过氧化氢酶活性的化学发光法测定

本文以Ｌｕｍｉｎｏｌ－Ｈ２Ｏ２－Ｃｏ２＾＋发光系统，测定过氧化氢酶活性，基质中过氧化氢的浓度在６．０×１０＾－３－５．３×１０＾－２ｍｏｌ／Ｌ之间与Ｉｃ１呈现良好的线性关系，ｒ＝０．９９５３，方法的变异系数为６．４％（ｎ＝５），最适ｐＨ约为７．４，与传统的光度法比较，具有一致性（ｒ＝０．９９）。     

苯巴比妥栓的制备及在家兔体内的药物动力学

目的：研制生物利用度较好的苯巴比妥栓剂。方法：以３种不同基质制成苯巴比妥栓剂，并比较它们在家兔体内的药物动力学。采用荧光偏振免疫分析法测定血药浓度，按二室血管外给药模型进行药物动力学参数模拟。结果：以水溶性基质脂肪酸聚氧乙烯醚（Ｓ－４０型）制成的栓剂的主要药动学参数分别为Ｋａ１．０１±０．２２ｈ－１，Ｔｍａｘ２．４２±０．１１ｈ，Ｃｍａｘ１１．１±１．３μｇ·ｍｌ－１，ＡＵＣ９２４±１１０μｇ·ｈ·ｍｌ－１，均明显优于以３６＃半合成脂肪酸酯和聚乙二醇－４０００为基质的栓剂（Ｐ＜０．０１）。结论：３种栓剂的释药性具有显著性差异，以脂肪酸聚氧乙烯醚（Ｓ－４０型）为基质的栓剂最好。     

高效液相色谱法测定雷登泰口服液中创木酚甘油醚,盐酸伪麻黄？…

采用高效液相色谱外标法测定雷登泰口服液中愈创木酚甘油醚，盐酸伪麻黄碱，氢溴酸右美沙芬的含量。色谱柱为ＳｐｈｅｒｉｓｏｒｂＣ８ ５μｍ４．６ｍｍ２５０ｍｍ，流动相为０．００２５ｍｏｌ．Ｌ＾－１己烷磺酸甲醇溶液－水（含２％三乙胺）－３ｍｏｌ．Ｌ＾－１磷酸（１．４：１．０：０．０６３），紫外检测器，检测波长２５７ｎｍ。结果愈创木酚甘油醚进样量在２．０－１０．０μｇ，盐酸为伪麻黄碱在０．３－１．５μｇ，氢     

氮杂双环中烯丙基区域性重排反应

以Ｌ－脯氨酸为原料，经四步反应得到Ｎ－烯丙基－１－酮基氮杂双环［４．３．０］壬烷溴化物和Ｎ－烯丙基－１－酮基氮杂双环［５．３．０］癸烷溴化物，它们在强碱作用下发生［２，３］－σ重排，生成９－烯丙基－１－酮基氮杂双环［４．３．０］壬烷和１０－烯丙基－１－酮基氮杂双环［５．３．０］癸烷。提出了可能的反应机理。     

高效液相色谱法测定西替利嗪尿药浓度

目的：建立测定西替利嗪尿药浓度的反相离子对高效液相色谱法（ＲＰ－ＨＰＬＣ）。方法：以Ｎｏｖａ－ｐａｋＣ１８、４μｍ色谱柱为分离柱，流动相为乙腈∶磷酸盐缓冲液（０．０２ｍｏｌ·Ｌ－１、ＮａＨ２ＰＯ４）∶三乙胺（５０∶５０∶０．１５，Ｖ／Ｖ），ｐＨ值３．０７，内含十二烷基硫酸钠（ＳＤＳ）０．０１０５ｍｏｌ·Ｌ－１，去氯羟嗪为内标，ＵＶ检测波长２２９ｎｍ。结果：方法线性范围为０．２～２０μｇ·ｍｌ－１（ｒ＝０．９９９９），平均回收率为９６．４％±２．３％，日内和日间精密度均小于５％。结论：采用ＲＰ－ＨＰＬＣ法测定盐酸西替利嗪片的正常人尿药浓度，简便，迅速，准确     

盐酸特拉唑嗪胶囊人体生物利用度及药物动力学研究

目的：对盐酸特拉唑嗪胶囊的人体内生物利用度进行研究。方法：单剂量口服盐酸特拉唑嗪胶囊和片剂２ｍｇ。血药浓度采用ＨＰＬＣ测定，数据用３Ｐ８７计算药动学参数。结果：盐酸特拉唑嗪胶囊剂的药动学参数：Ｋａ为８．２±４．０ｈ－１，Ｔ１／２为８．２±２．５ｈ，Ｔｍａｘ为０．６１±０．１１ｈ，Ｃｍａｘ为４３．５±８．５ｎｇ·ｍｌ－１，ＡＵＣ为３６７．４±３４．６ｎｇ·ｈ·ｍｌ－１；盐酸特拉唑嗪片剂的药动学参数：Ｋａ为６．４±７．４ｈ－１，Ｔ１／２为７．４±２．１ｈ，Ｔｍａｘ为０．９±０．４ｈ，Ｃｍａｘ为４３．１±４．８ｎｇ·ｍｌ－１，ＡＵＣ为３７１．３±４４．４ｎｇ·ｈ·ｍｌ－１。结论：两种剂型的药物动力学参数之间差异均无显著性（Ｐ＞０．０５），胶囊剂的相对生物利用度为９９．８８％。     

多发性骨髓瘤患者骨髓单个核细胞IL-6的表达

应用双标记免疫荧光技术检测了１６例多发性骨髓瘤患者和１９例缓解期血液病患者新鲜骨髓单个核细胞中ＩＬ－６表达情况，结果多发性骨髓瘤患者骨髓单个核细胞中ＩＬ－６表达阳性率为１５．４±６５％，基质细胞ＩＬ－６表达阳性率为４．５±１．２％；分别高于对照组的４．６±２．３％、２．６±１．１％（Ｐ＜０．０１）；另外多发性骨髓瘤组骨髓单个核细胞中基质细胞所占比率为６９±１．４％，也高于对照组的４．７±１．８％（Ｐ＜０．０１）。多发性骨髓瘤患者升高的ＩＬ－６可由基质细胞分泌，参与了本病的发病     

一种简易的检测人体血浆中沙丁胺醇浓度的HPLC法

建立了生种简易的反相高效液相色谱方法测定沙丁胺醇血药浓度。以含磷酸二（２－乙基己基）酯的氯信液进行提取，０．１ｍｏｌ／Ｌ盐酸反提，内标为丁酚胺。固定相为ＳｐｈｅｒｉｓｏｒｂＣ１８；流动相为：０．０３ｍｏｌ／Ｌ磷酸二氢铵（用磷酸调至ＰＨ２．６）－甲醇－乙腈（９２．２：３．４：４．４），流速１．５ｍＬ／ｍｉｎ。芝光检测器的激发波长为２２５ｎｍ，荧光波长为３１０ｎｍ。在血浆浓度０．５－５０ｎｇ／ｍＬ范围     

紫外分光光度法测定米非司酮血药浓度

目的：介绍应用紫外分光光度法测定米非司酮血药浓度的方法。方法：以氯仿为提取液，甲醇为溶媒，在３０４ｎｍ处进行测定。血浆标准曲线线性范围４～２４μｇ·ｍｌ－１（ｒ＝０．９９９７）。结果：平均回收率（９３．３±４．６）％，ＲＳＤ日内（２．１±０．８）％，ＲＳＤ日间（３．１±０．４）％。应用该法对１０例孕妇进行米非司酮血药浓度测定，其浓度在１０～２０μｇ·ｍｌ－１之间。结论：分析结果表明该方法简便可行。     

高效液相色谱法测定静注吡洛地尔兔血药浓度及药物动力学参数

本文应用反相高效液相色谱法测定兔静注吡洛地尔（１５ｍｇ／ｋｇ）血药浓度，样品用正庚烷提取。流动相以１０％三乙胺：甲醇液（甲醇：水＝９：１）＝５：９５。紫外检测波长为２５４ｎｍ，回收率８１．４％，日内和日间的ＲＳＤ值为２．４％、３．５％。最低检测血浓为２０ｎｇ／ｍｌ。用３Ｐ８７程序拟合为二室模型。α＝３．０８ｈ－１，β＝０．１８ｈ－１，Ｔ１／２＝４．０７ｈ，Ｋ１０＝０．９１ｈ－１，Ｋ１０＝０．６１ｈ－１，Ｖｃ＝１１．４５ＡＬ／ｋｇ，ＣＬ＝６．７３Ｌ／（ｋｇ·ｈ），ＡＵＣ＝２．２１（μｇ·ｈ）／Ｌ。     

正交试验法筛选活血通络巴布膏的基质处方

目的筛选活血通络巴布膏的基质处方。方法采用正交试验法,以黏着力、剥离性、涂展性、膏体均匀性、皮肤追随性和赋形性为指标,各基质及其用量为因素和水平进行L16(45)试验,得出最优配比组成。结果基质最佳配比为水∶甘油∶聚丙烯酸钠(PAANa):羧甲基纤维素钠(CMC):聚乙烯吡咯烷酮(PVP)=6.0∶4.0∶1.6∶0.4∶0.3。结论筛选的基质处方经济实用可行,与活血通络药物有良好的相容性。     

大黄紫草巴布剂基质处方研究

目的筛选大黄紫草巴布剂的基质处方。方法采用均匀设计方法,以初黏力、持黏力为评价指标,各基质及其用量为因素和水平进行均匀设计实验,采用SPSS16．0进行方程拟合,分析各因素对基质性能的影响并得出最优配比组成。结果巴布剂最佳配比为NP-700-氢氧化铝-甘油0．2％酒石酸溶液-4．0：0．2：20：10。结论该基质具有良好的外观和黏附性能,与大黄紫草提取物有良好的相容性。     

A novel mathematical model considering change of diffusion coefficient for predicting dissolution behavior of acetaminophen from wax matrix dosage form

From wax matrix dosage forms, drug and water-soluble polymer are released into the external solvent over time. As a consequence, the pore volume inside the wax matrix particles is increased and the diffusion coefficient of the drug is altered. In the present study, we attempted to derive a novel empirical mathematical model, namely, a time-dependent diffusivity (TDD) model, that assumes the change in the drug's diffusion coefficient can be used to predict the drug release from spherical wax matrix particles. Wax matrix particles were prepared by using acetaminophen (APAP), a model drug; glyceryl monostearate (GM), a wax base; and aminoalkyl methacrylate copolymer E (AMCE), a functional polymer that dissolves below pH 5.0 and swells over pH 5.0. A three-factor, three-level (3(3)) Box-Behnken design was used to evaluate the effects of several of the variables in the model formulation, and the release of APAP from wax matrix particles was evaluated by the paddle method at pH 4.0 and pH 6.5. When comparing the goodness of fit to the experimental data between the proposed TDD model and the conventional pure diffusion model, a better correspondence was observed for the TDD model in all cases. Multiple regression analysis revealed that an increase in AMCE loading enhanced the diffusion coefficient with time, and that this increase also had a significant effect on drug release behavior. Furthermore, from the results of the multiple regression analysis, a formulation with desired drug release behavior was found to satisfy the criteria of the bitter taste masking of APAP without lowering the bioavailability. That is to say, the amount of APAP released remains below 15% for 10 min at pH 6.5 and exceeds 90% within 30 min at pH 4.0. The predicted formulation was 15% APAP loading, 8.25% AMCE loading, and 400 μm mean particle diameter. When wax matrix dosage forms were prepared accordingly, the predicted drug release behavior agreed well with experimental values at each pH level. Therefore, the proposed model is feasible as a useful tool for predicting drug release behavior, as well as for designing the formulation of wax matrix dosage forms.     

Hydrophilic interaction chromatography-tandem mass spectrometry of donepezil in human plasma: Application to a pharmacokinetic study of donepezil in volunteers

A selective, sensitive and rapid hydrophilic interaction liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of donepezil in human plasma. Donepezil was twice extracted from human plasma using methyl tert-butyl ether at basic pH. The analytes were separated on an Atlantis HILIC Silica column with the mobile phase of acetonitrile: ammonium formate (50 mM, pH 4.0) (85:15, v/v) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9994) over the concentration range of 0.10-50.0 ng/mL and the lower limit of quantification was 0.1 ng/mL using 200 muL plasma sample. The coefficient of variation and relative error for intra-and inter-assay at four QC levels were 2.7 to 10.5% and -10.0 to 0.0%, respectively. There was no matrix effect for donepezil and cisapride. The present method was successfully applied to the pharmacokinetic study of donepezil after oral dose of donepezil hydrochloride (10 mg tablet) to male healthy volunteers.     

利多卡因对中性粒细胞NF-KB的表达和TNF-α诱导的中性粒细胞凋亡的离体研究

目的:观察利多卡因(lidocaine)对人体中性粒细胞(PMN)NF-kB的激活和PMN凋亡的影响.方法:将分离的人体PMN分为以下几个给药组:生理盐水对照组;TNF-α组(200 ng/L);TNF-α+lidocaine组(1.0 mmol/L);TNF-α+lidocaine组(2.0 mmol/L);TNF-α +lidocaine组(4.0 mmol/L)共同孵育3 h,用免疫蛋白印迹法观察利多卡因对NF-kB mRNA及其抑制因子(I-kB)mRNA表达,PCR法观察对蛋白含量的影响,以及流式细胞仪方法观察孵育12、24 h后对PMN凋亡的影响.结果:利多卡因组NF-kB mRNA表达显著降低,而I-kB mRNA表达显著增加;并且利多卡因2.0 mmol/L组和4.0 mmol/L组显著优于1.0 mmol/L组(P<0.05),而2.0 mmol/L组和4.0 mmol/L组之间差异无统计学意义.利多卡因在12、24 h(P<0.05)都可以显著抑制TNF-α诱导的PMN凋亡,而4.0 mmol/L组显著优于1.0 mmol/L组抗凋亡效果(P<0.05).结论:利多卡因1.0、2.0、4.0 mmol/L都可以显著下调TNF-α诱导的PMN p65 mRNA的表达,并且在12、24 h可以部分逆转TNF-α诱导的PMN凋亡.     

不同pH的溶出介质对HPMC骨架片释药的影响

目的探讨溶出介质的pH对难溶性药物的HPMC骨架片释药的影响.方法以甲氧苄胺嘧啶、卡马西平、磺胺甲恶唑和茶碱四种难溶型性药物为模型药物,测定四种pH缓冲溶液介质(pH1.0,pH4.0,pH6.0,pH7.5)下的药物的溶解度和释放度.结果难溶性药物的HPMC骨架片释药随着其溶解度的增加而加快.结论难溶性药物HPMC骨架片释药的差异主要与药物在不同pH的溶出介质中的溶解度有关.     

注射用氯诺昔康的制备及稳定性研究

目的制备注射用氯诺昔康并考察其稳定性。方法以含量、有关物质、pH值为指标,筛选处方及制备工艺;考察3批样品的稳定性。结果最佳处方为氯诺昔康4.0g、丙二醇4.0g、甘露醇100g、氢氧化钠1mol/L适量,以该处方制备的3批样品在市售包装条件下经加速、室温留样试验考察,质量稳定。结论处方设计合理,工艺可行。     

Topical Delivery of a Model Phenolic Drug: Alkyloxycarbonyl Prodrugs of Acetaminophen

PURPOSE: To determine whether the delivery of a phenolic parent drug by its alkyloxycarbonyl (AOC) prodrugs through hairless mouse skin would show similar dependencies on water and lipid solubilities that similar prodrugs of more polar heterocyclic amide and imide parent drugs have shown. METHODS: Flux through hairless mouse skin from suspensions in isopropyl myristate (J(MIPM)), solubilities in IPM (S(IPM)) and water (S(AQ)), and partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K(IPM:4.0)) were measured for two series of AOC derivatives of acetaminophen (APAP); their solubilities in pH 4.0 buffer (S4.0) were estimated from S(IPM)/K(IPM:4.0). Log J(MIPM) values were calculated from the n = 43 coefficients for the parameters in the transformed Potts-Guy (Roberts-Sloan) equation, and the average error of prediction (delta log J'(IPM)) was calculated. The J(MIPM), S(IPM), S4.0, and molecular weight (MW) data for this series and two other series were combined with the n = 43 database to give a n = 61 database, and new best fit coefficients were determined for the Roberts-Sloan equation: log J(MIPM) = x + y log S(IPM) + (1 - y) log S4.0 - z MW. RESULTS: All of the 4-AOC-APAP derivatives underperformed based on their predicted log J(MIPM) (delta log J'(MIPM) = 0.275 +/- 0.147 log units) and, although the two more water soluble members of this more lipid soluble series were more effective than APAP, they were only marginally so: <2 times. Addition of three new series to the n = 43 database for the Roberts-Sloan equation did not substantially change the coefficients to the parameters: x, y, z, and r2 = -0.322, 0.530, 0.00337 and 0.92, respectively. CONCLUSIONS: The topical delivery of a model phenolic drug by its AOC prodrugs through hairless mouse skin from IPM shows the same dependence on S(IPM), S4.0, and MW as the delivery of polar heterocycles by their similar prodrugs.     

地西他滨联合丙戊酸增强HL-60细胞hPer3基因的表达

目的探讨地西他滨(DCA)和丙戊酸(VPA)联用对白血病细胞株HL-60的作用及对human peri-od3基因(hPer3)的表达调控的影响。方法 DCA 1.0及4.0μmol·L-1,VPA 2.0 mmol·L-1,VPA 2.0 mmol·L-1+DCA 1.0μmol·L-1,VPA 2.0 mmo.L-1+DCA 4.0μmol·L-1作用HL-60细胞48 h。MTT法检测细胞存活,FITC-AnnexinⅤ/PI检测细胞凋亡,甲基化聚合酶链反应和实时荧光定量PCR检测hPer3基因启动子甲基化状态和mRNA表达,流式细胞术检测CD14表达率。结果 VPA 2.0+DCA 1.0联合用药组生长抑制率为(49.6±5.2)%,VPA 2.0+DCA 4.0联合用药组为(66.3±7.3)%,均高于其相应单药组,差异具有统计学意义(P<0.01)。VPA 2.0+DCA 1.0联合用药组〔早期:(167±3)%,晚期:(32±4)%〕和VPA 2.0+DCA 4.0联合用药组〔早期:(37±5)%,晚期:(36±5)%〕凋亡率均高于其相应单药组,差异具有统计学意义(P<0.01)。VPA 2.0+DCA 1.0联合用药组和VPA 2.0+DCA 4.0联合用药组hPer3启动子甲基化状态均明显低于其相应单药组。VPA2.0+DCA 1.0联合用药组和VPA 2.0+DCA 4.0联合用药组hPer3 mRNA表达分别为1.75±0.33和3.02±0.36,均明显高于其相应单药组,差异具有显著统计学意义(P<0.01)。VPA 2.0+DCA 1.0联合用药组和VPA 2.0+DCA 4.0联合用药组CD14表达率分别为(16.39±1.68)%和(14.82±0.94)%,均明显高于其相应单药组,差异具有显著统计学意义(P<0.01)。结论 DCA联合VPA能显著加强抗白血病效应,作用机制可能与上调hPer3基因的表达相关。     

Dietary tryptophan supplements attenuate amphetamine self-administration in the rat

Previously, it had been shown that lesions of cerebral 5-hydroxytryptamine (5-HT)-containing neurons and injections of drugs affecting 5-HT synthesis or receptor mediated function would alter amphetamine self-administration in the rat. The present study sought to ascertain whether diets enriched in L-tryptophan (L-TRY), the amino acid precursor to 5-HT, would: elevate cerebral 5-HT concentrations and affect amphetamine self-administration behavior. Diets containing 2.0 and 4.0% L-TRY increased cerebral 5-HT concentrations above those of rats on normal rat chow (0.26% L-TRY). The 4.0% diet elevated brain 5-HT to the same degree in rats exposed to the diet for 1, 2 or 3 days. When normal diets were restored, brain 5-HT concentrations rapidly returned to normal. Animals trained to self-administer d-amphetamine, when given access to the L-TRY enriched diets, significantly reduced their daily amphetamine self-injection during exposure periods. When normal rat chow was restored a delay in recovery to pre-diet amphetamine self-administration was observed: 1 day with the 2.0% L-TRY diet and 2 days with the 4.0% L-TRY diet. The 4.0% L-TRY diet failed to alter saline-frustration responding indicating the diet did not produce decrements in motor performance. When animals were placed on the 4.0% L-TRY diet and allowed access to amphetamine for 1 day then exposed to saline, a profound decrease in saline-frustration responding was observed.(ABSTRACT TRUNCATED AT 250 WORDS)