丹参总酚酸生物黏附漂浮微丸体外释放和大鼠药代动力学研究

杨丹丹　黎迎　朱春燕

摘要：目的 制备丹参总酚酸生物黏附漂浮微丸，延长其在体内的滞留时间，提高其口服生物利用度。方法 采用挤出滚圆法，分别以壳聚糖、羟丙基甲基纤维素（HPMC）和卡波姆为黏附材料，十八醇为漂浮材料，微晶纤维素为成型剂，制备丹参总酚酸黏附漂浮微丸。考察制备的2种黏附漂浮微丸的体外释放及其在大鼠体内生物利用度。结果 体外释放试验结果表明，空白微丸中丹酚酸B在4 h即释放完全，而制备的2种黏附漂浮微丸的体外释放时间达12 h。大鼠体内药代动力学研究结果表明，大鼠分别灌胃丹参总酚酸原料药、丹参总酚酸壳聚糖微丸、丹参总酚酸HPMC微丸后，丹酚酸B在大鼠体内Tmax分别为（12.00±2.74）min、（17.00±7.58）min、（27.00±12.55）min，丹参总酚酸壳聚糖微丸、丹参总酚酸HPMC微丸相對生物利用度分别为177.08%、172.03%。结论 丹参总酚酸黏附漂浮微丸在体外释放缓慢，黏附漂浮微丸可延长药物在体内的滞留时间，提高丹参总酚酸在大鼠体内的口服生物利用度。

关键词：丹参总酚酸；生物黏附漂浮；微丸；体外释放；药代动力学

DOI：10.3969/j.issn.1005-5304.2018.06.019

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2018）06-0077-05

Study on in Vitro Release of Salvianolic Acid Bioadhesive Floating Pellets

and Pharmacokinetics in Rats

YANG Dan-dan， LI Ying， ZHU Chun-yan

Institute of Medicinal Plant Development， Chinese Academy of Medical Sciences and Peking Union Medical College， Beijing 100193， China

Abstract： Objective To prepare salvianolic acid bioadhesive floating pellets； To prolong its residence time in vivo； To improve the oral bioavailability. Methods Salviae miltiorrhizae total phenolic acid adhering floating pellets were prepared by extrusion-spheronization. Chitosan， HPMC and carbomer were used as adherent material， stearyl alcohol was used as floating material and MCC as forming agent. The in vitro release of two adherent floating pellets were prepared and their bioavailability in rats were investigated. Results The results of in vitro release test showed that the salvianolic acid B in the blank pellets was completely released at 4 h， and the two adherent floating pellets prepared in vitro were released for 12 h. The results of pharmacokinetic studies in rats showed that after intragastric administration of salvianolic acid， salvianolic acid chitosan pellets and salvianolic acid HPMC pellets， Tmax were （12.00±2.74）min， （17.00±7.58）min and （27.00±12.55）min， respectively. The relative bioavailability of salvianolic acid chitosan pellets and salvianolic acid HPMC pellets were 177.08% and 172.03%， respectively. Conclusion Salvia total phenolic acid adherent floating pellets release slowly in vitro， and floating pellets can prolong the retention time in vivo and increase the oral bioavailability of salvianolic acid in rats.

Keywords： salvianolic acid； bioadhesive floating； pellets； release in vitro； pharmacokinetics

丹参为唇形科鼠尾草属丹参Salvia miltiorrhiza Bge.的干燥根及根茎，又名大红袍、红根赤参、血丹参等，始载于《神农本草经》，其活性成分主要分为两大类，即脂溶性成分和水溶性成分。丹参总酚酸是丹参的水溶性提取物[1]，其中以丹酚酸B含量最高。

本课题组在前期对丹参总酚酸理化性质的考察中发现，丹参总酚酸主要成分丹酚酸B的油水分配系数与pH值呈负相关，在胃部pH值条件下的油水分配系数明显高于在肠中。……