正乳贴凝胶贴膏体外透皮特性与皮肤安全性评价研究

Study on in Vitro Transdermal Properties and Skin Safety Evaluation of Zhengrutie Cataplasm

关键词:  正乳贴凝胶贴膏  体外透皮特性  指标成分  累积透过率  经皮水分流失  皮肤安全性

Key words:  Zhengrutie cataplasm  in vitro skin permeation features  index component  cumulative penetration rate  trans epidermal water loss  skin safety

摘要:

目的 研究藏药新药正乳贴凝胶贴膏(以下简称“正乳贴”)的体外透皮特性，并采用不同种属动物(豚鼠、新西兰兔)实验对其皮肤用药安全性进行评价。方法 采用立式Franz扩散池法进行体外透皮试验，以巴马香幼猪皮肤作为透过屏障，分别采用HPLC和GC测定接收介质中山栀苷甲酯+8-O-乙酰山栀苷甲酯、冰片和樟脑的浓度，计算累积透过量及透过率，考察正乳贴的体外透皮特性；采用Buehler试验，研究正乳贴敷于豚鼠皮肤后的致敏情况，并观察正乳贴单次或多次给药敷于新西兰兔完整及破损皮肤处后皮肤的刺激情况。结果 正乳贴在24 h内山栀苷甲酯+8-O-乙酰山栀苷甲酯、冰片和樟脑的累积透过量分别为14.14，348.21，490.97 μg·cm^-2，累积透过率分别为6.2%，10.2%，15.3%，平均透过速率分别为0.59，14.51，20.46 μg·cm^-2·h^-1。正乳贴对豚鼠皮肤未发现致敏反应，对新西兰兔完整皮肤无刺激性，对破损皮肤有轻度刺激作用。结论 正乳贴体外透皮性能良好，各指标成分体外透皮过程均符合零级动力学方程；对豚鼠及新西兰兔皮肤无刺激及致敏作用，皮肤外用安全可靠，具备良好的临床应用价值。

Abstract:

OBJECTIVE To study the in vitro transdermal characteristics of Tibetan new drugs hereinafter referred to as Zhengrutie cataplasm, and to evaluate the safety of skin medication by using different species of animals(guinea pigs, New Zealand rabbits). METHODS The improved vertical Franz diffusion cell method was used for in vitro transdermal testand the skin of Bama miniature pig was used as the permeation barrier. The cumulative permeation amount and rate of geniposide methyl ester and 8-O-acetyl geniposide methyl ester, borneol and camphor in the receiving medium were determined by HPLC and GC, respectively, to investigate the in vitro transdermal characteristics of Zhengrutie cataplasm. Buehler test was used to study the sensitization of Zhengrutie cataplasm on guinea pig skin. Observed the skin irritation after single or multiple application of Zhengrutie cataplasm on intact and damaged skin of New Zealand rabbits. RESULTS The cumulative permeation amount of the sum of geniposide methyl ester and 8-O-acetyl geniposide methyl ester, borneol and camphor within 24 h were 14.14, 348.21, 490.97 μg·cm^-2, respectively. The cumulative permeation amount were 6.2%, 10.2% and 15.3%, respectively. The average permeation amount were 0.59, 14.51 and 20.46 μg·cm^-2·h^-1. No allergic reaction to guinea pig skin, no irritation to intact skin of New Zealand rabbits, mild irritation to damaged skin. CONCLUSION The in vitro transdermal performance of Zhengrutie cataplasm is good. The in vitro transdermal process conforms to the zero-order kinetic equation. It has no irritation and sensitization effect on the skin of guinea pigs and New Zealand rabbits. It is safe and reliable for skin external use and has good clinical application value.