Application of tetrahydropalmatine in the preparation of anti-cisplatin toxicity drugs

A technology of tetrahydropalmatine and levocordantine, which is applied in the field of application of tetrahydropalmatine in the preparation of anti-cisplatin toxicity drugs, can solve the problems of small effect and enhanced nephrotoxicity of cisplatin, and achieve the purpose of weakening toxicity and reducing nephrotoxicity Effect

Active Publication Date: 2017-12-26
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cimetidine competitively inhibits MATEs more than OCT2, but enhances cisplatin nephrotoxicity
For cisplatin ototoxicity or neurotoxicity, anti-oxidation and free radical scavenging methods are commonly used in clinic to antagonize, but the effect is very little

Method used

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  • Application of tetrahydropalmatine in the preparation of anti-cisplatin toxicity drugs
  • Application of tetrahydropalmatine in the preparation of anti-cisplatin toxicity drugs
  • Application of tetrahydropalmatine in the preparation of anti-cisplatin toxicity drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 Concentration-dependent toxicity of cisplatin on MDCK-hOCT2, MDCK-hOCT2 / hMATE1 and mock cells

[0024] 1.1 Seeding cells on a 96-well plate

[0025] Select MDCK-hOCT2, MDCK-hOCT2 / hMATE1 and mock cells in the logarithmic growth phase (constructed by Zhejiang University School of Pharmacy, see a: Lei Hongmei et al. for specific construction methods, stably express hMATE1 and co-express hMATE1 and hOCT1 or hOCT2 cells Model construction. Acta Pharmaceutica Sinica, 2015, 50(7): 842-847. b: Wang K., et al., Involvement of organic cation transporter 2 inhibition in potential mechanisms of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry , 2014,53: 90-98), digest and collect cells. Resuspend the cells with fresh medium and adjust the cell density to 4.0 × 10 4 cells / mL, inoculated in 96-well cell plate at 0.2 mL / well.

[0026] 1.2 MTT experiment

[0027] After the cells were cultured for 24 h, the medium was discarded, and the medium containing...

Embodiment 2

[0030] Embodiment 2 tetrahydropalmatine, including (-)-THP, (+)-THP and (±)-THP to MPP + Inhibition of accumulation on MDCK-hOCT2 and MDCK-hMATE1 cells

[0031] Select MDCK-hOCT2, MDCK-hOCT2 / hMATE1 and MDCK-hMATE1 cells in the logarithmic growth phase (constructed by Zhejiang University School of Pharmacy, see a: Lei Hongmei et al. for specific construction methods, stably express hMATE1 and co-express hMATE1 and hOCT1 or Construction of hOCT2 cell model. Acta Pharmaceutica Sinica, 2015,50(7):842-847.b:Wang K., et al., Involvement of organic cation transporter 2 inhibition in potential mechanisms of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry , 2014,53: 90-98), digest and collect cells. Resuspend the cells with fresh medium and adjust the cell density to 2.0 × 10 5 Cells / mL, inoculated at 0.5 mL / well in a 24-well cell plate for culture, when the cells grow to 90% confluence, they can be used for accumulation experiments.

[0032] MDCK-hOCT2 and MDCK-...

Embodiment 3

[0033] Example 3 (-)-THP, (+)-THP and (±)-THP on the toxicity of cisplatin on MDCK-hOCT2 and MDCK-hOCT2 / hMATE1 cells

[0034] 3.1 MTT experiment

[0035] Select MDCK-hOCT2 and MDCK-hOCT2 / hMATE1 in the logarithmic growth phase (constructed by the School of Pharmacy, Zhejiang University, see a: Lei Hongmei et al., for the construction of a cell model that stably expresses hMATE1 and co-expresses hMATE1 and hOCT1 or hOCT2 .Acta Pharmaceutica Sinica, 2015,50(7):842-847.b:Wang K., et al., Involvement of organic cation transporter 2 inhibition in potential mechanisms of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry , 2014,53: 90-98), digest and collect cells. Resuspend the cells with fresh medium and adjust the cell density to 4.0 × 10 4 mL -1 , inoculated in 96-well cell plate at 0.2 mL / well. After the cells were cultured for 24 h, the medium was discarded, and a cisplatin medium solution containing 1-100 μmol / L (-)-THP, (+)-THP and (±)-THP was added to cont...

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PUM

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Abstract

The present invention provides a use of tetrahydropalmatine in preparing an anti-cisplatin toxicity medicament, the toxicity comprising renal toxicity, ototoxicity, and neurotoxicity.

Description

technical field [0001] The invention belongs to the use of medicine, and relates to the application of tetrahydropalmatine in reducing the toxicity caused by cisplatin, including nephrotoxicity, ototoxicity and neurotoxicity. technical background [0002] Cisplatin is one of the most clinically effective broad-spectrum antineoplastic drugs and is widely used in the treatment of various solid tumors such as ovarian cancer, prostate cancer, lung cancer, and breast cancer. However, its severe side effects include nephrotoxicity, ear Toxicity and neurotoxicity limit its clinical application, especially nephrotoxicity and ototoxicity are the most serious. Although protective measures such as hydration therapy or forced diuresis are used clinically, the incidence of nephrotoxicity of cisplatin is still as high as 25-35%, and it occurs immediately in the initial stage of treatment. Through mechanisms such as oxidative stress, DNA damage, and inflammatory response, cisplatin can le...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4375A61P39/02
CPCA61K9/00A61K31/4375
Inventor 李丽萍蒋惠娣周慧曾苏
Owner ZHEJIANG UNIV
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