二阶导数光谱法同时测定双组分体系中阿司匹林和水杨酸的含量

目的：建立二阶导数紫外光谱法同时测定双组分体系中阿司匹林和水杨酸浓度。方法：配制阿司匹林和水杨酸的系列标准溶液,记录样品在230～350nm的紫外扫描图谱,并求二阶导数光谱;采用二阶导数光谱法和等吸收波长法分别测定混合物中阿司匹林和水杨酸的含量,计算回收率。结果：二阶导数光谱法测定双组分体系中阿司匹林的平均回收率为（100.32±0.94）%,水杨酸的平均回收率为（100.34±0.61）%;等吸收波长法能够准确测定混合体系中阿司匹林的含量,测定回收率为（99.66±1.17）%,但水杨酸测定误差较大,平均回收率为（104.16±3.65）%。结论：二阶导数光谱法操作简便,结果准确,可同时准确测定双组分体系中阿司匹林和水杨酸的含量。     

GC/MS同时测定尿中吗啡和可待因含量

建立了GC/MS同时测定尿中吗啡和可待因含量的分析方法。线性范围为20—1000ng/ml(r==0.9997);方法回收率是:吗啡86.8±7.9%,可待因84.7±7.0%。天内测定RSD<10%,天间测定RSD<15%。该法已用于生物样品中吗啡和可待因的测定。     

哈西奈德脂质体制备方法的选择及其含量与包封率的测定

目的选择制备哈西奈德脂质体的方法并测定其含量与包封率。方法采用注入法、冻融法、薄膜分散法制备哈西奈德脂质体;用超速离心法分离游离药物;高效液相色谱法测定含量与包封率。结果冻融法、注入法、薄膜分散制备的脂质体哈西奈德含量分别为99.23%±0.13%,98.37%±0.19%,99.36%±0.16%;包封率分别为83.17%±2.21%,77.19%±1.37%,87.28%±1.49%。在选定的色谱条件下,哈西奈德与辅料能完全分离,在4~40 mg/L范围内,药物浓度与峰面积呈良好线性关系(r=0.999 9),平均回收率为101.02%,RSD为0.64%。结论薄膜分散法制备的脂质体包封率较高;超速离心-高效液相色谱法操作简便、准确、重复性好,可用于测定哈西奈德脂质体的含量和包封率。     

双波长等吸收紫外法同时测定复方阴道泡腾片中酮康唑与替硝唑含量

目的 建立同时测定酮康唑和替硝唑含量的双波长等吸收紫外分光光度法.方法 建立双波长法测定酮康唑和替硝唑含量的标准曲线,并考察检测方法的精密度和回收率.结果 选择317nm作为替硝唑的测定波长,221nm作为酮康唑的含量测定波长,并以352nm作为参比波长.二者标准曲线方程为:A=0.029C+0.0168;A=0.456C-0.0742,高、中、低浓度的平均回收率分别为(100.2±0.70)%;(99.4±0.92)%,测定的日内精密度RSD分别为0.62%,1.03%;日间精密度RSD为1.13%,1.42%.结论 双波长等吸收紫外光度法同时测定酮康唑和替硝唑含量的方法学特异性好,精密度和回收率符合测定要求,测定结果可靠.     

HPLC法测定葛根总黄酮固体脂质纳米粒的载药量及包封率

目的：建立HPLC法同时测定葛根总黄酮固体脂质纳米粒中4种异黄酮类成分的包封率及载药量。方法采用RP-HPLC法,Kromasil C18（4.6mm ×250mm,5μm）色谱柱;甲醇-0.1%枸橼酸溶液为流动相梯度洗脱;流速1.0mL/min,柱温40℃,检测波长250nm。采用高速离心法分离固体脂质纳米粒中游离药物。结果3-羟基葛根素、葛根素、大豆苷和大豆苷元线性关系良好,平均回收率分别为（100.28±2.52）%、（100.26±2.33）%、（100.08±3.35）%及（100.44±3.48）%。3批次葛根总黄酮固体脂质纳米粒中3＇-羟基葛根素、葛根素、大豆苷和大豆苷元的包封率分别为（84.35±0.45）%、（86.84±0.48）%、（89.52±0.86）%及（93.80±0.50）%,其载药量分别为（10.37±0.36）%、（14.19±0.52）%、（16.79±0.34）%及（20.00±0.97）%。结论本法简单快速、结果准确可靠,可同时测定葛根总黄酮固体脂质纳米粒4种成分的载药量与包封率。     

用极谱法和比色法测定环磷酰胺

用极谱法和比色法分析环磷酰胺(下简称CP)及其制剂,乃依据CP 与亚硝酸的反应。用阴极扩散波作CP 的直流极谱测定,其准确度为99.98±1.09%。此波形良好,电极反应不可逆。通过差示脉冲极谱分析可测定由0至10ppm 的CP,当浓度在10～60ppm 时,总准确度为100.16±0.99%.同时利用柠檬黄色的亚硝基衍生物的吸收度与CP 浓度间的线性关系可进行比色分析,准确度为100.2±u.99%.     

一测多评法同时测定竭红跌打酊中5种成分的含量

目的建立一测多评法同时测定竭红跌打酊中羟基红花黄色素A、儿茶素、表儿茶素、巴西苏木素和(±)原苏木素B的含量。方法采用Agilent Zorbax SB-C_(18)色谱柱(4.6 mm×250 mm,5μm);流动相:乙腈-0.2%磷酸溶液,梯度洗脱;检测波长:403 nm(检测羟基红花黄色素A)和280 nm[检测儿茶素、表儿茶素、巴西苏木素和(±)原苏木素B];流速:0.9 ml/min;柱温:35℃。以儿茶素为内标,建立竭红跌打酊中该成分与羟基红花黄色素A、表儿茶素、巴西苏木素和(±)原苏木素B的相对校正因子,计算其含量。通过外标法测定结果和一测多评法计算结果进行对比,验证所建立方法的可行性。结果羟基红花黄色素A、儿茶素、表儿茶素、巴西苏木素和(±)原苏木素B分别在6.98～139.60、10.12～202.40、5.76～115.2、3.82～76.40、2.18～43.60μg/ml范围内线性关系良好,平均加样回收率分别为98.26%、100.09%、97.79%、97.25%、96.96%,RSD分别为0.88%、0.71%、1.29%、0.85%、1.43%。一测多评法计算结果与外标法测定结果无显著差异。结论一测多评法可以用于竭红跌打酊中5个成分含量的同时测定及质量控制。     

复方布洛芬苯海拉明软胶囊溶出度测定方法

建立了同时测定布洛芬和苯海拉明的含量反相高效液相法,确定以C18柱,流动相为乙腈-磷酸盐缓冲盐-甲醇为3∶2∶5,流速为1.0 mL.min-1,检测波长为210 nm的色谱条件;通过对溶出转速、介质和溶出曲线等条件考察,建立了本软胶囊溶出度的测定方法。结果:布洛芬在55.1～551μg.mL-1浓度范围内呈良好的线性关系,苯海拉明在6.9～69μg.mL-1浓度范围内呈良好的线性关系,布洛芬和盐酸苯海拉明的平均回收率分别100.8%±0.7%和101.4%±0.6%,溶出度测定结果限度为30 min大于标示量的80%。     

高效液相色谱法测定活络灵胶囊中泼尼松龙和吲哚美辛含量及含量均匀度

在ShimpakCLC-ODS柱上,甲醇-0.02mol/L醋酸钠溶液(62:38)为流动相,高效液相色谱法同时测定活络灵胶囊中泼尼松龙和吲哚美辛。紫外检测波长254nm。二组分线性关系良好,6次测定的平均回收率±RSD%分别为100.1%±0.04%,996%±0.22%。本法用于制剂的含量及含量均匀度测定,切实可行.     

磺胺药与红霉素琥珀酸乙酯口服混悬液的分析

本文介绍用高效液相色谱法和自动比法法分别测定口服混悬液中磺胺药及红霉素琥珀酸乙酯的含量。高效液相色谱法测定乙酰磺胺异噁唑(甲)和三磺胺嘧啶(Trisulfapyrimidines,乙)的方法速度快,专一性高,稳定性好,红霉素琥珀酸乙酯(丙)不干扰,相对标准偏差为±2.1～3.1%,回收率为100.2%。自动比浊法测定丙时,磺胺药无干扰,相对标准偏差为±1.3或±3.5%,回收率为97.7%。作者采用二个配方。混悬液Ⅰ:丙200mg/5ml;     

复方制剂的相关概念探讨

目的：梳理与复方制剂相关的概念,为完善中国复方制剂监管政策提供依据。方法：对2012年底前国内外与复方制剂有关的文献和指南,比较分析复方制剂相关概念的内涵。结果与结论：复方制剂相关的概念国外包括固定剂量复方制剂、多效药片／丸、组合药物、组合包装药品等,中国有复方制剂、复合药;在中国复合药是一个笼统称谓,其实质是西药复方制剂,并不是法定专有名称;国外的固定剂量复方制剂有明确的注册分类原则,而中国复方制剂则没有。     

奥扎格雷钠联合复方丹参注射液治疗脑梗死疗效观察

目的 观察奥扎格雷钠联合复方丹参注射液治疗急性脑梗死的治疗效果.方法 用奥扎格雷钠联合复方丹参注射液治疗40例,另40例接受单纯复方丹参注射液治疗.结果治疗组与对照组总有效率分别为87.5%和67.5%（P〈0.05）.结论 奥扎格雷钠联合复方丹参注射液是一种治疗脑梗死的有效方法.     

In Vitro and in Vivo Trans-Esterification of 1-[2(R)-(2-Amino-2-Methylpropionylamino)-3-(1H-Indol-3-yl)Propionyl]-3(S)-Benzyl-Piperidine-3-Carboxylic Acid Ethyl Ester and the Effects of Ethanol on Its Pharmacokinetics in Rats

PURPOSE: To investigate the in vitro trans-esterification of 1-[2(R)-(2-amino-2-methylpropionylamino)-3-(1H-indol-3-yl)propionyl]-3(S)-benzyl-piperidine-3-carboxylic acid ethyl ester (compound A) and to determine the effects of ethanol on its in vivo pharmacokinetics in male Sprague-Dawley rats. METHODS: The effects of deuterated [d5]ethanol on the hydrolysis and trans-esterification of compound A in rat plasma and rat liver microsomes in the presence or absence of bis(p-nitrophenyl) phosphate (BNPP), a carboxylesterase inhibitor, were investigated. Following an oral pretreatment with deuterated ethanol in conjunction with an intravenous dose of compound A to rats, the pharmacokinetics of compound A and deuterated compound A were evaluated. RESULTS: It was observed that the amount of deuterated compound A generated increased with increasing amounts of deuterated ethanol in incubates, whereas the amount of hydrolyzed product (compound B) decreased. BNPP inhibited both the hydrolysis and the trans-esterification of compound A. Furthermore, the pharmacokinetics of compound A in rats receiving ethanol was altered, such that the plasma clearance decreased by 1.5-fold and the elimination rate constant decreased by 2-fold. Deuterated compound A was determined, confirming that trans-esterification proceeded in vivo; approximately one third of the intravenous dose of compound A underwent trans-esterification. CONCLUSIONS: In the presence of ethanol, compound A underwent trans-esterification catalyzed by carboxylesterases. Ethanol pretreatment resulted in a decrease in the in vivo clearance of compound A mainly due to trans-esterification with ethanol.     

GLUT1介导的脑靶向去甲文拉法辛前药的设计与合成

目的合成一种由葡萄糖转运蛋白1(GLUT1)介导的脑靶向去甲文拉法辛前药。方法将苄基保护的去甲文拉法辛与己二酸单叔丁酯在缩合剂DCC作用下成酯Ⅱ,经三氟乙酸脱除叔丁基保护后,再与1,2,3,4-四-O-三甲硅基-α-D-吡喃葡萄糖在缩合剂DCC的作用下成酯,在酸性条件下脱除三甲硅基保护,最后催化氢化脱除苄基保护得到目标化合物。结果与结论合成了目标化合物脑靶向去甲文拉法辛前药;目标化合物及重要中间体均经1HNMR和MS确证。     

Interaction with indinavir to enhance systemic exposure of an investigational HIV protease inhibitor in rats,dogs and monkeys

1. The use of a beneficial interaction between indinavir and compound A, a potent investigational HIV protease inhibitor to enhance systemic exposure of compound A, was investigated. 2. When administrated alone, compound A underwent extensive hepatic first-pass metabolism in rats and monkeys, resulting in low oral bioavailability. 3. In vitro studies with liver microsomes revealed that compound A metabolism was mediated exclusively by CYP3A enzymes in rats, dogs and monkeys. Indinavir, which also was metabolized predominantly by CYP3A enzymes, extensively inhibited compound A metabolism in microsomes, whereas compound A showed weak inhibitory potency on indinavir metabolism. 4. Consistent with in vitro observations, co-administration of the two compounds resulted in a 17-fold increase in oral AUC of compound A in rats owing to the inhibition of metabolism of compound A by indinavir, whereas compound A did not affect indinavir metabolism as indicated by the unchanged indinavir AUC. Similarly, the systemic exposure of compound A in dogs and monkeys was increased substantially following oral co-administration with indinavir by 7- and > 50-fold, respectively. 5. Enhancement in compound A systemic exposure by indinavir in humans, as predicted based on the in vivo animal and in vitro human liver microsomal data, was confirmed in subsequent clinical studies.     

Inhibition of DNA topoisomerase II catalytic activity by the antiviral agents 7-chloro-1,3-dihydroxyacridone and 1,3,7-trihydroxyacridone.

Previously we reported that the antiproliferative and antiviral actions of 7-chloro-1,3 dihydroxyacridone (compound 1) and its derivatives may be mediated through the inhibition of mammalian DNA topoisomerase II. In the present work, we have extended our investigation into the mechanism of topoisomerase II inhibition by these agents. Both compound 1 and its 7-OH derivative, compound 2, inhibited topoisomerase II catalytic activity in vitro, yet neither agent affected the activity of topoisomerase I. DNA unwinding assays indicated that compound 1 and compound 2 bound to DNA, although no correlation was found between DNA unwinding and topoisomerase II catalytic inhibition. Neither agent enhanced topoisomerase II-mediated DNA cleavage in vitro; however, both compound 1 and compound 2 antagonized breaks induced by etoposide and amsacrine. Experiments indicate that interference with etoposide-stimulated breaks results from inhibition of topoisomerase II * DNA binding by compound 1. These findings suggest that compound 1 and its derivatives may represent a novel structural class of topoisomerase II catalytic inhibitors.     

复方甘草酸苷片联合复方氟米松软膏治疗慢性湿疹疗效分析

目的：对慢性湿疹患者应用复方甘草酸苷片联合复方氟米松软膏治疗的临床疗效进行分析研究。方法：选取于我院收治的慢性湿疹患者122例,并随机分为参照组和实验组各61例,分别应用复方氟米松软膏和复方甘草酸苷片联合复方氟米松软膏治疗的效果进行对照研究。结果：实验组患者的基本痊愈率、治疗总有效率均明显高于参照组[59.16%、91.80% VS 24.59%、70.49%].结论：慢性湿疹患者应用复方甘草酸苷片联合复方氟米松软膏治疗的临床疗效十分理想,值得大力推广。     

薄荷脑-羟丙基-β-环糊精包合物的红外光谱分析

目的建立红外光谱分析鉴定薄荷脑-羟丙基-β-环糊精包合物形成并表述其分子结构信息的方法。方法采用红外光谱仪测定薄荷脑、羟丙基-β-环糊精、薄荷脑与羟丙基-β-环糊精1∶1混合物及薄荷脑与羟丙基-β-环糊精配比不同时包合物的溴化钾压片在室温下的红外光谱。同时还测定了薄荷脑及其包合物在变温情况下的红外光谱。结果比较薄荷脑、羟丙基-β-环糊精、薄荷脑与羟丙基-β-环糊精1∶1混合物和薄荷脑-羟丙基-β-环糊精包合物的红外光谱,薄荷脑的一些特征峰在包合物中消失了,另一些特征峰向高波数方向发生了位移,而羟丙基-β-环糊精及其薄荷脑包合物的红外光谱则非常相似。但薄荷脑与羟丙基-β-环糊精1∶1混合物与其包合物的光谱特征频率有着明显的差异。在升温的情况下,薄荷脑及其包合物红外光谱最明显的变化反映在羟基特征频率随着温度升高向高波数方向发生位移。结论红外光谱表征证明薄荷脑与羟丙基-β-环糊精相互作用形成分子间氢键,并已嵌入其疏水空腔中形成包合物。同时包合物的热稳定性比薄荷脑有改善,但随温度升高仍有变化。     

曲美他嗪联合复方丹参滴丸治疗慢性心功能不全的疗效分析

目的探讨了曲美他嗪联合复方丹参滴丸治疗慢性心功能不全的疗效和不良反应。方法我院于2009年至2011年共收治慢性心功能不全300例,按照随机分层分组法随机分为三组,曲美他嗪组,复方丹参滴丸组以及联用组,每组患者100例。曲美他嗪组给予口服曲美他嗪进行治疗;复方丹参滴丸组给予口服复方丹参滴丸进行治疗;联合组给予曲美他嗪和复方丹参滴丸联合治疗。治疗8周后对治疗前后左室射血分数(LVEF)以及疗效进行分析。结果与治疗前比较,三组患者LVEF均有提高,联合组提高更显著(P<0.05)。联合组治疗有效率明显高于曲美他嗪组和复方丹参滴丸组,比较具有统计学意义(P<0.05)。结论曲美他嗪联合复方丹参滴丸治疗慢性心功能不全疗效显著,值得临床推广使用。     

Evidence for a multivalent interaction of symmetrical, N-linked, lidocaine dimers with voltage-gated Na+ channels

The interaction of symmetrical lidocaine dimers with voltage-gated Na+ channels (VGSCs) was examined using a FLIPR membrane potential assay and voltage-clamp. The dimers, in which the tertiary amines of the lidocaine moieties are linked by an alkylene chain (two to six methylene units), inhibited VGSC activator-evoked depolarization of cells heterologously-expressing rat (r) Na(v)1.2a, human (h) Na(v)1.5, and rNa(v)1.8, with potencies 10- to 100-fold higher than lidocaine (compound 1). The rank order of potency (C4 (compound 4) > C3 (compound 3) > or = C2 (compound 2) = C5 (compound 5) = C6 (compound 6) > compound 1) was similar at each VGSC. Compound 4 exhibited strong use-dependent inhibition of hNa(v)1.5 with pIC50 values < 4.5 and 6.0 for tonic and phasic block, respectively. Coincubation with local anesthetics but not tetrodotoxin attenuated compound 4-mediated inhibition of hNa(v)1.5. These data suggest that the compound 4 binding site(s) is identical, or allosterically coupled, to the local anesthetic receptor. The dissociation rate of the dimers from hNa(v)1.5 was dependent upon the linker length, with a rank order of compound 1 > compound 5 = compound 6 > compound 2 > compound 3. The observation that both the potency and dissociation rate of the dimers was dependent upon linker length is consistent with a multivalent interaction at VGSCs. hNa(v)1.5 VGSCs did not recover from inhibition by compound 4. However, "chase" with free local anesthetic site inhibitors increased the rate of dissociation of compound 4. Together, these data support the hypothesis that compound 4 simultaneously occupies two binding sites on VGSCs, both of which can be bound by known local anesthetic site inhibitors.