CN114984087B

CN114984087B - Traditional Chinese medicine composition, decoction and pharmaceutical composition, and preparation method and application thereof

Info

Publication number: CN114984087B
Application number: CN202110230761.6A
Authority: CN
Inventors: 高秀梅; 张伯礼; 王小莹; 赵英强; 杨剑; 王跃飞; 张晗; 谭旺晓; 薛志峰; 王凯月; 崔英
Original assignee: Tianjin University of Traditional Chinese Medicine
Current assignee: Tianjin University of Traditional Chinese Medicine
Priority date: 2021-03-02
Filing date: 2021-03-02
Publication date: 2023-04-25
Anticipated expiration: 2041-03-02
Also published as: CN114984087A

Abstract

The application provides a traditional Chinese medicine composition, decoction, a medicine composition, a preparation method and application thereof. The preparation raw materials of the active ingredients of the pharmaceutical composition comprise: 4-60 parts of roasted astragalus, 1-9 parts of tetrandra root, 1-15 parts of semen lepidii, 3-20 parts of selfheal, 3-15 parts of radix salviae miltiorrhizae, 1-9 parts of bran-fried bighead atractylodes rhizome and 1-9 parts of liquorice. The traditional Chinese medicine composition, decoction or pharmaceutical composition can be used for preparing medicines for preventing and/or treating chronic heart failure related diseases.

Description

Traditional Chinese medicine composition, decoction and pharmaceutical composition, and preparation method and application thereof

Technical Field

The application relates to the technical field of medicines, in particular to a traditional Chinese medicine composition, decoction and a pharmaceutical composition, and a preparation method and application thereof.

Background

Chronic heart failure (hereinafter abbreviated as heart failure) is traditionally classified as heart arthralgia, heart water, heart distention and the like, and the disease is located in the heart and mainly relates to the lung, spleen and kidney. Modern medicine considers chronic heart failure as a chronic clinical syndrome in which cardiac structure or function is impaired due to myocardial lesions or cardiac overload, etc., resulting in reduced ventricular filling and/or ejection. The disease is one of three diseases in the 21 st century cardiovascular field, has the characteristics of high morbidity, high disability rate and high mortality rate, seriously damages the physical health of human beings, influences the life quality of people and causes obvious economic burden on the medical health care system worldwide. Its main causes include myocardial infarction, hypertension and pulmonary hypertension. Wherein myocardial infarction and hypertension can lead to left heart failure and pulmonary arterial hypertension can lead to right heart failure.

Myocardial infarction is myocardial necrosis caused by coronary artery ischemia and hypoxia, and is a serious consequence of coronary heart disease. At present, most of myocardial infarction treatment is reperfusion or direct coronary intervention treatment, but the reperfusion or intervention treatment needs an experienced doctor to operate, so that a certain operation risk exists, and great economic pressure is brought to a patient. Western medicines for treating myocardial infarction are mostly beta receptor blockers, calcium blockers, glycerin nitrate and the like, but the medicines have certain limitations, and people with related contraindications and discomfort need to be paid attention to when the western medicines are used.

Hypertension is the most common chronic disease, no operation method for treating hypertension exists at present, and 5 types of antihypertensive drugs can be selected for clinical use, but generally need to be taken for life. In addition, antihypertensive drugs for treating hypertension can be used in the early stage, but a doctor is required to select drugs for personalized treatment according to the crowd type and complications, which requires a high level of expertise.

Western medicine treatment schemes for pulmonary hypertension are usually anti-infection, heart strengthening, diuretic, vascular dilation and the like, and the adopted medicines have higher cost, high administration frequency, stronger dependence and poor compliance of patients, and have certain side effects such as arrhythmia, acid and alkali electrolyte disorder and the like. And the difficulty of the operation such as lung transplantation is high, and the operation can bring great pain and economic burden to patients.

At present, the traditional Chinese medicine compound for treating chronic heart failure related diseases is relatively lacking, the compatibility of medicines for different doctors for the same patient is different in center of gravity, the clinical medicine has strong dependence on clinical experience of doctors, and the problems of medication disorder and the like exist.

Disclosure of Invention

Based on the diagnosis and treatment of the traditional Chinese medicine, the application provides a traditional Chinese medicine composition, a pharmaceutical composition and decoction for preventing and/or treating chronic heart failure related diseases through the verification of clinical experience and preclinical scientific research. The application also provides a preparation method of the pharmaceutical composition and application of the pharmaceutical composition in preparing medicines for preventing and/or treating chronic heart failure related diseases.

A first aspect of the present application provides a traditional Chinese medicine composition comprising or consisting of: 4-60 parts of roasted astragalus, 1-9 parts of tetrandra root, 1-15 parts of semen lepidii, 3-20 parts of selfheal, 3-15 parts of radix salviae miltiorrhizae, 1-9 parts of bran-fried bighead atractylodes rhizome and 1-9 parts of liquorice.

A second aspect of the present application provides a decoction obtained by decocting the present application of a Chinese medicinal composition with water and filtering.

A third aspect of the present application provides a pharmaceutical composition comprising or being prepared from the following ingredients: 4-60 parts of roasted astragalus, 1-9 parts of tetrandra root, 1-15 parts of semen lepidii, 3-20 parts of selfheal, 3-15 parts of radix salviae miltiorrhizae, 1-9 parts of bran-fried bighead atractylodes rhizome and 1-9 parts of liquorice.

A fourth aspect of the present application provides a process for the preparation of a pharmaceutical composition of the present application comprising the steps of subjecting the starting material to reflux with a solvent, filtering and concentrating the filtrate.

A fifth aspect of the present application provides the use of a traditional Chinese medicine composition according to the first aspect of the present application or a decoction according to the second aspect or a pharmaceutical composition according to the third aspect of the present application in the manufacture of a medicament for the prevention and/or treatment of a disease associated with chronic heart failure.

The decoction and the pharmaceutical composition prepared from the traditional Chinese medicine composition show the effects of increasing left ventricular ejection fraction, increasing short-axis shortening rate, improving heart structure and improving heart function in a chronic heart failure model caused by myocardial infarction or hypertension, and the effects of relieving right cardiac hypertrophy and improving right ventricular function in a chronic heart failure model caused by pulmonary hypertension, so that the traditional Chinese medicine composition, the decoction and the pharmaceutical composition can be used for preventing and/or treating chronic heart failure related diseases, and further can be used for preparing medicines for preventing and/or treating chronic heart failure related diseases.

The traditional Chinese medicine composition, decoction or medicinal composition has the characteristics of low cost, reliable source, good medicinal effect, good market prospect and the like, and the traditional Chinese medicine composition, decoction or medicinal composition has the advantages of firm foundation of early-stage research work, definite medicinal curative effect and reduced risk of subsequent development.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present application, and that other embodiments may be obtained according to these drawings without inventive effort to a person skilled in the art.

FIG. 1 is a high performance liquid chromatogram, A is a chromatogram of a mixed reference solution, and B is a chromatogram of a solution of a pharmaceutical composition A as a test substance; wherein 1 is quercetin-3-O-beta-D-glucose-7-O-beta-D-Dragon Shan Shuangtang glycoside, 2 is calycosin glycoside, 3 is rosmarinic acid, 4 is salvianolic acid B, and 5 is glycyrrhizic acid.

FIG. 2 is echocardiography and ejection fraction results for a blank, sham, and LAD procedure group in a LAD-induced heart failure model; panel A is the echocardiogram of the blank, panel B is the echocardiogram of the sham surgery group, panel C is the echocardiogram of the LAD surgery group, and panel D is the ejection fraction results of the blank, sham surgery group and LAD surgery group.

FIG. 3 shows the results of ultrasonic testing of cardiac structures in rats of each group 6 weeks after administration in the LAD-induced heart failure model.

FIG. 4 shows the results of evaluation of cardiac function in each group of rats after 6 weeks of administration in the LAD-induced heart failure model.

FIG. 5 shows the results of organ indexes of rats in each group after 6 weeks of administration in the LAD-induced heart failure model.

FIG. 6 shows HE staining results of hearts of rats in the LAD-induced heart failure model 6 weeks after administration; wherein, the A graph is blank group, the B graph is false operation group, the C graph is model group, the D graph is Sha Kuba trovaptan group, the E graph is low dose group, the F graph is medium dose group, the G graph is high dose group, the upper graph in each graph is 40 times of mirror result, marked as 40×, the lower graph is 400 times of mirror result, marked as 400×.

FIG. 7 shows Masson staining of hearts of each group of rats after 6 weeks of administration in the LAD-induced heart failure model; panel A is blank, panel B is sham, panel C is model, panel D is Sha Kuba triamcinolone acetonide, panel E is low dose, panel F is medium dose, panel G is high dose, the upper panel in each panel is 40 x under the mirror, marked 40 x, the lower panel is 400 x under the mirror, marked 400 x.

FIG. 8 shows the results of ultrasonic testing of cardiac structures in mice of each group after 4 weeks of administration in the TAC-induced heart failure model.

FIG. 9 shows the results of evaluation index of cardiac function of each group of mice after 4 weeks of administration in TAC-induced heart failure model.

FIG. 10 shows the results of organ weights and indices of mice in each group after 4 weeks of administration in the TAC-induced heart failure model.

FIG. 11 shows HE staining results of hearts of mice in each group after 4 weeks of administration in a TAC-induced heart failure model.

FIG. 12 shows the results of sirius red staining of hearts of mice of each group after 4 weeks of administration in TAC-induced heart failure model.

Fig. 13 is a graph showing the right ventricular systolic pressure and mean pulmonary artery pressure results for each group of rats after 3 weeks of administration in the monocrotaline induced heart failure model.

FIG. 14 shows the results of evaluation index of right ventricular function of rats of each group after 3 weeks of administration in a monocrotaline induced heart failure model.

FIG. 15 shows the results of organ indexes of rats in each group after 3 weeks of administration in a monocrotaline-induced heart failure model.

FIG. 16 shows HE staining of the free wall of the right ventricle of each group of rats after 3 weeks of administration in the monocrotaline induced heart failure model.

Detailed Description

The following description of the embodiments of the present application will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all, of the embodiments of the present application. All other embodiments, which can be made by one of ordinary skill in the art without undue burden from the present disclosure, are within the scope of the present disclosure.

The inventor finds that the Chinese medicinal composition of the application is prepared from radix astragali preparata and red sage root as monarch drugs, the radix astragali preparata has the effects of strengthening body resistance and tonifying qi, and the radix salviae miltiorrhizae is matched for activating blood circulation and removing blood stasis, and the two have the effects of tonifying qi and activating blood, and can be used for qi deficiency and blood stasis of chronic heart failure; the tetrandra and the semen lepidii are used as ministerial drugs, the tetrandra is good in descending property and is used as a key drug for treating wind and water, and the tetrarhizoma lepidii which is good in dredging a water channel and purging lung and relieving asthma is used as a ministerial drug together with the semen lepidii to enhance the ability of inducing diuresis and relieving swelling; the bran-fried atractylodes macrocephala and the selfheal are taken as adjuvant drugs, the bran-fried atractylodes macrocephala has the effects of tonifying qi, strengthening spleen and eliminating dampness, so that the effects of inducing diuresis to alleviate edema of the semen lepidii and the stephania tetrandra are enhanced, the effects of qi-tonifying and exterior-securing of the roasted astragalus are enhanced, the selfheal has the effects of relieving swelling and resolving masses, the effects of inducing diuresis to alleviate edema of ministerial drugs are enhanced, and the effects of activating blood and removing stasis of the monarch drug salvia miltiorrhiza are enhanced; glycyrrhrizae radix is used as guiding drug to harmonize the drugs. The Chinese medicinal herbs are used for treating qi deficiency and blood stasis of chronic heart failure, and internal retention of water, and symptoms such as chest distress, suffocating breath or asthma, swelling of lower limbs and the like.

In some embodiments of the first aspect of the present application, the traditional Chinese medicine composition comprises or consists of: 8-50 parts of roasted astragalus, 2-8 parts of tetrandra root, 3-12 parts of semen lepidii, 5-15 parts of selfheal, 4-12 parts of radix salviae miltiorrhizae, 3-9 parts of bran-fried bighead atractylodes rhizome and 2-8 parts of liquorice.

Before administration, the Chinese medicinal composition can be decocted with water by using methods known in the art, and decoction obtained after decocting the Chinese medicinal composition is taken during administration.

In some embodiments of the third aspect of the present application, the feedstock is or comprises: 8-50 parts of roasted astragalus, 2-8 parts of tetrandra root, 3-12 parts of semen lepidii, 5-15 parts of selfheal, 4-12 parts of radix salviae miltiorrhizae, 3-9 parts of bran-fried bighead atractylodes rhizome and 2-8 parts of liquorice.

In some embodiments of the third aspect of the present application, the medicament is a tablet, capsule, granule, powder, patch, ointment, gel, suppository, solution, suspension, or emulsion.

In some embodiments of the third aspect of the present application, the pharmaceutical composition may be obtained by subjecting the starting material to steps of reflux with a solvent, filtration and concentration of the filtrate.

In some embodiments of the third aspect of the present application, the pharmaceutical composition may be obtained by subjecting the starting material to the steps of: heating and refluxing the raw materials with solvent for 2 times, wherein the solvent amount is 6-10 times of the raw materials, and the steps are 1 st time, 2 nd time, 3h, 2 nd time, 1 nd hour, 2 nd hour, filtering, mixing filtrates, and concentrating the filtrate under reduced pressure.

In some embodiments of the fourth aspect of the present application, the method of making comprises subjecting the feedstock to the steps of: heating and refluxing the raw materials for 2 times by using a solvent, wherein the mass ratio of the solvent volume to the raw materials is (6-10): 1, 1 st time for 2-3h, 2 nd time for 1-2h, filtering, combining filtrates, and concentrating the filtrate under reduced pressure.

The solvent used in the preparation method is not limited as long as the object of the present application can be achieved, and for example, water, an aqueous ethanol solution or ethanol may be used, and after the reflux extraction, the solvent may be further treated by ethanol precipitation to remove a part of the inactive ingredients.

The chronic heart failure related diseases in the present application include chronic heart failure and cardiovascular diseases capable of causing chronic heart failure, such as coronary heart disease, pulmonary heart disease, myocardial infarction, pulmonary arterial hypertension, and the like.

In some embodiments of the fifth aspect of the present application, the chronic heart failure-related disease is selected from at least one of coronary heart disease, myocardial infarction, pulmonary arterial hypertension, complications caused by pulmonary arterial hypertension.

In some embodiments of the fifth aspect of the present application, the complication caused by pulmonary arterial hypertension is selected from at least one of chronic obstructive emphysema, chronic pulmonary heart disease, left heart failure, right heart failure, and liver function injury.

The terms used herein, unless explicitly stated or defined, have their ordinary meanings as known to those skilled in the art.

As used herein, the term "treatment" has its ordinary meaning and herein particularly refers to the treatment of an animal subject who may be suffering from chronic heart failure or who is at risk of suffering from chronic heart failure with a medicament of the present application in the hope of producing a therapeutic, curative, palliative, and the like effect on the disease. Similarly, as used herein, the term "preventing" has its ordinary meaning and herein particularly refers to treating an animal subject who may be suffering from chronic heart failure or who is at risk of suffering from chronic heart failure with a medicament of the present application in the hope of producing a preventing, arresting, blocking, etc. effect on the disease.

As used herein, the term "pharmaceutical composition" has its ordinary meaning and may refer herein to a composition of a raw material, i.e. a crude plant material, of the present application, or an extract composition of the raw material, i.e. a crude plant material, or a formulation, e.g. a pharmaceutical formulation, from which the aforementioned extract is further processed. In addition, the "pharmaceutical composition" of the present application may also exist or be provided in the form of a health product, a functional food, a food additive, or the like. The pharmaceutical compositions of the present application can be prepared by extracting, separating and purifying means commonly used in pharmaceutical production, by conventional techniques in the pharmaceutical field, particularly in the formulation field, to obtain the active ingredient of the raw materials of the pharmaceutical composition of the present application, optionally mixing with one or more pharmaceutically acceptable excipients, and then preparing the desired dosage form.

The "pharmaceutically acceptable excipient" useful in the pharmaceutical compositions of the present application may be any excipient conventional in the art of pharmaceutical formulation, the choice of the particular excipient being dependent upon the mode of administration or type and state of disease used to treat the particular patient. The preparation of pharmaceutical compositions for specific modes of administration is well within the knowledge of those skilled in the pharmaceutical arts. For example, pharmaceutically acceptable excipients may be used, including diluents, carriers, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorption carriers, lubricants, etc., which are conventional in the pharmaceutical arts. Flavoring agent, antiseptic, sweetener, etc. can be added into the pharmaceutical composition if necessary.

The pharmaceutical composition of the present application may be a pharmaceutical formulation suitable for oral, parenteral or topical administration. The pharmaceutical composition can be prepared into various forms such as tablets, powder, granules, capsules, oral liquid and the like.

The medicaments of the various formulations can be prepared according to the conventional method in the pharmaceutical field. In particular, pharmaceutical compositions according to the present application, the pharmaceutical dosage forms include, but are not limited to: tablets, capsules, granules, powders, injections, powders for injection, transdermal patches, ointments, gels, suppositories, oral solutions, oral suspensions, emulsions for injection, oral emulsions, sustained-release tablets, controlled-release tablets and the like. The medicaments of the various formulations can be prepared according to the conventional method in the pharmaceutical field.

When the pharmaceutical compositions or pharmaceutical compositions of the present application are administered as a medicament to a subject human or animal, they may be administered as such, i.e., without any of the above pharmaceutically acceptable excipients, the pharmaceutical compositions or pharmaceutical compositions of the present application are administered directly to a patient as such; or may be administered to a human or animal in a composition containing, for example, 1-99% (more preferably, for example, 10-90%) of a pharmaceutical composition (which may be in the form of an extract of a crude drug of the present application) or a pharmaceutical composition (which may be in the form of an extract of a crude drug of the present application) in combination with a pharmaceutically acceptable excipient.

The actual dosage level and time course of administration of the active ingredient in the pharmaceutical compositions or pharmaceutical compositions of the present application may be varied as appropriate so that the amount of active ingredient is effective to achieve the desired therapeutic response for a particular subject, composition and method of administration without toxicity to the subject.

As used herein, the term "individual" or "animal individual" has its ordinary meaning, and may refer herein to an animal individual suffering from or likely to suffer from chronic heart failure, and may also refer to an animal individual used for some purpose, e.g., for scientific research purposes. Specifically, the subject is, for example, an animal subject, particularly a mammalian subject, such as a human, pig, dog, cat, cow, sheep, horse, rat, mouse, rabbit, guinea pig, monkey, or the like. More specifically, the subject described herein is a rat, mouse.

The experimental materials and methods used in the examples below are conventional materials and methods unless otherwise specified.

Preparation example 1A Chinese medicinal composition of the present application

Weighing the following raw materials in proportion: 300g of roasted astragalus, 75g of tetrandra root, 125g of pepperweed seed, 150g of selfheal, 200g of red sage root, 150g of bighead atractylodes rhizome stir-fried with bran and 50g of liquorice to obtain the traditional Chinese medicine composition.

PREPARATION EXAMPLE 2 decoction of the present application

Weighing the following raw materials in proportion: 300g of roasted astragalus, 75g of stephania tetrandra, 125g of semen lepidii, 150g of selfheal, 200g of red sage root, 150g of bighead atractylodes rhizome fried with bran and 50g of liquorice are soaked in cold water for 2 hours, the raw materials are put into a marmite, water is added to submerge the raw materials, the raw materials are boiled by fire, then the raw materials are decocted by slow fire for 30-60 minutes, and then the decoction is filtered by gauze, and the filtered filtrate is the decoction.

PREPARATION EXAMPLE 3A pharmaceutical composition of the present application

300g of roasted astragalus, 75g of stephania tetrandra, 125g of semen lepidii, 150g of selfheal, 200g of red sage root, 150g of bighead atractylodes rhizome fried with bran and 50g of liquorice are taken, 8400mL of water is added, heating reflux is carried out for 2.5h, gauze is used for filtering, primary filtrate is obtained, 8400mL of water is then added, heating reflux is carried out for 1.5h, gauze is used for filtering, secondary filtrate is obtained, filtrate is combined, and filtrate is concentrated under reduced pressure, so that the pharmaceutical composition A and 1213.9g of the application are obtained.

PREPARATION EXAMPLE 4 Another pharmaceutical composition of the present application

40g of roasted astragalus, 60g of stephania tetrandra, 80g of semen lepidii, 110g of selfheal, 120g of red sage root, 60g of bighead atractylodes rhizome fried with bran and 70g of liquorice are taken, 3600mL of water is added, heating reflux is carried out for 2.5h, gauze is used for filtering, primary filtrate is obtained, 3600mL of water is then added, heating reflux is carried out for 1.5h, gauze is used for filtering, secondary filtrate is obtained, filtrate is combined, and filtrate is concentrated under reduced pressure, thus obtaining the pharmaceutical composition B and 586.5g.

PREPARATION EXAMPLE 5 Another pharmaceutical composition of the present application

250g of roasted astragalus, 40g of stephania tetrandra, 55g of semen lepidii, 65g of selfheal, 70g of radix salviae miltiorrhizae, 35g of bighead atractylodes rhizome fried with bran and 40g of liquorice are taken, 4800mL of water is added, heating reflux is carried out for 2h, gauze is used for filtering to obtain primary filtrate, 4800mL of water is then added, heating reflux is carried out for 2h, gauze is used for filtering to obtain secondary filtrate, the filtrates are combined, and the filtrate is concentrated under reduced pressure to obtain the pharmaceutical composition C and 636.4g.

Example 1 determination of the content of the specified Components in the pharmaceutical composition of the present application

The content of quercetin-3-O-beta-D-glucose-7-O-beta-D-longmono-bisglycoside, calycosin glycoside, rosmarinic acid, salvianolic acid B and glycyrrhizic acid in the pharmaceutical composition is determined by High Performance Liquid Chromatography (HPLC).

Chromatographic conditions: high performance liquid chromatograph: shimadzu LC-20A (Shimadzu Japan) high performance liquid chromatograph (SPD-M20A detector, LC-20AT pump, SIL-20ACHT autosampler, CTO-20AC column incubator, LC Solution workstation); chromatographic column:

C ₁₈ (4.6 mm. Times.150 mm,5 μm); flow rate: 1.0mL/min; mobile phase a was 0.1% aqueous formic acid (v/v) and mobile phase B was methanol, gradient elution procedure: 0-10min 3-19% B,10-15min 19-23% B,15-30min 23-43% B,30-50min 43-97% B; column temperature: 40 ℃; sample injection amount: 20. Mu.L; PDA detection wavelength: 254nm.

Taking 2540 mug of quercetin-3-O-beta-D-glucose-7-O-beta-D-dragon Shan Shuangtang glycoside, 4970 mug of calycosin glycoside, 4970 mug of rosmarinic acid, 2960 mug of salvianolic acid B and 4990 mug of glycyrrhizic acid, precisely weighing, adding methanol for dissolving, and fixing the volume by using 50% methanol to 5mL, thus preparing a mixed reference solution of 6 mug/mL of quercetin-3-O-beta-D-glucose-7-O-beta-D-longmonodisaccharide glycoside, 2 mug/mL of calycosin glycoside, 7 mug/mL of rosmarinic acid, 100 mug/mL of salvianolic acid B and 5 mug/mL of glycyrrhizic acid. Taking 0.4g of the pharmaceutical composition A obtained in preparation example 3, precisely weighing, placing in a 50mL conical flask, adding 25mL of 50% methanol, performing ultrasonic treatment for 30min, taking out, standing to room temperature, centrifuging for 10min, and taking supernatant to obtain a sample solution. Respectively precisely sucking 20 μl of the mixed reference solution and the sample solution, and injecting into high performance liquid chromatograph, and measuring under the above chromatographic conditions.

The high performance liquid chromatogram obtained by detection is shown in figure 1, wherein the chromatogram of the mixed reference substance solution is shown in figure 1A, the chromatogram of the solution of the pharmaceutical composition A as the test sample is shown in figure 1B, and the content result is obtained by calculating according to an external standard method: in the medicine composition A, the content of quercetin-3-O-beta-D-glucose-7-O-beta-D-gentiobioside is 0.06%, the content of calycosin is 0.03%, the content of rosmarinic acid is 0.16%, the content of salvianolic acid B is 1.67%, and the content of glycyrrhizic acid is 0.08%.

Example 2 action of the pharmaceutical composition of the present application in animal models of LAD-induced chronic heart failure

Materials: small animal ultrasonic instrument: canada Visual Sonics, model Vevo 2100; sha Kuba triptan sodium: beijing Nohua pharmaceutical Co., ltd, SDH395; HE staining kit: g1005, a Whansai Weir Biotech Co., ltd; masson staining kit: g1006, whansai Weibull biotechnology Co., ltd. Experimental animals: 200 Sprague-Dawely (SD) healthy adult male rats weighing 230-250g, provided by Beijing Vetong Liwa laboratory animal technology Co., ltd, with an animal qualification number of 1100111911049930.

Left anterior descending coronary artery Ligation (LAD) is the most effective modeling method for replicating myocardial infarction. After the rats were adaptively raised for one week, they were randomly divided into a blank group (9), a sham operation group (9) and a LAD operation group (42), wherein the blank group was not operated, the sham operation group was operated by sham operation, and the LAD operation group was operated by LAD operation. Echocardiography and left ventricular Ejection Fraction (EF) measurements were performed on each group of rats 6 weeks after surgery, and the results are shown in fig. 2.

As can be seen from fig. 2, panels a, B and C, after 6 weeks of surgery, the left ventricular upper chamber wall was significantly thinner, the chamber wall movement was reduced, and the ventricular cavity was enlarged in LAD surgery group rats (panel C) compared to blank group (panel a), sham surgery group (panel B) rats; as can be seen from the graph D, the fraction of the rats in the LAD surgery group was reduced to 40% (ΔΔΔp <0.001, to blank ratio; # # P <0.001, compared to sham group). From this, it was found that myocardial infarction rats developed heart failure after 6 weeks of LAD surgery, indicating successful molding.

The LAD rats were randomly grouped into 5 groups, which were designated model group, sha Kuba valsartan group, low dose group, medium dose group, and high dose group, respectively, according to the differences of administration, and the model group was 10, and the rest were 8.

Rats in each experimental group were dosed 1 time a day after successful molding and were dosed continuously by gavage for 6 weeks. Wherein, the Sha Kuba/valsartan group is given with Sha Kuba of a 3.75mg/mL aqueous solution of the trovartan sodium and the dosage is 0.5mL/100g; a low dose group to which 69.93mg/mL of the aqueous solution of pharmaceutical composition A of the present application was administered in an amount of 0.5mL/100g; a medium dose group to which 139.86mg/mL of the aqueous solution of pharmaceutical composition A of the present application was administered in an amount of 0.5mL/100g; a high dose group to which 279.72mg/mL of the aqueous solution of pharmaceutical composition A of the present application was administered in an amount of 0.5mL/100g; blank, sham and model groups were given 0.5mL/100g physiological saline daily per body weight. Wherein, sha Kuba/l/valsartan sodium is a common medicament for treating heart failure, as a positive control in this application.

After the end of administration, the heart structure, heart function, organ indexes and ventricular remodeling conditions of the rats are detected, and the therapeutic effect of the pharmaceutical composition of the application on chronic heart failure after myocardial infarction is evaluated.

(1) And (3) heart structure detection: after the last administration, the heart structure change condition of each group of rats is detected by using a small animal ultrasonic instrument, the result is shown in figure 3, and compared with a blank group and a false operation group, the upper chamber wall of a model group of rats is obviously thinned and flattened, the chamber wall movement is obviously weakened, obvious left chamber expansion occurs, and the heart structure change of the model group of rats is indicated, and heart failure symptoms occur; in each administration group (low dose group, medium dose group and high dose group), the wall thinning degree of the rat is obviously reduced, and the wall movement is enhanced; the pharmaceutical composition and the positive control drug can improve the heart structure change caused by heart failure.

(2) Heart function detection: the left ventricular ejection fraction, short axis shortening rate, end-diastolic left ventricular volume, end-systolic left ventricular volume, end-diastolic ventricular septum thickness, end-systolic ventricular septum thickness, end-diastolic left ventricular inner diameter, end-systolic left ventricular inner diameter of each group of rats were examined by a small animal sonicator, and as a result, as shown in fig. 4, compared with the blank group and the false operation group, the left ventricular ejection fraction, the short axis shortening rate, the end diastole ventricular interval thickness and the end systole ventricular interval thickness of the model group rats are obviously reduced, the end-diastole left chamber volume, end-systole left chamber volume, end-diastole left chamber inner diameter, end-systole left chamber inner diameter increases significantly (n=5, ΔΔp <0.001, to blank ratio; # # P <0.001 compared to sham group), indicating significant impairment of cardiac function in rats in the model group. After treatment with the positive drug and the pharmaceutical composition of the present application, the left ventricular ejection fraction and the short axis shortening rate of each of the administered rats were significantly increased compared to the model group (n=5, P <0.01, P <0.001, compared to the model group); rats in the low dose group had significant improvement in end-diastole left chamber volume, end-systole left chamber volume, end-diastole left chamber inner diameter, end-systole left chamber inner diameter compared to the model group (n=5, P <0.05, P <0.01, P <0.001, compared to the model group); the middle dose group rats had significant improvement in end-diastolic left chamber volume, end-systolic left chamber volume, end-diastolic chamber interval thickness, end-systolic chamber interval thickness, end-diastolic left chamber inner diameter, end-systolic left chamber inner diameter compared to the model group (n=5, <0.01, <0.001, < P, compared to the model group); the high dose group rats had significant improvement in end-systole left chamber volume, end-diastole chamber interval thickness, end-systole chamber interval thickness, end-diastole left chamber inner diameter, end-systole left chamber inner diameter compared to the model group (n=5, <0.05, <0.001, < to the model group); the rat wall motion of each administration group is obviously enhanced, the left ventricular ejection fraction is obviously increased, and the short axis shortening rate is obviously increased, so that the myocardial contractility is improved, the cardiac blood supply is ensured, and the pharmaceutical composition has the effect of improving the cardiac function.

(3) And (3) detecting visceral organ indexes:

after detection by a small animal ultrasonic instrument, each group of rats is fasted overnight and the materials are sacrificed every other day. The abdominal cavity of the rat was dissected, the abdominal aorta was collected, left standing at room temperature for 45 minutes, and the supernatant was collected after centrifugation. The abdominal cavity thoracic cavity of the rat was cut, the lung, heart, liver, spleen and kidney were carefully separated and cut with an ophthalmic scissors, residual blood was washed with physiological saline, and then excess liquid was sucked dry with a filter paper, and the weights of the organs were weighed, and the indices of the organs were calculated as compared with the body weight. After measuring the heart weight, the left ventricle and the rest are separated, the left ventricle weight is weighed, and the weight ratio of the left ventricle to the body weight is calculated. The results are shown in FIG. 5.

As can be seen from fig. 5, the heart index of the sham operated rats was significantly reduced compared to the blank (n=5, #p <0.01, compared to the blank); the heart index of the rats in the sham operation group has a significant difference (n=5, delta P <0.01 and the ratio of the rats in the sham operation group to the model group), namely, the heart index of the rats in the model group is significantly increased compared with the sham operation group, which indicates that the rats in the model group have cardiac hypertrophy and the rest organs have no significant change; after administration, each administration group has an improving effect on cardiac index, and has no obvious toxic or side effect on other organs.

(4) Ventricular remodeling result detection:

hematoxylin-eosin staining (HE staining), one of the staining methods commonly used in paraffin section techniques. Hematoxylin dye solution is alkaline, and mainly causes chromatin in nuclei and nucleic acid in cytoplasm to be purple blue; eosin is an acid dye that primarily reds the cytoplasmic and extracellular matrix components. The application uses HE staining to stain hearts. Masson staining, one of the staining methods used to show fibers in tissue, collagen fibers appear blue and muscle fibers appear red.

Taking rat hearts, washing residual blood with normal saline, fixing with 4% paraformaldehyde, performing HE staining and Masson staining, observing images under a microscope, and evaluating ventricular remodeling conditions. The results are shown in fig. 6 and 7.

Fig. 6 shows HE staining results, wherein panel a is a blank group, panel B is a sham operation group, panel C is a model group, panel D is Sha Kuba troxartan group, panel E is a low dose group, panel F is a medium dose group, and panel G is a high dose group. The symptoms can be obviously improved to different degrees in each administration group (D-G graph), which shows that the pharmaceutical composition can reduce the infarct size and improve myocardial infarction.

The Masson staining results are shown in fig. 7, wherein the graph a is a blank group, the graph B is a sham operation group, the graph C is a model group, the graph D is Sha Kuba troxartan group, the graph E is a low dose group, the graph F is a medium dose group, and the graph G is a high dose group. After administration, the myocardial collagen fiber proliferation of rats in each administration group (D-G graph) is obviously reduced compared with that in a model group, which shows that the pharmaceutical composition can reduce myocardial infarction area, improve myocardial fibrosis and further inhibit ventricular remodeling.

From the results, the pharmaceutical composition can increase the left ventricular ejection fraction and the short-axis shortening rate, improve the heart structure and function, improve myocardial fibrosis, inhibit ventricular remodeling and further prevent and/or treat chronic heart failure in a chronic heart failure model caused by myocardial infarction.

Example 3 action of the pharmaceutical composition of the present application in animal models of TAC-induced chronic heart failure

Materials: the small animal ultrasonic instrument, sha Kuba triamcinolone acetonide and HE staining kit are the same as those of example 2; sirius red staining kit: g1018, a division of Sieve Biotechnology, wuhan Sieve. Animal selection: 160 male C56BL/6 mice with the age of 6-8 weeks, weight of 20+/-2 g, and sources: beijing Vitolihua laboratory animal technologies Co.

The constriction of the Transverse Aorta (TAC) can cause left ventricular afterload to be accentuated, mimicking chronic heart failure caused by clinical hypertension. After one week of adaptive feeding, mice were randomly divided into a blank group (15), a sham operation group (15) and a TAC operation group (130), wherein the blank group was not operated, the sham operation group was operated with the sham operation, and the TAC operation group was operated with the TAC operation. The model was validated on the basis of left room Ejection Fraction (EF) 4 weeks after surgery, with TAC surgery group mice EF at 30% -50%, it was seen that heart failure occurred in the mice 4 weeks after TAC surgery, indicating successful modeling.

TAC surgery mice were randomly grouped into 5 groups, each designated model group, sha Kuba valsartan group, low dose group, medium dose group, high dose group, each 12, depending on the administration.

The mice of each experimental group were dosed 1 time a day after the end of molding, and were dosed continuously by gastric lavage for 4 weeks. Wherein, the Sha Kuba/valsartan group is given with 1.3mg/mL Sha Kuba of a water solution of the trovartan sodium and the dosage is 0.1mL/10g; a low dose group to which 136.5mg/mL of the aqueous solution of pharmaceutical composition B of the present application was administered in an amount of 0.1mL/10g; a medium dose group to which 273mg/mL of the aqueous solution of pharmaceutical composition B of the present application was administered in an amount of 0.1mL/10g; a high dose group to which 546mg/mL of the aqueous solution of pharmaceutical composition B of the present application was administered in an amount of 0.1mL/10g; blank, sham and model groups were given 0.1mL/10g physiological saline daily per body weight. Among them, sha Kuba/l/sartan sodium is a commonly used drug for treating heart failure in the prior art, and is used as a positive control in the present application.

After the end of administration, the heart structure, heart function, organ indexes and ventricular remodeling conditions of the mice are detected, and the therapeutic effect of the pharmaceutical composition of the application on chronic heart failure after hypertension is evaluated.

(1) And (3) heart structure detection: after the last administration, the heart structure change condition of each group of mice is detected by using a small animal ultrasonic instrument, the result is shown in figure 8, and compared with a blank group and a false operation group, the upper chamber wall of a model group of mice is obviously thinned and flattened, the chamber wall movement is obviously weakened, obvious left chamber expansion occurs, and the heart structure change of the model group of mice is indicated, and heart failure symptoms occur; in each administration group, the wall thinning degree of the mice is obviously reduced, and the wall movement is enhanced; the pharmaceutical composition and the positive control drug can improve the heart structure change caused by heart failure.

(2) Heart function detection: the left ventricular ejection fraction, short axis shortening rate, end-diastolic ventricular septum thickness, end-systolic ventricular septum thickness, end-diastolic left ventricular inner diameter, end-systolic left ventricular inner diameter, end-diastolic left ventricular back wall thickness, end-systolic left ventricular back wall thickness, end-diastolic left ventricular volume, and end-systolic left ventricular volume were examined by a small animal sonicator, and as a result, as shown in fig. 9, it was found that the model group mice had significantly reduced left ventricular ejection fraction and short axis shortening rate, and the end-systolic left ventricular inner diameter, end-diastolic left ventricular back wall thickness, and end-systolic left ventricular back wall thickness (n=5, #p <0.05, compared to the sham group), and the end-diastolic ventricular septum thickness, the end-diastolic left ventricular inner diameter, the end-diastolic left ventricular volume, and the end-systolic left ventricular volume had a tendency to increase, indicating that the model group mice had developed myocardial hypertrophy and ventricular dilatation. After treatment with the positive drug and the pharmaceutical composition of the present application, the left ventricular ejection fraction of the mice in the low dose group was significantly improved compared to the model group, and the short-axis shortening rate of the mice in the Sha Kuba troxartan group, the low dose group and the medium dose group was significantly improved (n=5, P <0.05, compared to the model group); the low dose group and the high dose group mice had a significant improvement in left chamber diameter at systole compared to the model group, and had a trend to improve both left chamber volume at diastole and left chamber volume at systole (n=5, P <0.05 compared to the model group); the pharmaceutical composition can significantly improve the myocardial hypertrophy and the ventricular dilatation of mice, and has the effect of improving cardiac function.

(3) Organ weight and index detection:

drawing materials after detection by a small animal ultrasonic instrument, taking eyeballs for blood taking after anesthesia of each group of mice, taking cores, livers, spleens, lungs, kidneys, adrenals and left ventricles, peeling tissues around organs, weighing, and calculating each organ index compared with the body weight, wherein each organ index is the ratio of the weight of each organ to the body weight. The hind limb tibia on the right side of the mouse was taken, the length was measured with a vernier caliper, and the ratio of the heart weight to the tibia length was calculated. The results are shown in FIG. 10.

As can be seen from fig. 10, the heart weight, left ventricular weight, heart/weight ratio, left ventricular/weight ratio of the model mice were significantly increased compared to the sham group, and the heart weight/tibia length ratio tended to be increased (n=5, #p <0.05 compared to the sham group), i.e., the model mice exhibited myocardial hypertrophy, with no significant change in the remaining viscera; the heart weight and the left ventricle weight of the mice in the low-dose group and the high-dose group after administration have the tendency to be reduced, and the heart/weight ratio, the left ventricle/weight ratio and the heart weight/tibia length ratio also have the corresponding reduction, so that the pharmaceutical composition of the application can improve the myocardial hypertrophy of heart failure mice to a certain extent, and has no obvious toxic or side effect on other organs.

(4) Ventricular remodeling result detection:

sirius red staining is used to show one of the staining methods of fibers in tissue, collagen fibers are red and muscle fibers are yellow. The study takes mouse hearts, carries out HE staining and sirius red staining, and evaluates ventricular remodeling. The results are shown in fig. 11 and 12.

FIG. 11 is a HE staining result, wherein the right panel in each group is a partial enlarged view of the left panel; as can be seen from the left graph (field of view 1 mm) of each group, the hearts of the mice in the model group are obviously increased compared with the blank group and the sham operation group, the chamber walls (shown by thin arrows in the left graph) and the chamber spaces (shown by thick arrows in the left graph) are obviously thickened, and the heart chambers are enlarged and are obvious in myocardial hypertrophy; as can be seen from the right images (50 μm in visual field) of each group, mice in the blank group and the sham operation group have normal cardiac muscle and orderly myocardial cells, and mice in the model group have pathological phenotypes such as disorder, necrosis, loss of normal structure and the like (shown by arrows in the right images); the case phenotype of each administration group heart failure mouse is replaced by myocardial cells which are orderly arranged after administration, the heart volume is reduced, and the myocardial hypertrophy is improved.

FIG. 12 shows the result of sirius red staining, and it can be seen from the figure that the heart collagen fibers of mice in the model group are significantly increased (as shown by the arrow in the figure) compared with those in the blank group and the sham operation group, and the heart collagen fibers are represented as myocardial fibrosis. After administration, the cardiac collagen fibers of the mice in each administration group are obviously reduced compared with the model group, which shows that the pharmaceutical composition can reduce the cardiac collagen fibers, improve myocardial fibrosis and further inhibit ventricular remodeling.

From the results, the pharmaceutical composition can increase the left ventricular ejection fraction and the short-axis shortening rate, improve the heart structure and function, improve the cardiac hypertrophy and the ventricular dilatation, improve the cardiac fibrosis, inhibit the ventricular remodeling and further prevent and/or treat the chronic heart failure in a chronic heart failure model caused by hypertension.

Example 4 action of the pharmaceutical composition of the present application in an animal model of monocrotaline-induced chronic heart failure

Materials: millar pressure sensor catheter: AD Instruments; the small animal ultrasonic apparatus and the HE staining kit are the same as in example 2. Animal selection: sprague-Dawely (SD) healthy adult male rats 60, weight 230-250g, source: chinese food and drug inspection institute.

The monocrotaline is a pyrrolidine alkaloid extracted from monocrotaline seeds, and is converted into monocrotaline by mixed functional oxidase of liver in a rat body, the monocrotaline damages pulmonary vascular endothelial cells, thereby causing progressive proliferation of pulmonary artery smooth muscle cells, causing progressive increase of pulmonary artery pressure, further causing overload of right ventricular pressure, causing hypertrophy of right ventricle of the rat, and establishing a right heart failure model.

After one week of adaptive feeding, 50 rats were randomly assigned to a blank group, a model group, a low dose group, a medium dose group, and a high dose group, each group having 10 rats. Wherein, the single intraperitoneal injection of monocrotaline with the mass fraction of 2% of 60mg/kg (monocrotaline is dissolved in physiological saline-ethanol solution (physiological saline: absolute ethanol=8:2)) of each group except for a blank group is fed for 3 weeks to induce a right heart failure model, and the blank group is given 0.3mL/100g of physiological saline-ethanol solution (physiological saline: absolute ethanol=8:2) according to the body weight.

Rats in each experimental group were dosed 1 time daily for 3 weeks after molding, followed by continuous gavage. Wherein, the low dose group is given 55.125mg/mL of the aqueous solution of the pharmaceutical composition C of the application, and the dosage is 6mL/kg; a medium dose group to which 110.25mg/mL of the aqueous solution of pharmaceutical composition C of the present application was administered in an amount of 6mL/kg; a high dose group to which 220.5mg/mL of the aqueous solution of pharmaceutical composition C of the present application was administered in an amount of 6mL/kg; the blank group and the model group were administered with 6mL/kg of physiological saline per day according to the body weight.

Each group of rats was monitored daily for weight change starting on day one, a weight curve was drawn and each group of deaths was counted on day 42. After the end of administration, the right ventricular systolic pressure, the average pulmonary artery pressure, the right ventricular function, the organ indexes and the myocardial hypertrophy of the rat are detected, and the treatment effect of the pharmaceutical composition on chronic heart failure after pulmonary arterial hypertension is evaluated.

(1) Right ventricular systolic pressure, mean pulmonary arterial pressure detection: groups of rats were anesthetized with 3mg/kg chloral hydrate. The skin was first cut 1cm along the right side of the rat neck, exposing the right jugular vein. Then, the right jugular vein was separated passively, carefully separated, the distal end was ligated and then v-cut, a polyethylene catheter (PE-50) filled with heparin sodium solution was inserted into the vein using a Millar pressure sensor catheter, and the catheter was slightly fixed with the blood vessel with a suture to reduce bleeding. Slowly pushing the catheter, inserting the catheter into the right ventricle along the superior vena cava, adjusting the head angle of the catheter, observing and recording the right ventricular systolic pressure after the stable right ventricular systolic pressure waveform appears, and recording and analyzing data by using a PowerLab data acquisition system; the catheter angle was adjusted by rotation further into the pulmonary artery and the average pulmonary artery pressure was recorded for each group of rats. The results are shown in FIG. 13.

As can be seen from fig. 13, the right ventricular systolic pressure and the mean pulmonary artery pressure of the rats in the model group were significantly increased over that in the blank group (n=6, # # # P <0.0001, compared to the blank group); the low dose rats had significant improvement in right ventricular systolic pressure and mean pulmonary artery pressure (n=6, P <0.05, P <0.01, compared to the model group) after administration compared to the model group, and the medium dose rats had significant improvement in mean pulmonary artery pressure (n=6, P <0.05, compared to the model group), indicating that the pharmaceutical composition of the present application was able to significantly reduce right ventricular systolic pressure and mean pulmonary artery pressure in heart failure rats.

(2) Right ventricular function detection: the pulmonary artery acceleration time, pulmonary artery acceleration time/pulmonary artery ejection time, pulmonary artery pressure peak and tricuspid valve annulus displacement of each group of rats were detected by a small animal ultrasonic apparatus to evaluate the right ventricle function of the rats. The results are shown in FIG. 14. The results of fig. 14 show that the pulmonary artery acceleration time, pulmonary artery acceleration time/pulmonary artery ejection time, pulmonary artery pressure peak, tricuspid valve annulus displacement of rats in the model group were significantly reduced compared to the blank group (n=6, # # # P <0.0001 compared to the blank group), and that the pulmonary artery acceleration time/pulmonary artery ejection time, pulmonary artery pressure peak, tricuspid valve annulus displacement were significantly improved compared to the model group after administration of the medium dose group rats (n=6, # # P <0.05 compared to the model group); the tricuspid valve annulus displacement was significantly improved (n=6, P <0.05, P <0.001, compared to model), for both the low and high dose groups, and there was a trend towards improvement in pulmonary artery acceleration time, pulmonary artery acceleration time/pulmonary artery ejection time, pulmonary artery pressure peak. The medicine composition of the application has obvious improvement effect on the right heart function of rats after administration.

(3) And (3) detecting visceral organ indexes: after the pressure detection is finished, the abdominal cavity of the rat is opened, blood is taken from abdominal aorta, the thoracic cavity of the rat is opened, the lung, heart, liver, spleen and kidney are separated and taken, the lung index, liver index and spleen index are calculated compared with the body weight, the result is shown in fig. 15, and the result shows that the lung index, liver index and spleen index of the rat in the model group are obviously increased compared with that in the blank group (n=6, # # P <0.001, # # P <0.0001 and compared with the blank group), and the lung, liver and spleen edema of the rat in the model group are indicated. After administration, the liver index of the high-dose group rats is remarkably improved compared with the model group (n=6, P <0.05 compared with the model group), the lung index and spleen index of the low-dose group rats tend to be improved, and the kidneys are not remarkably changed; the pharmaceutical composition has obvious improvement effect on liver edema of rats, has a certain improvement effect on pulmonary edema and spleen edema, and has no obvious toxic or side effect on kidneys.

The entire atrial portion was trimmed along the lower edge of the mouse auricle, leaving the ventricles. The right ventricular hypertrophy was evaluated by shearing the right ventricular free wall along the ventricular septum edge, weighing the right ventricular free wall, and calculating the right ventricular hypertrophy index as compared to the weight of the left ventricle and the ventricular septum. The results of the heart index and right heart hypertrophy index of each group of rats are shown in fig. 15, and it can be seen that the heart index and right heart hypertrophy index of the rats in the model group are significantly increased (n=6, # # # P <0.0001, compared with the blank group), i.e., the rats in the model group have obvious right heart hypertrophy; after administration, the cardiac index of the rats in the medium dose group was significantly improved compared with the model group (n=6, P <0.05 compared with the model group), and the right cardiac hypertrophy index of the rats in the medium dose group and the high dose group was significantly improved compared with the model group (n=6, P <0.01, P <0.001 compared with the model group), indicating that the pharmaceutical composition of the present application can significantly reduce right cardiac hypertrophy, thereby significantly improving cardiac function.

(4) Myocardial hypertrophy detection:

taking the free wall of the right ventricle of the rat, washing the residual blood with normal saline, fixing with 4% paraformaldehyde, performing HE staining, observing images under a microscope, and analyzing the hypertrophy condition of myocardial cells. As a result, as shown in FIG. 16, it was found that the model rats had a myocardial texture disorder and myocardial cell hypertrophy; the symptoms are obviously improved after the pharmaceutical composition is given, which indicates that the pharmaceutical composition can obviously improve myocardial hypertrophy and inhibit the development of heart failure.

From the above results, the pharmaceutical composition can reduce right ventricular systolic pressure, reduce average pulmonary artery pressure, improve right ventricular function, reduce liver edema, improve pulmonary edema and spleen edema, reduce right cardiac hypertrophy and improve myocardial hypertrophy in a right ventricular heart failure model caused by pulmonary arterial hypertension, thereby preventing and/or treating chronic heart failure.

In summary, the pharmaceutical composition of the application has the effects of increasing left ventricular ejection fraction, increasing short axis shortening rate, improving heart structure, improving heart function, improving cardiac hypertrophy and ventricular dilatation, improving cardiac fibrosis and inhibiting ventricular remodeling in a chronic heart failure model caused by myocardial infarction or hypertension, and has the effects of reducing right cardiac hypertrophy and improving right ventricular function in a chronic heart failure model caused by pulmonary arterial hypertension, so that the pharmaceutical composition of the application can be used for preventing and/or treating chronic heart failure. In addition, in the LAD-induced animal model, the pharmaceutical composition can improve myocardial hypertrophy, ventricular dilatation and myocardial fibrosis; in a monocrotaline-induced right heart failure animal model, the pharmaceutical composition can reduce right ventricular systolic pressure, reduce average pulmonary artery pressure, relieve liver edema and improve pulmonary edema and spleen edema; the medicine composition can be used for treating complications caused by myocardial infarction, pulmonary hypertension and pulmonary hypertension.

The foregoing description is only of the preferred embodiments of the present application and is not intended to limit the scope of the present application. Any modifications, equivalent substitutions, improvements, etc. that are within the spirit and principles of the present application are intended to be included within the scope of the present application.

Claims

1. A traditional Chinese medicine composition for preventing and/or treating chronic heart failure is characterized by being prepared from the following raw materials: 4-60 parts of roasted astragalus, 1-9 parts of tetrandra root, 1-15 parts of semen lepidii, 3-20 parts of selfheal, 3-15 parts of radix salviae miltiorrhizae, 1-9 parts of bran-fried bighead atractylodes rhizome and 1-9 parts of liquorice.

2. The traditional Chinese medicine composition for preventing and/or treating chronic heart failure according to claim 1, which is characterized by being prepared from the following raw materials: 8-50 parts of roasted astragalus, 2-8 parts of tetrandra root, 3-12 parts of semen lepidii, 5-15 parts of selfheal, 4-12 parts of radix salviae miltiorrhizae, 3-9 parts of bran-fried bighead atractylodes rhizome and 2-8 parts of liquorice.

3. Decoction for preventing and/or treating chronic heart failure, characterized in that it is obtained by decocting the traditional Chinese medicine composition according to claim 1 or 2 with water and filtering.

4. A pharmaceutical composition for preventing and/or treating chronic heart failure, which is characterized by being prepared from the following raw materials in parts by weight: 4-60 parts of roasted astragalus, 1-9 parts of tetrandra root, 1-15 parts of semen lepidii, 3-20 parts of selfheal, 3-15 parts of radix salviae miltiorrhizae, 1-9 parts of bran-fried bighead atractylodes rhizome and 1-9 parts of liquorice.

5. The pharmaceutical composition for preventing and/or treating chronic heart failure according to claim 4, wherein the raw materials are: 8-50 parts of roasted astragalus, 2-8 parts of tetrandra root, 3-12 parts of semen lepidii, 5-15 parts of selfheal, 4-12 parts of radix salviae miltiorrhizae, 3-9 parts of bran-fried bighead atractylodes rhizome and 2-8 parts of liquorice.

6. The pharmaceutical composition for preventing and/or treating chronic heart failure according to any of claims 4-5, characterized in that the medicament is a tablet, capsule, granule, powder, patch, ointment, gel, suppository, solution, suspension or emulsion.

7. A method for preparing a pharmaceutical composition for preventing and/or treating chronic heart failure according to any one of claims 4-5, comprising the steps of subjecting the raw materials to reflux with a solvent, filtering and concentrating the filtrate.

8. The method of claim 7, comprising subjecting the feedstock to the steps of: heating and refluxing the raw materials for 2 times by using a solvent, wherein the mass ratio of the solvent volume to the raw materials is (6-10): 1, 1 st time for 2-3h, 2 nd time for 1-2h, filtering, combining filtrates, and concentrating the filtrate under reduced pressure.

9. Use of a traditional Chinese medicine composition according to any one of claims 1-2 or a decoction according to claim 3 or a pharmaceutical composition according to any one of claims 4-5 for the manufacture of a medicament for the prevention and/or treatment of chronic heart failure.