HPLC法测定奥硝唑葡萄糖注射液含量及有关物质

目的 　测定奥硝唑葡萄糖注射液含量及有关物质。 方法 　HPLC法 ,用 C1 8柱 ,以甲醇 -水 ( 3 0∶ 70 )为流动相 ,检测波长为 2 85 nm,柱温40℃。 结果 　奥硝唑在 2 0～ 2 5 0μg· m L- 1 浓度范围内峰面积与浓度呈良好线性关系 ,相关系数为 0 .9999,平均回收率 99.2 %～ 99.8%,RSD0 .3 %～ 0 .4%。 结论 　该检测法检测奥硝唑葡萄糖注射液 ,两主要杂质与奥硝唑主峰的分离度符合规定     

奥硝唑与甲硝唑治疗细菌性阴道病及滴虫性阴道炎的成本-效果分析

目的　评价奥硝唑与甲硝唑治疗细菌性阴道病及滴虫性阴道炎的疗效、不良反应及成本 效果。方法　将 80例细菌性阴道病及 4 0例滴虫性阴道炎患者随机分成 2组 ,分别口服奥硝唑 (A)和甲硝唑 (B) ,对奥硝唑与甲硝唑治疗细菌性阴道病及滴虫性阴道炎的疗效、不良反应并运用药物经济学成本效果分析法及成本进行评价。结果　奥硝唑与甲硝唑治疗细菌性阴道病及滴虫性阴道炎总有效率基本相同 ,分别为 95 .0 0 %和 90 .0 0 % (P >0 .0 5 ) ,92 .5 0 %和 95 .0 0 % (P >0 .0 5 ) ;不良反应发生率分别为 3.75 % ,17.5 % (P <0 .0 1) ;成本 效果比分别为 0 .78和 0 .80 ,0 .18和 0 .17(P <0 .0 1)。结论　奥硝唑与甲硝唑均能有效治疗细菌性阴道病及滴虫性阴道炎。甲硝唑成本 效果比优于奥硝唑。但其不良反应发生率与奥硝唑有显著性差异     

高效液相色谱法测定母乳中奥硝唑的方法学研究

目的 :建立高效液相色谱测定母乳中奥硝唑浓度的方法。方法 :以C8 柱 (4 0mm×150mm ,5μm)为色谱柱 ,甲醇 -水(30∶70)为流动相。母乳样品用乙腈直接沉淀蛋白 ,无须经过有机溶剂提取直接进样分析。结果 :母乳中内源性物质不干扰奥硝唑的测定 ,奥硝唑在2 0～30 0μg/ml浓度范围内峰面积与浓度线性关系良好 (r=0 9997) ,最低检测限为0 49μg/ml。平均回收率为 (99 67±0 54) % ,高、中、低3种浓度的日内RSD≤2 5 % ,日间RSD≤2 1 %。结论 :本方法简便、快速、准确 ,重现性好 ,可应用于奥硝唑在母乳中的药动学研究     

奥硝唑凝胶剂的制备及质量控制

目的　制备奥硝唑凝胶剂并建立质量控制方法。方法 　以丙二醇为保湿剂、卡波姆为基质配制水溶性凝胶剂 ,用紫外分光光度法测定奥硝唑的含量。结果 　凝胶剂有良好的涂布性 ,奥硝唑在波长 3 12 nm处有最大吸收 ,经处理以后基质在此波长无干扰 ,在 3 .14～ 18.83μg· m L- 1浓度范围内 ,浓度与吸光度呈良好的线性关系 (r=0 .9997) ,平均回收率为 10 0 .2 % (RSD=1.16% )。 结论 　奥硝唑凝胶剂的制备工艺简便、性质稳定 ,质量控制方法准确可靠。     

HPLC法测定奥硝唑片中有关物质的含量

目的建立一种高效液相色谱法测定奥硝唑片中的有关物质的方法。方法色谱柱:用十八烷基硅烷健合硅胶为填充剂;以甲醇-水-冰醋酸(30∶69∶1)为流动相;流速1.0 mL.min-1;检测波长为315 nm。结果 2-甲基-5-硝基咪唑、奥硝唑的最小检出限分别为0.002%、0.01%,奥硝唑峰与杂质峰分离良好,空白辅料对奥硝唑片中的有关物质检查无干扰。结论此法精密度高、稳定性好,可用于奥硝唑片中相关物质的测定。     

反相高效液相色谱法同时测定复方奥硝唑栓中两组分的含量

目的 :建立以反相高效液相色谱法同时测定复方奥硝唑栓中两组分含量的方法。方法 :色谱柱为SymmetryC18 柱 ,流动相为甲醇 -0 01mol/L磷酸二氢钾缓冲液 (30∶70) ,流速为1 0ml/min ,检测波长为305nm ,以替硝唑为内标。结果 :奥硝唑在5～80μg/ml浓度范围内线性关系良好 (r=0 9997) ,平均回收率为 (100 65±2 20) %;左氧氟沙星在2 5～40μg/ml浓度范围内线性关系良好 (r=0 9999) ,平均回收率为 (98 86±1 28) %。结论 :本方法操作简便 ,测定结果准确 ,可用于复方奥硝唑栓的质量控制。     

奥硝唑片、奥硝唑胶囊人体生物等效性研究

目的 :比较试验制剂国产奥硝唑片及国产奥硝唑胶囊与参比制剂进口奥硝唑片的生物等效性。方法 :18名健康志愿者 ,单剂三交叉口服试验制剂奥硝唑片、奥硝唑胶囊和参比制剂 1.5 g ,于药前和药后0 .5 ,1,1.5 ,2 ,3,4 ,6 ,8,12 ,2 4 ,36 ,4 8,72h取肘静脉血 ,用高效液相色谱法测定奥硝唑经时血药浓度 ,数据经 3P97处理得药代动力学参数 ,根据试验制剂和参比制剂AUC计算相对生物利用度。同时对主要药代动力学参数进行方差分析、双单侧t检验和 (1- 2α)置信区间分析 ,评价试验制剂和参比制剂的生物等效性。结果 :试验制剂奥硝唑片、奥硝唑胶囊和参比制剂主要药代动力学参数t1/ 2 ( β) 分别为 (16 .2 9± 2 .199) ,(16 .0 8± 2 .317)和 (15 .84 9± 2 .2 6 4 ) ,tpeak分别为 (1.75± 0 .4 93) ,(1.75± 0 .4 93)和 (1.75± 0 .4 79)h ,Cmax分别为(2 1.5 34± 3.5 3) ,(2 1.936± 3.314 ) ,(2 0 .85± 5 .939) μg·ml-1,AUC0～ 72 分别为 (44 4 .5 6± 5 5 .872 ) ,(44 6 .4 98± 5 5 .138)、(433.30 9± 5 8.5 2 1) μg·ml-1·h-1,AUC0～∞ 分别为 (46 2 .94 9± 5 5 .35 4 ) ,(46 5 .2 2 1± 5 6 .73) ,(45 1.6 6 8± 5 7.971) μg·ml-1·h-1,奥硝唑片、奥硝唑胶囊相对生物利用度分别为 10 2 .91± 8.93%     

奥硝唑与甲硝唑治疗滴虫性阴道炎的疗效观察

目的：观察奥硝唑与甲硝唑在治疗滴虫性阴道炎中的临床疗效。方法选取2011年5月-2013年5月本院收治的滴虫性阴道炎患者80例,根据患者治疗方法不同分为奥硝唑组和甲硝唑组。奥硝唑组患者采用奥硝唑治疗,甲硝唑组患者则采用甲硝唑治疗,分别治疗1个疗程后比较两组患者疗效并记录不良反应发生情况。结果奥硝唑组总有效率高于甲硝唑组,差异有统计学意义（ P ＜0.05）;奥硝唑组发生胃肠道反应6例,头晕2例,皮疹0例,不良反应发生率为20.0%;甲硝唑组患者发生胃肠道反应21例,头晕5例,皮疹1例,不良反应发生率为67.5%。两组不良反应发生率比较,差异有统计学意义（P ＜0.05）。结论在治疗滴虫性阴道炎上,奥硝唑较甲硝唑疗效更为确切,治愈率更高,安全性更好,不良反应发生率更低。     

奥硝唑与双唑泰栓治疗滴虫性阴道炎疗效比较

目的观察奥硝唑与双唑泰栓治疗滴虫性阴道炎的效果及安全性。方法滴虫性阴道炎患者100例,随机分为2组,奥硝唑组50例,口服奥硝唑0.5g,2次/d,疗程为5d,双唑泰栓组50例,每日1枚外用,疗程为7d。结果奥硝唑与双唑泰栓组痊愈率分别为96%和72%（P〈0.05）,总有效率分别为100%和92%（P〉0.05）;不良反应发生率分别为10%和8%（P〉0.05）。结论奥硝唑治疗滴虫性阴道炎具有疗效强、疗程短、痊愈率高等特点。     

奥硝唑氯化钠注射液与注射用头孢西丁钠配伍稳定性考察

目的 考察室温[(20±1)℃]下,奥硝唑氯化钠注射液与注射用头孢西丁钠配伍的稳定性,为临床合理用药提供科学依据.方法 采用反相高效液相色谱法-二极管阵列检测器同时测定配伍液中奥硝唑与头孢西丁钠0～6 h内的含量变化,并观察配伍液的外观及pH.结果 奥硝唑与头孢西丁钠的检测波长分别为318、237 nm;奥硝唑与头孢西丁钠的回归方程分别为Y奥=0.7444 X奥+3.0667(r=0.9998,n=6)和Y西=0.6549 X西+6.2667(r=0.9996,n=6),结果 表明在奥硝唑50.8～304.8 mg/L、头孢西丁钠101.6～609.6 mg/L浓度范围内与峰面积呈良好的线性关系;精密度试验测得奥硝唑峰面积相对标准偏差(RSD)为0.58%;头孢西丁钠峰面积RSD为0.65%;重复性试验测得奥硝唑峰面积RSD为0.84%;头孢西丁钠峰面积RSD为0.92%;稳定性试验测得奥硝唑与头孢西丁钠峰面积RSD分别为0.52%、0.89%.6 h内配伍液外观、pH及含量均无明显变化.结论 在室温条件下,奥硝唑氯化钠注射液与注射用头孢西丁钠6 h内可以配伍使用.     

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.     

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.

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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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

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.