A traditional Chinese medicine composition for treating heart failure and its preparation method and application

Abstract

The present invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating heart failure, its preparation method, and its use. The raw materials of the traditional Chinese medicine composition of the present invention include 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. The traditional Chinese medicine composition for treating heart failure provided by the present invention can invigorate qi, promote blood circulation, and promote diuresis, and also has significant therapeutic effects on heart failure with reduced ejection fraction.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating heart failure, and a preparation method and 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, the treatment of heart failure with reduced left ejection fraction (HFrEF, LVEF ≤ 40%) has evolved into a "golden triangle" treatment model (angiotensin-converting enzyme inhibitor (ACEI) / angiotensin II receptor blocker (ARB) + beta-blocker (BB) + mineralocorticoid receptor antagonist (MRA)), with the primary goal of improving long-term HF prognosis. With the emergence of a variety of new HF treatment drugs that can improve prognosis, including angiotensin receptor neprilysin inhibitors (ARNIs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and soluble guanylate cyclase (sGC) stimulators, and particularly the extensive evidence of clinical benefit of ARNIs and SGLT2i, the drug treatment model for improving HFrEF prognosis has evolved from the "golden triangle" to the "new quadruple" combination, namely (ARNI or ACEI / ARB) + SGLT2i + BB + MRA). However, the adverse reactions caused by chemical drugs used in modern medicine and the inability to tolerate conventional treatment are unavoidable. 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 falls under the category of wheezing, edema, and palpitations in Traditional Chinese Medicine (TCM). Ancient texts, including the Yellow Emperor's Classic of Internal Medicine, Synopsis of the Golden Chamber, and Treatise on the Causes and Symptoms of Various Diseases, provide extensive discussion of heart failure-related symptoms. The basic TCM syndromes of heart failure are characterized by underlying deficiency and superficial excess, or a mixture of both. The underlying deficiency is primarily characterized by qi deficiency, while the superficial excess is primarily characterized by blood stasis. Commonly used prescriptions in clinical practice include Zhenwu Decoction, Tingli Dazaoshaifei Decoction, and Linggui Zhugan Decoction. Traditional Chinese medicines include salvia miltiorrhiza, astragalus, Panax notoginseng, epimedium, and cinnamon twigs. Commonly used Chinese patent medicines in clinical practice include Qili Qiangxin Capsules, Shenqi Yiqi Dropping Pills, and Musk Heart Protecting Pills.

[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 bark, 3-7 parts of peanut rhizomes, 4-8 parts of litchi seeds, 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 conducted 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 entirely targeted at the treatment of heart failure.

[0007] Chinese invention patent application CN102688407A discloses a Chinese medicine composition for treating chronic heart failure, belonging to the field of medical technology. The raw materials of the Chinese medicine composition are composed of the following components in parts by weight: 10-15 parts of Pseudostellariae Radix, 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. This invention can significantly improve the problem of cardiogenic edema in patients with chronic heart failure who are resistant to diuretics. While promoting 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 this pharmaceutical composition are easily available, the preparation method is simple, and the efficacy is definite in cell experiments, animal experiments, and clinical trials, and no toxic side effects have been found in humans. This prescription is mainly for improving cardiogenic edema, and is not formulated from a comprehensive perspective such as myocardial damage, inflammatory factor levels, myocardial fibrosis levels, and pathology. 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 traditional Chinese medicine composition for treating chronic heart failure, as well as its preparation method and application. By refining the prescription, a streamlined prescription with rigorous compatibility and synergistic effect can be achieved, which can significantly improve the therapeutic effect of heart failure.

[0010] In order to achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows:

[0011] A traditional Chinese medicine composition for treating heart failure consists of the following ingredients in parts 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.

[0012] 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.

[0013] Preferably, the preparation comprises 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.

[0014] Preferably, the preparation 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.

[0015] Another object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps:

[0016] (1) Soak ginseng in water and boil it to obtain ginseng residue and decoction 1;

[0017] (2) Soak the astragalus root, salvia miltiorrhiza root, corn silk and ginseng residue in water, and boil them to obtain decoction 2;

[0018] (3) Mix decoction 1 and decoction 2 evenly to obtain a concentrated thick paste or concentrate and then dry it.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] Preferably, in step (2), the soaking time is 1-3 hours, more preferably 1-2 hours, and even more preferably 2 hours.

[0024] Preferably, in step (2), the decoction is performed 1-3 times, and the decoction time for each time is 1-3 hours.

[0025] The third object of the present invention is to provide a traditional Chinese medicine composition for treating heart failure, which is composed of 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 Leonurus japonicus and 8-20 parts of dried tangerine peel.

[0026] Preferably, the raw materials of the traditional 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 Leonurus japonicus, and 10-15 parts of dried tangerine peel.

[0027] Preferably, the raw materials are composed of the following ingredients in parts 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.

[0028] Preferably, the raw materials are composed of the following components 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.

[0029] A fourth object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps:

[0030] (1) Soak ginseng in water and boil it to obtain ginseng residue and decoction 1;

[0031] (2) Soak the astragalus root, salvia miltiorrhiza root, corn silk, chuanxiong root, red peony root, poria cocos, motherwort, tangerine peel and ginseng residue in water and boil them to obtain decoction 2;

[0032] (3) Mix decoction 1 and decoction 2 evenly to obtain a concentrated thick paste or concentrate and then dry it.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] 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, poria, motherwort, tangerine peel and ginseng residue, more preferably 8-10 times, and even more preferably 9 times.

[0037] Preferably, in step (2), the soaking time is 1-3 hours, more preferably 1-2 hours, and even more preferably 2 hours.

[0038] Preferably, in step (2), the decoction is performed 1-3 times, and the decoction time for each time is 0.5-2 hours; more preferably, the decoction is performed 2 times, and the decoction extraction time for each time is 1 hour.

[0039] Preferably, in step (3), after concentration, conventional steps of drying, crushing, and screening in the art may be further included to prepare the Chinese medicine composition into powder or granule form.

[0040] The fifth object of the present invention is to provide the use of the above-mentioned traditional Chinese medicine composition, or the traditional Chinese medicine composition prepared by the above-mentioned preparation method, in the preparation of drugs for treating heart failure.

[0041] Preferably, the heart failure is heart failure with reduced ejection fraction.

[0042] 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.

[0043] The sixth object of the present invention is to provide a medicine, which includes the above-mentioned traditional Chinese medicine composition, or the traditional Chinese medicine composition prepared by the above-mentioned preparation method.

[0044] The drug can be prepared into dosage forms such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, and lozenges. Suitable drug carriers in the art can be selected for different dosage forms.

[0045] The pharmaceutical carrier used can be a 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.

[0046] When preparing compositions for oral dosage forms, any convenient pharmaceutical medium can be used. For example, water, ethanol, oils, alcohols, flavoring agents, preservatives, colorants, and the like can be used to form oral liquid formulations, such as suspensions and solutions; while carriers, such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, emulsifiers, lubricants, binders, and disintegrants can be used to form oral solid formulations, such as powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or nonaqueous techniques.

[0047] 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 compressed into a free-flowing form (such as powder or granules) in a suitable machine, and can be prepared by mixing with a binder, lubricant, inert diluent, surfactant or dispersant. Molded tablets can be molded in a suitable machine, i.e., a powdered mixture moistened with an inert liquid diluent, preferably containing about 0.05 mg to about 5 g of active ingredient per tablet, and preferably containing about 0.05 mg to about 5 g of active ingredient per sachet or capsule. For example, a preparation intended for oral administration to the human body 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. Unit dosage forms typically contain about 1 mg to about 2 g of active ingredient, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0048] Pharmaceutical compositions suitable for parenteral administration of the present invention can be prepared as aqueous solutions or suspensions of the active compound and can include suitable surfactants, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycol, and oil mixtures thereof. In addition, preservatives can be added to prevent the harmful growth of microorganisms.

[0049] Medicine of the present invention can be the form that is suitable for topical use, for example aerosol, cream, ointment, lotion, powder or the like.In addition, composition can be suitable form and be used 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% compound, prepare cream or ointment with required consistency.

[0050] The medicament of the present invention can be in a form suitable for rectal administration, wherein the carrier is a solid. It is best to prepare the mixture into unit dose suppositories. 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.

[0051] 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, binders, 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 concentrate.

[0052] In the clinical practice of traditional Chinese medicine, attention should be paid to the key pathogenesis of symptoms. As the saying goes, "the method is established according to the symptoms, and the prescription is based on the method." The key pathogenesis of heart failure can be summarized as "deficiency," "stasis," and "water." Therefore, the key to its treatment lies in "tonifying deficiency," "resolving stasis," and "promoting diuresis." The present invention is based on this.

[0053] In the formula, astragalus root is sweet and warm, a sacred herb for replenishing qi, especially the qi of the heart and lungs. Ginseng replenishes the heart qi, spleen qi, and primordial qi. Together, astragalus root and ginseng replenish both zong qi and primordial qi, strengthening the heart qi and promoting blood circulation. These two herbs serve as the monarch herbs, replenishing the "qi deficiency" of heart failure. Salvia miltiorrhiza is bitter and slightly cold, entering the pericardium and liver meridians to activate blood circulation and dissipate blood stasis. It is a herb that removes stasis, promotes new blood circulation, regulates menstruation and smoothes the meridians, serving as the minister herb to treat the "blood stasis" of heart failure. Corn silk is sweet and mild, promoting urination and reducing edema, serving as the adjuvant herb to benefit the "water retention" of heart failure. The entire formula works together to invigorate qi, activate blood circulation, and promote diuresis.

[0054] The heart, located in the upper Jiao (the center of Yang), is the Yang within Yang. When heart Qi is weak, blood stagnates and stagnates. Chuanxiong, red peony root, and motherwort are added to the formula to promote blood circulation and dissipate blood stasis, assisting the auxiliary herbs in dispelling the blood stasis associated with heart failure. Poria cocos and sweet and mild herbs dissipate dampness, further promoting the dispersal of water retention associated with heart failure. Tangerine peel invigorates the spleen, dissipates dampness, and regulates Qi in the middle Jiao (the center of the Jiao). The overall formula builds upon the foundational formula with a rigorous combination of ingredients, further demonstrating its Qi-invigorating, blood-activating, and diuretic properties.

[0055] The beneficial effects of the present invention are:

[0056] (1) The present invention achieves synergistic effects by combining Astragalus, Ginseng, Salvia miltiorrhiza and Corn Silk in a specific ratio. The formula is concise and effective, and has a significant therapeutic effect on heart failure.

[0057] (2) The present invention further adds a specific proportion of Chuanxiong, red peony root, Poria, Leonurus japonicus, and dried tangerine peel to the formula, which makes the efficacy more clear and the therapeutic effect further improved.

[0058] (3) The two formulas 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

[0059] Figure 1 Echocardiogram of mice in the control group.

[0060] Figure 2 Echocardiogram of mice in the model group.

[0061] Figure 3 Echocardiogram of mice in the positive group.

[0062] Figure 4 This is the echocardiogram of the mice in the Example 1 group.

[0063] Figure 5 This is the echocardiogram of mice in group 2 of Example 2.

[0064] Figure 6 This is the echocardiogram of mice in the comparative example 1 group.

[0065] Figure 7 This is the echocardiogram of mice in group 2 of the comparative example.

[0066] Figure 8 This is the echocardiogram of the mice in group 3 of the comparative example.

[0067] Figure 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.

[0068] Figure 10 The expression diagram of myocardial injury-related indicators in different groups of mice.

[0069] Figure 11 The expression diagram of inflammatory response-related indicators in different groups of mice.

[0070] Figure 12 The expression diagram of α-SMA, a fibrosis-related indicator, in different groups of mice.

[0071] Figure 13These are the H&E and Masson staining images of the myocardium of mice in different groups.

[0072] Figure 14 The results of WGA staining and semi-quantitative analysis of the left ventricle of mice in different groups. DETAILED DESCRIPTION

[0073] The following non-limiting examples are provided to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way. The following is merely an illustrative description of the scope of the present invention, and those skilled in the art may make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of protection claimed in this application.

[0074] The present invention will be further described below by way of specific examples. The various chemical reagents used in the examples of the present invention were obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all by weight. Unless otherwise specified, it is understood that the experiments were conducted at room temperature.

[0075] Example 1-Example 2

[0076] The formula of Example 1-Example 2 is shown in Table 1 below.

[0077] Table 1

[0078]

[0079] The preparation method of Example 1 is as follows:

[0080] (1) Ginseng slices: soak in 10 times the amount of water 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;

[0081] (2) Soak the Astragalus root, corn silk, Danshen 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. Combine the decoctions and filter to obtain decoction 2.

[0082] (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.

[0083] The preparation method of Example 2 is as follows:

[0084] (1) Ginseng slices, soaked in 10 times the amount of water for 7 hours, then decocted for 2 hours, decocted twice, combined the decoctions, filtered to obtain decoction 1 and ginseng residue;

[0085] (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;

[0086] (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.

[0087] Example 3-Example 6

[0088] The formulations of Examples 3 to 6 are shown in Table 2 below.

[0089] Table 2

[0090]

[0091] The preparation method of Example 3 is as follows:

[0092] (1) Add 8 times the amount of water to the ginseng slices and soak for 3 hours, then boil for 1 hour, boil three times, combine the decoctions, and filter to obtain the ginseng residue and decoction 1;

[0093] (2) Soak the Astragalus root, corn silk, Danshen 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.

[0094] (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.

[0095] The preparation method of Example 4 is as follows:

[0096] (1) Add 12 times the amount of water to the ginseng slices and soak for 8 hours, then decoct for 1 hour three times. Combine the decoctions and filter to obtain the ginseng residue and decoction 1;

[0097] (2) Soak the Astragalus root, corn silk, Danshen slices and the ginseng residue obtained in (1) in 12 times the amount of water for 3 hours and then decoct. Decoction is repeated 3 times, each time for 1 hour. Combine the decoctions and filter to obtain decoction 2.

[0098] (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.

[0099] The preparation method of Example 5 is as follows:

[0100] (1) Ginseng slices, soak in 8 times water for 3 hours, then decoct for 1 hour, decocting three times, combining the decoctions, filtering to obtain decoction 1 and ginseng residue;

[0101] (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, and then boil for 3 hours. Filter to obtain decoction 2;

[0102] (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.

[0103] The preparation method of Example 6 is as follows:

[0104] (1) Ginseng slices: soak in 12 times the amount of water for 10 hours, then boil for 3 hours, and filter to obtain decoction 1 and ginseng residue;

[0105] (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 three times, each time for 1 hour. Combine the decoctions, filter, and obtain decoction 2;

[0106] (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.

[0107] Comparative Example 1

[0108] 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. The difference between this comparative example and Example 1 is that it does not contain ginseng, but adds an equal amount of Codonopsis.

[0109] The preparation method is as follows:

[0110] (1) Add 10 times the amount of water to Codonopsis pilosula slices and soak for 6 hours, then decoct for 2 hours. Decoction is performed twice, and the decoctions are combined and filtered to obtain Codonopsis pilosula residue and decoction 1;

[0111] (2) Soak the Astragalus, Corn Silk, Danshen 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. Combine the decoctions and filter to obtain Decoction 2.

[0112] (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.

[0113] Comparative Example 2

[0114] The formula of this comparative example 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 bean.

[0115] The difference from Example 1 is that a portion of corn silk is replaced with psyllium seeds and red beans having similar effects.

[0116] The preparation method is as follows:

[0117] (1) Ginseng slices: soak in 10 times the amount of water 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;

[0118] (2) Soak the astragalus root, corn silk, salvia miltiorrhiza slices, plantain seeds, red bean 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. Combine the decoctions and filter to obtain decoction 2.

[0119] (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.

[0120] Comparative Example 3

[0121] The formula of this comparative example is as follows by weight: 10 parts of astragalus, 8 parts of ginseng, 25 parts of salvia miltiorrhiza, and 60 parts of corn silk.

[0122] The difference from Example 1 is that the weight ratio of the components is different, and the rest are the same.

[0123] 1. Drug efficacy experiment

[0124] 1. Materials and Methods

[0125] 1.1 Experimental Animals

[0126] SPF male C57BL / 6 mice, 8 weeks old, weighing 22–24 g, were purchased from Beijing Biotechnology Co., Ltd. (license number: SCXK(Beijing)2019-0010). The experimental procedures were performed after one week of acclimatization, housed at a temperature of 20–26°C and a humidity of 40%–70%.

[0127] 1.2 Experimental drugs

[0128] Blank control group: distilled water;

[0129] Experimental group: Chinese medicine compositions prepared according to Examples 1-2 and Comparative Examples 1-3;

[0130] isoproterenol hydrochloride (ISO, MCE);

[0131] Positive control drug: sacubitril / valsartan sodium tablets (Nocinto, specification 100 mg, Novartis);

[0132] 1.3 Experimental Reagents

[0133] The main reagents used in this experiment are shown in Table 3.

[0134] Table 3

[0135]

[0136] Note: The full name of Shanghai ELISA is Shanghai ELISA Biotechnology Co., Ltd.

[0137] 1.4 Experimental Instruments

[0138] The main experimental instruments used in this study are shown in Table 4.

[0139] Table 4

[0140]

[0141] 2. Experimental Methods

[0142] 2.1 Model replication

[0143] After 7 days of adaptive feeding, all mice in the control group, except for the control group, were treated with drug-induced heart failure models by subcutaneous injection of ISO (30 mg / kg / day). Ultrasound diagnosis was performed after 14 consecutive days of administration, and an LVEF value of ≤45% was used as the standard for successful model establishment.

[0144] 2.2 Animal grouping

[0145] 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 formula group BHF), Example 2 group (complete heart failure formula group QHF), comparative example group 1, comparative example group 2, and comparative example group 3.

[0146] 2.3 Drug delivery design

[0147] 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.

[0148] 2.4 Index detection

[0149] During the experiment, cardiac ultrasound examinations were performed 14 days after subcutaneous ISO injection and after oral administration. Following administration, blood was collected and centrifuged, and pathological tissue samples were collected for testing of relevant indicators. Animal care during the experiment complied with the animal ethics requirements stipulated in the "Regulations on the Administration of Laboratory Animals" of the National Science and Technology Commission.

[0150] 2.4.1 Color Doppler Ultrasound Examination of the Hearts of Mice in Each Group

[0151] Detection time point: 14 days after subcutaneous injection of ISO and oral administration.

[0152] Procedure: After anesthesia, mice were fixed in the supine position on a surgical board. Thoracic hair was removed using a small animal shaver and depilatory cream before ultrasound examination. M-mode echocardiography was obtained with the transducer positioned at the level of the papillary muscles, with the M-mode sampling line perpendicular to the ventricular septum, atria, and left ventricle. Left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVISd) were measured, and the average of three cardiac cycles was used to calculate left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (FS).

[0153] 2.4.2 Myocardial injury index detection

[0154] After ultrasound testing, the mice's eyeballs were removed for blood collection, and the serum was separated for later use. Myocardial injury-related markers, including B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), troponin I (cTnI), troponin T (cTnT), and creatine kinase isoenzyme (CK-MB), were measured using ELISA.

[0155] 2.4.3 Detection of inflammatory factor levels

[0156] The levels of inflammatory factors TNF-α, IL-1β, IL-6, INF-γ, and hs-CRP in the circulating system were detected by ELISA.

[0157] 2.4.4 Myocardial fibrosis level detection

[0158] The α-SMA level, a marker related to myocardial fibrosis, was detected by ELISA.

[0159] 2.4.5 Cardiac histopathology

[0160] The heart tissue was removed and fixed with 10% neutral formaldehyde solution, embedded in paraffin, and sliced ​​(4-6 μm). H&E staining, Masson staining, and WGA staining of the left ventricle were performed and observed under a microscope.

[0161] 2.5 Statistical analysis

[0162] All experimental data were processed using SPSS 27.0 statistical software and expressed as mean ± standard deviation. One-way analysis of variance (ANOVA) was used when the data conformed to a normal distribution and homogeneity of variance. Multiple comparisons between groups were performed using the LSD method. F values ​​were corrected for heterogeneity of variance using the Welch method, and further multiple comparisons were performed using the Dunnett T3 method. P < 0.05 was considered statistically significant.

[0163] 3. Results

[0164] 3.1 Effects of Xinshuai Recipe on Cardiac Function in Mice

[0165] The results of color ultrasound examination of the hearts of mice in each group are shown in Table 5 and Figures 1-9 shown.

[0166] After intraperitoneal injection of ISO, the LVEF and FS values ​​of the mice in the model group were significantly decreased compared with those in the control group (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 in mice; after 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).

[0167] After gavage of mice with heart failure basic formula (BHF, Chinese medicine composition in Example 1) and heart failure complete formula (QHF, Chinese medicine composition in Example 2), the cardiac function of mice with heart failure can be significantly corrected. Compared with the model group, LVEF and FS values ​​were significantly increased (P < 0.05); LVIDd value was significantly reduced (basic formula P < 0.05, complete formula P < 0.01), LVIDs value was reduced, but there was no significant difference in Example 1 group, while it was significantly decreased in Example 2 group (P < 0.01); compared with the positive drug group, there was no significant difference between Example 1 group and Example 2 group, indicating that the heart failure formula, whether it is the basic formula of Example 1 group or the complete formula of Example 2 group, can significantly improve the cardiac function in the state of heart failure, and there is no difference in efficacy with Noxintu; compared with the model group, the cardiac function of comparative example group 1, comparative example group 2, and comparative example group 3 was slightly improved, but there was no statistical difference.

[0168] Table 5

[0169]

[0170] 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.

[0171] 3.2 Effects of Xinxiu Recipe on Myocardial Injury Markers in Mice

[0172] The results of myocardial injury index detection in each group are shown in Table 6. Figure 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 cardiac troponin T (cTnT) were significantly increased in the model group compared with the control group (P < 0.01). The level of cardiac troponin I (cTnI) was also increased, but there was no statistical difference.

[0173] Compared with the model group, the levels of myocardial injury-related indicators in all drug-treated groups showed significant improvement, as evidenced by significant decreases in BNP, ANP, CK-MB, and cTnT levels (P < 0.01 or P < 0.05). After drug administration, cTnI levels were lower than in the model group, but the difference was not significant. This indicates that the Heart Failure Recipe, whether the basic formula in Example 1 or the complete formula in Example 2, can significantly improve myocardial status, and there were no differences between the drug-treated groups.

[0174] Table 6

[0175]

[0176] 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.

[0177] 3.3 Effects of Xinshuai prescription on inflammatory factors in the heart failure environment of mice

[0178] The results of inflammatory factor levels in each group of mice are shown in Table 7. Figure 11 shown.

[0179] After intraperitoneal injection of ISO, the model group showed severe myocardial damage compared with the control group, and the expression of inflammatory factors TNF-α, IL-1β, IL-6, INF-γ, and hs-CRP were significantly increased (P < 0.05, P < 0.01). After treatment, the expression of inflammatory factors was significantly improved compared with the ISO group (P < 0.05). No statistical difference was found between the treatment groups.

[0180] Table 7

[0181]

[0182] 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.

[0183] 3.4 Effect of Xinshuai Recipe on Fibrosis-Related Indicators α-SMA

[0184] The results of myocardial fibrosis level detection in each group of mice are shown in Table 8. Figure 12 shown.

[0185] After ISO administration, myocardial damage and subsequent myocardial fibrosis occurred. Compared with the control group, the myocardial damage in the model group was more severe, and the expression of α-smooth muscle actin (α-SMA) was significantly increased (P < 0.05). After treatment, the expression of α-SMA was significantly improved compared with the ISO group (P < 0.05). No statistical difference was found between the treatment groups.

[0186] Table 8

[0187]

[0188] Note: #Compared with the control group: P < 0.05; *Compared with the model group: P < 0.05.

[0189] 3.5 Effect of Xinshuai Recipe on Histopathology of Heart Failure Mice

[0190] When myocardial damage and cardiac function of heart failure mice undergo significant changes, the pathological tissue staining results are as follows:

[0191] The results of H&E and MASSON staining are as follows Figure 13 As shown: Microscopic observation after H&E and MASSON staining of the heart tissue of the mice in the control group showed normal myocardial structure and morphology, neatly arranged myocardial fibers, and no fibrosis was observed; microscopic observation after HE and MASSON staining of the heart tissue of the 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 the mice in the E group 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 the mice in the BHF and QHF groups were significantly improved.

[0192] The WGA staining of the left ventricle was semi-quantitatively analyzed and the corresponding data were statistically analyzed (see Table 8). The model group showed significant differences compared with the normal group (P < 0.01). After treatment, the E group, BHF group, and QHF group all showed significant changes compared with the ISO group (P < 0.01, P < 0.05). There was no statistical difference between the treatment groups (see Table 9, Figure 14 shown).

[0193] Table 9

[0194]

[0195] Note: #Compared with the control group: P < 0.05; *Compared with the model group: P < 0.05.

[0196] In summary, the traditional water decoction of heart failure prescriptions, whether basic or complete, has important effects on improving cardiac function, reducing inflammatory response, and inhibiting myocardial fibrosis in the ISO-induced heart failure model in mice.

[0197] 2. Clinical Cases

[0198] 1. Wang, female, 48 years old, visited the hospital on June 21, 2024, complaining of dilated cardiomyopathy for more than 3 years. On May 12, 2024, ultrasound showed left ventricular end-diastolic anteroposterior diameter of 66mm, left ventricular end-systolic anteroposterior diameter of 54mm, EF30%, and low blood pressure of 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%, and indicators such as left ventricular enlargement and cardiac function were improved.

[0199] 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), cardiomegaly, pericardial effusion, coronary heart disease, old myocardial infarction, etc., and then visited the hospital on August 5 of the same year. Examination showed extensive anterior wall myocardial infarction, heart failure, EF 20%. After taking the Chinese medicine composition of Example 4 of the present invention for several weeks, ultrasound showed that the left ventricular posterior wall thickness was 10 mm (8-11 mm), and the left ventricular motion, ventricular septum continuity, atrial septum continuity, etc. were all normal, EF 45%, FS 23%, indicating that the cardiac function indicators were significantly improved.

[0200] 3. Mr. Wang, male, 62 years old, 8 years after coronary artery bypass grafting, visited our hospital on November 12, 2023. He was short of breath and weak, with EF 32% and FS 19%. After taking the Chinese medicine composition of Example 5 of the present invention for several weeks, his EF was 50%, FS 25%, and the left atrial meridian was high normal, indicating that the cardiac function indicators were greatly improved.

[0201] 4. Xiao, male, 58 years old, visited our hospital on September 1, 2023. He was diagnosed with heart failure and dilated cardiomyopathy after examination. 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.

[0202] This document uses specific examples to illustrate the inventive concept in detail. The above embodiments are only intended to help understand the core concept of the present invention. It should be noted that any obvious modifications, equivalent substitutions, or other improvements made by a person skilled in the art without departing from the inventive concept should be included within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating heart failure, characterized in that: The raw materials are calculated by weight and are prepared from the following ingredients: 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.

2. The Chinese medicine composition according to claim 1, characterized in that The raw materials are calculated by weight and are prepared from the following ingredients: 100 parts of astragalus, 20 parts of ginseng, 60 parts of salvia miltiorrhiza, 80 parts of corn silk, 30 parts of chuanxiong, 30 parts of red peony root, 20 parts of poria, 30 parts of motherwort and 20 parts of tangerine peel.

3. The method for preparing the Chinese medicine composition according to any one of claims 1 to 2, 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 root, salvia miltiorrhiza root, corn silk, chuanxiong root, red peony root, poria cocos, motherwort, tangerine peel and ginseng residue 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 it.

4. Use of the Chinese medicine composition according to any one of claims 1 to 2 in the preparation of a medicament for treating heart failure.

5. A drug, characterized in that The medicine comprises the traditional Chinese medicine composition according to any one of claims 1 to 2.

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