Zhang Chun-feng, Yang Zhong-lin, Luo Jia-bo
School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China.
Yao Xue Xue Bao. 2006 Aug;41(8):772-7.
To investigate the effects and permeation mechanism of D-limonene and L-limonene on transdermal delivery of ligustrazine hydrochloride (LH).
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.
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.
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.
研究D-柠檬烯和L-柠檬烯对盐酸川芎嗪（LH）经皮给药的影响及渗透机制。
采用Franz型扩散池体外测定LH透过猪皮的渗透通量。通过傅里叶变换红外光谱（FTIR）估算C-H伸缩振动吸收的峰位移动和峰面积。用扫描电子显微镜（SEM）观察经促渗剂处理的角质层（SC）的形态变化，并首次提出表观密度这一新概念来估算SC的脱屑程度。
对映体促渗剂的经皮通量高于对照组和氮酮，两者之间无统计学差异（P>0.05）。但L-柠檬烯的滞后时间是D-柠檬烯的2.55倍。FTIR结果表明，SC脂质中C-H伸缩振动的峰位移动和峰面积减小取决于促渗剂。对映体渗透促进剂D-柠檬烯和L-柠檬烯能够不同程度地扰乱和提取SC脂质。L-柠檬烯对脂质的扰乱和提取活性强于D-柠檬烯。SEM研究表明，脂质的提取取决于所选的渗透促进剂。
D-柠檬烯是最有效的促渗剂，其LH经皮通量最大，滞后时间最短。结果表明，对映体促渗剂对LH的渗透增强机制是多方面的，包括扰乱和提取SC脂质，可能还包括立体选择性机制。
