HPLC测定非诺贝特缓释胶囊的有关物质

目的 建立非诺贝特缓释胶囊有关物质的HPLC测定方法。方法 采用Kromasil-100-5 C₁₈柱,流动相为乙腈-水（用磷酸调节pH至3.0）（67：33）;流速1.0 mL·min^-1;检测波长为286 nm;柱温为40℃;进样量为10 μL。结果 非诺贝特与其他杂质的分离度较好,非诺贝特的线性范围为0.54~3.23 μg·mL^-1（r=0.999 9）,检测限为0.03 μg·mL^-1。结论 建立的方法简便、准确、专属性强,可作为非诺贝特缓释胶囊有关物质的检测方法。     

非诺贝特片仿制药与原研药溶出度一致性评价研究

目的 建立非诺贝特片溶出度曲线测定方法,评价国内10家仿制药产品与原研药品溶出曲线的相似性。方法 用含0.025 mol·L^-1 SDS的pH 1.0盐酸溶液、pH 4.0缓冲液、pH 6.8缓冲液和水溶液4种溶出介质,分别考察非诺贝特片仿制药与原研片的溶出状况,并通过计算相似因子（f₂）评价溶出曲线的相似性。结果 国内仅1家企业产品与原研片在4种溶出介质中的溶出曲线均相似,其余企业产品与原研片相比溶出行为均不一致。结论 该方法适用于非诺贝特片的溶出曲线测定,可为非诺贝特片质量一致性评价提供参考。     

非诺贝特双层渗透泵片在Beagle犬体内的药动学研究

目的 研究非诺贝特双层渗透泵片在犬体内的药动学特征,并评价受试制剂和参比制剂的生物等效性。方法 采用LC-MS测定比格犬体内的血药浓度,采用DAS 2.1.1软件计算药动学参数。结果 受试制剂和参比制剂血浆中非诺贝特酸的C_max分别为（1 100.0±771.2）、（924.3±564.0）ng/mL,t_max分别为（6.7±8.5)、（2.5±0.5）h,AUC0-t分别为（17 841.1±12 220.7）、（17 615.5±12 870.2）ng·h/mL;t_1/2分别为（17.7±8.2）、（16.4±3.3）h,MRT_0-t分别为（24.7±4.0）、（24.5±5.2）h,受试制剂中非诺贝特酸的平均相对生物利用度为（104.7±12.4）%。结论 受试制剂非诺贝特渗透泵片和参比制剂非诺贝特缓释胶囊具有生物等效性。     

HPLC法测定非诺贝特胶囊中非诺贝特的含量

摘 要 目的：建立非诺贝特胶囊中非诺贝特的含量测定方法。方法: 采用HPLC法,色谱柱：Dikma Diamonsil C₁₈柱（150 mm×4.6 mm,5 μm）,流动相：乙腈-水（70∶30,用磷酸调节pH值至2.5）,检测波长：286 nm,流速：1.0 ml·min^-1,柱温：30℃,进样量：20 μl。 结果: 非诺贝特浓度在10.07～60.42 μg·mL^-1范围内线性关系良好（r=0.999 6）,平均回收率为99.26%,RSD为0.5%（n=6）。结论:本法简便、准确、专属性强,可用于该制剂的含量测定。     

非诺贝特体外溶出度考察及其微粉化制剂的研究

目的考察不同厂家非诺贝特固体制剂体外溶出度以及微粉化对非诺贝特溶出度的影响。方法分别以 40 % (φ)乙醇溶液、5 0 % (φ)乙醇溶液、5g/L十二烷基硫酸钠溶液、1 0g/L十二烷基硫酸钠溶液为溶出介质 ,对 4种市售非诺贝特固体制剂的体外溶出度进行考察。采用球磨机制备微粉化非诺贝特 ,对其溶出度进行测定。结果 1 0 g/L十二烷基硫酸钠溶液中微粉化制剂的溶出速率明显快于其余 3种非微粉化制剂 ,初步探讨了非诺贝特固体制剂体外溶出度标准。用相似因子法对自制微粉化胶囊和法国生产的微粉化胶囊的溶出实验数据进行统计分析 ,结果表明两者溶出行为相似 ,相似因子f2 =72 4(5 0≤f2 ≤ 1 0 0 )。结论不同厂家非诺贝特固体制剂的溶出度差异较大 ,微粉化工艺能显著提高非诺贝特的溶出度     

杨梅醇与5-对氟苄氧基杨梅醇的制备及其对人肝癌HepG2细胞活性的影响

目的 体外观察杨梅醇与5-对氟苄氧基杨梅醇（myricanol 5-fluorobenzyloxy ether,5FEM）对人肝癌细胞HepG₂活性的影响。方法 制备杨梅醇与5FEM,杨梅醇（25,12.5,6.25 μg·mL^-1）、5FEM（25,12.5,6.25 μg·mL^-1）作用于HepG₂细胞,实时细胞分析系统记录96 h细胞指数,观察杨梅醇与5FEM对HepG₂细胞增殖和迁移的影响。结果 杨梅醇与5FEM对HepG₂细胞的增殖和迁移均有较好的抑制作用,且呈现较好的量效关系,相等剂量下,5FEM的作用优于杨梅醇。结论 杨梅醇与5FEM能有效抑制HepG₂细胞的增殖和迁移。     

人脐带间充质干细胞复方电解质注射液制剂的制备及稳定性研究

目的 探索人脐带间充质干细胞复方电解质注射液制剂稳定性。方法 人脐带间充质干细胞（密度5×10⁵/mL）分别与复方电解质注射液及0.9%氯化钠注射液（分别设加/不加2%人血白蛋白组）制备制剂,通过观察24 h内不同时间节点凋亡变化趋势优选出制剂方案;探讨该制剂的光照稳定性、热循环稳定性、加速稳定性以及长期稳定性。结果 复方电解质注射液制剂较0.9%氯化钠注射液制剂细胞凋亡水平低;2%白蛋白添加能够有效降低细胞凋亡水平。光照对复方电解质注射液添加2%白蛋白细胞制剂无严重影响;温度波动能导致细胞存活率快速下降;高温对细胞制剂状态有较大影响,导致絮状物大量出现,细胞存活率快速下降;在低温条件下,该制剂能长时间保持细胞存活率。结论 复方电解质注射液添加2%白蛋白是一种优良的人脐带间充质干细胞制剂方法。     

星点设计-效应面法优化硼酸乳膏基质配方及质量控制

摘 要 目的：优化硼酸乳膏基质配方,考察制剂成品质量。方法: 采用星点设计效应面法,以乳膏黏度为评价指标,优化脂肪醇醚-6（和）硬脂醇、鲸蜡硬脂醇聚醚-25、十六醇、十八醇、异硬脂醇异硬脂酸酯、霍霍巴油、轻质液状石蜡的用量;考察优化后制剂的外观性状、粒度、黏度、稳定性及硼酸的含量。结果: 配方中含脂肪醇醚-6-鲸蜡硬脂醇聚醚-25（3∶2）50 g、十六醇-十八醇（3∶7）65 g、异硬脂醇异硬脂酸酯 霍霍巴油-轻质液状石蜡（5∶3∶2）125 g时,制得的成品为白色半流体乳膏,硼酸含量为标示量的98.50%,粘度为1.64×10⁴ mPa·s,预测值与实测值相当,制剂稳定性较好。结论:星点设计 效应面法优化硼酸乳膏基质配方方法简单、精密度高、预测性好,制剂成品稳定、质量可控。     

微波消解-ICP-MS测定洁白胶囊中重金属含量

目的 建立电感耦合等离子体质谱法（ICP-MS）测定洁白胶囊中Pb、Cd、As、Hg、Cu等重金属元素的方法,为洁白胶囊用药安全提供依据。方法 微波消解样品,以30.0 μg·L^-1的Sc 45、In 115作内标,采用ICP-MS同时测定上述5种元素的含量。结果 5种元素方法检出限为0.000 5~0.021 1 mg·kg^-1,线性关系良好（r>0.99）,加样回收率为98.2%~105.4%,RSD为2.3%~3.5%。本次测定的19批洁白胶囊中重金属含量为Pb：0.2~1.0 mg·kg^-1;Cd：0.012~0.027 mg·kg^-1;As：0.18~1.52 mg·kg^-1;Hg：0~0.151 mg·kg^-1;Cu：1.4~2.5 mg·kg^-1。参照药用植物及制剂外经贸绿色行业标准和新加坡进口中药材和中成药标准,结果符合规定。结论 该方法简便易行,准确度灵敏度高、重复性良好,适用于洁白胶囊中5种重金属的测定。     

番薯藤提取物抗痤疮丙酸杆菌有效部位筛选研究

目的 研究番薯藤提取物对痤疮丙酸杆菌的体外抑菌作用,并对其有效部位进行筛选。方法 采用固体平板法、试管2倍比稀释法测定番薯藤水、醇提物对痤疮丙酸杆菌的抑菌圈大小和最低抑菌浓度（minimum inhibitory concentration,MIC）,采用系统溶剂法对番薯藤醇提物进行梯度提取,分别得到石油醚层、二氯甲烷层、乙酸乙酯层、正丁醇层和水层5个不同极性部位,并确定其有效部位及相应的MIC、最低杀菌浓度（minimum bactericidal concentration,MBC）。结果 番薯藤醇提物对痤疮丙酸杆菌有较强抑制作用,其MIC为50 mg·mL^-1。其中石油醚部位的抑菌作用最强,MIC为12.5 mg·mL^-1,MBC为25 mg·mL^-1;其次为正丁醇部位,MIC为25 mg·mL^-1,MBC为100 mg·mL^-1。结论 番薯藤醇提物对痤疮丙酸杆菌存在体外抑制作用,其有效成分主要集中于石油醚和正丁醇部位。     

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.     

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.     

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.