Composition for chronic heart failure as well as preparation method and application thereof

Abstract

The invention provides a composition for chronic heart failure as well as a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The composition for treating chronic heart failure is prepared from radix fici simplicissimae, radix codonopsis, fried semen lepidii, radix peucedani, cassia twig, poria cocos, rhizoma atractylodis macrocephalae, radix salviae miltiorrhizae, rhizoma chuanxiong, exocarpium citri grandis and herba epimedii. According to the composition, the myocardial cell apoptosis level of a heart failure rat can be greatly reduced to be close to the normal level; when the composition disclosed by the invention is combined with western medicines, the myocardial cell apoptosis level of a heart failure rat can be reduced to be lower than that of a non-heart failure rat; when the composition is used together with western medicines, the side effects of the western medicines can be reduced.

Description

Technical Field

[0001] The present invention provides a composition for chronic heart failure, a preparation method and application thereof, and relates to the technical field of traditional Chinese medicine. Background Art

[0002] Heart failure is a severe and terminal stage of various heart diseases, characterized by high morbidity, mortality, and rehospitalization rates. Chronic heart failure (HF) refers to a complex clinical syndrome caused by any structural or functional abnormality of the heart, resulting in impaired ventricular filling or ejection capacity. The progressive deterioration of cardiac function during HF is the result of repeated loss of cardiomyocytes and / or the gradual deterioration of the contractile function of the remaining cardiomyocytes.

[0003] "A Study on Medication Patterns in Ancient and Modern Traditional Chinese Medicine for the Treatment of Chronic Heart Failure," by Zhang Guijing of Guangzhou University of Chinese Medicine, reveals that patients with yang deficiency often receive a core formula consisting of aconite root, astragalus root, poria cocos, rhizome of orientalis, salvia miltiorrhiza, scutellaria baicalensis, cinnamon twig, and atractylodes macrocephala; a core formula consisting of ophiopogon japonicus, astragalus root, poria cocos, salvia miltiorrhiza, atractylodes macrocephala, schisandra chinensis, and liquorice root; a core formula consisting of astragalus root, atractylodes macrocephala, salvia miltiorrhiza, poria cocos, ophiopogon japonicus, scutellaria baicalensis, codonopsis pilosula, ligusticum chuanxiong, and cinnamon twig for patients with phlegm-dampness, consisting of poria cocos, pinellia tuber, atractylodes macrocephala, scutellaria baicalensis, cinnamon twig, and liquorice root. However, this study has not been validated on a large number of heart failure patients, nor has there been any research on combined treatment with Western medicine.

[0004] Chinese patent CN116270833A discloses a traditional Chinese medicine composition, combination drug, and application for treating chronic heart failure. The composition comprises the following components: 10-30 parts astragalus, 10-30 parts codonopsis, 5-15 parts stir-fried scutellaria baicalensis seeds, 3-16 parts apricot kernels, 5-15 parts cassia twig, 10-25 parts poria, 5-15 parts atractylodes, 3-10 parts roasted liquorice root, 10-25 parts salvia miltiorrhiza, 8-15 parts ligusticum, and 3-10 parts dried tangerine peel. This invention can reduce the number of patients with heart function grades III and IV and increase the number of patients with grade I, but its therapeutic efficacy and the efficacy of individual treatments need to be improved.

[0005] In their study, "Effects of Xinkang Tablets on Cardiomyocyte Apoptosis Rate, Collagen Volume Fraction, and Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats with Adriamycin-Induced Heart Failure," Lü Hongxue et al. reported that Xinkang Tablets, consisting of 15g of Tripterygium wilfordii seeds, 10g of Apricot kernel, 15g of Astragalus membranaceus, 10g of Trigonella ternate, 30g of Poria cocos, and 6g of Tangerine peel, exhibited anti-cardiomyocyte apoptosis and anti-myocardial fibrosis effects, thereby delaying myocardial interstitial remodeling. However, this study was conducted solely on rats, and no studies have reported on its effects in humans. Summary of the Invention

[0006] In response to the above technical problems, the present invention provides a composition for chronic heart failure, a preparation method thereof, and an application thereof.

[0007] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] In one aspect, the present invention provides a composition for chronic heart failure, comprising: five-fingered ginseng, codonopsis pilosula, stir-fried scutellaria baicalensis seeds, peucedanum chinense, cinnamon twig, poria, atractylodes macrocephala, salvia miltiorrhiza, ligusticum chuanxiong, tangerine peel and epimedium.

[0009] Furthermore, the weight ratio of the quinquefolius, codonopsis pilosula and peucedanum peucedanum is: (10-20): (10-20): (5-15).

[0010] Preferably, the weight ratio of the quinquefolius, codonopsis pilosula and peucedanum peucedanum is: (10-15): (15-20): (10-15).

[0011] Preferably, the weight ratio of the quinquefolius, codonopsis pilosula and peucedanum peucedanum is 15:15:10.

[0012] Furthermore, the weight ratio of the Chuanxiong rhizome, Huajuhong and Epimedium is: (5-15): (5-10): (5-15).

[0013] Preferably, the weight ratio of Chuanxiong, Huajuhong and Epimedium is: (5-10): (5-10): (10-15).

[0014] Preferably, the weight ratio of Chuanxiong, Huajuhong and Epimedium is 10:5:10.

[0015] Furthermore, the ratio of the total weight of the five-fingered ginseng, codonopsis pilosula, and peucedanum to the total weight of chuanxiong, tangerine peel, and epimedium is: (35-45): (25-30).

[0016] Preferably, the ratio of the total weight of the five-fingered ginseng, codonopsis pilosula, and peucedanum to the total weight of chuanxiong, tangerine peel, and epimedium is: (40-45): (25-30).

[0017] Preferably, the ratio of the total weight of the Codonopsis pilosula, lily bulb, and dried tangerine peel to the total weight of the Angelica sinensis, safflower, earthworm, and Panax notoginseng is 40:25.

[0018] Furthermore, the composition includes the following raw materials in parts by weight: 10-20 parts of five-fingered ginseng, 10-20 parts of codonopsis pilosula, 5-15 parts of stir-fried scutellaria baicalensis seeds, 5-15 parts of peucedanum chinense, 5-15 parts of cinnamon twigs, 10-20 parts of poria, 5-15 parts of atractylodes macrocephala, 10-20 parts of salvia miltiorrhiza, 5-15 parts of ligusticum chuanxiong, 5-10 parts of tangerine peel and 5-15 parts of epimedium.

[0019] Preferably, the composition comprises the following raw materials in parts by weight: 10-15 parts of five-fingered peach, 15-20 parts of Codonopsis pilosula, 5-10 parts of stir-fried scutellaria baicalensis seeds, 10-15 parts of Peucedanum chinense, 5-10 parts of cinnamon twigs, 15-20 parts of Poria cocos, 5-10 parts of Atractylodes macrocephala, 15-20 parts of Salvia miltiorrhiza, 5-10 parts of Chuanxiong, 5-10 parts of Citrus aurantium and 10-15 parts of Epimedium.

[0020] Preferably, the composition comprises the following raw materials in parts by weight: 15 parts of five-fingered peach, 15 parts of Codonopsis pilosula, 10 parts of stir-fried scutellaria baicalensis seeds, 10 parts of Peucedanum chinense, 10 parts of cinnamon twigs, 15 parts of Poria cocos, 10 parts of Atractylodes macrocephala, 15 parts of Salvia miltiorrhiza, 10 parts of Chuanxiong, 5 parts of Citrus aurantium, and 10 parts of Epimedium.

[0021] In a second aspect, the present invention provides a method for preparing a composition, comprising the following steps:

[0022] (1) Soak all raw materials in water;

[0023] (2) Decoction of Citrus aurantium and Prunus mume for 20-30 min, filter, and obtain solution 1;

[0024] (3) Adding five-fingered ginseng, codonopsis, stir-fried scutellaria, peucedanum, cinnamon twig, poria, atractylodes, salvia miltiorrhiza, ligusticum chuanxiong, tangerine peel and epimedium to the medicinal solution obtained in step (2), and decocting for 1-2 hours to obtain medicinal solution 2;

[0025] (4) Add cinnamon twig and scutellaria baicalensis seed to the medicinal solution 2 obtained in step (3), decoct for 15-25 minutes, and filter to obtain the product.

[0026] Furthermore, the soaking time in step (1) is 30-60 minutes.

[0027] In a third aspect, the present invention provides a medicine comprising the above composition and pharmaceutically acceptable excipients.

[0028] In a fourth aspect, the present invention provides a combined medicine comprising the above composition and a Western medicine.

[0029] Furthermore, the western medicine is at least one of a diuretic, sacubitril / valsartan sodium tablets, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and beta-blockers.

[0030] In a fifth aspect, the present invention provides a composition for use in preparing a medicament for treating and / or preventing abnormal cardiac function.

[0031] Furthermore, the abnormal cardiac function is heart failure.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] (1) The present invention combines five-fingered ginseng, Codonopsis pilosula, stir-fried scutellaria baicalensis seeds, Peucedanum chinense, cinnamon twig, Poria cocos, Atractylodes macrocephala, Salvia miltiorrhiza, Chuanxiong rhizome, Citrus aurantium and Epimedium, and by adjusting the dosage relationship of five-fingered ginseng, Codonopsis pilosula and Peucedanum chinense, as well as Chuanxiong rhizome, Citrus aurantium and Epimedium, the apoptosis level of myocardial cells in rats with heart failure is significantly reduced to a level close to normal.

[0034] (2) The composition of the present invention has no side effects in animal experiments and clinical trials.

[0035] (3) When the composition of the present invention is used in combination with Western medicine, it can significantly reduce the level of myocardial cell apoptosis in rats with heart failure, even lower than that in rats without heart failure; in animal experiments and clinical trials, the composition of the present invention can also reduce the side effects of Western medicine. DETAILED DESCRIPTION

[0036] The present invention is described below through specific embodiments to make the technical solution of the present invention easier to understand and grasp, but the present invention is not limited thereto. The described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments.

[0037] The endpoints and any value of the scope disclosed in this article are not limited to this accurate scope or value, and these scopes or values should be understood as comprising values close to these scopes or values.For numerical range, between the endpoint values of each scope, between the endpoint values of each scope and a separate point value, and between the separate point value, can be combined with each other and obtain one or more new numerical ranges, and these numerical ranges should be considered as specifically disclosed in this article. Unless the context clearly indicates otherwise, the singular form "one", "a kind of" and "described" as used herein include singular and plural indicators. The numerical range stated by endpoint is included in all numerical values and fractions within the corresponding range, and the stated endpoint.

[0038] The "pharmaceutically acceptable excipients" described herein include inert diluents, dispersants and / or granulating agents, surfactants and / or emulsifiers, disintegrants, binders, preservatives, buffers, lubricants, and / or oils. Excipients (e.g., cocoa butter and suppository waxes), colorants, coating agents, sweeteners, flavoring agents, and fragrances may also be present in the pharmaceutical composition.

[0039] The "medicament" described in the present invention can be prepared by any method known in pharmacy. Generally speaking, these preparation methods include associating the aforementioned Chinese herbal compound (i.e., the first active ingredient) with a carrier or excipient and / or one or more other auxiliary ingredients, and then, if necessary and / or desired, shaping and / or packaging the product into a desired single-dose or multi-dose unit.

[0040] The "drugs" of the present invention can be prepared according to known methods, such as those described in the general rules for preparation in the Chinese Pharmacopoeia (2020 edition), the Japanese Pharmacopoeia, 16th edition, the United States Pharmacopoeia, and the European Pharmacopoeia, 9th edition. It depends on the dosage form.

[0041] The first active ingredient and pharmaceutically acceptable excipients in the "medicament" of the present invention will vary depending on the nature, size, and / or condition of the subject being treated and further depending on the route of administration of the composition. The medicament may contain between 0.1% and 100% (w / w) of the first active ingredient.

[0042] As used herein, "treating," unless otherwise indicated, means reversing, alleviating, inhibiting the progression of, or preventing the condition or disorder to which the term applies, or one or more symptoms of such condition or disorder. The term "treating," as used herein, refers to the act of treating, as "treating" is defined immediately above.

[0043] The Chinese herbal compound or pharmaceutical composition of the present invention can also be used as one of the raw materials contained in medicines, functional foods or health products.

[0044] The "decoction" mentioned in the present invention refers to decoct the medicinal liquid until the weight is equal to that of the raw materials, and the raw materials are the weight of the initial raw materials before preparation.

[0045] Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without inventive effort shall fall within the scope of protection of the present invention. The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0046] The composition for chronic heart failure of the present invention is mainly used to treat heart failure of the type of qi (yang) deficiency, blood stasis and water retention, with qi (yang) deficiency as the root and blood stasis and water retention as the symptoms. In the prescription, five-fingered ginseng and codonopsis are sweet and warm, invigorate the spleen and benefit the lungs and invigorate qi, and are good at treating asthma and cough due to deficiency. The two are both monarch drugs. Epimedium is sweet and warm, warms and invigorates yang qi, while cinnamon twig is pungent and warm, promotes yang and eliminates dampness. Combined with Poria cocos, it can dissipate dampness and promote diuresis, while Atractylodes macrocephala can invigorate the spleen and promote diuresis, taking the meaning of Wuling Powder. The four drugs are used together to achieve the effects of warming yang, transforming qi and promoting diuresis. Trichosanthes is an important drug for the qi of the lungs, and is good at purging the lungs and promoting diuresis. The "Compendium of Materia Medica" states: "Those with water-qi distension and urgency in the lungs must use this drug." Stir-frying removes its coldness and retains its bitter and pungent nature. Peucedanum chinense can reduce qi and relieve asthma. The two drugs are used together to promote lung function, relieve asthma, reduce qi and promote diuresis. Danshen removes blood stasis and promotes new growth, while Chuanxiong is a blood-tonifying herb. Together, these two herbs activate blood circulation and dissolve blood stasis. These eight herbs are collectively referred to as assistant herbs. Huajuhong regulates qi, strengthens the spleen, and dispels dampness, assisting the aforementioned monarch and assistant herbs and enhancing their effectiveness. Furthermore, when combined with nourishing herbs, it promotes nourishment without stagnation, thus serving as an adjuvant.

[0047] 1. Examples and Comparative Examples

[0048] Example 1 A composition for chronic heart failure

[0049] The invention is composed of the following raw materials in parts by weight: 20 parts of five-fingered ginseng, 10 parts of codonopsis pilosula, 15 parts of stir-fried scutellaria baicalensis seeds, 5 parts of peucedanum, 15 parts of cinnamon twigs, 10 parts of poria, 15 parts of atractylodes macrocephala, 10 parts of salvia miltiorrhiza, 15 parts of ligusticum chuanxiong, 10 parts of tangerine peel and 5 parts of epimedium.

[0050] Example 2 A composition for chronic heart failure

[0051] The recipe is composed of the following raw materials in parts by weight: 10 parts of five-fingered ginseng, 20 parts of codonopsis pilosula, 5 parts of stir-fried scutellaria baicalensis seeds, 15 parts of peucedanum, 5 parts of cinnamon twigs, 20 parts of poria, 5 parts of atractylodes macrocephala, 20 parts of salvia miltiorrhiza, 5 parts of ligusticum chuanxiong, 10 parts of tangerine peel and 15 parts of epimedium.

[0052] Example 3 A composition for chronic heart failure

[0053] The invention is composed of the following raw materials in parts by weight: 15 parts of five-fingered ginseng, 15 parts of codonopsis pilosula, 10 parts of stir-fried scutellaria baicalensis seeds, 10 parts of peucedanum chinense, 10 parts of cinnamon twigs, 15 parts of poria, 10 parts of atractylodes macrocephala, 15 parts of salvia miltiorrhiza, 10 parts of ligusticum chuanxiong, 5 parts of tangerine peel and 10 parts of epimedium.

[0054] Comparative Example 1

[0055] The difference from Example 3 is that the weight ratios of Rhizoma Cibotii, Codonopsis pilosula and Peucedanum chinense are different.

[0056] The invention is composed of the following raw materials in parts by weight: 9 parts of five-fingered ginseng, 27 parts of codonopsis pilosula, 10 parts of stir-fried scutellaria baicalensis seeds, 4 parts of peucedanum, 10 parts of cinnamon twigs, 15 parts of poria, 10 parts of atractylodes macrocephala, 15 parts of salvia miltiorrhiza, 10 parts of ligusticum chuanxiong, 5 parts of tangerine peel and 10 parts of epimedium.

[0057] Comparative Example 2

[0058] The difference from Example 3 is that the weight ratios of Chuanxiong, Huajuhong and Epimedium are different.

[0059] The invention is composed of the following raw materials in parts by weight: 15 parts of five-fingered ginseng, 15 parts of codonopsis pilosula, 10 parts of stir-fried scutellaria baicalensis seeds, 10 parts of peucedanum chinense, 10 parts of cinnamon twigs, 15 parts of poria, 10 parts of atractylodes macrocephala, 15 parts of salvia miltiorrhiza, 17 parts of ligusticum chuanxiong, 4 parts of tangerine peel and 4 parts of epimedium.

[0060] Comparative Example 3

[0061] The difference from Example 3 is that the ratio of the total weight of Rhizoma Coptidis, Codonopsis pilosula, and Peucedanum chinense to the total weight of Rhizoma Chuanxiong, Citrus aurantium, and Epimedium is different.

[0062] The invention is composed of the following raw materials in parts by weight: 11.25 parts of five-fingered ginseng, 11.25 parts of codonopsis pilosula, 10 parts of stir-fried scutellaria baicalensis seeds, 7.5 parts of peucedanum chinense, 10 parts of cinnamon twigs, 15 parts of poria cocos, 10 parts of atractylodes macrocephala, 15 parts of salvia miltiorrhiza, 14 parts of ligusticum chuanxiong, 7 parts of tangerine peel and 14 parts of epimedium.

[0063] The preparation methods of Examples 1-3 and Comparative Examples 1-3 are:

[0064] (1) Soak all raw materials in water;

[0065] (2) Decoction of Citrus aurantium and Prunus mume for 25 min, filter, and obtain solution 1;

[0066] (3) Add five-fingered ginseng, codonopsis pilosula, stir-fried scutellaria baicalensis seeds, peucedanum chinense, cinnamon twig, poria, atractylodes macrocephala, salvia miltiorrhiza, ligusticum chuanxiong, tangerine peel and epimedium to the liquid obtained in step (2), and boil for 1 hour to obtain liquid 2;

[0067] (4) Add cinnamon twig and scutellaria baicalensis seed to the medicinal solution 2 obtained in step (3), decoct for 25 minutes, and filter to obtain the product.

[0068] Comparative Example 4

[0069] The difference from Example 3 is that the preparation method is different.

[0070] The invention is composed of the following raw materials in parts by weight: 15 parts of five-fingered ginseng, 15 parts of codonopsis pilosula, 10 parts of stir-fried scutellaria baicalensis seeds, 10 parts of peucedanum chinense, 10 parts of cinnamon twigs, 15 parts of poria, 10 parts of atractylodes macrocephala, 15 parts of salvia miltiorrhiza, 10 parts of ligusticum chuanxiong, 5 parts of tangerine peel and 10 parts of epimedium.

[0071] The preparation method is:

[0072] (1) Soak all raw materials in water for 30 minutes;

[0073] (2) Add all the raw materials to water and boil for 110 minutes, then filter to obtain the product.

[0074] Comparative Example 5

[0075] It is prepared according to the formula and preparation method described in Chinese patent CN116270833A.

[0076] The preparation is composed of the following raw materials in parts by weight: 20 parts of astragalus, 20 parts of codonopsis, 10 parts of stir-fried scutellaria, 8 parts of apricot kernel, 10 parts of cinnamon twig, 15 parts of poria, 10 parts of atractylodes, 5 parts of roasted licorice, 15 parts of salvia miltiorrhiza, 10 parts of chuanxiong and 5 parts of tangerine peel.

[0077] The preparation method is as follows: add all the raw materials to water and boil until the concentrated decoction is 100 mL.

[0078] Comparative Example 6

[0079] It is prepared according to the formula and preparation method described in "Effects of Xinkang Tablets on Myocardial Cell Apoptosis Rate, Collagen Volume Fraction, and Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats with Heart Failure Induced by Adriamycin".

[0080] Xinkang Tablets: 15 parts of scutellaria baicalensis seeds, 10 parts of apricot kernels, 15 parts of astragalus, 10 parts of trigonosciadium japonicum, 30 parts of poria, and 6 parts of dried tangerine peel.

[0081] The preparation method is: crush and add distilled water, boil into solution, and filter to obtain the product.

[0082] Comparative Example 7

[0083] According to the prescription in "Research on the Medication Rules of Ancient and Modern Literature on the Treatment of Chronic Heart Failure with Traditional Chinese Medicine", 15 parts of Astragalus, 10 parts of Atractylodes, 15 parts of Salvia miltiorrhiza, 15 parts of Poria, 15 parts of Ophiopogon, 10 parts of Trichosanthes, 15 parts of Codonopsis, 10 parts of Chuanxiong, and 10 parts of cinnamon twig.

[0084] Preparation method:

[0085] (1) Soak all raw materials in water for 30 minutes;

[0086] (2) Add all the raw materials to water and boil for 110 minutes, then filter to obtain the product.

[0087] 2. Animal Experiments

[0088] 1. Experimental methods

[0089] (1) Experimental animals: Healthy male Sprague Dawley (SD) rats.

[0090] Modeling method: 2.5 mg / kg of doxorubicin was injected intraperitoneally for 6 times within 2 weeks to establish a rat heart failure model. Five weeks after the first intraperitoneal injection, cardiac ultrasound was used to detect and calculate FS (left ventricular fractional shortening).

[0091] (2) Grouping: Rats were intraperitoneally injected with an equal amount of solvent as the blank group. Rats with enlarged central cavity and FS < 30% were selected and randomly divided into the model group and the drug group. The above groups were divided into 10 rats in each of the model group and the blank group, and 120 rats in the drug group.

[0092] (3) Administration: Rats were randomly divided into groups of 10 and administered orally with Examples 1-3 (10 g / kg), Comparative Examples 1-7 (10 g / kg), a Western medicine (22.5 μg / kg digoxin), and a combination of 22.5 μg / kg digoxin and 10 g / kg Example 3. The blank and model groups were administered orally with an equal amount of distilled water once daily for 35 consecutive days.

[0093] 2. Experimental results

[0094] Rat ventricular tissue was obtained, paraffin-embedded, and sectioned, and then the following experimental steps were performed:

[0095] (1) Dewaxing: Soak the paraffin sections in xylene at room temperature for 5 minutes, then replace the xylene and soak for another 5 minutes; soak in anhydrous ethanol for 5 minutes; then soak in anhydrous ethanol for 5 minutes; perform gradient elution: soak in 95% ethanol for 3 minutes; soak in 85% ethanol for 3 minutes; soak in 75% ethanol for 3 minutes; soak in 50% ethanol for 3 minutes; soak in PBS at room temperature for 5 minutes.

[0096] (2) 3% hydrogen peroxide at room temperature for 10 minutes.

[0097] (3) Soak in deionized water at room temperature for 5 minutes and repeat once.

[0098] (4) Remove excess liquid and perform microwave heat repair of antigens: Place tissue sections in 0.01 M sodium citrate buffer solution (pH 6.0), heat in a microwave oven for 5 minutes until boiling, turn off the power, cool to room temperature, and then wash three times with PBS for 3 minutes each time.

[0099] (5) Block with 5% BSA for 30 min.

[0100] (6) Add TUNNEL reaction mixture (reaction mixture: add 5 μL enzyme solution for every 95 μL marker solution): cover with film and incubate at 37°C for 1 hour; remove the film and soak in PBS at room temperature for 5 minutes, repeat twice;

[0101] (7) Add Converter-POD reaction solution: Cover with film and incubate at 37°C for 30 min; remove the film and soak in PBS at room temperature for 5 min, repeat twice; add 100 μL of DAB color development solution and react at room temperature for about 10 min; rinse with deionized water and dehydrate, seal and examine under a microscope.

[0102] (8) TUNNEL expression was observed in six fields of view per slice, and the experimental results were expressed as the average of the cell apoptosis rate under the six fields of view. PBS buffer (pH 7.2-7.4), 0.01 M sodium citrate buffer solution (pH 6.0): Boster Biotechnology Co., Ltd. TUNNEL kit: In Situ Cell Death Detection Kit, PO D, (Cat. No. 11 684817910; Lot: 10768100), ROCHE; DAB colorimetric kit: Boster Biotechnology Co., Ltd.

[0103] The results are shown in Table 1.

[0104] Table 1

[0105]

[0106]

[0107] ###: compared with the blank group, p<0.001, *: compared with the model group, p<0.05, ***: compared with the model group, p<0.001, &: compared with Example 3, p<0.05, &&: compared with Example 3, p<0.01.

[0108] The myocardial cell apoptosis rate in the model group was significantly increased compared to the blank group and there was a significant difference, proving that the modeling was successful. The myocardial cell apoptosis rate in Examples 1-3 was significantly decreased compared to the model group and there was a significant difference, proving that Examples 1-3 can reduce rat myocardial cell apoptosis and effectively alleviate heart failure. Comparative Examples 1-3 differ from the present invention in components, Comparative Example 4 has a different preparation method from the present invention, and Comparative Examples 5-7 are prior art. Although their myocardial cell apoptosis rates decreased compared to the model group, they were higher than Examples 1-3 and there was a significant difference.

[0109] When the drugs were used in combination, the apoptosis rate of myocardial cells in rats was significantly lower than that in the western medicine group and the example group, and even lower than that in the blank group.

[0110] During the administration period, there were no side effects in Examples 1-3 and Comparative Example 4, 30% of the rats in the Western medicine group had side effects of decreased activity and loss of appetite, 10% of the rats in the Comparative Examples 1-3 and Comparative Examples 5-7 groups had side effects of diarrhea, and there were no side effects in the combination medication group.

[0111] Experiments show that the composition of the present invention can significantly reduce the apoptosis rate of myocardial cells in rats with heart failure models to a level close to normal; the composition of the present invention has no side effects during administration; the composition of the present invention, when used in combination with Western medicine, can further reduce the apoptosis rate of myocardial cells in rats with heart failure models, even lower than that of the blank group; the composition of the present invention, when used in combination with Western medicine, can reduce the side effects of Western medicine.

[0112] 3. Clinical Trials

[0113] The clinical trials of the present invention were carried out in strict compliance with the Good Clinical Practice Guidelines for Drug Clinical Trials.

[0114] 1. Source of cases

[0115] All cases were selected from patients with chronic heart failure admitted to the outpatient and inpatient departments of the Department of Cardiology at Dongguan Hospital of Traditional Chinese Medicine between September 2022 and December 2024. A total of 120 cases were included (with the total clinical effective rate as the primary effect indicator, and the sample size estimation method of two independent sample frequency comparison in non-inferiority trials was used to determine the need for 30 cases per group). Doll's clinical case randomization table was used for randomization. No significant differences were found in gender, age, disease duration, and cardiac function grade between the groups (P>0.05), indicating comparability.

[0116] The baseline data of the patients are shown in Table 2.

[0117] Table 2

[0118]

[0119] 2. Western medicine diagnostic standards: The diagnostic standards for chronic heart failure are based on the "Guidelines for the Diagnosis and Treatment of Chronic Heart Failure in China 2018" formulated by the Cardiovascular Branch of the Chinese Medical Association.

[0120] 3. Case inclusion criteria

[0121] (1) A history of chronic heart failure for more than 3 months or clinical symptoms of heart failure for more than 3 months. The diagnosis of chronic heart failure refers to the "2018 Chinese Guidelines for the Diagnosis and Treatment of Chronic Heart Failure" issued by the Chinese Society of Cardiology;

[0122] (2) aged between 18 and 85 years;

[0123] (3) Heart function classification is II-IV (NYHA); patients who have received Western medicine treatment must have their clinical manifestations stable for more than one week, and the dosage of Western medicine should not be increased.

[0124] 4. Exclusion criteria

[0125] (1) Acute heart failure, acute myocarditis, acute coronary syndrome;

[0126] (2) Patients with severe lung, liver, or kidney dysfunction or serious primary diseases or malignant tumors of the endocrine, nervous, or hematopoietic systems;

[0127] (3) Patients with hemodynamic instability, malignant arrhythmia, severe valvular heart disease, obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, pulmonary embolism, and severe infection.

[0128] (4) Pregnant or breastfeeding women;

[0129] (5) People with dementia or mental disorders.

[0130] 5. Termination criteria

[0131] (1) Serious adverse events occur;

[0132] (2) Subjects are unwilling to continue the clinical trial;

[0133] (3) Important deviations occurred during the clinical trial, such as poor compliance, making it difficult to evaluate the treatment effect.

[0134] 6. Research Methods

[0135] Clinical patients were randomly divided into western medicine group and combined treatment group.

[0136] Western medicine group: Only Western medicine treatment recommended by the "Guidelines for the Diagnosis and Treatment of Heart Failure in China 2018" was given: those with congestive symptoms or signs were given diuretics, sacubitril valsartan sodium / ACEI / AR B, and beta-blockers; those without congestive symptoms or signs were given ACEI / ARB and beta-blockers; specific medications: diuretics were furosemide or hydrochlorothiazide (drugs and doses were selected according to clinical needs); sacubitril valsartan sodium tablets were started at 50 mg / bid and gradually titrated to the target dose of 100 mg / d-200 mg / d; ACEI type was benazepril, with a starting dose of 2.5 mg / d, and gradually titrated to the target dose of 10 mg / d-20 mg / d; those who could not tolerate ACEI were given AR As an alternative to steroids (B), irbesartan should be used, starting at 75 mg / day and titrated gradually to a target dose of 300 mg / day. Beta-blockers include metoprolol tartrate (starting dose 6.25 mg / bid, target dose 50 mg / bid) or metoprolol succinate (starting dose 11.875 mg / day to 23.75 mg / day, target dose 142.5 mg / day to 190.0 mg / day). For patients with pulmonary insufficiency, bisoprolol (starting dose 1.25 mg / day, target dose 10 mg / day) should be used. The maintenance dose of digoxin should be 0.125 mg / day to 0.25 mg / day. The course of treatment is 6 weeks.

[0137] Combined treatment group: In addition to the drug treatment, the composition of Example 3 (15g of Prunus mume, 15g of Codonopsis pilosula, 10g of stir-fried Lepidium sativum seeds, 10g of Peucedanum chinense, 10g of Cinnamomum cassia twig, 15g of Poria cocos, 10g of Atractylodes macrocephala, 15g of Salvia miltiorrhiza, 10g of Ligusticum chuanxiong, 5g of Citrus aurantium, and 10g of Epimedium) was added. One dose was taken daily, divided into two doses, morning and evening. The course of treatment was 6 weeks.

[0138] 7. Experimental Results

[0139] ①Evaluate the NYHA cardiac function classification of clinical patients before and after treatment.

[0140] NYHA cardiac function classification:

[0141] Heart function class I: The patient has heart disease but is not restricted in physical activity. Normal physical activity does not cause excessive fatigue, palpitations, dyspnea, or angina.

[0142] Heart function class II: The patient has heart disease and physical activity is slightly limited. They feel comfortable at rest, but normal physical activity can cause fatigue, palpitations, dyspnea, or angina.

[0143] Heart function class III: The patient has heart disease, and physical activity is greatly restricted. While resting, they feel comfortable, but even light physical activity causes fatigue, palpitations, dyspnea, or angina.

[0144] Heart function level IV: The patient has heart disease and is completely unable to perform physical activities. Symptoms of chronic heart failure or angina may persist even at rest. Any physical activity will aggravate the symptoms.

[0145] ② Measure blood routine, urine routine, blood biochemistry and BNP before and after treatment.

[0146] ③ The ejection fraction (LVEF) was measured before and after treatment. The left ventricular end-diastolic dimension (LVEDD) and end-systolic dimension (LVESD) were measured by echocardiography, and the LVEF was calculated using the formula.

[0147] Formula: LVEF=(LVEDD-LVESD) / LVEDD 3 ×100%.

[0148] ④ According to the 6-Minute Walk Test Guidelines issued by the American Thoracic Society in 2002, patients were asked to walk back and forth in a straight 30-meter corridor before and after treatment, and their maximum walking distance, i.e., 6MWT, was recorded.

[0149] ⑤The Minnesota Heart Failure Quality of Life Scale was used to score the patients before and after treatment.

[0150] Before and after treatment, clinical patients filled out the Minnesota Life Quality of Heart Failure Scale (MLHFQ) according to their own conditions.

[0151] The distribution of cardiac function grades before and after treatment is shown in Table 3 , and the results of BNP, 6MWT, MLHFQ, and LVEF are shown in Table 4 .

[0152] Table 3

[0153]

[0154] Table 4

[0155]

[0156] #: Comparison between the Western medicine group before and after treatment, p<0.05; *: Comparison between the Western medicine group after treatment and the combined treatment group after treatment, p<0.05; &: Comparison between the combined treatment group before and after treatment, p<0.05.

[0157] When Western medicine was used alone, the number of patients with heart function level IV did not decrease, and patients with heart function level III accounted for 30%. After the combined treatment of Example 1 of the present invention and Western medicine, patients with heart function level III and IV were converted to patients with heart function level I and II, and the effect was significantly improved.

[0158] In the Western medicine group, clinical patients experienced side effects, including one or more of hypotension, nausea, vomiting, and fatigue, accounting for 10%. In the combined treatment group, no patient experienced side effects.

[0159] The combined treatment of Example 1 of the present invention and Western medicine significantly reduced the patient's BNP index, and there was a significant difference compared with the Western medicine group; the combined treatment improved the patient's 6MWT, and there was a significant difference compared with the Western medicine group; the combined treatment reduced the patient's MLHFQ score, and there was a significant difference compared with the Western medicine group; the combined treatment increased the patient's ejection fraction value, and there was a significant difference compared with the Western medicine group.

[0160] Experimental results demonstrate that the present invention is effective in treating heart failure. Furthermore, when used in combination with Western medication, the present composition can reduce the severity of heart failure (grades III and IV) in patients with milder heart failure (grades I and II). Furthermore, the present composition can further reduce BNP and MLHFQ scores, and improve 6MWT and ejection fraction, in addition to Western medication. Furthermore, the present composition can also reduce the side effects of Western medication when used in combination with Western medication.

[0161] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for chronic heart failure, characterized in that: include: Five-fingered ginseng, Codonopsis pilosula, stir-fried scutellaria baicalensis seeds, Peucedanum chinense, cinnamon twig, Poria cocos, Atractylodes macrocephala, Salvia miltiorrhiza, Ligusticum chuanxiong, Citrus aurantium and Epimedium.

2. The composition according to claim 1, characterized in that The weight ratio of the five-fingered ginseng, codonopsis pilosula and peucedanum peucedanum is: (10-20): (10-20): (5-15).

3. The composition according to claim 1, characterized in that The weight ratio of the Chuanxiong rhizome, the red orange peel and the epimedium is: (5-15): (5-10): (5-15).

4. The composition according to claim 1, characterized in that The ratio of the total weight of the five-fingered ginseng, codonopsis pilosula, and peucedanum to the total weight of chuanxiong, tangerine peel, and epimedium is: (35-45): (25-30).

5. The composition according to claim 1, characterized in that The composition comprises the following raw materials in parts by weight: 10-20 parts of five-fingered ginseng, 10-20 parts of codonopsis pilosula, 5-15 parts of stir-fried scutellaria baicalensis seeds, 5-15 parts of peucedanum chinense, 5-15 parts of cinnamon twigs, 10-20 parts of poria, 5-15 parts of atractylodes macrocephala, 10-20 parts of salvia miltiorrhiza, 5-15 parts of ligusticum chuanxiong, 5-10 parts of tangerine peel and 5-15 parts of epimedium.

6. The method for preparing the composition according to any one of claims 1 to 5, characterized in that: The steps include: (1) Soak all raw materials in water; (2) Decoction of Citrus aurantium and Prunus mume for 20-30 min, filter, and obtain solution 1; (3) Adding five-fingered ginseng, codonopsis, stir-fried scutellaria, peucedanum, cinnamon twig, poria, atractylodes, salvia miltiorrhiza, ligusticum chuanxiong, tangerine peel and epimedium to the medicinal solution obtained in step (2), and decocting for 1-2 hours to obtain medicinal solution 2; (4) Add cinnamon twig and scutellaria baicalensis seed to the medicinal solution 2 obtained in step (3), decoct for 15-25 minutes, and filter to obtain the product.

7. A drug, characterized in that The invention comprises the composition according to any one of claims 1 to 5 or the composition prepared by the preparation method according to claim 6 and pharmaceutically acceptable excipients.

8. A combined drug, characterized in that The invention comprises the composition according to any one of claims 1 to 5 or the composition prepared by the preparation method according to claim 6 and a western medicine; the western medicine is at least one of a diuretic, sacubitril / valsartan sodium tablets, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and beta-blockers.

9. Use of the composition according to any one of claims 1 to 5 or the composition prepared by the preparation method according to claim 6 in the preparation of a medicament for treating and / or preventing abnormal cardiac function.

10. The use according to claim 9, characterized in that The abnormal cardiac function is heart failure.

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