【作者】 沈腾； 徐惠南； 翁伟宇； 张建芳； 崔磊；

【Author】 SHEN Teng, XU Hui-nan, WENG Wei-yu, ZHANG Jian-fang, CUI Lei (Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China)

【机构】 复旦大学药学院药剂学教研室；

【摘要】 目的考察低分子量肝素钠(LMWH)口服纳米乳的肠道吸收。方法利用伪三元相图筛选了LMWH 纳米乳处方NE-PEG和NE-Imw;利用激光散射仪测定粒径;建立体外消化模型考察LMWH纳米乳的消化速度和程度;以含或不含SNAC载体的LMWH溶液剂作为对照,在体原位肠袢实验考察LMWH两种纳米乳的绝对药理利用度(PA％)。结果纳米乳NE-PEG和NE-Imw的粒径为27-30hm。NE-Imw体外消化 30min时酯解率为95．14％、释放脂肪酸达0．9686mmol,分别为NE-PEG的7倍(13．58%)和9倍 (0．1080mmol)。在体空肠吸收实验表明LMWH溶液剂和含SNAC载体的LMWH溶液剂的PA％分别为1．02％和13．24％;LMWH纳米乳NE-Imw和NE-PEG空肠吸收的APTT最大值分别增加5倍和3倍,PA％分别为 15．24％和4．9％;NE-Imw促LMWH肠吸收程度与载体SNAC相当。结论LMWH纳米乳肠吸收程度与其消化程度呈正相关。本课题为进一步研制LMWH口服给药系统奠定了理论基础和实验依据。更多还原

【Abstract】 Purpose To study on the intestinal absorption of the nanoemulsion of low molecular weight heparin(LMWH). Methods Pseudo-ternary phase diagrams were constructed to obtain the LMWH nanoemulsion formulations: NE-PEG and NE-Imw. Particle size and size distribution was measured by dynamic laser light scattering. Establishing an in vitro lipolysis model was to investigate the rate and extent of lipolysis of LMWH nanoemulsions. Compared to the LMWH solutions with or without SNAC carrier, the pharmacologic availability(PA%) of the two nanoemulsions was explored with in situ rat intestinal absorption. Results The particle size of NE-PEG and NE-Imw was 27-30nm. The digestion percent and the amount of released fatty acids of NE-Imw during 30-minute in vitro digestion was 95.14% and 0.9686mmol, 7 times (13.58%) and 9 times(0.1080mmol) of NE-PEG The in situ jejunum absorption test showed the PA% of LMWH solutions with and without SNAC carrier was 13.24% and 1.02%. NE-Imw and NE-PEG made the APTT rise to a maximum of 5 times and 3 times baseline through in situ jejunum absorption, and PA% was 15.24% and 4.9%. The extent of LMWH intestinal absorption promoted by NE-Imw was corresponded to that of SNAC carrier. Conclusion A positive correlation was found between the extent of intestinal absorption of LMWH nanoemulsion and its lipolysis extent. The study provided the theoretical foundation and experiment evidence for preparing oral drug delivery system of LMWH.更多还原