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Application of paeonol to preparation of medicine activating hERG ion channel

An ion channel and paeonol technology, applied in the field of biomedicine, can solve the problems of few drugs and few drugs or compounds, and achieve the effect of avoiding complicated time-consuming, avoiding preclinical testing, and increasing K+ efflux.

Inactive Publication Date: 2016-04-06
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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Problems solved by technology

[0004] People have been trying to find drugs that can resist the inhibitory effect of myocardial hERG ion channels, that is, antagonists or activators of myocardial hERG ion channels, but there are very few drugs or compounds that can activate hERG ion channels (since the first report in 2005). Since drugs that can activate hERG ion channels, there are still very few drugs that can activate hERG ion channels)

Method used

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  • Application of paeonol to preparation of medicine activating hERG ion channel
  • Application of paeonol to preparation of medicine activating hERG ion channel
  • Application of paeonol to preparation of medicine activating hERG ion channel

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Embodiment 1

[0016] Paeonol can be obtained from pharmaceutical raw materials or reagent companies, and it needs to be dissolved in dimethyl sulfoxide (DMSO) because of its low water solubility. Dissolve 0.0167g paeonol in 1ml DMSO as the mother solution, then take the corresponding amount from the mother solution, prepare a series of drug concentrations of 10μM, 30μM, 100μM, 300μM, 1000μM in the extracellular solution, and store in a refrigerator at 4°C for later use. The formula of extracellular fluid is: NaCl137mM, KCl4mM, CaCl 2 1.8mM, MgCl 2 1.0mM, glucose10mM, HEPES10mM, adjust the pH to 7.4 with 1M NaOH. 稳定转染了hERG离子通道的中国仓鼠卵巢细胞(CHO)(B.D.Walker,S.M.Valenzuela,C.B.Singleton,S.N.Breit&1T.J.Campbell.InhibitionofHERGchannelsstablyexpressedinamammaliancelllinebytheantianginalagentperhexilinemaleate.BritishJournalofPharmacology127,243-251(1999))以HAMSF-12配于10 % fetal bovine serum (FBS), at 37 ° C, 5% CO2 incubator routine culture. Before the experiment, the cells were digested with 0.05% t...

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Abstract

The invention discloses application of paeonol to preparation of medicine activating an hERG ion channel, and belongs to secondary development and utilization of traditional Chinese medicine effective components. Paeonol has the function of remarkably activating the hERG ion channel, can increase K+ external flow, has the potential in resisting and treating long QT syndromes and has the prospect that paeonol can be developed into medicine preventing acquired long QT syndromes. At present, paeonol is clinically used for treatment of relevant cardiovascular diseases and inflammation prevention, so that paeonol is applied in the aspect of prevention of the acquired long QT syndromes. Complex and time-consuming pre-clinical tests can be avoided.

Description

Technical field: [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of paeonol in the preparation of drugs for activating hERG ion channels. Background technique: [0002] Acquired Long QT Syndrome (AquiredLongQTSyndrome), also known as QT syndrome, is a heart rhythm disorder. The electrocardiogram of patients with this syndrome shows QT interval prolongation, T wave and (or) U wave abnormality. Symptomatic ventricular arrhythmia, especially torsades de pointes (TdP), tends to cause palpitations and dizziness, which can lead to fainting and death in severe cases. The syndrome can be congenital or acquired, and the latter is mostly caused by adverse drug reactions (inhibition of myocardial hERG ion channels). It has been reported that many drugs have been forced to withdraw from the market. In addition, quite a few newly developed drugs have the effect of inhibiting hERG ion channels, thereby inducing long QT syndrome, whic...

Claims

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Application Information

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IPC IPC(8): A61K31/12A61P9/06
CPCA61K31/12
Inventor 李志远黄荣奇龙雁林佐贤马文波
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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