Traditional Chinese medicine composition as well as preparation method and application thereof

By using traditional Chinese medicine compositions with specific compatibility relationships, the problems of the side effects of traditional Chinese and Western medicine and the inadequate efficiency of traditional Chinese medicine compositions are solved, and the effect of efficient improvement of cardiac function and reducing myocardial fibrosis is achieved, with clinical efficiency exceeding 90%.

CN119524096AActive Publication Date: 2025-02-28SHAANXI ACAD OF TRADITIONAL CHINESE MEDICINE +1
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Patent Information

Application Number
CN202411800475.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-09
Publication Date
2025-02-28
Estimated Expiration
2044-12-09

AI Technical Summary

Technical Problem

In the treatment of chronic heart failure, the long-term use of Western medicine may cause a variety of side effects, and the clinical effectiveness of traditional Chinese medicine compositions does not exceed 85%, making it difficult to meet the needs of efficient treatment.

Method used

A Chinese medicine composition is adopted, consisting of red ginseng, atria tablets, cornus officinalis, raw rehmannia, astragalus, rhodiola, dried ginger, poria, Panax notoginseng powder, celestialis, red peony root and coptis chinensis. By decorating water and adding Panax notoginseng powder, a Chinese medicine composition with a specific relationship between the monarch and ministers and the medicine is prepared.

Benefits of technology

The clinically effective Chinese medicine composition is more than 90%, which can improve cardiac function, reduce the serum NT-proBNP, ANP, ET-1, and AngII levels of rats with heart failure, reduce the degree of myocardial fibrosis, delay ventricular remodeling, and thus improve heart failure.

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Abstract

The invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition and a preparation method and application thereof. 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 radix aconiti lateralis preparata, 15-30 parts of pulp of dogwood fruit, 10-20 parts of radix rehmanniae, 15-30 parts of radix hedysari, 6-15 parts of rhodiola rosea, 6-12 parts of dried ginger, 15-30 parts of poria cocos, 2-6 parts of pseudo-ginseng powder, 15-30 parts of semen lepidii, 10-15 parts of radix paeoniae rubra and 5-10 parts of coptis chinensis. The invention also discloses a preparation method of the traditional Chinese medicine composition and application of the traditional Chinese medicine composition in preparation of medicines for treating heart failure. Researches show that the traditional Chinese medicine composition can relieve heart failure by relieving the myocardial fibrosis degree and delaying ventricular remodeling, so that a new thought is provided for treating heart failure.
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Description

Technical Field

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

[0002] Heart failure is caused by various chronic myocardial diseases and long-term ventricular overload due to any reasons such as myocardial infarction, cardiomyopathy, hemodynamic overload, inflammation, etc., resulting in primary or secondary weakening of myocardial contractility, making the heart unable to pump out blood supply commensurate with venous return and body tissue metabolism, 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 is mostly organic cardiovascular disease that has undergone 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 organ and tissue perfusion, and systemic congestion gradually appear. The goal of treating heart failure is not only to improve symptoms and improve the 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 rate of heart failure.

[0003] Western medicine mainly uses the following types of drugs to treat chronic heart failure: angiotensin-converting enzyme inhibitors, diuretics, beta-blockers, angiotensin II receptor blockers and aldosterone inhibitors. However, long-term use of Western medicine may cause hypokalemia, hyperkalemia and hypotension, transient deterioration of renal function, dry cough, angioedema, hyperkalemia, and easily induce or aggravate bradyarrhythmias, hypotension, fluid retention or worsening of heart failure.

[0004] Heart failure belongs to the categories of "heart water", "palpitations", "asthma", "edema", and "heart failure" in traditional Chinese medicine. Lei Zhongyi deeply studied ancient Chinese medical books and believed that patients with heart failure have long-term damaged heart qi, and qi deficiency can develop into qi and yin deficiency over time. Long-term illness enters the collaterals, and long-term illness will cause blood stasis in the collaterals. Water, phlegm, dampness, and blood stasis grow in the body without transformation, further damaging the kidney yang. He proposed the theory of treating the heart from the kidney and formulated a Chinese medicine composition for nourishing the heart and activating blood to treat the yin and yang deficiency and phlegm, stasis, and water retention type of chronic heart failure. Lei Lao believed that the symptoms of this disease are deficiency in the root and excess in the superficial, and the emphasis is on replenishing the deficiency to cultivate the root, and expelling the evil to treat the symptoms. At present, many patent medicines and injections are used in clinical practice, such as Xinlikang, which replenishes qi and yin, activates blood circulation and removes blood stasis, and promotes diuresis and swelling; Nuanxin Capsules, which have the effects of replenishing qi and warming the heart, promoting yang and removing blood stasis; Qili Qiangxin Capsules, which replenish heart qi, activate blood circulation and dredge collaterals, etc. The clinical efficacy of the above drugs does not exceed 85%.

[0005] In view of this, there is a need to provide a Chinese medicine composition with excellent efficacy in treating heart failure. Summary of the invention

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

[0007] In order to solve the above technical problems, the present invention adopts the following technical solutions.

[0008] The first aspect of the present invention provides a Chinese medicine composition, which is prepared from the following raw materials:

[0009] 10-15 portions of red ginseng, 5-10 portions of processed aconite root, 15-30 portions of cornus fruit, 10-20 portions of raw rehmannia, 15-30 portions of red astragalus, 6-15 portions of rhodiola rosea, 6-12 portions of dried ginger, 15-30 portions of poria, 2-6 portions of notoginseng powder, 15-30 portions of scutellaria baicalensis seeds, 10-15 portions of red peony root, and 5-10 portions of coptis root.

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

[0011] 10-13 parts of red ginseng, 8-10 parts of processed aconite root, 15-20 parts of cornus fruit, 16-20 parts of raw rehmannia, 20-30 parts of red astragalus, 10-15 parts of rhodiola rosea, 6-11 parts of dried ginger, 15-22 parts of poria, 3-6 parts of notoginseng powder, 18-30 parts of scutellaria baicalensis, 10-13 parts of red peony root, and 8-10 parts of coptis chinensis.

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

[0013] 10 parts of red ginseng, 10 parts of processed aconite root, 20 parts of cornus fruit, 20 parts of raw rehmannia, 20 parts of red astragalus, 10 parts of rhodiola rosea, 6 parts of dried ginger, 20 parts of poria, 3 parts of notoginseng powder, 30 parts of scutellaria baicalensis, 10 parts of red peony root, and 10 parts of coptis root.

[0014] The second aspect of the present invention provides a method for preparing the Chinese medicine composition, comprising the following steps:

[0015] Weigh red ginseng, processed aconite root, cornus fruit, raw rehmannia, red astragalus, rhodiola rosea, dried ginger, poria, scutellaria baicalensis, red peony root, and coptis chinensis according to weight proportions and set aside.

[0016] The weighed Chinese medicinal raw materials are added with water and boiled, the medicinal decoction is collected, and Panax notoginseng powder is added to the medicinal decoction and mixed evenly to obtain the Chinese medicinal composition.

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

[0018] Decoction the prepared aconite root first, then add cornus fruit, raw rehmannia, red astragalus, rhodiola rosea, dried ginger, poria, scutellaria baicalensis, red peony root, and coptis chinensis, and add water equivalent to 6 to 8 times the mass of the medicinal material mixture in total, decoct, and collect the decoction of the medicinal material mixture.

[0019] Add red ginseng into water equivalent to 6 to 8 times the mass of red ginseng and boil it, and collect the red ginseng decoction.

[0020] The mixture decoction and the red ginseng decoction are combined to obtain a medicinal decoction.

[0021] The third aspect of the present invention provides the use of the traditional Chinese medicine composition in the preparation of a medicine 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 medicine includes the Chinese medicine composition and pharmaceutically acceptable excipients.

[0025] In some embodiments of the present invention, the dosage form of the drug is water pills, drop 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 to prepare a preparation for inhibiting excessive activation of the renin-angiotensin-aldosterone system.

[0027] In the present invention, the relationship between the monarch and minister of the Chinese medicine composition is:

[0028] The main medicines are: red ginseng and processed aconite root.

[0029] The assistant drugs are: Astragalus, Rhodiola, Panax notoginseng, Cornus officinalis, dried ginger and Poria.

[0030] Auxiliary drugs are: Trichosanthes kirilowii and Paeonia lactiflora.

[0031] The adjuvant drugs are: raw Rehmannia root and Coptis chinensis.

[0032] The recipe for nourishing the heart and activating blood circulation uses red ginseng and the pungent and hot processed aconite root as the main medicine. Red ginseng has the effects of greatly replenishing vital energy, nourishing the spleen and lungs, promoting the production of body fluids, calming the mind and improving intelligence. Aconite root is warm in nature and has strong medicinal power. It not only has the effect of warming the kidney yang and warming the spleen and earth to help the yang qi, but is also good at restoring yang and rescuing adverse conditions, replenishing fire and supporting yang, and dispersing cold and relieving pain. The two medicines are matched, which has the effect of replenishing qi and warming yang, and helps the heart pulse to run, so as to treat the heart from the kidney. The auxiliary medicine is red astragalus, which can replenish the deficiency of the five internal organs, nourish the vital energy, and strengthen the spleen and stomach. It can not only promote the spleen qi to strengthen the acquired foundation, but also replenish the deficiency of lung qi, replenish qi and consolidate the exterior, and can also promote diuresis and reduce swelling. Qi can promote blood circulation. The circulation of blood vessels depends on the promotion of qi. If qi is deficient, the pulse will not flow and blood stasis will stagnate; together with red ginseng, it replenishes qi to promote blood circulation, so-called "qi flows and blood flows". Dried ginger warms the middle and dispels cold, restores yang and dredges the meridians; cornus fruit nourishes the liver and kidneys, astringes and consolidates the body, and helps aconite warm and tonify the spleen and kidneys; rhodiola rosea invigorates qi and activates blood circulation, dredges the meridians and calms asthma; poria invigorates the spleen, promotes diuresis and eliminates dampness; panax notoginseng regulates qi and activates blood circulation, reduces swelling and relieves pain, and has the effect of removing blood stasis and promoting newness. The so-called "bringing forth the new through the old", the combination of the above medicines plays the role of invigorating qi, promoting blood circulation and promoting water circulation, and warming and transporting water and dampness. With scutellaria baicalensis to purge the lungs and calm asthma, promote diuresis and reduce swelling, red peony root clears heat and cools blood, disperses blood stasis and relieves pain, they help the monarch and ministers to promote diuresis and dredge the meridians, and lead the evil out. The use of raw Rehmannia root can cool blood and activate blood circulation, nourish Yin and blood, and replenish the damaged Yin fluid. When used together with the above medicines, Yin generates Yang, and Yin and Yang are mutually rooted and used. Yin seeks Yang, and Yang seeks Yin. It has the effect of balancing Yin and Yang, treating the heart from the kidney, and can restrain the warm and dry nature of the main medicine. The use of Coptis chinensis is intended to restrain the pungent and dry toxicity of Aconite, and it belongs to the heart meridian, which has the function of guiding the meridians and reporting to the messenger. The combination of various medicines can warm and replenish Yin and Yang, activate blood circulation and resolve phlegm, and dredge the meridians and promote diuresis.

[0033] Compared with the prior art, the present invention has the following beneficial effects: the use of the Chinese medicine composition of the present invention can improve the LVEF value of cardiac function, and can significantly reduce the serum NT-proBNP, ANP, ET-1, and AngII levels of rats with heart failure, indicating that the Chinese medicine composition may inhibit the excessive activation of the RAAS system by regulating the levels of ANP, ET-1, and AngII, thereby reversing ventricular remodeling and improving cardiac function; it can also reduce the percentage of myocardial collagen ratio, reduce the content of MMP-2 and MMP-9 mRNA, and down-regulate the expression level of TGF-β1 protein. At the same time, the clinical effective rate of the Chinese medicine composition of the present invention is 90%, which has a higher effective rate under the same syndrome conditions, indicating that the 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The bar graphs are comparative LVEFs of rats in each group 8 weeks after modeling and 4 weeks after drug administration.

[0035] Figure 2 It is a bar graph showing the changes in NT-proBNp concentration in the serum of rats in each group.

[0036] Figure 3 The bar graph shows the changes in ANP concentration in the serum of rats in each group.

[0037] Figure 4 The bar graph shows the changes in ET-1 concentration in the serum of rats in each group.

[0038] Figure 5 The bar graph shows the changes in AngII concentration in the serum of rats in each group.

[0039] Figure 6 Figure 1 is the Masson staining result of myocardial tissue of rats in each group; A is the Masson staining result of myocardial tissue of rats in YXD group; B is the Masson staining result of myocardial tissue of rats in YXG group; C is the Masson staining result of myocardial tissue of rats in KT group; D is the Masson staining result of myocardial tissue of rats in Model group; E is the Masson staining result of myocardial tissue of rats in Sham group.

[0040] Figure 7 The figure is a bar graph comparing the collagen volume fraction of myocardial tissue in each group of rats.

[0041] Figure 8 The bar graph shows the relative expression of MMP-2 mRNA in myocardial tissue of rats in each group.

[0042] Fig. 9 The bar graph shows the relative expression of MMP-9 mRNA in myocardial tissue of rats in each group.

[0043] Fig.10 This is a representative picture of TGF-β1 protein expression in each group detected by Western blot.

[0044] Fig.11 This is a bar graph of the relative expression of TGF-β1 in myocardial tissue of rats in each group. DETAILED DESCRIPTION

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

[0046] 1. Experimental Drugs

[0047] Table 1 Experimental drugs

[0048] Components of Chinese medicine composition Tong Ren Tang, Beijing, China Captopril Tablets Sinopharm Shantou Jinshi Pharmaceutical Co., Ltd. Urethane China Caoyang Second Reagent Factory 0.9% Sodium Chloride Injection Sichuan Kelun Pharmaceutical Co., Ltd. Heparin Sodium Injection Shanghai First Biochemical Pharmaceutical Co., Ltd. Isoflurane Hebei Yipin Pharmaceutical Co., Ltd.

[0049] Example 1

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

[0051] A traditional Chinese medicine composition for treating heart failure comprises: 10g of red ginseng, 10g of prepared aconite root, 20g of cornus fruit, 20g of raw rehmannia, 30g of red astragalus, 15g of rhodiola rosea, 10g of dried ginger, 30g of poria, 3g of notoginseng powder, 30g of scutellaria baicalensis, 15g of red peony root, and 8g of coptis root.

[0052] Example 2

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

[0054] A traditional Chinese medicine composition for treating heart failure comprises: 15g red ginseng, 5g processed aconite root, 30g cornus fruit, 10g raw rehmannia, 30g red astragalus, 15g rhodiola rosea, 12g dried ginger, 30g poria, 6g notoginseng powder, 15g scutellaria baicalensis, 15g red peony root, and 5g coptis root.

[0055] Example 3

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

[0057] A traditional Chinese medicine composition for treating heart failure comprises: 13g of red ginseng, 8g of prepared aconite root, 15g of cornus fruit, 16g of raw rehmannia, 15g of red astragalus, 6g of rhodiola rosea, 10g of dried ginger, 15g of poria, 2g of notoginseng powder, 20g of scutellaria baicalensis, 13g of red peony root, and 8g of coptis root.

[0058] Example 4

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

[0060] A traditional Chinese medicine composition for treating heart failure comprises: 12g of red ginseng, 7g of prepared aconite root, 16g of cornus fruit, 12g of raw rehmannia, 13g of red astragalus, 7g of rhodiola rosea, 11g of dried ginger, 22g of poria, 4g of notoginseng powder, 18g of scutellaria baicalensis, 11g of red peony root, and 9g of coptis root.

[0061] Example 5

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

[0063] A traditional Chinese medicine composition for treating heart failure comprises: 15g of red ginseng, 10g of prepared aconite root, 30g of cornus fruit, 20g of raw rehmannia, 30g of red astragalus, 15g of rhodiola rosea, 12g of dried ginger, 30g of poria, 6g of notoginseng powder, 30g of scutellaria baicalensis, 15g of red peony root, and 10g of coptis root.

[0064] Example 6

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

[0066] A traditional Chinese medicine composition for treating heart failure comprises: 14g red ginseng, 7g processed aconite root, 25g cornus fruit, 17g raw rehmannia root, 18g red astragalus, 8g rhodiola rosea, 11g dried ginger, 25g poria, 2g notoginseng powder, 18g scutellaria baicalensis, 15g red peony root, and 9g coptis root.

[0067] Example 7

[0068] A method for preparing a Chinese medicine composition for treating heart failure is as follows:

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

[0070] Weigh red ginseng, processed aconite root, cornus fruit, raw rehmannia, red astragalus, rhodiola rosea, dried ginger, poria, scutellaria baicalensis, red peony root, and coptis chinensis for later use.

[0071] Boil the prepared aconite root for 30 minutes first, then add cornus fruit, raw rehmannia, red astragalus, rhodiola rosea, dried ginger, poria, scutellaria baicalensis, red peony root, and coptis chinensis, add water equivalent to 8 times the amount of the medicinal material mixture, boil twice, each time for 30 minutes, and collect the mixed decoction.

[0072] Decoction of red ginseng was performed, and water equivalent to 6 times of the red ginseng was added. Decoction was performed once for 60 minutes each time, and the decoction of red ginseng was collected.

[0073] Combine the mixture decoction and the red ginseng decoction to obtain a medicinal decoction, pour the Panax notoginseng powder into the final prepared medicinal decoction, stir evenly, and obtain the product.

[0074] The clinical efficacy of the Chinese medicine compositions in the above examples is more than 90%, so the effect is described below by taking the Chinese medicine composition prepared by the preparation method of Example 7 using the raw materials described in Example 1 as an example.

[0075] Example 8

[0076] A water pill for treating heart failure, 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, and the Chinese medicine composition is prepared according to the process conditions in Example 7. After concentration, it is prepared into water pills. The hygroscopicity and fluidity of the water pills are examined to see whether they meet the quality standards of water pills. After meeting the standards, the bulk density and angle of repose are measured. According to the preparation quality standard system, it is determined whether the water pills meet the quality standards. The content of effective ingredients such as ginsenoside Rg1, ginsenoside Re, and ginsenoside Rh in the Chinese medicine composition for treating heart failure is measured to control the product quality. Combined with the requirements for the stability test of new Chinese medicines, the stability of this preparation is investigated. If the product quality and stability meet the standards, it means that the preparation is successful.

[0078] Example 9

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

[0080] 1. Research on the mechanism of Chinese medicine composition for treating chronic heart failure based on network pharmacology and molecular docking prediction, as follows:

[0081] Through network pharmacology and molecular docking, the effective and significant components of traditional Chinese medicine compositions for the treatment of chronic heart failure are explored and the specific mechanism of action is predicted. The effective compound components and related potential target information of traditional Chinese medicine compositions for the treatment of heart failure are collected and sorted through TCMSP and Pubchem databases and relevant literature. GeneCards and OMIM databases were used to screen targets related to chronic heart failure, and the two databases were deduplicated to obtain a data set of disease targets related to chronic heart failure; the targets of the traditional Chinese medicine composition for the treatment of heart failure and the disease targets were taken as the intersection targets, and the core targets were screened out; the Metascape database was used to analyze and predict the mechanism of action of the traditional Chinese medicine composition for the treatment of heart failure in treating chronic heart failure; it was speculated that the mechanism of the traditional Chinese medicine composition for the treatment of heart failure in treating chronic heart failure may be: ① Alleviate myocardial cell inflammation and oxidative stress response, inhibit myocardial cell apoptosis and vascular endothelial cell senescence, thereby enhancing myocardial cell vitality and function; ② Prevent atherosclerosis, improve myocardial ischemia and myocardial ischemia-reperfusion injury, and protect cardiac function; ③ Regulate cell activity factors, weaken myocardial fibrosis, and inhibit ventricular remodeling to perform molecular docking of the core effective ingredients of the traditional Chinese medicine composition for nourishing the heart and activating blood circulation and key core targets.

[0082] Molecular docking verification showed that the five main chemical components of the traditional Chinese medicine composition for the treatment of heart failure, namely quercetin, β-sitosterol, kaempferol, herbaceous acid, and paeoniflorin, all had good binding activity with the core targets of chronic heart failure. This study predicts that the mechanism of action of the traditional Chinese medicine composition for the treatment of heart failure in the treatment of chronic heart failure is to promote myocardial cell and angiogenesis, inhibit myocardial cell apoptosis and inflammatory response process, reduce myocardial fibrosis, and delay ventricular structural remodeling after the effective compound components bind to the core target genes, such as IL6, TNF, AKT1, VEGFA, CASP3, and EGFR, and then regulate related signaling pathways, such as MAPK pathway, HIF-1 pathway, PI3K-Akt pathway, and Toll-like receptor pathway, thereby exerting the pharmacological effect of treating chronic heart failure.

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

[0084] In this experiment, 100 SPF SD rats aged 1.5 months and weighing 150g±20g were randomly selected as the sham operation group after adaptive feeding for one week, and 8 rats were threaded without ligation, and 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 surgery, the rats were fed routinely for 8 weeks, fasted for 12 hours, and the chest hair of the rats was removed to prepare the skin for testing cardiac function.

[0085] Cardiac function tests are as follows:

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

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

[0088] 3. The effects of the Chinese medicine composition for treating heart failure on overactivation of the RAAS system and myocardial fibrosis in rats with chronic heart failure are as follows:

[0089] According to the left ventricular ejection fraction, i.e., LVEF, the heart failure model rats that meet the requirements are randomly divided into a model control group, a positive drug captopril group, a low-dose group of a Chinese medicine composition for treating heart failure, and a high-dose group of a Chinese medicine composition for treating heart failure by a random number table method; the model control group is gavaged with drinking water equal to the amount of the Chinese medicine composition for treating heart failure. Among them, the model control group is represented by Model, the positive drug group is represented by KT, the low-dose group of a Chinese medicine composition for treating heart failure is represented by YXD, and the high-dose group of a Chinese medicine composition for treating heart failure is represented by YXG. The Chinese medicine composition for treating heart failure is prepared in Example 1.

[0090] The equivalent dose of each group of rats was calculated according to the Pharmacological Experimental Methods edited by Xu Shuyun as follows:

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

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

[0093] ③ The equivalent dose of captopril in rats was 12.5 mg crude drug / kg / d. The rats were ground into powder and dissolved in distilled water to prepare a solution with a concentration of 1.25 mg crude drug / mL. The rats were weighed before daily gavage, with 1 mL of the drug administered for every 100 g of their body weight.

[0094] ④ Model group: The rats were weighed before daily gavage, and 1 mL of drinking water was gavaged for every 100 g of rat body weight.

[0095] ⑤ Sham operation group: The rats were weighed before daily gavage, and 1 mL of drinking water was gavaged for every 100 g of rat body weight.

[0096] Four weeks after intragastric administration, the general condition of the rats was observed, and blood and heart tissue were collected. Elisa was used to detect the levels of NT-proBNP, plasma angiotensin II, AngII, endothelin-1, ET-1, atrial natriuretic peptide, and ANP. Immunohistochemistry and REAL-TIMEPCR were used to detect the mRNA levels of matrix metalloproteinases MMP-2 and MMP-9 in myocardial tissue. Western blotting was used to detect the changes in myocardial TGF-β1 expression. Masson staining was used to observe the degree of myocardial fibrosis.

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

[0098] Table 2 Comparison of LVEF in each group of rats 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, Figure 2 to Figure 5 As shown in the figure, the levels of NT-proBNp, ANP, ET-1, and AngII in the high-dose group of the Chinese medicine composition, the captopril control group, and the model group were significantly higher than those in the sham operation group (P<0.01), indicating that the RAAS system of rats was continuously activated when heart failure occurred, and neurohumoral factors including ANP, ET-1, and AngII participated in the entire process of ventricular remodeling. Both the captopril and Chinese medicine composition groups could reduce the levels of NT-proBNp, ANP, ET-1, and AngII (P<0.01), which significantly reduced the levels of ANP, ET-1, and AngII in the blood, confirming that the RAAS system activated during heart failure was inhibited, thereby improving ventricular remodeling and heart failure. It also reveals that the mechanism of the Chinese medicine composition in treating heart failure may have the effect of inhibiting excessive activation of the RAAS system.

[0103] Table 3 Comparison of NT-proBNP, ANP, ET-1 and AngII concentrations in the serum 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 As shown in the figure, Masson staining showed that the percentage of myocardial collagen CVF in the Chinese medicine combination group, captopril control group and model group was significantly increased compared with the sham operation group, 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 Chinese medicine combination group and captopril group was significantly reduced, P<0.01, indicating that both the Chinese medicine combination and captopril can inhibit ventricular remodeling after myocardial infarction, suggesting that the Chinese medicine combination has the effect of reducing myocardial fibrosis, thereby alleviating heart failure.

[0107] Table 4 Comparison of collagen volume fraction of myocardial tissue in each group n=6

[0108] Grouping Myocardial tissue collagen volume fraction, % YXD 6.61±2.81** YG 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 tissue were detected by PCR. Figure 8 As shown in the figure, compared with the normal control group, the MMP-2 mRNA content in the model group increased significantly, P < 0.01. Compared with the model group, the MMP-2 mRNA content in the low-dose Chinese medicine combination group and the captopril group decreased significantly, P < 0.01. Compared with the model group, the MMP-2 mRNA content in the high-dose Chinese medicine combination group decreased significantly, P < 0.01.

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

[0112] Grouping MMP-2 mRNA 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 group, *P<0.05, **P<0.01.

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

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

[0116] Grouping MMP-9 mRNA 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 group, *P<0.05, **P<0.01.

[0118] As shown in Table 7, Fig.10 and Fig.11 As shown, Western blot was used to detect the expression of TGF-β1 protein in myocardial tissue. Compared with the normal control group, the expression of TGF-β1 protein in the model group was significantly increased, P<0.01. Compared with the model group, the expression of TGF-β1 protein in the low-dose and high-dose groups of the Chinese medicine combination was significantly decreased, P<0.01. Compared with the model group, the expression of TGF-β1 protein in the captopril group was also decreased, P<0.01.

[0119] Table 7 Relative expression of TGF-β1 in myocardial tissue 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] The use of the Chinese medicine composition described in the present invention can improve the LVEF value of cardiac function and significantly reduce the serum NT-proBNP, ANP, ET-1, and AngII levels of rats with heart failure, indicating that the Chinese medicine composition may inhibit the excessive activation of the RAAS system by regulating the levels of ANP, ET-1, and AngII, thereby reversing ventricular remodeling and improving cardiac function; it can also reduce the percentage of myocardial collagen, reduce the content of MMP-2 and MMP-9 mRNA, and down-regulate the expression level of TGF-β1 protein, indicating that the 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 may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall 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 equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A Chinese medicine composition, characterized in that: The Chinese medicine composition is made from the following raw materials in parts by weight: 10-15 portions of red ginseng, 5-10 portions of processed aconite root, 15-30 portions of cornus fruit, 10-20 portions of raw rehmannia, 15-30 portions of red astragalus, 6-15 portions of rhodiola rosea, 6-12 portions of dried ginger, 15-30 portions of poria, 2-6 portions of notoginseng powder, 15-30 portions of scutellaria baicalensis seeds, 10-15 portions of red peony root, and 5-10 portions of coptis root.

2. The method for preparing the Chinese medicine composition according to claim 1, characterized in that: The following steps are involved: Weigh red ginseng, processed aconite root, cornus fruit, raw rehmannia root, red astragalus root, rhodiola rosea, dried ginger, tuckahoe, scutellaria baicalensis, red peony root, and coptis root according to weight and set aside; The weighed Chinese medicinal raw materials are added with water and boiled, the medicinal decoction is collected, and Panax notoginseng powder is added to the medicinal decoction, and the mixture is mixed evenly to obtain the Chinese medicinal composition.

3. The preparation method according to claim 2, characterized in that: The process of adding water and boiling is: First, the prepared aconite root is decocted, and then cornus fruit, radix rehmanniae, radix astragali, rhodiola rosea, dried ginger, tuckahoe, radix scutellariae, radix paeoniae rubrae, and rhizoma coptidis are added, and a total of water equivalent to 6 to 8 times the mass of the medicinal material mixture is added for decocting, and the decoction of the medicinal material mixture is collected; Add red ginseng into water equivalent to 6 to 8 times the mass of red ginseng and boil it, and collect the red ginseng decoction; The mixture decoction and the red ginseng decoction are combined to obtain a medicinal decoction.

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

5. Use of the Chinese medicine composition as claimed in claim 1 in preparing a medicine for treating heart failure.

6. The use according to claim 5, characterized in that The heart failure is caused by heart disease.

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

8. The use according to claim 5, characterized in that The medicine comprises the Chinese medicine composition and pharmaceutically acceptable excipients.

9. The use according to claim 5, characterized in that The dosage form of the medicine is water pill, drop pill, honey pill, granule, powder, capsule, soft capsule, tablet, mixture or oral solution.

10. The use according to claim 5, wherein the drug is used to prepare a preparation for inhibiting excessive activation of the renin-angiotensin-aldosterone system.

Citation Information

Patent Citations

  • Traditional Chinese medicine composition for treating heart failure and preparation method thereof

    CN101085200A