超声波对盐酸青藤碱凝胶经皮渗透的促进作用  

The effect of phonophoresis on transdermal delivery of sinomenine hydrochloride gel in vitro

作　　者：李立安[1] 赵健乐[2] 李新平[3] 王鸿[4] 高建青[3] 

机构地区：[1]杭州师范大学附属医院暨杭州市第二人民医院药剂科,杭州310015 [2]武警浙江总队杭州医院物理康复中心 [3]浙江大学药物制剂研究所 [4]浙江医学高等专科学校药剂教研室

出　　处：《中华物理医学与康复杂志》2010年第5期328-332,共5页Chinese Journal of Physical Medicine and Rehabilitation

基　　金：杭州市医药卫生科技计划项目（2006B020）

摘　　要：目的 研究超声波对盐酸青藤碱经皮渗透的影响.方法 取离体Sprague-Dawley大鼠皮肤,置于改良Franz扩散池,皮肤角质层朝上,并均匀涂抹盐酸青藤碱凝胶,保持扩散体系温度为（32±0.5）℃,接受介质采用20%聚乙二醇400生理盐水溶液.实验分为药物被动经皮渗透组（对照组）和药物超声波透入组（超声波组）.对照组不加超声波作用,超声波组按超声波作用参数不同分为Ta组（频率800 kHz,强度0.75 W/cm2,作用时间10 min）、Tb组（频率1 MHz,强度0.70 W/cm2,作用时间10 min）、Tc组（频率1 MHz,强度0.35 W/cm^2,作用时间10 min）、Td组（频率800 kHz,强度1.50 W/cm^2,作用时间10 min）和Te组（频率800 kHz,强度1.50 W/cm^2,作用时间5 min）.每组均同时进行6个平行实验,每个平行实验持续时间为8 h,每隔1 h分别吸取接受室溶液,并加入空白接受介质,测定接受液药物浓度,计算平均累积单位面积渗透量Q（μg/cm^2）和平均稳态透皮速率Js（μg/cm^2/h）,并进行比较.结果 对照组Q8h值为（20.65±10.23）μg/cm^2,Js值为（3.02±0.11）μg/cm^2/h;Ta、Tb组的Q8h和Js值均明显高于对照组（P〈0.05）;Tb组Q8h和Js值明显高于Tc组（P〈0.05）;Td组Q8h和Js值明显高于Ta组和Te组（P〈0.05）.超声波透入后,皮肤组织切片经光学显微镜观察没有明显改变,扫描电子显微镜下可见角质层表面呈现粗糙、多孔状.结论 超声波透入对盐酸青藤碱的经皮吸收有明显促进作用,渗透效果与超声波强度、作用时间有关,超声波作用的强度在0～1.5 W/cm^2范围内,对皮肤组织比较安全.Objective To study the effect of phonophoresis on transdermal delivery of sinomenine hydrochloride （ SH ） gel in vitro. Methods Ultrasound at one of two frequencies （ 800 kHz or 1 MHz） was applied with a sonicator with a transducer in this study. The skin of male Sprague-Dawley rats was used as the model and SH gel was used as the ultrasound couplant. The permeation rate of SH was detected using a modified Franz diffusion cell maintained at 32±0.5℃ and filled with 20% polyethylene glycol 400 physiological saline solution. The transdermal phonophoresis experiments were carried out in five groups： Group Ta, f=800 kHz, / = 0.75 W/cm2, t = 10 min：Group Tb,f=1 MHz,I=0.7 W/cm2, t=10 min; Group Tc,f=1 MHz,I=0.35 W/cm2, t=10 min; Group Td,f=800 kHz, I = 1.5 W/cm2, t = 10 min and Group Tc,f=800 kHz, I=1.5 W/cm2,t=5 min. There was also a control group （C） in which the SH was allowed to diffused passively. Samples were withdrawn at the indicated intervals and the concentration of SH was determined by high-performance liquid chromatography. The transdermal parameters such as average accumulated delivery quantity per unit area Q8h, average transdermal steady delivery rate J, and Tlag were calculated. Results The Q8h and Js of the control group were 20.65±10.23 μ/cm2 and 3.02±0.11μ/cm2/h respectively. The phonophoresis parameters in groups Ta and Tb were, on average, significantly higher than in the control group. The parameters in group Tb were significantly larger, on average, than in Te. In group Td the parameters were significantly larger than in groups Ta and Te. Conclusions The results show that phonophoresis can enhance the transdermal delivery of SH. Phonophoresis variables such as frequency and time influence its effects on drug permeation. Almost no change was observed in the structure of the skin after phonophoresis, though under a scanning electron microscope the surface of the corneum appeared rough and porous. Phonophoresis is there-fore an effective and safe method for SH transdermal deliv

关 键 词：盐酸青藤碱 经皮渗透 超声波透入 

分 类 号：R285[医药卫生—中药学]