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Application of abt-263 combined with angiotensin-converting enzyme inhibitors and its products

A technology of ABT-263, 1.ABT-263, applied in cardiovascular system diseases, medical preparations containing active ingredients, drug combinations, etc., to reduce fibrosis, reduce activation, and improve cardiac function.

Active Publication Date: 2022-03-11
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] There are no reports on the senolytic agent ABT-263 for myocardial remodeling after myocardial infarction, nor the combination of ABT263 and captopril for myocardial remodeling after myocardial infarction

Method used

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  • Application of abt-263 combined with angiotensin-converting enzyme inhibitors and its products
  • Application of abt-263 combined with angiotensin-converting enzyme inhibitors and its products
  • Application of abt-263 combined with angiotensin-converting enzyme inhibitors and its products

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Detection of myocardial infarction and the level of myocardial infarction and fibrosis in the surrounding area of ​​mice after 4 weeks of drug treatment

[0034] (1) Construction of a mouse model of myocardial infarction (MI)

[0035] 12-month-old wild-type (WT) mice (purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.) were used to construct the myocardial infarction (MI) model. After fasting for 4-6 hours, each mouse was weighed with an electronic scale and recorded. According to the body weight, the mice were anesthetized with pentobarbital sodium, and the injection method was intraperitoneal injection, and the dosage was calculated according to 50 mg / kg. The limbs of the mice were fixed, and after the fur of the operation area was disinfected, the hair on the neck and chest of the mice was scraped off with a dermatome. Separate the skin, muscle and other tissues to expose the trachea, open and connect the animal ventilator, observe the re...

Embodiment 2

[0048] Detection of ABT263 and / or captopril treatment after myocardial infarction, inflammation level in myocardial infarction and surrounding areas, and molecular histological expression of NLRP3 signaling pathway:

[0049] In order to clarify whether treatment with senescent cell scavenger ABT263 and / or captopril can correct chronic inflammation and NLRP3 signaling pathway after myocardial infarction, 12-month-old WT mice were used to construct myocardial infarction model, and then mice were given normal saline and senescent cell scavenger. Agent ABT263, captopril, ABT263 combined with captopril administered by intragastric administration, myocardial infarction model construction, animal model grouping and mouse normal saline, senescent cell scavenging agent ABT263, captopril and ABT263 combined with captopril administered The stomach is equivalent to Example 1.

[0050] The levels of inflammatory factors IL-1β, IL-6, TNF-α and RANTES in the infarction area of ​​mice with my...

Embodiment 3

[0059] Detection of ABT263 and / or captopril treatment after myocardial infarction, inflammation level of myocardial infarction and surrounding area and protein expression level of NLRP3 signaling pathway molecules:

[0060] In order to further clarify the changes in the expression levels of chronic inflammation and NLRP3 signaling pathway-related proteins after the treatment of myocardial infarction by the senescent cell scavenger ABT263 and / or captopril, 12-month-old WT mice were used to construct the myocardial infarction model, and the mice were given physiological Saline, senescent cell scavenging agent ABT263, captopril, and ABT263 combined with captopril were intragastrically administered, as in Example 1. Detection of inflammatory factors IL-1β, pro-IL-1β, TNF-α and NLRP3 signaling pathway-related proteins NLRP3, ASC, Caspase-1-p40, Caspase-1-p20 in the infarction area of ​​mice with myocardial infarction 4 weeks later by immunoblotting and Caspase-1-p10.

[0061] see ...

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Abstract

The invention discloses the application of ABT‑263 combined with an angiotensin-converting enzyme inhibitor in the preparation of a product for treating ventricular remodeling after myocardial infarction, and belongs to the technical field of medicine. The inventors found that ABT-263 combined with angiotensin-converting enzyme inhibitors can significantly improve cardiac function, reduce myocardial infarction and surrounding fibrosis, reduce myocardial inflammation and activation of NLRP3 signaling pathway molecules, and then inhibit ventricular weight loss after myocardial infarction. It provides a new treatment plan for the clinical treatment of ventricular remodeling after myocardial infarction.

Description

technical field [0001] The invention relates to the application of ABT-263 combined with an angiotensin-converting enzyme inhibitor and its products, which belong to the technical field of medicine. Background technique [0002] The number of deaths caused by cardiovascular system diseases has long occupied the first place in the number of all-cause deaths, among which myocardial infarction (myocardial infarction, MI) ranks first among the causes of death from cardiovascular system diseases. In recent years, the incidence of MI has been increasing year by year, causing enormous health and economic pressure for the whole society. Studies have shown that the incidence of MI increases gradually with age, suggesting that MI may be one of the diseases of aging. With the promotion of acute coronary artery stent implantation, the mortality rate of acute myocardial infarction has been significantly reduced, but the ventricular remodeling after acute myocardial infarction, which lea...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/5377A61K31/401A61P9/10A61P9/00
CPCA61K31/5377A61K31/401A61P9/10A61P9/00A61K2300/00
Inventor 靳建亮顾鑫王芳周佳雯
Owner NANJING MEDICAL UNIV
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