D-柠檬烯和L-柠檬烯对盐酸川芎嗪透皮吸收的影响

目的研究手性对映体D-柠檬烯和L-柠檬烯对盐酸川芎嗪透皮吸收的影响及其作用机制。方法采用Franz-扩散池测定盐酸川芎嗪通过离体猪皮的透过量；红外光谱法测定角质层脂质中C-H对称和不对称伸缩振动吸收峰峰位及其峰面积；采用扫描电镜观察皮肤表面形态学变化，并新引入量化的概念——表观密度衡量角质鳞片脱落的程度。结果D-柠檬烯和L-柠檬烯对盐酸川芎嗪的促透量均高于对照组和氮酮组，这两种对映体促透剂产生的促透量无统计学差异(P>0.05)， L-柠檬烯的时滞是D-柠檬烯的2.55倍。红外光谱结果显示： 角质层脂质中的C-H伸缩振动吸收峰位移和峰面积的变化取决于所用的促透剂；两种对映体促透剂均引起对称振动和不对称振动吸收峰位移增大和峰面积减少。扫描电镜结果表明，不同的促透剂抽提角质层中的脂质，引起角质鳞片不同程度的脱落。结论D-柠檬烯和L-柠檬烯的促透量均高于对照组和氮酮组，并且以D-柠檬烯的时滞最短。两种对映体促透剂对盐酸川芎嗪的促透机制是多种原因共同作用的结果。

Effects of D-limonene and L-limonene on transdermal absorption of ligustrazine hydrochloride

Aim To investigate the effects and permeation mechanism of D-limonene and L-limonene on transdermal delivery of ligustrazine hydrochloride(LH).Methods Transdermal flux of LH through porcine skin was determined in vitro by Franz-type diffusion cells.The peak shift and peak areas of C-H stretching vibration absorption were estimated by Fourier transform-infrared(FTIR).Morphological changes in the stratum corneum(SC) treated with enhancers were observed by a scanning electron microscope(SEM) and apparent density,a new concept,was proposed to estimate the desquamated extent of SC for the first time.Results There were no statistic difference(P>0.05) between the transdermal fluxs of the enantiomer enhancers which were higher than those of control and azone.But the lag time of L-limonene was 2.55 times than that of D-limonene.The FTIR results revealed that the shift and decreased peak area of C-H stretching vibrations in the SC lipids were dependent on the enhancers.The enantiomers permeation enhancers,D-limonene and L-limonene,were able to perturb and extract the SC lipids to different extent.The disordering and extracting lipids activity of L-limonene was stronger than that of D-limonene.SEM studies demonstrated that the extraction of lipids was depended on the selected penetration promoters.Conclusion D-limonene was the most effective enhancer which had the greater transdermal flux of LH and the least lag time.The results showed that the permeation enhancement mechanism of the enantiomer enhancers to LH was multiple ones including disordering and extracting the SC lipids and probably including stereoselective mechanism.