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Application of a kind of indanone derivative in preparation of medicine for treating sepsis

A kind of technology of sepsis and derivatives, applied in the application field of indanone derivatives in the preparation of drugs for treating sepsis

Active Publication Date: 2022-03-22
唐怡庭
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no report about the application of indenone derivatives in the treatment of sepsis

Method used

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  • Application of a kind of indanone derivative in preparation of medicine for treating sepsis
  • Application of a kind of indanone derivative in preparation of medicine for treating sepsis
  • Application of a kind of indanone derivative in preparation of medicine for treating sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: Compounds inhibit primary macrophage pyroptosis induced by LH (LPS+HMGB1) activation of Caspase11

[0051] High-mobility group box 1 protein (HMGB1) is a kind of protein that is highly conserved and widely expressed in mammals. It mainly exists in the nucleus under normal conditions. The medium is released to the outside of the cell and plays an important pathogenic role in diseases or tissue damage (Regulation of post-translational modifications of HMGB1 during immune responses. Antioxid Redox Signal. 2016 Apr 20; 24(12): 620-34.). Invention It was found that HMGB1 released by hepatocytes in sepsis can transport circulating LPS to the cytoplasm of vascular endothelial cells and macrophages, and initiate Caspase-11-mediated pyroptosis (The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-DependentLethality in Sepsis.Immunity.2018 Oct 16; 49(4):740-753.). During the above process, liver cells recognize circulating LPS through their own expressed TLR4 recep...

Embodiment 2

[0063] Example 2: Compounds inhibit LPS entry into cells to inhibit Caspase11-dependent pyroptosis

[0064] 1. Experimental steps: Extract the primary peritoneal macrophages of WT mice, resuspend the cells in RPMI-1640 complete medium to adjust the concentration and plant them in a 6-well plate, 2×10^6 cells / well, wash the cells twice with DBPS after adhering to the wall overnight Change to 1640 serum-free medium. Compound 10 μM final concentration was added to the cells for pre-incubation for 1 h, then the mixture of LPS 1 μg / ml+HMGB 1400 ng / ml (pre-incubated at room temperature for 20 min) was added to stimulate the cells for 2 h, after the cells were washed 3 times with DPBS, the cells were digested with 300 μl / well of 0.25% trypsin, 400μl / well 1640 complete medium to stop the digestion, gently pipet the cells into a 1.5ml sterile enzyme-free EP tube, wash the cells 3 times with DPBS, add 0.005% digitonin (digitonin) 200μl / EP tube and lyse on ice for 10-15min , 13000rpm, c...

Embodiment 3

[0066] Example 3: Protective effect of compounds on mice with endotoxemia

[0067] 1. Experimental procedure: select mice weighing 25-30 g, and divide them into LPS+DMSO group, LPS+compound group and DMSO complete control group. The compound was dissolved in DMSO, and the concentration of the stock solution was 40 mg / ml. The compound was dosed at 4 mg / kg, 100 μl per mouse, injected intraperitoneally 1 hour in advance, and then injected with LPS 10 mg / kg, 100 μl per mouse; in the LPS+DMSO group, DMSO 100 μl was injected intraperitoneally 1 hour in advance, and then injected LPS 10 mg / kg, 100 μl per mouse. DMSO complete control group was injected intraperitoneally with DMSO 100μl / rat. The survival rate of mice in each group was observed within 5 days.

[0068] 2. Experimental results: the experimental results of this embodiment are as follows Figure 5 shown, from Figure 5 It can be seen that after using the compound, the survival rate of endotoxemia mice is improved, which...

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Abstract

The invention discloses the application of an indanone derivative in preparing a medicine for treating sepsis. The structure of the indanone derivative is as follows: the indanone derivative has certain effects on sepsis and endotoxemia. The therapeutic effect can effectively improve the survival rate of mice with sepsis and endotoxemia, and provide new therapeutic methods and drugs for clinical treatment of sepsis.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of an indanone derivative in the preparation of medicines for treating sepsis. Background technique [0002] Sepsis (sepsis, also known as sepsis) is an infection-induced critical illness characterized by multiple organ failure. Its common clinical symptoms include fever, rapid breathing rate and heartbeat, and unconsciousness. Severe sepsis can lead to insufficient blood flow to supply tissues and even lead to organ failure and septic shock, seriously threatening the lives of patients. At present, treatment such as early fluid resuscitation, early use of antibiotics and organ function support has reduced the mortality rate of sepsis to a certain extent, but sepsis is still the leading cause of death in intensive care unit (ICU) patients. [0003] The pathogenesis of sepsis is very complex. In recent years, some studies have revealed a new pathogenesis of sepsis: cyste...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/136A61P31/04
CPCA61K31/136A61P31/04
Inventor 唐怡庭吕奔
Owner 唐怡庭
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