【摘要】 目的考察不同吸收促进剂对低分子肝素(LMWH)肠渗透的影响,确定LMWH最佳肠吸收部位及其最佳吸收促进剂。方法采用体外透膜装置考察LMWH经肠道各段的渗透能力以及不同吸收促进剂对LMWH经大鼠十二指肠和结肠的促渗透效果;以部分凝血活酶时间(APTT)为指标,采用在体原位肠袢实验考察Imwitor 742对LMWH经十二指肠或结肠给药后吸收的影响。结果LMWH经十二指肠渗透最多,其次是空肠、回肠和结肠。所试吸收促进剂均能增加LMWH的透肠速率,在十二指肠的促渗顺序为:Imwitor 742>牛磺胆酸钠>癸酸钠>聚山梨酯80>卵磷脂;在结肠的促渗顺序为:Imwitor 742>癸酸钠>牛磺胆酸钠>聚山梨酯80>卵磷脂。各促进剂均对结肠作用敏感,但LMWH渗透系数和累积渗透量仍以十二指肠最高。1%Imwitor 742使LMWH经大鼠十二指肠吸收的最大APTT增加3.6倍,结肠吸收的最大APTT增加2.5倍,十二指肠吸收好于结肠。结论十二指肠是LMWH肠道吸收的最佳部位。Imwitor 742是LMWH良好的肠道吸收促进剂。更多还原

【Abstract】 OBJECTIVE To investigate the effects of different rat intestinal regions and different intestinal enhancers on the transport properties of low molecular weight heparin(LMWH).METHODS The permeation of LMWH across the intestinal mucosae and the effects of various absorption enhancers on the duodenum and colon permeability of LMWH were examined by means of isolated intestinal membranes from rats in a in vitro transepithelial system.The effects of Imwitor 742 on LWMH intestinal absorption were studied using rat in situ duodenal and colonic in situ instillations.Their absorption was determined by activated partial thromboplastin time(APTT).RESULTS Regional differences were observed in the permeation of LMWH across intestinal membranes;the order of membrane permeability was duodenum>jejunum>ileum>colon.Overall,the permeation of LMWH was relatively poor.All absorption enhancers promoted the permeation of LMWH across the duodenunal and colonic membranes.The rank order of duodenal permeation was Imwitor 742 >sodium taurocholate>sodium caprate > Tween 80 >lecithin and that in colonic in situ permeation was Imwitor 742>sodium caprate>sodium taurocholate >Tween 80>lecithin.In general,the absorption-enhancing effects of these agents were more predominant in the colon than in the duodenum,but the permeation amount in the duodenum was more than in the colon.In the rat duodenual and colonic in situ instillations,1% Imwitor 742 promoted LMWH absorption.When duodenal instillations,the maximum clotting time was 3.6 times higher than the baseline.When colonic instillations,the peak APTT was 2.6 times higher than the baseline.CONCLUSION Deodenum was found to be the best site of absorption.Imwitor 742 are good at increasing the intestinal absorption of LMWH.更多还原