复方氨溴索氯雷他定胶囊溶出度测定方法的研究

目的：建立HPLC法测定复方氨溴索氯雷他定胶囊中盐酸氨溴索和氯雷他定的溶出度方法。方法：以0.1mol/L盐酸溶液1 000 ml为溶出介质,转速为50 r/mi n,取样时间为20 min,以溶出度第二法（桨法）测定。采用KromasilC18（50 mm×4.6 mm,5μm）色谱柱,磷酸盐缓冲液-乙腈（1∶1）的流动相,检测波长为247 nm,柱温为室温。结果：盐酸氨溴索的线性方程Y=1.4×106X-2.298×104（r=0.999 7）,在6～36 mg/L浓度范围内线性良好,平均回收率为100.63%,RSD为0.7%;氯雷他定线性方程：Y=2.2×106X-9 278.9（r=0.999 9）,在1～6 mg/L浓度范围内线性关系均良好,平均回收率为99.60%,RSD为1.8%。结论：本方法准确可靠,适用于该制剂的质量控制。     

HPLC测定盐酸乐卡地平片的溶出度

目的采用HPLC法测定盐酸乐卡地平片的溶出度。方法按《中国药典》2010年版溶出度测定第二法,以含0.3%吐温80的0.1 mol·L-1盐酸500 m L为溶出介质,转速为50 r·min-1,45 min时采样。采样后用HPLC法测定,色谱柱为Sun Fire C18,流动相为0.15 mol·L-1高氯酸钠溶液(p H3)-乙腈(39∶61),柱温30℃,流速1.0 m L·min-1,检测波长240 nm,以外标法测定溶出度。结果盐酸乐卡地平2.036~40.72μg·m L-1与峰面积的线性关系良好(r=0.999 9),平均回收率为100.2%,RSD=0.98%(n=9),溶出度符合规定。结论所用方法专属性强、结果准确、稳定性好,适于盐酸乐卡地平溶出度的测定。     

高效液相色谱法测定复方锌布颗粒中布洛芬的溶出度

目的建立高效液相色谱方法测定复方锌布颗粒中布洛芬的溶出度。方法按照中国药典2010年版二部溶出度测定方法第二法,以磷酸氢二钠-枸橼酸缓冲液(p H=5.5±0.02)900 m L为溶出介质,转速为50 r·min-1,采用HPLC法测定布洛芬的浓度。HPLC法中选用Agilent HC C18柱(250 mm×4.6 mm,5μm),以乙腈-磷酸二氢铵溶液(取磷酸二氢铵2.0 g,加水适量使溶解,加磷酸1 m L,用水稀释至1000m L)(70:30)为流动相,检测波长为263 nm。结果该方法线性范围为16.29~814.5μg·m L-1(r=1.000),平均回收率为100.5%,RSD为0.4%(n=3)。结论本法简便、准确,能较好的区分不同生产工艺产品溶出行为的差异,在一定程度上反应了该产品的内在质量。     

五个厂家氯雷他定片或胶囊体外溶出度比较

目的:比较5个厂家的氯雷他定片剂或胶囊剂的溶出度,为临床用药提供参考.方法:采用转篮法进行体外溶出度实验,以紫外分光光度法进行含量测定,计算其累积溶出百分率,并以威布尔方程拟合溶出参数,用方差分析对组间溶出参数进行统计学处理,采用Q检验进行两两检验.结果:5个厂家的氯雷他定片或胶囊的体外溶出度均符合2005年版国家药典标准的规定,但各厂家氯雷他定片或胶囊的溶出度参数m、Kr、T50、T30、Td、T80间存在显著性差异(P<0.05).结论:不同厂家氯雷他定片或胶囊的溶出参数存在差异,临床用药时应加以注意.     

盐酸依匹斯汀胶囊溶出度试验方法的建立及溶出曲线的评价

目的:建立盐酸依匹斯汀胶囊溶出度试验方法,并与市售产品进行溶出曲线评价,考察其有效性。方法:采用篮法,以水为溶出介质,转速为75 r·min-1,并对其与市售产品进行溶出曲线评价。溶出液色谱条件:色谱柱为Agilent Zorbax SB-CN柱(250 mm×4.6 mm,5μm);流动相为乙腈-0.05 mol.L-1磷酸盐缓冲溶液(35∶65);流速为1.0 mL·min-1;检测波长为220 nm;柱温为30℃。结果:盐酸依匹斯汀在0.10～24.12μg.mL-1范围内呈良好线性关系,r=0.999 9,因此采用此法检测本品溶出度,能达到要求,并且与市售产品溶出曲线相似。结论:溶出度的考察更能体现药品的有效性,该方法专属、灵敏、简便,可用于测定盐酸依匹斯汀胶囊的溶出度。     

复方硫酸氢氯吡格雷阿司匹林双层片的制备和溶出度测定

目的建立复方硫酸氢氯吡格雷阿司匹林双层片的制备和溶出度测定方法,通过比较自制品和市售产品的体外溶出行为,考察其有效性。方法制备复方硫酸氢氯吡格雷双层片,采用反相高效液相色谱法测定含量。色谱条件:色谱柱为Ultimate XB-C18柱(250mm×4.6mm,5μm),流动相为乙腈-水-磷酸(体积比40∶60∶2),检测波长为235nm,流速为1.0mL·min-1;采用桨法,以pH值2.0盐酸缓冲液为溶出介质,转速为75 r·min-1测定溶出度;采用f2因子比较法,考察体外溶出行为。结果硫酸氢氯吡格雷和阿司匹林的质量浓度在20~200mg·L-1内与峰面积具有良好的线性关系(r=0.999 9)。硫酸氢氯吡格雷与阿司匹林的平均回收率分别为100.2%和99.8%。自制品和市售品的溶出曲线一致。结论制备方法简单易行。所建立的溶出度测定方法专属、高效、简便,可用于测定复方硫酸氢氯吡格雷阿司匹林双层片的溶出度。     

氯雷他定分散片的制备及影响因素考察

目的制备符合质量要求的氯雷他定分散片。方法采用湿法制粒,单冲压片制备氯雷他定分散片。正交试验优选处方,对优化处方进行分散时限和溶出度考察。结果优选处方制备的氯雷他定分散片质量稳定。结论所选的处方因素对溶出度影响不大,对分散时限有较大影响。     

国产地氯雷他定片溶出度方法的建立

目的： 建立有效区分地氯雷他定片质量并具有国际通用性的溶出度HPLC测定方法。 方法：采用桨法,以0.1 mol.L-1盐酸溶液为溶出介质,转速50 r.min-1,采用高效液相色谱法测定溶出度,以辛烷基硅烷键合硅胶为填充剂,流动相为甲醇-0.5%三氟醋酸溶液(用三乙胺调pH值至6.3)(55:45),流速：1.0ml.min-1,柱温：30℃,检测波长247 nm。结果：地氯雷他定在1.02~204.20μg.mL-1的浓度范围内,线性关系良好(r=1),平均回收率为100.5%,RSD为0.3%(n=9),国内片剂在30min时的溶出度均在95%以上。结论：本方法准确、简单方便且高效,测定结果均一性良好,可有效地用于地氯雷他定片溶出度的测定。     

阿伐斯汀胶囊的溶出度研究

目的建立测定阿伐斯汀胶囊溶出度的方法。方法采用高效液相色谱法,色谱柱为Agilent Zorbax SB C18色谱柱(150 mm×4.6 mm,5μm);流动相:乙腈–四氢呋喃–2%三乙胺(用50%磷酸调节p H值至6.9)(12∶8∶80);检测波长为307 nm;柱温为40℃;体积流量为1.0 m L/min;进样量为20μL。溶出度测定采用桨法,以水为溶出介质,溶出介质体积为500 m L,转速为50 r/min,20 min取样。结果阿伐斯汀在1.63~24.40μg/m L与峰面积线性关系良好(r=1.000);平均回收率为99.87%,RSD值为0.38%(n=9)。3批样品的溶出度分别为98.00%、98.00%、96.00%(n=6)。结论本方法准确可靠,简单易行,专属性强,适用于阿伐斯汀胶囊的溶出度测定。     

LC—MS／MS法测定人血浆中地氯雷他定及其代谢产物3-羟基地氯雷他定的浓度

目的:建立 LC-MS/MS 法测定人血浆中地氯雷他定及其主要代谢产物3-羟基地氯雷他定的浓度。方法:血浆样品经碱化后用乙醚提取,采用液相色谱-质谱联用法检测。色谱条件为分析柱 CAPCELL PAK C_(18)(50 mm×2.0 mm,5 μm),预柱Octadecyl C_(18)(4.0 mm×3.0 mm);流动相:甲醇-乙腈-5 mmol·L~(-1)甲酸铵水溶液(30:20:50);流速0.2 mL·min~(-1);柱温40℃;进样量10 μL。质谱条件为电喷雾离子源(ESI),正离子扫描;选择性监测质荷比(m/z)为311.1/259.1(地氯雷他定),327.1/275.1(3-羟基地氯雷他定),315.1/263.1(D_4-地氯雷他定,内标),331.1/279.1(D_4-3-羟基地氯雷他定,内标)带正电荷的分子离子峰。结果:地氯雷他定、3-羟基地氯雷他定的线性范围均为0.05～10.0 ng·mL~(-1),定量下限均为0.05 ng·mL~(-1),批内、批间 RSD 均小于10%。结论:该方法简便,灵敏度高,专属性强,可用于地氯雷他定及其代谢产物的临床药动学和生物等效性研究。     

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.     

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.