kit method.

[0177] 2. Results

[0178] (1) It was found by observation that after injection of isopropyl hydrochloride, the J point of the electrocardiogram of the model group of rats was significantly lowered from 15s, and the J point lowering value of each drug administration group was significantly shortened to different degrees, among which the lowering value of Example 4 group was closest to that of the normal group, and there was no significant difference. The specific values are shown in Table 1:

[0179] Table 1 Influence on electrocardiogram of rats with myocardial ischemic injury caused by isopropyl hydrochloride

[0180]

[0181]

[0182] Compared with the normal control group, **p<0.01; compared with the model group, && p<0.01.

[0183] 1- normal control group; 2- model group; 3- positive control drug group; 4- Example 3 group; 5- Example 4 group; 6- Comparative Example 2 group; 7- Comparative Example 5 group.

[0184] (2) Influence on serum biochemical indicators of rats with myocardial ischemic injury.

[0185] As shown in Table 2, when the rat myocardial ischemia, serum LDH, CK activity increased significantly, compared with the model group, each administration group composition high, medium and low dose can reduce the activity of LDH, CK in varying degrees, of which, the embodiment 4 group reduced degree is lowest, the difference is significant.

[0186] Table 2 on the influence of isoproterenol hydrochloride induced myocardial ischemia injury serum index of rats

[0187]

[0188] Compared with the normal control group, **p<0.01; compared with the model group, && p<0.01.

[0189] 1-normal control group; 2-model group; 3-positive control drug group; 4-embodiment 3 group; 5-embodiment 4 group; 6-contrast embodiment 2 group; 7-contrast embodiment 5 group.

[0190] The pharmacodynamic examples of the application respectively use Yixinshu granules and Xuesaitong granules as positive control drugs, which have the functions of promoting blood circulation to remove blood stasis, dredging vessels and activating collaterals, and can be used for heart vessel obstruction, chest stuffiness and pain, chest pain and angina pectoris. From the above test results, it can be concluded that the traditional Chinese medicine composition of the application can effectively relieve the clinical symptoms of coronary heart disease, and has high clinical application value.

Claims

1. A traditional Chinese medicine composition for relieving or treating coronary heart disease of phlegm and blood stasis type, characterized in that, The traditional Chinese medicine composition is made of the following traditional Chinese medicine by weight: Radix Astragali 6.5~26 weight parts Radix Salviae Miltiorrhizae 10.8~17.5 weight parts Coicis Semen 6.5~27.5 weight parts Citrus Reticulatae 2.5~9 weight parts Brassica Campus 6~15 weight parts Rhizoma Bupleuri 5~9.5 weight parts Glycyrrhizae Radix 1~18.5 weight parts The Radix Astragali is a mixture of raw Radix Astragali and fried Radix Astragali, with a weight ratio of 1:1; the Glycyrrhizae Radix is a mixture of raw Glycyrrhizae Radix and fried Glycyrrhizae Radix, with a weight ratio of 1:2; the Rhizoma Bupleuri is warm Rhizoma Bupleuri.

2. The traditional Chinese medicine composition of claim 1, wherein, The traditional Chinese medicine composition is made of the following traditional Chinese medicine by weight: Radix Astragali 22 weight parts Radix Salviae Miltiorrhizae 13.5 weight parts Coicis Semen 20 weight parts Citrus Reticulatae 5.5 weight parts Brassica Campus 15 weight parts Rhizoma Bupleuri 8.5 weight parts Glycyrrhizae Radix 9 weight parts.

3. The traditional Chinese medicine composition of claim 1, wherein, The traditional Chinese medicine composition can be prepared into a traditional Chinese medicine preparation with pharmaceutically acceptable excipients, and the traditional Chinese medicine preparation is one or more of granules, tablets, pills, capsules or liquid oral preparations.

4. The traditional Chinese medicine composition of claim 3, wherein, The traditional Chinese medicine preparation is a mixture or granules.

5. The traditional Chinese medicine composition of claim 1, wherein, The preparation method of the traditional Chinese medicine composition is as follows: (1) the above traditional Chinese medicine materials are crushed into fine powder, sieved and prepared for use; (2) the traditional Chinese medicine materials are first heated and refluxed with 55~75% ethanol for 120~180 minutes, the first extract is obtained at 60~70℃ with a relative density of 1.05~1.12; the residues are added with water and secondly boiled for 120~240 minutes, the second filtrate is collected and concentrated at 50~60℃ with a relative density of 1.15~1.20 to obtain the second extract; (3) the first extract and the second extract are mixed; (4) pharmaceutically acceptable excipients are added and dried to prepare conventional oral preparations.

6. The traditional Chinese medicine composition of claim 1, wherein, The preparation method of the traditional Chinese medicine composition is as follows: (1) the above traditional Chinese medicine materials are crushed into fine powder, sieved and prepared for use; (2) 1 / 2 of Radix Astragali and Rhizoma Bupleuri and 1 / 4 of Brassica Campus are taken to extract volatile oil, the volatile oil is taken and wrapped with β-cyclodextrin, and the remaining residues are prepared for use; (3) the residues of step (2) and the remaining traditional Chinese medicine materials are first heated and refluxed with 55~75% ethanol for 120~180 minutes, the first extract is obtained at 60~70℃ with a relative density of 1.05~1.12; the residues are added with water and secondly boiled for 120~240 minutes, the second filtrate is collected and concentrated at 50~60℃ with a relative density of 1.15~1.20 to obtain the second extract; (4) the first extract, the second extract and the volatile oil wrapped with β-cyclodextrin are mixed; (5) pharmaceutically acceptable excipients are added to prepare conventional oral preparations.

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