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Application of compound Isaridin E or pharmaceutical salt thereof in preparation of antithrombotic drugs

A technology of antithrombotic drugs and medicinal salts, applied in the field of medicine and biology, can solve the problems of no antithrombotic effect, increase the risk of bleeding in patients, and bleeding, so as to improve the pathological situation of pulmonary embolism, inhibit platelet thrombus, and have small bleeding side effects Effect

Active Publication Date: 2022-02-22
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the above drugs have side effects of bleeding, which increases the risk of bleeding in patients. Therefore, there has been an urgent need to develop new antiplatelet drugs. The ideal antiplatelet drug should not affect the normal blood coagulation function while exerting antithrombotic effect
[0005] At present, the anti-bacteria and anti-phytopathogenic fungi of cyclic depsipeptide Isaridin compounds are mainly concentrated on the effect, and there is no report on the research results of antithrombotic effect

Method used

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  • Application of compound Isaridin E or pharmaceutical salt thereof in preparation of antithrombotic drugs
  • Application of compound Isaridin E or pharmaceutical salt thereof in preparation of antithrombotic drugs
  • Application of compound Isaridin E or pharmaceutical salt thereof in preparation of antithrombotic drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Effects of Compound ISE on Platelet Inflammation, Aggregation Function and Activation in Vitro

[0033] (1) Materials and methods

[0034] 1. Drug preparation

[0035] The compound Isaridin E was provided by the research group of Professor Liu Lan, School of Oceanography, Sun Yat-sen University (chemical formula as figure 1 ), as a white crystalline solid, stored at room temperature. Grind into powder when used, dissolve in DMSO to prepare storage solution (incubation concentration is 12.5 μM, 25 μM, 50 μM, 100 μM, control dosing volume to 2.5 μl), store at 4°C for later use. Plavix (clopidogrel) was purchased from Sanofi (75 mg tablet), ground into a powder, dissolved in DMSO to prepare a storage solution (incubation concentration of 20 μM, controlled dosing volume of 2.5 μl), and stored at 4°C for later use.

[0036] The structural formula of compound Isaridin E is as follows:

[0037]

[0038] Wherein, (A) is a planar structural formula. (B) is a three-dimens...

Embodiment 2

[0067] Effect of Compound Saridin E on Arterial and Venous Thrombosis in Mice

[0068] (1) Materials and methods

[0069] 1. Drug preparation

[0070]The compound Isaridin E was ground into powder and dissolved in a solution system of 4% DMSO, 10% Tween-80, 15% propylene glycol and 71% saline (the concentration ratio of the system was obtained from a preliminary experiment, and it can be guaranteed while reducing the toxicity of the solvent as much as possible. The drug is completely dissolved), administered by intragastric administration according to the preset concentration (ISE dosage is 12.5mg / kg·d, 25mg / kg·d, 50mg / kg·d and 100mg / kg·d respectively, and the administration volume is 200 mg / kg·d. -600 μl). Plavix (clopidogrel) was purchased from Sanofi (75mg tablet), and it was ground into powder during administration, dissolved in normal saline for intragastric administration (the dosage was 10mg / kg·d, which was the recommended dosage according to the instructions) In con...

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Abstract

The invention discloses application of a compound Isaridin E or a pharmaceutical salt thereof in preparation of antithrombotic drugs, and relates to the technical field of medical biology. The invention discloses the application of the marine-derived compound Isaridin E in preparation of antithrombotic drugs for the first time. The compound has a remarkable improvement effect on arterial thrombosis and venous embolism models, and the antithrombotic drug effect of the compound is similar to that of clopidogrel, but the bleeding side effect is remarkably reduced. The medicine can significantly inhibit platelet activation and aggregation, and inhibit platelet-mediated inflammatory response. The invention develops a brand new medical application of the marine compound Isaridin E, and the marine compound Isaridin E can be used for treating abnormal activation of platelets and researching and developing antithrombotic drugs for thrombotic related diseases.

Description

technical field [0001] The invention relates to the field of medical biotechnology, in particular to the application of compound Isaridin E or a pharmaceutically acceptable salt thereof in the preparation of antithrombotic drugs. Background technique [0002] According to statistics, one-fourth of the global death causes are related to thromboembolic diseases, which can be roughly divided into arterial thrombosis and venous thrombosis according to the location of thrombus obstruction, among which ischemic heart disease and ischemic stroke are the main arterial thromboembolic diseases. Diseases, deep venous thrombosis (Deep Venous Thrombosis, DVT) and pulmonary embolism (Pulmonary Thromboembolism, PTE) are the main venous thrombosis (Venous Thromboembolism, VTE). Arterial thrombosis mainly occurs in high-shear stress sites such as the coronary system and the cerebral circulatory system, and abnormal platelet activation and coagulation pathway activation are the main inducing ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/12A61K9/08A61K9/00A61P7/02A61P29/00
CPCA61K38/12A61K9/0019A61K9/08A61K9/0053A61P7/02A61P29/00Y02A50/30
Inventor 王冠蕾刘岚盘妮李子成李智泓陈森华姜明华
Owner SUN YAT SEN UNIV
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