肝素和低分子肝素口腔给药系统的研究Oral cavity delivery - 药学学报.PDF

药学学报 Acta Pharmaceutica Sinica 2010, 45 ( 10) : 1317 1321 ·1317 · 肝素和低分子 素口腔给药系统的研究 丁, 侯惠民* (药物制剂国家工程研究中心, 上海 201203) 摘要: 本研究分别比较了肝素 (unfractionated heparin, UFH) 和低分子肝素 (low molecular weight heparin, LMWH) 通过口服和口腔给药吸收的差别, 筛选出适合两种药物口腔给药的吸收促进剂, 并采用生物黏附材料 卡波普和海藻酸钠制备了两种 物的口腔给药膜剂。采用活化部分凝血活酶时间 (activated partial thromboplastin time, APTT) 法测定了经口服、口腔和皮下注射给药后大鼠血浆中的肝素和低分子肝素。吸收促进剂 (Labrasol) 对促进膜剂中的药物经大鼠口腔途径吸收的作用有限。离子电渗技术能显著增加UFH 和LMWH 通过口腔途径 给药的吸收量, 促进二者通过口腔黏膜吸收。 关键词: 肝素; 低分子肝素; 大分子药物; 离子电渗; 口腔; 活化部分凝血活酶时间; 膜剂 中图分类号: R943 文献标识码:A 文章编号: 05 13-4870 (2010) 10-13 17-05 Oral cavity delivery system of unfractionated and low molecular weight heparin * LI Ding, HOU Hui-min (National Pharmaceutical Engineering Research Center, Shanghai 201203, China) Abstract: The difference between absorption of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) after oral and oral cavity administration were studied respectively, and the compatible enhancer for oral cavity delivery system of both drugs was found. The LMWH and UFH films were prepared with two bioadhesive materials Carbopol and alginate sodium for oral cavity delivery. The activated partial thromboplastin time (APTT) was used to determine LMWH and UFH in plasma after oral, oral cavity and sc administration in rats. The results show that the enhancer (Labrasol) can increase the absorption of LMWH and UFH through oral cavity in rats but not obviously. The ora