磷脂固体分散体对槲皮素溶出促进作用的研究

目的研究磷脂固体分散体对槲皮素溶出的促进作用。方法用溶剂法制备了不同比例的槲皮素的磷脂固体分散体 ,与其相应的物理混合物及槲皮素的PVP或PEG4 0 0 0 (1∶1)固体分散体并进行了溶出的对比研究。结果所制得固体分散体均可改善槲皮素的溶出 ,而质量比为 1∶1的槲皮素 磷脂固体分散体的溶出促进作用最为显著。DSC和X射线粉末衍射的研究表明 ,在质量比为1∶1的槲皮素 磷脂固体分散体中 ,槲皮素以无定形的状态分散于载体磷脂中 ,其熔点吸热峰消失。结论槲皮素溶出度的增大与其无定形的存在状态、磷脂对其的润湿作用以及磷脂在水中可形成脂质体有关     

固体分散技术提高磷脂复合物中姜黄素的溶出度

采用固体分散技术提高磷脂复合物中姜黄素的体外溶出度。结果表明,姜黄素、姜黄素磷脂复合物、姜黄素-PVP(1∶2,w/w)固体分散体、姜黄素磷脂复合物-PVP(1∶2,w/w)固体分散体在含0.2%十二烷基硫酸钠的0.1mol/L盐酸中120min累积溶出度分别为0.7%、13.6%、28.0%和98.4%,且磷脂复合物-PVP(1∶2,w/w)固体分散体5min累积溶出72.6%。     

葛根素固体分散体的制备及大鼠体内生物利用度研究

本文采用新型的固体分散体技术,将葛根素,磷脂与PVP制成固体分散体,对其理化性质进行研究,考察固体分散体在大鼠体内的药一时曲线,计算其在大鼠体内的药动学参数,并与葛根素原料比较,研究固体分散体的相对生物利用度。结果表明以磷脂和PVP为载体制备的固体分散体（药物-磷脂-PVP,2：4：1）的表观油水分配系数最好,固体分散体相对生物利用度较纯葛根素提高了2．53倍。     

萝芙木生物碱中育亨宾在薄层色谱原位的傅立叶变换表面增强拉曼光谱研究

目的：建立一种新的方法，在中草药萝芙木提取液薄层色谱分离斑点原位测育亨宾生物碱的表面增强拉曼光谱。方法：将萝芙木生物总碱氯仿提取液经薄层色谱分离，展开剂：氯仿—丙酮—二乙胺(5：4：1)；应用银溶胶(银微粒直径50～120nm)作表面增强基底，测萝芙木主要有效成分之一育亨宾在薄层原位的傅立叶变换表面增强拉曼光谱，激发光波长1064nm。结果：在薄层色谱直径约2mm斑点原位，样品的傅立叶变换表面增强拉曼光谱与纯固体样品的傅立叶变换拉曼光谱的主要特征峰波数基本一致，相对强度出现一些变化，指纹区最强峰是表征吲哚环骨架伸缩振动、波数为1590cm^-1附近的峰。育亨宾分子以吲哚环共轭体系的π电子与表面增强活性物质银晶体微粒表面相互作用引起拉曼散射的显著增强。结论：该法可将提取液中微量育亨宾在薄层色谱分离，快速、直接进行高灵敏度分子光谱检测。     

双波长薄层扫描法测定冠心通脉灵片中葛根素的含量

采用双波长薄层扫描法测定了冠心通脉灵片中葛根素的含量。氯仿 -甲醇 -水 (5∶ 2∶ 0 .2 )为展开剂 ,葛根素 Rf=0 .48,锯齿反射扫描 ,λS=2 70 nm,λR= 370 nm,SX=3,平均回收率为 99.60 % ,RSD =1 .1 3%     

热熔挤出法增加布洛芬的溶出度并掩盖其苦味

目的:制备布洛芬固体分散体,以增加布洛芬的溶出度并掩盖其苦味。方法:取布洛芬原料药与丙烯酸树脂Eudragit EPO,以1∶1.5(w/w)混合,采用热熔挤出法制备布洛芬固体分散体。用差示扫描量热法和粉末X射线衍射法分析布洛芬在Eudragit EPO中的分散状态。测定固体分散体、物理混合物和市售布洛芬片剂的溶出度,并评价布洛芬固体分散体的掩味效果。结果:布洛芬晶体结构的特征峰在差示扫描量热和粉末X射线衍射图中消失。在磷酸盐缓冲液中,固体分散体的溶出速度大于物理混合物和布洛芬片。志愿者对布洛芬固体分散体的味觉评价优于物理混合物和布洛芬原料。结论:热熔挤出法制备的Eudragit EPO固体分散体能增加布洛芬的溶出度,并有明显的掩味效果。     

氟比洛芬聚丙烯酸树脂RL/RS固体分散体的制备

目的制备氟比洛芬固体分散体并考察其体外释药特性。方法以氟比洛芬为主药,分别以聚丙烯酸树脂Eudragit RL、RS及RL/RS混合物为载体,卵磷脂为乳化剂,以溶剂法制备固体分散体。以体外溶出半衰期t1/2为指标,优选固体分散体的最佳制备方法。结果氟比洛芬固体分散体的最佳处方比例为:药物∶载体=1∶9,RL∶RS=2∶1,卵磷脂浓度为0.2%。固体分散体体外溶出测定采用小杯法,测定波长为247 nm,分别采用紫外分光光度法和差示扫描热量法进行定量、定性分析。结论制备所得氟比洛芬固体分散体体外溶出缓慢、平稳、完全,达到提高生物利用度、12 h给药1次的缓释设计目的,可进一步制成其他剂型。     

降糖丸中葛根素的薄层扫描测定

目的 :建立薄层扫描法测定降糖丸中葛根素含量的方法。方法 :固定相为硅胶GF254,流动相为氯仿 -甲醇 -水 (7∶2 5∶0 25) ,检测波长为254nm ,参比波长为370nm。结果 :葛根素在0 4μg～2 0μg 范围内呈良好的线性关系 ,平均回收率为99 4 %(n=5) ,RSD为1 37 %。结论 :本方法准确、可靠 ,可用于测定降糖丸中葛根素的含量。     

薄层色谱—荧光分光光度法测定葛根中葛根素的含量

建立了薄层色谱 -荧光分光光度法测定葛根中葛根素含量的方法。以甲醇为溶剂进行提取 ,以氯仿-甲醇 -水 ( 7∶ 4∶ 0 .2 5)展开 ,刮下斑点后用甲醇洗脱 ,在 Ex=355nm ,Em=4 60 nm处测定荧光强度 ,线性范围为 0 .0 1～ 0 .0 8μg/ ml( r=0 .9998) ,平均回收率为 98.0 % ,RSD <5%。     

清上祛痛胶囊中葛根素的含量测定

目的 :建立清上祛痛胶囊的含量测定方法。方法 :薄层扫描法测定波长λR =370nm ;展开剂为氯仿 -甲醇 -水 (80∶35∶10)10℃以下放置过夜的下层液 ;紫外光灯 (365nm )定位。结果 :葛根素的平均回收率为98 43 % ,RSD为1 45 %。结论 :本法简便、准确、可靠 ,可作为该制剂质量控制指标之一。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.