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Application of Toonacillin in preparation of medicine for preventing or treating cardiotoxicity generated by antitumor chemotherapy medicine

A technology of antineoplastic drugs and chemotherapeutic drugs, which is applied in the direction of antineoplastic drugs, drug combinations, and pharmaceutical formulas, and can solve problems such as prominent cardiotoxicity and side effects, and achieve the effects of low cost, reduced cardiotoxicity, and high price

Active Publication Date: 2022-07-29
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But at the same time, the long-term survival of patients increases the cumulative amount of anticancer drugs taken, which highlights the side effects of related cardiotoxicity, especially the cardiotoxicity of anthracyclines is still the most common and serious anticancer treatment. Cardiovascular Adverse Reactions
Although anthracyclines are constantly being introduced, the problem of cardiotoxicity still exists due to the similar core structure

Method used

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  • Application of Toonacillin in preparation of medicine for preventing or treating cardiotoxicity generated by antitumor chemotherapy medicine
  • Application of Toonacillin in preparation of medicine for preventing or treating cardiotoxicity generated by antitumor chemotherapy medicine
  • Application of Toonacillin in preparation of medicine for preventing or treating cardiotoxicity generated by antitumor chemotherapy medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1. Toonacilin reduces the increase in the death rate of H9C2 cells caused by doxorubicin

[0048] H9C2 cells were seeded into 96-well plates at 6,000 cells / well, incubated for 24 hours, treated with drugs, added with MTT 24 hours later, and detected with a microplate reader 4 hours later to calculate the survival rate.

[0049] The result is as figure 1 As shown, in the presence of only doxorubicin, H9C2 cells died in a dose-dependent manner, with IC50 of 3.603+0.2850 (μM). It increased to 8.727+0.4014 (μM).

Embodiment 4

[0050] Example 4. Toonacilin reduces the increase of ROS level in H9C2 cells caused by doxorubicin

[0051] H9C2 cells were seeded into 96-well plates at 6,000 cells / well, and treated with drugs after 24 hours of incubation. The experimental groups were: 1, blank control; 2, 2 μM doxorubicin; 3, 20 μM toonacilin; 4, 2 μM doxorubicin +20 μM toonacilin; 5, 2 μM doxorubicin+10 μM LY294002; 6, 2 μM doxorubicin+20 μM toonacilin+10 μM LY294002. After 24 hours of incubation, the medium was aspirated and discarded, ROS probe DCFH-DA diluted with serum-free medium was added and incubated in the dark for 20 minutes, followed by fixation with 4% paraformaldehyde for 10 minutes, DAPI staining for 10 minutes, and finally under a fluorescence microscope. Observe the fluorescence intensity.

[0052] figure 2 For the quantitative results of the fluorescence data, in the presence of only doxorubicin, the intracellular fluorescence intensity was significantly stronger than that in the blank gr...

Embodiment 2

[0053] Example 2. Toonacilin reduces mitochondrial damage in H9C2 cells caused by adriamycin

[0054] H9C2 cells were seeded into a 96-well plate at 6000 cells / well, and drug treatment was performed after incubation for 24 hours. The experimental grouping and drug concentration were the same as those in Example 4. After 24 hours of incubation, the medium was aspirated and discarded, and the mitochondrial red probe mito-traker red diluted with serum-free medium was added for 20 minutes in the dark, then fixed with 4% paraformaldehyde for 10 minutes, and stained with DAPI for 10 minutes. The fluorescence intensity was observed under a microscope.

[0055] image 3 For the quantitative results of the fluorescence data, in the presence of only doxorubicin, the intracellular fluorescence intensity was significantly weakened compared with the blank group, indicating mitochondrial damage, while the fluorescence intensity of the toonacilin combined treatment group rebounded, indicati...

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Abstract

The invention belongs to the field of natural product pharmacology, and particularly relates to application of Toonacillin or pharmaceutically acceptable salt thereof in preparation of drugs for preventing or treating cardiotoxicity generated by antitumor chemotherapy drugs, and the Toonacillin can inhibit myocardial cell apoptosis, active oxygen level rise, mitochondrial injury and other events caused by the chemotherapy drugs. Meanwhile, decline of heart injury indexes can be observed in a mouse model. The compound can be used as a myocardial protection active component or a medicine composition component in a chemotherapy regimen of a drug-resistant patient, and the cardiotoxicity of the chemotherapy medicine is reduced while the killing effect of the chemotherapy medicine is recovered.

Description

technical field [0001] The invention belongs to the field of natural product pharmacology, in particular to the application of Toonacilin in the preparation of a drug for preventing or treating cardiotoxicity produced by an anti-tumor chemotherapeutic drug. Background technique [0002] In recent years, the prognosis of patients with malignant tumors has been improving due to advances in surgical treatment, radiotherapy, and chemotherapy with anticancer drugs. However, at the same time, the long-term survival of patients increases the cumulative amount of anticancer drugs, which highlights the side effects of related cardiotoxicity, especially the cardiotoxicity of anthracyclines, which is still the most common and serious anticancer treatment related. Cardiovascular adverse reactions. Despite the continuous introduction of anthracyclines, the problem of cardiotoxicity persists due to the similar structure of the parent nucleus. The common mechanisms are mostly related to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/341A61K31/704A61P9/00A61P35/00
CPCA61K31/341A61K31/704A61P9/00A61P35/00A61K2300/00
Inventor 孔令义罗俊崔乐天
Owner CHINA PHARM UNIV
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