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Application of glycyrrhizic acid in preparation of sunitinib malate cardiotoxicity reduction drug

A technology of sunitinib maleate and cardiotoxicity, applied in the field of application of glycyrrhizic acid in the preparation of medicines for alleviating the cardiotoxicity of sunitinib maleate

Active Publication Date: 2013-09-11
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far there is no report on its protective effect on the cardiotoxicity induced by sunitinib maleate

Method used

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  • Application of glycyrrhizic acid in preparation of sunitinib malate cardiotoxicity reduction drug
  • Application of glycyrrhizic acid in preparation of sunitinib malate cardiotoxicity reduction drug
  • Application of glycyrrhizic acid in preparation of sunitinib malate cardiotoxicity reduction drug

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Experimental program
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Effect test

Embodiment 1

[0018] Rat primary cardiomyocytes were inoculated in a 96-well plate, and a blank control group, a Sunitinib maleate (Sunitinib) monotherapy group and a glycyrrhizic acid (GA) pretreatment group were set up. Each group set up 5 concentration gradients, 2-fold dilution. Each concentration was replicated in triplicate. After the cells adhered to the wall, glycyrrhizic acid (GA) was added and cultured in the incubator for 24 hours. Then add different concentrations of sunitinib maleate (Sunitinb), continue to cultivate in the incubator for 48 hours, add 5 mg / ml MTT solution, incubate for another 4 hours, then aspirate the liquid and add DMSO to completely dissolve formazan The absorbance was measured at 570 nm with a microplate reader. As shown in Table 1, after the action of 0.3125, 0.625, 1.25, 2.5, 5 and 10 mM sunitinib maleate (Sunitinib), the growth of rat primary cardiomyocytes was inhibited in a dose-dependent manner, while glycyrrhizic acid (GA) After 25 and 50 mM pret...

Embodiment 2

[0021] Forty ICR male mice were randomly divided into 4 groups, 10 in each of the blank control group, Sunitinib model group and Glycyrrhizic acid (GA) pretreatment group. The blank control group was given the same amount of normal saline; the glycyrrhizic acid (GA) single use group was given 10 mg / kg glycyrrhizic acid; 100 mg / kg Sunitinib maleate (Sunitinib). The glycyrrhizic acid (GA) pretreatment group was given 10 mg / kg glycyrrhizic acid, orally administered for four consecutive days, and 100 mg / kg Sunitinib maleate (Sunitinib) by intragastric administration on the fourth day. The mice were weighed every day and the survival of the mice was recorded, and the administration was continued for 30 days. Twenty-four hours after the last administration, the electrocardiogram (Lead II) of the mice in each group was traced in a quiet environment, and the QRS complex wave and S-T wave of the mice were calculated. Afterwards, the mice in each group were removed from the eyes to co...

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Abstract

The invention provides an application of a glycyrrhizic acid composition in preparation of a sunitinib malate cardiotoxicity reduction drug. The composition comprises sunitinib malate and glycyrrhizic acid according to a ratio of 1:2.5, 1:5, 1:10, 1:20, 1:40, 1:80, and 1:160. In vivo experiment and in vitro experiment results show that the glycyrrhizic acid provides a significant protection effect for cardiotoxicity induced by sunitinib malate, and be provided for preventing and reducing sunitinib malate cardiotoxicity and improving cardiac functions after taking sunitinib malate so as to ensure clinical applications of the sunitinib malate.

Description

technical field [0001] The invention belongs to medicinal use, and relates to the use of natural plant extract glycyrrhizic acid in the preparation of medicines for alleviating cardiotoxicity caused by sunitinib maleate. Background technique [0002] Sunitinib maleate is a small-molecule multi-target tyrosine kinase inhibitor (TKIs), which has broad anti-tumor spectrum and strong anti-tumor effect, and is widely used in clinical treatment of advanced renal cell carcinoma (RCC) , Gastrointestinal stromal tumor (GIST) and other tumors and other malignant tumors. There are many adverse reactions of sunitinib maleate, the most serious being dose-dependent cardiotoxicity, which can lead to dose-dependent cardiotoxicity such as myocarditis and ischemic heart failure in patients during the clinical use of sunitinib maleate. Toxicity not only affects the quality of life of patients, but also seriously limits its clinical use. At present, there is no effective protective agent for ...

Claims

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Application Information

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IPC IPC(8): A61K31/704A61P39/02A61P9/00
Inventor 何俏军杨波罗沛华杨晓春王金成朱虹应美丹
Owner ZHEJIANG UNIV
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