A traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism, and its preparation method and application.

Abstract

This invention discloses a traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism, and its application. The composition comprises the following raw materials: Danshen (Salvia miltiorrhiza), Roucongrong (Cistanche deserticola), Chishao (Paeonia lactiflora), Chuanxiong (Ligusticum chuanxiong), Dangshen (Codonopsis pilosula), Huangqi (Astragalus membranaceus), Guizhi (Cinnamomum cassia), and Suanzaoren (Ziziphus jujuba var. spinosa). This invention also discloses the preparation method of the above-mentioned traditional Chinese medicine composition and its application in the preparation of drugs for preventing and treating heart failure after myocardial infarction. The traditional Chinese medicine composition of this invention mainly improves cardiac microcirculation perfusion and energy metabolism in post-myocardial infarction failure by improving myocardial blood flow perfusion, protecting microvascular structure, and improving energy supply through promoting glycolysis, thereby effectively preventing and treating heart failure after myocardial infarction.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology. More specifically, it relates to a traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism, as well as its preparation method and application. Background Technology

[0002] Effective prevention and treatment of heart failure is a key focus and challenge in the cardiovascular field. Currently, the 5-year survival rate for patients with NYHA class III and IV heart failure remains below 50%. Myocardial infarction (MI) is one of the leading causes of heart failure. Adverse ventricular remodeling following MI forms the structural basis of ischemic heart failure (HF). It has been reported that approximately 30% of MI patients experience adverse ventricular remodeling within 6 months. The occurrence of heart failure after myocardial infarction is closely related to cardiac microcirculatory disturbances and energy metabolism disorders. After myocardial infarction, the microcirculation in the damaged area changes, leading to slowed blood flow, increased vascular permeability, and tissue edema, thereby affecting the supply of oxygen and nutrients to cardiac tissues. Furthermore, myocardial infarction also causes disturbances in cardiac energy metabolism, preventing cardiac cells from effectively utilizing energy and further exacerbating cardiac function damage. Currently, treatment methods for improving heart failure after myocardial infarction mainly include drug therapy, interventional therapy, and surgical treatment. However, these treatments often only relieve symptoms and are insufficient to fundamentally improve cardiac microcirculation and energy metabolism. Therefore, developing a treatment to improve heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism is a key issue that urgently needs to be addressed in the field of cardiovascular disease research. Summary of the Invention

[0003] To address the aforementioned technical problems, one objective of this invention is to provide a novel traditional Chinese medicine composition that can effectively improve cardiac microcirculation perfusion and energy metabolism, thereby effectively preventing and treating heart failure after myocardial infarction.

[0004] Another object of the present invention is to provide a method for preparing the above-mentioned traditional Chinese medicine composition.

[0005] Another object of the present invention is to provide various traditional Chinese medicine preparations based on the above-mentioned traditional Chinese medicine composition.

[0006] Another object of the present invention is to provide the application of the above-mentioned traditional Chinese medicine composition and preparation in the preparation of drugs for preventing and treating heart failure after myocardial infarction.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides a traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism. The raw materials of the traditional Chinese medicine composition include: Salvia miltiorrhiza, Cistanche deserticola, Paeonia lactiflora, Ligusticum chuanxiong, Codonopsis pilosula, Astragalus membranaceus, Cinnamomum cassia, and Ziziphus jujuba var. spinosa.

[0009] Preferably, the raw materials of the traditional Chinese medicine composition, by weight, include: 15-40 parts of Salvia miltiorrhiza, 6-40 parts of Cistanche deserticola, 3-20 parts of Paeonia lactiflora, 6-30 parts of Ligusticum chuanxiong, 6-20 parts of Codonopsis pilosula, 20-40 parts of Astragalus membranaceus, 10-20 parts of Cinnamomum cassia, and 10-40 parts of Ziziphus jujuba var. spinosa.

[0010] The herbal composition of this invention is mainly used for patients with heart failure after myocardial infarction, with symptoms such as chest pain and tightness, or pain radiating to the shoulder and back, cyanosis of the lips, soreness and weakness of the lower back and knees, fatigue, palpitations, and edema. In the early stages of heart and kidney disease, the inventors, through extensive screening, discovered that the herbal composition of this invention can significantly improve cardiac function in rat models, reduce heart failure markers, and decrease the area of ​​myocardial infarction. The mechanism may be through improving myocardial blood perfusion, protecting microvascular structure, and improving energy supply by promoting glycolysis, thereby improving microcirculatory perfusion and energy metabolism in the failing heart after myocardial infarction, thus preventing and treating heart failure after myocardial infarction.

[0011] In the prescription of this invention, the principal herbs are Cistanche deserticola and Salvia miltiorrhiza. Cistanche deserticola: sweet, salty, and warm in nature, it enters the kidney and large intestine meridians, tonifying the kidney and replenishing essence, moistening the intestines and promoting bowel movements. The *Compendium of Materia Medica* states: "Cistanche deserticola nourishes the gate of life, replenishes kidney qi, and is a medicine for replenishing essence and blood. It tonifies yang without causing dryness, warms and invigorates kidney yang, and tonifies kidney deficiency." Salvia miltiorrhiza: According to *Essentials of Materia Medica*, bitter and red in color, it enters the heart and pericardium meridians. Its functions include promoting blood circulation and removing blood stasis, regulating menstruation and relieving pain, clearing the heart and relieving irritability, cooling blood and eliminating carbuncles; its red color enters the heart meridian, breaking up stagnant blood and replenishing new blood, thus possessing both blood-activating and blood-nourishing effects in one herb.

[0012] The main ingredients are Astragalus membranaceus, Paeonia lactiflora, and Ziziphus jujuba var. spinosa. Astragalus membranaceus: sweet, slightly warm. It enters the spleen and lung meridians. Its functions include tonifying qi and raising yang, strengthening the defensive qi and consolidating the exterior, promoting diuresis and reducing swelling, generating fluids and nourishing blood, promoting circulation and relieving pain, promoting pus drainage and healing, and promoting wound healing and tissue regeneration. Paeonia lactiflora: bitter, slightly cold. It enters the liver and spleen meridians. It clears heat and cools the blood, promotes blood circulation and removes blood stasis, and can assist Salvia miltiorrhiza in enhancing its blood-activating effect. Ziziphus jujuba var. spinosa: sweet, sour, neutral. It enters the liver, gallbladder, and heart meridians. It nourishes the heart and liver, calms the mind and soothes the nerves, astringes sweat, and generates fluids. It is an essential medicine for nourishing the heart and calming the nerves, especially suitable for those with deficiency of yin and blood in the heart and liver, and those suffering from insomnia, palpitations, and excessive dreaming due to lack of nourishment of the heart.

[0013] The adjuvant herbs are cinnamon twig and codonopsis. Cinnamon twig: pungent, sweet, and warm; enters the heart, lung, and bladder meridians. It induces sweating and relieves muscle tension, warms and unblocks the meridians, assists yang qi transformation, and calms rebellious qi. This pungent, sweet, and warm herb can warm and support spleen yang to aid water metabolism, warm kidney yang, expel cold pathogens to assist bladder qi transformation, and eliminate dampness and phlegm. It can also assist heart yang, unblock blood vessels, and stop palpitations. Codonopsis: sweet and slightly bitter, slightly warm; enters the spleen, lung, heart, and kidney meridians. It is mainly used to treat severe illness, chronic illness, blood loss, and fluid depletion leading to exhaustion of vital energy, fatigue, and weak pulse. It is suitable for insomnia, excessive dreaming, palpitations, forgetfulness, and excessive sweating due to deficiency of heart qi.

[0014] The herb used is Chuanxiong (Ligusticum striatum). Chuanxiong is pungent and warm in nature, and enters the liver, gallbladder, and pericardium meridians. It is a qi-regulating herb in the blood, which invigorates blood circulation, dispels wind and relieves pain. It is pungent, warm, fragrant and dry, and moves without staying still. It can both disperse and ascend to the top of the head, and also enter the blood and descend to the sea of ​​blood. It has the functions of dispersing, relieving depression, unblocking and relieving pain.

[0015] In this invention, by way of example, the traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism includes, by weight, the raw materials of the traditional Chinese medicine composition as follows: 15 parts of Salvia miltiorrhiza, 10 parts of Cistanche deserticola, 12 parts of Paeonia lactiflora, 10 parts of Ligusticum chuanxiong, 20 parts of Codonopsis pilosula, 30 parts of Astragalus membranaceus, 10 parts of Cinnamomum cassia, and 15 parts of Ziziphus jujuba var. spinosa.

[0016] For example, the traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism includes, by weight, the raw materials of the traditional Chinese medicine composition as follows: 15 parts of Salvia miltiorrhiza, 6 parts of Cistanche deserticola, 3 parts of Paeonia lactiflora, 6 parts of Ligusticum chuanxiong, 6 parts of Codonopsis pilosula, 20 parts of Astragalus membranaceus, 10 parts of Cinnamomum cassia, and 10 parts of Ziziphus jujuba var. spinosa.

[0017] For example, the traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism includes, by weight, the raw materials of the traditional Chinese medicine composition as follows: 40 parts of Salvia miltiorrhiza, 40 parts of Cistanche deserticola, 20 parts of Paeonia lactiflora, 30 parts of Ligusticum chuanxiong, 20 parts of Codonopsis pilosula, 40 parts of Astragalus membranaceus, 20 parts of Cinnamomum cassia, and 40 parts of Ziziphus jujuba var. spinosa.

[0018] The basic formula of the above-mentioned traditional Chinese medicine composition of the present invention can be adjusted according to clinical symptoms during specific implementation to improve cardiac microcirculation perfusion and energy metabolism in post-myocardial infarction failure and to improve certain specific clinical symptoms, thereby further enhancing the adaptability of the composition of the present invention and improving the therapeutic effect. These adjustments made based on the basic formula of the present invention are also within the scope of protection of this application.

[0019] Secondly, the present invention provides a method for preparing a traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism, the preparation method comprising:

[0020] According to the formula, take the following herbs: Salvia miltiorrhiza, Cistanche deserticola, Paeonia lactiflora, Ligusticum chuanxiong, Codonopsis pilosula, Astragalus membranaceus, Cinnamomum cassia, and Ziziphus jujuba var. spinosa. Grind them into powder, mix them, add 6-10 times their weight of water, soak for 0.5-2 hours, then decoct 2-3 times, each time for 40-60 minutes. Combine the decoctions, filter, and concentrate the filtrate under reduced pressure until each milliliter of liquid is equivalent to 0.2-3g of raw herbs, thus obtaining the aforementioned traditional Chinese medicine composition; or...

[0021] After crushing the *Salvia miltiorrhiza* according to the formula, extract it by reflux with 6-10 times its weight of 60-80% ethanol aqueous solution 2-3 times, each time for 1-2 hours. After each extraction, filter, collect and combine the filtrates, recover the ethanol, and concentrate the filtrate under reduced pressure to obtain a *Salvia miltiorrhiza* alcohol extract containing 0.1-1g of crude drug per milliliter of the extract. Then, combine the remaining *Salvia miltiorrhiza* residue with the formula-prescribed amounts of *Cistanche deserticola*, *Paeonia lactiflora*, *Ligusticum chuanxiong*, *Codonopsis pilosula*, *Astragalus membranaceus*, *Cinnamomum cassia*, and *Ziziphus jujuba* seed, and decoct with 6-10 times its weight of water 2-3 times, each time for 40-60 minutes. Combine the decoctions, filter, and combine the filtrate with the *Salvia miltiorrhiza* alcohol extract. Further concentrate to obtain a traditional Chinese medicine composition with 0.2-3g of crude drug per milliliter of the extract; or...

[0022] According to the formula, take the amount of Salvia miltiorrhiza and grind it into a fine powder for later use; combine the formula amounts of Cistanche deserticola, Paeonia lactiflora, Ligusticum chuanxiong, Codonopsis pilosula, Astragalus membranaceus, Cinnamomum cassia and Ziziphus jujuba var. spinosa, decoct them 2-3 times with 6-10 times the weight of water, each time for 40-60 minutes, combine the decoctions, filter, and concentrate the filtrate under reduced pressure to the point that each milliliter of the decoction is equivalent to 0.2-3g of raw herbs. Then add the fine powder of Salvia miltiorrhiza to the concentrated liquid and mix well to obtain the Chinese herbal composition.

[0023] Thirdly, the present invention provides a traditional Chinese medicine preparation for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism, wherein the raw materials of the traditional Chinese medicine preparation include the above-mentioned traditional Chinese medicine composition.

[0024] Depending on actual needs, the traditional Chinese medicine preparations may also include pharmaceutically acceptable excipients. Various preparations are manufactured using conventional pharmaceutical processes, such as decoctions, granules, pills, capsules, tablets, powders, and oral liquids.

[0025] This invention also provides the application of the above-mentioned traditional Chinese medicine composition and preparation in the preparation of any of the following drugs:

[0026] 1) Improves cardiac function in patients with heart failure after myocardial infarction;

[0027] 2) Reduce the area of ​​myocardial infarction;

[0028] 3) Reduce the level of the heart failure marker NT-proBNP;

[0029] 4) Improves pathological changes and myocardial fibrosis in myocardial tissue;

[0030] 5) Promotes blood perfusion and maintains microvascular homeostasis;

[0031] 6) Protects the mitochondrial structure of myocardial tissue;

[0032] 7) By increasing the protein expression level of PFKFB3, glycolysis is promoted and energy supply is improved;

[0033] 8) Prevention and treatment of heart failure after myocardial infarction.

[0034] In addition, unless otherwise specified, all raw materials of the traditional Chinese medicine composition of the present invention can be obtained commercially available. Any range of traditional Chinese medicine composition described in the present invention, including any value between the endpoints and any sub-ranges formed by the endpoints or any value between the endpoints, can achieve the purpose of improving cardiac microcirculation perfusion and energy metabolism in post-myocardial infarction failure, thereby effectively preventing and treating post-myocardial infarction heart failure.

[0035] The beneficial effects of this invention are as follows:

[0036] Heart failure is a major disease in my country, with high incidence and mortality rates, seriously threatening human health. In recent years, modern medical research has gradually discovered that after myocardial infarction, the microcirculation in the damaged area changes, leading to slowed blood flow, increased vascular permeability, and tissue edema, thereby affecting the supply of oxygen and nutrients to the heart tissue. Furthermore, myocardial infarction can also cause disorders in cardiac energy metabolism, preventing heart cells from effectively utilizing energy and further aggravating cardiac function damage. The herbal composition of this invention has a rigorous formulation. From a scientific perspective, it can improve microcirculation myocardial perfusion and energy metabolism disorders, preventing further aggravation of myocardial damage. From the perspective of traditional Chinese medicine theory, it has the effects of tonifying the kidneys and strengthening the body, promoting blood circulation and removing blood stasis, and simultaneously tonifying and clearing the meridians. Through research on its pharmacological mechanism, it has been found that it can significantly improve cardiac function in rat animal models, reduce heart failure markers, and decrease the area of ​​myocardial infarction. The mechanism may be through improving myocardial blood perfusion, protecting microvascular structure, and improving energy supply by promoting glycolysis, thereby improving microcirculation perfusion and energy metabolism in the failing heart after myocardial infarction. Attached Figure Description

[0037] Figure 1 This demonstrates the intersection between traditional Chinese medicine compositions and disease targets;

[0038] Figure 2 PPI network is constructed by showing the intersection of genes;

[0039] Figure 3 Show the top 10 genes of the intersection;

[0040] Figure 4 GO enrichment and KEGG functional enrichment of differentially expressed genes;

[0041] Figure 5 Schematic diagram of ultrasound (Note: Sham sham surgery group; Model group; low-dose group of HBAF (1.4g / kg) traditional Chinese medicine composition; high-dose group of HBAF (2.8g / kg) traditional Chinese medicine composition; positive control group of DAPA (1mg / kg); compared with before treatment, **P<0.05, ***P<0.01);

[0042] Figure 6 TTC staining images (Note: Sham sham surgery group; Model group; HBAF (1.4 g / kg) low-dose traditional Chinese medicine combination group; HBAF (2.8 g / kg) high-dose traditional Chinese medicine combination group; DAPA (1 mg / kg) positive control group; compared with before treatment, **P<0.05, ***P<0.01);

[0043] Figure 7 The results of NT-proBNP ELISA detection are shown in the figure (Note: Sham sham operation group; Model group; HBAF (1.4g / kg) low-dose group of traditional Chinese medicine composition; HBAF (2.8g / kg) high-dose group of traditional Chinese medicine composition; DAPA (1mg / kg) positive control group; compared with before treatment, ns P>0.05, **P<0.05, ***P<0.01);

[0044] Figure 8 HE staining results are shown in the figure (Note: Sham sham operation group; Model group; HBAF (1.4g / kg) low-dose group of traditional Chinese medicine composition; HBAF (2.8g / kg) high-dose group of traditional Chinese medicine composition; DAPA (1mg / kg) positive control group; compared with before treatment, ns P>0.05, **P<0.05, ***P<0.01);

[0045] Figure 9 Masson staining results are shown in the image (Note: Sham sham operation group; Model group; HBAF (1.4 g / kg) low-dose traditional Chinese medicine combination group; HBAF (2.8 g / kg) high-dose traditional Chinese medicine combination group; DAPA (1 mg / kg) positive control group; compared with before treatment, ns P>0.05, **P<0.05, ***P<0.01);

[0046] Figure 10 Schematic diagram of the effectiveness of traditional Chinese medicine composition in promoting myocardial blood flow perfusion (Note: Sham sham operation group; Model group; HBAF (1.4g / kg) low-dose traditional Chinese medicine composition group; HBAF (2.8g / kg) high-dose traditional Chinese medicine composition group; DAPA (1mg / kg) positive control group; compared with before treatment, nsP>0.05, **P<0.05, ***P<0.01);

[0047] Figure 11 Schematic diagram of the effectiveness of traditional Chinese medicine composition in maintaining microvascular homeostasis (Note: Sham sham operation group; Model group; HBAF (1.4g / kg) low-dose traditional Chinese medicine composition group; HBAF (2.8g / kg) high-dose traditional Chinese medicine composition group; DAPA (1mg / kg) positive control group);

[0048] Figure 12 Schematic diagram showing the effective promotion of CD31 and VE-Cadherin expression by traditional Chinese medicine composition (Note: Sham sham operation group; Model group; HBAF (1.4g / kg) low-dose traditional Chinese medicine composition group; HBAF (2.8g / kg) high-dose traditional Chinese medicine composition group; DAPA (1mg / kg) positive control group; compared with before treatment, ns P>0.05, **P<0.05, ***P<0.01);

[0049] Figure 13 Schematic diagram of the effect of traditional Chinese medicine composition on mitochondrial structure (Note: Sham sham operation group; Model group; HBAF (1.4g / kg) low-dose group of traditional Chinese medicine composition; HBAF (2.8g / kg) high-dose group of traditional Chinese medicine composition; DAPA (1mg / kg) positive control group);

[0050] Figure 14 A schematic diagram comparing differential metabolites in myocardial tissue glucose energy metabolism;

[0051] Figure 15 Schematic diagram of differential metabolites in glucose energy metabolism of myocardial tissue;

[0052] Figure 16 A schematic diagram of differential abundance scores and KEGG annotations for differentially metabolized products in myocardial tissue glucose energy metabolism.

[0053] Figure 17 Schematic diagram of the effect of traditional Chinese medicine composition on PFKFB3 expression (Note: Sham sham operation group; Model group; HBAF (1.4g / kg) low-dose traditional Chinese medicine composition group; HBAF (2.8g / kg) high-dose traditional Chinese medicine composition group; DAPA (1mg / kg) positive control group; compared with before treatment, ns P>0.05, **P<0.05, ***P<0.01). Detailed Implementation

[0054] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0055] Example 1: A traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism.

[0056] Raw material formula: Danshen 15g, Roucongrong 10g, Chishao 12g, Chuanxiong 10g, Dangshen 20g, Huangqi 30g, Guizhi 10g, Suanzaoren 15g.

[0057] After pulverizing Salvia miltiorrhiza, it was extracted twice by reflux with 8 times its weight of 75% ethanol aqueous solution, each time for 1 hour. After each extraction, the extract was filtered, the filtrates were collected and combined, the ethanol was recovered, and the filtrate was concentrated under reduced pressure to obtain a Salvia miltiorrhiza alcohol extract containing 1g of raw drug per milliliter of the extract. The remaining Salvia miltiorrhiza residue after extraction was then combined with the other raw materials (Cistanche deserticola, Paeonia lactiflora, Ligusticum chuanxiong, Codonopsis pilosula, Astragalus membranaceus, Cinnamomum cassia, and Ziziphus jujuba var. spinosa) used to make the traditional Chinese medicine composition. The mixture was decocted twice with 8 times its weight of water, each time for 60 minutes. The decoctions were combined, filtered, and the filtrates were combined with the Salvia miltiorrhiza alcohol extract. The mixture was then further concentrated to obtain a traditional Chinese medicine composition with 3g of raw drug per milliliter of the extract.

[0058] Example 2: A traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism.

[0059] Raw material formula: 15g of Salvia miltiorrhiza, 6g of Cistanche deserticola, 3g of Paeonia lactiflora, 6g of Ligusticum chuanxiong, 6g of Codonopsis pilosula, 20g of Astragalus membranaceus, 10g of Cinnamomum cassia, and 10g of Ziziphus jujuba var. spinosa.

[0060] The danshen (Salvia miltiorrhiza) is pulverized into a fine powder and set aside. The other raw materials used to make the traditional Chinese medicine composition (Cistanche deserticola, Paeonia lactiflora, Ligusticum chuanxiong, Codonopsis pilosula, Astragalus membranaceus, Cinnamomum cassia, and Ziziphus jujuba var. spinosa) are combined and decocted three times with 10 times their weight of water, each time for 60 minutes. The decoctions are combined, filtered, and the filtrate is concentrated under reduced pressure until each milliliter of the decoction is equivalent to 3g of raw herbs. Then, the danshen powder is added to the concentrated liquid and mixed well to obtain the traditional Chinese medicine composition.

[0061] Example 3: A traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism.

[0062] Raw material formula: 40g of Salvia miltiorrhiza, 40g of Cistanche deserticola, 20g of Paeonia lactiflora, 30g of Ligusticum chuanxiong, 20g of Codonopsis pilosula, 40g of Astragalus membranaceus, 20g of Cinnamomum cassia, and 40g of Ziziphus jujuba var. spinosa.

[0063] After pulverizing all the above raw materials, mix them together, add 6 times the weight of water and soak for 2 hours, then decoct twice, each time for 60 minutes. Combine the decoctions, filter, and concentrate the filtrate under reduced pressure until each milliliter of the decoction is equivalent to 3g of raw herbs, thus obtaining the Chinese herbal composition.

[0064] Example 4: Clinical observation of the efficacy of the traditional Chinese medicine composition of the present invention in preventing and treating heart failure.

[0065] Thirty-two patients with heart failure following myocardial infarction who visited our hospital were randomly divided into two groups of 16 each. Both groups received routine Western medicine treatment, while the observation group received additional treatment with the traditional Chinese medicine composition of this invention (the traditional Chinese medicine composition prepared in Example 1). The results showed that after treatment, the TCM syndrome in the observation group was better than that in the control group, and the total effective rate was also better in the observation group.

[0066] Table 1 Comparison of TCM syndrome scores before and after treatment in the two groups (scores, X±s)

[0067]

[0068]

[0069] Table 2 Comparison of LVEF indices before and after treatment in the two groups (%, X±s)

[0070]

[0071] Table 3 Comparison of clinical efficacy between the two groups (cases, %)

[0072]

[0073] Example 5: Basic research on the improvement of cardiac microcirculation perfusion and energy metabolism in post-myocardial infarction failure by the traditional Chinese medicine composition of the present invention (the traditional Chinese medicine composition of Example 1).

[0074] 1.1 Construction of the Drug-Target-Disease Network Diagram of the Effective Components of the Traditional Chinese Medicine Composition: The intersection of the main effective active components of the drug with the targets of ischemic heart failure was obtained to identify the key targets for treating ischemic heart failure. A "drug-target-disease" network diagram was constructed using Cytoscape 3.7.1 software. In the diagram, nodes represent genes, proteins, or active components; edges represent the connections between active components and interacting targets. The network diagram allows for a deeper exploration of the mechanism of action of this traditional Chinese medicine composition in treating ischemic heart failure.

[0075] Experimental results:

[0076] The intersection of the targets of the traditional Chinese medicine composition and heart failure genes yielded 180 common targets. A PPI network was constructed using these intersection genes, resulting in a network graph with 165 nodes and 1442 edges. The top 10 genes are potential therapeutic targets; their functions are concentrated in inflammation, immune response, and cell proliferation, as discussed in [link to relevant documentation]. Figure 1-3 .

[0077] 1.2 GO and KEGG functional enrichment of differentially expressed genes: In order to further clarify the potential mechanism of action of the traditional Chinese medicine composition of the present invention, this study used the DAVID (https: / / david.ncifcrf.gov / ) online database to perform GO and KEGG functional enrichment of differentially expressed genes. P<0.05 was considered statistically significant.

[0078] Experimental results:

[0079] The mechanisms by which traditional Chinese medicine compositions act on heart failure include: energy metabolism-related pathways (AGE-RAGE signaling, HIF-1 signaling, and diabetic cardiomyopathy), calcium signaling pathway, platelet activation, and adrenergic signaling in cardiomyocytes. (See [link to relevant documentation]). Figure 4 .

[0080] 1.3 Detection of Cardiac Function Improvement by Traditional Chinese Medicine Composition: A rat model of post-myocardial infarction heart failure was established by ligating the left anterior descending coronary artery (LAD) for 3 days, followed by echocardiography showing an ejection fraction (EF) ≤ 50%. The experimental groups were: ① sham-operated group; ② HF model group; ③ HF + low-dose traditional Chinese medicine composition (HBAF) group (1.4 g / kg); ④ HF + high-dose HBAF group (2.8 g / kg); ⑤ HF + positive control drug (DAPA) group. Echocardiography was performed on rats 4 weeks after intervention.

[0081] Experimental results:

[0082] After 4 weeks of intervention, left ventricular ejection fraction (EF) and fractional shortening (FS) were significantly improved in rats with heart failure following myocardial infarction, thus improving cardiac function. (See [link to relevant documentation]). Figure 5 .

[0083] 1.4 Detection of Myocardial Infarction Area Improved by Traditional Chinese Medicine Composition: The modeling and grouping methods were the same as above. After 4 weeks of drug intervention, rat hearts were collected, frozen for 15 minutes, and cut into cross-sections (1-2 mm). The sections were stained with 2% TTC phosphate buffer (pH 7.4), incubated at 37°C in the dark for 30 minutes, and then placed in 10% formaldehyde solution overnight before mounting. Under a microscope, the infarcted area was stained white, and the non-infarcted area was stained red.

[0084] Experimental results:

[0085] TTC staining showed that after 4 weeks of intervention with the traditional Chinese medicine composition, the myocardial MI area in rats with post-myocardial infarction heart failure was significantly reduced. Figure 6 .

[0086] 1.5 Detection of NT-proBNP in rats treated with traditional Chinese medicine composition using ELISA kit: Blood was collected from the abdominal aorta of each group of rats, anticoagulated with heparin, and centrifuged at 3000 r / min for 10 min after resting for 15-20 min. Serum was collected, and the NT-proBNP content in the serum of each group of mice was detected according to the kit instructions.

[0087] Experimental results:

[0088] After 4 weeks of treatment with the traditional Chinese medicine composition, heart failure markers in rats with post-myocardial infarction heart failure were significantly reduced. (See...) Figure 7 .

[0089] 1.6 Treatment of myocardial pathological changes with traditional Chinese medicine composition: Myocardial tissue was taken out and immediately immersed in 4% paraformaldehyde solution. It was fixed at room temperature for 24 hours, then dehydrated with graded ethanol, embedded in paraffin, and paraffin sections were prepared. After hematoxylin-eosin (HE) staining, the sections were mounted with neutral resin and observed under an optical microscope (100) to observe the size, arrangement and infiltration of myocardial cells.

[0090] Experimental results:

[0091] After 4 weeks of treatment with the traditional Chinese medicine composition, the pathological changes in the myocardial tissue of rats with post-myocardial infarction heart failure were significantly improved, and cell swelling and inflammatory cell infiltration were reduced. Figure 8 .

[0092] 1.7 Treatment of myocardial fibrosis with traditional Chinese medicine composition: The tissue around the left ventricular infarction of rats was dewaxed and dehydrated, stained with Masson's solution, phosphomolybdic acid and aniline blue, and the degree of myocardial fibrosis in mice was observed under a light microscope.

[0093] Experimental results:

[0094] After 4 weeks of treatment with the traditional Chinese medicine composition, myocardial collagen fiber deposition in rats with post-myocardial infarction heart failure was significantly improved. Figure 9 .

[0095] 1.8 The traditional Chinese medicine composition effectively promotes blood perfusion in failing myocardial tissue and maintains microvascular homeostasis.

[0096] (1) Laser speckle detection showed that after 4 weeks of intervention with the traditional Chinese medicine composition, it could significantly promote terminal blood flow perfusion in rats with heart failure after myocardial infarction. Figure 10 .

[0097] (2) Two-photon microscopy analysis of microvascular walls based on FITC macromolecular dextran staining showed that after 4 weeks of intervention with the traditional Chinese medicine composition, microvascular homeostasis could be effectively maintained in rats with post-myocardial infarction heart failure. The traditional Chinese medicine can reduce microvascular thinning caused by myocardial infarction, maintain the structural integrity of microvessels, and reduce leakage. (See...) Figure 11 .

[0098] (3) Western blot results of VE-Cadherin and CD31 showed that after 4 weeks of intervention with the traditional Chinese medicine composition, it could effectively protect endothelial cells in the myocardial tissue of rats with post-myocardial infarction and heart failure, and improve the barrier function and integrity of vascular endothelium, which helps maintain effective blood circulation. (See [reference needed]). Figure 12 .

[0099] 1.9 The traditional Chinese medicine composition effectively protects the mitochondrial structure of failing myocardial tissue and promotes glycolysis to improve energy supply.

[0100] (1) Electron microscopy results showed that after 4 weeks of intervention with the traditional Chinese medicine composition, it could effectively protect the mitochondrial structure of myocardial tissue in rats with post-myocardial infarction and heart failure. Figure 13 .

[0101] (2) Targeted quantitative detection of energy metabolites by liquid chromatography-tandem mass spectrometry showed that after 4 weeks of intervention with the traditional Chinese medicine composition, the content of key glycolytic substrates in the myocardial tissue of rats with post-myocardial infarction heart failure increased, and ATP energy supply increased. Compared with the model group, the traditional Chinese medicine group significantly upregulated the content of metabolites such as glutamine, alanine, lysine, DL-glyceric acid, guanosine, cyclic adenosine monophosphate, uridine diphosphate-N-acetylglucosamine, adenosine triphosphate, uridine 5-monophosphate, adenosine monophosphate, inosine-1-phosphate, pyruvate, lactic acid, succinic acid, fructose 1,6-bisphosphate, D-xylitol 5-phosphate, D-ribose-5-phosphate disodium salt, D-ribulose 5-phosphate, sedoheptulose 7-phosphate, and dihydroxyacetone phosphate. (See attached table) Figure 14-16 .

[0102] (3) Western blot results of PFKFB3 showed that after 4 weeks of intervention with the traditional Chinese medicine composition, the protein expression level of PFKFB3 was effectively increased, and glycolysis was promoted. (See...) Figure 17 .

[0103] summary

[0104] Effective prevention and treatment of heart failure is a key focus and challenge in the cardiovascular field. Currently, the 5-year survival rate for patients with NYHA class III and IV heart failure remains below 50%. Myocardial infarction is one of the leading causes of heart failure. Although revascularization and drug therapy can effectively restore blood flow to the epicardial coronary arteries, their effect on the microcirculation, which supplies more than 50% of the myocardium, is limited. Impaired microcirculation severely hinders myocardial tissue repair, thereby triggering adverse ventricular remodeling and leading to heart failure. Therefore, improving microcirculation has become a crucial treatment strategy for the prevention and treatment of post-myocardial infarction heart failure. This traditional Chinese medicine composition can significantly improve cardiac function in rats with post-myocardial infarction heart failure, reduce myocardial infarction area, decrease the content of the heart failure marker NT-proBNP, improve pathological changes and myocardial fibrosis in myocardial tissue, promote blood perfusion and maintain microvascular homeostasis, protect the mitochondrial structure of myocardial tissue, and promote glycolysis and improve energy supply by increasing the protein expression of PFKFB3.

[0105] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15-40 parts of Salvia miltiorrhiza, 6-40 parts of Cistanche deserticola, 3-20 parts of Paeonia lactiflora, 6-30 parts of Ligusticum chuanxiong, 6-20 parts of Codonopsis pilosula, 20-40 parts of Astragalus membranaceus, 10-20 parts of Cinnamomum cassia, and 10-40 parts of Ziziphus jujuba var. spinosa.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of Salvia miltiorrhiza, 10 parts of Cistanche deserticola, 12 parts of Paeonia lactiflora, 10 parts of Ligusticum chuanxiong, 20 parts of Codonopsis pilosula, 30 parts of Astragalus membranaceus, 10 parts of Cinnamomum cassia, and 15 parts of Ziziphus jujuba var. spinosa.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of Salvia miltiorrhiza, 6 parts of Cistanche deserticola, 3 parts of Paeonia lactiflora, 6 parts of Ligusticum chuanxiong, 6 parts of Codonopsis pilosula, 20 parts of Astragalus membranaceus, 10 parts of Cinnamomum cassia, and 10 parts of Ziziphus jujuba var. spinosa.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 40 parts of Salvia miltiorrhiza, 40 parts of Cistanche deserticola, 20 parts of Paeonia lactiflora, 30 parts of Ligusticum chuanxiong, 20 parts of Codonopsis pilosula, 40 parts of Astragalus membranaceus, 20 parts of Cinnamomum cassia, and 40 parts of Ziziphus jujuba var. spinosa.

5. A method for preparing the traditional Chinese medicine composition for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism as described in any one of claims 1-4, characterized in that, The preparation method includes: According to the formula, take the following herbs: Salvia miltiorrhiza, Cistanche deserticola, Paeonia lactiflora, Ligusticum chuanxiong, Codonopsis pilosula, Astragalus membranaceus, Cinnamomum cassia, and Ziziphus jujuba var. spinosa. Grind them into powder, mix them, add 6-10 times their weight of water, soak for 0.5-2 hours, then decoct 2-3 times, each time for 40-60 minutes. Combine the decoctions, filter, and concentrate the filtrate under reduced pressure until each milliliter of liquid is equivalent to 0.2-3g of raw herbs, thus obtaining the aforementioned traditional Chinese medicine composition; or... After crushing the *Salvia miltiorrhiza* according to the formula, extract it by reflux with 6-10 times its weight of 60-80% ethanol aqueous solution 2-3 times, each time for 1-2 hours. After each extraction, filter, collect and combine the filtrates, recover the ethanol, and concentrate the filtrate under reduced pressure to obtain a *Salvia miltiorrhiza* alcohol extract containing 0.1-1g of crude drug per milliliter of the extract. Then, combine the remaining *Salvia miltiorrhiza* residue with the formula-formulated amounts of *Cistanche deserticola*, *Paeonia lactiflora*, *Ligusticum chuanxiong*, *Codonopsis pilosula*, *Astragalus membranaceus*, *Cinnamomum cassia*, and *Ziziphus jujuba* seed, and decoct with 6-10 times its weight of water 2-3 times, each time for 40-60 minutes. Combine the decoctions, filter, and combine the filtrate with the *Salvia miltiorrhiza* alcohol extract. Further concentrate to obtain a traditional Chinese medicine composition with 0.2-3g of crude drug per milliliter of the extract; or... According to the formula, take the amount of Salvia miltiorrhiza and grind it into a fine powder for later use; combine the formula amounts of Cistanche deserticola, Paeonia lactiflora, Ligusticum chuanxiong, Codonopsis pilosula, Astragalus membranaceus, Cinnamomum cassia and Ziziphus jujuba var. spinosa, decoct them 2-3 times with 6-10 times the weight of water, each time for 40-60 minutes, combine the decoctions, filter, and concentrate the filtrate under reduced pressure to the point that each milliliter of the decoction is equivalent to 0.2-3g of raw herbs. Then add the fine powder of Salvia miltiorrhiza to the concentrated liquid and mix well to obtain the Chinese herbal composition.

6. A traditional Chinese medicine preparation for preventing and treating heart failure after myocardial infarction by promoting cardiac microcirculation perfusion and energy metabolism, characterized in that, The raw materials for the traditional Chinese medicine preparation include the traditional Chinese medicine composition as described in any one of claims 1-4.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, The traditional Chinese medicine preparation also includes pharmaceutically acceptable excipients.

8. The traditional Chinese medicine preparation according to claim 6 or 7, characterized in that, The dosage forms of the traditional Chinese medicine preparations are decoctions, granules, pills, capsules, tablets, powders, or oral liquids.

9. The use of the traditional Chinese medicine composition according to any one of claims 1-4, the traditional Chinese medicine composition prepared by the preparation method according to claim 5, or the traditional Chinese medicine preparation according to any one of claims 6-8 in the preparation of a drug for preventing and treating heart failure after myocardial infarction.

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