丁桂散脐部给药的体内药动学研究  

Pharmacokinetics of Active Ingredients in Dinggui PowdeRWith Umbilical Administration

作　　者：张永太[1] 李佳璇 姜晓炜 冯年平[1] Zhang Yongtai;Li Jiaxuan;Jiang Xiaowei;Feng Nianping(Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China)

机构地区：[1]上海中医药大学中药学院,上海201203

出　　处：《成都中医药大学学报》2023年第4期40-45,共6页Journal of Chengdu University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82074031);上海市东方学者特聘教授资助资金(TP2020054);上海高水平地方高校创新团队(慢性筋骨病损研究与转化)支持项目(SYZ20220315)。

摘　　要：目的:探讨丁桂散在正常和溃疡性结肠炎(Ulcerative Colitis,UC)大鼠脐部给药的体内药代动力学特征。方法:采用5%的2,4,6-三硝基苯磺酸/乙醇联合冰水浴致寒证UC大鼠。正常-脐部、UC-脐部、UC-旁开组,UC-灌胃组分别于正常及UC模型大鼠神阙穴或旁开经皮给以醋调丁桂散,口服组灌胃给予醋调丁桂散,各给药组给药剂量均相同。HPLC法测定丁香酚和肉桂酸的血药浓度,以DAS2.1.1软件拟合药动学参数。结果:各组血药浓度均可维持较长时间。与各经皮给药组相比,口服组吸收最快,两种所测成分的T_(max)最小。口服组两种成分的C_(max)最大,但与UC-脐部组相比无统计学差异(P>0.05)。另外口服组肉桂酸AUC_(0→t)在各组中最大,显著大于UC-脐部组(P<0.05),丁香酚AUC_(0→t)与UC-脐部组无显著差异(P>0.05)。UC-脐部组两种成分的T_(max)最大,但C_(max)、AUC_(0→t)与UC-旁开组相比无显著差异(P>0.05)。另外,UC-脐部组丁香酚的C_(max)、AUC_(0→t)均显著高于正常-脐部组(P<0.05),而该两组的肉桂酸的以上参数间无统计学差异(P>0.05)。结论:经皮给药与口服相比,表现出缓慢吸收的性能。大鼠脐部给药与旁开给药相比,丁香酚与肉桂酸未体现特异性吸收转运行为,这可能与大鼠包括脐部和旁开在内的腹部皮肤结构相似有关,提示脐部给药的研究应选择灵长类实验动物为宜。Objective:To investigate the in vivo pharmacokinetic characteristics of Dinggui Powder(powder of clove and cinnamon mixed by equal weight)in normal and ulcerative colitis(UC)-born rats administered in the umbilical region.Methods:A 5%2,4,6-trinitrobenzenesulfonic acid/ethanol combined with ice water bath was used to induce UC symptoms caused by cold factors in rats.The rats were randomly divided into 4 groups,including normal-umbilical,UC-umbilical,UC-paracentral,and UC-gavage(oral administration)groups,which were administered with vinegar-adjusted Dinggui Powder at the umbilical region or paracentral region of normal and UC model rats respectively,and the oral administration group was administered with vinegar-adjusted Dinggui Powder by gavage.The dose administered was the same for all dosing groups,and the blood concentrations of eugenol and cinnamic acid were determined by HPLC.The pharmacokinetic parameters were fitted with DAS2.1.1 software.Results:Dinggui Powder showed a significant slow-release effect after administration,and blood concentrations of the test ingredients were maintained for a longer period of time in all groups.Compared to each transdermal administration group,the oral administration group showed the fastest absorption and the smallest Tmax for eugenol and cinnamic acid.The Cmax of the two ingredients was greatest in the oral administration group but was not statistically different compared to the UC-umbilical group(P>0.05).Besides,the AUC0t of cinnamic acid was the largest among the groups in the oral administration group,significantly greater than in the UC-umbilical group(P<0.05),but the AUC0t of eugenol was not significantly different from that of the UC-umbilical group(P<0.05).Among the transdermal administration groups,the Tmax of the two ingredients was the largest in the UC-umbilical group,but the Cmax and AUC0t were not significantly different compared to the UC-paracentral group(P>0.05).In addition,Cmax and AUC0t of eugenol were significantly higher in the UC-umbilical group than

关 键 词：丁香 肉桂 经皮 脐部给药 丁香酚 肉桂酸 药动学 

分 类 号：R289[医药卫生—方剂学] R285[医药卫生—中药学]