RP-HPLC法控制复方赖诺普利片质量方法研究

目的 建立控制复方赖诺普利片质量的方法，方法 采用夏相高效液相色谱法。色谱系统为ODS柱，以乙腈—水(20：80)为流动相，检测波长为215nm，结果 本法可同时测定复方赖诺普利片中赖诺普利和氢氯噻嗪的含量，并且有效检测复方赖诺普利片中有关物质变化，结论 本法快速、简便、准确。     

高效液相色谱法同时测定复方氨氯地平片中苯磺酸氨氯地平和赖诺普利的含量

目的:以高效液相色谱法同时测定复方氨氯地平片中苯磺酸氨氯地平和赖诺普利的含量。方法:采用高效液相色谱法梯度洗脱的方法,以赛分C18色谱柱,流速1.8 mL.min-1,检测波长210 nm为测定色谱条件。结果:苯磺酸氨氯地平和赖诺普利测定的线性范围分别为10～200μg.mL-1和20～400μg.mL-1,线性方程分别为Y=20.40X-0.1036和Y=38.17X+4.470;苯磺酸氨氯地平和赖诺普利平均回收率(n=9)分别为100.8%±0.78%和101.3%±0.60%。结论:本方法准确、快速,适合复方氨氯地平片中药物含量的同时检测。     

RP-HPLC法测定赖诺普利片剂中有关物质

目的:建立赖诺普利片剂中有关物质的RP-HPLC检测方法,为赖诺普利片剂的质量控制提供有效的分析手段。方法:色谱柱:Lichrospher C18(150 mm×4.6 mm,5μm),流动相:乙腈-磷酸二氢钠缓冲液(pH5.2)(10∶90),流速:1.0 mL/min,检测波长:215 nm,柱温:45℃,进样量:20μL。结果:赖诺普利浓度在16~260 mg/mL范围内线性关系良好(r=0.9995),赖诺普利最低检测限为3.92 ng,辅料对主药和降解产物的检测无影响,主药和降解产物能很好的分离检出。结论:本法准确、简便,适用于赖诺普利片剂中有关物质检测。     

高效液相色谱法测定复方赖诺普利片的溶出度

目的：建立复方赖诺普利片（每片含赖诺普利10．0mg、氢氯噻嗪12．5mg）溶出度的HPLC测定方法。方法：以0．1mol·L^-1盐酸900ml为溶出介质,转速为50r·min^-1,用高效液相色谱法测定,检测波长210nm。结果：赖诺普利、氢氯噻嗪分别在1．8～37．4μg·m^-1和2．5—49．9μg·ml^-1范围内线性关系良好（r=0．9999）,平均回收率分别为100．2％,100．6％;RSD分别为0．67％,0．95％（n=9）。赖诺普利、氢氯噻嗪30min的累计溶出度分别达80％和70％以上。结论：该法操作简便、准确、可靠,适用于复方赖诺普利片的质量研究。     

复方赖诺普利片治疗中国人群原发性高血压的临床试验设计

复方赖诺普利片限定在单药使用不满意时方可使用,对设计要求较高。本文介绍复方赖诺普利片治疗中国人群原发性高血压的临床试验设计,包括病例选择、试验设计、例数估算等。     

赖诺普利/氢氯噻嗪复方片在中国健康志愿者中的药代动力学研究(英文)

本研究描述了赖诺普利/氢氯噻嗪复方片在中国健康人体内的药代动力学特征。9名受试对象分别服用高、中、低3种剂量的复方片剂,结果表明,两种药物的AUC和Cmax都随着剂量的增加显著增加,但3种剂量间AUC/Dose、Cmax/Dose和tmax无明显差别。赖诺普利和氢氯噻嗪在涉及剂量范围内呈线性代谢特征。8名健康受试者在多次服用赖诺普利/氢氯噻嗪复方片后,与第1次服药比较,达稳态后的赖诺普利的AUC、Cmax和Cmin有所增加,其中AUC和Cmax显著增加;氢氯噻嗪的AUC、Cmax、Cmin和tmax有所增加,其中AUC和Cmin显著增加。达稳态后,赖诺普利的波动指数(FI)为2.29,浓度较为平稳,而氢氯噻嗪的波动指数FI为4.09,浓度相对波动较大。     

分光光度法和荧光分光光度法测定单一和多组分制剂中的赖诺普利

赖诺普利(lisinopril)是抗高血压药。本文介绍用分光光度法和荧光法测定片剂中的赖诺普利,方法简单、灵敏。A法是药物在pH9.5的水溶液中与氯醌反应生成黄色,在346nm测定;B法是赖诺普利与二氯萘醌反应产生强紫色,在580nm测定;C法是药物与乙酰丙酮和甲醛反应生成有色缩合物,在356nm测定,在475nm(λex410nm)有强荧光。此法也可测定在氢氯噻嗪二元混合物中的赖诺普利;D法是测定赖诺普利的第一和第二衍生光谱。赖诺普利可在其降解产物存在时测定。本法适合商品制剂快速质量控制。仪器和试剂　UV-Vis分光光度计,荧光分光光度计,1cm石英比色杯,…     

赖诺普利迟释型缓释片的制备及其体外释放研究

目的:制备赖诺普利迟释型缓释片,并对其体外释放度进行测定。方法:以羟丙甲纤维素(HPMC)为片芯骨架材料,乙基纤维素为阻滞材料,聚乙二醇(PEG)为致孔剂,利用包衣技术制备赖诺普利迟释型缓释片。以6、10、16、22 h的累积释放度(Q6 h、Q10 h、Q16 h、Q22 h)为指标,采用正交试验优化HPMC型号、用量和PEG用量,并进行验证。比较自制赖诺普利迟释型缓释片、自制赖诺普利缓释片芯和市售赖诺普利片在0.1 mol/L盐酸溶液中22 h内的Q。结果:最优处方为HPMC型号为K100M,占片芯质量比例为35%,PEG比例为40%,即600片赖诺普利迟释型缓释片中含赖诺普利18 g、乳糖54 g、HPMC(K100M)48 g、PEG 1.6 g、10%聚维酮乙醇溶液适量、硬脂酸镁1%、微粉硅胶1%、乙基纤维素2.4 g;所制3批赖诺普利迟释型缓释片的Q6 h、Q10 h、Q16 h、Q12 h的均值分别为11.17%、29.55%、62.38%、82.63%。自制赖诺普利缓释片芯Q10 h达80%以上,Q14 h为95.60%;市售赖诺普利片的Q5 min即达80%以上,Q1 h为97.95%;自制赖诺普利迟释型缓释片Q6 h仅为13.97%,Q22 h为84.12%,其释放特征符合零级动力学模型。结论:成功制得体外延迟4 h释放药物,并可缓慢释放22 h的赖诺普利迟释型缓释片。     

LC-MS法测定人血浆中赖诺普利样品前处理方法改进

目的:改进人血浆中赖诺普利的LC-MS测定法. 方法:通过对样品前处理方法的改进,减少样品对离子源的污染和血浆内源性物质对待测物色谱峰的干扰;通过对复溶样品所用溶液的pH值的调整,改善色谱峰形;通过提高色谱柱温度,提高传质速率,改善色谱峰形.色谱柱为Sepax GP-C18(2.1 mm×150 mm,5 μm)柱,流动相为20 mmolL-1醋酸铵(含0.1 %甲酸)-甲醇(75∶ 25,v/v),内标为甲硝唑,检测仪器为Agilent 1100 LC-MSD,离子源为ESI,检测离子为m/z 406.3(赖诺普利)、m/z 172.1(内标),裂解电压为150 V.结果:赖诺普利与内标的峰形良好,色谱图中杂峰较少,在2～300 ngmL-1浓度范围内赖诺普利与内标峰面积比值与浓度线性关系良好,最低定量限为2 ngmL-1.本法提取回收率为91.6 %～96.4 %,批内和批间的精密度均小于15 %. 结论:该方法灵敏度高,无杂质干扰,分析速度快,可以应用于临床血药浓度的测定和药代动力学研究.     

复方赖诺普利片人体药动学考察

目的：研究复方赖诺普利片在健康人体内药动学特征。方法：单剂量：空腹口服复方赖诺普利片1片（每片复方赖诺普利片含赖诺普利10mg、氢氯噻嗪12．5mg）。多剂量：多次给药连续9d，每天服药1次．每次1片。采用LC-MS法测定血浆中赖诺普利、氢氯噻嗪的浓度，计算药动学参数．以考察复方赖诺普利片多剂量口服达稳态过程和稳态药动学特征。结果：单剂量口服受试制剂：赖诺普利的tmax为（7．3±1．2）h；Cmax为（42．5±6．8）μg·L^-1；t（1/2）为（8．6±1．8）h；MRT为（20．1±3．0）；AUC（0-72）为（545．1±147．4）ng·h·L^-1。氢氯噻嗪的tmax为（2．8±0．7）h；Cmax为（81．6±22．7）μg·L^-1；t（1/2）为（13．7±2．0）h；MRT为（10．4±2．0）；AUC（0-48）为（679．8±280．7）ng·h·L^-1。多剂量口服受试制剂：赖诺普利的AUCss为（576．9±124．4）ng·h·L^-1，Css-max为（47．7±13．2）μg·L^-1，Css-min为（6．2±1．8）μg·L^-1．Css-av为（24．0±5．2）μg·L^-1，DF为（1．71±0．24）．tmax为（7．3±1．1）h，t（1/2）为（13．1±2．7）h；氢氯噻嗪的AUCss为（731．4±224．9）ng·h·L^-1，Css-max为（101．0±31．6）μg·L^-1，Css-min为（8．4±3．8）μg·L^-1，Css-av为（30．5±9．4）μg·L^-1，DF为（3．1±1．2），tmax为（3．0±0．9）h，t（1/2）为（8．8±1．6）h。结论：复方赖诺普利片主要药动学参数单剂量和多剂量给药差异无显著性，复方赖诺普利片在人体内无蓄积。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.