刘欣妍;徐铃燕;王永洁;刘鑫;赵颖;兰海;吴清;
LIU Xin-yan;XU Ling-yan;WANG Yong-jie;LIU Xin;ZHAO Ying;LAN Hai;WU Qing;School of Chinese Materia Medica,Beijing University of Chinese Medicine;

• 1:北京中医药大学中药学院

摘要(Abstract)：

为探究花椒挥发油在微乳凝胶中对复杂成分的促透作用,揭示花椒挥发油微乳凝胶的经皮促透机制。该研究首先以系列不同log P药物作为模型药物简化并表征中药复杂成分,将其包载于花椒挥发油微乳凝胶中,采用改良Franz扩散池法,考察系列模型药的体外透皮行为;然后,采用衰减全反射傅利叶变换红外光谱(ATR-FTIR)、差示扫描量热法(DSC)及HE染色技术探究花椒挥发油及其微乳凝胶对角质层分子及微观结构的影响。结果显示花椒挥发油及其微乳凝胶对亲脂性和亲水性药物均具有较好的促透作用,当药物log P为-0. 5时促透效果最好,其促透机制均与影响角质层脂质有序排列,改变脂质流动性、蛋白质构象和破坏角质层结构的完整性有关,且两者促透作用及角质层破坏作用强弱为:5%花椒挥发油>花椒挥发油微乳凝胶。这说明将花椒挥发油包载于微乳凝胶中,仍具有较好的促透效果,虽促透作用不及花椒挥发油本身,但能降低对皮肤的刺激性,使用更为安全,对富含花椒挥发油的中药外用制剂的开发和临床应用具有指导作用。
This study aimed to investigate the transdermal enhancing effect of essential oil from Zanthoxylum bungeanum(Z. bungeanum oil) in microemulsion gel(ZO-ME-gel) on permeation of different components,and reveal the transdermal enhancing mechanism of ZO-ME-gel. A series of components with different log P values were selected as model drugs and encapsulated in ZO-ME-gel to simplify and characterize the complex components of traditional Chinese medicine. The transdermal behavior of the model drugs was further examined using the improved Franz diffusion cell method. Then attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR),differential scanning calorimetry(DSC) studies and hematoxylin-eosin(HE) staining were used to investigate the effects of Z. bungeanum oil and ZO-ME-gel on keratin,intercellular lipids and microstructure of the stratum corneum(SC). The results showed that Z. bungeanum oil and ZO-ME-gel had a good transdermal enhancing effect on both hydrophilic and lipophilic drugs,and the best effect was achieved when log P value was-0. 5. The transdermal enhancing mechanism of Z. bungeanum oil and ZO-ME-gel was related to affecting the order of the SC lipids,changing lipid fluidity and protein conformation,and disrupting the integrity of the SC structure. 5% Z. bungeanum oil had greater transdermal enhancing effect and destruction of SC structure than ZO-ME-gel. These results suggested that Z. bungeanum oil loaded in microemulsion gel still had a good transdermal enhancing effect although the effect was not as great as Z. bungeanum oil itself,in addition,ZO-ME-gel was less irritating to the skin and safer to use,which had a guiding role in the development and clinical application of Z. bungeanum oil-containing traditional Chinese medicine topical preparations.

关键词(KeyWords)： 促透机制;花椒挥发油;微乳凝胶;衰减全反射傅里叶变换红外光谱;差示扫描量热法;HE染色
transdermal enhancing mechanism;essential oil from Zanthoxylum bungeanum;microemulsion gel;ATR-FTIR;DSC;hematoxylin-eosin staining

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81473365)

作者(Author): 刘欣妍;徐铃燕;王永洁;刘鑫;赵颖;兰海;吴清;
LIU Xin-yan;XU Ling-yan;WANG Yong-jie;LIU Xin;ZHAO Ying;LAN Hai;WU Qing;School of Chinese Materia Medica,Beijing University of Chinese Medicine;

Email:

DOI: 10.19540/j.cnki.cjcmm.20190910.301

参考文献(References)：

• [1]张臻，高天慧，傅超美，等．中药丸剂剂型理论与应用现状关键问题分析[J]．中国中药杂志，2017,42(12):2408.
• [2] Lan Y,Wu Q,Mao Y Q,et al. Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum Maxim. as a natural transdermal penetration enhancer[J]. J Zhejiang Univ Sci B,2014,15:153.
• [3]王艳宏，刘书博，王锐，等．中药挥发油促透皮吸收及透皮吸收作用的研究进展[J]．中国实验方剂学杂志，2017,23(3):192.
• [4]钟芮娜，汪小涵，王欣桐，等．石菖蒲挥发油自纳米乳的制备与质量评价[J]．中国中药杂志，2018,43(20):4062.
• [5]李佳佳，郑鹏，顿佳颖，等．提取-共沸精馏耦合技术与水蒸气蒸馏法提取中药挥发油比较研究[J]．中国现代中药，2018,20(11):1436.
• [6] Fumiyoshi Y,Mitsuru H. Mechanistic and empirical modeling of skin permeation of drugs[J]. Adv Drug Delivery Rev,2003,55:1185.
• [7] Patel H,Ten B W,Cronin M T. Quantitative structure-activity relationships(QSARs)for the prediction of skin permeation of exogenous chemicals[J]. Chemosphere,2002,48:603.
• [8]徐铃燕，谢远平，康倩，等．单纯形网格法优化外用中药不同油水分配系数多成分微乳制剂处方[J]．中草药，2017,48(19):3961.
• [9] Huang L F,Shi H L,Gao B,et al. Decichine enhances hemostasis of activated platelets via AMPA receptors[J]. Thromb Res,2014,133:848.
• [10] Kumar S,Zakrewsky M,Chen M,et al. Peptides as skin penetration enhancers:Mechanisms of action[J]. J Control Release,2015,199:168.
• [11] Gurbuz A,Ozhan G,Gungor S,et al. Colloidal carriers of isotretinoin for topical acne treatment:skin uptake,ATR-FTIR and in vitro cytotoxicity studies[J]. Arch Dermatol Res,2015,307:607.
• [12] Leroy M,Lafleur M,Auger M,et al. Characterization of the structure of human skin substitutes by infrared microspectroscopy[J]. Anal Bioanal Chem,2013,405:8709.
• [13] Hathouta R M. Development and characterization of colloidal soft nano-carriers for transdermal delivery and bioavailability enhancement of an angiotensinⅡreceptor blocker[J]. Eur J Pharm Biopharm,2012,82:230.
• [14] Hussain A,Samad A,Singh S K,et al. Nanoemulsion gel-based topical delivery of an antifungal drug:in vitro activity and in vivo evaluation[J]. Drug Deliv,2016,23:652.
• [15] Wang C X,Zhu J X,Zhang D,et al. Ionic liquid-microemulsions assisting in the transdermal delivery of dencichine:preparation,in-vitro and in-vivo evaluations,and investigation of the permeation mechanism[J]. Int J Pharm,2018,535:120