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New application of antiplatelet thrombolysin

An anti-platelet and thrombolytic technology, which is applied in the field of medicine, can solve problems such as metabolic dysfunction, pro-inflammatory imbalance, and reduce the body's anti-inflammatory effects, and achieve the effects of inhibiting inflammation, inhibiting inflammatory reactions, and increasing blood flow velocity

Active Publication Date: 2021-10-15
ZHAOKE PHARMA HEFEI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Normally, the inflammatory response plays a protective role in the body, but when the inflammatory response is too strong, a large number of inflammatory mediators will be produced, which will cause the imbalance of anti-inflammatory and pro-inflammatory in the body, and pro-inflammatory factors such as TNF-α, IL-1β and IL-6 Mediators can induce the body to produce a large number of secondary inflammatory mediators, such as PGE 2 , PAF, and some adhesion factors, etc. These inflammatory mediators can mediate the interaction between inflammatory cells and vascular endothelial cells, reduce the body's anti-inflammation, cause metabolic dysfunction, and cause systemic inflammatory response syndrome

Method used

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  • New application of antiplatelet thrombolysin
  • New application of antiplatelet thrombolysin
  • New application of antiplatelet thrombolysin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 Antiplatelet Thrombolysin Inhibits the Binding of αMβ2 Integrin to Platelets

[0035] Platelets from mice and humans were mixed with control IgG (10 μg / ml), BD34 (anti-PD1 antibody, 10 μg / ml), BSA (bovine serum albumin, 0.2 μg / ml) and anfibatide (anti-platelet Thrombolysin 0.2μg / ml) pre-incubated for 30min, and then HEPES-Tyrode buffer (20mM HEPES, pH 7.4, 136mM NaCl, 2.7mM KCl, 12mMNaHCO 3 ,2mM MgCl 2 , and 5.5mM glucose) to wash the platelets, wash the platelets with or without 0.5mM MnCl 2 The treated recombinant human αMβ2 integrin (10 μg / ml) was incubated at 37°C for 30 minutes, unbound αMβ2 was washed away, and the remaining platelets were incubated with 5 μg / ml IgG-FITC or goat anti-human β2 antibody, and detected by flow cytometry.

[0036] αMβ2, also known as Mac-1 or CD11b / CD18, is a member of the integrin family and is the main factor that mediates cell and extracellular matrix and intercellular adhesion. It can recognize and bind to the correspon...

Embodiment 2

[0039] Example 2 Anti-platelet thrombolysin reduces TNF-α-induced platelet-neutrophil aggregation in wt mouse model

[0040] Neutrophils are the first immune cells to reach the site of infection. They are released into the blood after they differentiate into mature cells carrying particulate matter in the bone marrow. In the absence of infection, neutrophils remain in a quiescent state Exist in peripheral blood, but once bacteria invade, the body will quickly recruit neutrophils to the infection site, neutrophils jointly produce a variety of bactericidal substances through phagocytosis, release proteases from granules, and neutrophils At the same time, neutrophils also secrete chemokines to recruit other immune cells to the infection site and jointly eliminate the infectious agent.

[0041] However, overactivated neutrophils will be recruited to some important organs. In these organs, the bactericidal substances carried by activated neutrophils will be released locally in larg...

Embodiment 3

[0046] Example 3 Inhibitory Effect of Antiplatelet Thrombolysin on TNF-α-Induced Inflammation

[0047] TNF-α is an important pro-inflammatory cytokine, which has physiological functions such as participation in immunity, anti-tumor, anti-virus, and regulation of specific gene expression, and plays a vital role in the regulation of the immune-inflammation coordinated signal network. If TNFα is overexpressed, it will cause inflammatory response diseases and natural immune diseases.

[0048] WT mice were taken, and TNF-α was injected into the scrotum after anesthesia, and BSA 50ng / gBW and Anfibatide (25, 50ng / gBW) were administered 3 hours later, and the real-time microscopic observation and recording were made in vivo. WT mouse platelets were labeled with calcein AM, respectively, with IgG (10 μg / ml), anti-PDI (10 μg / ml), BSA (0.2 μg / ml), anfibatide (0.2 μg / ml), anfibatide+anti-PDI After pre-incubation, according to the number of platelets 2x10 9 Each TNF-α mouse was injected ...

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Abstract

The invention relates to the field of medicine, and discloses the application of anti-platelet thrombolysin in the preparation of anti-inflammatory drugs. Experiments have confirmed that the anti-platelet thrombolysin of the present invention can inhibit the interaction between platelets and leukocytes mediated by αMβ2 integrin, reduce the aggregation between neutrophils, and also reduce the combination between platelets and neutrophils, Thereby play the role of inhibiting inflammation, has a good prospect of clinical application.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a new application of anti-platelet thrombolysin in the preparation of anti-inflammatory drugs. Background technique [0002] Inflammation refers to exogenous and endogenous damage factors that cause a variety of damage to cells. A series of complex reactions occur locally and throughout the body to confine and eliminate damage factors, remove and absorb necrotic tissue, and repair Injury is a defensive response of the body. [0003] The factors that cause the body's inflammatory response include external biological factors, physical and chemical factors, autologous necrotic tissue, and allergic reactions. Vascular response is the central link in the inflammatory process, and some inflammatory factors can directly damage the vascular endothelium, causing increased vascular permeability. However, many inflammatory factors do not directly act on local vascular tissue, but mainly cause infl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/48A61P29/00
CPCA61K38/48A61P29/00A61K38/1703A61K38/4806
Inventor 楚在玹李小羿戴向荣
Owner ZHAOKE PHARMA HEFEI
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