紫外分光光度法测定伊曲康唑注射液的含量

目的 建立紫外分光光度法测定伊曲康唑注射液含量的测定方法。方法 采用紫外分光光度法测定伊曲康唑注射液的含量,测定波长为262nm。结果 线性范围0～38.08μg·ml^-1,伊曲康唑的平均回收率为99.1%,RSD为0.24%,r=0.9999(n=6)。结论 该法方便快速准确,可作为伊曲康唑注射液含量测定的方法。     

伊曲康唑混悬滴眼液的研制及质量评价

目的:制备伊曲康唑混悬滴眼液,并对其质量进行评价。方法:以沉降体积比为考察指标,采用正交试验对羧甲基纤维素钠、吐温80、枸橼酸钠的质量分数进行优化,采用紫外分光光度法测定伊曲康唑的含量;对优化处方后制备的样品进行质量检查和稳定性考察,取健康新西兰白色家兔10只进行眼刺激性实验。结果:羧甲基纤维素钠、吐温80、枸橼酸钠的质量分数分别为2.5%、0.1%、2.5%。伊曲康唑检测质量浓度在4.48～38.08μg/ml范围内与峰面积积分值线性关系良好(r=0.9999),平均回收率为99.98%,RSD=0.11%(n=3)。按优化处方制备的伊曲康唑混悬滴眼液的性状、pH值、含量、粒度及沉降体积比均符合2010年版《中国药典》规定;伊曲康唑含量在第0、1、2、3个月分别为100.5%、99.6%、99.8%、99.9%,其他各项指标无明显变化;眼刺激性实验结果符合要求。结论:该滴眼液制备工艺简单、质量稳定,紫外分光光度法测定其含量简便、准确。     

两种伊曲康唑胶囊溶出度的比较

目的 考察不同厂家伊曲康唑胶囊的溶出度并评价其质量.方法 选用桨法、紫外分光光度法测定伊曲康唑胶囊的含量,并对溶出参数进行统计分析.结果 两个厂家的伊曲康唑胶囊均符合制剂溶出质量规定,溶出参数差异不具有统计学意义(P>0.05).结论 两个产家的伊曲康唑胶囊溶出度无显著差异,在临床使用时疗效无明显差异,可供临床用药.     

伊曲康唑-羟丙基-β-环糊精包合物颗粒的制备与质量控制

目的制备伊曲康唑-羟丙基-β-环糊精包合物颗粒，并对其进行质量控制。方法采用加热搅拌法，在酸性条件下将伊曲康唑制备成羟丙基-β-环糊精包合物，采用制备颗粒一般方法制备伊曲康唑-羟丙基-β-环糊精包合物颗粒。采用紫外分光光度法对其进行质量控制。 结果伊曲康唑-羟丙基-β-环糊精包合物颗粒制备工艺简单，增加伊曲康唑的溶出度，质量控制方法简单易行。结论该制备工艺简便，增加了伊曲康唑的溶出度。     

伊曲康唑包合物注射液的制备及理化性质考察

目的制备伊曲康唑注射液并考察其理化性质。方法以羟丙基β环糊精(HP βCD)为增溶剂,采用溶液 搅拌法制备伊曲康唑包合物注射液,采用HPLC法测定伊曲康唑的含量。结果HP βCD对药物具有较好的增溶作用,伊曲康唑注射液的pH值、渗透压、澄明度等性质均符合要求。结论伊曲康唑包合物注射液符合《中华人民共和国药典》注射剂质量标准     

伊曲康唑脂质体在大鼠体内药动学研究

目的：研究伊曲康唑脂质体在大鼠体内的药动学。方法：大鼠尾静脉注射伊曲康唑脂质体及伊曲康唑注射液,建立液相-质谱联用分析（LC—MS／MS）方法测定血浆中的伊曲康唑药物浓度。结果：伊曲康唑血浓度在10～1600ng·ml^-1范围内线性良好（r=0．9989）,伊曲康唑脂质体及市售伊曲康唑注射液大鼠体内MRT分别为（3．68±0．19）h和（1．70±0．06）h,AUC分别为（155．47±13．84）mg·L^-1·h和（87．12±5．55）mg·L^-1·h,差异具有统计学意义（P〈0．01）。结论：伊曲康唑脂质体具有一定的缓释作用。     

反相高效液相色谱法测定伊曲康唑脂质体药物含量及包封率

目的:建立测定伊曲康唑脂质体药物含量及包封率的 RP-HPLC 法。方法:采用 Diamonsil C_(18)柱(250 mm×4.6 mm,5μm);流动相:甲醇-0.5%醋酸铵-乙醚(15:4:1);流速:1.0 mL·min~(-1);紫外检测波长:262 nm;进样量:20 μL;柱温:35℃。采用 Sephadex G-50分离伊曲康唑脂质体中的游离药物。结果:在本色谱条件下伊曲康唑与辅料及溶剂峰分离良好,伊曲康唑浓度在1.2～48.0μg·mL~(-1)范围内线性关系良好(r=0.9999,n=7),回收率在98.0%～101.0%之间,日内及日间RSD 均小于2%(n=5)。结论:该方法准确可靠、简单快速,可用于伊曲康唑脂质体含量及包封率的测定。     

硝酸舍他康唑泡腾胶囊的制备工艺和含量测定

目的研究硝酸舍他康唑泡腾胶囊的制备工艺及含量测定。方法确定处方的组成,制备泡腾胶囊,并用紫外分光光度法测定硝酸舍他康唑的含量。结果紫外分光光度法测定硝酸舍他康唑含量的标准曲线为A=0．0075p＋0．0096（r=0．9997）,在质量浓度10～90mg·L^-1内吸光度与质量浓度之间的线性关系良好。结论该泡腾胶囊的制备方法简单,用紫外分光光度法测定含量,方法可靠。     

伊曲康唑纳米晶体的制备与表征

目的：制备伊曲康唑纳米晶体并进行药剂学性质表征。方法：采用湿法介质研磨结合冷冻干燥工艺制备伊曲康唑纳米晶体;采用马尔文激光粒度测定仪测定伊曲康唑纳米晶体的粒径和多分散系数（PDI）;采用扫描电镜观察伊曲康唑粒子的形态;采用差示扫描量热法、红外光谱法、X-射线粉末衍射法研究伊曲康唑纳米化前后晶型和化学结构变化情况;采用浆法比较伊曲康唑纳米化前后及市售胶囊在pH 1.2、pH 4.0、pH 6.8的溶液以及水等4种溶出介质中的溶出行为。结果：制备的伊曲康唑纳米晶体平均粒径为317 nm,PDI值0.29;纳米化前后伊曲康唑晶型和化学结构没有发生明显改变;在pH 1.2、pH 4.0、pH 6.8的溶液以及水等4种溶出介质中,药物溶出速率快慢顺序为伊曲康唑纳米晶体> 市售伊曲康唑胶囊> 物理混合物及伊曲康唑原料药。结论：采用湿法介质研磨结合冷冻干燥工艺,可以制备平均粒径小且较为均匀的伊曲康唑纳米晶体;纳米化后伊曲康唑仍为结晶态;制成纳米晶体可以明显改善伊曲康唑的溶出性能,利于改善药物的口服吸收。     

伊曲康唑片含量测定和有关物质检查方法探讨

本文探讨了HPLC法测定伊曲康唑片的含量及其有关物质。采用DiamonsilTMC18色谱柱;乙腈-磷酸二氢钾(0.01mol.L-1磷酸二氢钾的水溶液,含0.2%三乙胺,用磷酸调pH至3.5)(65∶35)为流动相;检测波长:261nm;流速:1ml.min-1;伊曲康唑与其相邻杂质峰能完全分离,伊曲康唑在0.174~348.8μg.ml-1浓度范围内线性关系良好,r2=0.9999。平均回收率100.2%,RSD为0.76%。该法简便、准确、专属性好,可以用于伊曲康唑片的含量测定及有关物质检查。     

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.

     

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.     

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.     

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.     

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.