Jiuwei decoction traditional Chinese medicine compound and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a modified Zhenwu decoction traditional Chinese medicine compound and application thereof. The traditional Chinese medicine compound of the modified true Wu decoction is prepared from the following raw materials in parts by weight: 10 to 30 parts of radix aconiti lateralis praeparata slices, 6 to 18 parts of sun-dried ginseng, 10 to 30 parts of poria cocos, 8 to 24 parts of raw rhizoma atractylodis macrocephalae, 10 to 30 parts of radix paeoniae alba, 20 to 60 parts of pubescent holly root and 4 to 12 parts of rhodiola rosea. Clinical observation finds that the flavored Zhenwu decoction is an effective drug for resisting HFpEF, and can reverse cardiac hypertrophy of HFpEF mice, relieve pulmonary edema conditions, remarkably improve the diastolic function, improve HFpEF cardiac hypertrophy, improve cardiac diastolic dysfunction, improve myocardial injury and collagen deposition and improve myocardial cell mitochondrial injury.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a modified Zhenwu decoction and application thereof. BACKGROUND

[0002] The prior art (Peng Z L, et al. Systematic evaluation of clinical efficacy of Zhenwu decoction in treating chronic heart failure with heart-kidney yang deficiency [J]. Chinese Journal of Traditional Chinese Medicine, 2017(35):3101-3106.) discloses that Zhenwu decoction is composed of aconite, paeonia, atractylodes, poria, and ginger, and has a good effect on patients with chronic heart failure with heart-kidney yang deficiency in clinical practice. However, at present, the treatment of heart-kidney yang deficiency heart failure by Zhenwu decoction is mainly limited to the regulation of water and electrolyte metabolism (warming yang and promoting water excretion), and lacks intervention on the problems of progressive deterioration of cardiac function caused by myocardial mitochondrial ultrastructure damage, ATP synthesis deficiency and abnormal energy metabolism. Moreover, with the aging process of the population, heart failure with preserved ejection fraction (HFpEF) will gradually become the main form of chronic heart failure in the future, and also become one of the important unsolved problems in current cardiology.

[0003] Current research believes that HFpEF is mainly characterized by diastolic dysfunction, but it also has systolic dysfunction, limited systolic function reserve, pulmonary hypertension, right ventricular dysfunction, vascular and endothelial abnormalities, cardiac chronotropic insufficiency, left atrial dysfunction, and peripheral abnormalities. The complex interaction of all these pathophysiological mechanisms drives the symptoms and outcome of HFpEF patients to worsen, and also makes drug development for HFpEF challenging. Compared with the breakthroughs of drugs such as sacubitril valsartan, vericiguat and dapagliflozin in the treatment of HFrEF, there is no recognized treatment method that can change the clinical course and prognosis of HFpEF. Based on the heterogeneity and complexity of HFpEF, referring to the design idea of sacubitril valsartan (ARNI) (angiotensin II receptor-angiotensin converting enzyme dual inhibition), starting from multiple pathways and multiple targets, it may be a breakthrough point for the research of HFpEF drugs.

[0004] Traditional Chinese medicine believes that HFpEF belongs to the category of “asthma” and “edema”, and the pathogenesis is based on qi deficiency and yang deficiency, and blood stasis and water retention. The treatment principle is to tonify qi and warm yang, and tonify qi and activate blood. However, although the disease is located in the heart, the root of qi deficiency and yang deficiency is still in the kidney. Moreover, studies have shown that kidney yang is closely related to the pathological mechanisms of water and electrolyte metabolism and myocardial energy metabolism in the development of HFpEF. Therefore, for the treatment of HFpEF, the core pathogenesis is “heart-kidney yang deficiency, water and dampness, and blood stasis”, and it is more valuable to start from the heart and kidney, tonify kidney essence to nourish heart qi, and warm kidney yang to assist heart yang. Therefore, it is of great practical significance to develop a safe and effective traditional Chinese medicine composition that can assist in the treatment of HFpEF. SUMMARY

[0005] The present application aims to provide a flavored Zhenwu Decoction and application thereof. The flavored Zhenwu Decoction is used for treating heart failure, which is a syndrome of "heart-kidney yang deficiency, water-dampness flooding, and blood stasis blocking collaterals", to solve the clinical defects of the existing Zhenwu Decoction, which is only suitable for water-dampness retention syndrome and cannot intervene in the core pathology of HFpEF with yang deficiency and blood stasis.

[0006] According to a first aspect of the present application, a flavored Zhenwu Decoction is provided, which is composed of the following raw materials by weight: 10-30 parts of Danfupian, 6-18 parts of Shengsaishen, 10-30 parts of Fuling, 8-24 parts of Shengbaishu, 10-30 parts of Baishao, 20-60 parts of Maodongqing, and 4-12 parts of Hongjingtian.

[0007] In some embodiments, the flavored Zhenwu Decoction is composed of the following raw materials by weight: 10-20 parts of Danfupian, 6-15 parts of Shengsaishen, 10-20 parts of Fuling, 8-20 parts of Shengbaishu, 10-20 parts of Baishao, 20-40 parts of Maodongqing, and 4-10 parts of Hongjingtian.

[0008] In some embodiments, the flavored Zhenwu Decoction is composed of the following raw materials by weight: 15 parts of Danfupian, 9 parts of Shengsaishen, 15 parts of Fuling, 12 parts of Shengbaishu, 15 parts of Baishao, 30 parts of Maodongqing, and 6 parts of Hongjingtian.

[0009] In the prescription, Danfupian (Danfupian) warms the heart and kidney to assist the primordial yang, Shengsaishen strengthens the heart and spleen to supplement the primordial qi, both of which warm yang and supplement qi, restore yang and consolidate deficiency, strengthen the heart and warm the kidney, invigorate the spleen and supplement the lung, restore the root of yin and yang, and are the source of healthy blood, which are the monarch; Baishu invigorates the spleen and expels dampness, Fuling benefits water and calms the heart, both of which expel dampness and water to drain fluid, assist Danfupian and Shengsaishen to eliminate the misfortune of yang deficiency and water flooding, which are the ministers; Baishao nourishes yin, promotes blood circulation and benefits water, Maodongqing clears heat, promotes blood circulation and unblocks collaterals, Hongjingtian supplements qi, promotes blood circulation and unblocks collaterals, all of which promote blood circulation, benefit water and unblock collaterals, assist Baishu and Fuling to resolve the stagnation of water and blood, and Baishao and Maodongqing are slightly cool and sour, which can nourish yin and clear heat to prevent the whole prescription from being too dry and hot, which are the assistants. The whole prescription can warm yang and supplement qi, benefit water and expel dampness, and promote blood circulation and unblock collaterals.

[0010] The whole prescription focuses on the development process of chronic heart failure, which is "yang deficiency and water-dampness accumulation, and stagnation of qi and blood", Zhenwu Decoction and Dushen Decoction mainly warm yang, dispel cold, expel dampness and benefit water, and Shaoyao can "remove blood stasis, benefit urination, unblock blood vessels, and remove water and qi", which is used for blood stasis and water retention. The overall prescription strengthens the invigoration of blood circulation and unblocking of collaterals on the basis of the original prescription, which is more suitable for heart failure patients than the original prescription.

[0011] Considering that heart and kidney yang deficiency type HFpEF is often accompanied by symptoms of yang deficiency and blood stasis, the modified Zhenwu Decoction compound contains raw ginseng, hairy holly, and rhodiola rosea, which can synergistically activate coronary endothelial function, inhibit myocardial fibrosis, and repair mitochondrial energy metabolism, specifically improving patients' ventricular contractility and microcirculatory disorders. This addresses the clinical deficiency of existing Zhenwu Decoction formulas, which only target the water retention type and cannot intervene in the core pathology of yang deficiency and blood stasis type HFpEF.

[0012] All raw materials were prepared in accordance with the Chinese Pharmacopoeia (2020 Edition) and the National Standards for Processing Traditional Chinese Medicine Decoction Pieces (hereinafter referred to as the "National Processing Standards"). Specific sources: Prepared aconite root slices: Processed products of Aconitum carmichaelii, which is the plant Aconitum carmichaelii of the Ranunculaceae family. Aconitum carmichaelii Debx Panax ginseng C. A. Mey. Processed products from the root of the plant.

[0013] Sun-dried ginseng: A product made by digging up ginseng roots, washing them, and then drying them in the sun. The ginseng in question is the ginseng plant, belonging to the Araliaceae family. Poria cocos (Schw.) Wolf Atractylodes macrocephala Koidz. The dried roots and rhizomes.

[0014] Poria cocos: a fungus belonging to the Polyporaceae family. Paeonia lactiflora Pall. The dried sclerotia.

[0015] Raw Atractylodes macrocephala: Atractylodes macrocephala, a plant of the Asteraceae family Ilex pubescens Hook. et Arn. The dried rhizome.

[0016] White peony: Paeonia lactiflora, a plant in the Ranunculaceae family. Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba The dried root.

[0017] Ilex pubescens: Ilex pubescens, a plant in the Aquifoliaceae family Figure 1 The dried root.

[0018] Rhodiola rosea: Rhodiola rosea, a plant in the Crassulaceae family. Figure 2 The dried roots and rhizomes.

[0019] According to another aspect of the present invention, a traditional Chinese medicine preparation obtained from the above-mentioned modified Zhenwu Decoction is provided. This preparation can be formulated into common existing dosage forms such as decoctions, granules, powders, tablets, pills, or capsules. This facilitates clinical administration.

[0020] In some embodiments, when traditional Chinese medicine preparations are formulated into common dosage forms, pharmaceutically acceptable excipients may be added. The excipients used are carriers or excipients commonly used in the art, including but not limited to starch, lactose, glucose, sodium carboxymethyl cellulose, ethyl cellulose and methyl cellulose, malt, gelatin, polyols (such as propylene glycol, glycerol, mannitol), tablets, etc., to help improve the stability or activity of the drug, or to produce an acceptable taste or smell when taken orally.

[0021] According to another aspect of the present application, there is provided a preparation method of the above-mentioned traditional Chinese medicine preparation, when it is prepared into a decoction, comprising the following steps: The raw materials are soaked in water and then decocted twice: in the first time, 8-12 times of water of the total mass of the raw materials is added, soaked for 0.5-1 hours, heated to boiling, kept at a slight boiling for 0.5-2 hours, and then separated to obtain the first decoction and the residue; in the second time, the residue obtained after the first decoction is taken, 6-10 times of water of the total mass of the raw materials is added, heated to boiling, kept at a slight boiling for 0.5-1 hours, and then separated to obtain the second decoction and the residue; the first decoction and the second decoction are combined, filtered to obtain the filtrate, and then the preparation is obtained.

[0022] When taken, one dose of the decoction is taken per day, and taken twice, and each time 200-250 ml is taken.

[0023] According to another aspect of the present application, there is provided an application of the above-mentioned traditional Chinese medicine compound of Zhenwu decoction with added ingredients or the traditional Chinese medicine preparation in the preparation of a medicine for treating heart failure with preserved ejection fraction.

[0024] In some embodiments, the application of the above-mentioned traditional Chinese medicine compound of Zhenwu decoction with added ingredients or the traditional Chinese medicine preparation in the medicine for treating heart failure with preserved ejection fraction of the syndrome type of water-dampness spreading and blood stasis blocking the collaterals can reduce the NT-proBNP level of the patient, relieve the symptoms related to heart failure, and improve the quality of life of the patient, wherein relieving the symptoms related to heart failure includes improving myocardial hypertrophy, improving diastolic dysfunction of the heart, improving myocardial injury and collagen deposition, and improving mitochondrial injury of myocardial cells. This is because the core pathogenesis of heart failure with preserved ejection fraction is "heart-kidney yang deficiency of Shaoyin, water-dampness spreading, and blood stasis blocking the collaterals", and the syndrome type of water-dampness spreading and blood stasis blocking the collaterals is a common syndrome type of HFpEF, and thus the traditional Chinese medicine compound of Zhenwu decoction with added ingredients or the traditional Chinese medicine preparation of the present application can be used for the treatment of heart failure with preserved ejection fraction of the syndrome type of water-dampness spreading and blood stasis blocking the collaterals.

[0025] The beneficial effects of the present application include: The Zhenwu decoction with added ingredients is an effective medicine for resisting HFpEF, can reverse the cardiac hypertrophy of HFpEF mice, reduce the pulmonary edema, and significantly improve the diastolic function of the heart, and can improve myocardial hypertrophy, improve diastolic dysfunction of the heart, improve myocardial injury and collagen deposition, and improve mitochondrial injury of myocardial cells. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 3 is a comparison chart of the heart appearance of each group of mice and related indexes reflecting the cardiac hypertrophy and pulmonary edema of the mice; A represents the heart appearance of each group of mice, B represents the column chart of the body weight of each group of mice, C represents the heart weight / tibia length ratio (HW / TL) of each group of mice, and D represents the wet / dry lung ratio of each group of mice.

[0027] Figure 4 are B-Mode images of the heart of mice in each group.

[0028] Figure 5 are comparisons of indexes related to left ventricular systolic function of mice in each group. B represents a column chart of left ventricular fractional shortening (LVFS) of mice in each group, and C represents a column chart of left ventricular ejection fraction (LVEF) of mice in each group.

[0029] Figure 6 are Doppler blood flow images (A) and tissue Doppler representative images (B) of the apical four-chamber section of mice in each group.

[0030] Figure 7 are indexes related to diastolic function of mice in each group. C represents a column chart of the ratio of passive left ventricular filling peak velocity E (cm / S) to mitral annulus root diastolic early peak velocity e' (cm / S), and D represents a column chart of the ratio of passive left ventricular filling peak velocity E (cm / S) to atrial systolic peak flow velocity A (cm / S).

[0031] Figures 1-7 are staining images of the heart tissue of HFpEF mice in each group, in which A is an HE staining image, and B is a Masson staining and picro-sirius red staining image.

[0032] Figure 1 are mitochondrial damages of myocardial cells of HFpEF mice in each group. DETAILED DESCRIPTION

[0033] The application will be described in further detail below with specific examples. It should be noted that the following examples are only intended to better explain the application and do not limit the scope of protection of the application. The process steps not disclosed in the examples are prior art. Unless otherwise specified, the raw materials below are commercially available. In this application, "micro-boiling" refers to the state in which the liquid just reaches the boiling point with a few bubbles, at which time the liquid temperature is between 93-100°C (standard atmospheric pressure).

[0034] Example 1 The flavored Zhenwu Decoction of this example is prepared from the following components: Duanfupian 15g, Shengsaishen 9g, Fuling 15g, Shengbaishu 12g, Baishao 15g, Maodouqing 30g, and Hongjingting 6g.

[0035] Exemplarily, the preparation method thereof includes the following steps: First decoction: put Duanfupian, Shengsaishen, Fuling, Shengbaishu, Baishao, Maodouqing, and Hongjingting into water, add 10 times the amount of water, heat to boiling, keep micro-boiling for 1 hour, and filter (200 mesh); Second decoction: add 6 times the amount of water, heat to boiling, keep micro-boiling for 0.5 hour, and filter (200 mesh); After the medicine liquid is prepared, the medicine liquid of the first decoction and the second decoction is mixed and concentrated, and the animal experiment dosage is calculated according to the human dosage.

[0036] Example 2 The flavored Zhenwu decoction of the present example is prepared from the following components: light Fufang tablet 30 g, raw sun-dried ginseng 18 g, Fuling 30 g, raw Baishu 24 g, Baijiao 30 g, Mao Dongqing 30 g, and Hongjingtian 12 g.

[0037] Example 3 The flavored Zhenwu decoction of the present example is prepared from the following components: light Fufang tablet 12 g, raw sun-dried ginseng 9 g, Fuling 10 g, raw Baishu 10 g, Baijiao 10 g, Mao Dongqing 20 g, and Hongjingtian 4 g.

[0038] Next, to explore the effect of the flavored Zhenwu decoction of the present application on the animal model of heart failure with preserved ejection fraction (HFpEF), the flavored Zhenwu decoction prepared in Example 1 is used for the following experiments.

[0039] I. Grouping 8-week-old C57BL / 6j male mice are randomly divided into sham operation group (Sham), HFpEF model group (Model), flavored Zhenwu decoction low-dose group (JWZWD-L), flavored Zhenwu decoction medium-dose group (JWZWD-M), flavored Zhenwu decoction high-dose group (JWZWD-H), and empagliflozin group after adaptive feeding for 1 week.

[0040] II. Modeling Except for the sham operation group, the rest of the mice are subjected to aortic arch constriction (TAC) + DOCA slow-release tablet subcutaneous implantation. The modeling method is as follows: 1% sodium pentobarbital 0.1 ml / 10 g is used for intraperitoneal injection to anesthetize the mice, and after the righting reflex disappears, the mice are fixed on the operating table. A 0.5 cm transverse incision is made on the upper edge of the sternum handle → the skin and subcutaneous tissue are cut open → the sternum handle is cut open along the midline for 3-4 mm, the two lobes of the thymus are pried apart to the head side with microforceps, and the aortic arch, innominate artery, and left common carotid artery bifurcation are visible. The connective tissue at the lower edge of the arch is gently torn with a curved forceps to form a 1 mm wide "window", a 7-0 suture needle is passed through the window from below the arch, and a 1.5 cm thread end is brought out; a pre-bent 27 G cushion needle is placed parallel to the anterior wall of the arch; after tying the aorta with two directionally opposite square knots, the cushion needle is quickly pulled out, and the arch diameter is instantly reduced to 0.4 mm, and the distal end shows obvious pulsatile enhancement; the thread is cut to leave a 1 mm thread end, and no active bleeding is checked. The mouse's back skin is cut open to form a transverse incision, the skin and subcutaneous tissue are bluntly separated with forceps, and the DOCA (deoxycorticosterone acetate) slow-release tablet is inserted between the skin and subcutaneous tissue, and the skin is sutured.

[0041] Then, the chest is closed with 6-0 suture, and the skin is sutured with 4-0 suture. The sham operation group is only cut open the sternum, the chest is closed and sutured, and no further operation is performed.

[0042] III. Administration After the mice were stable, they were given intragastric administration. According to the body surface area conversion, the mouse dose of Jiawei Zhenwu Decoction was 14.43 g / kg. The Jiawei Zhenwu Decoction low-dose group was given 0.5 times the human equivalent dose, i.e., 7.215 g / kg, the medium-dose group was given 1 times the human equivalent dose, i.e., 14.43 g / kg, and the high-dose group was given 2 times the human equivalent dose, i.e., 28.86 g / kg. According to the body surface area conversion, the mouse dose of empagliflozin was 1.3 g / Kg. The intragastric administration volume of each group was 0.1 ml / 10 g. The sham operation group and the model group were given the same amount of normal saline once a day for 1 month.

[0043] IV. Detection After one month, the mice were detected as follows: 1. Heart ultrasound After anesthesia with 2-3% isoflurane oxygen mixture, the mice were fixed after anesthesia, and the chest hair was removed with depilatory cream. The standard M-type effect was obtained on the long and short axis sections of the parasternal side to obtain indicators such as left ventricular short axis fractional shortening (LVFS) and left ventricular ejection fraction (LVEF). The passive left ventricular filling peak velocity, atrial contraction peak flow velocity A (cm / S), and mitral annulus diastolic early peak velocity e' (cm / S) were obtained from the mitral valve Doppler flow image of the four-chamber apical section, and the heart rate was maintained at 300-450 times / min.

[0044] 2. Morphological observation of heart Before the end of the experiment, the mice were weighed, and then the eyeball was taken after intraperitoneal injection of sodium pentobarbital anesthesia. Then the heart was removed at the midline incision of the chest, and the heart cavity was washed clean by gently squeezing the heart. After the residual water was absorbed with filter paper, the heart morphology was observed, and the whole heart was weighed, and the tibia length was measured.

[0045] 3. Detection of pulmonary edema After opening the chest, the heart and lung lobes were taken out, separated, rinsed, and the surface water was absorbed. The weight was measured, placed in a 1.5 ml centrifuge tube, and dried in a 60°C oven with the cap open. After 48 hours, the weight was measured again.

[0046] V. Experimental results The experimental results are shown in the accompanying Levene . Among them, One-Way ANOVA GraphPad prism 8.0 was used for data statistical analysis and plotting. When the data met the normality test, the Bonferroni test was further used for variance homogeneity test. When the variance was homogeneous, the One-Way ANOVA test was used for the Dunnett's T3The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. Kruskal-Wallis H The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. Figure 3 The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. Figure 5 The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P＜0.05 The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P＜0.05 The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P＜0.01 The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P＜0.001。 The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed.

[0047] The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. Levene The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. One-Way ANOVA The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. Bonferroni The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. One-Way ANOVA The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. Dunnett's T3 The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. Kruskal-Wallis H The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. ​ The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. ​ The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. P The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed.

[0048] The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed. The data were analyzed by Student's t-test when the data were normally distributed, and by the Mann-Whitney U test when the data were not normally distributed.

[0049] Further, the systolic and diastolic functions of the heart of the HFpEF mice were detected by ultrasound. The results showed that the medium-dose of the modified Zhenwu Decoction had the best effect on improving the diastolic function of the heart. The efficacy of the medium-dose of the modified Zhenwu Decoction was comparable to that of empagliflozin. In summary, the modified Zhenwu Decoction is an effective drug against HFpEF, which can reverse the cardiac hypertrophy of the HFpEF mice, reduce pulmonary edema, and significantly improve the diastolic function of the heart.

[0050] The effects of the modified Zhenwu Decoction on myocardial injury and collagen deposition in the heart of the HFpEF mice were detected by histopathological staining. The results showed that significant myocardial injury and collagen deposition were observed in the heart of the HFpEF mice, while the low-, medium- and high-dose of the modified Zhenwu Decoction could improve the histopathological injury and collagen deposition in the heart of the HFpEF mice. In addition, the results showed that the medium-dose of the modified Zhenwu Decoction had a better effect on improving the myocardial injury and collagen deposition than the low- and high-dose of the modified Zhenwu Decoction.

[0051] In addition, the effects of the modified Zhenwu Decoction on mitochondrial injury in the myocardial cells of the HFpEF mice were detected. The results showed that the mitochondrial injury in the myocardial cells of the HFpEF mice was significant, which was manifested as mitochondrial edema, loss of mitochondrial ridge and rupture. The results showed that the intervention of the modified Zhenwu Decoction could significantly reverse the mitochondrial injury in the myocardial cells of the HFpEF mice. In addition, the results were consistent with the previous results, and the results also showed that the medium-dose of the modified Zhenwu Decoction had the best efficacy.

[0052] Therefore, the modified Zhenwu Decoction is an effective drug against HFpEF, which can reverse the cardiac hypertrophy of the HFpEF mice, reduce pulmonary edema, and significantly improve the diastolic function of the heart.

[0053] The above only describes some specific embodiments of the present application. Those skilled in the art can make several modifications and improvements without departing from the inventive concept, which are all within the protection scope of the present application.

Claims

1. A modified Zhenwu Decoction, a traditional Chinese medicine compound, characterized in that... It is composed of the following raw materials in parts by weight: 10-30 parts of lightly ground aconite root, 6-18 parts of sun-dried ginseng, 10-30 parts of Poria cocos, 8-24 parts of raw Atractylodes macrocephala, 10-30 parts of white peony root, 20-60 parts of Ilex pubescens, and 4-12 parts of Rhodiola rosea.

2. The modified Zhenwu Decoction compound herbal formula according to claim 1, characterized in that, It is composed of the following raw materials in parts by weight: 10-20 parts of lightly ground aconite root, 6-15 parts of sun-dried ginseng, 10-20 parts of Poria cocos, 8-20 parts of raw Atractylodes macrocephala, 10-20 parts of white peony root, 20-40 parts of Ilex pubescens, and 4-10 parts of Rhodiola rosea.

3. The modified Zhenwu Decoction compound herbal formula according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 15 parts of lightly ground aconite root, 9 parts of sun-dried ginseng, 15 parts of Poria cocos, 12 parts of raw Atractylodes macrocephala, 15 parts of white peony root, 30 parts of Ilex pubescens, and 6 parts of Rhodiola rosea.

4. A traditional Chinese medicine preparation prepared from the modified Zhenwu Decoction traditional Chinese medicine compound according to any one of claims 1-3, wherein the traditional Chinese medicine preparation includes decoction, granules, powder, tablets, pills or capsules.

5. The traditional Chinese medicine preparation according to claim 4, characterized in that, It also includes medically acceptable excipients.

6. The use of the modified Zhenwu Decoction traditional Chinese medicine compound according to any one of claims 1-3 in the preparation of a drug for treating chronic heart failure.

7. The use of the modified Zhenwu Decoction traditional Chinese medicine compound according to any one of claims 1-3 in the preparation of a drug for treating heart failure with preserved ejection fraction.

8. The application according to claim 7, characterized in that, The syndrome of heart failure with preserved ejection fraction is characterized by water retention and blood stasis obstructing the collaterals.

9. The use of the modified Zhenwu Decoction traditional Chinese medicine compound according to any one of claims 1-3 in the preparation of a drug that reduces the NT-proBNP level in patients with heart failure due to water retention and blood stasis, and relieves heart failure-related symptoms, wherein the heart failure-related symptoms include at least one of the following symptoms: myocardial hypertrophy, diastolic dysfunction, myocardial injury and collagen deposition, and myocardial cell mitochondrial damage.

10. The use of the traditional Chinese medicine preparation according to claim 4 in the preparation of a drug for treating chronic heart failure or heart failure with preserved ejection fraction.

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