微透析采样进行蛇床子软膏的皮肤局部药动学研究.docVIP

微透析采样进行蛇床子软膏的皮肤局部药动学研究 　　[摘要] 目的 建立蛇床子素在体皮肤微透析采样方法，研究蛇床子软膏在SD大鼠体内的局部药动学。 方法 采用浓差法考察浓度、流速对探针体外回收率的影响；减量法研究探针的体内回收率稳定性。SD大鼠植入皮肤探针后将蛇床子软膏涂敷于探针所在皮肤表面，测定微透析液中蛇床子素浓度，绘制药时曲线，计算药动学参数。 结果 随着灌流速度的增大，探针体外回收率有所下降，且回收率大小?c蛇床子素的浓度无关；探针体内回收率为（44.29±1.28）%，体内12 h基本保持稳定；蛇床子软膏给药后，蛇床子素在皮肤组织内的透皮速率约为9.3402 μg/min，AUC0-t为8105.4 μg/（mL?min），平均滞留时间为979.8 min，能较长时间维持在较高水平。 结论 在体皮肤微透析法可用于蛇床子软膏局部药动学研究。 　　[关键词] 蛇床子软膏；皮肤微透析；局部药动学；经皮给药 　　[中图分类号] R285.5 [文献标识码] A [文章编号] 1673-7210（2017）04（c）-0021-05 　　[Abstract] Objective To establish a method of skin microdialysis technology in vivo in order to study the local pharmacokinetics of Fructus Cnidii Ointments in rats. Methods The effect of different flow rate and concentration on the probe recovery in vitro were investigated by gain and loss method. Recovery by loss was used to study the stability of the probe recovery in vivo. The Fructus Cnidii Ointments was applied to the skin surface where the skin probe was implanted. The osthole concentration of skin microdialysates was determined， the time curve of osthole concentration was drawn and pharmacokinetic parameters was calculated. Results The recovery of probe decreased as the follow rate increased and irrespective of osthole concentration； the recovery of skin probe in vivo was （44.29±1.28）% and basically stable within 12 hours； After Fructus Cnidii Ointments for transdermal administration， ostholepenetration rate in skin was 9.3402 μg/min， AUC0-t was 8105.4 μg/（mL?min）， and mean residence time was 979.8 min， which showed ostholecan maintain for a long time at a higher level. Conclusion Skin microdialysis can be used to study the pharmacokinetic of Fructus Cnidii Ointments. 　　[Key words] Fructus Cnidii Ointments； Skin microdialysis； Local pharmacokinetics； Transdermal drug delivery 　　蛇床子为伞形科植物蛇床Cnidium monnieri（L.）Cuss.的干燥成熟果实，具有解毒杀虫、燥湿祛风的功效，主要用于外治外阴湿疹、妇人阴痒、湿疹疥癣等[1]。蛇床子素是从蛇床子中提取的主要有效成分，具有抗菌、杀虫、抗炎镇痛等作用，尤适于外用治疗湿疹疥癣等皮肤病[2]。笔者在前期研究蛇床子软膏的制备及处方筛选的基础上[3-4]，进一步研究了蛇床子软膏中蛇床子素的体内皮肤局部药动学。虽然对蛇床子有效成分蛇床子素的