Use of LY-311727 for the preparation of a medicament for the treatment of myocardial infarction

Abstract

This invention belongs to the field of pharmaceutical technology, specifically relating to the application of LY-311727 in the preparation of drugs for treating myocardial infarction. This invention is the first to discover that LY-311727 can comprehensively intervene in the disease process of myocardial infarction through four pathological mechanisms: improving cardiac function, inhibiting ventricular remodeling, alleviating myocardial fibrosis, and reducing cardiomyocyte apoptosis. It significantly increases ejection fraction and fractional shortening in model animals, reduces heart weight / body weight ratio and heart weight / tibia length ratio, reduces fibrosis area and downregulates the expression of fibrosis marker proteins, while simultaneously reducing the number of apoptotic cells and regulating the expression of apoptosis-related proteins Bax / Bcl-2 / c-cas-3. LY-311727 provides a novel drug strategy and active ingredient for the treatment of myocardial infarction, possessing clear clinical application value and development prospects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of LY-311727 in the preparation of drugs for treating myocardial infarction. Background Technology

[0002] In recent years, the incidence and mortality rates of cardiovascular diseases have been rising year by year, seriously endangering human life and health. Among various cardiovascular events, acute myocardial infarction (AMI) occupies a central position due to its rapid onset and poor prognosis. The pathophysiological process of AMI begins with the rupture of coronary atherosclerotic plaques followed by thrombus formation, leading to a sudden interruption of myocardial blood supply and subsequently irreversible myocardial cell necrosis. Following this, the damaged heart initiates compensatory geometrical remodeling, primarily in the left ventricle. This process involves cardiomyocyte hypertrophy, abnormal activation of interstitial fibroblasts, and excessive deposition of extracellular matrix (ECM), ultimately driving the progressive development of myocardial fibrosis. Extensive basic and clinical evidence indicates that myocardial fibrosis is not only the structural pathological basis for the progressive deterioration of cardiac function after AMI, but also an independent risk factor for the occurrence and progression of ischemic heart failure, malignant ventricular arrhythmias, and sudden cardiac death. Of particular note is that myocardial fibrosis is present in almost all forms of cardiovascular disease (including hypertensive heart disease, dilated cardiomyopathy, diabetic cardiomyopathy, and end-stage heart failure). Therefore, targeted intervention for myocardial fibrosis has become a core scientific proposition for improving the long-term prognosis of cardiovascular disease and reducing long-term mortality.

[0003] While considerable research has been conducted on treatments for myocardial infarction, current clinical protocols still have significant limitations. Current clinical treatments primarily rely on reperfusion therapies such as thrombolysis, interventional procedures, and surgery. These methods can only achieve vascular recanalization, salvage some dying myocardium, and reduce the risk of acute-phase death, but they cannot effectively inhibit the ongoing myocardial cell apoptosis and myocardial fibrosis processes following myocardial infarction, nor can they reverse pathological cardiac remodeling. Long-term cardiac function impairment and poor prognosis remain prominent issues for patients. Furthermore, there is a lack of effective small-molecule therapeutics with clear targeting that can simultaneously inhibit myocardial apoptosis and myocardial fibrosis and block the pathological progression after myocardial infarction. Therefore, targeted interventions for secondary damage caused by myocardial infarction are very limited. Summary of the Invention

[0004] To address the aforementioned issues, this invention provides the application of LY-311727 in the preparation of drugs for treating myocardial infarction, offering a new drug option and active ingredient for the treatment of myocardial infarction.

[0005] To achieve the above objectives, the specific technical solution of the present invention is as follows: The first aspect of the present invention provides the use of LY-311727 in the preparation of a drug for treating myocardial infarction, wherein the CAS number of LY-311727 is 164083-84-5.

[0006] Furthermore, the drug is used to improve cardiac function, inhibit ventricular remodeling, reduce myocardial fibrosis, and / or reduce cardiomyocyte apoptosis.

[0007] Furthermore, the improvement in cardiac function includes increasing ejection fraction and / or fractional shortening.

[0008] Furthermore, the inhibition of ventricular remodeling includes reducing the heart weight / body weight ratio and / or the heart weight / tibia length ratio.

[0009] Furthermore, the reduction of myocardial fibrosis includes reducing the fibrotic area and / or downregulating the protein expression levels of fibrosis markers.

[0010] Furthermore, the fibrosis markers are Fibronectin, Collagen, and / or α-SMA.

[0011] Furthermore, the reduction of cardiomyocyte apoptosis includes reducing the number of apoptotic cells, downregulating the expression of pro-apoptotic proteins, and / or upregulating the expression of anti-apoptotic proteins.

[0012] Furthermore, the pro-apoptotic protein is Bax and / or cleaved caspase-3; the anti-apoptotic protein is Bcl-2.

[0013] A second aspect of the present invention provides a drug for treating myocardial infarction, wherein the drug has LY-311727 as its sole effective active ingredient.

[0014] Furthermore, the effective dose range of LY-311727 is 9.9 mg / kg body weight / 7 days to 10.1 mg / kg body weight / 7 days.

[0015] Furthermore, the effective dose range of LY-311727 is 10 mg / kg body weight / 7 days.

[0016] Furthermore, the drug also contains a pharmaceutically acceptable carrier.

[0017] Furthermore, the dosage form of the drug is an injection.

[0018] Furthermore, the injection is an injection solution or a sterile powder for injection.

[0019] Furthermore, the solvent of the injection solution includes physiological saline.

[0020] Furthermore, the injection solution is obtained by mixing LY-311727, dimethyl sulfoxide, and physiological saline; the ratio of LY-311727, dimethyl sulfoxide, and physiological saline is 5 mg: 4 μL: 4 mL.

[0021] Further, the injection solution is prepared by the following steps: according to the ratio of LY-311727, dimethyl sulfoxide and physiological saline, dimethyl sulfoxide is added to LY-311727 to aid dissolution, then physiological saline is added, the solution is dissolved by sonication, and then filtered through a 0.22 μm microporous membrane for sterilization.

[0022] Furthermore, when the injection is used in mice, the volume of the injection is 200 μL / 25g, the number of administrations is ≥2, and the interval between single administrations is 6 days.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides the application of LY-311727 in the preparation of drugs for treating myocardial infarction. Experiments show that LY-311727 can significantly improve myocardial structural disorder in mice with myocardial infarction, inhibit excessive cardiomyocyte apoptosis, downregulate the expression of myocardial fibrosis-related proteins, alleviate myocardial fibrosis and pathological myocardial hypertrophy, and significantly improve impaired cardiac function. This application clarifies for the first time the pharmacodynamic effect of LY-311727 in the treatment of myocardial infarction: LY-311727 exerts its effects simultaneously on both pathological structural repair and cardiac function protection through a multi-dimensional synergistic mechanism of "anti-fibrosis—anti-apoptosis—inhibition of remodeling," providing a novel drug strategy for the clinical treatment of myocardial infarction. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 Animal experiment flowchart.

[0026] Figure 2 LY-311727 improves cardiac function indicators in mice with myocardial infarction. Figure 2 In the image, A represents a representative M-mode ultrasound image of the heart in each group of mice; Figure 2 B in the figure represents a scatter plot of the left ventricular ejection fraction (LVEF) in mice. Figure 2 C in the figure represents the statistical histogram of the left ventricular shortening rate (LVFS) in mice; Figure 2 D in the figure is a scatter plot of the statistical histogram of the change in the heart weight / body weight ratio (HW / BW); Figure 2 In the figure, E represents a scatter plot of the statistical histogram of the change in the heart weight / tibia length ratio (HW / TL); * indicates p <0.05, **** indicates p <0.0001, ns represents no statistical difference.

[0027] Figure 3 LY-311727 alleviates the pathological changes of myocardial hypertrophy and myocardial fibrosis in mice with myocardial infarction. Figure 3 In the image, A represents a pathological staining image of myocardial tissue, from top to bottom: H&E staining, WGA fluorescence staining, and whole-heart Masson trichrome staining; each row of images, from left to right, represents the Sham+Vehicle group, the MI+Vehicle group, and the MI+LY-311727 group; the scale bars for each row from top to bottom are: 20μm, 20μm, 1mm; Figure 3 In the figure, B is a scatter plot of the cross-sectional area of ​​cardiomyocytes. Figure 3 In the chart, C represents a scatter plot of the percentage of myocardial fibrosis area; **** indicates... p <0.0001.

[0028] Figure 4 LY-311727 downregulates the expression of myocardial fibrosis marker proteins in mice with myocardial infarction. Figure 4 A in the image is a Western Blot electrophoresis diagram of fibrosis marker proteins. The protein bands from top to bottom are Fibronectin (265 kDa), Collagen I (139 kDa), α-SMA (42 kDa), and internal control GAPDH (37 kDa). Figure 4 B in the figure represents a scatter plot of the statistical histogram of the fold change in the relative expression level of Fibronectin protein (Fibronectin / GAPDH). Figure 4 C in the figure represents the fold change in the relative expression level of Collagen I protein (Collagen I / GAPDH) in a scatter plot. Figure 4 In the figure, D represents a scatter plot of the statistical histogram of the fold change in the relative expression level of α-SMA protein (α-SMA / GAPDH); ** indicates p <0.01, **** indicates p <0.0001.

[0029] Figure 5 LY-311727 reduces apoptosis of cardiomyocytes in mice with myocardial infarction. Figure 5In the image, A represents a TUNEL apoptosis fluorescence staining image of myocardial tissue. The top row shows a combined fluorescence image of TUNEL (green apoptosis signal), DAPI (blue cell nucleus), and TNNI3 (red cardiomyocytes), while the bottom row shows a red fluorescence base image of TNNI3 cardiomyocytes. Each group contains an independent field of view, and the groups from left to right are: Sham+Vehicle group, MI+Vehicle group, and MI+LY-311727 group. Figure 5 B in the text stands for TUNEL + A scatter plot of the percentage of positive apoptotic cells; **** indicates... p <0.0001.

[0030] Figure 6 LY-311727 regulates the expression of apoptosis-related proteins in mice with myocardial infarction. Figure 6 A in the image is a Western Blot electrophoresis diagram of apoptosis-related proteins. The protein bands from top to bottom are: activated cleavage type Caspase-3 (c-Cas-3, 19 kDa), pro-apoptotic protein Bax (21 kDa), anti-apoptotic protein Bcl2 (26 kDa), and internal control GAPDH (37 kDa). Figure 6 In the figure, B represents the fold change of c-Cas-3 protein relative expression level (c-Cas-3 / GAPDH) in the scatter plot. Figure 6 C in the figure represents the fold change in the relative expression level of Bax protein (Bax / GAPDH) in a scatter plot. Figure 6 In the figure, D represents the fold change of Bcl2 protein relative expression (Bcl2 / GAPDH) in the histogram scatter plot; * indicates p <0.05, ** indicates p <0.01, *** indicates p <0.001, **** indicates p <0.0001. Detailed Implementation

[0031] The specific embodiments of the present invention are described in detail below, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise specified, the experimental methods described in the embodiments of the present invention are conventional methods, and the materials and reagents used in the following embodiments are commercially available unless otherwise specified.

[0032] LY-311727 was purchased from MCE Company, part number HY-107393.

[0033] Example 1 A drug for treating myocardial infarction: Weigh 5.0 mg of LY-311727 and place it in a sterile centrifuge tube. Add 4 μL of dimethyl sulfoxide (DMSO) to aid dissolution, then bring the volume to 4 mL with physiological saline. After sonication, filter the solution through a 0.22 μm microporous membrane to remove bacteria, thus obtaining the LY-311727 solution, which is the drug for treating myocardial infarction.

[0034] Example 2: Construction of experimental animal model and anesthesia treatment Flowchart as follows Figure 1 As shown, 8-week-old male C57BL / 6 mice were anesthetized by intraperitoneal injection of tribromoethanol (200 mg / kg). The mice were endotracheally intubated and connected to a rodent respirator (set to a rate of 110 breaths / min and a tidal volume of 0.8 mL). Uniform chest cavity movement was observed to confirm successful intubation. The skin was gently incised along the line connecting the left axilla to the xiphoid process, and the muscles between the second and third ribs were bluntly dissected to expose the heart. The left anterior descending coronary artery (LAD) was ligated using a 7-0 atraumatic suture needle. Whitening of the left apex region accompanied by ST-segment elevation was considered a successful establishment of the myocardial infarction (MI) model. The chest cavity was closed and the wound sutured. After the mice regained spontaneous breathing, the intubation tube was removed, and the mice were placed in a normal room temperature environment for feeding. The sham surgery group mice underwent the same surgical procedures but without ligation of the left anterior descending coronary artery. Mice were randomly divided into three groups: MI+LY-311727 group (i.e., LY-311727 group), MI+Vehicle group (i.e., MI group), and Sham+Vehicle group (i.e., Vehicle group), with 6 mice in each group.

[0035] MI+LY-311727 group: Mice with myocardial infarction model were treated with LY-311727. Starting on the first day after LAD ligation, the LY-311727 solution prepared in Example 1 was injected intraperitoneally at a dose of 10 mg / kg and a volume of 200 μL / 25 g body weight. The injection was administered once on the first and seventh days after surgery.

[0036] MI+Vehicle group: Mice with myocardial infarction were given an equal volume of LY-311727 solution as a solvent. The administration volume was 200 μL / 25 g body weight, administered once each on day 1 and day 7 post-surgery.

[0037] Sham+Vehicle group: Sham-operated mice were given an equal volume of LY-311727 solution as a solvent. The solvent solution was injected intraperitoneally starting on day 1 post-surgery at a volume of 200 μL / 25 g body weight, and administered once each on day 1 and day 7 post-surgery.

[0038] On the 14th day after surgery, echocardiography was performed on mice in each group. After the echocardiography, the mice were euthanized, and the hearts were quickly removed by thoracotomy. After rinsing with PBS, a portion of the heart tissue was fixed in 4% paraformaldehyde for histopathological examination, and another portion was flash-frozen in liquid nitrogen and then transferred to a −80 °C freezer for storage for subsequent molecular biological examination.

[0039] Example 3: LY11727 improves cardiac dysfunction and heart weight in mice induced by myocardial infarction (MI). Mouse cardiac function, including ejection fraction (EF) and fractional shortening (FS), was assessed using mouse echocardiography. The method was as follows: Mice were anesthetized and fixed on a control table according to the method described in Example 2. After hair removal, coupling gel was applied to the left chest. The small animal ultrasound probe was placed near the heart, and echocardiography was performed using a Vevo 2100 echocardiography system (10-MHz, 2D M-mode). At least three consecutive cardiac cycles were recorded, and the average value was analyzed. The parameters measured included left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS).

[0040] Echocardiographic analysis showed that LY-311727 significantly improved cardiac function in mice with myocardial infarction, including a reduction in ejection fraction and fractional shortening. Simultaneously, the heart-to-body weight ratio and heart-to-tibia length ratio were significantly decreased in these mice. Figure 2 ).

[0041] Example 4: LY-31172 significantly improved cardiomyocyte volume and fibrosis area in mice with myocardial infarction. Myocardial tissue was collected from mice with myocardial infarction model, fixed, routinely embedded in paraffin, and sectioned. H&E, WGA, and Masson staining were performed, respectively.

[0042] H&E staining: Sections were dewaxed sequentially with xylene (I, II) for 5 min each, followed by anhydrous ethanol for 5 min, 95%, 80%, and 70% ethanol for 2 min each, and distilled water for 2 min for hydration. After washing with distilled water, the sections were stained with hematoxylin for 10 min, rinsed with running water, differentiated with differentiation solution for 30 s, soaked in tap water for 15 min to regain blue color, stained with eosin for 1 min, rinsed with running water and soaked for 2 min, and finally dehydrated with 95% ethanol (I, II) and 100% ethanol (I, II) for 1 min each, cleared with xylene-carbolic acid (3:1) for 1 min, and xylene (I, II) for 1 min each, mounted with neutral resin, and observed under an optical microscope for morphological changes in myocardial tissue.

[0043] WGA staining: After dewaxing, sections were placed in a staining chamber containing citric acid retrieval solution (pH 9.0) and microwaved on high for 4.5 min until just boiling, then on medium-low for 5 min, and allowed to cool naturally to room temperature. Sections were washed three times with 1×PBS for 5 min each time; blocked with 5% BSA (diluted with PBS) at room temperature for 1 h; stained for 1 h under light-protected conditions with WGA working solution diluted 1:100 with PBS (20 μL total volume per tissue); washed three times with PBS for 5 min each time; mounted with DAPI and observed under a microscope.

[0044] Masson staining: After routine dewaxing and hydration, sections were stained with Weigert iron hematoxylin staining solution for 8 min, differentiated with acidic ethanol differentiation solution, washed with water, and then blued with Masson blue solution and washed with water. After washing with distilled water for 1 min, sections were stained with Ponceau red and fuchsin staining solution for 8 min. After washing with weak acid working solution (distilled water: weak acid solution = 2:1) for 1 min, treated with phosphomolybdic acid solution for 2 min, and washed with weak acid working solution for 1 min. After staining with aniline blue staining solution for 2 min, sections were washed with weak acid working solution for 1 min. After rapid dehydration with 95% ethanol, sections were dehydrated three times with anhydrous ethanol (10 s each time), cleared with xylene three times (2 min each time), mounted with neutral resin, and observed under a microscope.

[0045] like Figure 3 As shown, H&E staining, WGA staining, and Masson staining data indicate that LY-31172 significantly improved myocardial arrangement disorder, cardiomyocyte size, and fibrosis area in mice with myocardial infarction.

[0046] Example 5: LY-31172 reduces fibrotic damage in mice with myocardial infarction. In this embodiment, Western blot technology was used to perform quantitative analysis of protein expression to detect the effect of LY-31172 on the expression levels of fibrosis marker proteins (Fibronectin, Collagen I and α-SMA) in the cardiac tissue of mice after myocardial infarction. The specific experimental method is as follows.

[0047] (1) Protein quantification: Mouse heart tissue was homogenized and total protein was extracted. Protein concentration was detected using a BCA protein concentration assay kit. BCA working solution (A solution:B solution = 50:1) was prepared according to the instructions. 19 μL PBS, 1 μL of the test protein, and 200 μL BCA mixture were added to each well of a 96-well plate. The mixture was shaken and incubated at 37℃ for 20 min. The absorbance was measured at 562 nm. The protein concentration of each sample was calculated based on the standard curve. RIPA lysis buffer was used to adjust the protein content and volume of each sample. Protein loading buffer was added, and the samples were denatured at 100℃ for 10 min. The samples were stored at -20℃ for later use.

[0048] (2) Preparation of SDS-polyacrylamide gel (SDS-PAGE): Prepare SDS-polyacrylamide gel according to the instructions of the PAGE gel kit. Pour the lower gel mixed with the coagulant into a clean and dry gel plate and seal it with anhydrous ethanol. After the lower gel solidifies, discard the ethanol, add the upper gel mixed with the coagulant and insert a 15-hole comb. After solidification, it is ready for use.

[0049] (3) Electrophoresis: Remove the comb, fix the gel plate, install the electrophoresis tank, and add the electrophoresis buffer. Add the prepared protein sample and protein marker to the corresponding gel channels. First, adjust the voltage to 70 V, observe the protein enter the lower gel, then adjust it to 110 V, and electrophoresis for 2 hours until the target protein molecules are fully expanded, then stop electrophoresis.

[0050] (4) Transfer: Remove the gel plate, rinse off the excess electrophoresis solution with water, stack the gel and NC membrane, install the transfer tank, pour in the pre-cooled transfer solution at 4°C, and transfer the membrane at a constant current of 300 mA in an ice bath environment.

[0051] (5) Blocking: After the transfer is completed, take out the NC membrane, add the rapid blocking solution, and block on a horizontal shaker at room temperature for 15 minutes.

[0052] (6) Primary antibody incubation: Wash the blocked NC membrane with PBS, then put it into the diluted antibody and incubate overnight at 4°C on a shaker.

[0053] (7) Secondary antibody incubation: Take out the NC membrane that has been incubated with primary antibody overnight, wash it three times with PBS-T buffer, 10 minutes each time. Incubate with 800 rabbit / mouse secondary antibody (secondary antibody:PBS = 1:10000) for 50 minutes at room temperature in the dark, and wash it three times with PBS-T buffer, 10 minutes each time. Scan the membrane using an Odyssey infrared fluorescence scanner imaging system, using GAPDH as an internal control for calibration.

[0054] Figure 4 Western blot results showed that LY-311727 significantly improved the expression of fibroblast marker proteins, including Fibronectin, Collagen I, and α-SMA, in the cardiac tissue of mice with myocardial infarction.

[0055] Example 6: LY-31172 reduces the number of apoptosis-positive cells in mice with myocardial infarction. To investigate the effect of LY-31172 on cardiomyocyte apoptosis after myocardial infarction, this example used TUNEL staining to detect the number of apoptotic positive cells in mouse heart tissue sections. The specific operation steps are as follows.

[0056] (1) Dewaxing: Take paraffin sections of myocardial tissue and dewax the sections; (2) Antigen retrieval: Place the sections in a staining box containing 1× sodium citrate antigen retrieval solution (pH 6.0, which can be diluted with an equal volume of pure water using 2× retrieval solution), heat in a microwave oven to boiling (8 min, after observing the generation of bubbles, adjust to low heat and maintain 100℃ for 5 min), remove and cool naturally to room temperature; (3) Permeabilization treatment: After soaking the sections in 1×PBS, add PBS solution containing 1% Triton X-100, incubate at room temperature for 10 min to increase cell membrane permeability, then wash 3 times with 1×PBS, 5 min each time. (4) Blocking: Shake off excess liquid, add 5% BSA (pre-stored at 4℃), block at room temperature for 1 h to block non-specific binding. After blocking, wash with 1×PBS and draw circles with an oil pen to prevent antibody diffusion. (5) Primary antibody incubation: Shake off the sections, add the corresponding primary antibody diluted with 3% BSA, and incubate overnight at 4℃ in a humidified chamber. The next day, wash three times with PBST, 5 min each time. (6) Fluorescent secondary antibody incubation: Add fluorescently labeled secondary antibody under light-protected conditions, incubate at room temperature for 1 h, then wash three times with PBS, 5 min each time. (7) Proteinase K treatment: Add proteinase K solution containing 20 μg / mL without DNase (prepared with PBS), incubate at 37℃ for 30 min to further permeate the nuclear membrane. Then wash three times with PBS, making sure to wash away proteinase K. (8) TUNEL reaction: Prepare TUNEL detection solution according to the kit instructions (mix 5 μL TdT enzyme with 45 μL fluorescent labeling solution). Add the mixture to the tissue, incubate at 37℃ in the dark for 1 h, so that the terminal deoxynucleotidyl transferase catalyzes the fluorescently labeled dUTP to bind to the 3'-OH end of the broken DNA. After incubation, wash three times with PBS, 5 min each time. (9) Mounting: Mount with anti-fluorescence quenching mounting medium containing DAPI, observe and photograph under a fluorescence microscope.

[0057] The results are as follows Figure 5 As shown, TUNEL staining revealed that LY-311727 significantly reduced the number of apoptotic cells.

[0058] Example 7: LY-31172 inhibits the expression of pro-apoptotic genes and upregulates the expression of anti-apoptotic genes in the cardiac tissue of mice with myocardial infarction. The protein expression levels of pro-apoptotic and anti-apoptotic genes in the cardiac tissue of mice with myocardial infarction were determined using the Western Blot method described in Example 5. The results are as follows: Figure 6 As shown, LY-311727 significantly reduced the protein expression levels of pro-apoptotic genes Bax and c-cas-3, while the anti-apoptotic gene Bcl-2 was significantly upregulated by LY-311727.

[0059] It should be noted that when numerical ranges are involved in this invention, it should be understood that both endpoints of each numerical range, as well as any value between the two endpoints, can be selected. Since the steps and methods used are the same as in the embodiments, preferred embodiments are described here to avoid redundancy. Although preferred embodiments of the invention have been described, those skilled in the art, once they understand the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of this invention.

[0060] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. The application of LY-311727 in the preparation of drugs for treating myocardial infarction, characterized in that, The CAS number of the LY-311727 is 164083-84-5.

2. The application according to claim 1, characterized in that, The drug is used to improve cardiac function, inhibit ventricular remodeling, reduce myocardial fibrosis, and / or reduce cardiomyocyte apoptosis.

3. A drug for treating myocardial infarction, characterized in that, The drug has LY-311727 as its sole active ingredient.

4. The drug according to claim 3, characterized in that, The effective dose range of LY-311727 is 9.9 mg / kg body weight / 7 days to 10.1 mg / kg body weight / 7 days.

5. The drug according to claim 3, characterized in that, The drug also includes a pharmaceutically acceptable carrier.

6. The drug according to claim 5, characterized in that, The drug is available in either injectable or oral formulation.

7. The drug according to claim 6, characterized in that, The injection is an injection solution or a sterile powder for injection.

8. The medicament according to claim 7, characterized in that, The solvent for the injection solution includes physiological saline.

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