双黄连冻干粉透过人胎盘屏障的药物成分研究

目的:建立中、晚期人胎盘屏障体外模型,采用高效液相色谱技术,研究双黄连冻干粉透过人胎盘屏障的药物成分。方法:采用Ussing chamber技术建立中、晚期人胎盘屏障体外模型,预平衡30 min后,分别于母体池加入不同浓度双黄连冻干粉溶液,60 min后在胎儿池取样,应用高效液相色谱技术,分析样品中所含药物成分。色谱柱为Zorbax-C₁₈,流动相为乙腈-1%甲酸水溶液(梯度洗脱),流速为1.0 mL·min^-1,检测波长为280 nm,柱温为25℃,进样量为10 μL。结果:双黄连冻干粉透过妊娠中期人胎盘屏障体外模型样品中未检测到待测成分,透过妊娠晚期人胎盘屏障体外模型样品中检测到黄芩苷、连翘苷、木犀草素和汉黄芩苷。结论:妊娠晚期应用双黄连冻干粉可造成胎儿宫内暴露,对其胎盘透过液的胚胎毒性研究将成为评价双黄连冻干粉妊娠期应用安全性的关键。

Objective:To establish a mid and late human placental barrier in vitro model,and study the ingredients of freeze-dried Shuanghuanglian powder that can pass through the placental barrier using high performance liquid chromatography(HPLC) technology.Methods:A mid and late human placental barrier in vitro model was established,then different concentrations of Shuanghuanglian were added in maternal sides after balance for 30 min.Sixty min after dosing in fatal sides,the ingredients were analyzed using high performance liquid chromatography(HPLC) technique.HPLC was performed on a column of Agilent Zorbax-C₁₈ with mobile phase of acetonitrile -1% formic acid aqueous solution(gradient elution) at a flow rate of 1.0 mL·min^-1.The detection wavelength was 280 nm,column temperature was 25℃,and the sample volume was 10 μL.Results: The composition of Shuanghuanglian could not pass through middle stage human placental barrier in vitro model.The ingredients of Shuanghuanglian passing through later stage human placental barrier were baicalin, forsythin,luteolin and wogonoside.Conclusion:The application of Shuanghuanglian in late pregnancy can cause fetal exposure,for which reason the study of the liquid toxicity should be the key to evaluating the security of Shuanghuanglian application in pregnancy.

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