拉米夫定治疗慢性乙型肝炎及乙型肝炎病毒携带者的疗效评价

目的：观察拉米夫定对慢性乙型病毒性肝炎和病毒携带的疗效。方法：将92例病人分为治疗组50例，对照组42例，治疗组用拉米夫定100mg.d^-1。疗程52wk。治疗前后作肝功能。HBV－二对半HBV－DNA的测定。结果：治疗12wk时，治疗组与对照组ALT复常率的差异无的统计学意义（P＞0．05），但对于HBV－DNA阴转率，治疗组显高于对照组（P＜0．01）。治疗52wk时，治疗组ALT复常率和HBV－DNA阴转率分别为79．4％，74．0％，而对照组为46．9％和7．1％（P＜0．05），结论：拉米夫定能有效地抑制乙肝病毒的复制，是治疗慢性乙型肝炎的安全有效药物。     

同时包载人参3种成分的透明质酸修饰的纳米脂质载体的制备及表征

目的制备包载人参3种成分的透明质酸(hyaluronic acid,HA)修饰的纳米脂质载体(HA-OUR-NLC),并对其进行表征。方法采用纳米脂质体(nanostructured lipid,NLC)包载人参中3种难溶性有效成分齐墩果酸(oleanolic acid,OA)、熊果酸(ursolic acid,UA)、人参皂苷Rg3(ginsenoside Rg3,Rg3)制备纳米脂质载体(OUR-NLC);然后采用HA作为靶向因子,经电荷吸附作用进行修饰。采用动态透析法进行释放度实验。通过流式细胞仪及MTT法考察HA-OUR-NLC对SMMC-7721细胞的细胞摄取及细胞毒性情况。结果采用溶剂超声分散法制备的OUR-NLC外观呈现淡蓝色乳光。并通过电荷吸附法成功制备了HA-OUR-NLC。其形态圆整,分布均匀。体外释放表明其具有一定的缓释作用。摄取实验表明HA-OUR-NLC能被SMMC-7721细胞所摄取。MTT实验结果表明,HA-OUR-NLC对SMMC-7721细胞增殖具有抑制作用。结论采用溶剂超声分散法制备的HA-OUR-NLC具有较好的理化性质和稳定性,且具备一定的缓释长效作用。     

芹黄素纳米脂质载体制剂的制备及理化性质考察

目的:制备芹黄素纳米脂质载体制剂并进行质量评价。方法:采用高温乳化-低温固化法制备芹黄素纳米脂质载体制剂,并对其形态、粒径、表面电位、包封率、载药量、体外释药等特性进行考察。结果:得到的芹黄素纳米粒为类球形,粒径分布均匀,平均粒径为212.1 nm,Zeta电位为-14.65 mV,平均包封率为82.4%,平均载药量为0.97%,体外2 h累积释药30%,随后释药过程趋于缓慢。结论:所制备的芹黄素纳米脂质载体制剂性质稳定,有良好的应用前景。     

Absence of developmental toxicity in a canine model after infusion of a hemoglobin-based oxygen carrier: Implications for risk assessment

Bovine-derived hemoglobin-based oxygen carriers (HBOCs) have been investigated for use in humans (HBOC-201) and approved for veterinary medicine (HBOC-301). We infused pregnant beagles with HBOC-201 to test whether HBOC-induced developmental toxicity previously observed in rats would occur in a species devoid of an inverted visceral yolk sac (invVYS). Phase 1 assessed developmental toxicity of 6 g/kg HBOC-201 on gestational day (GD) 21. Phase 2 investigated single infusions of 6 g/kg HBOC-201 on one of GDs 21, 25, 29 or 33. Phase 3 studied multiple sequential infusions on GDs 21, 23,25,27,29, 31, and 33 at 0.52 g/kg/day (3.6 g/kg total dose). Mild to moderate maternal toxicity occurred in all phases. There was an unequivocal absence of developmental toxicity in all phases. Overall, our hypothesis that HBOC, which interferes with the function of the invVYS, would not affect the offspring in dogs was supported. The implications relative to human risk are discussed.     

Folate and cell penetrating peptide modification effects on penetration behavior of nanostructured lipid carriers using multicellular tumor spheroids

Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructuredlipid carriers (NLC). Real-time penetration of folate- or cell penetrating peptide (CPP)-modified NLC was evaluated using a multicellular tumor spheroid (MTS) established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.     

经皮给药系统促透方法及其联用研究进展

查阅近年来国内外有关经皮给药系统的文献,介绍纳米载体和物理促透法的作用机制,及各种促透方法联用研究进展。透皮促透方法在经皮给药系统中的应用,改善了药物的皮肤渗透性差,克服了皮肤角质层屏障等问题。而且几种促透方法联用可发挥协同作用使促透效果更佳,推动了经皮给药系统的发展。经皮给药系统具有无首过效应、血药浓度稳定、毒副作用小等优点。近年来多种促透新方法和新技术被用于经皮给药系统,提高药物的渗透能力,使得大部分药物经皮制剂的开发成为可能,今后应加强对透皮促透方法联用及其作用机制的研究,有望推动经皮给药制剂的发展。     

熊果酸磷脂复合物纳米结构脂质载体的制备及其体内药动学研究

目的 制备熊果酸磷脂复合物纳米结构脂质载体,并考察其体内药动学.方法 乳化-超声分散法制备熊果酸磷脂复合物纳米结构脂质载体,测定粒径、Zeta电位、包封率、载药量、体外释药.大鼠灌胃给药(12.5 mg/mL)后,于0.25、0.75、1、1.5、2、2.5、3、4、6、8、12 h采血,HPLC法测定熊果酸血药浓度,...     

Effect of haemodilution with diaspirin cross-linked haemoglobin on the oxygen reserve in a rodent model of surgical blood loss

The efficacy of pre-operative haemodilution is limited by the reduction in haemoglobin concentration. Acellular haemoglobin-based oxygen carriers provide an alternative to colloid as a haemodiluent, potentially extending the safe limits of this procedure. The aim of this investigation was to determine whether haemodilution with a cross-linked haemoglobin solution, diaspirin cross-linked haemoglobin solution (DCLHb), would enhance the oxygen reserve compared to pentastarch. Sprague Dawley rats were placed in a metabolic box to directly measure systemic oxygen consumption (VO2). Rats were randomized to be haemodiluted to a cellular haemoglobin of 80 g L(-1) with either DCLHb or pentastarch. Oxygen reserve was assessed during isovolemic haemorrhage by determining the critical oxygen delivery (DO2crit) and haemoglobin concentration at the point of oxygen supply dependency (OSD). Following haemodilution and for the duration of the experiment, cardiac index (CI) was significantly lower and systemic vascular resistance was significantly higher in the DCLHb than the pentastarch group. The DO2crit (3.2 +/- 0.4 mL minAg(-1) and 3.4 +/- 0.5 mL minAg(-1), DCLHb versus pentastarch) and cellular haemoglobin concentration (51 +/- 9 g L(-1) and 48 +/- 9 g L(-1)), at which rats entered OSD were similar in both groups. Total haemoglobin concentration (cellular and plasma DCLHb) and arterial oxygen content were significantly higher in the DCLHb group (total haemoglobin, 66 +/- 8 g L(-1) and arterial content, 9.2 +/- 1.4 mL dL(-1)) compared to the pentastarch group (total haemoglobin, 48 +/- 9 g L(-1) and arterial content, 7.3 +/- 1.4 mL dL(-1)). Oxygen extraction ratios increased from baseline levels to 0.53 +/- 0.07 and 0.56 +/- 0.1, for the DCLHb and pentastarch groups, respectively, and were not significantly different. The increase in arterial oxygen content from DCLHb in plasma was offset by the decrease in CI observed in this group. Plasma DCLHb did not extend the limits of haemodilution beyond the capacity of the cellular haemoglobin concentration.