Use of a traditional Chinese medicine composition in the preparation of a medicine for preventing and / or treating chronic heart failure

Abstract

The application belongs to the field of medicine, and particularly relates to a use of a traditional Chinese medicine composition in preparation of a medicine for preventing and / or treating chronic heart failure. Specifically, the traditional Chinese medicine composition is prepared from Radix Polygoni Multiflori, Aloe, Semen Cassiae, Radix et Rhizoma Ginseng, Fructus Lycii, Colla Corii Asini, Fructus Aurantii Immaturus and Rhizoma Atractylodis. The pharmacodynamic experiment results show that the traditional Chinese medicine composition can obviously improve the state of rats caused by injection of doxorubicin hydrochloride, such as dry and withered fur, lazy and lying, inactivity, reduced food intake, shortness of breath and the like; can obviously increase the survival rate of the rats; can obviously increase the ejection fraction and shorten fraction; pathological observation shows that the traditional Chinese medicine composition can obviously reduce the myocardial cell remodeling of the rats with chronic heart failure, which indicates that the traditional Chinese medicine composition has a definite effect of treating chronic heart failure, and has a potential application value in preparation of a medicine for preventing and / or treating chronic heart failure.

Description

Technical Field

[0001] This invention belongs to the field of medicine, specifically relating to the use of a traditional Chinese medicine composition in the preparation of drugs for the prevention and / or treatment of chronic heart failure. Background Technology

[0002] Chronic heart failure (CHF) is a complex clinical syndrome resulting from any structural or functional abnormality of the heart, leading to impaired ventricular filling or ejection. It represents the end-stage of many cardiovascular diseases, with primary clinical manifestations including dyspnea, fluid retention, and fatigue. Due to population aging and increased life expectancy, the prevalence of CHF is increasing annually. A study of 4 million people found that approximately 3 out of every 1,000 patients develop CHF each year. The survival rate for patients diagnosed with CHF also drops sharply from an initial 75.9% to 12.7% within 1 to 15 years. Furthermore, the risk of relapse and worsening is high, and frequent emergency room visits and hospitalizations significantly increase the burden on patients. Therefore, improving the quality of life for patients with CHF is crucial for global public health and the economy.

[0003] Currently, Western medicine's treatment of chronic heart failure has shifted from short-term measures such as diuretics, cardiotonics, and vasodilators to long-term, restorative strategies primarily using neuroendocrine inhibitors. The aim is to remodel the heart, break the vicious cycle, and alter the biological properties of the failing heart. However, despite these advancements, Western medicine still suffers from limitations such as single-target drug therapy, long treatment cycles, high drug dependence, significant side effects, and less than ideal efficacy. Traditional Chinese medicine (TCM), with its holistic approach and syndrome differentiation, regulates the patient's Qi, blood, and body fluids holistically. This not only improves symptoms but also enhances the patient's resistance to pathogens, reducing the frequency of recurrent episodes due to various triggering factors. TCM offers advantages such as fewer side effects, longer-lasting efficacy, and better patient compliance.

[0004] Chinese patent CN100453105C discloses a composition and its preparation method that have the functions of relieving constipation, detoxifying, and reducing weight and lipids. This composition is prepared from Polygonum multiflorum, Aloe vera, Cassia tora, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala, and Citrus aurantium, and has a good therapeutic effect on constipation caused by internal accumulation of toxins and deficiency of yin fluid. Related products are already on the market, with the generic name "Shouhui Tongbian Capsules" and the trade name "Shunyishu".

[0005] The patents related to this product include Chinese patent CN113995801A, which discloses the use of Shouhui Tongbian Capsules in the preparation of hangover remedies; Chinese patent CN113117006A, which discloses the use of a traditional Chinese medicine composition, specifically the application of Shouhui Tongbian Capsules in the preparation of anti-aging drugs or cosmetics; and Chinese patent CN114522204A, which discloses the use of a traditional Chinese medicine composition, specifically the use of Shouhui Tongbian Capsules in the preparation of drugs for the prevention, treatment, or improvement of tinnitus, etc.

[0006] There are currently no reports on the use of the compositions of the present invention in the preparation of medicaments for the prevention and / or treatment of chronic heart failure. Summary of the Invention

[0007] The purpose of this invention is to provide the use of a traditional Chinese medicine composition in the preparation of a drug for the prevention and / or treatment of chronic heart failure.

[0008] The traditional Chinese medicine composition is prepared from Polygonum multiflorum, aloe vera, cassia seed, ginseng, wolfberry, donkey-hide gelatin, immature bitter orange, and Atractylodes macrocephala.

[0009] Furthermore, the ingredients, by weight, are as follows: Polygonum multiflorum 60-150 parts by weight, Aloe vera 100-200 parts by weight, Cassia seed 80-180 parts by weight, Lycium barbarum 30-150 parts by weight, Colla corii asini 30-150 parts by weight, Ginseng 20-100 parts by weight, Atractylodes macrocephala 20-100 parts by weight, and Citrus aurantium 50-200 parts by weight.

[0010] Furthermore, the ingredients are as follows by weight: 120 parts by weight of Polygonum multiflorum, 160 parts by weight of Aloe vera, 140 parts by weight of Cassia seed, 75 parts by weight of Lycium barbarum, 75 parts by weight of donkey-hide gelatin, 50 parts by weight of ginseng, 50 parts by weight of Atractylodes macrocephala, and 120 parts by weight of Citrus aurantium.

[0011] The traditional Chinese medicine composition can also be prepared into a clinically acceptable dosage form by adding other pharmaceutically acceptable excipients.

[0012] Furthermore, the clinically acceptable dosage forms are: granules, oral solutions, mixtures, pills, syrups, capsules, and tablets.

[0013] Furthermore, the clinically acceptable dosage form is a capsule.

[0014] Furthermore, the capsule is Shouhui Tongbian Capsules.

[0015] The preparation methods of the above-mentioned traditional Chinese medicine composition are existing technologies, including but not limited to the following methods: preparation methods disclosed in patents CN100453105C, CN109464570B, and CN113117006A.

[0016] Furthermore, the preparation method of the Shouhui laxative capsules includes the following steps:

[0017] (1) Grind the donkey-hide gelatin into a fine powder, pass it through an 80-mesh sieve, and set aside;

[0018] (2) Ginseng, Polygonum multiflorum, Cassia seed and aloe were extracted twice by reflux with 60% ethanol. The first time, 10 times the amount of ethanol was added and the second time, 8 times the amount of ethanol was added. Each extraction lasted 2 hours. The extracts were filtered separately and the filtrates were combined to obtain filtrate I for later use.

[0019] (3) Add water to wolfberry, atractylodes macrocephala and immature bitter orange and decoct twice. For the first decoction, add 8 times the amount of water, soak for 1 hour, decoct for 1.5 hours and filter. For the second decoction, add 6 times the amount of water, decoct for 1.5 hours and filter. Combine the filtrates and concentrate to a clear extract with a relative density of 1.10 to 1.20 (80℃). Place at room temperature, stir and add ethanol to make the purity reach 60% (20℃), refrigerate and stand for more than 24 hours, filter and obtain filtrate II for later use.

[0020] (4) Combine the filtrate I obtained in step (2) with the filtrate II obtained in step (3), concentrate it to a thick paste with a relative density of 1.30-1.35 (70℃), dry it, pulverize it, add the fine powder of donkey-hide gelatin prepared in step (1) and an appropriate amount of dextrin, mix it evenly, granulate it by dry method, and fill it into capsules to obtain the product.

[0021] In this invention, the term "prevention or treatment" and other similar synonyms include relieving, reducing, or improving symptoms of a disease or condition; preventing other symptoms; improving or preventing the underlying metabolic causes of symptoms; inhibiting a disease or condition, such as preventing its progression; alleviating a disease or condition; improving a disease or condition; relieving symptoms caused by a disease or condition; or stopping the symptoms of a disease or condition. Furthermore, the term includes the purpose of prevention. The term also includes achieving therapeutic and / or preventive effects. A therapeutic effect refers to the cure or improvement of the underlying disease being treated. Furthermore, the cure or improvement of one or more physiological symptoms associated with the underlying disease is also a therapeutic effect; for example, an improvement in the patient's condition is observed even though the patient may still be affected by the underlying disease. Regarding preventive effects, the composition may be administered to patients at risk of developing a specific disease, or to patients exhibiting one or more physiological symptoms of a disease, even if a disease diagnosis has not yet been made.

[0022] Compared with the prior art, the technical solution of the present invention has achieved the following beneficial technical effects: The traditional Chinese medicine composition of the present invention can significantly improve the state of rats induced by doxorubicin hydrochloride injection, such as dry fur, lethargy, reluctance to move, reduced food intake, and shortness of breath; it can significantly increase the survival rate of rats; it can significantly increase the ejection fraction and shorten the ejection fraction; pathological observation found that the traditional Chinese medicine composition of the present invention can significantly reduce myocardial cell remodeling in rats with chronic heart failure, indicating that the traditional Chinese medicine composition of the present invention has a clear therapeutic effect on chronic heart failure. Description of the Drawings

[0023] Appendix Figure 1 HE staining results of the heart Specific Embodiments

[0024] The present invention will be further described in detail below with reference to specific embodiments. The following embodiments provide detailed implementation manners and specific operation procedures to illustrate the technical solutions of the present invention, but do not limit the protection scope of the present invention. Those of ordinary skill in the art who modify or equivalently replace the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention still fall within the protection scope of the present invention.

[0025] Pharmacodynamic Example: Study on the Pharmacodynamic Effect of Shouhui Laxative Capsule on Rats with Chronic Heart Failure Induced by Doxorubicin Hydrochloride for Injection 1. Materials

[0026] 1.1 Experimental Animals

[0027] Wistar rats, male, weighing 200 - 240 g, 6 - 8 weeks old, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. The license number for the use of experimental animals is: SYXK (Lu) 20230023. They were housed in Laboratory 167 of the New Drug Pharmacology Center (GLP) of Lunan Pharmaceutical Group Co., Ltd. The feeding conditions were: room temperature 20 - 26 °C, daily temperature difference ≤ 4 °C; relative humidity 40% - 70%; lighting: artificial lighting, 12 h / 12 h light - dark alternation; ventilation rate: ≥ 15 times / hour; fed with SPF mouse and rat growth and reproduction feed, with free access to water and food. All operations related to experimental animals in the study were strictly carried out in accordance with the international laboratory animal ethical behavior guidelines "Guide for the Care and Use of Laboratory Animals".

[0028] 1.2 Reagents

[0029] Shouhui Laxative Capsule (Lunan Houpu Pharmaceutical Co., Ltd., batch number 231103);

[0030] Qili Qiangxin Capsule (Shijiazhuang Yiling Pharmaceutical Co., Ltd., batch number B2304018);

[0031] Doxorubicin Hydrochloride for Injection (Han晖 Pharmaceutical Co., Ltd., batch number 22068611);

[0032] 2. Experimental Methods

[0033] 2.1 Model Establishment

[0034] After 7 days of quarantine, 15 qualified rats were randomly selected as the normal group (C), and the remaining rats were injected with doxorubicin hydrochloride 2 mg / kg via the tail vein to induce the rat model. The injection was performed once a week for a total of 6 times.

[0035] 2.2 Grouping and Dosing

[0036] After two rat modeling experiments, the rats in the model group were randomly divided into four groups: model group (V), low-dose group (L), medium-dose group (M), high-dose group (H), and positive control group (QL), with 15 rats in each group. At the start of the drug administration, the normal group and model group were given purified water by gavage; the low-dose group, medium-dose group, and high-dose group were given Shouhui Tongbian capsules at 100 mg / kg / d, 200 mg / kg / d, and 400 mg / kg / d, respectively, by gavage; and the positive control group was given Qili Qiangxin capsules (324 mg / kg / d) by gavage. This continued until the end of the experiment.

[0037] 2.3 Observation Indicators and Detection Methods

[0038] 2.3.1 General observations and survival rate

[0039] Throughout the experiment, the rats' general condition was observed and recorded daily, including mortality, activity level, mental state, whether their food intake decreased, fur color, and bowel movements.

[0040] 2.3.2 Cardiac contractile function test

[0041] One hour after the last administration of each group of animals, they were anesthetized by intraperitoneal injection of 0.5 ml / 100 g of 8% chloral hydrate. The rats were fixed in a supine position on a rat board, and the cardiac contractile function of the rats was tested using a color echocardiogram with coupling gel applied to the smallest probe. The ejection fraction (EF) and fractional shortening (FS) of the rats were measured for three consecutive cardiac cycles, and the average value was taken.

[0042] 2.3.3 Pathological section examination

[0043] Heart specimens were fixed in 10% formalin for 24 hours, routinely harvested, dehydrated, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE).

[0044] Observe the following cardiac lesions under an optical microscope: whether there is hypertrophy, degeneration, or necrosis of myocardial fibers, and whether there is congestion, edema, or inflammatory cell infiltration in the interstitium.

[0045] 2.4 Statistical Analysis

[0046] All data are expressed as mean ± SD. SPSS 19.0 statistical software was used for data analysis. One-way ANOVA was used for comparisons between two or more groups, and the chi-square test was used for statistical analysis of categorical data. A p-value < 0.05 was considered statistically significant.

[0047] 3. Experimental Results and Analysis

[0048] 3.1 General observation and survival rate

[0049] The normal group rats were agile, had glossy fur, and were able to eat and drink normally. The model group rats had dry, brittle fur, were lethargic, curled up, showed little interest in activity, had reduced food intake, and exhibited shortness of breath. The positive control group and the rats in each group treated with Shouhui Tongbian capsules showed significant improvement in fur and mental state compared to the model group, with a significant reduction in symptoms.

[0050] The survival rate results are shown in Table 1: Compared with the model group, the survival rate of rats was significantly increased by the administration of Shouhui Tongbian capsules at doses of 200 mg / kg and 400 mg / kg. * p<0.05).

[0051] 3.2 Cardiac contractile function test

[0052] The experimental results are shown in Table 1. Compared with the normal group, the model group showed a significant decrease in EF and FS. ** p<0.01, indicating successful model preparation; compared with the model group, EF and FS were significantly increased in each drug-treated group ( # p<0.05, ## p<0.01 indicates that Shouhui Tongbian Capsules have a clear therapeutic effect on chronic heart failure.

[0053] Table 1. Effects of Shouhui Tongbian Capsules on Survival Rate and Cardiac Contractile Function in Rats with Chronic Heart Failure

[0054]

[0055] 3.3 Pathological Changes

[0056] HE staining results are shown in […]. Figure 1 In the normal group, cardiomyocytes were neatly arranged, and myocardial fibers were short columnar with visible striations. The cardiomyocyte nuclei were oval, relatively large, and lightly stained, located in the center of the muscle fibers; no cardiomyocyte hypertrophy was observed. In the model group, apoptosis or necrosis of muscle fibers and interstitium was observed, myocardial fibers thickened and elongated, cells were loosely arranged, striations were unclear or disappeared, local tissue fibrosis was present, and inflammatory cell infiltration was observed in the interstitium. After treatment with different doses of the "invention," the pathological changes were significantly alleviated.

[0057] The above efficacy examples demonstrate that the herbal composition of this invention can significantly improve the symptoms induced by doxorubicin hydrochloride injection in rats, such as withered fur, lethargy, reluctance to move, reduced food intake, and shortness of breath; it can significantly increase the survival rate of rats; it can significantly increase ejection fraction and shorten ejection fraction; pathological results show that the herbal composition of this invention can significantly alleviate myocardial cell remodeling in rats with chronic heart failure. The herbal composition of this invention has a clear therapeutic effect on chronic heart failure and has potential application value in the preparation of drugs for the prevention and / or treatment of chronic heart failure.

Claims

1. The use of a traditional Chinese medicine composition in the preparation of a drug for the prevention and / or treatment of chronic heart failure, characterized in that, The traditional Chinese medicine composition is prepared from Polygonum multiflorum, aloe vera, cassia seed, ginseng, wolfberry, donkey-hide gelatin, immature bitter orange, and atractylodes macrocephala, in parts by weight as follows: Polygonum multiflorum 60-150 parts by weight, aloe vera 100-200 parts by weight, cassia seed 80-180 parts by weight, wolfberry 30-150 parts by weight, donkey-hide gelatin 30-150 parts by weight, ginseng 20-100 parts by weight, atractylodes macrocephala 20-100 parts by weight, and immature bitter orange 50-200 parts by weight.

2. The use as described in claim 1, characterized in that, The traditional Chinese medicine composition comprises, by weight, 120 parts of Polygonum multiflorum, 160 parts of Aloe vera, 140 parts of Cassia tora, 75 parts of Lycium barbarum, 75 parts of donkey-hide gelatin, 50 parts of ginseng, 50 parts of Atractylodes macrocephala, and 120 parts of Citrus aurantium.

3. The use as described in claim 1 or 2, characterized in that, The traditional Chinese medicine composition can also be prepared into a clinically acceptable dosage form by adding other pharmaceutically acceptable excipients.

4. The use as described in claim 3, characterized in that, The clinically acceptable dosage forms are granules, oral solutions, mixtures, pills, syrups, capsules, and tablets.

5. The use as described in claim 4, characterized in that, The clinically acceptable dosage form is capsules.

6. The use as described in claim 5, characterized in that, The capsule is Shouhui Tongbian Capsule.

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