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Astaxanthin and doxorubicin combined preparation and application thereof

A technology of doxorubicin and astaxanthin, applied in the direction of drug combination, medical preparations containing active ingredients, cardiovascular system diseases, etc., to reduce myocardial toxicity and improve anti-tumor activity

Inactive Publication Date: 2020-07-03
JIANGSU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, the combined treatment of 2 μM astaxanthin + 1 μM doxorubicin is the best

Method used

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  • Astaxanthin and doxorubicin combined preparation and application thereof
  • Astaxanthin and doxorubicin combined preparation and application thereof
  • Astaxanthin and doxorubicin combined preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1 Effect of Astaxanthin on Viability of Cardiomyocytes Injured by Adriamycin

[0016] One-day-old newborn SD suckling mice (provided by the Experimental Animal Center of Jiangsu University) were taken, and the apex of the heart was taken, and routinely digested with trypsin (Sigma Company) to obtain cardiomyocytes.

[0017] Suspend the cells in DMEM medium (Gibico) containing 10% fetal bovine serum (HyClone) at 37°C in 5% CO 2 After culturing for 2 h, the obtained cardiomyocytes were purified. according to 10 5 cells / mL were inoculated in a 96-well plate and cultured for 48 hours. Doxorubicin DOX (Sigma Company) was dissolved in physiological saline, with a final concentration of 10 μM; astaxanthin AST (Sigma Company) was dissolved in double-distilled water, with a final concentration of 25 μM, and then diluted to 20 μM, 15 μM, 10 μM, and 5 μM, respectively. The obtained cardiomyocytes were processed as follows:

[0018] ①Control group (Control group): 200μL...

Embodiment 2

[0032] Example 2 Effect of Astaxanthin on Cardiomyocyte Injury Caused by Adriamycin

[0033] One-day-old newborn SD suckling mice were taken, and the apex of the heart was taken, and cardiomyocytes were obtained by routine digestion with trypsin.

[0034] Suspend cells in DMEM medium containing 10% fetal bovine serum at 37°C, 5% CO 2 After culturing for 2 h, the obtained cardiomyocytes were purified. according to 10 5 cells / mL were inoculated in a 96-well plate and cultured for 48 hours. Doxorubicin was dissolved in normal saline, with a final concentration of 10 μM; astaxanthin was dissolved in double-distilled water, with a final concentration of 25 μM, and then diluted to 20 μM, 15 μM, 10 μM, and 5 μM, respectively. The obtained cardiomyocytes were processed as follows:

[0035] ①Control group (Control group): 200μL DMEM

[0036] ②1μM doxorubicin DOX group: 180μL DMEM+20μL DOX

[0037] ③0.5 μM astaxanthin AST+1 μM doxorubicin DOX group: 160 μL DMEM+20 μL AST+20 μL DOX...

Embodiment 3

[0046] Example 3 Effect of Astaxanthin and Adriamycin Combined Administration on Mitochondrial Membrane Potential

[0047] One-day-old newborn SD suckling mice were taken, and the apex of the heart was taken, and cardiomyocytes were obtained by routine digestion with trypsin.

[0048] Suspend cells in DMEM medium containing 10% fetal bovine serum at 37°C, 5% CO 2 After culturing for 2 h, the obtained cardiomyocytes were purified. according to 10 5 cells / mL were inoculated in a 6-well plate and cultured for 48 h. Doxorubicin was dissolved in normal saline with a final concentration of 10 μM; astaxanthin was dissolved in double distilled water with a final concentration of 20 μM. The obtained cardiomyocytes were processed as follows:

[0049] ①Control group (Control group): 2.5mL DMEM

[0050] ②1μM doxorubicin DOX group: 2.25mL DMEM+0.25mL DOX

[0051] ③2μM astaxanthin AST+1μM doxorubicin DOX group: 2mL DMEM+0.25mL AST+0.25mL DOX

[0052] After 24 hours of drug treatment,...

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Abstract

The invention provides an astaxanthin and doxorubicin combined preparation and an application thereof. The astaxanthin and doxorubicin combined preparation comprises astaxanthin and doxorubicin, wherein the molar concentration ratio of astaxanthin to doxorubicin is (0.5-2.5) to 1; and preparation is an injection preparation or an oral preparation. The astaxanthin and doxorubicin combined preparation is applied to doxorubicin cardiomyopathy. Influence of the astaxanthin and doxorubicin combined preparation on doxorubicin side effects are analyzed from the aspects of myocardial cell activity, mitochondrial membrane potential, inflammatory factor NF-kB signal path; and in addition, relevant experiments of astaxanthin on the doxorubicin anti-tumor activity are carried out, and prove that the astaxanthin can lower doxorubicin cardiotoxicity by protecting mitochondria and regulating the inflammatory factor NF-kB signal path, and has the effect of improving the doxorubicin anti-tumor activity, wherein the best effect can be achieved by joint treatment of 2[mu]m of astaxanthin and 1[mu]m of doxorubicin.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a combined preparation of astaxanthin and doxorubicin and its application. Background technique [0002] Doxorubicin is an anthracycline tumor antibiotic, which is widely used in clinical practice and has a very significant effect on leukemia, lymphoma, breast cancer, lung cancer and other tumor diseases. Doxorubicin also has strong toxic and side effects on cardiomyocytes. As the dose increases, it can induce cardiomyopathy and even lead to heart failure in patients. Most researchers believe that doxorubicin may be related to oxidative stress, free radical damage, calcium overload, and apoptosis. Therefore, there have been many anti-oxidants, free radical scavengers, calcium ion inhibitors and other drugs. But so far clinical research has not found an effective drug against adriamycin myocardial injury. In addition, some drugs reduce the anti-tumor activity of doxorubicin ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/122A61K31/704A61P9/00A61P35/00
CPCA61K31/122A61K31/704A61P9/00A61P35/00
Inventor 高恶斌刘坤叶鹏林朱杨杰
Owner JIANGSU UNIV
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