A traditional Chinese medicine composition, its preparation method and application

Abstract

The present invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition, a preparation method thereof, and an application thereof. The traditional Chinese medicine composition is prepared from the following raw medicinal materials in parts by weight: 10 to 15 parts of red ginseng, 5 to 10 parts of prepared aconite root, 15 to 30 parts of cornel fruit, 10 to 20 parts of rehmannia root, 15 to 30 parts of astragalus membranaceus var. mongholicus, 6 to 15 parts of rhodiola rosea, 6 to 12 parts of dried ginger, 15 to 30 parts of poria cocos, 2 to 6 parts of panax notoginseng powder, 15 to 30 parts of semen lepidii, 10 to 15 parts of radix paeoniae rubra, and 5 to 10 parts of coptis chinensis. The present invention also discloses a preparation method of the traditional Chinese medicine composition and an application of the traditional Chinese medicine composition in the preparation of a drug for treating heart failure. Research shows that the traditional Chinese medicine composition can improve heart failure by reducing the degree of myocardial fibrosis and delaying ventricular remodeling, providing a new idea for the treatment of heart failure.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition, a preparation method thereof, and an application thereof. Background Art

[0002] Heart failure is caused by various chronic cardiomyopathies and long-term ventricular overload due to any reason such as myocardial infarction, cardiomyopathy, hemodynamic overload, inflammation, etc., resulting in a primary or secondary weakening of myocardial contractility, so that the heart cannot pump out a blood supply commensurate with venous return and the metabolic needs of body tissues, which is called chronic heart failure. Since chronic heart failure is almost always accompanied by obvious obstructive congestion (congestion) of various organs, it is also called congestive heart failure. Chronic heart failure mostly occurs in organic cardiovascular diseases after a compensatory process of varying lengths. When myocardial contractility is severely impaired and the heart and blood circulation lose their compensatory ability, symptoms of reduced cardiac output, insufficient perfusion of organs and tissues, and systemic congestion gradually appear. The goal of treating heart failure is not only to improve symptoms and quality of life, but also to target the mechanism of myocardial remodeling, delay and prevent the development of myocardial remodeling, and reduce the hospitalization rate and mortality of heart failure.

[0003] The main treatments for chronic heart failure in Western medicine are as follows: angiotensin-converting enzyme inhibitors, diuretics, β-blockers, angiotensin II receptor blockers, and aldosterone inhibitors. However, long-term use of Western medicine treatment may cause hypokalemia, hyperkalemia, hypotension, transient deterioration of renal function, dry cough, angioedema, hyperkalemia, easy induction or exacerbation of bradyarrhythmia, hypotension, fluid retention, or deterioration of heart failure.

[0004] Heart failure belongs to the categories of "heart edema", "palpitation", "dyspnea", "edema", "heart failure", etc. in traditional Chinese medicine. Lei Zhongyi deeply studied ancient traditional Chinese medicine books and believed that patients with heart failure have long-term damage to heart qi. Over time, qi deficiency can develop into qi and yin deficiency. Prolonged illness enters the collaterals, and the collaterals of prolonged illness will surely be stagnated. Phlegm, dampness, and blood stasis are generated in the body and cannot be transformed, further consuming the kidney yang. Therefore, he proposed the theory of treating the heart from the kidney and formulated a traditional Chinese medicine composition for nourishing the heart and promoting blood circulation to treat the yin and yang deficiency, phlegm, stasis, and water retention type of chronic heart failure. Lei Lao believes that the disease characteristics of this disease are deficiency in origin and excess in superficiality, with the emphasis on tonifying deficiency to cultivate the root yuan and expelling excess pathogens to treat the superficiality. Currently, many proprietary Chinese medicines and injections are applied clinically, such as Xinlikang with the effects of tonifying qi and yin, promoting blood circulation to remove blood stasis, and promoting diuresis to reduce edema; Nuanxin Capsule with the effects of tonifying qi to warm the heart and promoting yang to activate blood circulation; Qili Qiangxin Capsule with the effects of tonifying heart qi and promoting blood circulation to dredge collaterals. The clinical effective rates of the above drugs do not exceed 85%.

[0005] In view of this, there is a need to provide a traditional Chinese medicine composition with excellent curative effect for treating heart failure. Summary of the Invention

[0006] The present invention provides a traditional Chinese medicine composition, a preparation method thereof and an application. The traditional Chinese medicine composition is used for treating heart failure, and the clinical effective rate exceeds 90%.

[0007] To solve the above technical problems, the present invention adopts the following technical solutions.

[0008] In the first aspect of the present invention, a traditional Chinese medicine composition is provided. The traditional Chinese medicine composition is prepared from the following raw materials:

[0009] 10 to 15 parts of red ginseng, 5 to 10 parts of processed aconite root, 15 to 30 parts of cornel fruit, 10 to 20 parts of rehmannia root, 15 to 30 parts of astragalus membranaceus var. mongholicus, 6 to 15 parts of rhodiola rosea, 6 to 12 parts of dried ginger, 15 to 30 parts of poria cocos, 2 to 6 parts of panax notoginseng powder, 15 to 30 parts of semen lepidii, 10 to 15 parts of radix paeoniae rubra, 5 to 10 parts of coptis chinensis.

[0010] In some embodiments of the present invention, the traditional Chinese medicine composition is made from the following raw materials in parts by weight:

[0011] 10 to 13 parts of red ginseng, 8 to 10 parts of processed aconite root, 15 to 20 parts of cornel fruit, 16 to 20 parts of rehmannia root, 20 to 30 parts of astragalus membranaceus var. mongholicus, 10 to 15 parts of rhodiola rosea, 6 to 11 parts of dried ginger, 15 to 22 parts of poria cocos, 3 to 6 parts of panax notoginseng powder, 18 to 30 parts of semen lepidii, 10 to 13 parts of radix paeoniae rubra, 8 to 10 parts of coptis chinensis.

[0012] In some specific embodiments of the present invention, the traditional Chinese medicine composition is made from the following raw materials in parts by weight:

[0013] 10 parts of red ginseng, 10 parts of processed aconite root, 20 parts of cornel fruit, 20 parts of rehmannia root, 20 parts of astragalus membranaceus var. mongholicus, 10 parts of rhodiola rosea, 6 parts of dried ginger, 20 parts of poria cocos, 3 parts of panax notoginseng powder, 30 parts of semen lepidii, 10 parts of radix paeoniae rubra, 10 parts of coptis chinensis.

[0014] In the second aspect of the present invention, a preparation method of the traditional Chinese medicine composition is provided, including the following steps:

[0015] Weigh red ginseng, processed aconite root, cornel fruit, rehmannia root, astragalus membranaceus var. mongholicus, rhodiola rosea, dried ginger, poria cocos, semen lepidii, radix paeoniae rubra, and coptis chinensis according to the weight parts and set aside.

[0016] Decoct the weighed traditional Chinese medicine raw materials in water, collect the decoction of the medicine, and add panax notoginseng powder to the decoction of the medicine and mix evenly to obtain the traditional Chinese medicine composition.

[0017] In some embodiments of the present invention, the process of decocting in water is as follows:

[0018] Decoct the prepared aconite slices first, and then add fructus corni, rehmannia root, astragalus membranaceus, rhodiola rosea, dried ginger, poria cocos, semen lepidii, radix paeoniae rubra, and coptis chinensis. In total, add water with a mass 6 to 8 times that of the medicinal material mixture, and conduct decoction. Collect the decoction of the medicinal material mixture.

[0019] Add ginseng rubra to water with a mass 6 to 8 times that of ginseng rubra and decoct. Collect the decoction of ginseng rubra.

[0020] Combine the decoction of the mixture and the decoction of ginseng rubra to obtain the medicinal decoction.

[0021] The third aspect of the present invention provides the use of the described traditional Chinese medicine composition in the preparation of a drug for treating heart failure.

[0022] In some embodiments of the present invention, the heart failure is caused by heart disease.

[0023] In some embodiments of the present invention, the heart disease includes at least one of coronary heart disease, cardiomyopathy, cor pulmonale, congenital heart disease, rheumatic heart disease, and viral myocarditis.

[0024] In some embodiments of the present invention, the drug includes the described traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0025] In some embodiments of the present invention, the dosage form of the drug is water pills, dripping pills, honey pills, granules, powders, capsules, soft capsules, tablets, mixtures, or oral liquids.

[0026] In some embodiments of the present invention, the drug is used for preparing a preparation for inhibiting the excessive activation of the renin-angiotensin-aldosterone system.

[0027] In the present invention, the monarch-minister compatibility relationship of the traditional Chinese medicine composition is as follows:

[0028] The monarch drugs are: ginseng rubra, prepared aconite slices.

[0029] The minister drugs are: astragalus membranaceus, rhodiola rosea, notoginseng, fructus corni, dried ginger, poria cocos.

[0030] The assistant drugs are: semen lepidii, radix paeoniae rubra.

[0031] The guiding drug is: raw rehmannia root, coptis chinensis.

[0032] Yangxin Huoxue Decoction uses red ginseng and processed aconite root, which is pungent and extremely hot, as the monarch drugs. Red ginseng can greatly tonify primordial qi, invigorate the spleen and benefit the lungs, promote the production of body fluids, calm the mind and improve intelligence. Aconite root is warm in nature and has a powerful medicinal effect. It not only warms the kidney yang and warms the spleen earth to assist yang qi, but is also good at rescuing yang from collapse, tonifying fire and assisting yang, dispelling cold and relieving pain. The combination of the two drugs has the effect of benefiting qi and warming yang, assisting the operation of the heart meridian, and treating the heart from the kidney. The ministerial drugs include red astragalus, which can tonify the deficiencies of the five zang-organs, cultivate and supplement primordial qi, strengthen the spleen and stomach, can both raise the spleen qi to strengthen the acquired foundation, and can also tonify the deficiency of the lung qi, benefit qi and consolidate the exterior, and also can promote diuresis and reduce edema. Qi can promote blood circulation, and the operation of blood vessels depends on the promotion of qi. If qi is deficient, the vessels will not function and blood stasis will occur internally; it promotes blood circulation by supplementing qi together with red ginseng, so-called "when qi moves, blood moves". Dry ginger warms the middle-jiao and dispels cold, restores yang and unblocks the vessels. Cornus officinalis tonifies the liver and kidney, astringes and arrests discharge, and assists aconite root in warming and tonifying the spleen and kidney. Rhodiola rosea benefits qi and activates blood circulation, unblocks the vessels and relieves asthma. Poria cocos strengthens the spleen and promotes diuresis and percolates dampness. Notoginseng promotes qi and activates blood circulation, reduces swelling and relieves pain, and has the effect of removing stasis and promoting new growth, so-called "pushing out the old and bringing forth the new". The above herbs are combined to achieve the effects of promoting qi transformation, activating blood circulation and promoting diuresis, warming and transporting water and dampness. Semen lepidii is used as an adjuvant drug to purge the lung and relieve asthma, promote diuresis and reduce edema. Red peony root clears heat and cools blood, disperses stasis and relieves pain, and together they assist the monarch and ministerial drugs in promoting diuresis and unblocking the vessels, and leading out pathogenic factors. The envoy drug is raw rehmannia root, which cools blood and activates blood circulation, nourishes yin and blood, and replenishes the deficient yin fluid. When combined with the above herbs, yin generates yang, yin and yang mutually root and interact, seeking yang from yin and seeking yin from yang, achieving the wonderful effect of balancing yin and yang and treating the heart from the kidney, and can also restrict the warm and dry nature of the monarch drugs; the intention of using Coptis chinensis is, on the one hand, to restrict the pungent, dry and toxic nature of aconite root, and on the other hand, it enters the heart meridian and has the function of guiding the meridian. The combination of all herbs warms and tonifies yin and yang, activates blood circulation and dissipates phlegm, unblocks the vessels and promotes diuresis.

[0033] Compared with the prior art, the present invention has the following beneficial effects: Using the traditional Chinese medicine composition of the present invention can improve the LVEF value of cardiac function, and can significantly reduce the levels of serum NT-proBNP, ANP, ET-1, and AngII in heart failure rats, indicating that the traditional Chinese medicine composition may reverse ventricular remodeling and improve cardiac function by regulating the levels of ANP, ET-1, and AngII and inhibiting the excessive activation of the RAAS system; it can also reduce the percentage of myocardial collagen, reduce the content of MMP-2 and MMP-9mRNA, and down-regulate the expression level of TGF-β1 protein. At the same time, the clinical effective rate of the traditional Chinese medicine composition of the present invention is 90%, and it has a higher effective rate under the same syndrome type conditions, indicating that the traditional Chinese medicine composition can improve heart failure by reducing the degree of myocardial fibrosis and delaying ventricular remodeling, providing a new idea for the treatment of heart failure. Description of the Drawings

[0034] Figure 1 Bar graph of the comparison of LVEF of rats in each group 8 weeks after modeling and 4 weeks after administration.

[0035] Figure 2 Bar graph of the change in the concentration of NT-proBNp in the serum of rats in each group.

[0036] Figure 3 Bar graph showing the changes in ANP concentration in the sera of rats in each group.

[0037] Figure 4 Bar graph showing the changes in ET-1 concentration in the sera of rats in each group.

[0038] Figure 5 Bar graph showing the changes in AngII concentration in the sera of rats in each group.

[0039] Figure 6 Graph showing the results of Masson staining of myocardial tissues of rats in each group; among them, A is the graph of the results of Masson staining of myocardial tissues of rats in the YXD group; B is the graph of the results of Masson staining of myocardial tissues of rats in the YXG group; C is the graph of the results of Masson staining of myocardial tissues of rats in the KT group; D is the graph of the results of Masson staining of myocardial tissues of rats in the Model group; E is the graph of the results of Masson staining of myocardial tissues of rats in the Sham group.

[0040] Figure 7 Bar graph comparing the collagen volume fractions of myocardial tissues of rats in each group.

[0041] Figure 8 Bar graph showing the relative expression levels of MMP-2 mRNA in myocardial tissues of rats in each group.

[0042] Figure 9 Bar graph showing the relative expression levels of MMP-9 mRNA in myocardial tissues of rats in each group.

[0043] Figure 10 Graph showing the expression of representative TGF-β1 protein detected by Western blot in each group.

[0044] Figure 11 Bar graph showing the relative expression levels of TGF-β1 in myocardial tissues of rats in each group. Detailed implementation mode

[0045] The present invention will be described in detail below with reference to specific embodiments, but it should not be construed as a limitation of the present invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well-known to those skilled in the art. The materials, reagents, etc. used in the following embodiments can be obtained from commercial sources unless otherwise specified. In the following embodiments, 1 g represents one weight part.

[0046] I. Experimental drugs

[0047] Table 1 Experimental drugs

[0048] Components of the traditional Chinese medicine composition Beijing Tongrentang of China Captopril tablets Shantou Jinshi Pharmaceutical Co., Ltd. of China National Pharmaceutical Group Urethane Caoyang No. 2 Reagent Factory of China 0.9% Sodium chloride injection Sichuan Kelun Pharmaceutical Co., Ltd. Heparin sodium injection Shanghai No. 1 Biochemical Pharmaceutical Co., Ltd. Isoflurane Hebei Yipin Pharmaceutical Co., Ltd.

[0049] Example 1

[0050] A traditional Chinese medicine composition for treating heart failure is as follows:

[0051] The composition of a traditional Chinese medicine composition for treating heart failure: 10 g of red ginseng, 10 g of prepared aconite root, 20 g of cornelian cherry fruit, 20 g of rehmannia root, 30 g of astragalus membranaceus var. mongholicus, 15 g of rhodiola rosea, 10 g of dried ginger, 30 g of poria cocos, 3 g of notoginseng powder, 30 g of semen lepidii, 15 g of red peony root, 8 g of coptis chinensis.

[0052] Example 2

[0053] A traditional Chinese medicine composition for treating heart failure is as follows:

[0054] The composition of a traditional Chinese medicine composition for treating heart failure: 15 g of red ginseng, 5 g of prepared aconite root, 30 g of cornelian cherry fruit, 10 g of rehmannia root, 30 g of astragalus membranaceus var. mongholicus, 15 g of rhodiola rosea, 12 g of dried ginger, 30 g of poria cocos, 6 g of notoginseng powder, 15 g of semen lepidii, 15 g of red peony root, 5 g of coptis chinensis.

[0055] Example 3

[0056] A traditional Chinese medicine composition for treating heart failure is as follows:

[0057] The composition of a traditional Chinese medicine composition for treating heart failure: 13 g of red ginseng, 8 g of prepared aconite root, 15 g of cornelian cherry fruit, 16 g of rehmannia root, 15 g of astragalus membranaceus var. mongholicus, 6 g of rhodiola rosea, 10 g of dried ginger, 15 g of poria cocos, 2 g of notoginseng powder, 20 g of semen lepidii, 13 g of red peony root, 8 g of coptis chinensis.

[0058] Example 4

[0059] A traditional Chinese medicine composition for treating heart failure is as follows:

[0060] The composition of a traditional Chinese medicine composition for treating heart failure: 12 g of red ginseng, 7 g of prepared aconite root, 16 g of cornelian cherry fruit, 12 g of rehmannia root, 13 g of astragalus membranaceus var. mongholicus, 7 g of rhodiola rosea, 11 g of dried ginger, 22 g of poria cocos, 4 g of notoginseng powder, 18 g of semen lepidii, 11 g of red peony root, 9 g of coptis chinensis.

[0061] Example 5

[0062] A traditional Chinese medicine composition for treating heart failure is as follows:

[0063] The composition of a traditional Chinese medicine composition for treating heart failure: 15 g of red ginseng, 10 g of prepared aconite root, 30 g of cornelian cherry fruit, 20 g of rehmannia root, 30 g of astragalus membranaceus var. mongholicus, 15 g of rhodiola rosea, 12 g of dried ginger, 30 g of poria cocos, 6 g of notoginseng powder, 30 g of semen lepidii, 15 g of red peony root, 10 g of coptis chinensis.

[0064] Example 6

[0065] A traditional Chinese medicine composition for treating heart failure is as follows:

[0066] Composition of a traditional Chinese medicine composition for treating heart failure: 14 g of red ginseng, 7 g of prepared aconite root, 25 g of cornel fruit, 17 g of rehmannia root, 18 g of astragalus membranaceus var. mongholicus, 8 g of rhodiola rosea, 11 g of dried ginger, 25 g of poria cocos, 2 g of panax notoginseng powder, 18 g of semen lepidii, 15 g of red peony root, 9 g of coptis chinensis.

[0067] Example 7

[0068] Preparation method of a traditional Chinese medicine composition for treating heart failure is as follows:

[0069] The traditional Chinese medicine compositions provided in the above Examples 1 to 6 are all prepared according to the following steps:

[0070] Weigh red ginseng, prepared aconite root, cornel fruit, rehmannia root, astragalus membranaceus var. mongholicus, rhodiola rosea, dried ginger, poria cocos, semen lepidii, red peony root, and coptis chinensis, and set aside.

[0071] First decoct the prepared aconite root for 30 minutes, add cornel fruit, rehmannia root, astragalus membranaceus var. mongholicus, rhodiola rosea, dried ginger, poria cocos, semen lepidii, red peony root, and coptis chinensis, add water equivalent to 8 times the amount of the medicinal material mixture, decoct 2 times, 30 minutes each time, and collect the mixed decoction.

[0072] Decoct red ginseng with water, add water equivalent to 6 times the amount of red ginseng, decoct 1 time, 60 minutes each time, and collect the red ginseng decoction.

[0073] Combine the mixed decoction and the red ginseng decoction to obtain the medicinal decoction, pour the panax notoginseng powder into the finally decocted medicinal decoction, and stir evenly to obtain.

[0074] The clinical effective rates of the traditional Chinese medicine compositions in the above examples all exceed 90%. Therefore, only the traditional Chinese medicine composition prepared by using the raw materials described in Example 1 and the preparation method of Example 7 is taken as an example for effect description.

[0075] Example 8

[0076] A water pill for treating heart failure is as follows:

[0077] According to the properties of each single herb in the prescription, clinical requirements and dosage form characteristics, all the Chinese medicinal materials in the prescription are extracted by water decoction, the traditional Chinese medicine composition is prepared according to the technological conditions in Example 7, concentrated and then prepared into water pills, and the hygroscopicity and fluidity of the water pills are examined to see if they meet the quality standards of water pills. After meeting the standards, the bulk density and angle of repose are measured, and it is determined whether the water pills meet the quality standards according to the preparation quality standard system. The contents of effective components such as ginsenoside Rg1, ginsenoside Re, and ginsenoside Rh in the traditional Chinese medicine composition for treating heart failure are measured to control the product quality. Combining with the requirements of the stability test of new traditional Chinese medicines, the stability of this preparation is investigated. If the product quality and stability both meet the standards, it indicates successful preparation.

[0078] Example 9

[0079] Application of a traditional Chinese medicine composition for treating heart failure is as follows:

[0080] 1. Mechanism study on treating chronic heart failure with a traditional Chinese medicine composition for treating heart failure predicted by network pharmacology and molecular docking is as follows:

[0081] Through network pharmacology and molecular docking techniques, explore the effective and significant components of the traditional Chinese medicine composition for treating heart failure in treating chronic heart failure and predict the specific mechanism of action. Collect and sort out the effective compound components and related potential target information of the traditional Chinese medicine composition for treating heart failure through TCMSP, Pubchem databases and referring to relevant literature. Use GeneCards and OMIM databases to screen the targets related to chronic heart failure, and obtain the disease target dataset related to chronic heart failure after removing duplicates from the two databases; take the intersection of the targets of the traditional Chinese medicine composition for treating heart failure and the disease targets, and screen out the core targets; use the Metascape database to analyze and predict the mechanism of action of the traditional Chinese medicine composition for treating heart failure in treating chronic heart failure; it is speculated that the mechanism of the traditional Chinese medicine composition for treating heart failure in treating chronic heart failure may be: ① reducing myocardial cell inflammation and oxidative stress responses, inhibiting myocardial cell apoptosis and vascular endothelial cell senescence, thereby enhancing myocardial cell vitality and function; ② preventing atherosclerosis, improving myocardial ischemia and myocardial ischemia-reperfusion injury, and protecting heart function; ③ regulating cell active factors, weakening myocardial fibrosis, and inhibiting ventricular remodeling to perform molecular docking of the core effective components and key core targets of the traditional Chinese medicine composition for nourishing the heart and promoting blood circulation.

[0082] Through molecular docking verification, it is found that the five main chemical components of the traditional Chinese medicine composition for treating heart failure, namely quercetin, β-sitosterol, kaempferol, herniarin, and paeoniflorin, all have good binding activities with the core targets of chronic heart failure. This study predicts that the mechanism of action of the traditional Chinese medicine composition for treating heart failure in treating chronic heart failure is that after the effective compound components bind to the core target genes such as IL6, TNF, AKT1, VEGFA, CASP3, and EGFR, by regulating related signaling pathways such as the MAPK pathway, HIF-1 pathway, PI3K-Akt pathway, Toll-like receptor pathway, etc., it promotes myocardial cell and blood vessel neogenesis, inhibits the process of myocardial cell apoptosis and inflammatory response, reduces myocardial fibrosis, and delays ventricular structural remodeling, thereby exerting the pharmacological effect of treating chronic heart failure.

[0083] 2. Construction of a chronic heart failure rat model is as follows:

[0084] In this experiment, 100 SPF-grade SD rats at 1.5 months of age with a body weight of 150 g ± 20 g were adaptively fed for 1 week. Then, 8 rats were randomly selected for sham operation group which only passed the thread without ligation, denoted as sham; 92 rats were ligated with the left anterior descending coronary artery and fed routinely for 8 weeks to establish a rat model of chronic heart failure after myocardial infarction. After the operation, after 8 weeks of routine feeding, the rats were fasted for 12 hours, and the chest hair of the rats was removed and the skin was prepared for detecting cardiac function.

[0085] The detection of cardiac function is as follows:

[0086] Anesthesia: With the assistance of an anesthesia machine, the rats in the model group were placed in a small animal anesthesia box. The ventilation volume was set at 1.5 L / min - 2 L / min, and the inhaled isoflurane volume fraction was 2%. After the anesthesia took effect, conductive gel was applied to the electrode plate in advance, and the four limbs of the rats were fixed with adhesive tape. The rats were fixed in the supine position on the operating table. Physiological indexes such as the body temperature, heart rate, and respiration of the rats can be displayed in real time through a physiological information collector. During the detection, the heart rate of the rats can be controlled at 300 beats / min - 400 beats / min.

[0087] A high-resolution small animal ultrasonic detection system and a high-frequency probe were used to detect the cardiac function of the mice. The parameters of the detection system were: probe frequency 21 MHZ, measurement rate 200 mm / s, and measurement depth 3 cm. The data of left ventricular end-diastolic volume and end-systolic volume were obtained through two-dimensional imaging mode. The data measured in three cardiac cycles were taken, and the average value was used as a reference index. In the model group, rats with LVEF < 55% were established as the heart failure model group.

[0088] The effects of the traditional Chinese medicine composition for treating heart failure on the over-activation of the RAAS system and myocardial fibrosis in rats with chronic heart failure are as follows:

[0089] According to the left ventricular ejection fraction, that is, LVEF, the eligible rats with heart failure model were randomly grouped by the random number table method, divided into model control group, positive drug captopril group, low-dose group of traditional Chinese medicine composition for treating heart failure, and high-dose group of traditional Chinese medicine composition for treating heart failure; the model control group was intragastrically administered with the same amount of drinking water as the traditional Chinese medicine composition for treating heart failure. Among them, the model control group is denoted as Model, the positive drug group is denoted as KT, the low-dose group of traditional Chinese medicine composition for treating heart failure is denoted as YXD, and the high-dose group of traditional Chinese medicine composition for treating heart failure is denoted as YXG. The traditional Chinese medicine composition for treating heart failure was prepared in Example 1.

[0090] The equivalent dosage of each group of rats was calculated according to "Pharmacological Experiment Methods" edited by Xu Shuyun as follows:

[0091] ① The equivalent dose of the traditional Chinese medicine composition for treating heart failure in the low-dose group of rats was 20.9 g crude drug / kg / d, and the decoction concentration was 2.09 g crude drug / mL. Before each daily gavage, the rats were weighed, and 1 mL of the traditional Chinese medicine was gavaged per 100 g of the rat body weight.

[0092] ② The equivalent dose of the traditional Chinese medicine composition for treating heart failure in the high-dose group of rats was 41.8 g crude drug / kg / d, and the decoction concentration was 4.18 g crude drug / mL. Before each daily gavage, the rats were weighed, and 1 mL of the traditional Chinese medicine was gavaged per 100 g of the rat body weight.

[0093] ③ The equivalent dose of captopril in the rats of the captopril group was 12.5 mg crude drug / kg / d. After being ground into powder, it was dissolved in distilled water to prepare a solution with a concentration of 1.25 mg crude drug / mL. Before each daily gavage, the rats were weighed, and 1 mL was gavaged per 100 g of the rat body weight.

[0094] ④ Model group: Before each daily gavage, the rats were weighed, and 1 mL of drinking water was gavaged per 100 g of the rat body weight.

[0095] ⑤ Sham operation group: Before each daily gavage, the rats were weighed, and 1 mL of drinking water was gavaged per 100 g of the rat body weight.

[0096] After 4 weeks of gavage, the general condition of the rats was observed, blood and heart tissues were collected, and the levels of NT-proBNP, plasma angiotensin II (AngII), endothelin-1 (ET-1), and atrial natriuretic peptide (ANP) were detected by ELISA; the mRNA levels of matrix metalloproteinases MMP-2 and MMP-9 in the myocardial tissue were detected by immunohistochemistry and REAL-TIME PCR; the change in the expression of myocardial TGF-β1 was detected by Western blotting; and the degree of myocardial fibrosis was observed by Masson staining.

[0097] Results: As shown in Table 2, Figure 1 compared with the sham-operated rats, the LVEF values of the rats in each group were significantly decreased 8 weeks after ligation of the left anterior descending branch, P < 0.01, indicating that the cardiac function of the rats was significantly impaired after myocardial infarction; after 4 weeks of drug administration, compared with the model group, the LVEF value in the KT group increased, P < 0.01; the LVEF value in the YXG group increased, P < 0.01; and the LVEF value in the YXD group was statistically significant, P < 0.05.

[0098] Table 2 Comparison of LVEF of rats in each group 8 weeks after modeling and 4 weeks after drug administration, n = 7,

[0099]

[0100]

[0101] Note: Compared with the model group, *P<0.05, **P<0.01; compared with the sham operation group, *P<0.05, **P<0.01.

[0102] As shown in Table 3, Figures 2 to 5 the levels of NT-proBNp, ANP, ET-1, and AngII in the high-dose traditional Chinese medicine composition group, captopril control group, and model group were significantly higher than those in the sham operation group, P<0.01, indicating that the RAAS system was continuously activated during heart failure in rats, and neurohumoral factors including ANP, ET-1, and AngII participated in the entire process of ventricular remodeling. Both captopril and the traditional Chinese medicine composition group could reduce the levels of NT-proBNp, ANP, ET-1, and AngII, P<0.01, significantly decreasing the levels of ANP, ET-1, and AngII in the blood, confirming that the activated RAAS system during heart failure was inhibited, thereby improving ventricular remodeling and heart failure. It also revealed that the mechanism of the traditional Chinese medicine composition in treating heart failure might be to inhibit the excessive activation of the RAAS system.

[0103] Comparison of the concentrations of NT-proBNP, ANP, ET-1, and AngII in the sera of rats in each group, n = 7 - 12,

[0104]

[0105] Note: Compared with the model group, *P<0.05, **P<0.01; compared with the sham operation group, *P<0.05, **P<0.01.

[0106] As shown in Table 4, Figure 6 and Figure 7 it was found through Masson staining that compared with the sham operation group, the percentage of myocardial collagen CVF in the traditional Chinese medicine composition group, captopril control group, and model group all increased significantly, P<0.01, indicating that ventricular remodeling occurred in the myocardium of each experimental group. Compared with the model group, the percentage of myocardial collagen in the traditional Chinese medicine composition group and captopril group both decreased significantly, P<0.01, indicating that both the traditional Chinese medicine composition and captopril could inhibit ventricular remodeling after myocardial infarction, suggesting that the traditional Chinese medicine composition had the effect of reducing myocardial fibrosis, thereby alleviating heart failure.

[0107] Comparison of the collagen volume fraction in the myocardial tissues of each group, n = 6

[0108] Grouping Collagen volume fraction of myocardial tissue, % YXD 6.61±2.81** YXG 4.64±2.29** KT 8.41±2.56** Model 19.45±5.01** Sham 4.69±1.17

[0109] Note: Compared with the model group, *P<0.05, **P<0.01; compared with the sham operation group, *P<0.05, **P<0.01.

[0110] The levels of MMP-2 mRNA and MMP-9 mRNA in myocardial tissues were detected by PCR assay. As shown in Table 5, Figure 8 compared with the normal control group, the content of MMP-2 mRNA in the model group increased significantly, P < 0.01. Compared with the model group, the content of MMP-2 mRNA in the low-dose traditional Chinese medicine composition group and the captopril group decreased significantly, P < 0.01. Compared with the model group, the content of MMP-2 mRNA in the high-dose traditional Chinese medicine composition group decreased significantly, P < 0.01.

[0111] Table 5 Relative expression levels of MMP-2 mRNA in myocardial tissues of rats in each group, n = 3 - 7,

[0112] Grouping MMP-2mRNA YXD, n = 7 2.49±1.08** YXG, n = 7 2.27±0.96** KT, n = 3 1.76±0.86** Model, n = 3 9.24±6.41** Sham, n = 7 0.96±0.74

[0113] Note: Compared with the model group, *P < 0.05, **P < 0.01; compared with the sham operation, *P < 0.05, **P < 0.01.

[0114] As shown in Table 6, Figure 9 compared with the normal control group, the content of MMP-9 mRNA in the model group increased significantly, P < 0.01; compared with the model group, the content of MMP-9 mRNA in the low-dose and high-dose traditional Chinese medicine composition groups decreased significantly, P < 0.01. Compared with the model group, the content of MMP-9 mRNA in the captopril group decreased significantly, P < 0.05.

[0115] Table 6 Relative expression levels of MMP-9 mRNA in myocardial tissues of rats in each group, n = 3 - 7,

[0116] Grouping MMP-9mRNA YXD, n = 7 3.03±2.27** YXG, n = 7 1.77±1.5** KT, n = 3 1.63±1.08** Model, n = 3 21.32±20.95** Sham, n = 7 2.32±2.08

[0117] Note: Compared with the model group, *P < 0.05, **P < 0.01; compared with the sham operation, *P < 0.05, **P < 0.01.

[0118] As shown in Table 7, Figure 10 and Figure 11 simultaneously, the expression of TGF-β1 protein in myocardial tissues was detected by Western blot. Compared with the normal control group, the expression content of TGF-β1 protein in the model group increased significantly, P < 0.01. Compared with the model group, the expression content of TGF-β1 protein in the low- and high-dose traditional Chinese medicine composition groups decreased significantly, P < 0.01. Compared with the model group, the expression content of TGF-β1 protein in the captopril group also decreased, P < 0.01.

[0119] Table 7 Relative expression levels of TGF-β1 in myocardial tissues of rats in each group, n = 3 - 7,

[0120]

[0121]

[0122] Note: Compared with the model group, *P<0.05, **P<0.01; compared with the sham operation group, *P<0.05, **P<0.01.

[0123] Using the traditional Chinese medicine composition described in the present invention can improve the LVEF value of cardiac function, and can significantly reduce the levels of serum NT-proBNP, ANP, ET-1, and AngII in heart failure rats, indicating that this traditional Chinese medicine composition may reverse ventricular remodeling and improve cardiac function by regulating the levels of ANP, ET-1, and AngII and inhibiting the excessive activation of the RAAS system; it can also reduce the percentage of myocardial collagen, the content of MMP-2 and MMP-9 mRNA, and down-regulate the expression level of TGF-β1 protein, indicating that the traditional Chinese medicine composition can improve heart failure by reducing the degree of myocardial fibrosis and delaying ventricular remodeling.

[0124] Although the preferred embodiments of the present invention have been described, those skilled in the art can make additional changes and modifications once they learn the basic creative concepts. Therefore, the appended claims are intended to be construed as including the preferred embodiments and all changes and modifications falling within the scope of the present invention.

[0125] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these modifications and variations.

Claims

1. A traditional Chinese medicine composition for treating chronic heart failure, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10-15 parts of red ginseng, 5-10 parts of prepared aconite root, 15-30 parts of cornel fruit, 10-20 parts of rehmannia root, 15-30 parts of astragalus membranaceus var. mongholicus, 6-15 parts of rhodiola rosea, 6-12 parts of dried ginger, 15-30 parts of poria cocos, 2-6 parts of panax notoginseng powder, 15-30 parts of semen lepidii, 10-15 parts of red peony root, 5-10 parts of coptis chinensis.

2. The preparation method of the traditional Chinese medicine composition according to claim 1, wherein It includes the following steps: Weigh red ginseng, prepared aconite root, cornel fruit, rehmannia root, astragalus membranaceus var. mongholicus, rhodiola rosea, dried ginger, poria cocos, semen lepidii, red peony root, and coptis chinensis according to the parts by weight, and set aside; Decoct the weighed traditional Chinese medicine raw materials with water, collect the decoction of the medicine, and add panax notoginseng powder to the decoction of the medicine, and mix evenly to obtain the traditional Chinese medicine composition.

3. The preparation method according to claim 2, characterized in that, The process of decocting with water is as follows: First decoct the prepared aconite root, and then add cornel fruit, rehmannia root, astragalus membranaceus var. mongholicus, rhodiola rosea, dried ginger, poria cocos, semen lepidii, red peony root, and coptis chinensis. A total of 6-8 times the mass of water equivalent to the medicinal material mixture is added for decoction, and the decoction of the medicinal material mixture is collected; Add red ginseng to water for decoction in an amount 6-8 times the mass of red ginseng, and collect the decoction of red ginseng; Combine the decoction of the mixture and the decoction of red ginseng to obtain the decoction of the medicine.

4. The preparation method according to claim 3, characterized in that, The time for the first decoction is 30-40 minutes, the number of decoctions is 1-2 times, and the time for decoction is 20-60 minutes.

5. Use of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicament for treating chronic heart failure.

6. The application according to claim 5, wherein The chronic heart failure is caused by heart disease.

7. The application according to claim 6, characterized in that The heart disease includes at least one of coronary heart disease, cardiomyopathy, pulmonary heart disease, congenital heart disease, rheumatic heart disease, and viral myocarditis.

8. The application according to claim 5, characterized in that The medicament includes the traditional Chinese medicine composition and pharmaceutically acceptable excipients.

9. The application according to claim 5, characterized in that The dosage form of the medicament is water pills, dripping pills, honey pills, granules, powders, capsules, soft capsules, tablets, mixtures or oral liquids.

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