Traditional Chinese medicine composition for treating heart failure as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating heart failure and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 40 to 100 parts of radix astragali seu hedysari, 8 to 20 parts of radix ginseng, 20 to 30 parts of radix salviae miltiorrhizae and 20 to 35 parts of corn stigma. The traditional Chinese medicine composition for treating heart failure provided by the invention can tonify qi, activate blood and promote urination, and also has a remarkable treatment effect on ejection fraction reduction type heart failure.

Description

Technical Field

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

[0002] Heart failure (HF) refers to a complex clinical syndrome of symptoms and signs caused by abnormal cardiac structure or function, leading to ventricular contraction or filling disorders. HF is a serious and terminal stage of various heart diseases and the most important cardiovascular disease.

[0003] In addition, the terminal stages of hypertension and coronary heart disease also manifest as heart failure.

[0004] In clinical practice, for the treatment of heart failure with reduced ejection fraction (HFrEF, LVEF≤40%), a "golden triangle" treatment model [angiotensin-converting enzyme inhibitor (ACEI) / angiotensin II receptor antagonist (ARB) + β-blocker (BB) + mineralocorticoid receptor antagonist (MRA)] has been formed, with the main goal of improving the long-term prognosis of heart failure. With the continuous emergence of a variety of new heart failure treatment drugs that can improve prognosis, including angiotensin receptor neprilysin inhibitors (ARNI), sodium-glucose co-transporter 2 inhibitors (SGLT2i), soluble guanylate cyclase (sGC) stimulators, etc., especially the large amount of clinical benefit evidence of ARNI and SGLT2i, the drug treatment model for improving the prognosis of HFrEF has been upgraded from the "golden triangle" to the "new quadruple", that is, (ARNI or ACEI / ARB) + SGLT2i + BB + MRA. However, the adverse reactions of chemical drugs used in modern medicine and the inability to tolerate conventional treatments are unavoidable. Regardless of whether it is the Golden Triangle or the New Quadruple, the 5-year mortality and disability rate of patients with chronic heart failure is still over 50%.

[0005] Heart failure belongs to the category of wheezing, edema, palpitations, etc. in traditional Chinese medicine. There are rich discussions on the symptoms related to heart failure in ancient books, including "Huangdi Neijing", "Jingui Yaolue", "Zhubingyuanhoulun", etc. The basic TCM syndrome characteristics of heart failure are deficiency of the root and excess of the side, and mixed deficiency and excess. The deficiency of the root is mainly qi deficiency, and the excess of the side is mainly blood stasis. Commonly used prescriptions in clinical practice include Zhenwu Decoction, Tingli Dazao Xiefei Decoction, Linggui Shugan Decoction, etc. Chinese medicine involves salvia miltiorrhiza, astragalus, Panax notoginseng, epimedium, cinnamon twig, etc. Commonly used Chinese patent medicines in clinical practice include Qili Qiangxin Capsule, Shenqi Yiqi Drop Pills, Shexiang Baoxin Pills, etc.

[0006] Chinese invention patent application CN109481595A discloses a Chinese medicine preparation and exercise training method for protecting diabetic heart damage, wherein the Chinese medicine preparation for protecting diabetic heart damage includes the following raw materials in parts by weight: 10-14 parts of Astragalus, 15-19 parts of Chinese yam, 4-8 parts of ginseng, 3-7 parts of Scrophularia, 5-9 parts of Anemarrhena, 5-9 parts of Corn Silk, 10-14 parts of Lycium barbarum, 15-19 parts of Agrimoniae, 5-9 parts of Portulaca Oleracea, 4-8 parts of Lycium barbarum, 3-7 parts of peanut rhizomes, 4-8 parts of litchi kernels, 5-9 parts of silkworm cocoon shells and 5-9 parts of pomegranate peels. The extract of the invention can have a certain therapeutic effect on heart damage caused by diabetes, and experiments are used to explore the combination of aerobic exercise and Chinese medicine compound. The formula of the invention involves many types of Chinese medicinal materials, the key points of the prescription are not prominent, the safety is unclear, and it is not completely aimed at the treatment of heart failure.

[0007] Chinese invention patent application CN102688407A discloses a Chinese medicine composition for treating chronic heart failure, which belongs to the field of medical technology. The raw materials of the Chinese medicine composition are composed of the following components by weight: 10-15 parts of Radix Pseudostellariae, 10-20 parts of Rhizoma Alismatis, 10-15 parts of Radix Astragali, 10-20 parts of Radix Salviae Miltiorrhizae, 20-30 parts of Stigma Corni, and 5-10 parts of Cinnamomum cassiae. The invention can significantly improve the problem of cardiogenic edema in patients with chronic heart failure who are resistant to diuretics. While diuresis, the drug can improve cardiac function, relieve patient symptoms, improve patient quality of life, prolong survival time, and has little effect on blood electrolytes. The raw materials of the pharmaceutical composition are easy to obtain, the preparation method is simple, the cell experiment, animal experiment and clinical trial have definite efficacy, and no toxic side effects have been found to the human body. The prescription is mainly based on improving cardiogenic edema, and is not formulated from a comprehensive perspective such as myocardial damage, inflammatory factor level, myocardial fibrosis level, and pathology, so its therapeutic effect is still limited.

[0008] Therefore, the current traditional Chinese medicine treatment for heart failure still requires a traditional Chinese medicine composition that can improve from multiple angles to achieve more significant and efficient therapeutic effects. Summary of the invention

[0009] The purpose of the present invention is to provide a Chinese medicine composition for treating chronic heart failure, and a preparation method and application thereof, which can significantly improve the therapeutic effect on heart failure by refining the prescription to achieve a streamlined prescription with rigorous compatibility and synergistic effect.

[0010] To achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows: A traditional Chinese medicine composition for treating heart failure, which comprises the following ingredients by weight: 40-100 parts of astragalus, 8-20 parts of ginseng, 20-30 parts of salvia miltiorrhiza and 20-35 parts of corn silk.

[0011] Preferably, the raw materials are composed of the following components in parts by weight: 40-60 parts of astragalus, 8-10 parts of ginseng, 25-30 parts of salvia miltiorrhiza and 30-35 parts of corn silk.

[0012] Preferably, the invention is composed of the following ingredients in parts by weight: 55-65 parts of astragalus, 8-12 parts of ginseng, 25-35 parts of salvia miltiorrhiza and 25-35 parts of corn silk.

[0013] Preferably, the preparation method comprises the following ingredients in parts by weight: 60 parts of astragalus, 10 parts of ginseng, 30 parts of salvia miltiorrhiza and 30 parts of corn silk.

[0014] Another object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps: (1) Soak ginseng in water and boil it to obtain ginseng residue and decoction 1; (2) Soak the astragalus, salvia miltiorrhiza, corn silk and ginseng residues in water, and boil them to obtain decoction 2; (3) Mix decoction 1 and decoction 2 evenly to obtain a concentrated thick paste or concentrate and then dry to obtain a thick paste.

[0015] Preferably, in step (1), the amount of water added is 8-12 times the mass of ginseng, more preferably 8-10 times, and even more preferably 10 times.

[0016] Preferably, in step (1), the soaking time is 3-10 h, more preferably 3-8 h, more preferably 6-8 h, and even more preferably 6 h.

[0017] Preferably, in step (1), the decoction is performed 1-3 times, and the decoction time for each time is 1-3 hours. More preferably, the decoction is performed 2 times, and the decoction time for each time is 2 hours.

[0018] Preferably, in step (2), the amount of water added is 8-12 times the total weight of the astragalus, salvia miltiorrhiza, corn silk and ginseng residues, more preferably 8-10 times, and even more preferably 10 times.

[0019] Preferably, in step (2), the soaking time is 1-3 hours, more preferably 1-2 hours, and even more preferably 2 hours.

[0020] Preferably, in step (2), the decoction is performed 1-3 times, and the decoction time for each time is 1-3 hours.

[0021] The third object of the present invention is to provide a traditional Chinese medicine composition for treating heart failure, which comprises the following ingredients in parts by weight: 40-100 parts of astragalus, 8-20 parts of ginseng, 20-60 parts of salvia miltiorrhiza, 20-80 parts of corn silk, 8-30 parts of chuanxiong, 20-30 parts of red peony root, 10-20 parts of poria, 10-30 parts of motherwort and 8-20 parts of tangerine peel.

[0022] Preferably, the raw materials of the Chinese medicine composition are composed of the following ingredients in parts by weight: 30-70 parts of astragalus, 10-15 parts of ginseng, 30-40 parts of salvia miltiorrhiza, 30-40 parts of corn silk, 15-20 parts of chuanxiong, 30-35 parts of red peony root, 30-40 parts of poria, 30-45 parts of motherwort, and 10-15 parts of tangerine peel.

[0023] Preferably, the raw materials are composed of the following ingredients by weight: 50-70 parts of astragalus, 10-12 parts of ginseng, 30-35 parts of salvia miltiorrhiza, 30-35 parts of corn silk, 15-18 parts of chuanxiong, 30-33 parts of red peony root, 30-35 parts of poria, 30-35 parts of motherwort, and 10-12 parts of tangerine peel.

[0024] Preferably, the raw materials are composed of the following ingredients in parts by weight: 60 parts of astragalus, 10 parts of ginseng, 30 parts of salvia miltiorrhiza, 30 parts of corn silk, 15 parts of chuanxiong, 30 parts of red peony root, 30 parts of poria, 30 parts of motherwort and 10 parts of tangerine peel.

[0025] The fourth object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps: (1) Soak ginseng in water and boil it to obtain ginseng residue and decoction 1; (2) Soak the astragalus, salvia miltiorrhiza, corn silk, chuanxiong, red peony root, tuckahoe, motherwort, tangerine peel and ginseng residue in water, and boil to obtain decoction 2; (3) Mix decoction 1 and decoction 2 evenly to obtain a concentrated thick paste or concentrate and then dry to obtain a thick paste.

[0026] Preferably, in step (1), the amount of water added is 8-12 times that of ginseng, more preferably 8-10 times, and even more preferably 10 times.

[0027] Preferably, in step (1), the soaking time is 3-10 hours, more preferably 3-8 hours, more preferably 6-8 hours, and even more preferably 6 hours.

[0028] Preferably, in step (1), the decoction is performed 1-3 times, and the decoction time for each time is 1-3 hours; more preferably, the decoction is performed 2 times, and the decoction time for each time is 2 hours.

[0029] Preferably, in step (2), the amount of water added is 8-12 times the total weight of the astragalus, salvia miltiorrhiza, corn silk, chuanxiong, red peony root, tuckahoe, motherwort, tangerine peel and ginseng residues, more preferably 8-10 times, and even more preferably 9 times.

[0030] Preferably, in step (2), the soaking time is 1-3 hours, more preferably 1-2 hours, and even more preferably 2 hours.

[0031] Preferably, in step (2), the decoction is performed 1-3 times, and the time for each decoction is 0.5-2 hours; more preferably, the decoction is performed 2 times, and the time for each decoction is 1 hour.

[0032] Preferably, in step (3), after concentration, conventional drying, crushing and screening steps in the art may be further included to prepare the traditional Chinese medicine composition in the form of powder or granules.

[0033] The fifth object of the present invention is to provide the use of the above-mentioned Chinese medicine composition, or the Chinese medicine composition prepared by the above-mentioned preparation method in the preparation of drugs for treating heart failure.

[0034] Preferably, the heart failure is heart failure with reduced ejection fraction.

[0035] Preferably, the treatment of heart failure includes improving left ventricular ejection fraction (LVEF), improving B-type natriuretic peptide (BNP), regulating troponin I (cTnI) levels, regulating troponin T (cTnT) levels, regulating creatine kinase isoenzyme (CK-MB) levels, regulating atrial natriuretic peptide (ANP) levels, controlling the levels of inflammatory factors TNF-α, IL-1β, IL-6, INF-γ and hs-CRP in the circulation system, and regulating the level of myocardial fibrosis α-SMA in heart failure.

[0036] The sixth object of the present invention is to provide a medicine, which comprises the above-mentioned Chinese medicine composition, or the Chinese medicine composition prepared by the above-mentioned preparation method.

[0037] The drug can be prepared into dosage forms such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, and lozenges, and suitable drug carriers in the art can be selected for different dosage forms.

[0038] The pharmaceutical carrier used can be solid, liquid or gas. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0039] When preparing the composition for oral dosage form, any convenient pharmaceutical medium can be used. For example, water, ethanol, oil, alcohol, flavoring agent, preservative, coloring agent, etc. can be used to form oral liquid preparations, such as suspensions and solutions; while carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulating agents, emulsifiers, lubricants, binders, disintegrants can be used to form oral solid preparations, such as powders, capsules and tablets. Tablets and capsules are the preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or non-aqueous techniques.

[0040] Tablets containing the Chinese medicine composition of the present invention can be prepared by tableting or molding, and one or more auxiliary ingredients or adjuvants can be used. The active ingredient can be tableted in a free-flowing form (such as powder or granules) in a suitable machine, and can be mixed with a binder, a lubricant, an inert diluent, a surfactant or a dispersant to prepare a tablet. Molded tablets can be molded in a suitable machine, that is, a powdered mixture moistened with an inert liquid diluent, each tablet preferably contains about 0.05 mg to about 5 g of active ingredient, and each sachet or capsule preferably contains about 0.05 mg to about 5 g of active ingredient. For example, a preparation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active drug, mixed with an appropriate and convenient carrier material, which may account for about 5% to 95% of the total composition. The unit dosage form usually contains about 1 mg to about 2 g of active ingredient, usually 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0041] The pharmaceutical composition suitable for parenteral administration in the present invention can be prepared as an aqueous solution or suspension of the active compound, and can include a suitable surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycol and its oil mixture. In addition, preservatives can be added to prevent the harmful growth of microorganisms.

[0042] Medicine of the present invention can be in the form suitable for topical use, for example aerosol, cream, ointment, lotion, powder or the like. In addition, composition can be in the form suitable for transdermal administration device. Can use Chinese medicine composition of the present invention, prepare these prescriptions by conventional processing method. For example, by mixing hydrophilic material and water, and about 5wt% to about 10wt% of compound, prepare cream or ointment with required consistency.

[0043] The medicine of the present invention can be in a form suitable for rectal administration, wherein the carrier is a solid. Preferably, the mixture is made into a unit dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories can be prepared by first forming a composition containing a softened or melted carrier, followed by cooling and shaping in a mold.

[0044] In addition to the above-mentioned carrier components, the above-mentioned pharmaceutical preparations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, adhesives, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. In addition, other excipients, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, colorants and flavoring agents, etc., may be added, and the components containing the Chinese medicine composition of the present invention may also be prepared in the form of powder or concentrated solution.

[0045] In clinical practice of TCM, attention should be paid to the key pathogenesis of syndromes. As the saying goes, "methods are established according to syndromes, and prescriptions are derived from methods." The key pathogenesis of heart failure can be summarized as "deficiency," "stasis," and "water." Therefore, the key to its treatment lies in "tonifying deficiency," "removing stasis," and "promoting water." The present invention is based on this.

[0046] In the formula, Astragalus is sweet and warm, and is a holy medicine for replenishing qi, especially good at replenishing the qi of the heart and lungs; Ginseng replenishes the heart qi, spleen qi, and primordial qi. Astragalus and ginseng are combined to replenish the ancestral qi and primordial qi, so that the heart qi is strong and the blood can flow. The two medicines are the main medicines to replenish the "qi deficiency" of heart failure; Salvia miltiorrhiza is bitter and slightly cold, enters the pericardium and liver meridians, can activate blood circulation and remove blood stasis, is good at entering the blood, and is a medicine for removing blood stasis, promoting new blood, regulating menstruation and smoothing the meridians. It is a ministerial medicine to treat the "blood stasis" of heart failure; Corn silk is sweet and light, promotes urination and eliminates edema, and is an adjuvant medicine to benefit the "water retention" symptom of heart failure. The whole formula is compatible, and it has the effects of replenishing qi, activating blood circulation, and promoting diuresis.

[0047] Heart is located in the upper part of the body and is the Yang among Yang. When the heart is weak, the blood will stagnate and become stagnant. Chuanxiong, red peony root and motherwort are added to the prescription to promote blood circulation and remove blood stasis, and to help the ministers to strengthen the removal of "blood stasis" caused by heart failure; Poria cocos and sweet and mild herbs can penetrate dampness to strengthen the function of promoting the flow of "water retention" caused by heart failure; Tangerine peel can invigorate the spleen and remove dampness, and regulate the Qi in the middle part of the body. The efficacy of the whole prescription is based on the basic prescription, and the compatibility is rigorous, which further highlights the efficacy of invigorating Qi, promoting blood circulation and promoting diuresis.

[0048] The beneficial effects of the present invention are: (1) The present invention achieves a synergistic effect by combining astragalus, ginseng, salvia miltiorrhiza and corn silk in a specific ratio. The formula is concise and effective, and the therapeutic effect on heart failure is significant.

[0049] (2) The present invention further adds a specific proportion of Chuanxiong, red peony root, Poria, Leonurus japonicus and dried orange peel to the formula, which makes the medicinal effect more obvious and the therapeutic effect is further improved.

[0050] (3) The two formulations of the present invention are combined based on the key pathogenesis of chronic heart failure and exert a synergistic effect. They can significantly enhance the cardiac function of heart failure with reduced ejection fraction, including improving left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP), and can effectively regulate the levels of troponin I (cTnI), troponin T (cTnT), creatine kinase isoenzyme (CK-MB) and atrial natriuretic peptide (ANP), effectively control the levels of inflammatory factors TNF-α, IL-1β, IL-6, INF-γ and hs-CRP in the circulatory system, significantly regulate the level of myocardial fibrosis α-SMA, and have a significant effect on myocardial remodeling. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 Echocardiogram of mice in the control group.

[0052] Figure 2 Echocardiogram of mice in the model group.

[0053] Figure 3 Echocardiogram of mice in the positive group.

[0054] Figure 4 This is the echocardiogram of mice in group 1 of Example 1.

[0055] Figure 5 This is the echocardiogram of mice in group 2 of Example 2.

[0056] Figure 6 This is the echocardiogram of mice in the comparative example 1 group.

[0057] Figure 7 This is the echocardiogram of mice in group 2 of the comparative example.

[0058] Figure 8 This is the echocardiogram of mice in group 3 of the comparative example.

[0059] Fig. 9 The graph shows the measurement results of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS), left ventricular end-diastolic diameter (LVIDd), and left ventricular end-systolic diameter (LVISd) of mice in different groups.

[0060] Fig.10 The expression diagram of myocardial injury-related indicators in different groups of mice.

[0061] Fig.11 The expression diagram of inflammatory response-related indicators in different groups of mice.

[0062] Fig.12 The expression diagram of α-SMA, a fibrosis-related indicator, in different groups of mice.

[0063] Fig.13These are the microscopic images of the myocardium of mice in different groups stained with H&E and Masson staining.

[0064] Fig.14 Shown are the results of WGA staining and semi-quantitative analysis of the left ventricle of mice in different groups. DETAILED DESCRIPTION

[0065] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present application.

[0066] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all weight contents. Unless otherwise specified, it is understood that the process is carried out at room temperature.

[0067] Example 1-Example 2 The formula of Example 1-Example 2 is shown in Table 1 below.

[0068] Table 1

[0069] The preparation method of Example 1 is as follows: (1) Add 10 times the amount of water to ginseng slices, soak for 6 hours, and then decoct for 2 hours. Decoction is performed twice, and the decoctions are combined and filtered to obtain ginseng residue and decoction 1; (2) Soak the astragalus, corn silk, salvia miltiorrhiza slices and the ginseng residue obtained in (1) in 9 times the amount of water for 2 hours and then decoct. Decoction is repeated twice, each time for 1 hour. The decoctions are combined and filtered to obtain decoction 2. (3) Decoction 1 and decoction 2 are mixed and concentrated to obtain a thick paste. The thick paste is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0070] The preparation method of Example 2 is as follows: (1) Ginseng slices, soaked in 10 times water for 7 hours, decocted for 2 hours, decocted twice, combined the decoctions, filtered to obtain decoction 1 and ginseng residue; (2) Add 8 times the amount of water to the remaining raw medicinal materials and the ginseng residue obtained in (1), soak for 2 hours, and then decoct twice, each time for 1 hour. Combine the decoctions, filter, and obtain decoction 2; (3) Decoction 1 and decoction 2 are mixed evenly to form a thick extract; the thick extract is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0071] Example 3-Example 6 The formulations of Example 3 to Example 6 are shown in Table 2 below.

[0072] Table 2

[0073] The preparation method of Example 3 is as follows: (1) Add 8 times the amount of water to ginseng slices, soak for 3 hours, then decoct for 1 hour, decoct three times, combine the decoctions, filter and obtain ginseng residue and decoction 1; (2) Soak the astragalus, corn silk, salvia miltiorrhiza slices and the ginseng residue obtained in (1) in 8 times the amount of water for 1 hour and then decoct for 3 hours. Combine the decoctions and filter to obtain decoction 2; (3) Decoction 1 and decoction 2 are mixed and concentrated to obtain a thick paste. The thick paste is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0074] The preparation method of Example 4 is as follows: (1) Add 12 times the amount of water to ginseng slices, soak for 8 hours, and then decoct for 1 hour three times. Combine the decoctions and filter to obtain ginseng residue and decoction 1; (2) Soak the astragalus, corn silk, salvia miltiorrhiza slices and ginseng residue obtained in (1) in 12 times the amount of water for 3 hours and then decoct. Decoction is repeated for 3 times, each time for 1 hour. The decoctions are combined and filtered to obtain decoction 2. (3) Decoction 1 and decoction 2 are mixed and concentrated to obtain a thick paste. The thick paste is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0075] The preparation method of Example 5 is as follows: (1) Ginseng slices, soaked in 8 times water for 3 hours, then decocted for 1 hour, decocted three times, combined the decoction, filtered to obtain decoction 1 and ginseng residue; (2) Add 10 times the amount of water to the remaining raw medicinal materials and the ginseng residue obtained in (1), soak for 1 hour, boil for 3 hours, filter, and obtain decoction 2; (3) Decoction 1 and decoction 2 are mixed evenly to form a thick extract; the thick extract is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0076] The preparation method of Example 6 is as follows: (1) Ginseng slices, soak in 12 times water for 10 hours, then boil for 3 hours, filter to obtain decoction 1 and ginseng residue; (2) Add 12 times the amount of water to the remaining raw medicinal materials and the ginseng residue obtained in (1), soak for 3 hours, and then decoct for 3 times, each time for 1 hour. Combine the decoctions, filter, and obtain decoction 2; (3) Decoction 1 and decoction 2 are mixed evenly to form a thick extract; the thick extract is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0077] Comparative Example 1 The formula of this comparative example is as follows: 60 parts of Astragalus, 30 parts of Codonopsis, 30 parts of Salvia and 30 parts of Corn Silk by weight. The difference between this comparative example and Example 1 is that it does not contain ginseng, but adds an equal amount of Codonopsis.

[0078] The preparation method is as follows: (1) Add 10 times the amount of water to Codonopsis pilosula slices and soak for 6 hours, then decoct for 2 hours, decoct twice, combine the decoctions, and filter to obtain Codonopsis pilosula residue and decoction 1; (2) Soak the astragalus, corn silk, salvia miltiorrhiza slices and the codonopsis pilosula residue obtained in (1) in 9 times the amount of water for 2 hours and then decoct. Decoction is repeated twice, each time for 1 hour. The decoctions are combined and filtered to obtain decoction 2. (3) Decoction 1 and decoction 2 are mixed and concentrated to obtain a thick paste. The thick paste is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0079] Comparative Example 2 The formula of this comparative ratio is as follows by weight: 60 parts of astragalus, 10 parts of ginseng, 30 parts of salvia miltiorrhiza, 10 parts of corn silk, 10 parts of plantain seeds and 10 parts of red beans.

[0080] The difference from Example 1 is that a portion of corn silk is replaced with psyllium and adzuki bean having similar effects.

[0081] The preparation method is as follows: (1) Add 10 times the amount of water to ginseng slices, soak for 6 hours, and then decoct for 2 hours. Decoction is performed twice, and the decoctions are combined and filtered to obtain ginseng residue and decoction 1; (2) Soak the astragalus, corn silk, salvia miltiorrhiza decoction pieces, plantain seeds, red beans and the ginseng residue obtained in (1) in 9 times the amount of water for 2 hours and then decoct. Decoction is repeated twice, each time for 1 hour. The decoctions are combined and filtered to obtain decoction 2. (3) Decoction 1 and decoction 2 are mixed and concentrated to obtain a thick paste. The thick paste is dried, crushed, and passed through an 80-mesh sieve to obtain a Chinese medicine composition.

[0082] Comparative Example 3 The formula of this comparative ratio is as follows by weight: 10 parts of astragalus, 8 parts of ginseng, 25 parts of salvia miltiorrhiza, and 60 parts of corn silk.

[0083] The difference from Example 1 is that the weight ratio of the components is different, and the rest is the same.

[0084] 1. Drug efficacy experiment 1. Materials and Methods 1.1 Experimental animals SPF male C57BL / 6 mice, 8 weeks old, weight (22-24 g), were purchased from Sibeifu (Beijing) Biotechnology Co., Ltd., license number: SCXK (Beijing) 2019-0010. Feeding conditions: temperature 20-26 ° C, humidity 40%-70%, and experimental research procedures were carried out after one week of adaptive feeding.

[0085] 1.2 Experimental drugs Blank control group: distilled water; Experimental group: Chinese medicine compositions prepared in Example 1-Example 2 and Comparative Example 1-Comparative Example 3; isoproterenol hydrochloride (ISO, MCE); Positive control drug: sacubitril-valsartan sodium tablets (Nocinto, specification 100 mg, Novartis); 1.3 Experimental reagents The main reagents used in this experiment are shown in Table 3.

[0086] Table 3

[0087] Note: The full name of Shanghai ELISA is Shanghai ELISA Biotechnology Co., Ltd.

[0088] 1.4 Experimental instruments The main experimental instruments used in this study are shown in Table 4.

[0089] Table 4

[0090] 2. Experimental Methods 2.1 Model replication After 7 days of adaptive feeding, all groups of mice except the control group were given a drug-induced heart failure model, i.e., subcutaneous injection of ISO (30 mg / Kg / day). Ultrasound diagnosis was performed after 14 consecutive days of administration, and LVEF value ≤ 45% was used as the standard for successful model establishment.

[0091] 2.2 Animal grouping After the model was successfully established, the mice were randomly divided into 8 groups, with 10 mice in each group, namely control group (Control), model group (ISO), positive drug group (E), Example 1 group (basic heart failure prescription group BHF), Example 2 group (complete heart failure prescription group QHF), comparative example group 1, comparative example group 2, and comparative example group 3.

[0092] 2.3 Drug delivery design The control group and the model group were gavaged with an equal amount of distilled water; the positive drug group was gavaged with 10 mg / kg of sacubitril / valsartan sodium; the Example 1 group was gavaged with 19.7 g of crude drug / kg of the Chinese medicine composition prepared in Example 1; the Example 2 group was gavaged with 34.9 crude drug / kg of the Chinese medicine composition prepared in Example 2, and the administration cycle was 4 weeks; the Comparative Example 1-Comparative Example 3 groups were gavaged with 19.7 g of crude drug / kg of the Chinese medicine composition prepared in Comparative Example 1-Comparative Example 3, respectively.

[0093] 2.4 Index detection During the experiment, cardiac ultrasound was performed after subcutaneous injection of ISO14 days and after intragastric administration; after administration, blood was centrifuged and pathological tissue samples were taken for testing of relevant indicators. The treatment of animals during the experiment complied with the animal ethics requirements stipulated in the "Regulations on the Administration of Laboratory Animals" of the State Science and Technology Commission.

[0094] 2.4.1 Color Doppler Ultrasound Examination of the Hearts of Mice in Each Group Detection time point: 14 days after subcutaneous injection of ISO and oral administration.

[0095] Operation method: After anesthesia, the mouse was fixed on the surgical board in the supine position. The hair on the mouse chest was removed with a small animal shaver and depilatory cream before ultrasound examination. The probe was placed at the level of the papillary muscle and the M-mode sampling line was perpendicular to the ventricular septum, atrium and left ventricle to obtain an M-mode echocardiogram. The left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVISd) were measured, and the average of three cardiac cycles was taken to calculate the left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (FS).

[0096] 2.4.2 Myocardial injury index detection After the ultrasound test, the mice's eyeballs were removed to collect blood, and the serum was separated for later use. The levels of myocardial injury-related indicators: B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), troponin I (cTnI), troponin T (cTnT), and creatine kinase isoenzyme (CK-MB) were detected by ELISA.

[0097] 2.4.3 Detection of inflammatory factor levels The levels of inflammatory factors TNF-α, IL-1β, IL-6, INF-γ, and hs-CRP in the circulation system were detected by ELISA.

[0098] 2.4.4 Detection of myocardial fibrosis level The α-SMA level, an index related to myocardial fibrosis, was detected by ELISA.

[0099] 2.4.5 Cardiac histopathology The heart tissue was removed, fixed with 10% neutral formaldehyde solution, embedded in paraffin, sliced ​​(4-6 μm), and stained with H&E, Masson staining, and WGA staining of the left ventricle, and observed under a microscope.

[0100] 2.5 Statistical analysis All experimental data were processed by SPSS 27.0 statistical software and expressed as mean ± standard deviation. One-way ANOVA was used when the data met the normal distribution and variance homogeneity, and LSD method was used for multiple comparisons between groups. Welch method was used to correct the F value when variance homogeneity was not met, and Dunnett T3 method was used for further multiple comparisons. P < 0.05 was considered statistically significant.

[0101] 3. Results 3.1 Effects of Xinshuai Recipe on Cardiac Function in Mice The results of color ultrasound examination of the hearts of mice in each group are shown in Table 5 and Figure 1-Figure 9 shown.

[0102] After intraperitoneal injection of ISO, compared with the control group, the LVEF and FS values ​​of the mice in the model group were significantly decreased (P < 0.05), and the LVIDd and LVIDs values ​​were significantly increased (P < 0.05), indicating that this method successfully replicated the congestive heart failure model of mice; after the administration of the positive drug (Noxinto), the cardiac function of the heart failure mice was significantly changed. Compared with the model group, the FS and LVEF values ​​were significantly increased (P < 0.05, P < 0.01), and the LVIDd and LVIDs were significantly decreased (P < 0.01).

[0103] After gavage of mice with the basic heart failure formula (BHF, the Chinese medicine composition of Example 1) and the complete heart failure formula (QHF, the Chinese medicine composition of Example 2), the cardiac function of the mice with heart failure can be significantly corrected. Compared with the model group, the LVEF and FS values ​​were significantly increased (P < 0.05); the LVIDd value was significantly reduced (basic formula P < 0.05, complete formula P < 0.01), and the LVIDs value was reduced, but there was no significant difference in the Example 1 group, while it was significantly decreased in the Example 2 group (P < 0.01); compared with the positive drug group, there was no significant difference between the Example 1 group and the Example 2 group, indicating that the heart failure formula, whether it is the basic formula of the Example 1 group or the complete formula of the Example 2 group, can significantly improve the cardiac function under the state of heart failure, and has no difference in efficacy with Noxinto; compared with the model group, the cardiac function of the comparative example 1 group, the comparative example 2 group, and the comparative example 3 group was slightly improved, but there was no statistical difference.

[0104] Table 5

[0105] Note: #Compared with the control group: P < 0.05; *Compared with the model group: P < 0.05; **Compared with the model group: P < 0.01.

[0106] 3.2 Effects of Xinshuai Recipe on Myocardial Injury Markers in Mice The results of myocardial injury index detection in each group are shown in Table 6. Fig.10 After intraperitoneal injection of ISO, the levels of myocardial injury markers B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), creatine kinase isoenzyme (CK-MB), and troponin T (cTnT) in the model group were significantly increased compared with the control group (P < 0.01), and the level of troponin I (cTnI) was also increased, but there was no statistical difference.

[0107] Compared with the model group, the levels of myocardial injury-related indicators in the drug-treated groups were significantly improved, as shown by the significant decreases in BNP, ANP, CK-MB and cTnT levels (P < 0.01 or P < 0.05); after drug administration, the level of cTnI was lower than that in the model group, but the difference was not significant. This shows that the heart failure prescription, whether it is the basic prescription of Example 1 or the full prescription of Example 2, can significantly improve the myocardial state, and there is no difference between the drug-treated groups.

[0108] Table 6

[0109] Note: #Compared with the control group: P < 0.05; ##Compared with the control group: P < 0.05; *Compared with the model group: P < 0.05; **Compared with the model group: P < 0.01.

[0110] 3.3 Effects of the Heart Failure Recipe on Inflammatory Factors in the Heart Failure Environment of Mice The results of the inflammatory factor levels in each group of mice are shown in Table 7. Fig.11 shown.

[0111] After intraperitoneal injection of ISO, the myocardial damage of mice in the model group was severe compared with that in the control group, and the expression of inflammatory factors TNF-α, IL-1β, IL-6, INF-γ and hs-CRP was significantly increased (P<0.05, P<0.01). After treatment, the expression of inflammatory factors was significantly improved compared with that in the ISO group (P<0.05). There was no statistical difference between the drug-treated groups.

[0112] Table 7

[0113] Note: #Compared with the control group: P < 0.05; ##Compared with the control group: P < 0.01; *Compared with the model group: P < 0.05; **Compared with the model group: P < 0.01.

[0114] 3.4 Effect of Xinshuai Fang on fibrosis-related marker α-SMA The results of myocardial fibrosis level detection in each group of mice are shown in Table 8. Fig.12 shown.

[0115] After ISO administration, myocardial injury occurred and myocardial fibrosis occurred. Compared with the control group, the myocardial injury of mice in the model group was severe, and the expression of α-smooth muscle actin α-SMA was significantly increased (P < 0.05). After treatment, compared with the ISO group, the expression of α-SMA was significantly improved (P < 0.05). There was no statistical difference between the drug-treated groups.

[0116] Table 8

[0117] Note: #Compared with the control group: P < 0.05; *Compared with the model group: P < 0.05.

[0118] 3.5 Effect of Xinshuai prescription on histopathology of heart failure mice When myocardial damage and cardiac function of heart failure mice undergo significant changes, the results of pathological tissue staining are as follows: H&E and MASSON staining results are as follows Fig.13 As shown: Microscopic observation after H&E and MASSON staining of the heart tissue of mice in the control group showed that the myocardial structure and morphology were normal, the myocardial fibers were neatly arranged, and no fibrosis was observed; microscopic observation after HE and MASSON staining of the heart tissue of mice in the ISO group showed disordered myocardial structure, widened septa, obvious fibrosis, increased collagen deposition, and myocardial dissolution; compared with the ISO group, the pathological phenomena such as disordered myocardial structure, widened septa, obvious fibrosis, and increased collagen deposition in the heart tissue of mice in group E were improved; compared with the ISO group, the pathological phenomena such as disordered myocardial structure, widened septa, obvious fibrosis, and increased collagen deposition in the heart tissue of mice in group BHF and QHF were significantly improved.

[0119] The WGA staining of the left ventricle was semi-quantitatively analyzed and the corresponding data were statistically analyzed (see Table 8). The model group was significantly different from the normal group (P < 0.01); after drug treatment, compared with the ISO group, the E group, the BHF group, and the QHF group all showed significant changes (P < 0.01, P < 0.05). There was no statistical difference between the drug-treated groups (see Table 9, Fig.14 as shown).

[0120] Table 9

[0121] Note: #Compared with the control group: P < 0.05; *Compared with the model group: P < 0.05.

[0122] In summary, the traditional decoction of heart failure prescription, whether basic or complete, has important effects on improving cardiac function, reducing inflammatory response, and inhibiting myocardial fibrosis in the ISO-induced mouse heart failure model.

[0123] 2. Clinical Cases 1. Wang, female, 48 years old, visited the hospital on June 21, 2024, complaining of dilated cardiomyopathy for more than 3 years. Ultrasound on May 12, 2024 showed left ventricular end-diastolic anteroposterior diameter of 66mm, left ventricular end-systolic anteroposterior diameter of 54mm, EF30%, low blood pressure 80-105 / 40-60mmHg. She took the Chinese medicine composition of Example 3 of the present invention for several weeks, and had a cardiac ultrasound on August 14, 2024. The results showed: left ventricular end-diastolic anteroposterior diameter of 63mm, left ventricular end-systolic anteroposterior diameter of 52mm, EF 38%, FS 19%, left heart enlargement and cardiac function indicators were improved.

[0124] 2. Cheng, male, 49 years old, was admitted to the hospital for treatment from July 9 to 20, 2022 due to acute exacerbation of chronic heart failure, heart function grade III (NYHA classification), heart enlargement, pericardial effusion, coronary heart disease, old myocardial infarction, etc., and then went to the hospital for treatment on August 5 of the same year. Examination showed extensive anterior wall myocardial infarction, heart failure, EF 20%, and took the Chinese medicine composition of Example 4 of the present invention for several weeks. Ultrasound showed that the posterior wall thickness of the left ventricle was 10mm (8-11mm), and the left ventricular motion, ventricular septum continuity, atrial septum continuity, etc. were all normal, EF 45%, FS 23%, indicating that the heart function indicators were significantly improved.

[0125] 3. Mr. Wang, male, 62 years old, 8 years after coronary artery bypass grafting, visited our hospital on November 12, 2023, and was currently suffering from shortness of breath and fatigue, EF 32%, FS 19%. After taking the Chinese medicine composition of Example 5 of the present invention for several weeks, EF 50%, FS 25%, and left atrial meridian high normal value, indicating that the cardiac function indicators were greatly improved.

[0126] 4. Xiao, male, 58 years old, visited our hospital on September 1, 2023. He was diagnosed with heart failure and dilated cardiomyopathy. He took the Chinese medicine composition of Example 6 of the present invention for several weeks. On May 8, 2024, ultrasound showed EF42%. He continued to take the medicine. On December 26, 2024, ultrasound showed EF52%, indicating that the ejection fraction index was significantly improved.

[0127] The invention concept is described in detail using specific examples herein, and the description of the above embodiments is only used to help understand the core idea of ​​the invention. It should be pointed out that any obvious modification, equivalent substitution or other improvement made by a person of ordinary skill in the art without departing from the invention concept should be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating heart failure, characterized in that: The raw materials are composed of the following components by weight: 40-100 parts of astragalus, 8-20 parts of ginseng, 20-30 parts of salvia miltiorrhiza and 20-35 parts of corn silk.

2. The Chinese medicine composition according to claim 1, characterized in that: The raw materials are composed of the following components by weight: 40-60 parts of astragalus, 8-10 parts of ginseng, 25-30 parts of salvia miltiorrhiza and 30-35 parts of corn silk.

3. The Chinese medicine composition according to claim 1, characterized in that The invention is composed of the following ingredients by weight: 60 parts of astragalus, 10 parts of ginseng, 30 parts of salvia miltiorrhiza and 30 parts of corn silk.

4. The method for preparing the Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) Soak ginseng in water and boil it to obtain ginseng residue and decoction 1; (2) Soak the astragalus, salvia miltiorrhiza, corn silk and ginseng residues in water, and boil them to obtain decoction 2; (3) Mix decoction 1 and decoction 2 evenly, and concentrate to obtain a thick paste. Alternatively, concentrate and then dry to obtain a thick paste.

5. The preparation method according to claim 4, characterized in that: In step (1), the amount of water added is 8-12 times that of ginseng, the soaking time is 3-8 hours, the number of decoctions is 1-3 times, and the decoction time each time is 1-3 hours; And / or, in step (2), the amount of water added is 8-12 times the total weight of the astragalus, salvia, corn silk and ginseng residues, the soaking time is 1-3 hours, the number of decoctions is 1-3 times, and the decoction time each time is 1-3 hours.

6. A Chinese medicine composition for treating heart failure, characterized in that: The raw materials are composed of the following components by weight: 40-100 parts of astragalus, 8-20 parts of ginseng, 20-60 parts of salvia miltiorrhiza, 20-80 parts of corn silk, 8-30 parts of chuanxiong, 20-30 parts of red peony root, 10-20 parts of tuckahoe, 10-30 parts of motherwort and 8-20 parts of tangerine peel.

7. The Chinese medicine composition according to claim 6, characterized in that: The raw materials are composed of the following components by weight: 60 parts of astragalus, 10 parts of ginseng, 30 parts of salvia miltiorrhiza, 30 parts of corn silk, 15 parts of chuanxiong, 30 parts of red peony root, 30 parts of tuckahoe, 30 parts of motherwort, and 10 parts of tangerine peel.

8. The method for preparing the Chinese medicine composition according to any one of claims 6 to 7, characterized in that: The following steps are involved: (1) Soak ginseng in water and boil it to obtain ginseng residue and decoction 1; (2) Soak the astragalus, salvia miltiorrhiza, corn silk, chuanxiong, red peony root, tuckahoe, motherwort, tangerine peel and ginseng residue in water, and boil to obtain decoction 2; (3) Mix decoction 1 and decoction 2 evenly to obtain a concentrated thick paste or concentrate and then dry to obtain a thick paste.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 or any one of claims 6 to 7, or the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 5 or claim 8 in the preparation of a medicament for treating heart failure.

10. A drug, characterized in that The medicine comprises the Chinese medicine composition according to any one of claims 1 to 3 or any one of claims 6 to 7, or the Chinese medicine composition prepared according to the preparation method according to any one of claims 4 to 5 or claim 8.

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