Application of oxibenzophenone in preparation of medicine for treating pathological cardiac hypertrophy and / or heart failure

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of oxibenzophenone in preparation of a medicine for treating pathological cardiac hypertrophy and / or heart failure. Research results in myocardial cells of primary newborn rats show that Exibenzophenone can inhibit pathological hypertrophy of myocardial cells induced by phenylephrine (PE). Animal experiments show that the epoxybenzophenone can improve cardiac dysfunction induced by aortic arch constriction (TAC) and reduce cardiac hypertrophy and cardiac tissue fibrosis. The invention provides a new drug research and development approach and a drug action target for treating pathological cardiac hypertrophy and heart failure, and has very important medicinal value.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to the use of ethyphenidone in the preparation of a drug for treating pathological myocardial hypertrophy and / or heart failure. Background Art

[0002] Cardiovascular disease is one of the most serious health hazards to human health. Pathological cardiac hypertrophy (CH) is a key pathological basis and a common pathological stage in the progression of various cardiovascular diseases to heart failure. With the increasing aging of the population, the number of people suffering from heart failure is expected to rise further, undoubtedly posing a serious challenge to the prevention and treatment of cardiovascular diseases. During the course of cardiovascular disease, the patient's heart is chronically stimulated by multiple factors such as elevated blood pressure and myocardial damage, which can gradually develop into CH and ultimately into heart failure, a process that has a profound negative impact on the patient's prognosis. Currently, although clinical treatment options include β-blockers, calcium channel blockers, antiarrhythmic drugs, disopyramide, spironolactone, and simvastatin, these drugs primarily focus on symptom improvement and are unable to fundamentally inhibit the pathological progression of CH. Therefore, there is an urgent need to explore new and more effective strategies for the intervention of CH to improve the prognosis of patients with cardiovascular disease and reduce the incidence of heart failure.

[0003] Exifone, chemically known as 2,3,3',4,4',5'-hexahydroxybenzophenone, is a benzophenone molecule synthesized in France in the 1970s. Initial studies found this compound to be beneficial in treating microcirculatory disorders and led to its development as a mind-enhancing agent, primarily for improving cognitive function in Alzheimer's and Parkinson's diseases. The benzophenone structure of exifone makes it an excellent UV absorber, while its polyhydroxybenzene properties contribute to its strong antioxidant activity and tyrosinase inhibition. Exifone also exhibits free radical scavenging properties, leading to the synthesis of structurally related derivatives as neuroprotective antioxidants. Furthermore, exifone has been shown to be a potent activator of histone deacetylase 1 (HDAC1), demonstrating neuroprotective effects on neurons derived from induced pluripotent stem cells from patients with tauopathies. However, currently, there is no application of ethoxybenzone in the preparation of drugs for pathological myocardial hypertrophy and heart failure on the market. Summary of the Invention

[0004] The purpose of the present invention is to provide the use of ethyphenidyl in the preparation of drugs for treating pathological myocardial hypertrophy and / or heart failure. The present invention's research shows that ethyphenidyl can inhibit pathological hypertrophy of myocardial cells induced by phenylephrine (PE), improve cardiac dysfunction induced by aortic arch constriction (TAC), and reduce myocardial hypertrophy and cardiac tissue fibrosis. It provides a new drug development approach and drug target for the treatment of pathological myocardial hypertrophy and heart failure, and has very important pharmaceutical value. In-depth exploration of the mechanism of action of ethyphenidyl in pathological myocardial hypertrophy not only has important theoretical research significance, but is also likely to provide new intervention strategies for the treatment of cardiovascular diseases, and has significant clinical application value.

[0005] The present invention provides the use of ethyphenidone in preparing a medicine for treating pathological myocardial hypertrophy and / or heart failure.

[0006] As a preferred embodiment, the pathological myocardial hypertrophy includes at least one of the following: cardiac dysfunction, myocardial cell hypertrophy and increased degree of fibrosis.

[0007] The present invention also provides the use of ethyphenone in preparing medicine for improving cardiac dysfunction.

[0008] The present invention also provides the use of ethyphenone in preparing a medicine for reducing myocardial hypertrophy.

[0009] The present invention also provides the use of ethyphenone in preparing a medicine for reducing cardiac tissue fibrosis.

[0010] The present invention also provides a medicine for treating pathological myocardial hypertrophy and / or heart failure, wherein the active ingredients include ethoxybenzone and pharmaceutically acceptable excipients.

[0011] As a preferred embodiment, the pharmaceutically acceptable excipients include: one or more of a buffer, an encapsulating agent, a filler, an adhesive, a transdermal absorbent, a wetting agent, a disintegrant, an absorption accelerator, a surfactant, a colorant, a flavoring agent and an adsorption carrier.

[0012] As a preferred embodiment, the drug is in the form of tablets, pills, powders, granules, capsules, decoctions, injections or suppositories.

[0013] As a preferred embodiment, the dosage of ethyphenidone is 25 to 75 mg / kg based on the body weight of the mouse.

[0014] As a preferred embodiment, when the drug is in the form of an injection, it further comprises a solvent, and the solvent includes an animal solvent and a cell solvent;

[0015] The animal solvent includes: 5% DMSO + 30% PEG300 + 5% Tween 80 + 60% PBS;

[0016] The cell solvent includes: DMSO.

[0017] Beneficial effects: The present invention provides the use of isoflurane in the preparation of drugs for the treatment of pathological myocardial hypertrophy and / or heart failure. The research results of the present invention in primary neonatal rat cardiomyocytes showed that isoflurane can inhibit the pathological hypertrophy of cardiomyocytes induced by phenylephrine (PE). Animal experiments have shown that isoflurane can improve cardiac dysfunction induced by aortic arch constriction (TAC), reduce myocardial hypertrophy and cardiac tissue fibrosis. The present invention provides a new drug development approach and drug target for the treatment of pathological myocardial hypertrophy and heart failure, and has very important pharmaceutical value. In-depth exploration of the mechanism of action of isoflurane in pathological myocardial hypertrophy not only has important theoretical research significance, but is also likely to provide new intervention strategies for the treatment of cardiovascular diseases, and has significant clinical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments are briefly introduced below.

[0019] Figure 1 The results of CCK8 cell survival assay in cardiomyocytes treated with different concentrations of Exifone in Example 1; N=8, ***, P<0.001;

[0020] Figure 2 The area of ​​cardiomyocytes after Exifone treatment detected by immunofluorescence staining in Example 2; A is a phenotypic diagram, scale: 100 μm; B is a statistical diagram; N=6, **, P<0.01; ***, P<0.001;

[0021] Figure 3 The results of cardiac function tests after treatment of mice with different concentrations of Exifone in Example 3 are shown; A is a representative image of mouse cardiac ultrasound; B is the statistical results of ejection fraction (EF) of mouse cardiac ultrasound; C is the statistical results of fractional shortening (FS) of mouse cardiac ultrasound;

[0022] Figure 4 The results of HE staining of the heart, liver, spleen, lung, and kidney tissue structures of mice treated with different concentrations of Exifone in Example 3 are shown;

[0023] Figure 5These are the cardiac function test results of mice with TAC-induced pathological myocardial hypertrophy treated with Exifone in Example 4; A is a representative image of mouse cardiac ultrasound; B is the statistical results of ejection fraction (EF) of mouse cardiac ultrasound; C is the statistical results of fractional shortening (FS) of mouse cardiac ultrasound; *, P < 0.05; **, P < 0.01; ***, P < 0.001;

[0024] Figure 6 This is the result of Exifone treatment in Example 4 that can reduce TAC-induced mouse heart weight, where A is the mouse heart weight; B is the result of mouse heart weight relative to tibia length; ***, P<0.001;

[0025] Figure 7 The results of WGA staining to measure the myocardial cross-sectional area in mice with TAC-induced pathological myocardial hypertrophy treated with Exifone; A is a representative image of the myocardial cross-sectional area of ​​mice stained with WGA, with the green color representing the outline of myocardial tissue cells labeled with WGA. Scale bar: 50 μm; B is the statistical results of the myocardial cross-sectional area of ​​each treatment group after WGA staining; **, P < 0.01; ***, P < 0.001;

[0026] Figure 8 The results of Masson staining to detect cardiac fibrosis in mice with TAC-induced pathological myocardial hypertrophy treated with Exifone; A is a representative image of cardiac fibrosis in mice stained with Masson staining, with blue representing the cardiac fibrosis area, scale bar: 100 μm; B is the statistical result of the percentage of cardiac fibrosis area in each treatment group after Masson staining; ***, P < 0.001. DETAILED DESCRIPTION

[0027] The present invention provides the use of ethyphenidol in the preparation of a medicament for treating pathological myocardial hypertrophy and / or heart failure. As a specific embodiment, the pathological myocardial hypertrophy includes at least one of the following: cardiac dysfunction, myocardial cell hypertrophy, and increased degree of fibrosis.

[0028] The present invention also provides the use of exifone in the preparation of a medicament for ameliorating cardiac dysfunction. Examples of the present invention demonstrate that exifone can inhibit PE-induced pathological hypertrophy of myocardial cells by immunofluorescence staining of the area of ​​myocardial cells after treatment with exifone. Furthermore, by examining cardiac ultrasound, ejection fraction (EF), and fractional shortening of cardiac ultrasound in mice, exifone treatment can improve TAC-induced cardiac dysfunction in mice.

[0029] The present invention also provides the use of exifone in the preparation of a medicament for reducing myocardial hypertrophy. The present invention demonstrates that treatment with exifone can reduce TAC-induced heart weight in mice and inhibit TAC-induced increases in myocardial cross-sectional area, as measured by heart weight, heart weight to tibial length, and myocardial cross-sectional area in mice.

[0030] The present invention also provides the use of exifone in the preparation of a medicament for reducing cardiac tissue fibrosis. The present invention shows that by detecting the degree of cardiac fibrosis in TAC-induced pathological myocardial hypertrophy mice treated with exifone, it was found that exifone treatment can reduce TAC-induced cardiac fibrosis in mice.

[0031] The present invention also provides a drug for treating pathological myocardial hypertrophy and / or heart failure, the active ingredient comprising oxaliplatin and a pharmaceutically acceptable excipient. In a specific embodiment, the pharmaceutically acceptable excipient includes one or more of a buffer, an encapsulating agent, a filler, a binder, a transdermal absorbent, a wetting agent, a disintegrant, an absorption enhancer, a surfactant, a colorant, a flavoring agent, and an adsorption carrier. In a specific embodiment, the drug may be formulated in the form of tablets, pills, powders, granules, capsules, decoctions, injections, or suppositories.

[0032] The present invention provides an amount of Exifone of 25 to 75 mg / kg based on the body weight of the mouse. As a specific embodiment, the amount of Exifone can be 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, or 75 mg / kg, as well as any value in between, based on the body weight of the mouse. The present invention demonstrates that when Exifone is injected into mice at doses of 25 mg / kg, 50 mg / kg, and 75 mg / kg, it was found that Exifone at doses of 25 mg / kg, 50 mg / kg, and 75 mg / kg had no effect on the cardiac function of the mice, and had no effect on the structural integrity of the heart, liver, spleen, lung, and kidney tissues of the mice.

[0033] As a specific embodiment, when the drug is in the form of an injection, it further comprises a solvent, and the solvent includes an animal solvent and a cell solvent;

[0034] The animal solvent includes: 5% DMSO + 30% PEG300 + 5% Tween 80 + 60% PBS;

[0035] The cell solvent includes: DMSO.

[0036] In a specific embodiment of the present invention, when conducting animal experiments, ethyphenidyl is dissolved using an animal solvent, and when conducting cell experiments, ethyphenidyl is dissolved using a cell solvent.

[0037] To further illustrate the present invention, the use of the ethyphenidone provided by the present invention in the preparation of a medicament for treating pathological myocardial hypertrophy and / or heart failure is described in detail below with reference to the examples, but these examples should not be construed as limiting the scope of protection of the present invention.

[0038] Unless otherwise specified, the present invention has no special requirements for the raw materials, and commercially available products known to those skilled in the art can be used.

[0039] The present invention's Exifone (manufacturer: Taoshu Biological; product number: T20080) requires a solvent to dissolve the Exifone when used. The solvent of the present invention is configured as follows:

[0040] Solvent (animal): 5% DMSO (manufacturer: Taoshu Biological; catalog number: T0341) + 30% PEG300 (manufacturer: Taoshu Biological; catalog number: T7022) + 5% Tween 80 (manufacturer: Taoshu Biological; catalog number: T13947) + 60% PBS (manufacturer: Sangon; catalog number: B548117);

[0041] Solvent (cells): DMSO (Manufacturer: Taoshu Biological; Product No.: T0341).

[0042] Example 1

[0043] 1. Isolation, Culture, and Grouping of Neonatal Rat Cardiomyocytes (NRCMs)

[0044] Sprague-Dawley rat pups, 1 to 3 days old, were selected. The chests of the newborns were disinfected with 75% alcohol. The hearts were removed in a cleanroom, rinsed in 1× ADS solution on ice, and dehydrated. The hearts were minced to 1–2 mm and transferred to a sterilized glass bottle. 20 mL of trypsin-collagenase digestion solution was added and the cells were incubated at 37°C at 120 rpm for 10 min per cycle. The cell suspension was collected into a 50 mL centrifuge tube and digested with horse serum (5:1 volume ratio) to terminate the digestion. The cells were centrifuged at 1000 rpm for 5 min, and the supernatant was discarded. The cells were resuspended in NRCM medium (a mixture of high-glucose DMEM, 10% horse serum, 5% fetal bovine serum, and 1% penicillin-streptomycin) and digested repeatedly for 10 cycles until the tissue was completely dissociated. The cell suspension was filtered through a 100 μm filter, aliquoted into 10 cm culture dishes, and incubated at 37°C for 60 min to remove fibroblasts. After centrifugation (1000 rpm, 5 min), resuspend the cells and separate the cardiomyocytes from the fibroblasts by Percoll gradient centrifugation (3000 rpm, 30 min). Resuspend the cardiomyocytes in NRCM medium, count and plate the cells, and culture them in a 37°C, 5% CO2 incubator. Subsequent experiments were performed when the cells were well attached and growing.

[0045] 2. Treat NRCM cells with different concentrations (0 μM, 1 μM, 10 μM, 20 μM, 50 μM, 100 μM) of Exifone (manufacturer: Taoshu Biological; catalog number: T20080) for 48 h.

[0046] 3. Add 10 μL of CCK-8 solution (Manufacturer: Biyuntian; Catalog No.: C0037) to each treatment and continue incubating in the cell culture incubator for 1 hour. Measure the absorbance at 450 nm using a microplate reader. Calculate the cell viability based on the absorbance value. The relative viability formula is: (absorbance of the experimental group - absorbance of the blank control) / (absorbance of the positive control - absorbance of the blank control) × 100%.

[0047] according to Figure 1 As shown in Table 1, treatment of NRCM with 1 μM and 10 μM Exifone had no effect on cell activity, while 20 μM, 50 μM, and 100 μM Exifone significantly inhibited cardiomyocyte activity.

[0048] Table 1 Cellularity test results

[0049]

[0050] Example 2

[0051] 1. Myocardial Pathological Hypertrophy Model

[0052] After NRCM (neonatal rat cardiomyocytes obtained in Example 1) adhered to the wall, the NRCM culture medium was replaced with serum-free culture medium and starved for 8 h. Phenylephrine (PE, 100 μM, manufacturer: Sigma-Aldrich; product number: PHR1017) was added in the dark for 48 h to induce pathological hypertrophy of the cardiomyocytes, thereby obtaining a pathological myocardial hypertrophy model.

[0053] 2. Exifone processing

[0054] Myocardial hypertrophy model and neonatal rat cardiomyocytes were treated with 10 μM Exifone for 48 h.

[0055] The myocardial hypertrophy model and neonatal rat cardiomyocytes were treated with DMSO for 48 hours.

[0056] 3. Perform α-actinin fluorescence staining on the cells treated in step 2: Collect the cells after Exifone treatment for 48 hours and discard the culture medium. Next, fix them with 4% paraformaldehyde (PFA), fix them for 20 minutes, and then wash them three times with PBS. Subsequently, use 0.5% TritonX-100 to break the membrane and block it with 5% BSA. Next, add the primary antibody α-actinin and incubate it in a 4°C refrigerator overnight. The next day, wash it three times with PBS, then add the corresponding secondary antibody, incubate it at room temperature in the dark for 2 hours, and then wash it three times with PBS. Finally, use Hoechst 33342 to stain the cell nucleus, incubate it at room temperature in the dark for 20 minutes, and wash it again with PBS. Take pictures using a laser confocal microscope, and analyze the size of cardiomyocytes using ImageJ software.

[0057] Figure 2 Immunofluorescence staining was used to detect the area of ​​cardiomyocytes after Exifone treatment, N=6. Figure 2 As shown in Table 2, Exifone can inhibit the pathological hypertrophy of cardiomyocytes induced by PE.

[0058] Table 2 Relative myocardial cell size detection results

[0059]

[0060] Example 3

[0061] 1. Mouse Grouping and Exifone Administration

[0062] Thirty-two experimental mice purchased from Suzhou Huachuang Xinnuo Pharmaceutical Technology Co., Ltd. were randomly divided into a normal saline group, an Exifone 25 mg / kg group, an Exifone 50 mg / kg group, and an Exifone 75 mg / kg group.

[0063] Mice in the saline group were injected intraperitoneally with normal saline; mice in the exifone group were injected intraperitoneally with exifone at doses of 25 mg / kg, 50 mg / kg, and 75 mg / kg, once daily for two weeks.

[0064] 2. Echocardiography: After completing step 1, mice were anesthetized with isoflurane and cardiac function was assessed using a 30 MHz Visual Sonics 2100 small animal ultrasound imaging system. Three consecutive cardiac cycles were measured using M-mode images to assess systolic function, including left ventricular ejection fraction (EF) and fractional shortening (FS).

[0065] The results are as follows Figure 3 As shown, Figure 3 Middle A is a representative ultrasound image of mouse heart; Figure 3 Middle B is the statistical result of ejection fraction (EF) of mouse heart ultrasound; Figure 3 C in the middle is the statistical result of fractional shortening (FS) of mouse heart ultrasound. Figure 3 As can be seen from Table 3-4, 25mg / kg, 50mg / kg and 75mg / kg of Exifone had no effect on the cardiac function of mice.

[0066] Table 3 Statistical results of ejection fraction (EF) of mouse heart ultrasound

[0067]

[0068]

[0069] Table 4 Statistical results of fractional shortening (FS) of mouse cardiac ultrasound

[0070]

[0071] 3. HE staining: After euthanasia of mice in step 1, samples of the heart, liver, spleen, lung, and kidney were collected. After dehydration and paraffin embedding, paraffin sections were prepared. After dewaxing and hydration, the paraffin sections were stained using a HE staining kit (purchased from KeyGen Biosciences). After the sections were air-dried, they were mounted with neutral gum and observed and imaged under a microscope to assess the histological structure of the heart, liver, spleen, lung, and kidney.

[0072] according to Figure 4 It can be seen that 25mg / kg, 50mg / kg, and 75mg / kg Exifone had no effect on the structural integrity of mouse heart, liver, spleen, lung, and kidney tissues.

[0073] Example 4

[0074] 1. Mouse Grouping and Model Establishment

[0075] Sixty experimental mice purchased from Suzhou Huachuang Xinnuo Pharmaceutical Technology Co., Ltd. were randomly divided into pathological myocardial hypertrophy (TAC) group and sham operation (Sham) group;

[0076] TAC group: After full anesthesia, mice were placed in the supine position on a 37°C thermostatic pad. Hair was removed to expose the neck and chest skin, which was then disinfected with 75% ethanol. Under a stereoscope, the neck skin, muscles, and tissues overlying the trachea were separated linearly to expose the trachea. An endotracheal tube was inserted and secured through the two tracheal cartilage rings below the glottis. Under a stereoscope, a 0.8 cm long incision was made longitudinally from the midline of the sternum. The sternum was then cut to the second rib. The sternum was retracted with retractors on both sides, and the thymus was separated with microforceps. The aortic arch was carefully identified by carefully separating the adipose tissue. A 7-0 suture was used to pass through the aortic arch between the left common carotid artery and the right brachiocephalic artery. A 27G needle was placed parallel to the aortic arch and secured with a knot using the 7-0 suture. The 27G needle was then slowly withdrawn.

[0077] Sham group: The procedure was identical to the TAC group, except that the ligation was omitted. After surgery, carefully observe the mouse for respiratory distress; if so, clear the airway immediately. After waking, remove the mouse from the incubator and return it to its cage.

[0078] 2. Exifone administration

[0079] On the day of TAC or sham surgery, mice in the saline group were intraperitoneally injected with normal saline; mice in the exifone group were intraperitoneally injected with 50 mg / kg exifone once daily for 4 consecutive weeks.

[0080] 3. Echocardiography: After completing step 2, mice were anesthetized with isoflurane, and cardiac function was assessed using a 30 MHz Visual Sonics 2100 small animal ultrasound imaging system. Three consecutive cardiac cycles were measured using M-mode images to assess systolic function, including left ventricular ejection fraction (EF) and fractional shortening (FS).

[0081] The results are as follows Figure 5 As shown, Figure 5 Middle A is a representative ultrasound image of mouse heart; Figure 5 Middle B is the statistical result of ejection fraction (EF) of mouse heart ultrasound; Figure 5 C in the middle is the statistical result of fractional shortening (FS) of mouse heart ultrasound. Figure 5 As shown in Tables 5-6, Exifone treatment can improve TAC-induced cardiac dysfunction in mice.

[0082] Table 5 Statistical results of ejection fraction (EF) of mouse heart ultrasound

[0083]

[0084] Table 6 Statistical results of fractional shortening (FS) of mouse cardiac ultrasound

[0085]

[0086]

[0087] 4. Measure heart weight and tibia length: After step 2, remove the heart, measure the heart weight of the mouse using an analytical balance, and measure the tibia length of the mouse using a vernier caliper.

[0088] The results are as follows Figure 6 As shown, Figure 6 A in the middle is the weight of mouse heart; Figure 6 B is the result of the mouse tibia weight being longer than the tibia. Figure 6 As shown in Tables 7-8, Exifone treatment can reduce the heart weight of mice induced by TAC.

[0089] Table 7 Statistical results of mouse heart weight

[0090]

[0091] Table 8 Statistical results of mouse viscera weight relative to tibia length

[0092]

[0093] 5. Wheat Germ Agglutinin (WGA) Staining: After euthanizing mice in step 2, hearts were removed, placed in OCT complex, and frozen at -80°C. Cryosections of mouse heart tissue were prepared using a cryostat and stained with WGA (Sigma-Aldrich; Cat. No. L4895). After mounting with 50% glycerol in the dark, images were acquired using a fluorescence microscope (Zeiss), and cardiomyocyte cross-sectional area was measured using ImageJ.

[0094] The results are as follows Figure 7 As shown, Figure 7 Middle A is a representative image of the cross-sectional area of ​​the mouse myocardium stained with WGA, with the green color representing the outline of the myocardial tissue cells labeled with WGA, scale bar: 50 μm; Figure 7 Middle B is the statistical result of myocardial cross-sectional area in each treatment group after WGA staining. Figure 7 As shown in Table 9, Exifone treatment can inhibit the increase in myocardial cross-sectional area induced by TAC.

[0095] Table 9 Statistical results of myocardial cross-sectional area in each treatment group after WGA staining

[0096]

[0097] 6. Masson's Staining: After euthanizing the mice in step 2, the hearts were removed, dehydrated, and paraffin-embedded for paraffin sections. After dewaxing and hydration, the paraffin sections were stained for collagen fibers using a Masson's Trichrome staining kit (Manufacturer: KeyGen Biotechnology; Catalog No.: KGE1113-8). After the tissue sections were air-dried, they were mounted with neutral gum and observed and imaged under a microscope to assess changes in myocardial collagen fibers. ImageJ was used to quantify collagen fiber content.

[0098] The results are as follows Figure 8 As shown, Figure 8 A is a representative image of mouse cardiac fibrosis stained with Masson staining, blue represents the cardiac fibrosis area, scale bar: 100μm; B is the statistical result of the percentage of cardiac fibrosis area in each treatment group after Masson staining. Figure 8 As shown in Table 10, Exifone treatment can reduce TAC-induced cardiac fibrosis in mice.

[0099] Table 10 Statistical results of the proportion of cardiac fibrosis area in each treatment group after Masson staining

[0100]

[0101]

[0102] Thus, the present invention's research results in primary neonatal rat cardiomyocytes demonstrate that exiphenone can inhibit phenylephrine (PE)-induced pathological cardiomyocyte hypertrophy. Animal experiments have also shown that exiphenone can improve cardiac dysfunction induced by aortic arch constriction (TAC) and reduce myocardial hypertrophy and cardiac tissue fibrosis. This invention provides a new drug development approach and drug target for the treatment of pathological myocardial hypertrophy and heart failure, and has significant pharmaceutical value.

[0103] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. Use of oxaliplatin in the preparation of a drug for treating pathological myocardial hypertrophy and / or heart failure.

2. The use according to claim 1, characterized in that The pathological myocardial hypertrophy includes at least one of the following: cardiac dysfunction, myocardial cell hypertrophy and increased degree of fibrosis.

3. Application of ethoxybenzone in the preparation of drugs for improving cardiac dysfunction.

4. The use of oxaliplatin in the preparation of drugs for reducing myocardial hypertrophy.

5. Application of ethoxybenzone in the preparation of drugs for reducing cardiac tissue fibrosis.

6. A drug for treating pathological myocardial hypertrophy and / or heart failure, characterized in that: The active ingredients include ethoxybenzone and pharmaceutically acceptable excipients.

7. The drug according to claim 6, characterized in that The pharmaceutically acceptable excipients include: one or more of a buffer, an encapsulating agent, a filler, an adhesive, a transdermal absorbent, a wetting agent, a disintegrant, an absorption accelerator, a surfactant, a colorant, a flavoring agent and an adsorption carrier.

8. The drug according to claim 6, characterized in that The preparation forms of the drug include tablets, pills, powders, granules, capsules, decoctions, injections or suppositories.

9. The drug according to claim 6, characterized in that Based on the body weight of the mouse, the dosage of the ethyphenidone is 25 to 75 mg / kg.

10. The drug according to claim 8, characterized in that When the drug is in the form of an injection, it also includes a solvent, which includes an animal solvent and a cell solvent; The animal solvent includes: 5% DMSO + 30% PEG300 + 5% Tween 80 + 60% PBS; The cell solvent includes: DMSO.

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