Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of compounds acting on choline or tmao-related targets in the preparation of drugs for preventing and/or reversing clopidogrel resistance

A clopidogrel resistance and compound technology, applied in the directions of hydroxy compound active ingredients, drug combinations, drug delivery, etc., can solve problems such as increased bleeding risk, and achieve the effects of inhibiting NOX) activity, inhibiting Nrf2 activity, and reducing TMAO generation.

Active Publication Date: 2021-12-21
普灵生物(南京)有限公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, more potent antiplatelet agents of the same class are often associated with an increased risk of bleeding

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of compounds acting on choline or tmao-related targets in the preparation of drugs for preventing and/or reversing clopidogrel resistance
  • Application of compounds acting on choline or tmao-related targets in the preparation of drugs for preventing and/or reversing clopidogrel resistance
  • Application of compounds acting on choline or tmao-related targets in the preparation of drugs for preventing and/or reversing clopidogrel resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Animal experiment

[0035] 1. Male, 6-8-week-old C57BL / 6J mice (body weight 18±1 g) were purchased from the Animal Model Center of Nanjing University, and fed water and common food according to the requirements of routine animal experiments.

[0036] After obtaining the approval of the animal experiment ethics review application, according to different research purposes, the mice were randomly divided into groups: normal saline (solvent) control group (Ctrl), TMAO group, choline group (choline), choline + DMB group, daily Oral administration continued for 14 days. The specific doses for intragastric administration are as follows: TMAO (6mg / day), choline (50mg / day), DMB (1.2μmol / day), refer to relevant literature (Wang Z et al., Cell2015; 163:1585-95; ZhuW et al. al., Cell 2016; 165:111-24). After intragastric administration of normal saline (solvent control, Ctrl), TMAO, choline, and choline+DMB respectively for 14 days, the concentration of TMAO in mouse plasma was d...

Embodiment 2

[0044] 2. Cell experiments

[0045] 1. HepG2 cells were selected as the human hepatocyte model to detect whether the effects of different doses of TMAO (0, 50, 100, 200 μM) on intracellular ROS production and Keap1 / Nrf2 protein expression were dose-dependent; combined ROS scavenger NAC (1mM ) can significantly inhibit the production of intracellular ROS induced by TMAO (100 μM), inhibit the increase of Nrf2 nuclear entry and the increase of Ces1 protein expression level; whether combined Nrf2 inhibitor ML385 (10 μM) can significantly inhibit the cell Upregulation of Nrf2 nuclear import and Ces1 protein expression levels. According to conventional cell culture methods, when the confluence of cultured HepG2 cells was 75%-85%, TMAO and / or other test compounds were added according to experimental groups, and the cells were cultured for another 24 hours. The ROS kit (DCFH-DA active oxygen fluorescent probe method) was used to detect the relative concentration of ROS in the cells, ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides the application of compounds acting on choline or trimethylamine oxide (TMAO)-related targets in the preparation of drugs for preventing and / or reversing clopidogrel resistance, said compounds comprising NOX inhibitors, ROS scavengers, Nrf2 One or more of inhibitors and intestinal microbial choline TMA lyase inhibitors. The present invention systematically explores the effects of choline or TMAO on the metabolic activation and antiplatelet effects of clopidogrel and its various intervention mechanisms, and provides a new treatment for effectively overcoming clopidogrel resistance associated with choline or TMAO in clinical practice Targets and prevention strategies.

Description

technical field [0001] The invention belongs to the technical field of drug research and development, and particularly relates to the application of compounds acting on choline or trimethylamine oxide (TMAO)-related targets in the preparation of drugs for preventing and / or reversing clopidogrel resistance. Background technique [0002] Clopidogrel is one of the "essential drugs" for antiplatelet therapy selected by the World Health Organization (WHO) (Patel A et al., Circ Cardiovasc Qual Outcomes 2015; 8:447-51). Since it was approved by the U.S. FDA in 1997, clopidogrel is one of the most commonly used drugs for clinicians in various countries to prevent thrombosis in vascular stents or recurrence of heart, cerebrovascular embolism or ischemic events. It is composed of aspirin The "dual antiplatelet therapy" is widely recognized as the "gold standard" of antiplatelet therapy. As a prodrug, clopidogrel itself has no pharmacological activity. After being orally absorbed int...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K31/12A61K31/198A61K31/427A61K31/045A61K31/4365A61P7/02
CPCA61K45/06A61K31/12A61K31/198A61K31/427A61K31/045A61K9/0053A61K31/4365A61P7/02A61K2300/00
Inventor 谢红光葛鹏新邰婷蒋立平吉金子米琼宇
Owner 普灵生物(南京)有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com