乳糖载体表面形态对吸入粉雾剂处方混合及分散性能的影响

乳糖的表面形态会对混合过程和吸入粉雾剂(DPI)处方的分散性能产生影响。本研究通过将乳糖(InhaLac230■)在高湿环境中放置72 h,得到了与未处理乳糖粒径相似、晶型相同,但表面较光滑的另一种载体颗粒。将2种乳糖颗粒与微粉化马来酸氯苯那敏分别进行混合,得到DPI粉末研究模型。测定了混合过程中不同混合时间点的粉末静电量和混合均匀度;并通过振荡筛分法分离从乳糖载体上脱离的药物,以考察药物与2种乳糖载体颗粒间结合力的大小。利用快速筛选撞击器(fast screening impactor,FSI)考察不同处方的体外分散表现。结果表明,表面光滑的乳糖载体与药物能更快及更好地混匀;混合粉末静电量随时间的变化能近似反映出混合的进程;高湿处理后乳糖与药物的结合更紧密,从而导致体外分散性能明显降低。此外,筛分后混合粉末中的药物含量与其体外分散表现具有相关性。

利用乳糖载体吸附性改善粉末直压奥氮平片的混合均匀度

本试验以奥氮平片为模型,探究了乳糖载体的吸附性能与粉末直压工艺制备小剂量、难溶性药物片剂时粉末混合均匀度的相关性。采用混合物料的混合均匀度为评价指标,以单因素法考察了不同规格乳糖载体的形态和用量、微粉化奥氮平粒径、混合方法和时间对乳糖载体吸附奥氮平的影响。结果表明,在采用圆形形貌和粗糙表面的喷雾干燥乳糖且其用量高于67%、微粉化奥氮平粒径d(0.9)≤39μm和混合10 min的条件下即可稳定乳糖载体对奥氮平的吸附,使制备过程中粉末混合均匀度的变异系数<2%。验证试验显示,3批奥氮平片的含量均匀度符合要求(A+2.4S<6)。本研究表明,在采用粉末直压工艺制备奥氮平片时,稳定乳糖载体对奥氮平的吸附可确保制备过程中粉末的混合均匀度。

Adenovirus-mediated expression of pig α(1,3) galactosyltransferase reconstructs Gal α(1,3) Gal epitope on the surface of human tumor cells

Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.

两种仪器用于乳糖粉末流动特性动态评价的对比研究

将乳糖Inhalac?120和Inhalac?400按100∶0、95∶5、90∶10、85∶15和80∶20(w/w)的比例混合,制成粉雾剂5种乳糖载体。分别采用FT4型粉末流动性测试仪和PFA粉体流变仪动态评价上述5种乳糖载体的流动性。采用FT4仪器得到的表征指标为稳定指数(SI)、基本流动能(BFE)、流量指数(FRI)和特别流动能(SE),而PFA仪器得到的表征指标为稳定系数(FS)、测速100 mm/s下的流动压实系数(CC100)、测速10和100 mm/s下的压实系数比(CC10/100)和内聚性指数(CI)。比较了SE和CI的变化趋势、BFE和CC100的重现性、FRI和CC10/100的区分度等,总结了两种仪器的适用性。本研究表明,两种仪器的流动稳定性测试结果相似,其中FT4仪器更适用于流动能评价,而PFA可区分乳糖粉末的内聚性;FRI和CC10/100结果相似,提示两种仪器均可评价动态流动性。