枸橼酸托瑞米芬片在不同介质中的溶出特性

分别以pH6.8 磷酸盐缓冲液和0.1mol/L HCl及其含0.1%、0.5%、1.0%十二烷基硫酸钠、10%乙醇的改性溶液作溶出介质,评价枸橼酸托瑞米芬片的溶出特性。测定结果显示,本品在pH6.8 磷酸盐缓冲液中几乎不溶出,60min时在后5种溶液中的溶出百分率分别为(44.26±13.00)%、(27.72±12.58)%、(46.20±9.68)%、(87.15±1.16)%和(78.27±9.38)%。后两者溶出参数b、T0.2、T0.3存在统计学差异(P<0.05)。     

盐酸马尼地平片仿制药与原研药的溶出度一致性评价

目的:建立盐酸马尼地平片的溶出度测定方法,并评价仿制药与原研药的质量一致性。方法:采用高效液相色谱法。色谱柱为Waters Symmetry C18,流动相为磷酸二氢钾溶液(磷酸二氢钾6.8 g溶于1 000 ml水中,用氢氧化钾溶液调节p H至4.6)-乙腈(49∶51,V/V),流速为1.0 ml/min,检测波长为228 nm,柱温为25℃,进样量为20μl。以0.1 mol/L盐酸溶液、醋酸-醋酸钠缓冲液(p H 4.0)、磷酸盐缓冲液(p H 6.8,加入0.5%十二烷基磺酸钠)为溶出介质,溶出介质体积为900 ml,转速为50 r/min,分别考察盐酸马尼地平片仿制药与原研药的溶出度,并通过计算相似因子(f2)评价二者溶出曲线的相似性。结果:盐酸马尼地平检测质量浓度线性范围为0.625~20μg/ml;仪器精密度、稳定性试验的RSD<2.0%;3种溶出介质中的回收率为92.86%~102.97%,RSD分别为1.9%、1.8%、2.7%(n=9)。3批盐酸马尼地平片仿制药与原研药在0.1 mol/L盐酸溶液中15 min时溶出度均大于85%,在醋酸-醋酸钠缓冲液(p H 4.0)和磷酸盐缓冲液(p H 6.8,加入0.5%十二烷基磺酸钠)中f2值均>50。结论:该方法适用于测定盐酸马尼地平片的溶出度;同时,盐酸马尼地平片仿制药与原研药的体外溶出曲线具有相似性,故认为质量一致性较好。     

尼莫地平片剂及胶囊剂溶出度的考察

目的:比较六个厂家的尼莫地平片剂及胶囊剂的溶出度,从而考察其内在的质量。方法:按照中国药典2000年版二部附录中有关溶出度及分光光度法的规定,分别测定16批供试品在水、15％乙醇溶液、0.1 mol/L盐酸溶液、磷酸盐缓冲液(pH 6.8)4种溶出介质中的溶出度。结果:从16批供试品在水、15％乙醇溶液、0.1mol/L盐酸溶液、磷酸盐缓冲液(pH 6.8)4种溶出介质中的溶出度的结果,看尼达尔片在水、0.1mol/L盐酸溶液、磷酸盐缓冲液(pH6.8)3种溶出介质中的溶出度略高于进口产品,较明显高于其他国产品牌,在15％乙醇溶液的介质中,尼达尔片与其他5种样品的溶出量基本一致。结论:尼达尔片由于以特殊工艺方法制成,采用了先进的固体分散技术,使有效成分以分子状态进入载体网状骨架中,形成非结晶性无定形物,从而使溶出 度提高,使之在质量上与进口及国内其他产品相比占优势。     

硝苯地平片剂溶出度的考察

目的考察不同生产企业生产的硝苯地平片剂的体外溶出度。方法分别以0.1 mol.L-1盐酸溶液、人工胃液(不含胃蛋白酶)、pH 4.5醋酸钠缓冲液、pH 6.8磷酸盐缓冲液和蒸馏水为溶出介质,采用紫外分光光度法检查;以质量分数为0.25%十二烷基硫酸钠为溶出介质,采用HPLC法检查,比较不同厂家硝苯地平片剂的体外溶出度。用相似因子法评价硝苯地平片剂在0.1 mol.L-1盐酸溶液、人工胃液(不含胃蛋白酶)、pH 4.5醋酸钠缓冲液、pH 6.8磷酸盐缓冲液和蒸馏水中的溶出行为。结果在质量分数为0.25%十二烷基硫酸钠溶液中,硝苯地平的溶出度在60 min均大于65%,而在其他溶出介质中的溶出度均达不到《英国药典》及《美国药典》中规定的标准。相似因子f2均在50~100之间。结论溶出介质的pH值对硝苯地平的溶出度没有影响。从整体来看,国产硝苯地平片剂的体外溶出行为与国外制剂相比有很大差距。     

高效液相色谱法测定腰息痛胶囊中对乙酰氨基酚溶出度的研究

目的建立腰息痛胶囊中对乙酰氨基酚的溶出度测定方法。方法采用转蓝法,以0.1mol/L盐酸溶液为溶出介质,转速为100r/min,取样时间为30min。液相色谱柱为CAPCELL PAK C18色谱柱(4.6×150mm,5μm);流动相为甲醇-0.5%冰醋酸溶液(20:80);检测波长为249nm;流速:1.0mL/min;柱温:30℃;进样体积10μL。结果乙酰氨基酚在0.2108～1.0540μg线性范围内(r=0.99999)呈良好的线性关系,平均回收率为99.4%。结论本法操作简便,结果准确可靠。能够用于测定腰息痛胶囊中对乙酰氨基酚的溶出度测定。     

用光纤过程监测不同厂家螺内酯片的溶出度

目的：对6个厂家生产的螺内酯片进行溶出度的实时监测,考察并评价其工艺质量。方法：采用光纤药物溶出度实时测定仪进行溶出度测定。采用桨法,以含0.1%十二烷基硫酸钠的0.1 mol/L盐酸溶液1 000 ml为溶出介质,设定水浴温度37℃,转速75 r/min,检测波长242 nm,参比波长550 nm,用3 mm探头监测螺内酯片的溶出曲线,对实时相对溶出百分率与溶出时间进行作图分析。结果：各厂家螺内酯片的溶出度均符合《中华人民共和国药典》规定,但溶出曲线和溶出速率存在差异。结论：利用光纤药物溶出度实时测定仪监测螺内酯片的溶出度,可以实时、连续、动态、定量地监测药物的溶出过程,直观地反映各厂家同种药品溶出过程的差异,为全面评价药品的内在质量提供参考。     

地巴唑片溶出度测定方法的研究

目的:建立地巴唑片溶出度测定方法.方法:以0.1mol/L盐酸溶液为溶出介质,采用紫外分光光度法测定.结果:该方法线性关系良好(r=0.9997),平均回收率为99.82%(RSD=0.51%).结论:本方法适用于地巴唑片的溶出度测定.     

两个厂家的烟酸片的溶出度比较

目的比较不同厂家烟酸片的溶出状况。方法采用0.1mol/L盐酸液,pH4乙酸盐缓冲液,pH6.8磷酸盐缓冲液和水4种介质900ml,采用转篮法,转速100r/min。采用紫外分光光度法,在262nm波长处测定吸光度,分别绘制溶出曲线。结果两厂家的溶出曲线有较大差异。结论应采用0.1mol/L盐酸液作为烟酸片溶出度测定的溶出介质。     

环孢素软胶囊溶出度HPLC检测方法改进研究

目的 :对环孢素软胶囊溶出度检测高效液相色谱(HPLC)方法进行改进。方法 :采用浆法,含0.1 mol/L HCl的0.5%十二烷基磺酸钠为溶出介质,转速75 rpm,分别于第15,30,45,60,75,90 min取样,测定4个厂家产品的溶出度,绘制溶出曲线。HPLC色谱条件为:C8(2)柱(4.6 mm×250 mm,5μm);0.1%三氟乙酸∶四氢呋喃∶乙腈∶0.5%三乙胺(磷酸调p H为2.4)(20∶25∶40∶15)为流动相,柱温60℃,流速1.0 m L/min;检测波长210 nm。结果:本方法线性范围为5~100μg/m L,定量限、检测限分别为2.6,0.86μg/m L。4个厂家的样品在90 min内溶出度均超过标示量的80%,但溶出曲线存在明显差别。结论:本方法准确、可靠,灵敏度高,能够区分不同厂家产品的溶出特征,适用于环孢素软胶囊溶出度的检测。     

人工牛黄甲硝唑胶囊中甲硝唑溶出度测定方法考察

目的建立人工牛黄甲硝唑胶囊中甲硝唑的最佳溶出度测定方法。方法采用《中国药典》2010年版二部溶出度测定法第一法(转篮法),以0.1 mol/L盐酸溶液900mL为溶出介质,转速为75r/min,取样时间为20min,采用紫外分光光度法测定溶出量。结果甲硝唑在4.228~21.14μg/mL范围内线性关系良好(r=0.9999);平均回收率为99.8%,RSD为0.5%(n=9)。结论本方法符合溶出度方法的建立原则,可控制人工牛黄甲硝唑胶囊的内在质量。     

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.     

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.