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Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure

A cardiomyopathy, old technology, applied in the field of therapeutic agents for cardiomyopathy, old myocardial infarction and chronic heart failure, can solve problems such as unclear therapeutic effect

Active Publication Date: 2019-11-22
斯特姆里姆有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, it is not clear whether the fragment peptide of HMGB1 protein has a therapeutic effect on cardiomyopathy and old myocardial infarction.

Method used

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  • Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure
  • Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure
  • Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0174] Efficacy Evaluation of HMGB1 Fragment Peptides on Dilated Cardiomyopathy

[0175] (1) Materials and methods

[0176] Dilated cardiomyopathy animal model J2N-k hamsters (18-week-old, male, 20 in total) were obtained from Japan SLC, and used for experiments after 2 weeks of domestication. J2N-k hamsters have a natural onset of dilated cardiomyopathy due to the deletion mutation of the δ-sarcoglycan gene (specifically, cardiomyocyte detachment and fibrosis begin around 5 weeks of age, and heart enlargement and cardiac Dysfunction and eventually death from congestive heart failure at about 1 year. J Biochem. 2003 Aug;134(2):269-76). In addition, a peptide composed of amino acid residues 1-44 (SEQ ID NO: 1) of human-derived HMGB1 protein was chemically synthesized by a solid-phase method. Hereinafter, this peptide is referred to as HMGB1 peptide (1-44), and is abbreviated as "1-44" in the drawings corresponding to the examples.

[0177] J2N-k hamsters were divided into ...

Embodiment 2

[0209] Efficacy Evaluation of HMGB1 Fragment Peptides on Dilated Cardiomyopathy (Long-term Observation)

[0210] (1) Materials and methods

[0211] Prepare 20 J2N-k hamsters in the same manner as in Example 1, divide them into HMGB1 peptide (1-44) administration group (n=11) and PBS administration group (control, n=9), and start administration from the 20th week of age. medicine. The test substance was administered by adding a solution of HMGB1 peptide (1-44) adjusted to a concentration of 1 mg / ml with PBS as a solvent in an amount of 3 ml / kg (3 mg / kg in terms of the amount of peptide administered) for 1 day. It was injected into the external jugular vein once for 4 consecutive days. For the control group, PBS was injected into the external jugular vein in an amount of 3 ml / kg once a day for 4 consecutive days. Then, while raising them under normal conditions, evaluation of cardiac function and survival rate was continued.

[0212] (2) Evaluation items

[0213] i) Cardi...

Embodiment 3

[0223] Efficacy evaluation of HMGB1 fragment peptide on the improvement of cardiac function after old myocardial infarction

[0224] (1) Materials and methods

[0225] SD rats (7 weeks old, male, body weight about 250 g) were anesthetized with the inhalational anesthetic sevoflurane (or isoflurane), and after a sufficient suppression state was obtained, endotracheal intubation was performed and deep anesthesia was maintained with the inhalational anesthetic. The thoracotomy was performed in the left fourth intercostal space in the supine position, and the proximal end of the left anterior descending coronary artery was ligated with 6-0 prolene suture to make a large-scale myocardial fiber model. Two weeks after the infarction was established, cardiac function was evaluated by echocardiography, and cases with large-scale infarction (LVEF<50%) were used as old myocardial infarction rat models (17 rats in total). In addition, the HMGB1 peptide (1-44) consisting of SEQ ID NO: 1...

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PUM

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Abstract

The present inventors have found that an HMGB1 fragment peptide having a specific amino acid sequence exhibits an effect to improve the function of the heart, prevent cardiomyocyte hypertrophy, prevent myocardial fibrosis and promote angiogenesis in an animal model with dilated cardiomyopathy, the specific HMGB1 fragment peptide also exhibits an effect to improve the function of the heart, preventauxocardia, prevent cardiomyocyte hypertrophy, prevent myocardial fibrosis and promote angiogenesis in an animal model with ischemic cardiomyopathy associated with old myocardial infarction, and thespecific HMGB1 fragment peptide exhibits an effect to prevent cardiomyocyte hypertrophy and prevent myocardial fibrosis in an animal model with hypertensive cardiomyopathy. On the basis of this finding, a pharmaceutical composition for preventing and / or treating cardiomyopathy, old myocardial infarction, and chronic heart failure associated with these diseases is provided, which contains an HMGB1fragment peptide having a specific amino acid sequence.

Description

technical field [0001] The present application relates to a pharmaceutical composition for preventing and / or treating cardiomyopathy, old myocardial infarction and chronic heart failure comprising fragment peptides of HMGB1 protein. Background technique [0002] Cardiomyopathy is defined as "myocardial disease accompanied by cardiac dysfunction". In many cases, it is accompanied by cardiac structural abnormalities such as cardiac enlargement, cardiomyocyte hypertrophy, and myocardial fibrosis. When it progresses, it will show symptoms of heart failure. Secondary cardiomyopathy sometimes improves with treatment of the underlying disease, but there is no definitive treatment for idiopathic cardiomyopathy. [0003] Myocardial infarction, which causes myocardial necrosis due to coronary artery occlusion, is a major underlying disease of heart disease that ranks among the leading causes of death in developed countries (No. 1 in the United States and No. 2 in Japan). Although the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P9/04A61P9/10
CPCA61P9/04A61P9/10A61K38/1709A61K38/17A61K38/19
Inventor 玉井克人泽芳树宫川繁木户高志后藤隆纯山崎尊彦
Owner 斯特姆里姆有限公司
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