超声导入对酮洛芬凝胶药物经皮促透效果的研究  

Study on the Enhanced Transdermal Permeation of Ketoprofen Gel Induced by Ultrasound

作　　者：蒋秀梅 方任华 牛文信 王维青 安悦 杨晶 王浩然 江昌照 叶金翠 JIANG Xiumei;FANG Renhua;NIU Wenxin;WANG Weiqing;AN Yue;YANG Jing;WANG Haoran;JIANG Changzhao;YE Jincui(Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province,Institute of Materia Medica,Hangzhou Medical College,Hangzhou 310013,China;Innovation Center of Yangtze River Delta Region Green Pharmaceuticals,Zhejiang University of Technology,Huzhou 313200,China;Nantong University Xinglin College,Nantong 226001,China)

机构地区：[1]杭州医学院,浙江省神经精神疾病药物研究重点实验室,杭州310013 [2]浙江工业大学长三角绿色制药协同创新中心,浙江湖州313200 [3]南通大学杏林学院,江苏南通226001

出　　处：《中国现代应用药学》2024年第11期1508-1514,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：浙江省基础公益研究计划项目(LHDMZ22H300013,LTGD23H300001);浙江省医药卫生科技计划项目(2023KY652);浙江省中医药科技计划项目(2022ZB222,2023ZL357,2023ZL356)。

摘　　要：目的研究物理经皮促透手段低频低功率超声对酮洛芬凝胶经皮吸收的促进作用。方法以酮洛芬凝胶为模型药物,比较超声处理和未处理组的离体经皮渗透量。并建立大鼠胶原蛋白致炎模型,评价2组药效学差异。最后通过药动学研究观察超声对酮洛芬凝胶体内过程的影响。结果与未进行超声处理相比,超声处理可将酮洛芬凝胶在给药24 h的离体皮肤累积渗透量提高3.5倍;使药动学中的AUC_(0-t)从(4289.02±763.58)ng·h·mL^(-1)提高至(11301.10±3386.30)ng·h·mL^(-1),T_(max)从(6.0±1.4)h提前至(3.0±2.0)h;另外,超声处理4 h后能显著提高酮洛芬凝胶在大鼠炎症模型中的抗炎作用,快速有效地降低蛋清致炎后的肿胀程度。结论本研究从皮肤渗透试验、药效学评价和药动学等方面证实了低频低功率超声可显著提高酮洛芬凝胶的经皮吸收量和吸收速率,增强其药效强度,是酮洛芬凝胶经皮给药的有效促进手段。OBJECTIVE To investigate the potential of low-frequency,low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel.METHODS Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group.Additionally,a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences.Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process.RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated.Significant pharmacokinetic improvements in AUC_(0-t) from(4289.02±763.58)ng·h·mL^(-1)to(11301.10±3386.30)ng·h·mL^(-1)and a reduction in T_(max) from(6.0±1.4)h to(3.0±2.0)h.Ultrasound notably improved the gel's anti-inflammatory effects in the rat model,effectively and rapidly reducing inflammation-induced swelling.CONCLUSION Low-frequency,low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency,from the aspects of skin permeation tests,pharmacodynamic evaluation,and pharmacokinetic studies,which is an effective penetration enhancer for transdermal administration of ketoprofen gel.

关 键 词：酮洛芬凝胶 超声导入 离体渗透 药效学 药动学 

分 类 号：R969.1[医药卫生—药理学]