生血宁片治疗缺铁性贫血982例

目的:在Ⅱ期临床研究的基础上扩大受试者范围,增加少年、老年、孕妇及术后的缺铁性贫血病人群体,进一步观察生血宁片的疗效和不良反应。方法:将982例确诊为缺铁性贫血的病人分为成年组(2 5 4例)、老年组(2 0 5例)、孕妇组(1 5 1例)、术后组(1 30例)、少年组(70例)和儿童组(1 81例) ,各组病人均口服生血宁片0 . 5g ,tid ,疗程为4周。结果:各组病人疗效相似,非儿童组有效率为85. 9%,儿童组有效率为85. 6 %;血常规各项指标(血红蛋白浓度、平均红细胞容积和平均红细胞血红蛋白量)、血清铁含量及总铁结合力均有显著改善。除少数受试者出现轻度恶心、腹部不适外,未见其他不良反应。结论:生血宁片是治疗各年龄组尤其是青少年和孕妇缺铁性贫血有效和安全的药物。     

鲨肝活性肽对对乙酰氨基酚致小鼠急性肝损伤的保护作用

目的探讨鲨肝活性肽(sHSS)对对乙酰氨基酚(AAP)致小鼠急性肝损伤的保护作用。方法用AAP(200 mg·kg^-1,ip)诱导小鼠急性肝损伤,用改良赖氏法测血清ALT和AST,通过光镜和电镜观察肝细胞显微和亚显微结构的变化,用流式细胞仪分析肝细胞凋亡,同时用RT-PCR方法分析Fas mRNA表达水平。结果sHSS 3.0和1.5 mg·kg^-1可显著降低肝损伤小鼠血清ALT和AST的水平;改善模型鼠肝组织细胞坏死及炎症反应;高剂量sHSS(3 mg·kg^-1)对肝线粒体具有保护作用,下调Fas mRNA的表达水平,并具有抗凋亡作用。结论sHSS对AAP诱导的肝损伤具有明显的保护作用,其机制可能与保护肝线粒体、抑制Fas基因表达及肝细胞凋亡有关。     

维生素E固化颗粒的制备及质量评价

分别采用不同型号的微粉硅胶或β-环糊精制备了维生素E固化颗粒,并以载药量、维生素E利用率和颗粒收率为评价指标进行筛选。结果表明,采用S80型微粉硅胶可制得载药量达60%的维生素E颗粒,明显优于β-环糊精颗粒(约6%)。用其直接粉末压片,所得片剂各项指标均符合中国药典2010年版标准。该片在高温(60℃)条件放置10 d,外观和含量未见明显变化;但在高湿[相对湿度(90±5)%、25℃]环境下片剂会吸潮,强光[(4 500±500)1x]条件下含量下降。     

几种亲水凝胶骨架材料相关性质的比较

以茶碱为模型药物,采用直接压片法制备亲水凝胶骨架片,从骨架片吸水性、膨胀性、溶蚀性及凝胶强度4个方面,全面比较了几种亲水凝胶骨架材料羟丙甲纤维素(hydroxypropylmethylcellulose,HPMC)、聚氧化乙烯(polyethylene oxide,PEO)、海藻酸钠[sodium alginate、低黏度NaAlg(L)、高黏度NaAlg(H)]和黄原胶(xanthan gum,XG)辅料性质和释药机制的差异。结果表明,吸水速率常数XG>>NaAlg(H)>PEO>NaAlg(L)>>HPMC;膨胀指数为XG>>PEO>>HPMC>>NaAlg;溶蚀速率NaAlg(L)>NaAlg(H)>>PEO80>PEO200>PEO300>XG≈PEO400≈K4M>K15M>PEO600≈K100M;凝胶层强度PEO>HPMC>XG>>NaAlg。对于PEO和HPMC骨架片,随着聚合物分子量增加,药物逐渐从以溶蚀机制为主的释放转移为以扩散机制为主的释放;对于NaAlg骨架片,药物主要以溶蚀机制释放;对于XG骨架片,药物主要以非Fick扩散机制释放。通过比较不同高分子材料之间的性能差异有助于合理设计和...     

Optimization and evaluation of lyophilized fenofibrate nanoparticles with enhanced oral bioavailability and efficacy

Abstract

The objective of this study was to enhance physiochemical properties as well as oral bioavailability of the poorly water soluble drug fenofibrate (FB), through preparation of amorphous solid dispersions (ASDs). ASDs were prepared via freeze drying using polyvinylpyrrolidone (PVP) K30 and poloxamer 188 as hydrophilic carriers. Formulations were optimized by 3² full factorial design (FFD) with PVP-K30 level (X₁) and poloxamer 188 level (X₂) as independent variables and particle size (Y₁), zeta potential (Y₂), drug content (Y₃) and dissolution rate (T90, [Y₄]) as dependent variables. Optimized FB nanoparticles were physicochemically evaluated and formulated into lyophilized sublingual tablets. Pharmacokinetic, pharmacodynamics and histological finding of optimized formulation were performed on rabbits. Y₁ and Y₄ were significantly affected by independent variables while Y₂ and Y₃ were not affected. Physicochemical characterization showed the drug was in amorphous state, nanometer range and pharmacophore of FB was preserved. Administration of optimized FB tablets to rabbits with fatty liver led to significant reduction (p?<?0.001) in serum lipids. Moreover, histological analysis of liver specimens confirmed the improved efficacy in animals with fatty liver. In this study, we confirmed that ASDs of FB had beneficial effects on managing fatty liver and serum lipids level in hyperlipidemic rabbits.     

盐酸莫西沙星片Beagle犬体内药代动力学

目的建立Beagle犬血浆样品中莫西沙星HPLC测定方法,研究Beagle犬口服盐酸莫西沙星片后体内药动学。方法色谱柱:依利特C18色谱柱(4.6mm×250mm,5μm);流动相:乙腈-0.05mol/L磷酸盐缓冲液(含0.01mol/L四丁基硫酸氢铵,pH=3.8)=15:85;检测波长:295nm;柱温:25℃;流速:1.0mL/min;进样量:20μL。Beagle犬口服盐酸莫西沙星片后定时取血,HPLC法测定血浆药物浓度,DAS2.0软件计算药动学参数。结果莫西沙星在Beagle犬体内的药-时曲线符合二室开放模型,主要药动学参数Tmax为(3.33±0.23)h,Cmax为(7.35±0.40)μg/mL,AUC为(118.37±13.05)μg/mL.h,t1/2α为(3.64±0.34)h,t1/2β为(13.49±0.50)h。结论此测定方法操作简单,专属性强,重现性好,所得药动学参数有助于对莫西沙星的进一步研究。     

Enhanced dissolution of sildenafil citrate as dry foam tablets

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5?kg, friability test <1% with a disintegration time <5?min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.     

药用炭剂治疗慢性肾功能不全的随机对照多中心临床研究

目的 观察国产药用炭剂片与胶囊（肠道毒素吸附剂）治疗慢性肾功能不全的疗效和安全性。方法 用多中心临床对照试验，187例患者口服治疗8周，比较治疗前后血肌酐、尿素水平和临床症状评分，并评价其安全性；对照药为包醛氧淀粉。结果 肌酐：治疗有效率分别为炭片组：33．3％，炭胶囊组：33．3％，包醛氧淀粉组：29．4％。尿素：治疗有效率分别为炭片组：50．0％，炭胶囊组：46．0％，包醛氧淀粉组：59．4％。经治疗后，3组患者临床症状评分较治疗前有显著改善。药用炭剂片、胶囊与包醛氧淀粉的药物不良反应发生率分别为4．8％，3．1％，1．5％。结论 国产药用炭剂作为肠道吸附剂，用于治疗慢性肾功能不全安全、有效。     

地稔总酚胃内漂浮片制备工艺的研究

目的:优选地稔总酚胃内漂浮片的制备工艺。方法:选择Ⅳ丙烯酸树脂、HPMCK4M,MCC101、十八醇为辅料,干法直接压片,以体外漂浮性能和体外释放性能为指标筛选地稔总酚胃内漂浮片的处方,并进一步研究压片压力对体外漂浮性能和体外释放性能的影响。结果:地稔总酚胃内漂浮片的最优处方和工艺为:地稔总酚有效部位、Ⅳ丙烯酸树脂和十八醇分别为处方比例的31%,MCC101为7%,加硬脂酸镁适量,干法直接压片,控制压力3~4 kg。结论:该工艺重现性好,为地稔总酚胃内漂浮片的制备提供依据。     

降脂灵片对压力超负荷所致大鼠心肌肥厚的影响

大鼠腹主动 脉部分狭窄５ ｗ ｋ 后,形成实 验性心肌肥厚模 型,心肌和左心 室重量明 显增加; 心肌过 氧化脂质（ Ｌ Ｐ Ｏ） 含 量显著增加,超氧 化物歧 化酶（ Ｓ Ｏ Ｄ） 活性 下降;心 肌 Ｃａ２ ＋ 和主 动脉 Ｃａ２ ＋ 含量 明显增加,与模 型组相比 Ｐ＜ ０ ．０１ 。给降脂灵片０ ．３５ ｇ／ ｋｇ 和 ０ ．７ｇ／ ｋｇ 后均能降低心肌 和左心室重 量;降低心肌 Ｌ Ｐ Ｏ 含量,增加 Ｓ Ｏ Ｄ 活性;降 低心肌 Ｃａ２ ＋ 和主 动脉 Ｃａ２ ＋ 的含 量。提示降脂灵 片抗心 肌肥厚作用与清 除氧自由基和 钙拮抗有关