青藤碱贴剂透皮吸收数据的灰色GM(1,1)拟合及与相关模型的比较研究

目的:对青藤碱贴剂的透皮吸收数据进行灰色GM(1,1)模型拟合并与相关模型进行比较。方法:采用Franz扩散池进行体外透皮实验,通过累加生成建立透皮吸收数据的灰色GM(1,1)模型。结果:以平均相对偏差和灰色绝对关联度为评价标准进行拟合精度的比较。结论:灰色GM(1,1)模型的拟合精度较高。

青藤碱贴剂的药动学研究

目的:研究青藤碱贴剂的药动学。方法:以Beagle犬为研究对象,以HPLC-UV为检测手段,测定给药以后不同时间点的血药浓度,拟合药动学参数。结果:建立了专属性的青藤碱血药浓度检测方法,青藤碱贴剂血药浓度达峰时间约8 h,MRT约13 h,达峰浓度约366 ng/mL,其体内行为属于一级速率、二室开放模型。结论:本方法灵敏、快速、选择性强,较好的满足青藤碱的药动学研究。

青藤碱贴剂透皮吸收实验接收液的筛选

目的:筛选青藤碱贴剂的接收液。方法:采用体外透皮实验法,以生理盐水-乙醇、PBS缓冲液、PBS缓冲液-乙醇溶液为考察对象,在不同时间点取样接收液,HPLC测定青藤碱浓度,以单位面积累积透皮量对时间进行零级、一级、Higuchi方程拟合,计算透皮速率常数。结果:表明零级拟合效果较好,Higuchi方程和一级拟合效果不佳。结论:PBS-ethanol接收液透皮速率较快,符合透皮吸收实验对接收液的要求。

微透析技术-同位素示踪法联用进行青藤碱贴剂的皮肤局部药代动力学研究

目的:进行青藤碱贴剂的皮肤局部药动学研究。方法:微透析技术与同位素示踪法联用,以HPLC-UV和液闪计数仪为检测工具,以微透析探针为采样手段,将线性微透析探针植入大鼠皮下组织,采用释放量法测定青藤碱皮肤相对损失率,实时、活体、动态监测青藤碱皮下组织浓度。皮肤微透析样品浓度经相对损失率校正后进行房室和非房室模型拟合。结果:房室模型拟合不佳。非房室模型参数显示皮肤药物浓度达峰时间约6.3 h,平均滞留时间MRT约18 h。结论:微透析法较好的采集了青藤碱贴剂经皮给药的皮肤局部药动学特征,是局部药动学良好的研究手段。

利用佐剂性关节炎大鼠进行青藤碱贴剂的药动学研究

目的:研究青藤碱贴剂在病理状态下的药动学规律。方法:以佐剂性关节炎大鼠为研究对象,以HPLC-UV为检测手段,测定给药以后不同时间点的血药浓度,计算药动学参数。结果:建立了专属性的血药浓度检测方法,青藤碱贴剂达峰时间约10h,MRT约24h,达峰浓度约455ng/mL,其体内行为属于一级速率、二室开放模型。结论:该方法灵敏、快速、正确、选择性强,较好的满足青藤碱的药动学研究,为合理用药提供参考。

Preparation and evaluation of sinomenine hydrochloride patch

The sinomenine hydrochloride （SH） patch, a topical drug delivery system, was prepared and characterized. The in vitro release was studied according to the paddle-over-disk method in the appendix of Chinese Pharmacopeia （appendix XD, 2005）. Stability of SH patch was evaluated at accelerated testing conditions （40 ℃, 75% RH）. Pharmacological and pharmacokinetics study were also performed. It was found that the release of SH from patches depended on pH value of the release medium. There were no significant differences between SH patches stored for 6 mon and those stored for 0 mon in the drug content, initial adhesion, lasting stickiness, peeling strength and in vitro release. SH patches exhibited better anti-inflammatory activity as well as analgesic efficacy. More importantly, primary pharmacokinetic parameters of SH patch, such as Cmax and AUC, were much lower than those of SH solution dosed orally. In conclusion, the patch might be a promising delivery system for SH, which bypassed the gastrointestinal tract and was a convenient, efficacious, safe and non-invasive delivery method.