化学促渗剂联合超声波导入对盐酸青藤碱凝胶经皮渗透的促进作用

Effect of Sonophoresis Combined with Chemical Enhancer on Transdermal Delivery of Sinomenine Hydrochloride Gel in Vitro

目的:考察化学促渗剂与超声波导入联合应用对盐酸青藤碱凝胶经皮渗透的影响。方法:制备盐酸青藤碱凝胶并将离体SD大鼠皮肤置于改良Franz扩散池,皮肤角质层朝上,并均匀涂上药物凝胶,保持扩散体系温度为(32±0.5)℃,接受室采用20%PEG-400生理盐水溶液。实验分为3组:第1组采用含10%丙二醇药物凝胶;第2组采用含有10%丙二醇和3%Azone复合促渗剂凝胶;第3组为预处理组,鼠皮分别经油酸和Azone预处理12h。3组分别进行被动扩散和超声波导入。每隔一定时间吸取接受室样品,并测定其中药物浓度,计算累积单位面积渗透量Q(μg.cm-2)和稳态透皮速率Js(μg.cm-2.h-1),并进行比较。结果:第1组超声波导入,药物经皮吸收参数Q8hr=(50.45±7.42)μg.cm-2,Js=(6.55±0.28)μg.cm-2.h-1;第2组超声波导入Q8hr=(184.6±48.10)μg.cm-2,Js=(22.59±3.47)μg.cm-2.h-1,均显示明显的协同促渗效果。而鼠皮经油酸及Azone预处理后超声波导入的Js则分别比单用超声波导入增加16.64倍和11.26倍。结论:化学促渗剂丙二醇、Azone、油酸和超声波导入显示了对盐酸青藤碱经皮渗透的协同促渗作用。

Objective：To study the effect of sonophoresis combined with chemical enhancer on transdermal delivery of sinomenine hydroehloride （SH） gel in vitro. Methods ： Ultrasound frequencies （ 800KHz ） were applied with a sonieator in the present study. Male SD rat＇s skin was used as model mid SH gel was used as ultrasound couplant. Modified Franz diffusion cells were used in the transdermal experiment. The experiments were carried out in three groups ： 1. gel contained 10%. 2- propanediol;2, gel contained 10%. 2-propanediol and 3% Azone;3. the rat＇s skin was pretreated by A.zone or oleic acid for 12 hours. Passive diffusion and sonophoresis was studied for eaeh group. The sample solution was withdrawn and the fresh receive solution was added per hour. The concentration of SH samples was determined by HPLC ,and the transdermal parameters per unit cumulative absorbing quantity（Qshr） and steady state penetration rate（Js） of SH was calculated. Results ：The transdermal parameters Qghr and Js of sonoporesis of SH gel containing 10% 2-propanediol were （50. 45 ±7. 42） μg·cm^-2 and（6.55±0. 28）μg·cm^2· h^ -1 .respectively. The Qsh, and Js of sonoporesis with gel containing 3% Azone were（ 184. 6±48. 10）μg·cm^-2 and（22.59 ±3.47）μg·cm^2·h^-1 ,respectively,which showed it was more effective than used enhancer alone. Furthermore,the Qsh, of sonophoresis in the group that the skin was pretreated by oleie acid was（ 1694. 6 ±486. 51 ）μg·cm^ -2 ,and it was（ 1190. 3 ±412.95）μg·cm^-2 in the group that the skin was pretreated by Azone. Also, Js were increased 16. 64 and 11.26 times compared with that using sonophoresis alone. Conclusion：Sonophoresis combined with chemical enhancers such as Azone, oleic acid, and 2-propanediol showed a synergistic effect on SH transdermal delivery.