米托蒽醌聚乳酸缓释毫微粒冻干针剂的体外释药物特性研究

选择含１％维生素Ｃ的生理盐水作释药介质，用动态透析系统和分光光度法考察了不同分子量聚乳酸毫微粒冻干针剂的体外释药特性。分离子量聚乳酸毫微粒的释药速度明显慢于低分子量的聚乳酸毫微粒。通过选择适应分子量的聚乳酸制备毫微粒可控制其释药速度。     

米托蒽醌聚乳酸缓释毫微粒针剂的制备

在单因素实验的基础上用均匀设计优化了米托蒽醌聚乳酸缓释微粒的制备方法。空白和载药微粒的平均粒径分别为１２９．９６和１３３．１５ｎｍ;包封率为９９．２３％;载药量为１３．５６％;制备收率为９９．３％。以乳和支架剂制得的冻干针剂外型美观、理化性质稳定,再分散后平均粒径为１５２．０２ｎｍ。用动态透析系统考察了不同分子量聚乳酸毫微粒冻干针剂的体外释药特性,结果显示高分子量聚乳酸微粒的释药速度明显慢于低分子     

米托蒽醌聚乳酸缓释毫微粒冻干针剂在动物体内的靶向性研究

目的：比较肝靶向米托蒽醌聚乳酸缓释毫微粒（ＤＨＡＱ－ＰＬＡ－ＮＰ）冻干针剂和ＤＨＡＱ水针剂在小鼠体内的分布规律,验证前者的肝靶向性。方法：采用ＨＰＬＣ法测定静注ＤＨＡＱ－ＰＬＡ－ＮＰ和ＤＨＡＱ水针剂后小鼠血液、心、肝、脾、肺、肾的药物浓度,由此计算各器官的相对百分含量。结果：ＤＨＡＱ－ＰＬＡ－ＮＰ冻干针剂在肝脏的分布明显高于ＤＨＡＱ水针剂,在其它器官中的含量则低于水针剂,给药２４小时后药物在肝中的     

米托蒽醌毫微粒静脉冻干注射剂的研究

通过实验制备了米托蒽醌毫微粒冻干注射剂。结果表明，冻干前后米托蒽醌毫微粒形态、粒径、ｐＨ均无显著变化；含水量合格，再分散性良好，制剂稳定；抗肝癌效果明显优于水针剂，毒性略低于水针剂。可望推广生产用于临床。并建立了聚氰基丙烯酸正丁酯毫微粒中的药物测定的方法。     

阿柔比星A聚乳酸毫微粒冻干针剂的研制及体外药物释放规律的研究

研究阿柔比星Ａ聚乳酸毫微粒（ＡＣＲＢ－Ａ－ＰＬＡ－ＮＰ）冻干针剂的制备,并对其体外释药进行考察。根据低共熔点测定结果,以及外观、色泽、再分散性等质量参数为指标,制备出ＡＣＲＢ－Ａ－ＰＬＡ－ＮＰ冻干针剂,采用动脉透析法研究其体个释放规律。结果,制得的ＡＣＲＢ－ＡＰＬＡ－ＮＰ冻干针剂色泽均匀,再分散性良好。其体外释药可用３种方式表达。提示ＡＣＲＢ－Ａ－ＰＬＡ－ＮＰ冻干针剂有明显的缓释特征。     

米托蒽醌淀粉微球的体外释药考察

目的：考察米托蒽醌淀粉微球的体外释药特征。方法：用体外动态恒温透析法模拟释药,紫外可见分光光度法测定释药量。结果：释药介质种类,用量对释药存在影响。结论：米托蒽醌淀粉微球具有缓释作用。     

柱切换HPLC法研究米托蒽醌毫微粒冻干静脉注射剂的药代动力学

建立了血浆中米托蒽醌的柱切换高效液相色谱测定法,测定和比较了米托蒽醌溶液型注射剂和毫微粒冻干静脉注射剂在家兔体内的血药曲线,并研究比较了二者的药代动力学参数。米托恩醌毫微粒冻干注射剂使米托蒽醌在血中浓度大为降低,血中分布容积增大了近5倍,体内平均驻留时间延长了2倍多。表明米托蒽醌毫微粒有明显的体内长效作用,结合其体内分布试验研究结果,表明其具有明显肝靶向分布作用。     

米托蒽醌聚氰基丙烯酸正丁酯毫微粒的研究

用乳化聚合法制备了米托蒽醌聚氰基丙烯酸正丁酯毫微粒,并对其表面荷电特性、形态、大小及其分布、体外释药性质、载药量、初步稳定性和在动物体内的分布进行了研究。结果表明,粒径d_av=55.23nm,载药量为46.77%,包封率为84.89%,表面带负电荷。体外释药符合双相动力学规律。其胶体溶液能经受煮沸30min灭菌。经氚标记液闪计数技术测定证实其iv后主要集中于肝脏,并有一定的肝肿瘤和肝细胞的靶向性。提示其对于提高米托蒽醌抗肝癌的效果和降低其全身毒副作用有重要意义。     

阿柔比星A聚乳酸毫微粒冻干针剂小鼠体内分布研究

对阿柔比星Ａ冻干针剂与阿柔比星Ａ聚乳酸毫微粒冻干针剂给予小鼠尾静脉注射后体内分布比较，采用ＨＯＬＣ法分别测定小鼠给药后血液及主要脏器中ＡＣＲＢ０Ａ浓度。结果阿柔比星Ａ聚乳酸毫微粒在小鼠肝脏中的浓度高于对照品浓度。     

阿克拉霉素A聚乳酸毫微粒冻干针剂在兔体内的血浆药动学研究

目的 :研究阿克拉霉素A聚乳酸毫微粒冻干针剂在兔体内的血浆药代动力学。方法 :采用HPLC法测定给药后的血浆药物浓度。结果 :经3p87药动学程序处理 ,得到两种制剂的药代动力学参数。结论 :与阿克拉霉素A相比 ,阿克拉霉素A聚乳酸毫微粒具有显著的缓释特性     

米托蒽醌白蛋白微球和糖蛋白微球的体外释药规律

目的：考察米托蒽醌白蛋白微球和米托蒽醌联糖白蛋白球的体外释药规律。方法：采用动脉透析法释药,分光光度法测定米托蒽酯含量。结果：二者在体外释药符合双指数双相动力学规律,但后者达释药平衡快（约6小时）,累积释放量几科比前者小一倍。结论：两种微球的累积药分数经单因数经单因数经方差分析,具有显著差异。     

聚乳酸微囊药物含量的测定方法

采用溶解-沉淀相分离技术测定青蒿素衍生物12-O-(对硝基苯甲酰)还原青蒿素,操作简便,省时,其精确性和重现性都比常用的扩散-提取法为佳。     

烟酸缓释片在体外释放和体内吸收的相关性研究

目的：研究烟酸缓释片在体内外的相关性。方法：通过烟酸缓释片体外释放试验和体内动力学研究，考察其在体内外的相关性。结果：烟酸缓释片在人工胃液及人工肠液中均能缓慢释药，体内血药浓度维持时间长，体外释放百分率与体内吸收分数呈良好相关性。结论：烟酸缓释片在体外释放和体内吸收之间有明显的相关性。     

PREDICTION OF IN VIVO DRUG DISPOSITION FROM IN VITRO DATA BASED ON PHYSIOLOGICAL PHARMACOKINETICS

Because of the increasing availability of human liver samples we now have a greater ability to predict in vivo drug disposition and pharmacokinetics in man from in vitro metabolic and binding studies. Firstly, we review several successful attempts to predict in vivo metabolic clearances in experimental animals and humans from in vitro biochemical parameters such as plasma protein binding and hepatic metabolism, based on anatomically and physiologically realistic pharmacokinetic models. Despite the success of this approach, however, there are still some difficulties in predicting in vivo hepatic metabolism in man using in vitro human liver samples due to the large inter-individual differences arising from polymorphism (intrinsic variability) or differences in enzyme activity (extrinsic variability) due to the conditions under which liver samples have been kept. We propose a possible method to overcome these errors resulting from inter-individual differences by applying the concept of a scaling factor. In the kinetic models used in prediction, we often make a number of assumptions, e.g. rapid equilibrium between the blood and hepatocytes, availability of only the unbound drug for uptake and elimination, and homogeneous distribution of enzymes along the path taken by the blood in the liver. However, recent evidence suggests that these assumptions are not necessarily valid. As examples involving the first and second assumptions, respectively, there is the plasma-membrane-permeability-limited metabolism of a high-clearance drug, 4-methylumbelliferone, and the albumin-mediated uptake of amphiphatic drugs. The multiple-indicator dilution method (MID) is useful for estimating the membrane permeability of drugs in liver perfusion systems where the spatial organization and cell polarity of the liver are maintained. If the aforementioned factors are taken into consideration and membrane permeabilities using human hepatocytes and/or subcellular fractions such as microsomes are measured under conditions close to those in vivo, much more reliable predictions of drug hepatic clearance in man may become possible.     

异烟肼的体外透皮实验研究

异烟肼在体外透皮吸收实验中,能透过离体兔皮,月桂氮酮能明显促进其透皮吸收,其中以5%浓度为最佳。     

盐酸尼卡地平的体外大鼠皮肤渗透试验

用改良的扩散装置评价了盐酸尼卡地平（１）通过脱毛大鼠皮肤的渗透动力学以促渗剂月桂氮Ｚｈｕｏ酮（２）的作用。１的皮肤渗透符合零级动力学，但透皮流量很小，当加入２后，１的透皮量可增加约８０倍。     

有机药物中残留三氟醋酸测定方法的研究

目的：检查有机药物中残留的溶剂三氟醋酸。方法：将药物进行氧瓶燃烧破坏后,用苯素氟蓝比色法测定氟,再换算成三氟醋酸的量。结果：检测限为4．6μg的三氟醋酸,线性范围为5－30μg氟（r=0.9990)。结论：该检查方法较简便,灵敏,结果可靠。