水飞蓟宾纳米混悬剂的制备及大鼠体内药动学研究

目的:探讨静脉注射用水飞蓟宾纳米混悬剂的制备,并评价其大鼠静注给药后的药动学。方法:通过对水飞蓟宾纳米混悬剂理化性质及稳定性的评价,考察水飞蓟宾纳米混悬剂的制备方法、处方工艺,并以溶液剂为参照考察其在大鼠体内的药动学行为。结果:水飞蓟宾纳米混悬剂的平均粒径是(268.90±9.20)nm,多分散性为0.22±0.12。水飞蓟宾溶液剂及纳米混悬剂的药时曲线下面积分别为(34.92±0.98)μg·h·mL-1和(57.12±3.20)μg·h·mL-1,消除半衰期(t1/2)分别为(3.05±0.06)h和(6.14±0.42)h。结论:制备的水飞蓟宾纳米混悬剂理化性质比较稳定,与溶?液剂相比,延长了药物在体内的驻留时间,具有一定的缓释效果。     

亮菌甲素片在健康人体的药代动力学和相对生物利用度

目的 研究亮菌甲素片(利胆药)在健康人体的药代动力学和相对生物利用度.方法 用随机交叉给药自身为对照法,20名健康受试者单次口服亮菌甲素参比和受试制剂各40 mg;用液相色谱-串联质谱法测定血浆中亮菌甲素的浓度,计算两种制剂的药代动力学参数和相对生物利用度.结果 受试制剂和参比制剂主要药代动力学参数,tmax分别为(0.35±0.09)、(0.36±0.08)h;Cmax分别为(32.94±11.52)、(31.15±8.23)ng·mL-1;t1/2分别为(0.42±0.19)、(0.37±0.11)h;AUC0-t分别为(12.92±3.91)、(12.80±4.03)ng·h·mL-1;AUC0-∞分别为(13.10±3.93)、(12.95±4.07)ng·h·mL-1.受试制剂与参比制剂的平均相对生物利用度为(102.00±16.19)%.结论 亮菌甲素片参比制剂与受试制剂生物等效.     

亮菌甲素注射液与不同溶媒的配伍稳定性考察

目的 考察亮菌甲素与6种常用输液的配伍稳定性及其荧光强度随溶剂pH值的变化情况.方法 采用高效液相色谱法测定亮菌甲素注射液与0.9％氯化钠注射液、5％葡萄糖注射液、10％葡萄糖注射液、葡萄糖氯化钠注射液、木糖醇注射液及乳酸钠林格注射液配伍后亮菌甲素的含量,采用pH测定仪测定其酸碱度变化,同时观察溶液的颜色及澄明度.配置不同pH梯度的缓冲盐溶液,考察亮菌甲素在不同pH环境下荧光强度的变化.结果 本实验所建立的色谱条件对亮菌甲素注射液的检测专属性好,亮菌甲素在5.0 - 80 μg/mL浓度范围内与其峰面积呈良好的线性关系（r2 =0.999 9）.高、中、低3种浓度的平均回收率分别为103.72％（RSD=0.17％）、103.98％（RSD=0.01％）、103.67％（RSD=0.25％）;6种配伍溶液在24 h时测得的药物含量均在98.61％ - 100.29％范围内.当溶液pH为5-8时,呈蓝色荧光黄色液体;pH为4-5时,肉眼观察微弱蓝色荧光;pH为2-4时,肉眼观察为无色透明液体,在紫外灯下可见微弱蓝色荧光.结论 亮菌甲素在不同pH值的溶媒中的荧光强度不同,荧光的强弱不影响药物的稳定性,该药物与6种常用输液配伍后24 h内稳定性良好.     

盐酸吡硫醇脂质体在大鼠体内药动学研究

目的 研究盐酸吡硫醇脂质体注射液在大鼠体内的药动学行为,并与盐酸吡硫醇注射液进行比较,评价盐酸吡硫醇脂质体药动学特征。方法 采用大鼠股静脉给药,眼眶取血,UPLC/MS/MS法测定大鼠血浆中盐酸吡硫醇的浓度,运用MasslynxTM NT4.1软件进行数据采集;运用QuanLynxTM program进行数据分析。结果 脂质体及溶液剂的AUC0-t分别为（1817.093±197.832）、（2592.349±303.194）μg/(L?h);Cmax分别为（6080.502±549.12）、（9525.987±531.813）μg/L;t1/2分别（1.512±0.387）、（0.732±0.388）h。两制剂的药时过程均符合三隔室模型,两者药动学行为相似。结论 运用DAS2.0进行生物等效性评价,脂质体组与溶液剂组药动学参数均在等效置信区间内,两制剂生物等效。     

卡铂-乳酸/羟基乙酸共聚物微囊在家兔体内的药动学

目的 :考察卡铂 乳酸 /羟基乙酸共聚物微囊在家兔体内的药动学过程。方法 :健康家兔 8只 ,随机交叉试验 ,单剂量注射卡铂微囊混悬液和卡铂原料药溶液后 ,采用等离子体原子发射光谱法测定血药浓度 ,药 时数据经PKS计算机程序拟合 ,自动判别最佳模型及计算药动学参数。结果 :两种剂型的的药 时曲线符合三室模型 ,二者的药动学参数Cmax、t1/ 2 β、MRT、AUC、CL差异存在显著性 (P <0 .0 5 )。结论 :卡铂制成微囊后 ,在家兔体内具有明显的缓释作用 ,有效作用时间延长 ,有利于其抗肿瘤作用     

林可霉素溶液剂和片剂的生物利用度比较

本文采用微生物法测定了12名健康志愿者交叉口服750mg林可霉素溶液剂和片剂后的血药浓度,经IBM计算机药动学程序PKBP—NI的拟合和统计程序POMS分析,评价比较了这两种制剂的药动学参数和生物利用度。结果表明:溶液剂的口服吸收稍快于片剂,而片剂的吸收略优于溶液剂,但两者的药动学参数均无显著差异(p>0.05)。两者的生物利用度是相似的,其相对生物利用度F(AUC_(0→∞)溶液剂/AUC_(0→∞)片剂)为92.3%。     

Preparation of long - circulating oridion - containing miceile and its pharmacokinetics

目的 制备冬凌草甲素长循环胶束,对比普通冬凌草甲素磷脂/胆盐混合胶束和冬凌草甲素长循环胶束在大鼠体内的药动学差异.方法 用薄膜分散法制备冬凌草甲素长循环胶束和普通冬凌草甲素磷脂/胆盐混合胶束,测定粒径,HPLC法测定血浆中冬凌草甲素的浓度,并用DAS2.0软件计算药动学参数.结果 胶束粒径为14.53±1.19 nm,PDI为0.28±0.06.冬凌草甲素长循环胶束的体内T1/2为125.25±40.78 h,是普通胶束的12.8倍,AUC为168.04±39.01 μg·L-1·h-1,为普通胶束的5.8倍(P＜0.05).结论 所制备的冬凌草甲素长循环胶束与普通磷脂/胆盐混合胶束相比,其体内半衰期明显延长,生物利用度显著提高,具有长循环的效果.     

冬凌草甲素长循环胶束的制备及药动学性质的考察

目的制备冬凌草甲素长循环胶束,对比普通冬凌草甲素磷脂/胆盐混合胶束和冬凌草甲素长循环胶束在大鼠体内的药动学差异。方法用薄膜分散法制备冬凌草甲素长循环胶束和普通冬凌草甲素磷脂/胆盐混合胶束,测定粒径,HPLC法测定血浆中冬凌草甲素的浓度,并用DAS2.0软件计算药动学参数。结果胶束粒径为14.53±1.19 nm,PDI为0.28±0.06。冬凌草甲素长循环胶束的体内T1/2为125.25±40.78 h,是普通胶束的12.8倍,AUC为168.04±39.01μg.L-1.h-1,为普通胶束的5.8倍(P<0.05)。结论所制备的冬凌草甲素长循环胶束与普通磷脂/胆盐混合胶束相比,其体内半衰期明显延长,生物利用度显著提高,具有长循环的效果。     

“齐二药”亮菌甲素注射液毒性物质筛查研究

目的:对"齐二药"事件中亮菌甲素注射液进行毒性物质筛查研究,寻找发生原因及建立相关的应急检验方法。方法:对"齐二药"与大理药业有限公司生产的亮菌甲素注射液进行小鼠急性毒性试验(半数致死量LD50)比较;对亮菌甲素注射液中辅料聚乙二醇400进行小鼠急性毒性实验,筛查正常的辅料是否含有毒性物质;用气相色谱法测定2个厂家产品中二甘醇的含量,并用气-质联用色谱法对"齐二药"亮菌甲素注射液中二甘醇进行成分确证。结果:2个厂家的亮菌甲素注射液LD50分别为17.72、21.06mL·kg-1,二甘醇含量分别为293mg·mL-1、未检出;聚乙二醇400小鼠组均存活,并表现正常;气-质联用色谱法证实"齐二药"亮菌甲素注射液中含有二甘醇。结论:确认"齐二药"亮菌甲素注射液毒性增大是由二甘醇引起的;利用动物实验对毒性物质进行筛查可用于药品质量的应急检验。     

单剂量肌肉注射甲氨喋呤治疗异位妊娠的药物动力学

目的 研究单剂量肌注甲氨喋呤(MTX)治疗异位妊娠(EP)的药动学特点,并计算其参数.方法 给予9例输卵管异位妊娠患者im MTX(1 mg·kg-1),分别于给药0-24 h内多点采静脉血,用荧光偏振免疫法测定MTX的浓度,用3p97软件计算药动学参数.结果 MTX的药动学符合一级吸收的二室模型.结论 单剂肌注MTX的药动学研究有助于深入分析EP治疗成功与否的相关因素.     

pH对亮菌甲素稳定性的影响

采用经典恒温法考察亮菌甲素在不同pH水溶液中的稳定性。结果表明亮菌甲素在pH3时最稳定，而在强酸及中性偏碱条件下不稳定，pH8时的t0.9仅为2h。     

HPLC法测定人血浆中亮菌甲素琥珀酸单酯浓度

目的：建立测定人血浆中亮菌甲素琥珀酸单酯的高效液相色谱法。方法：色谱枉为DL—C18（150mm×4．6mm,5μm）,流动相：甲醇-10mmol乙酸铵水溶液-乙酸（45：55：0．5）;柱温25℃,流速1．0ml·min^-1,检测波长220nm。结果：亮菌甲素琥珀酸单酯方法最低检测浓度为5ng·ml^-1,线性范围0．05～10．00μg·ml^-1（r=0．9996）线性关系良好。亮菌甲素琥珀酸单酯日内RSD分别为2．09％～4．22％,日间RSD分别为3．72％～5．04％。方法回收率分别为94．38％～97．20％。结论：本试验建立的方法简便、快速、准确,适用于亮菌甲素琥珀酸单酯体内血药浓度和生物等效性的测定。     

Relative Bioavailability of Phenoxymethylpenicillin Preparations in a Cross-Over Study

Abstract In a cross-over study on 6 healthy volunteers, the serum concentrations and the bioavailability of 16 oral phenoxymethylpenicillin preparations have been compared. The dissolution rates of the tablets and capsules were studied. The preparations included 5 aquous solutions, 7 tablets or capsules, and 4 suspensions. The highest bioavailability was seen with the aquous solutions and the tablets or capsules containing the potassium salt of phenoxymethylpenicillin. Two calcium salt tablet brands showed lower serum mean concentrations and bioavailability than the other, potassium salt, tablets and capsules, but the differences were only statistically significant for one of the calcium salt tablets as compared to the tablet with the highest mean concentrations. The poorer bioavailability of the calcium salt tablets was reflected in longer dissolution times. The suspensions intended for paediatric use were significantly inferior to most of the other preparations. The lowest bioavailability was observed with a suspension containing the poorly soluble benzathine phenoxymethylpenicillin.     

3,5-二硝基水杨酸比色法测定亮菌口服液中多糖的含量

目的：建立亮菌口服液中的多糖含量测定方法。方法：以乙醇沉淀法分离多糖,用３,５－二硝基水杨酸比色法测定多糖含量。结果：样品加样平均回收率为９８．７５％,ＲＳＤ为０．７８％（ｎ＝５）。方法：方法操作简便,准确,重现性好,适用于亮菌口服液的质量控制。     

注射用姜黄素温敏凝胶在实体瘤内滞留时间的研究

目的:研究注射用姜黄素温敏凝胶在小鼠实体瘤内的滞留时间。方法:复制小鼠实体瘤模型,以亚甲蓝温敏凝胶和亚甲蓝水溶液为模型药物,直观考察温敏凝胶是否可延长滞留时间,确定所用方法的可行性。通过反相高效液相色谱法测定注射用姜黄素温敏凝胶于不同时间点时在小鼠实体瘤内的剩余量,从而确定其滞留时间,并与同浓度的注射用姜黄素混悬液对比。结果:亚甲蓝水溶液注射进入瘤体后会沿着针孔外渗,而亚甲蓝温敏凝胶无此现象。注射用姜黄素温敏凝胶在实体瘤内的滞留时间为43.02h,显著长于姜黄素混悬液的滞留时间(P<0.01)。结论:注射用姜黄素温敏凝胶在小鼠实体瘤内滞留时间较长,显示其具有一定的缓释作用。     

Bioequivalency of oral suspension formulations of cefixime

A study was performed in 24 healthy male subjects to establish that two suspension formulations of cefixime were bioequivalent to each other and to a reference oral solution. A single 400 mg oral dose of the drug was given in a randomized three-way crossover design as two suspensions (a research suspension (RS) used during clinical trials and a suspension intended for marketing (MS] and a reference oral solution (SOL). Each dose was separated from the other by a 3-day washout period. Mean peak serum concentrations (Cmax) were 4.67, 4.10, and 4.27 micrograms ml-1 after the MS, RS, and SOL, respectively. Although comparison (ANOVA) of the mean pharmacokinetic parameters for cefixime found significant differences (p less than 0.05) in Cmax, the time to Cmax, and area under the serum concentration time curve (AUC 0----infinity) values among the three formulations, the mean differences were less than 20 per cent. No significant differences (p greater than 0.05) were found in either the elimination half-life or renal clearance of unchanged drug. Overall, with a 98 per cent power to detect a 20 per cent difference in AUC0----infinity or urinary recovery values between the formulations tested, the results show that the MS was bioequivalent to the RS and that both suspensions were bioequivalent to the SOL.     

由齐齐哈尔第二制药“亮菌甲素事件”引发的思考

目的:探讨齐齐哈尔第二制药“亮菌甲素事件”带给我们的思考。方法:从齐齐哈尔第二制药“亮菌甲素事件”出发,分析当前我国药品生产、管理过程中存在的问题,寻找根源。结果与结论:制药企业应重视其社会责任,药品的监督管理不能缺位,应从该事件中吸取教训,从药品生产质量、注册审批、流通秩序、药品不良反应报告等全方位实施有效管理,才能防止类似事件再度发生。     

亮菌甲素(假密环菌甲素)含量测定方法的研究

亮菌甲素(3-乙酰基-5-羟甲基-7-羟基香豆素,简称甲素)系一种新的香豆素类化合物。首先由假密环菌(Armillariella tabescens(Scop.ex Fr.)Sing.)的菌丝体中提取所得,现已化学合成。甲素经临床试用,证明对急性胆道感染有一定的疗效。本文对其含量测定方法进行了研究。     

Development of a method for comprehensive and quantitative analysis of armillarisin succinate ester in its medicinal preparations by liquid chromatography-ion trap mass spectrometry

A rapid and sensitive method for the identification and quantification of armillarisin succinate ester (ASE), which is a patent drug, is described. The method used liquid chromatography-ion trap mass spectrometry (LC-IT-MS/MS). The ASE standard solution was directly infused into IT-MS for collecting MS(n) spectra. The major fragment ions of ASE were confirmed by MS(n) at m/z 333, 233, 202, 189 and 163 in negative ion mode, and m/z 335, 217, 189,175 and 161 in positive mode, respectively. The possible main fragment ions cleavage pathways were studied between in positive-ion mode and in negative-ion mode. Quantification was performed using the transitions m/z 333 --> 233 in negative mode. The method is reliable and reproducible, and the detection limit is 2 ng/mL. The method was validated in the concentration range of 1.0 - 50 microg/mL, intra- and inter-day precision ranged from 1.98% to 4.06%, and the accuracy was 97.5-106.2%. The mean recovery of ASE was 97.2-105.3% with RSD less than 4.35%. A LC-IT-MS/MS has successfully applied to determine the ASE in its medicinal preparations.