奥硝唑中空栓的制备及质量控制

目的:制备奥硝唑中空栓并建立其质量控制方法。方法:以半合成脂肪酸甘油酯为基质制成中空栓;采用紫外分光光度法测定主药奥硝唑含量,测定波长为316nm。结果:奥硝唑检测浓度在6.0~18.0μg/ml范围内线性关系良好(r=0.9 997),平均回收率为99.80%(RSD=0.75%,n=5)。结论:本方法简便、准确、重现性好,可用于奥硝唑中空栓的质量控制。     

双氯芬酸钠中空栓的制备及质量控制

目的:制备双氯芬酸钠中空栓并建立其质量控制方法。方法:以混合脂肪酸甘油酯为基质制备中空栓,采用紫外分光光度法测定其中主药的含量。结果:所制备制剂为乳白色栓剂;双氯芬酸钠检测浓度的线性范围为5～25μg·mL-1(r=0.9997),平均回收率为102.04%(RSD=1.08%)。结论:该制剂制备工艺简便可行,质量稳定可控。     

HPLC法同时测定小儿氨酚烷胺颗粒中3种成分的含量

目的建立同时测定小儿氨酚烷胺颗粒中对乙酰氨基酚、马来酸氯苯那敏、咖啡因的高效液相色谱含量测定方法。方法采用D iam onsil C18(4.6 mm×250 mm,5μm)色谱柱;甲醇-0.05 m ol/L磷酸二氢钾溶液(20∶80)(1%磷酸调pH3.0)为流动相;流速:1.0 m l/m in;检测波长:210 nm。结果对乙酰氨基酚的线性范围为0.490 2~29.412 0μg(r=1.000 0)、平均回收率(n=9)为100.3%,RSD为0.43%;马来酸氯苯那敏的线性范围为0.003 992~0.239 520μg(r=0.999 9),平均回收率(n=9)为100.5%,RSD为0.20%;咖啡因的线性范围为0.030 64~1.838 40μg(r=1.000 0),平均回收率(n=9)为100.5%,RSD为0.23%。结论本方法简便、结果准确,可用于制剂的含量测定和质量控制。     

复方小儿退热栓中对乙酰氨基酚含量测定及其均匀度研究

目的建立测定复方小儿退热栓中对乙酰氨基酚含量的高效液相色谱法,并研究其均匀度。方法色谱柱采用Agilent Zorbax SB-C18柱(250 mm×4.6 mm,5μm),流动相为甲醇-水(20∶80,V/V),流速1.0 m L/min,检测波长244 nm,柱温30℃,进样量10μL。结果对乙酰氨基酚进样量在0.0819~1.639μg范围内与峰面积线性关系良好(r=0.999 5);精密度、稳定性、重复性试验结果的RSD均小于1.0%;平均加样回收率为101.25%,RSD为0.87%(n=9);17批样品的平均含量为99.35%~107.37%,含量均匀度(A+2.2 S)为2.92~9.38。结论该方法简便准确,重复性好,专属性强,可用于复方小儿退热栓的质量控制。     

HPLC法同时测定小儿氨酚烷胺颗粒中3种成分的含量

目的建立同时测定小儿氨酚烷胺颗粒中对乙酰氨基酚、马来酸氯苯那敏、咖啡因的高效液相色谱含量测定方法。方法采用D iam onsil C18(4.6 mm×250 mm,5μm)色谱柱;甲醇-0.05 m ol/L磷酸二氢钾溶液(20∶80)(1%磷酸调pH3.0)为流动相;流速:1.0 m l/m in;检测波长:210 nm。结果对乙酰氨基酚的线性范围为0.490 2~29.412 0μg(r=1.000 0)、平均回收率(n=9)为100.3%,RSD为0.43%;马来酸氯苯那敏的线性范围为0.003 992~0.239 520μg(r=0.999 9),平均回收率(n=9)为100.5%,RSD为0.20%;咖啡因的线性范围为0.030 64~1.838 40μg(r=1.000 0),平均回收率(n=9)为100.5%,RSD为0.23%。结论本方法简便、结果准确,可用于制剂的含量测定和质量控制。     

痔舒宁中空栓的制备及质量控制

目的：制备痔舒宁中空栓并建立其质量控制方法。方法：以半合成脂肪酸甘油酯为基质制备中空栓,采用理化鉴别法及薄层色谱分析法对痔舒宁中空栓所含组分进行定性分析;采用高效液相色谱法对盐酸曲马多进行含量测定。结果：该制剂的一般检查项目均符合药典规定,薄层鉴别中供试品均斑点清晰,分离度好,且阴性对照无干扰;含量测定中,曲马多在50~300 μg·mL-1范围内线性关系良好（r=0.999 9）,平均回收率为99.92%（RSD 1.68%,n=6）,3批制剂检测平均含量99.23 mg/枚。结论：按照《中国药典》2015版及相关文献质量标准对痔舒宁中空栓进行质量检测,结果均符合规定。     

复方司帕沙星中空栓的制备及质量控制

目的:制备复方司帕沙星中空栓并建立其质量控制方法。方法:以司帕沙星、替硝唑为主药,半合成脂肪酸甘油酯为基质制备中空栓;采用双波长分光光度法测定其中主药含量,并考察室温留样6个月内的制剂稳定性,同时用家兔做阴道黏膜刺激性实验。结果:司帕沙星、替硝唑检测浓度的线性范围分别为2.0～10.0(r=0.9998)、4.0～20.0μg.mL-1(r=0.9995),平均回收率分别为98.41%(RSD=1.40%)、98.62%(RSD=0.40%);该制剂对阴道黏膜的刺激性小,室温贮存6个月内质量稳定。结论:该制剂制备及含量测定方法简单可行,且质量稳定、刺激性小,易于推广。     

对乙酰氨基酚栓国家药品评价性抽检工作中发现的问题及解决方案

目的:基于对乙酰氨基酚栓国评工作中发现的问题,建立新的对乙酰氨基酚栓的含量测定方法并开展相关探索性研究。方法:采用Agilent C₁₈ plus(250 mm×4.6 mm, 5μm)色谱柱,对对乙酰氨基酚栓的含量进行测定,以0.05 mol·L^-1醋酸铵溶液-甲醇(85∶15)为流动相,流速为1 mL·min^-1,检测波长257 nm。结果:对乙酰氨基酚在1.5～300μg·mL^-1范围内呈现良好的线性关系(r=1.000),平均回收率(n=9)为100.1%、精密度低至0.44%。建立了新的对乙酰氨基酚栓含量测定方法,解决了原方法样品制备困难、实验方法精密度差的问题。同时在质量标准中增加了含量均匀度检查项,有效控制了产品含量的均一性。结论:本方法专属性强,结果准确度高,重复性好,方法耐用性良好,很好的解决了国评实验中对乙酰氨基酚含量测定精密度及准确度差的问题,为有效控制该栓剂的质量提供一种准确实用的手段。     

HPLC法同时测定复方氨酚苯海拉明片中对乙酰氨基酚和咖啡因含量

目的:建立同时测定复方氨酚苯海拉明片中对乙酰氨基酚和咖啡因含量的高效液相色谱法。方法:采用Hypersil ODS2色谱柱(200 mm×4．6 mm,5μm),流动相:0．01 mol·L-1磷酸二氢钾溶液(用磷酸调节pH至2．6-甲醇(7∶3);检测波长:273 nm。结果:对乙酰氨基酚的线性范围为39．1～117．0μg·ml-1(r=0．999 9)、咖啡因的线性范围为4．0-12．0μg·ml-1 (r=0．999 8);对乙酰氨基酚平均回收率为99．3％(n=9),RSD=1．5％;咖啡因平均回收率为100．1％(n=9),RSD=1．9％。结论:本法简便,准确,重现性好,可用于该制剂的质量控制及评价。     

草珊瑚口服液的制备及质量控制

目的:探讨草珊瑚口服液的制备及质量控制方法.方法:以草珊瑚浸膏为原料制备草珊瑚口服液,并以芦丁为对照品控制制剂中所含草珊瑚相当于芦丁的含量.结果:芦丁对照品溶液在8～48 μg/mL浓度范围内与吸收度线性关系良好(r=0.999 7),平均加样回收率为100.03%,RSD=0.87%(n=6).结论:草珊瑚口服液的制备方法简便,质量控制满意,为一种较理想的医院制剂.     

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.     

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.