KR102178355B1 - Composition for treating heart disease - Google Patents

Abstract

The present application relates to a composition for treating heart disease, comprising gentisic acid.

Description

Composition for treating heart disease {COMPOSITION FOR TREATING HEART DISEASE}

The present application relates to a composition for treating heart disease, and in particular, to a composition for treating heart failure comprising gentisic acid.

Heart Failure (HF) refers to a group of diseases caused by the inability to properly supply the necessary blood to the body tissues due to a decrease in the relaxation function of the heart to accept blood or the contraction function to expel blood due to structural or functional abnormalities of the heart. . The most common and important symptom is difficulty breathing. Difficulty breathing is mainly caused by stagnation of blood in the heart (congestion), which increases the pressure to fill the ventricles, which causes blood to stagnate in the pulmonary blood vessels entering the heart, which can lead to coughing. Depending on the degree of dyspnea, dyspnea during exercise proceeds to dyspnea during exercise, dyspnea when lying down, and difficulty breathing at night with seizures.

The prevalence of heart failure is expected to increase steadily as the disease of patients with acute heart failure becomes chronic due to the aging of the population and the development of medical technology due to the increase in lifespan.In Korea, accurate statistics on the prevalence of heart failure have not been reported. It is estimated at 1 million. In addition, the number of heart failure patients is expected to increase as about 5.7 million new heart failure patients occur annually worldwide.

Republic of Korea Patent Publication No. 10-2011-0089671 relates to a method of manufacturing valsartan and a novel intermediate used therein. According to the manufacturing method of the above patent, high-purity valsartan can be obtained in high yield as an angiotensin II receptor antagonist, which is useful as an effective therapeutic agent for hypertension, heart failure, or myocardial infarction. Although angiotensin converting enzyme inhibitors or angiotensin receptor antagonists are used as the primary treatment for heart failure, the mortality rate due to heart failure is still high. In addition, congestion in the lungs occurs in heart failure, and drugs that can improve these symptoms can help improve heart failure. Therefore, the development of a new therapeutic agent capable of suppressing side effects is urgent.

The present application is to solve the problems of the prior art described above, and an object thereof is to provide a composition for treating heart disease.

However, the technical problem to be achieved by the embodiments of the present application is not limited to the technical problems as described above, and other technical problems may exist.

As a technical means for achieving the above technical problem, the first aspect of the present application provides a composition for treating heart disease, comprising gentisic acid.

According to one embodiment of the present application, the heart disease is heart failure, cardiac hypertrophy, cardiac fibrosis, angina pectoris, myocardial infarction, arteriosclerosis, heart valve disease, high blood pressure, hypotension, pulmonary heart, arrhythmia, ventricular fibrillation, pericarditis, endocarditis, and combinations thereof It may include a disease selected from the group consisting of, but is not limited thereto.

According to the exemplary embodiment of the present disclosure, the composition may be to reduce a heart weight (HW)/body weight (BW) ratio, but is not limited thereto.

According to the exemplary embodiment of the present disclosure, the composition may be to inhibit cardiac fibrosis, but is not limited thereto.

According to the exemplary embodiment of the present disclosure, the composition may be to inhibit type II pneumocyte hyperplasia, but is not limited thereto.

According to the exemplary embodiment of the present disclosure, the composition may further include a pharmaceutically acceptable carrier, but is not limited thereto.

According to an embodiment of the present application, the carrier is one selected from the group consisting of a buffer solution, sterile water for injection, general saline or phosphate buffered saline, sucrose, histidine, salt, polysorbate, and combinations thereof. However, it is not limited thereto.

According to the exemplary embodiment of the present disclosure, the composition may be administered by injection, oral administration or transdermal administration, but is not limited thereto.

The above-described problem solving means are merely exemplary and should not be construed as limiting the present application. In addition to the above-described exemplary embodiments, additional embodiments may exist in the drawings and detailed description of the invention.

According to the above-described problem solving means of the present application, the composition for treating heart disease of the present application can improve cardiac hypertrophy and cardiac fibrosis. More specifically, the composition for treating heart disease of the present application can restore a reduced left ventricular ejection fraction (EF) to a normal level that occurs in heart failure.

In addition, the composition for treating heart disease of the present application has an effect of blocking the activity of the renin-angiotensin system (RAS) in the tissue. The activity of the renin-angiotensin system is closely related to heart failure and hypertension.

In addition, even when the size of the lungs is increased due to congestion of the lungs and various diseases, the weight of the lungs can be reduced by the composition for treating heart disease of the present application.

Figure 1 (a) is a graph showing the EF value of heart failure according to each experimental group, and Figure 1 (b) is a graph showing the heart weight (HW) / body weight (BW) ratio according to each experimental group.
Figure 2 (a) is a picture comparing the size of the heart according to each experimental group, Figure 2 (b) is a graph showing the mRNA change of ANP according to each experimental group, Figure 2 (c) is according to each experimental group It is a graph showing the change in the mRNA of BNP, Figure 2 (d) is a graph showing the change in mRNA of skeletal α-actin according to each experimental group.
3(a) is an image of the result of Masson trichrome staining according to each experimental group, and FIG. 3(b) is a quantitative value of Masson trichrome staining according to each experimental group.
Figure 4 (a) is a graph showing the mRNA change of TGF-β1 according to each experimental group, Figure 4 (b) is a graph showing the mRNA change of collagen III according to each experimental group, Figure 4 (c) is It is a graph showing the mRNA change of fibronectin according to each experimental group, Figure 4 (d) is a graph showing the mRNA change of CTGF according to each experimental group, Figure 4 (e) is a graph showing the mRNA change of SMA according to each experimental group It is a graph.
Figure 5 (a) is a picture comparing the size of the lungs according to each experimental group, Figure 5 (b) is a graph showing the lung weight (LW) / body weight (BW) ratio according to each experimental group.
6 is an image showing H&E staining results according to each experimental group.

Hereinafter, exemplary embodiments of the present application will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art may easily implement the present application.

However, the present application may be implemented in various different forms and is not limited to the embodiments described herein. In addition, in the drawings, parts not related to the description are omitted in order to clearly describe the present application, and similar reference numerals are attached to similar parts throughout the specification.

Throughout this specification, when a part is said to be "connected" with another part, this includes not only the case that it is "directly connected", but also the case that it is "electrically connected" with another element interposed therebetween. do.

Throughout this specification, when a member is positioned "on", "upper", "upper", "under", "lower", and "lower" of another member, this means that a member is located on another member. It includes not only the case of contacting but also the case of another member being present between the two members.

Throughout the specification of the present application, when a certain part "includes" a certain component, it means that other components may be further included rather than excluding other components unless specifically stated to the contrary.

As used herein, the terms "about", "substantially" and the like are used at or close to the numerical value when manufacturing and material tolerances specific to the stated meaning are presented, and to aid understanding of the present application In order to prevent unreasonable use by unscrupulous infringers of the stated disclosures, either exact or absolute figures are used. In addition, throughout the specification of the present application, "step to" or "step of" does not mean "step for".

In the entire specification of the present application, the term "combination of these" included in the expression of the Makushi format refers to one or more mixtures or combinations selected from the group consisting of the components described in the expression of the Makushi format, and the component It means to include one or more selected from the group consisting of.

Throughout this specification, the description of "A and/or B" means "A or B, or A and B".

Throughout the present specification, "heart disease" means a disease in which a disease occurs in the heart.

Hereinafter, a composition for treating heart disease of the present application will be described in detail with reference to embodiments and examples and drawings. However, the present application is not limited to these embodiments and examples and drawings.

The first aspect of the present application provides a composition for treating heart disease, including gentisic acid.

The gentisic acid is one of dihydroxy benzoic acid. The gentisic acid is a derivative of benzoic acid, a metabolic decomposition product of aspirin, and is secreted by the liver. The gentisic acid includes not only gentisic acid represented by the following formula (1), but also all possible derivatives that can be prepared therefrom:

[Formula 1]

.

.

The composition for treating heart disease comprising gentisic acid according to the present application may be used as a preventive and therapeutic agent for heart failure. The gentisic acid may also improve cardiac hypertrophy and cardiac fibrosis. More specifically, the gentisic acid can restore the reduced left ventricular ejection fraction (EF) in heart failure to a normal level. In addition, the composition for treating heart disease of the present application has an effect of blocking the activity of the renin-angiotensin system (RAS) in the tissue. The activity of the renin-angiotensin system is closely related to heart failure and hypertension. In addition, even when the size of the lungs is increased due to pulmonary congestion and various diseases, the weight of the lungs can be reduced by gentisic acid.

According to one embodiment of the present application, the heart disease is heart failure, cardiac hypertrophy, cardiac fibrosis, angina pectoris, myocardial infarction, arteriosclerosis, heart valve disease, high blood pressure, hypotension, pulmonary heart, arrhythmia, ventricular fibrillation, pericarditis, endocarditis, and combinations thereof It may include a disease selected from the group consisting of, but is not limited thereto.

The heart failure refers to a disease that occurs when the heart fails to properly supply the necessary blood to the body tissues due to a decrease in the filling function (relaxation function) or the pump function (contraction function) that the heart receives blood due to a structural or functional abnormality of the heart. do.

The hypertrophy of the heart refers to a state in which the weight of the heart muscle increases due to the thickening of the heart, especially the ventricular wall (muscle). The basic concept of hypertrophy refers to a case in which a specific organ grows due to an increase in the volume of individual cells irrespective of the change in the number of cells for some reason. Cardiac hypertrophy occurs when the heart continuously does excessive work, and is also called cardiac hypertrophy.

The cardiac fibrosis refers to a phenomenon in which a part of the heart is hardened for some reason.

The angina refers to a disease that occurs when cardiovascular is narrowed due to causes such as arteriosclerosis, blood clots, and convulsions (spasm), and ischemia occurs in the myocardium.

The myocardial infarction refers to a disease in which cardiac blood vessels are blocked by a cause such as blood clots or spasms, and thus the heart muscle is damaged.

The arteriosclerosis refers to a senile lesion of an artery in which the elasticity of the arterial wall is lost and the lumen of the blood vessel is narrowed by the thickening of the wall and the deposition of lipids therein. Atherosclerosis is the basis for stroke and myocardial infarction.

The cardiac valvosis refers to a disease in which the valve is damaged due to various causes and thus abnormalities in the control function occur, and is generally divided into two types of stenosis and obstructive insufficiency.

The hypertension refers to a case where, for example, the highest blood pressure is 140 mmHg or more and the lowest blood pressure is 90 mmHg or more in a stable state. The level of hypertension is not recognized by one measurement, and when the maximum blood pressure is 140 mmHg or more and the diastolic blood pressure is 90 mmHg or more, measured at least twice or more in a stable state, it is called hypertension.

The hypotension refers to, for example, a diastolic blood pressure of 60 mmHg and a systolic blood pressure of 100 mmHg or less. When blood pressure decreases, the body reduces blood supply to organs that are not important for maintaining life, such as skin or muscles, and performs a compensatory action to increase blood supply to vital organs such as the brain, heart, and kidneys (kidneys). However, when the compensation function reaches its limit, the blood supply to the vital organs eventually decreases, leading to dysfunction, and life is endangered, which is also called'shock'.

The pulmonary heart refers to a state in which the vascular resistance of the pulmonary artery increases due to pulmonary disease, resulting in poor blood flow, resulting in malfunction of the right ventricle. Pulmonary heart is divided into acute and chronic, and acute is due to pulmonary embolism and pulmonary infarction. Chronic is caused by chronic lung diseases such as emphysema, bronchial asthma, pulmonary tuberculosis, silicosis, chronic bronchitis, and bronchiectasis.

The arrhythmia means the heart beating irregularly. The heart beats regularly about 60 times a minute in adults. However, too fast, late or irregular pulse beats are called arrhythmias.

The ventricular fibrillation refers to a state in which each part of the ventricle contracts randomly and irregularly in the beating of the heart.

The pericarditis refers to inflammation of the pericardium, and invades any of the inner and outer lobes of the pericardium, and is sometimes localized, but is usually multidisciplinary, and most often occurs secondary to systemic diseases, or may occur sequentially with other diseases.

The endocarditis refers mainly to infectious endocarditis, and refers to inflammation of the heart valve or the innermost membrane of the heart.

In order to investigate the possibility that gentisic acid can be used as a treatment for heart failure, heart failure animals were made using transverse aortic constriction (hereinafter referred to as'TAC'). After 6 weeks of TAC surgery, it was confirmed that cardiac function declined through echocardiography. After the composition containing gentisic acid was administered orally at 100 mg/kg daily for 3 weeks, changes in the expression of echocardiography, heart weight ratio, lung weight ratio, cardiac hypertrophy marker and fibrosis-related markers were investigated.

According to the exemplary embodiment of the present disclosure, the composition may be to reduce a heart weight (HW)/body weight (BW) ratio, but is not limited thereto. In heart failure, the decreased left ventricular ejection was recovered to the control level by the composition, and the heart weight ratio and lung weight ratio were recovered to a similar degree to that of the control group. This will be described in more detail later with reference to FIGS. 1B and 5B in an experimental example.

According to the exemplary embodiment of the present disclosure, the composition may be to inhibit cardiac fibrosis, but is not limited thereto. The expression of cardiac hypertrophy markers and fibrosis-related genes were also significantly reduced by the composition. This will be described in more detail later with reference to FIGS. 2 (b) to (d), 3 (a) and (b), and 4 (a) to (d) in an experimental example.

According to the exemplary embodiment of the present disclosure, the composition may be to inhibit type II pneumocyte hyperplasia, but is not limited thereto. In heart failure animals, type II pneumocyte hyperplasia is found in many lung tissues and the normal alveolar space is small. However, there is no such phenomenon due to the composition, and it shows normal findings as in the control group. Therefore, the composition showed a much better effect on reducing cardiac function and pathological structural changes of the lungs than bisoprolol, a beta-blocker used in clinical practice (Example Group E). This will be described later in more detail with reference to FIG. 6 in the experimental example.

Based on these results, it is suggested that gentisic acid is highly likely to be used as a treatment for heart failure.

According to the exemplary embodiment of the present disclosure, the composition may further include a pharmaceutically acceptable carrier, but is not limited thereto.

According to an embodiment of the present application, the carrier is one selected from the group consisting of a buffer solution, sterile water for injection, general saline or phosphate buffered saline, sucrose, histidine, salt, polysorbate, and combinations thereof. However, it is not limited thereto.

According to the exemplary embodiment of the present disclosure, the composition may be administered by injection, oral administration or transdermal administration, but is not limited thereto. The composition may be administered once a day or divided into several times a day.

The dosage of the composition according to the present invention is preferably adjusted appropriately according to the use, purpose of use, the condition of the patient, age, sex, weight, type of disease, degree of disease, drug type, administration route and duration. The effective dosage of the composition may be 10 mg/kg to 200 mg/kg. For example, the effective dosage of the composition is 10 mg/kg to 200 mg/kg, 10 mg/kg to 190 mg/kg, 10 mg/kg to 180 mg/kg, 10 mg/kg to 170 mg/kg , 10 mg/kg to 160 mg/kg, 10 mg/kg to 150 mg/kg, 10 mg/kg to 140 mg/kg, 10 mg/kg to 130 mg/kg, 10 mg/kg to 120 mg/kg , 10 mg/kg to 110 mg/kg, 20 mg/kg to 200 mg/kg, 20 mg/kg to 190 mg/kg, 20 mg/kg to 180 mg/kg, 20 mg/kg to 170 mg/kg , 20 mg/kg to 160 mg/kg, 20 mg/kg to 150 mg/kg, 20 mg/kg to 140 mg/kg, 20 mg/kg to 130 mg/kg, 20 mg/kg to 120 mg/kg , 20 mg/kg to 110 mg/kg, 30 mg/kg to 200 mg/kg, 30 mg/kg to 190 mg/kg, 30 mg/kg to 180 mg/kg, 30 mg/kg to 170 mg/kg , 30 mg/kg to 160 mg/kg, 30 mg/kg to 150 mg/kg, 30 mg/kg to 140 mg/kg, 30 mg/kg to 130 mg/kg, 30 mg/kg to 120 mg/kg , 30 mg/kg to 110 mg/kg, 40 mg/kg to 200 mg/kg, 40 mg/kg to 190 mg/kg, 40 mg/kg to 180 mg/kg, 40 mg/kg to 170 mg/kg , 40 mg/kg to 160 mg/kg, 40 mg/kg to 150 mg/kg, 40 mg/kg to 140 mg/kg, 40 mg/kg to 130 mg/kg, 40 mg/kg to 120 mg/kg , 40 mg/kg to 110 mg/kg, 50 mg/kg to 200 mg/kg, 50 mg/kg to 190 mg/kg, 50 mg/kg to 180 mg/kg, 50 mg/kg to 170 mg/kg, 50 mg/kg to 160 mg/kg, 50 mg/kg to 150 mg/kg, 50 mg/kg to 140 mg/kg, 50 mg/kg to 130 mg/kg, 50 mg/kg to 120 mg/kg, 50 mg/kg to 110 mg/kg, 60 mg/kg to 200 mg/kg, 60 mg/kg to 190 mg/kg, 60 mg/kg to 180 mg/kg, 60 mg/kg to 170 mg/kg, 60 mg/kg to 160 mg/kg, 60 mg/kg to 150 mg/kg, 60 mg/kg to 140 mg/kg, 60 mg/kg to 130 mg/kg, 60 mg/kg to 120 mg/kg, 60 mg/kg to 110 mg/kg, 70 mg/kg to 200 mg/kg, 70 mg/kg to 190 mg/kg, 70 mg/kg to 180 mg/kg, 70 mg/kg to 170 mg/kg, 70 mg/kg to 160 mg/kg, 70 mg/kg to 150 mg/kg, 70 mg/kg to 140 mg/kg, 70 mg/kg to 130 mg/kg, 70 mg/kg to 120 mg/kg, 70 mg/kg to 110 mg/kg, 80 mg/kg to 200 mg/kg, 80 mg/kg to 190 mg/kg, 80 mg/kg to 180 mg/kg, 80 mg/kg to 170 mg/kg, 80 mg/kg to 160 mg/kg, 80 mg/kg to 150 mg/kg, 80 mg/kg to 140 mg/kg, 80 mg/kg to 130 mg/kg, 80 mg/kg to 120 mg/kg, 80 mg/kg to 110 mg/kg, 90 mg/kg to 200 mg/kg, 90 mg/kg to 190 mg/kg, 90 mg/kg to 180 mg/kg, 90 mg/kg to 170 mg/kg, 90 mg/kg to 160 mg/kg, 90 mg/kg to 150 mg/kg, It may be 90 mg/kg to 140 mg/kg, 90 mg/kg to 130 mg/kg, 90 mg/kg to 120 mg/kg, 90 mg/kg to 110 mg/kg. Preferably, the effective dosage of the composition may be 100 mg/kg.

The present invention will be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present application.

[Example]

Preparation of experimental animals

All animal experiments were performed in accordance with the Guide to the Care and Use of Laboratory Animals (National Institute of Health, 8th edition, 2011) with approval of the Animal Testing Committee (CNU IACUC-H-2018-4) of Chonnam National University Medical School.

Cause heart failure

CD-1 male mice were anesthetized by intraperitoneal injection of a mixture of ketamine and xylazine, followed by partial aortic ligation (TAC). In the control group, the procedure was the same except that the blood vessels were not tied. A ventilator was used to allow the mice to breathe, and the thymus gland was removed, and the transverse aortic arch was tied with a 27 gauge needle using a 7-0 silk suture. The success of the TAC operation was confirmed by echocardiography. Three weeks after TAC surgery, drugs were administered by mouth to mice for three weeks.

The experimental group is divided into 5 groups, specifically, the control group (Sham), the TAC surgery group (TAC), and the TAC group (10 mg/kg/day) administered with low concentration of gentisic acid (Sigma) (TAC+Gentisic acid ( 10)), TAC group administered with high concentration of gentisic acid (Sigma) (100mg/kg/day) (TAC+Gentisic acid (100)), TAC group administered with bisoprolol (Selleck Chemicals) (0.5 mg/day) kg/day) (TAC+Bisoprolol (0.5)).

Heart function evaluation

The echocardiography was performed using a 13-MHz linear array converter and a Vivid S5 echocardiography system. Mice were anesthetized using tribromoethanol (avertin, 114 mg/kg, intraperitoneal injection). M-mode images and parameters were obtained from the long axis of the left ventricle of the papillary muscle. The posterior wall thickness, septum, left ventricular end systolic and diastolic diameter were measured in M mode. Fractional shortening (hereinafter referred to as'FS') and left ventricular ejection fraction (hereinafter referred to as'EF') were calculated. FS=(diastolic inner diameter-systolic inner diameter)/diastolic inner diameter×100%. EF=[(diastolic inner diameter cube-systolic inner diameter cube)/diastolic inner diameter cube]×100%.

Heart weight analysis and marker identification

Finally, 6 weeks after TAC surgery, the mice were killed, the heart and lungs were weighed, and the body weight was measured to determine the heart weight (HW)/body weight (BW) ratio. MRNA changes such as atrial natriuretic peptide (hereinafter referred to as'ANP'), brain natriuretic peptide (hereinafter referred to as'BNP'), and skeletal α-actin used as markers of cardiac hypertrophy and heart failure Was investigated by qRT-PCR. In addition, changes in proteins of ANP and BNP were confirmed by western blot method.

Cardiac fibrosis analysis

In order to analyze cardiac fibrosis occurring during heart failure, it was stained using Masson's trichrome staining method. As a method of knowing that collagen is formed, the area stained in blue is the area where collagen is deposited. Changes in mRNA and proteins such as collagen I, collagen III, CTGF, fibronectin, and smooth muscle α-actin, which are markers of fibrosis, were investigated.

Lung analysis

The change in the weight of the lungs was measured and pictures were taken. In addition, hematoxylin&eosin (hereinafter referred to as'H&E') staining was performed to measure vascular changes in the lungs.

[Experimental Example]

Figure 1 (a) is a graph showing the EF value of heart failure according to each experimental group, and Figure 1 (b) is a graph showing the heart weight (HW) / body weight (BW) ratio according to each experimental group.

Referring to (a) and (b) of FIG. 1, it is shown that gentisic acid significantly recovered the EF value of heart failure induced by TAC, and significantly reduced the increase in heart weight ratio.

Figure 2 (a) is a picture comparing the size of the heart according to each experimental group, Figure 2 (b) is a graph showing the mRNA change of ANP according to each experimental group, Figure 2 (c) is according to each experimental group It is a graph showing the change in the mRNA of BNP, Figure 2 (d) is a graph showing the change in mRNA of skeletal α-actin according to each experimental group.

Referring to (a) to (d) of FIG. 2, it is shown that gentisic acid inhibits cardiac hypertrophy and reduces the expression of cardiac hypertrophy markers in an animal model of heart failure. In particular, it can be seen that the higher the concentration of gentisic acid, the greater the effect of suppressing cardiac hypertrophy and reducing the expression of cardiac hypertrophy markers.

3(a) is an image of the result of Masson trichrome staining according to each experimental group, and FIG. 3(b) is a quantitative value of Masson trichrome staining according to each experimental group.

Referring to (a) and (b) of FIG. 3, the result of Masson trichrome staining showing that gentisic acid inhibits fibrosis of interstitial and perivascular interstitial and perivascular fibrosis in cardiac tissues in heart failure animal models. to be.

Figure 4 (a) is a graph showing the mRNA change of TGF-β1 according to each experimental group, Figure 4 (b) is a graph showing the mRNA change of collagen III according to each experimental group, Figure 4 (c) is It is a graph showing the mRNA change of fibronectin according to each experimental group, Figure 4 (d) is a graph showing the mRNA change of CTGF according to each experimental group, Figure 4 (e) is a graph showing the mRNA change of SMA according to each experimental group It is a graph.

Referring to FIGS. 4A to 4E, qRT- that gentisic acid reduces the expression of fibrotic markers (TGF-β1, collagen III, fibronectin, CTGF, SMA) expressed in cardiac tissues of heart failure animal models. You can check the PCR result. In particular, it can be seen that the higher the concentration of gentisic acid, the greater the effect of reducing the expression of fibrotic markers.

Figure 5 (a) is a picture comparing the size of the lungs according to each experimental group, Figure 5 (b) is a graph showing the lung weight (LW) / body weight (BW) ratio according to each experimental group.

5A and 5B, it is a result that gentisic acid significantly reduces the size of the lungs of the heart failure animal model by the level of the control group. In particular, it can be seen that the higher the concentration of gentisic acid, the smaller the lung size of the heart failure animal model and the lower the lung weight (LW)/body weight (BW) ratio.

6 is an image showing the H&E staining results according to each experimental group.

Referring to FIG. 6, H&E staining results show that gentisic acid normalizes the pathological structure of the lungs of the animal model of heart failure and suppresses type II pneumocyte hyperplasia. In particular, it can be seen that the higher the concentration of gentisic acid, the more inhibited the type II pneumocyte hyperplasia in the heart failure animal model as much as the control level.

The foregoing description of the present application is for illustrative purposes only, and those of ordinary skill in the art to which the present application pertains will be able to understand that other specific forms can be easily modified without changing the technical spirit or essential features of the present application. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not limiting. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as being distributed may also be implemented in a combined form.

The scope of the present application is indicated by the claims to be described later rather than the detailed description, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present application.

Claims (8)

In the composition for treating heart disease, comprising gentisic acid as an active ingredient,
The composition for treating heart disease blocks the activity of the renin-angiotensin system (RAS) in the tissue and reduces the weight of the lungs,
The heart disease is heart failure or cardiac hypertrophy,
Composition for treating heart disease.
delete The method of claim 1,
The composition is to reduce the heart weight (HW) / body weight (BW) ratio, a composition for treating heart disease.
The method of claim 1,
The composition is to inhibit cardiac fibrosis, a composition for treating heart disease.
The method of claim 1,
The composition is to inhibit type 2 pneumonia hyperplasia (type II pneumocyte hyperplasia), a composition for treating heart disease.
The method of claim 1,
The composition further comprises a pharmaceutically acceptable carrier, a composition for treating heart disease.
The method of claim 6,
The carrier is a buffer solution, sterile water for injection, general saline, phosphate buffered saline, sucrose, histidine, salt, polysorbate, including those selected from the group consisting of combinations thereof, heart disease treatment composition.
The method of claim 1,
The composition is to be administered by injection, oral administration or transdermal administration route, a composition for treating heart disease.

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