三七总皂苷油包水微乳的处方筛选及体内外评价  

Screening of panax notoginsenoside water in oil microemulsion formulations and their evaluation in vitro and in vivo

作　　者：韩旻[1] 傅韶[2] 方晓玲[3] 

机构地区：[1]浙江大学药学院,浙江杭州310058 [2]美国匹兹堡大学药学院,匹兹堡15282 [3]复旦大学药学院,上海200032

出　　处：《药学学报》2007年第7期780-786,共7页Acta Pharmaceutica Sinica

摘　　要：筛选口服油包水（W/O）微乳处方以提高三七总皂苷（panax notoginsenoside，PNS）中人参皂苷Rb1的体内肠吸收，分别采用大鼠体内肠吸收、脂质体和平行人工膜（parallel artificial membrane permeability assay，PAMPA）等模型分别研究微乳的体内药代动力学及体外对膜流动性和药物膜转运性质的影响。主要以磷脂/乙醇（SP/EtOH）为表面活性剂，与PNS水溶液（400mg·mL^-1）和不同油相分别制备11个W/O微乳处方。多数微乳处方可提高药物的大鼠体内肠吸收，其吸收促进作用除与所含表面活性剂有关外，不同油相的选用也会产生一定影响，其吸收促进作用大小为月桂酸甘油酯≈肉蔻豆酸异丙脂〉棕榈酸异丙脂〉棕榈酸异辛酯。长链（〉C14）脂肪酸酯的吸收促进作用低于中链脂肪酸酯（C8-C14）。多数微乳处方可不同程度的提高脂质体的膜流动性。PAMPA研究中，稀释后微乳（D-ME）中药物的有效透过系数（Pe）多数高于PNS对照溶液，表明微乳中的组分可以提高药物的膜透过能力，稀释前微乳（ME）的Pe与大鼠体内肠吸收具有相对较好的直线相关性（r=0.7740）。W/O微乳可以促进人参皂苷Rb1的肠吸收，吸收促进作用与其提高生物膜流动性有一定关系。PAMPA可以尝试引入制剂处方研究（如吸收促进剂等）的某些领域中。Water in oil （W/O） microemulsion formulation was developed to enhance intestinal absorption of ginsenoside Rb1 （ Rb1 ） of panax notoginseng （PNS）. Effects of W/O microemulsions on pharmaeokineties after intraduodenal administration, membrane fluidity and membrane transport of Rh1 were studied in rats, liposomes and parallel artificial membrane permeability assay （PAMPA）, respectively. Soybean phospholipids/ethanol （SP/EtOH） was selected as surfaetant/eosurfaetant, together with PNS 400 mg · mL^-1 solution and various kinds of oils, to prepare 11 W/O microemulsions. Most of the microemulsions can enhance Rb1 intestinal absorption significantly. Besides surfactant/cosurfactant, oil also had an effect on the enhanced absorption and the order of enhancement was as follows ： glyceryl laurate ≈ isopropyl myristate 〉 isopropyl palmitate 〉 2-ethylhexanol palmitate. The effection of absorption enhancement by the long chain glyceride （ 〉 C14 ） is lower than that by the medium chain glyceride （Cs - C14）. Most of W/O microemulsions were found to enhance the membrane fluidity of liposomes to different extents. In PAMPA analysis, efficient permeability coefficient （Pe） of diluted-microemulsion （D-ME） is mostly higher than that of PNS solution, which indicated the components of microemulision can facilitate the membrane permeability of the drug. Meanwhile, linearity correlation between Pe and ratio of relative bioavailability （Fr） was acquired for undiluted microemulison （ME）. Therefore, W/O microemulsions can enhance intestinal absorption of Rb1, and this effect may be attiributed to its enhancement on membrane fluidity to a certain degree. PAMPA analysis could be brought into not only the investigation of membrane transport of crude drug, but also conditioned preformulation research （ e. g. absorption enhancer etc. ）.

关 键 词：人参皂苷RB1 W/O微乳 膜流动性 平行人工膜 

分 类 号：R943.4[医药卫生—药剂学]