Traditional chinese medicine composition for treating cardiovascular and kidney diseases and method for preparing same

Abstract

Provided are a traditional Chinese medicine composition for treating cardiorenal syndrome and cardiac failure and a method for preparing same. The traditional Chinese medicine composition is prepared from the following raw materials: 3 to 20 parts of Cinnamomi ramulus, 3 to 25 parts of Atractylodis macrocephalae rhizoma, 3 to 25 parts of Jujubae fructus, 6 to 45 parts of Astragali radix, 2 to 20 parts of Panacis majoris rhizoma, 3 to 30 parts of Paeoniae rubra radix, 6 to 25 parts of Spatholobi caulis, 6 to 25 parts of Ginkgo folium, 6 to 35 parts of Poria, 3 to 20 parts of Zingiberis rhizoma recens, 2 to 25 parts of Citri fructus, 2 to 15 parts of Nigellae semen, 2 to 20 parts of Inulae flos, and 3 to 25 parts of Alismatis rhizoma. The traditional Chinese medicine composition has a regulatory effect on symptoms such as myocardial ischemia, myocardial hypertrophy, myocardial fibrosis, and renal fibrosis caused by cardiac failure and cardiorenal syndrome.

Description

Traditional Chinese medicine composition for treating cardiovascular and kidney diseases and preparation method thereof

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on June 1, 2022, with application number 202210615447.4 and invention name “Traditional Chinese medicine composition for treating cardiovascular and kidney diseases and its preparation method”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating cardiovascular and kidney diseases and a preparation method thereof. Background Art

[0003] Heart failure is caused by impaired cardiac or vascular function, which leads to sympathetic nervous system activation, which in turn continuously activates the renin-angiotensin-aldosterone system, creating a vicious cycle of persistent cardiac impairment. Cardiorenal syndrome refers to a disease characterized by acute or chronic dysfunction of the heart and / or kidneys, leading to further acute or chronic dysfunction of both. Cardiac manifestations include a persistent decrease in ejection fraction, blood output, and blood flow. On this basis, the heart's compensatory functions are activated, leading to myocardial ischemia, hypertrophy, and fibrosis, contributing to the continued progression of heart failure. Kidney manifestations include kidney damage, the development of a pathological state called renal fibrosis, which increases sodium and water reabsorption, decreases urine output, and causes edema. The Traditional Chinese Medicine (TCM) pathogenesis of heart failure and cardiorenal syndrome is qi deficiency and blood stasis, which impedes communication between the heart and kidneys. Over time, this leads to heart yang deficiency and the accumulation of phlegm and fluid.

[0004] Therefore, from the perspective of Traditional Chinese Medicine (TCM), the core treatments for heart failure and cardiorenal syndrome are to coordinately regulate heart and kidney function, warming yang and replenishing qi, promoting blood circulation and removing blood stasis, and resolving phlegm and promoting diuresis. Traditional Chinese medicine (TCM) offers unique clinical advantages in treating heart failure and cardiorenal syndrome, but currently, there are no specifically effective TCM combinations that can effectively treat these conditions. Furthermore, Western medicines for treating heart failure are ineffective and have limited efficacy in improving symptoms.

[0005] Summary of the Invention

[0006] In view of this, the present invention provides a Chinese medicine composition for treating cardiovascular and kidney diseases and a preparation method thereof. The composition provided by the present invention can significantly reduce the gene expression of B-type natriuretic peptide (NPPB), a gold indicator of heart failure induced by hypoxia / reoxygenation, reduce the expression of genes related to myocardial fibrosis and renal fibrosis induced by TGFβ, and significantly increase the blood flow velocity and cardiac output in a zebrafish heart failure model. This shows that the composition has a regulatory effect on pathological links such as myocardial ischemia, myocardial hypertrophy, myocardial fibrosis, and renal fibrosis caused by heart failure and cardiorenal syndrome, can effectively improve cardiac and renal function, and has the effect of inhibiting the progression of heart failure and inhibiting cardiorenal fibrosis, so as to achieve the therapeutic effect of treating cardiorenal syndrome and heart failure.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] The present invention provides a traditional Chinese medicine composition, which comprises the following components or their processed products in parts by weight:

[0009] 3-20 parts of cinnamon twig, 3-25 parts of white atractylodes, 3-25 parts of jujube, 6-45 parts of astragalus, 2-20 parts of ginseng, 3-30 parts of red peony root, 6-25 parts of millettia reticulata, 6-25 parts of ginkgo leaves, 6-35 parts of poria, 3-20 parts of ginger, 2-25 parts of citron, 2-15 parts of black cumin seeds, 2-20 parts of inula flower, and 3-25 parts of oriental rhizome.

[0010] In some embodiments of the present invention, cassia twigs are dried young branches of the Lauraceae plant cinnamon (Cinnamomum cassia Presl), which can warm the meridians and promote yang and qi transformation;

[0011] Atractylodes macrocephala is the dried rhizome of Atractylodes macrocephala Koidz., a plant of the Asteraceae family. It can invigorate the spleen and replenish qi, dry dampness and promote diuresis.

[0012] Jujube is the dried mature fruit of the plant Ziziphus jujuba Mill. of the Rhamnaceae family. It can replenish qi, nourish blood and soothe the mind.

[0013] Astragalus is the dried root of Astragalus membranaceus (Fisch.) Bge.var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. of the Leguminosae family. It can replenish Qi and raise Yang, promote diuresis and reduce swelling, promote the production of body fluids and nourish blood, and relieve stagnation and numbness.

[0014] Panax japonicus is the dried rhizome of Panax japonicus CAMey.var.major(Burk.)CYWu et KMFeng or Panax japonicus CAMey.var.bipinnatifidus(Seem.)CYWu et K.M.Feng, both of the Araliaceae family. It can nourish the lungs, nourish yin, and remove blood stasis. It is a Bai ethnic medicine and can be used to treat heart failure and cardiorenal syndrome caused by deficiency of both qi and yin.

[0015] Red peony root is the dried root of Paeonia lactiflora PalL or Paeonia veitchii Lynch, a plant of the Ranunculaceae family. It can clear away heat, cool blood, disperse blood stasis and relieve pain.

[0016] Millettia repens is the dried vine stem of Spatholobus suberectus Dunn, a plant of the Leguminosae family. It can invigorate blood circulation, replenish blood, and relax tendons and activate joints.

[0017] Ginkgo biloba is the dried leaf of Ginkgo biloba L., a plant of the Ginkgo family. It can invigorate blood circulation, dissipate blood stasis, dredge meridians and relieve pain, strengthen the lungs and relieve asthma, and clear turbidity and reduce lipids.

[0018] Poria cocos is the dried sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf, which can promote diuresis and eliminate dampness, strengthen the spleen and calm the mind.

[0019] Ginger is the fresh rhizome of Zingiber officinale Rosc., a plant of the Zingiberaceae family. It can warm the yang, resolve phlegm, and relieve cough.

[0020] The dried mature fruit of Citrus medica L. or Citrus wilsonii Tanaka, both Rutaceae plants, can relieve stomach upset, resolve phlegm, soothe the liver and regulate qi.

[0021] Nigella seeds are the dried mature seeds of the Ranunculaceae plant Nigella glandulifera Freyn et Sint., a Uyghur ethnic medicine that can nourish the kidneys and promote diuresis.

[0022] Inula japonica Thunb. or Inula britannica L., a plant of the Asteraceae family, is a dried inflorescence that can lower Qi, eliminate phlegm, and promote urination.

[0023] Alisma orientale (Sam.) Juzep., a plant of the Alismataceae family, is a dried tuber that can promote diuresis and eliminate dampness, clear turbidity and reduce lipids.

[0024] In some embodiments of the present invention, the above-mentioned traditional Chinese medicine composition includes the following components or their processed products: 9 parts of cinnamon twig, 10 parts of white atractylodes, 10 parts of jujube, 20 parts of astragalus, 9 parts of pearl ginseng, 12 parts of red peony root, 10 parts of Millettia reticulata, 10 parts of ginkgo leaves, 15 parts of Poria, 9 parts of ginger, 10 parts of citron, 6 parts of black cumin seeds, 9 parts of inula flower, and 10 parts of Alisma orientalis.

[0025] In some embodiments of the present invention, in the above-mentioned traditional Chinese medicine composition:

[0026] The above-mentioned pearl ginseng is replaced by ginseng, red ginseng, codonopsis, japonica ginseng, American ginseng and / or pseudoginseng; and / or

[0027] The above-mentioned Atractylodes macrocephala is replaced by stir-fried Atractylodes macrocephala and / or stir-fried Atractylodes macrocephala with bran; and / or

[0028] The above-mentioned Astragalus is replaced by roasted Astragalus; and / or

[0029] The above-mentioned red peony root is replaced by white peony root; and / or

[0030] The above ginger can be replaced with dried ginger and / or roasted ginger.

[0031] The present invention also provides a method for preparing the traditional Chinese medicine composition, which comprises extracting the components of the traditional Chinese medicine composition or their processed products in a prescribed amount with water.

[0032] In some embodiments of the present invention, in the above preparation method, the water extraction further includes the steps of concentration and / or drying.

[0033] In some embodiments of the present invention, in the above preparation method, the components of the traditional Chinese medicine composition or their processed products in the formula amount are pulverized separately to obtain fine powder, extracted with water, concentrated, and freeze-dried.

[0034] In some embodiments of the present invention, in the above preparation method, the water extraction includes decocting with water.

[0035] The present invention also provides the above-mentioned traditional Chinese medicine composition and the use of the traditional Chinese medicine composition prepared by the above-mentioned preparation method in preparing drugs for regulating cardiorenal function.

[0036] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition and the traditional Chinese medicine composition prepared by the above-mentioned preparation method in preparing medicines for preventing and / or treating heart failure, cardiorenal syndrome and / or coronary heart disease.

[0037] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition and the traditional Chinese medicine composition prepared by the above-mentioned preparation method in preparing a drug for increasing the blood flow velocity and / or cardiac output of a verapamil-induced zebrafish heart failure model.

[0038] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition and the traditional Chinese medicine composition prepared by the above-mentioned preparation method in preparing drugs for inhibiting myocardial ischemia, myocardial hypertrophy, myocardial fibrosis and / or renal fibrosis.

[0039] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition and / or the traditional Chinese medicine composition prepared by the above-mentioned preparation method in preparing a drug for improving symptoms of patients with chronic heart failure and / or reducing the expression level of NT-proBNP.

[0040] In some embodiments of the present invention, in the above application, the symptoms include: one or more of edema, wheezing, fatigue and / or shortness of breath.

[0041] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition and the traditional Chinese medicine composition prepared by the above-mentioned preparation method in preparing a drug for inhibiting the expression of NPPB gene, COL1A1 gene, COL5A1 gene and / or SERPINE1 gene.

[0042] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition in the clinical treatment of chronic heart failure, including the efficacy of improving patient symptoms and reducing plasma NT-proBNP levels.

[0043] The present invention also provides medicines, including the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition prepared by the above-mentioned preparation method, and pharmaceutically acceptable excipients.

[0044] The present invention also provides the use of the above-mentioned Chinese medicine composition, the Chinese medicine composition prepared by the above-mentioned preparation method and / or the above-mentioned medicine in treating any of the following diseases:

[0045] (I), heart failure;

[0046] (II), cardiorenal syndrome;

[0047] (III), coronary heart disease;

[0048] (IV), myocardial ischemia;

[0049] (V), cardiac hypertrophy;

[0050] (VI), myocardial fibrosis;

[0051] (VII) Renal fibrosis.

[0052] The present invention also provides a method for treating a disease, comprising taking the above-mentioned Chinese medicine composition, the Chinese medicine composition prepared by the above-mentioned preparation method and / or the above-mentioned medicine;

[0053] These diseases include:

[0054] (I), heart failure;

[0055] (II), cardiorenal syndrome;

[0056] (III), coronary heart disease;

[0057] (IV), myocardial ischemia;

[0058] (V), cardiac hypertrophy;

[0059] (VI), myocardial fibrosis;

[0060] (VII) Renal fibrosis.

[0061] The present invention provides a traditional Chinese medicine composition, which comprises the following components or their processed products in parts by weight:

[0062] 3-20 parts of cinnamon twig, 3-25 parts of white atractylodes, 3-25 parts of jujube, 6-45 parts of astragalus, 2-20 parts of ginseng, 3-30 parts of red peony root, 6-25 parts of millettia reticulata, 6-25 parts of ginkgo leaves, 6-35 parts of poria, 3-20 parts of ginger, 2-25 parts of citron, 2-15 parts of black cumin seeds, 2-20 parts of inula flower, and 3-25 parts of oriental rhizome.

[0063] This Chinese medicine composition uses Astragalus membranaceus and Nigella sativa as the main ingredients. Astragalus membranaceus replenishes qi and elevates yang, promoting diuresis and relieving swelling, while Nigella sativa tonifies the kidneys and promotes urination. The combination of the two can target the qi deficiency, yang deficiency, and water retention seen in heart failure and cardiorenal syndrome by tonifying qi, warming yang, and promoting diuresis. Cinnamon twig and Atractylodes macrocephala are the auxiliary ingredients in the formula, assisting Astragalus membranaceus in tonifying qi and warming yang. Cinnamon twig is pungent, sweet, and warming, warming yang and transforming qi, while Atractylodes macrocephala strengthens the spleen and eliminates dampness. The addition of Cinnamon twig further enhances the warming and transporting power of the body, strengthening the spleen and dispelling dampness. Red peony root and Millettia reticulata are also auxiliary ingredients, targeting blood stasis by promoting blood circulation and replenishing blood, dispersing stasis and relieving pain. Poria cocos and Alismatis rhizome are the adjuvant ingredients in the formula, and their combination doubles the diuretic and dampness-eliminating effect. Poria cocos, cinnamon twig, and Atractylodes macrocephala work together to promote yang and transform qi, strengthen the spleen and promote diuresis, providing a warming effect without being dry and beneficial without being harsh. Panax notoginseng and Ginkgo biloba serve as adjuvants, promoting blood circulation, removing blood stasis, and relieving pain. They assist Paeonia lactiflora and Millettia reticulata in promoting blood circulation and removing blood stasis. Panax notoginseng can also nourish the lungs and yin, and when combined with Paeonia lactiflora, it can astringe yin and moisten dryness. Blood stasis leads to water retention, while yang deficiency, unable to warm and circulate, results in phlegm and dampness. Ginkgo biloba and Alisma orientalis can also clear turbidity and reduce lipids, enhancing the overall effect of promoting blood circulation and promoting diuresis. Citron and Inula japonica serve as adjuvants, regulating qi and resolving phlegm, and can regulate the dampness and phlegm caused by heart failure and cardiorenal syndrome. Ginger and jujube serve as guiding herbs. Ginger is pungent and slightly warming, moving rather than staying still, and can assist Poria, Cinnamon, and Atractylodes lancea in warming the middle and strengthening the spleen. Jujube not only tonifies the middle and replenishes qi, but also harmonizes the other herbs. The combined effects of these herbs warm yang and replenish qi, promote blood circulation and remove blood stasis, and resolve phlegm and promote diuresis. Therefore, the Chinese medicine composition can significantly reduce the gene expression of B-type natriuretic peptide (NPPB), a gold indicator of heart failure induced by hypoxia / reoxygenation, reduce the expression of genes related to myocardial fibrosis and renal fibrosis induced by TGFβ, and significantly increase the blood flow velocity and cardiac output of the zebrafish heart failure model. Clinical human experience shows that the Chinese medicine composition has a good effect of improving the symptoms of patients with chronic heart failure and reducing the expression of NT-proBNP, indicating that the composition has a regulatory effect on pathological links such as myocardial ischemia, myocardial hypertrophy, myocardial fibrosis, and renal fibrosis caused by heart failure and cardiorenal syndrome, can effectively improve cardiac function and renal function, and has the effect of inhibiting the progression of heart failure and inhibiting cardiorenal fibrosis to achieve the therapeutic effect of cardiorenal syndrome and heart failure. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] FIG1 shows the regulation of B-type natriuretic peptide (NPPB) expression by a traditional Chinese medicine composition;

[0065] FIG2 shows the regulation of the expression of type I collagen α1 (COL1A1) and type V collagen α1 (COL5A1) by the traditional Chinese medicine composition;

[0066] FIG3 shows the regulation of the expression of plasminogen activator inhibitor 1 (SERPINE1) and type I collagen α1 (COL1A1) by the traditional Chinese medicine composition;

[0067] FIG4 shows the regulation of blood flow velocity and cardiac output by the Chinese herbal composition. DETAILED DESCRIPTION

[0068] The present invention discloses a Chinese medicine composition for treating cardiovascular and kidney diseases and a preparation method thereof. Those skilled in the art can refer to the contents of this article and appropriately improve the process parameters to achieve the desired effect. It should be noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in the present invention. The methods and applications of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0069] The raw materials and reagents used in the preparation of the composition, the expression of NPPB, a gold indicator of heart failure, in hypoxia / reoxygenation-induced cardiomyocytes AC16, the effects on the expression of type I collagen alpha 1 (COL1A1) and type V collagen alpha 1 (COL5A1) genes in TGFβ-induced human cardiac fibroblasts, the effects on the gene expression of plasminogen activator inhibitor 1 (SERPINE1) and type I collagen alpha 1 (COL1A1), and the detection of the effects of the traditional Chinese medicine composition on blood flow velocity and cardiac output using a zebrafish heart failure model can all be purchased from the market.

[0070] The present invention will be further described below in conjunction with the embodiments:

[0071] Example 1 Preparation of Chinese medicine composition

[0072] According to 9g of cinnamon twig, 10g of white atractylodes, 10g of jujube, 20g of astragalus, 12g of red peony root, 10g of millettia reticulata, 10g of ginkgo leaf, 15g of poria, 9g of ginger, 10g of citron, 9g of inula flower, 10g of oriental rhizome, 9g of radix scutellariae, and 6g of black cumin seeds, they were respectively ground into 80-100 mesh powder, added with 15 times the volume of distilled water for extraction, and subjected to standard reflux extraction for 2h. The extract was concentrated for 15min to a volume of 2mL, and the extract was decompressed in a vacuum freeze dryer and concentrated at -55°C with a concentration ratio of 30. The vacuum degree of freeze drying was 5Pa and the freezing time was 24h to prepare a freeze-dried extract powder. The composition was adjusted according to the prescription ratio to obtain a traditional Chinese medicine composition, and then the traditional Chinese medicine composition was dissolved in PBS to prepare a mother liquor.

[0073] Example 2 Effect of Chinese herbal composition on the expression of NPPB, a gold marker of heart failure, in hypoxia / reoxygenation-induced myocardial cells AC16

[0074] 1) AC16 cells were plated at 200,000 / well in a 12-well plate. After overnight culture, the normal control group was cultured in a normal incubator (20% oxygen concentration). The other groups were first cultured in a three-gas incubator under hypoxic (1% oxygen concentration) and sugar-free medium (glucose concentration 0 g / L) conditions for 6 h, then transferred to a normal incubator and cultured in normal medium (glucose concentration 3.15 g / L) for 24 h.

[0075] 2) The Chinese medicine composition prepared in Example 1 was applied to cells at a concentration of 400 μg / mL during 30 hours of hypoxia / reoxygenation;

[0076] 3) Wash the cells twice with PBS, extract RNA using a kit (Thermo, high-performance RNA-to-cDNA) and convert it to cDNA;

[0077] 4) qPCR reaction, program: 95°C, 3 min; (95°C, 3 s; 60°C, 30 s) 40 cycles;

[0078] Among them, the primer sequences are:

[0079] NPPB1:5'-TGGAAACGTCCGGGTTACAG-3' (as shown in SEQ ID NO: 1)

[0080] NPPB2: 5'-CTGATCCGGTCCATCTTCCT-3' (as shown in SEQ ID NO: 2)

[0081] 5) Data Processing: The gene expression level of the blank control group was set as 1. The gene expression level of the drug-treated group was greater than 1, indicating upregulation of gene expression, and less than 1, indicating downregulation. As shown in Figure 1 and Table 1, the Chinese medicine composition can inhibit the gene expression regulation of B-type natriuretic peptide (NPPB) in the AC16 cell model induced by hypoxia / reoxygenation, thereby exerting an anti-heart failure effect.

[0082] Table 1

[0083] Example 3 Effect of the Chinese herbal composition on the expression of type I collagen α1 (COL1A1) and type V collagen α1 (COL5A1) genes in human cardiac fibroblasts induced by TGFβ

[0084] 1) HCF cells were plated at 100,000 cells / well in a 12-well plate and treated with 10 ng / mL TGFβ for 48 h after overnight incubation.

[0085] 2) adding the Chinese medicine composition prepared in Example 1 at a final concentration of 800 μg / mL, and setting up a solvent control group (adding an equal volume of PBS), and treating the cells for a total of 48 hours;

[0086] 3) Wash the cells twice with PBS, extract RNA using a kit (Thermo, high-performance RNA-to-cDNA) and convert it to cDNA;

[0087] 4) qPCR reaction, program: 95°C, 3 min; (95°C, 3 s; 60°C, 30 s) 40 cycles.

[0088] Among them, the primer sequences are:

[0089] COL1A1-5'-GAGGGCCAAGACGAAGACATC-3' (as shown in SEQ ID NO: 3)

[0090] COL1A1'-5'-CAGATCACGTCATCGCACAAC-3' (as shown in SEQ ID NO: 4)

[0091] COL5A1-5'-TACCCTGCGTCTGCATTTCC-3' (as shown in SEQ ID NO: 5)

[0092] COL5A1'-5'-GCTCGTTGTAGATGGAGACCA-3' (as shown in SEQ ID NO: 6)

[0093] As shown in FIG2 and Table 2, the Chinese medicine composition can inhibit the expression of type I collagen α1 (COL1A1) and type V collagen α1 (COL5A1) in human cardiac fibroblasts induced by TGFβ, thereby exerting an anti-myocardial fibrosis effect.

[0094] Table 2

[0095] Example 4 Effect of Chinese herbal medicine composition on gene expression of plasminogen activator inhibitor 1 (SERPINE1) and type I collagen α1 (COL1A1)

[0096] 1) HK2 cells were plated at 80,000 cells / well in a 12-well plate. After overnight, they were serum-starved for 24 hours and then treated with 10 ng / mL TGFβ for 48 hours.

[0097] 2) adding the Chinese medicine composition prepared in Example 1 at a final concentration of 800 μg / mL, and setting up a solvent control group (adding an equal volume of PBS), and treating the cells for a total of 48 hours;

[0098] 3) Wash the cells twice with PBS, extract RNA using a kit (Thermo, high-performance RNA-to-cDNA) and convert it to cDNA;

[0099] 4) qPCR reaction, program: 95°C, 3 min; (95°C, 3 s; 60°C, 30 s) 40 cycles;

[0100] Among them, the primer sequences are:

[0101] SERPINE1-5'-AGTGGACTTTTCAGAGGTGGA-3' (as shown in SEQ ID NO: 7)

[0102] SERPINE1'-5'-GCCGTTGAAGTAGAGGGCATT-3' (as shown in SEQ ID NO: 8)

[0103] COL1A1-5'-GAGGGCCAAGACGAAGACATC-3' (as shown in SEQ ID NO: 3)

[0104] COL1A1'-5'-CAGATCACGTCATCGCACAAC-3' (as shown in SEQ ID NO: 4)

[0105] 5) Data processing: The gene expression level in the blank control group was set as 1. The gene expression level in the drug-treated group was considered up-regulated if it was greater than 1, and down-regulated if it was less than 1.

[0106] As shown in FIG3 and Table 3, the Chinese medicine composition can inhibit the expression of plasminogen activator inhibitor 1 (SERPINE1) and type I collagen α1 (COL1A1) in human renal tubular epithelial cells HK2 induced by TGFβ, thereby exerting an anti-renal fibrosis effect.

[0107] Table 3

[0108] Example 5: Effects of Chinese herbal compositions on blood flow velocity and cardiac output using a zebrafish heart failure model

[0109] 1) Randomly select 2 dpf wild-type AB strain zebrafish and place them in a 6-well plate, with 30 zebrafish per well;

[0110] 2) Add the Chinese medicine composition prepared in Example 1 at a final concentration of 2000 μg / mL, and set up a solvent control group (add an equal volume of sterile water) at the same time, and treat the zebrafish for a total of 4 hours;

[0111] 3) Except for the normal control group (no verapamil hydrochloride treatment), the other groups were given water-soluble verapamil hydrochloride to establish a zebrafish heart failure model at 28°C for 0.5 h;

[0112] 4) Ten zebrafish were randomly selected from each experimental group and placed under a heartbeat blood flow analyzer to record video. The data were collected using ViewPoint Application Manager software to analyze the blood flow velocity and cardiac output of the zebrafish.

[0113] As shown in FIG4 and Table 4, the Chinese medicine composition can increase the blood flow velocity and cardiac output in the verapamil-induced zebrafish heart failure model, thereby exerting an anti-heart failure effect.

[0114] Example 6

[0115] Ingredients: 3g cinnamon twig, 25g white atractylodes, 3g jujube, 6g astragalus, 20g panax ginseng, 3g red peony root, 6g millettia reticulata, 6g ginkgo leaf, 35g poria, 20g ginger, 2g citron, 15g black seed, 20g inula flower, 25g oriental rhizome.

[0116] The preparation method is the same as that of Example 1.

[0117] Example 7

[0118] Ingredients: 20g of cinnamon twig, 3g of white atractylodes, 25g of jujube, 45g of astragalus, 2g of pearl ginseng, 30g of red peony root, 25g of millettia reticulata, 25g of ginkgo leaf, 6g of poria, 3g of ginger, 25g of citron, 2g of black cumin seeds, 2g of inula flower, and 3g of oriental rhizome.

[0119] The preparation method is the same as that of Example 1.

[0120] Table 4

[0121] Example 8 Preparation of Composition Decoction

[0122] According to the ratio of each pair of medicine slices of cinnamon twig 9g, Atractylodes macrocephala 10g, jujube 10g, astragalus 20g, red peony root 12g, Millettia reticulata 10g, Ginkgo biloba 10g, Poria 15g, ginger 9g, citron 10g, Inula flower 9g, Alisma orientalis 10g, Panax notoginseng 9g, and Nigella cumin 6g, 7 pairs of medicine slices were weighed, added to 6L of water, and decocted for 1h to obtain a 7-day dosage of the traditional Chinese medicine composition water decoction.

[0123] Effects of the decoction of Example 9 on symptoms and NT-proBNP in patients with chronic heart failure

[0124] Twelve patients were recruited. After taking basic Western medicine treatment for heart failure (standardized basic Western medicine treatment according to the guidelines, referring to the 2022 AHA / ACC / HFSA guidelines for the management of heart failure, including ARNI / ACEI / ARB, β-blockers, MRA, SGLT2 inhibitors, cardiotonic drugs, diuretics, antiplatelet drugs, anticoagulants, statins, nitrates, hypoglycemic drugs, antihypertensive drugs, etc.), the patients still had symptoms such as wheezing, shortness of breath, edema, and fatigue. For details, see the "before" part of the symptom improvement statistics in Table 5, and the New York Heart Association functional grade statistics are shown in Table 5. While maintaining the Western medicine treatment regimen, the addition of the decoction of the Chinese medicinal composition prepared in Example 8 for two weeks or longer resulted in significant improvement in all patients' symptoms, as shown in Table 5. This was primarily reflected in the following: 100% efficacy (12 / 12) in improving wheezing; 100% efficacy (12 / 12) in improving fatigue; 90% efficacy (9 / 10) in improving edema, with two patients experiencing no edema; and 66.7% efficacy (8 / 12) in improving shortness of breath. Five patients underwent randomized plasma NT-proBNP testing before, during, or at the end of treatment with the decoction of the Chinese medicinal composition prepared in Example 8, demonstrating significant decreases in NT-proBNP levels (as shown in Table 6).

[0125] Table 5

[0126] In Table 5, "before" refers to the period after taking the basic Western medicine treatment for heart failure in Example 9; "after" refers to the period after taking the basic Western medicine treatment for heart failure in Example 9 and taking the decoction of the traditional Chinese medicine composition obtained in Example 8.

[0127] Table 6

[0128] In Table 6, "before treatment" refers to the period after taking the basic Western medicine treatment for heart failure in Example 9; "after treatment" refers to the period after taking the basic Western medicine treatment for heart failure in Example 9 and taking the decoction of the Chinese medicine composition obtained in Example 8.

[0129] Effect of the decoction of Example 10 on liver and kidney function in patients with chronic heart failure

[0130] The 12 patients recruited in Example 9 took the decoction of the Chinese medicine composition prepared in Example 8 for 2 weeks or more. As shown in Table 7, the patients' liver and kidney function-related alanine aminotransferase (kit,

[0131] There were no significant differences in the test values ​​for alanine aminotransferase (Beckman Coulter Inc, aspartate aminotransferase kit), aspartate aminotransferase (kit, Beckman Coulter Inc, aspartate aminotransferase kit), blood urea ammonia (kit, Beckman Coulter Inc, blood urea ammonia kit), and serum creatinine (kit, Beckman Coulter Inc, serum creatinine kit).

[0132] Table 7

[0133] The above describes in detail a Chinese medicine composition for treating cardiovascular and kidney diseases and a method for preparing the same provided by the present invention. This article uses specific examples to illustrate the principles and implementation methods of the present invention. The description of the above examples is only intended to help understand the method of the present invention and its core concept. It should be noted that for those skilled in the art, without departing from the principles of the present invention, several improvements and modifications may be made to the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

[0134] Sequence Listing

[0135]

[0136]

[0137]

Claims

1. A Chinese medicine composition, characterized in that: The composition includes the following components or their preparations in parts by weight: 3-20 parts of cinnamon twig, 3-25 parts of atractylodes, 3-25 parts of jujube, 6-45 parts of astragalus, 2-20 parts of pearl ginseng, 3-30 parts of red peony root, 6-25 parts of millettia reticulata, 6-25 parts of ginkgo leaves, 6-35 parts of poria, 3-20 parts of ginger, 2-25 parts of citron, 2-15 parts of nigella sativa seeds, 2-20 parts of inula flower, and 3-25 parts of oriental rhizome.

2. The Chinese medicine composition according to claim 1, characterized in that The invention comprises the following components or their processed products: 9 parts of cinnamon twig, 10 parts of atractylodes macrocephala, 10 parts of jujube, 20 parts of astragalus, 9 parts of ginseng, 12 parts of red peony root, 10 parts of millettia reticulata, 10 parts of ginkgo leaf, 15 parts of tuckahoe, 9 parts of ginger, 10 parts of citron, 6 parts of black cumin seeds, 9 parts of inula flower, and 10 parts of orientalis.

3. The Chinese medicine composition according to claim 1 or 2, characterized in that: The pearl ginseng is replaced by ginseng, red ginseng, codonopsis, bamboo ginseng, American ginseng and / or pseudoginseng; and / or The Atractylodes macrocephala is replaced by stir-fried Atractylodes macrocephala and / or stir-fried Atractylodes macrocephala with bran; and / or The astragalus is replaced by roasted astragalus; and / or The red peony root is replaced by white peony root; and / or The ginger can be replaced with dried ginger and / or roasted ginger.

4. The method for preparing the Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The components of the traditional Chinese medicine composition or their processed products are extracted with water.

5. The preparation method according to claim 4, characterized in that: The method further comprises the steps of concentration and / or drying after the water extraction.

6. The preparation method according to claim 4 or 5, characterized in that: The components of the traditional Chinese medicine composition or their processed products in the formula amount are crushed separately to obtain fine powder, extracted with water, concentrated and freeze-dried.

7. The preparation method according to any one of claims 4 to 6, characterized in that: The water extraction includes boiling with water.

8. Use of the Chinese medicine composition according to any one of claims 1 to 3 and / or the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7 in the preparation of drugs for regulating cardiorenal function.

9. Use of the Chinese medicine composition as claimed in any one of claims 1 to 3 and / or the Chinese medicine composition prepared by the preparation method as claimed in any one of claims 4 to 7 in the preparation of drugs for preventing and / or treating heart failure, cardiorenal syndrome and / or coronary heart disease.

10. Use of the Chinese medicine composition according to any one of claims 1 to 3 and / or the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7 in the preparation of a drug for increasing blood flow velocity and / or cardiac output in a verapamil-induced zebrafish heart failure model.

11. Use of the Chinese medicine composition according to any one of claims 1 to 3 and / or the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7 in the preparation of drugs for inhibiting myocardial ischemia, myocardial hypertrophy, myocardial fibrosis and / or renal fibrosis.

12. Use of the Chinese medicine composition according to any one of claims 1 to 3 and / or the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7 in the preparation of a drug for improving symptoms of patients with chronic heart failure and / or reducing the expression level of NT-proBNP.

13. Use of the Chinese medicine composition according to any one of claims 1 to 3 and / or the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7 in the preparation of a drug for inhibiting the expression of NPPB gene, COL1A1 gene, COL5A1 gene and / or SERPINE1 gene.

14. A drug, characterized in that The invention comprises the Chinese medicine composition according to any one of claims 1 to 3 and / or the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7 and pharmaceutically acceptable excipients.

15. Use of the Chinese medicine composition according to any one of claims 1 to 3, the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7, and / or the medicine according to claim 14 in treating any of the following diseases; (I) Heart failure; (II), cardiorenal syndrome; (III), coronary heart disease; (IV), myocardial ischemia; (V), myocardial hypertrophy; (VI), myocardial fibrosis; (VII) Renal fibrosis.

16. A method for treating a disease, characterized in that Taking the Chinese medicine composition according to any one of claims 1 to 3, the Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7, and / or the medicine according to claim 14; Such diseases include: (I) Heart failure; (II), cardiorenal syndrome; (III), coronary heart disease; (IV), myocardial ischemia; (V), cardiac hypertrophy; (VI), myocardial fibrosis; (VII) Renal fibrosis.

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