复方南星止痛膏活性成分在不同接收介质中的透皮扩散行为比较  

Comparison of Transdermal Diffusion Behavior of Active Ingredients from Compound Nanxing Zhitong Plaster in Different Receiving Media

作　　者：李璐[1] 周建明[1] 杨一帆[1] 王永香[1] 吴云[1] 王振中[1] 萧伟[1] 

机构地区：[1]江苏康缘药业股份有限公司中药制药过程新技术国家重点实验室

出　　处：《中国实验方剂学杂志》2018年第3期1-7,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家“重大新药创制”科技重大专项(2013ZX09402203)

摘　　要：目的：比较复方南星止痛膏活性成分在不同介质中的透皮扩散行为。方法：采用改良的Franz扩散池,以离体裸鼠的皮肤作为透皮屏障,以生理盐水,pH 7.4磷酸盐缓冲液和30%聚乙二醇400（PEG400）生理盐水为接收介质,比较复方南星止痛膏活性成分的透皮扩散行为。采用HPLC测定样品中肉桂酸、桂皮醛、丹皮酚、丁香酚、水杨酸甲酯的含量,流动相乙腈（A）-0.1%乙酸水溶液（B）梯度洗脱（0~8 min,20%~40%A;8~15 min,40%~60%A;15~20 mim,60%~80%A;20~25 min,80%A）,检测波长276 nm和320 nm。结果：生理盐水和pH 7.4磷酸盐缓冲液作为透皮扩散介质时,丁香酚、丹皮酚的扩散规律符合零级动力学及一级动力学方程;水杨酸甲酯的扩散符合Ritger-Peppas方程;肉桂酸与桂皮醛在生理盐水接收液中存在相互转化,10 h后,肉桂酸显著增加,桂皮醛大幅度下降;在pH 7.4磷酸盐缓冲液中,桂皮醛和肉桂酸释放10 h后趋于饱和,释放量不再增加。PEG400组丹皮酚、丁香酚符合零级动力学及一级动力学方程;肉桂酸及桂皮醛的转化不明显,12 h后,桂皮醛持续释放,肉桂酸释放完毕后即不再释放;水杨酸甲酯的透皮扩散更接近于Higuchi方程。结论：30%PEG400生理盐水作为接收介质时,各成分的透皮扩散速率明显较优,且可抑制桂皮醛向肉桂酸的转化,可作为复方南星止痛膏后续透皮扩散研究的接收介质。Objective： To study on transdermal diffusion behavior of active ingredients from compound Nanxing Zhitong plaster in different media. Method： The improved Franz diffusing cell was adopted with skin of nude mice in vitro as transdermal barrier. The transdermal diffusion behavior of active ingredients in compound Nanxing Zhitong plaster was carried with physiological saline, pH 7. 4 phosphate buffer solution or 30%polyethylene glycol（PEG） 400 normal saline as the receiving medium. The chromatographic condition was established to determine the contents of cinnamic acid,paeonol,eugenol,cinnamic aldehyde and methyl salicylate in the sample. HPLC separation was performed on detection wavelengths of 276 nm and 320 nm by using acetonitrile-0. 1% acetic acid aqueous solution as the mobile phase for gradient elution. Result： With physiological saline and pH 7. 4 phosphate buffer solution as the receiving media,the diffusion regulation of paeonol and eugenol accorded with zero order kinetics and the first-order kinetics equation, while the diffusion action of methyl salicylate accorded with Ritger-Peppas equation. Cinnamic acid and cinnamic aldehyde had reciprocal transformation in the physiological saline. After diffusion of 10 h,the release amount of cinnamic acid increased significantly,while cinnamic aldehyde had a big drop. Cinnamic acid and cinnamic aldehyde were no longer increased after 10 h with the saturation condition in pH 7. 4 phosphate buffer solution. With 30% PEG400 normal saline as the receiving medium, the diffusion regulation of paeonol and eugenol also accorded with zero order kinetics and the first-order kinetics equation, while the diffusion action of methyl salicylate was closer to the Higuchi equation. The transformation of cinnamic acid and cinnamic aldehyde was not obvious in 30% PEG400 normal saline,after diffusion of 12 h,the release amount of cinnamic acid released continuously,while cinnamic aldehyde was no longer released after the release finished. Conclusion： When 30% PEG400 norm

关 键 词：复方南星止痛膏 透皮扩散 肉桂酸 丹皮酚 丁香酚 桂皮醛 水杨酸甲酯 

分 类 号：R283.6[医药卫生—中药学] R944.21[医药卫生—中医学]