胶原蛋白作为蛋白类药物载体系统的应用

近几年来有效的蛋白类药物载体系统一直是药剂学领域研究的热点,为了延长蛋白类药物的疗效,人们对许多材料作为蛋白类药物载体系统进行了研究.胶原蛋白作为众多候选材料之一,目前有凝胶、膜、海绵等制剂以及近几年才出现的供皮下注射的微条.该文对胶原蛋白在蛋白类药物载体系统中的应用进行了介绍.     

关于新版药学类规划教材标准化的讨论

全国高等药学类专业用新版(第5轮)规划教材已经出版,各院校均在使用.这套系列教材共25本,其中药剂学、药物分析、生物化学、天然药物化学、药事管理学5本为普通高等教育"十五"国家规划教材,其余为高等医药教材建设研究会规划教材.这套教材适用于药学类专业本科教育,也可供其它相关专业使用.本文就有关标准化问题试作一讨论.     

HPLC测定人体血浆中替硝唑浓度

目的:建立替硝唑血药浓度测定方法,用于复方替硝唑片血药浓度研究。方法:采用高效液相色谱法。色谱柱为C18柱,流动相为12%乙腈水溶液(pH7.0),检测波长318nm。结果:样品组分在0.2～20μg.ml-1线性良好(r=0.9998),最低血浆药物检测浓度为0.02μg.ml-1。回收率为94.4%～98.3%,日内及日间RSD<5%。结论:本法简便、迅速、灵敏、准确,适合于临床药学研究需要。     

Comparison of powder produced by evaporative precipitation into aqueous solution (EPAS) and spray freezing into liquid (SFL) technologies using novel Z-contrast STEM and complimentary techniques.

The objective of this study was to compare the properties of particles formed by nucleation and polymer stabilization (e.g. evaporative precipitation into aqueous solution (EPAS)) versus rapid freezing (e.g. spray freezing into liquid (SFL)). Powders formed by EPAS and SFL, composed of danazol and PVP K-15 in a 1:1 ratio, were characterized using X-ray powder diffraction, modulated differential scanning calorimetry (MDSC), contact angle determination, dissolution, scanning electron microscopy (SEM), environmental scanning electron microscopy (ESEM), BET specific surface area, and Z-contrast scanning transmission electron microscopy (STEM). Large differences in particle morphologies and properties were observed and explained in terms of the particle formation mechanisms. Both techniques produced amorphous powders with high T(g) and low contact angle values. However, STEM analysis showed highly porous bicontinuous nanostructured 30nm particles connected by narrow bridges for SFL versus aggregated 500 nm primary particles for EPAS. The combination of STEM and other characterization techniques indicates solid solutions were formed for the SFL powders consistent with rapid freezing. In contrast, the EPAS particle cores are enriched in hydrophobic API and the outer surface is enriched in the hydrophilic polymer, with less miscibility than in the SFL powders. Consequently, dissolution rates are faster for the SFL particles, although both techniques enhanced dissolution rates of the API.     

Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study.

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.     

环孢素A固体分散体的制备及体外研究

 目的利用固体分散技术改善环孢素A(CsA)的溶解性能,提高其体外溶出速率。方法以Poloxamer188为载体,溶剂熔融法制备不同比例组成的环孢素A固体分散体,考察体外溶出速率及不同转速和不同溶出介质对溶出的影响,并配合X-射线粉末衍射分析药物在载体中的存在状态。对溶出度结果用Weibull分布模型进行拟合,计算体外溶出主要参数t_d和t₅₀,并进行方差分析。结果CsA在药物-载体比例为1:4或1:6的固体分散体中呈非晶态。固体分散体的溶出速率与相应物理混合物及原料药间存在极显著差异(P<0.01),溶出介质对药物溶出无显著性影响(P>0.05)。结论制成固体分散体能显著提高CsA的溶出速率。     

自卫颗粒抗胃黏膜损伤作用的实验研究

近年来加强胃黏膜防御功能的研究越来越受到国内外的重视.本实验通过预先给予大鼠灌服自卫颗粒,并与思密达作对照,观察自卫颗粒对大鼠胃黏膜损伤的预防保护作用,同时从表皮生长因子(EGF)、前列腺素E2(PGE2)角度探讨其可能的作用机理.     

芪丹颗粒剂治疗肺间质纤维化105例临床研究

目的:观察芪丹颗粒剂对肺间质纤维化患者的临床疗效.方法:选择105例肺间质纤维化患者作为治疗组,给予芪丹颗粒剂,对照组60例,给予强的松0.5mg/kg,两组疗程均为3～6个月,每1～3个月随诊1次.观察两组患者治疗后的症状、体征、肺部高分辨率CT(HRCT)及肺功能变化.结果:治疗6个月后,治疗组症状、体征改善率优于对照组(P＜0.05或P＜0.01);治疗组治疗3个月和6个月后,肺HRCT和肺功能改善率优于对照组(P＜0.05或P＜0.01).结论:芪丹颗粒剂可以不同程度地改善肺间质纤维化患者症状和体征,使患者肺功能停止恶化,且用药期间未见任何副作用,耐受性良好.     

三保心对大鼠体内外血栓形成的影响

目的:观察三保心对大鼠体内外血栓形成的影响.方法:大鼠灌服三保心高、中、低3种剂量(10g生药/kg、5g生药/kg、1g生药/kg)后,采用Chandler法造成体外血栓和电刺激颈总动脉形成体内血栓,观察三保心对体内外血栓形成的影响.结果:三保心高剂量组明显延长大鼠体内血栓形成时间(P<0.05);高、中、低各剂量组均能显著抑制大鼠体外血栓的形成,使血栓长度明显缩短,血栓湿重和干重明显减轻(P<0.05或P<0.01).结论:提示三保心具有抑制血栓形成的作用.     

含去痴灵水提物血清抑制M146L细胞分泌Aβ

目的:研究含去痴灵水提物血清对M146L细胞分泌的β淀粉样蛋白(β-amyloid protein)的影响,探讨去痴灵治疗阿尔茨海默病(Alzheimer's disease,AD)的可能性及作用机制.方法:采用血清药理学方法,制备含去痴灵水提物血清.体外培养稳定转染人类阿尔茨海默病β淀粉样前体蛋白(beta-amyloid protein precursor,APP)和突变型早老素1(prsenilin-1,PS1)基因的中华仓鼠卵巢上皮细胞系(M146L),使之高效产生β淀粉样蛋白42(Aβ42),建立Aβ42过度表达的细胞模型.加入含去痴灵水提物血清,用MTT法检测不同浓度(12%、6%、3%)的含药血清对M146L细胞毒作用,用ELISA法测定其对M146L细胞分泌Aβ42的影响.结果:3个浓度的含药血清对M146L存活均无影响,对细胞分泌的Aβ42有抑制作用,并呈现一定的量效关系.结论:一定剂量(12%、6%、3%)的含去痴灵水提物血清对M146L细胞分泌的Aβ42有明显的抑制作用,其机制尚待进一步研究.