Traditional Chinese medicine composition for improving heart and kidney function decline as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for improving heart and kidney function decline and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 20-40 parts of ginseng, 20-40 parts of rabdosia rubescens, 10-30 parts of pseudo-ginseng, 5-25 parts of glossy privet fruit, 5-25 parts of schisandra chinensis and 5-25 parts of cinnamon; the invention further discloses a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition has the beneficial effects that ginseng is used as a monarch drug to tonify qi, tonify heart and enhance cardiac contractility, which is a leading drug of the whole formula; rabdosia rubescens and pseudo-ginseng serve as ministerial drugs, rabdosia rubescens can clear away heat and toxic materials, pseudo-ginseng can promote blood circulation to remove blood stasis, and the ministerial drugs jointly assist the And glossy privet fruit, schisandra chinensis and cinnamon are used as adjuvant drugs to nourish liver and kidney, astringe and induce astringency, warm yang and dredge vessels, and promote the exertion of the efficacy of the whole prescription. All the medicines are combined to comprehensively regulate heart and kidney functions and improve the living quality of patients.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for improving the decline of cardiorenal function, and a preparation method and application thereof. Background Art

[0002] The heart and kidneys are the source of human life. They have the function of transporting and storing blood and are called the innate foundation of the human body. According to traditional Chinese medicine, human growth, reproduction and development are closely related to the heart and kidneys. As people age, their heart and kidney functions decline, especially in the elderly, which needs special attention.

[0003] The prevalence of heart failure (HF) is growing rapidly due to the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. According to the provisions of domestic and international prevention and treatment guidelines, patients' heart failure is divided into three categories: the first is heart failure with reduced ejection fraction (HFrEF), the second is heart failure with intermediate ejection fraction (HFmrEF), and the third is heart failure with preserved ejection fraction (HFpEF). HFpEF cases account for more than half of all HF cases, and the etiology is complex and there is a lack of effective treatment, especially for elderly patients (with many comorbidities). Compared with HFrEF, there is currently no drug for the treatment of HFpEF in the elderly. Basically, complications can only be alleviated and controlled by adjusting diet and a healthy and active lifestyle. Although the mortality rate of HFpEF is low, the frequency of readmission is high, which seriously affects the quality of life.

[0004] In the existing Chinese medicine compositions, the treatment plans for senile heart and kidney function decline mainly focus on a single medicinal material or a simple combination of medicinal materials. These plans usually aim to improve heart function or improve kidney function, and common prescriptions include qi-tonifying and blood-activating, yin-nourishing and kidney-tonifying, etc. For example, some commonly used prescriptions include ginseng, astragalus, salvia miltiorrhiza, etc., but most of these prescriptions only intervene in a single organ or system, lacking the comprehensive effect of comprehensively regulating heart and kidney function. In addition, animal experiments and clinical studies in the prior art have also failed to fully reveal the specific mechanism of its anti-aging effect. The existing prescriptions also have a certain degree of arbitrariness in drug combinations, and have failed to optimize the drug compatibility ratio based on scientific data and models, making their guidance in application relatively limited.

[0005] In view of this, the inventor conducted in-depth research on this demand, and thus the present case was produced. Summary of the invention

[0006] To solve the above problems, the inventors conducted in-depth animal experiments and molecular mechanism studies, revealing its specific pathway of action in the anti-aging process, and obtained a Chinese medicine composition for improving cardiorenal function decline and its preparation method and application, which can effectively improve senile cardiorenal function decline, achieve synchronous regulation of cardiorenal function, and overcome the limitation of the prior art of only intervening on a single organ.

[0007] The invention provides a traditional Chinese medicine composition for improving the decline of cardiorenal function, which comprises the following raw materials by weight: 20-40 parts of ginseng, 20-40 parts of rubescens, 10-30 parts of notoginseng, 5-25 parts of Ligustrum lucidum, 5-25 parts of Schisandra chinensis and 5-25 parts of cinnamon.

[0008] Preferably, the following raw materials are included by weight: 25-35 parts of ginseng, 25-35 parts of rubescens, 15-25 parts of Panax notoginseng, 10-20 parts of Ligustrum lucidum, 10-20 parts of Schisandra chinensis, and 10-20 parts of cinnamon.

[0009] Preferably, the following raw materials are included by weight: 28-32 parts of ginseng, 28-32 parts of rubescens, 18-22 parts of Panax notoginseng, 13-17 parts of Ligustrum lucidum, 13-17 parts of Schisandra chinensis, and 13-17 parts of cinnamon.

[0010] Preferably, the following raw materials are included by weight: 30 parts of ginseng, 30 parts of rubescens, 20 parts of Panax notoginseng, 15 parts of Ligustrum lucidum, 15 parts of Schisandra chinensis, and 15 parts of cinnamon.

[0011] The present invention also provides the use of the above-mentioned Chinese medicine composition in the preparation of a medicine for improving the decline of heart and kidney functions, especially in the preparation of a medicine for treating patients with heart failure and renal damage.

[0012] The present invention also provides a medicine for improving the decline of cardiorenal function, comprising the above-mentioned Chinese medicine composition for improving the decline of cardiorenal function and pharmaceutically acceptable excipients.

[0013] Preferably, the dosage form of the above-mentioned medicine is Chinese medicine decoction, decoction, granules, pills, capsules, tablets, tea, suspension, powder or oral solution.

[0014] The present invention also provides a method for preparing the above-mentioned drug for improving the decline of cardiorenal function, wherein the drug is a Chinese medicine decoction, and the preparation method thereof is as follows:

[0015] Step 1, weighing each raw material drug according to weight percentage, mechanically crushing and mixing evenly to obtain coarse powder;

[0016] Step 2, adding crude drug powder to an extraction reagent for extraction;

[0017] Step three, collecting the extract, centrifuging and filtering, and concentrating to obtain the drug.

[0018] Preferably, the extraction reagent in step 2 is water or alcohol, and the extraction is performed twice.

[0019] The beneficial effects produced by the technical solution of the present invention are as follows:

[0020] In the Chinese medicine composition of the present invention, ginseng is used as the main drug, which can invigorate qi and strengthen the heart, and enhance the contractility of the heart, and is the leading drug of the whole prescription; rubescens and Panax notoginseng are used as the assistant drugs, rubescens clears away heat and detoxifies, and Panax notoginseng promotes blood circulation and removes blood stasis, and they jointly assist the main drug in improving heart function; Ligustrum lucidum, Schisandra chinensis and Cinnamon bark are used as adjuvant drugs, which can nourish the liver and kidney, astringe and consolidate, warm yang and dredge meridians, and promote the efficacy of the whole prescription. Modern pharmacological studies have shown that the main drug ginseng in the prescription has significant antioxidant and myocardial function enhancement effects, the assistant drugs rubescens and Panax notoginseng can improve microcirculation and anti-thrombosis, the adjuvant drugs Ligustrum lucidum and Schisandra chinensis can protect liver and kidney functions and enhance immunity, and Cinnamon bark can improve blood circulation, warm yang and invigorate the kidney, and comprehensively regulate heart and kidney functions, thereby improving the quality of life of patients.

[0021] In addition to regulating the heart and kidney functions, the prescription of the present invention also has the effects of invigorating qi, activating blood circulation and detoxifying, achieving overall improvement of the heart and kidney functions of the elderly, and delaying the aging process of the organs by inhibiting the molecular signals related to inflammation and aging. In addition, the prescription of the present invention optimizes the compatibility ratio of the drugs through a scientifically designed combination of Chinese medicines, achieves synchronous conditioning of the heart and kidney functions, and overcomes the limitation of the prior art that only intervenes on a single organ; it also reveals the mechanism by which the Chinese medicine combination improves the heart and kidney functions by inhibiting the inflammatory signals of immune cells related to clonal hematopoiesis (CHIP), ensuring the high efficiency and safety of the prescription. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 The cardiac ultrasound comparison images of mice in each group;

[0024] Figure 2 The figure is a comparison of cardiac pathology of mice in each group;

[0025] Figure 3 Comparison of renal function and renal pathology of mice in each group;

[0026] Figure 4 Comparison of cardiac and renal inflammation and aging markers in each group of mice;

[0027] Figure 5Single-cell sequencing images of mouse immune cells in the blank control group, aging model group, and traditional Chinese medicine group;

[0028] Figure 6 Violin plots of single-cell sequencing expression of mouse aging and inflammatory markers;

[0029] Figure 7 Analysis of CHIP signal maps between groups for single-cell sequencing;

[0030] Figure 8 This is a diagram to verify the effect of traditional Chinese medicine on mouse immune cells through bone marrow transplantation;

[0031] Fig. 9 This is a diagram showing the effect of the Chinese medicine group on the macrophage-fibroblast interaction under in vitro co-culture conditions. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Therefore, the following detailed description of the embodiments provided by the present invention is not intended to limit the scope of the claimed invention, but merely represents the selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] Through in-depth animal experiments and molecular mechanism research, the inventors revealed its specific action pathway in the anti-aging process, and obtained a Chinese medicine composition for improving the decline of heart and kidney function, as well as its preparation method and application, which can effectively improve the decline of heart and kidney function in the elderly, achieve the synchronous conditioning of heart and kidney function, and overcome the limitation of the existing technology that only intervenes on a single organ. The specific implementation method is as follows:

[0034] The invention provides a traditional Chinese medicine composition for improving the decline of cardiorenal function, which comprises the following raw materials by weight: 20-40 parts of ginseng, 20-40 parts of rubescens, 10-30 parts of notoginseng, 5-25 parts of Ligustrum lucidum, 5-25 parts of Schisandra chinensis and 5-25 parts of cinnamon.

[0035] As a preferred embodiment, the following raw materials are included by weight: 25-35 parts of ginseng, 25-35 parts of rubescens, 15-25 parts of Panax notoginseng, 10-20 parts of Ligustrum lucidum, 10-20 parts of Schisandra chinensis, and 10-20 parts of cinnamon.

[0036] As a preferred embodiment, the following raw materials are included by weight: 28-32 parts of ginseng, 28-32 parts of rubescens, 18-22 parts of Panax notoginseng, 13-17 parts of Ligustrum lucidum, 13-17 parts of Schisandra chinensis, and 13-17 parts of cinnamon.

[0037] As a preferred embodiment, the following raw materials are included by weight: 30 parts of ginseng, 30 parts of rubescens, 20 parts of Panax notoginseng, 15 parts of Ligustrum lucidum, 15 parts of Schisandra chinensis, and 15 parts of cinnamon.

[0038] The present invention also provides the use of the above-mentioned Chinese medicine composition in the preparation of a medicine for improving the decline of heart and kidney functions, especially in the preparation of a medicine for treating patients with heart failure and renal damage.

[0039] The present invention also provides a medicine for improving the decline of cardiorenal function, comprising the above-mentioned Chinese medicine composition for improving the decline of cardiorenal function and pharmaceutically acceptable excipients.

[0040] As a preferred embodiment, the dosage form of the above-mentioned medicine is Chinese medicine decoction, decoction, granules, pills, capsules, tablets, tea, suspension, powder or oral solution.

[0041] The present invention also provides a method for preparing the above-mentioned drug for improving the decline of cardiorenal function, wherein the drug is a Chinese medicine decoction, and the preparation method thereof is as follows:

[0042] Step 1, weighing each raw material drug according to weight percentage, mechanically crushing and mixing evenly to obtain coarse powder;

[0043] Step 2, adding crude drug powder to an extraction reagent for extraction;

[0044] Step three, collecting the extract, centrifuging and filtering, and concentrating to obtain the drug.

[0045] As a preferred embodiment, the extraction reagent in step 2 is water or alcohol, and the extraction is performed twice.

[0046] The present invention is further described in detail below in conjunction with specific embodiments:

[0047] Example 1

[0048] A drug for improving the decline of heart and kidney function, wherein the raw materials include: 20 parts of ginseng, 20 parts of rubescens, 10 parts of notoginseng, 5 parts of Ligustrum lucidum, 5 parts of Schisandra chinensis, and 5 parts of cinnamon. The preparation method of the herbal decoction includes the following steps:

[0049] Step 1, weighing each raw material drug according to weight percentage, mechanically crushing and mixing evenly to obtain coarse powder;

[0050] Step 2, adding crude drug powder to water and extracting twice, and combining the two extracts;

[0051] Step 3, collecting the extract, centrifuging and filtering, and concentrating to obtain the concentrate of the embodiment.

[0052] Example 2

[0053] A drug for improving the decline of heart and kidney function, wherein the raw materials include: 25 parts of ginseng, 25 parts of rubescens, 15 parts of notoginseng, 10 parts of Ligustrum lucidum, 10 parts of Schisandra chinensis, and 10 parts of cinnamon bark. The preparation method of the herbal decoction is the same as that of Example 1.

[0054] Example 3

[0055] A drug for improving the decline of heart and kidney function, wherein the raw materials include: 28 parts of ginseng, 28 parts of rubescens, 18 parts of notoginseng, 13 parts of Ligustrum lucidum, 13 parts of Schisandra chinensis, and 13 parts of cinnamon. The preparation method of the herbal decoction is the same as that of Example 1.

[0056] Example 4

[0057] A drug for improving the decline of heart and kidney function, wherein the raw materials include: 30 parts of ginseng, 30 parts of rubescens, 20 parts of notoginseng, 15 parts of Ligustrum lucidum, 15 parts of Schisandra chinensis, and 15 parts of cinnamon. The preparation method of the herbal decoction is the same as that of Example 1.

[0058] Example 5

[0059] A drug for improving the decline of heart and kidney function, wherein the raw materials include: 32 parts of ginseng, 32 parts of rubescens, 22 parts of notoginseng, 17 parts of Ligustrum lucidum, 17 parts of Schisandra chinensis, and 17 parts of cinnamon. The preparation method of the herbal decoction is the same as that of Example 1.

[0060] Example 6

[0061] A drug for improving the decline of heart and kidney function, wherein the raw materials include: 35 parts of ginseng, 35 parts of rubescens, 25 parts of notoginseng, 20 parts of Ligustrum lucidum, 20 parts of Schisandra chinensis, and 20 parts of cinnamon bark. The preparation method of the herbal decoction is the same as that of Example 1.

[0062] Example 7

[0063] A drug for improving the decline of heart and kidney function, wherein the raw materials include: 40 parts of ginseng, 40 parts of rubescens, 30 parts of notoginseng, 25 parts of Ligustrum lucidum, 25 parts of Schisandra chinensis, and 25 parts of cinnamon bark. The preparation method of the herbal decoction is the same as that of Example 1.

[0064] After reasonable compounding of the components and optimization of the dosage, the inventors conducted the following experiments using the concentrate prepared in the above preferred embodiment 4 to verify its efficacy:

[0065] 1. Experimental Animals

[0066] Fifty SPF healthy male C57 mice (80±10 weeks old, weighing 20±3 g) and ten SPF healthy male C57 mice (8-10 weeks old, weighing 20±3 g) were purchased from the Experimental Animal Center of Guangzhou University of Chinese Medicine and raised in the SPF Animal Experimental Center of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The experimental environment: constant temperature of 20-25℃, relative humidity of 40-60%, light cycle of 12 hours, free access to food and water, and the experiment began after one week of adaptive feeding.

[0067] Experimental animal environment: clean grade environment.

[0068] 2. Experimental drugs

[0069] The experimental raw materials were purchased from the First Affiliated Hospital of Guangzhou University of Chinese Medicine. After being identified by the Chinese Medicine Identification Teaching and Research Office of Guangzhou University of Chinese Medicine, all the purchased medicinal materials were in compliance with the standards of the Pharmacopoeia of the People's Republic of China.

[0070] 3. Modeling and experimental grouping

[0071] Ten mice (8-10 weeks old) were selected to form ① blank control group.

[0072] Fifty mice (80±10 weeks old) were selected and fed adaptively for one week, and then randomly divided into five groups: ②Aging model group,

[0073] ③ Example 4 Chinese medicine low dose group,

[0074] ④ Example 4 Chinese medicine medium dose group,

[0075] 5. Example 4 Chinese medicine high dose group,

[0076] ⑥Dapagliflozin control group,

[0077] Among them, except for ① the blank control group using 8-week-old mice, each other group used naturally aged mice (80±10 weeks old) and injected angiotensin II for 4 weeks at a rate of 0.125 μL / hr to create a heart failure model, and 10 mice were selected as ② the aging model group; Example 4 Chinese medicine group ③④⑤ after modeling, according to the human-mouse body surface area conversion, adults are calculated as 60kg, then the Chinese medicine is 2g / kg, converted to mice (calculated as 0.02kg) is 2.25g / kg of raw medicinal materials, converted to mice is 15.6g / kg (medium dose), and low doses (7.3g / kg) and high doses (31.2g / kg) are set separately. The medicinal materials are decocted and concentrated to 0.2mL / mouse by gavage, once a day, for 10 consecutive weeks; ⑥ Dapagliflozin control group gave mice 10mg / kg suspension after modeling, once a day, for 10 consecutive weeks. The blank control group was gavaged with an equal amount of normal saline. After 10 weeks, echocardiography, tissue staining agent single-cell sequencing and other experiments were performed.

[0078] 4. Experimental scoring criteria

[0079] Animal experimental data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among multiple groups, followed by Turkey test for pairwise comparison. Repeated measurement test was used for time series data, and P < 0.05 was considered statistically significant.

[0080] 5. Experimental results

[0081] (1) The Chinese medicine composition of the present invention can effectively improve the cardiac function of elderly mice:

[0082] Figure 1 The following is a cardiac ultrasound comparison of mice in each group. Compared with the blank control group, the left ventricular ejection fraction, left ventricular end-systolic diameter, left ventricular pressure rise rate and left ventricular pressure drop rate of the aging model group were significantly decreased (P<0.05), indicating that the elderly mice had cardiac systolic and diastolic dysfunction. Compared with the aging model group, the left ventricular ejection fraction and left ventricular end-systolic diameter of the heart of the mice in the Chinese medicine group did not increase significantly (P>0.05), while the left ventricular pressure rise rate and left ventricular pressure drop rate increased significantly after 10 weeks of intervention (P<0.05), and there was no significant difference compared with the intervention of dapagliflozin (P>0.05), indicating that the Chinese medicine composition provided by the present invention can effectively alleviate aging-related cardiac diastolic disorders.

[0083] (2) The Chinese medicine composition of the present invention can effectively reduce cardiac fibrosis in aged mice:

[0084] Figure 2 The figure is a comparison of cardiac pathology of mice in each group. The immunofluorescence results show that compared with the blank control group, the co-staining area of ​​Collegan I and α-SMA in the aging model group increased significantly (P<0.05), indicating that cardiac fibrosis exists in elderly mice. Compared with the aging model group, the co-staining area of ​​Collegan I and α-SMA in the heart of mice in the Chinese medicine group decreased significantly (P<0.05), and there was no significant difference compared with the intervention of the dapagliflozin control group (P>0.05), indicating that the Chinese medicine composition provided by the present invention can effectively slow down the pathological state of cardiac fibrosis associated with aging.

[0085] (3) The Chinese medicine composition of the present invention can improve the renal function and fibrosis of elderly mice:

[0086] The renal function was detected by serum creatinine and the renal fibrosis was detected by MASSON staining. Figure 3 , Figure 3It is a comparison chart of kidney function and kidney pathology of each group of mice. Compared with the blank control group, the serum creatinine and fibrosis area of ​​the kidneys in the aging model group increased significantly (P<0.05), indicating that the elderly mice had decreased kidney function and fibrosis pathology. Compared with the aging model group, the serum creatinine and fibrosis area of ​​the kidneys of the Chinese medicine group mice decreased significantly (P<0.05), and there was no significant difference compared with the dapagliflozin control group (P>0.05), indicating that the Chinese medicine composition provided by the present invention can effectively alleviate the kidney function and fibrosis pathology associated with aging.

[0087] (4) The Chinese medicine composition of the present invention can alleviate the levels of inflammation and aging markers in elderly mice:

[0088] The mRNA levels of inflammatory markers (IL6, TNF) and aging markers (P21, S100A8) were detected in the heart and kidney tissues of each group of mice. Figure 4 , Figure 4 The following is a comparison chart of cardiac and renal inflammation and aging markers in each group of mice. The results showed that compared with the blank control group, the mRNA levels of inflammatory factors and aging markers in the aging model group increased significantly (P<0.05). Compared with the aging model group, the mRNA levels of inflammatory factors and aging markers in the Chinese medicine group mice decreased significantly (P<0.05), indicating that the Chinese medicine composition provided by the present invention can effectively alleviate the inflammation and aging signal process of immune cells.

[0089] (5) Single-cell sequencing revealed that the pharmacodynamic mechanism of the Chinese medicine composition of the present invention involves age-related clonal hematopoiesis (CHIP):

[0090] Figure 5 Single-cell sequencing was performed on mouse immune cells (CD45+ cells) in the blank control group, aging model group and traditional Chinese medicine group. Through the SinglR gene comparison annotation tool, a total of 6 immune cells, including granulocytes, macrophages, monocytes, NK cells, T cells, and B cells, were identified. Through GSEA enrichment analysis of immune cells, it was found that compared with the blank control group, the immune cell inflammatory response signals and CHIP-related gene sets in the aging model group were upregulated (P<0.05); compared with the aging model group, the inflammatory response signals and CHIP-related gene sets in the traditional Chinese medicine group were downregulated (P<0.05); considering that CHIP is an important factor in senile inflammation, we speculate that the Chinese medicine composition provided by the present invention can effectively alleviate the cardiorenal function of aging mice, which may be related to the inhibition of CHIP.

[0091] (6) Single-cell sequencing to detect levels of immune cell inflammation and aging markers:

[0092] Since CHIP immune cells usually show inflammatory and aging phenotypes, the mRNA of inflammatory factors (Tnf), chemokines (Ccl2, Cxcl2) and aging markers (Cdkn2a, S100a8, Spp1) of single-cell sequencing data were analyzed to obtain Figure 6 , Figure 6 It is a violin plot of single-cell sequencing expression of mouse aging and inflammatory markers, in which the Control group is a blank control group, the Model group is an aging model group, and the TCM group is a traditional Chinese medicine group. The results showed that compared with the blank control group, the mRNA levels of inflammatory factors, chemokines and aging markers in the aging model group increased significantly (P<0.05). Compared with the aging model group, the mRNA levels of inflammatory factors, chemokines and aging markers in the traditional Chinese medicine group decreased significantly (P<0.05), and there was no significant difference compared with the dapagliflozin control group (P>0.05), indicating that the traditional Chinese medicine composition provided by the present invention can effectively alleviate the inflammatory and aging signaling process of immune cells, which may be related to CHIP.

[0093] (7) Single-cell pseudo-time series analysis found that the Chinese medicine composition of the present invention inhibits the differentiation of immune cells into CHIP:

[0094] The inventors performed pseudo-time series analysis on single-cell data and firstly analyzed the classic CHIP signal (TET2 + / - Myeloid cell signal) to build a machine learning scoring model, and apply the monocle3 software package to construct the myeloid cell differentiation trajectory according to the level of CHIP signal. Figure 7 , Figure 7 The CHIP signal diagram of each group was analyzed by single-cell sequencing. The results showed that compared with the blank control group, the CHIP signal of the aging model group was significantly increased (P<0.05), and the cells significantly differentiated in the CHIP direction. Compared with the aging model group, the CHIP signal of the traditional Chinese medicine group was significantly decreased, and the cells differentiated less in the CHIP direction. This further revealed that the traditional Chinese medicine composition of the present invention can effectively inhibit the differentiation of immune cells in the CHIP direction.

[0095] (8) Animal experiments verify the efficacy of the Chinese medicine composition of the present invention on the CHIP model:

[0096] To directly test the hypothesis, the inventors used the characteristic representative model TET2 of CHIP + / - The bone marrow transplantation mouse model simulated CHIP carrying, and the heart and kidney macrophages (CD68+ cells) were sorted by flow cytometry for qPCR detection. Figure 8 , Figure 8 To verify the effect of traditional Chinese medicine on mouse immune cells through bone marrow transplantation. The results showed that compared with the blank control group, TET2 + / -The mRNA levels of inflammatory factors (Tnf) and aging markers (Spp1, S100a8) in the heart and kidney macrophages of bone marrow transplanted mice were significantly increased (P<0.05), while the mRNA levels of inflammatory factors (Tnf) and aging markers (Spp1, S100a8) in the mice intervened by the traditional Chinese medicine group were significantly decreased (P<0.05), indicating that the traditional Chinese medicine composition of the present invention can effectively inhibit the inflammatory and aging phenotypes of the CHIP model.

[0097] (9) In vitro experiments on inflammation: Chinese medicine inhibits fibrosis by inhibiting CHIP:

[0098] To further verify whether the Chinese medicine composition of the present invention has an anti-fibrotic effect by inhibiting CHIP, we + / - The bone marrow transplantation mouse model was given Chinese medicine or saline for 4 weeks, and F4 / 80 sorted macrophages were co-cultured with mouse fibroblasts for 48 hours to obtain Fig. 9 , Fig. 9 In vitro co-culture was used to verify the effect of the Chinese medicine group on the macrophage-fibroblast interaction. Immunofluorescence results showed that compared with the blank control group, TET2 + / - The level of fibroblast fibrosis marker (α-SMA) in the bone marrow transplanted mouse co-culture group was significantly increased (P<0.05), while the level of fibrosis marker in the Chinese medicine group was significantly decreased after intervention (P<0.05), indicating that the Chinese medicine composition of the present invention can inhibit fibroblast activation by inhibiting CHIP.

[0099] Typical cases:

[0100] Case 1: Patient Ji, male, 68 years old, suffers from heart failure with preserved ejection fraction (HFpEF) accompanied by chronic renal insufficiency (CKD stage 3), and has a 20-year history of hypertension. In the past six months, he has experienced shortness of breath and lower limb edema after activity, frequent paroxysmal dyspnea at night, and needs to lie on a high pillow. Cardiac ultrasound showed that the left ventricular ejection fraction (LVEF) was 52%, and the pro-BNP level was significantly elevated. Renal function tests showed that the serum creatinine level was 280 μmol / L, the urine volume decreased, and the nocturia increased. Chinese medicine syndrome differentiation is qi deficiency and yang decline, and water dampness stops. The Chinese medicine decoction prepared in Example 4 was given, 1 dose per day, decocted to 250 mL, taken in the morning and evening, and the course of treatment was 28 days. After treatment, the patient's nocturnal dyspnea was significantly relieved, shortness of breath after activity was alleviated, lower limb edema was basically subsided, urine volume increased, and the number of nocturia decreased. During the follow-up examination, LVEF increased to 55%, pro-BNP and serum creatinine levels decreased significantly to 240μmol / L, and the patient's overall condition improved significantly, indicating that this prescription has a good therapeutic effect in regulating heart and kidney failure.

[0101] Case 2: Patient Ni, female, 72 years old, had a history of type 2 diabetes for 15 years. In recent years, she gradually developed fatigue and decreased urine volume due to chronic renal insufficiency, accompanied by mild edema of the face and lower limbs. Renal function tests showed that the creatinine level was 310μmol / L and urine protein (++). The patient also often had increased nocturia and poor sleep quality. Chinese medicine diagnosed it as spleen and kidney deficiency and dampness and turbidity internal obstruction. The Chinese medicine decoction prepared in Example 4 was given, 1 dose per day, decocted to 300mL, taken in the morning and evening, and the course of treatment was 30 days. After treatment, the patient's edema basically subsided, urine volume increased, nocturia decreased, and creatinine levels dropped to 275μmol / L during reexamination, and urine protein was reduced. The patient's symptoms of fatigue were also alleviated, and the overall condition was significantly improved. This side shows significant efficacy in regulating the effect of elderly diabetes with renal insufficiency.

[0102] Case 3: Patient Chen, male, 74 years old, has suffered from coronary heart disease for 10 years. Recently, he came to the doctor for worsening chest tightness and palpitations. The patient's symptoms are particularly obvious at night, accompanied by intermittent precordial pain, which worsens after activity. The electrocardiogram showed the presence of T wave inversion, and cardiac ultrasound indicated an ejection fraction of 53%, which was consistent with the diagnosis of heart failure with preserved ejection fraction (HFpEF). Chinese medicine syndrome differentiation is weak heart yang, qi stagnation and blood stasis. The Chinese medicine decoction prepared in Example 4 was given, 1 dose per day, decocted to 250mL, taken in the morning and evening, and treated continuously for 21 days. After treatment, the frequency of chest tightness and palpitations in patients was significantly reduced, pain was relieved at night, and palpitations after activity improved. During the electrocardiogram review, T wave inversion improved, and the ejection fraction was slightly increased to 55%. This prescription is effective in warming yang and invigorating qi, and improving the symptoms of elderly coronary heart disease with heart failure.

[0103] Case 4: Patient Chen, female, 80 years old, has long suffered from hypertension and chronic renal failure (CKD stage 4). In the past six months, fatigue has worsened, accompanied by increased nocturia, obvious edema of the face and lower limbs, and poor blood pressure control. The patient also has heart failure with preserved ejection fraction (HFpEF), and the creatinine level rises to 430μmol / L. Chinese medicine syndrome differentiation is kidney yang deficiency and water dampness flooding syndrome. The Chinese medicine decoction prepared in Example 4 is given, 1 dose per day, decocted to 300mL, taken in the morning and evening, and treated continuously for 42 days. After the treatment, the patient's nocturia decreased, edema significantly subsided, blood pressure dropped to 140 / 90mmHg, and creatinine level dropped to 380μmol / L. The patient's fatigue symptoms were also alleviated, and the ability to do daily activities was improved. The treatment not only improved the patient's renal function, but also significantly improved the patient's quality of life.

[0104] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for improving the decline of cardiorenal function, characterized in that: The raw materials are as follows, measured by weight: 20-40 parts of ginseng, 20-40 parts of rubescens, 10-30 parts of notoginseng, 5-25 parts of Ligustrum lucidum, 5-25 parts of Schisandra chinensis, and 5-25 parts of cinnamon.

2. The Chinese medicine composition for improving the decline of cardiorenal function according to claim 1, characterized in that: The raw materials are as follows, measured by weight: 25-35 parts of ginseng, 25-35 parts of rubescens, 15-25 parts of notoginseng, 10-20 parts of Ligustrum lucidum, 10-20 parts of Schisandra chinensis, and 10-20 parts of cinnamon bark.

3. The Chinese medicine composition for improving the decline of cardiorenal function according to claim 1, characterized in that: The raw materials are as follows, measured by weight: 28-32 parts of ginseng, 28-32 parts of rubescens, 18-22 parts of notoginseng, 13-17 parts of Ligustrum lucidum, 13-17 parts of Schisandra chinensis, and 13-17 parts of cinnamon bark.

4. Use of the Chinese medicine composition for improving cardiorenal function decline according to any one of claims 1 to 3 in the preparation of a medicament for improving cardiorenal function decline.

5. A drug for improving the decline of cardiorenal function, characterized in that: The invention comprises the Chinese medicine composition for improving the decline of cardiorenal function as described in any one of claims 1 to 3 and pharmaceutically acceptable excipients.

6. The drug for improving the decline of cardiorenal function according to claim 5, characterized in that: The dosage form of the medicine is Chinese medicine decoction, decoction, granules, pills, capsules, tablets, tea, suspension, powder or oral solution.

7. The method for preparing the drug for improving the decline of cardiorenal function according to claim 5 or 6, characterized in that: The medicine is a Chinese medicine decoction, and its preparation method is as follows: Step 1, weighing each raw material drug according to weight percentage, mechanically crushing and mixing evenly to obtain coarse powder; Step 2, adding crude drug powder to an extraction reagent for extraction; Step three, collecting the extract, centrifuging and filtering, and concentrating to obtain the drug.

8. The preparation method according to claim 7, characterized in that: The extraction reagent in step 2 is water or alcohol, and the extraction is performed twice.

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