筋骨止痛凝胶中功效物质的体外透皮扩散行为研究  

Transdermal diffusion research on functional substances of Jingu Zhitong Gel

作　　者：李璐[1] 李家晴 刘文君[1] 曹亮[1] 章晨峰[1] 王振中[1] 肖伟[1] LI Lu;LI Jia-qing;LIU Wen-jun;CAO Liang;ZHANG Chen-feng;WANG Zhen-zhong;XIAO Wei(National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture,Jiangsu Kanion Pharmaceutical Co.,Ltd.,Lianyungang 222001,China)

机构地区：[1]江苏康缘药业股份有限公司中药制药过程控制与智能制造技术全国重点实验室,江苏连云港222001

出　　处：《中国中药杂志》2024年第8期2158-2168,共11页China Journal of Chinese Materia Medica

基　　金：江苏省重点研发计划(社会发展类)项目(SBE2022730151)。

摘　　要：该文探究筋骨止痛凝胶中功效物质的体外透皮扩散规律。采用干加热全自动透皮扩散取样系统,对筋骨止痛凝胶透皮扩散研究方法进行单因素考察,并建立筋骨止痛凝胶透皮接收液中阿魏酸,洋川芎内酯Ⅰ,肉桂酸,羟基-ε-山椒素,羟基-α-山椒素和羟基-β-山椒素6种功效成分的HPLC含量测定方法,对16 h内成分的透皮扩散规律进行研究。试验结果显示,优选筋骨止痛凝胶透皮扩散研究方法为大鼠皮作为透皮屏障,生理盐水作为接收介质,给药剂量0.3 g,采用乙酸乙酯萃取对接收液样品进行处理测定。透皮扩散结果显示,阿魏酸、肉桂酸和洋川芎内酯Ⅰ透皮规律表现为0~8 h释放显著增加,8~16 h释放减缓,释放过程扩散和溶蚀协同进行,阿魏酸、肉桂酸透皮扩散规律遵循Higuchi和Ritger-Peppas方程,洋川芎内酯Ⅰ遵循Higuchi方程。羟基-ε-山椒素、羟基-α-山椒素和羟基-β-山椒素透皮扩散曲线显示16 h内持续释放,释放表现为骨架溶蚀,扩散规律遵循零级方程,一级方程和Ritger-Peppas方程。研究结果表明,筋骨止痛凝胶中功效物质阿魏酸、洋川芎内酯Ⅰ、肉桂酸、羟基-ε-山椒素、羟基-α-山椒素和羟基-β-山椒素16 h内释放规律具有一定的缓控释作用,可维持平稳的血药浓度,12 h成分累积透过量能到达24 h的80%,符合其每日2次的临床用药规律。This study systematically explored the transdermal diffusion law of functional substances of Jingu Zhitong Gel(JGZTG).The transdermal diffusion research methods of JGZTG were investigated by single factor trial with the automated transdermal(dry-heat)sampling system.High performance liquid chromatography(HPLC)content determination method was established to determine the contents of ferulic acid,senkyunolide I,cinnamic acid,hydroxy-ε-xanthoxylin,hydroxy-α-xanthoxylin,and hydroxy-β-xanthoxylin in the transdermal diffusion solution of JGZTG.The transdermal diffusion law of the components within 16 h was investigated.The results showed that the optimal transdermal diffusion method of JGZTG was as follows:Rat skin was used as the transdermal barrier;normal saline was used as the receiving medium;the dosage of JGZTG was 0.3 g,and the receiving solution was extracted by ethyl acetate.The results of transdermal diffusion showed that the release of ferulic acid,cinnamic acid,and senkyunolide I increased significantly at 0-8 h and slowed down at 8-16 h.The drug release was a synergic process of diffusion and dissolution,in which ferulic acid and cinnamic acid followed Higuchi and Ritger-Peppas equations,and liguolactone I followed Higuchi equation.The transdermal diffusion curves of hydroxy-ε-zanthoxylin,hydroxy-α-zanthoxylin,and hydroxy-β-zanthoxylin showed continuous release within 16 h,and the drug release was skeleton dissolution.The diffusion law followed zero-order equation,first-order equation,and Ritger-Peppas equation.In clonclusion,it is a controlled release of ferulic acid,ligustrone I,cinnamic acid,hydroxy-ε-pyrroxylin,hydroxy-α-pyrroxylin,and hydroxy-β-pyrroxylin in JGZTG,which can maintain stable blood drug concentration with 16 h,and the cumulative transmittance of each component with 12 h can reach 80%of cumulative transmittance with 24 h,which is in line with the clinical drug use law of bis in die.

关 键 词：筋骨止痛凝胶 功效物质 透皮扩散 阿魏酸 洋川芎内酯Ⅰ 肉桂酸 花椒油素 羟基-ε-山椒素 羟基-α-山椒素 羟基-β-山椒素 

分 类 号：R284[医药卫生—中药学]