胰岛素自复乳化给药系统的制备与质量评价

目的 制备胰岛素自复乳化给药系统并评价其质量.方法 以自复乳的微观结构、体积平均粒径和自乳化速率为评价指标筛选较优处方,并考察其稳定性及体外释放特性.结果 优选的处方组成为内水相-中链甘油三酸酯-亲脂乳化剂-亲水乳化剂(21:24:6:9),平均粒径为6.74±0.55 μm,包裹进入复乳的胰岛素为86.8％±8.2％;于25℃静置30 d后,其显微形态及平均粒径等指标均未见明显变化;8h后胰岛素在体外的累计释放量达约80％,具一定缓释作用.结论 成功制备了胰岛素自复乳化给药系统,可为蛋白多肽类药物的口服给药提供新的方法.     

处方因素对亚微乳物理稳定性的影响

目的 初步探讨亚微乳处方中乳化剂及油相因素对其物理稳定性的影响.方法 采用高速剪切分散和高压均质乳化工艺制备亚微乳,单因素试验法考察处方中乳化剂与油相对亚微乳物理稳定性的影响;以平均粒径、D50值、D99值及ζ电位为指标,考察不同处方中亚微乳灭菌前后的物理稳定性,并留样观察其长期稳定性.结果 泊洛沙姆188与中链油相互配伍不能得到性质稳定的亚微乳,且单独以泊洛沙姆188为乳化剂的各处方制剂长期放置后平均粒径明显增大;聚乙二醇硬脂酸酯( HS15)与各油相结合制得的亚微乳均较稳定,长期放置后各项指标基本不变;聚山梨酯80与大豆油-中链油(1∶1)混合油或大豆油配伍制成的亚微乳在灭菌后产生较大粒径的乳滴,而与中链油相配伍可制得粒径较小且均匀分散的体系;蛋磷脂E80单独作为亚微乳乳化剂,乳化效果欠佳.结论 大豆油、中链油及混合油与不同性质的乳化剂相互作用可共同影响亚微乳的粒径,但不同制剂的处方对亚微乳ζ电位无显著影响.     

红霉素自乳化制剂处方研究

目的研究红霉素自乳化制剂(EM-SMEDDS),探求其最佳处方配比。方法测定红霉素在各种油相、乳化剂和组乳化剂中的溶解度,选择溶解度高者备用;采用滴定法绘制了油-乳化剂/助乳化剂-水体系伪三元相图,确定处方组成比例;考察加料顺序对EM-SMEDDS平均粒径和粒径分布的影响。采用均匀设计考察制备温度、混合乳化剂各组成比例、载药量与油相所占比例对平均粒径、粒径分布的影响,采用平均粒径、粒径分布、分散时间为评价指标,筛选出EM-SMEDDS的优化处方。结果处方中油相十四酸异丙酯(IPM)、聚氧乙烯蓖麻油(Cremophor EL)与聚乙二醇-8-甘油辛酸/癸酸酯(Labrasol)组成的混合乳化剂可以获得较好的乳化效果。制备方法为首先制备混合乳化剂,其次将混合乳化剂与油相混匀,最后加入药物,所得EM-SMEDDS乳滴平均粒径小于50 nm。结论红霉素自乳化制剂的最佳处方比例,以IPM为油相,油相与混合乳化剂质量比为3∶7,混合乳化剂中LAS与Cremophor E质量比为7∶13,载药量为10%。     

氟苯尼考自微乳制剂的研制

目的 制备了氟苯尼考自微乳.方法 通过测定氟苯尼考溶解度及绘制伪三相图,以成乳后的粒径、自乳化时间和色泽为指标,筛选处方中的油相、乳化剂和助乳化剂.结果 结果表明,氟苯尼考、油相Labrafil、乳化剂Cremophor EL、助乳化剂乙醇,四者比例为0.1:4:5:1时可获得较好的自乳化效果.制品平均粒径25nm,自微乳化可在3min内完全,在0.1mol/L盐酸中10～15min完全溶出.     

正交试验筛选影响雄黄乳膏剂基质的主要因素

目的:筛选影响雄黄乳膏剂基质的主要因素。方法:以凡士林在油相中的比例、乳化剂的用量、表面活性剂的亲水亲油平衡值(HLB)及乳化温度为考察因素,以基质的稳定性、伸展性和流变学性质为评价指标,采用正交试验筛选影响雄黄乳膏剂基质的主要因素。结果:影响雄黄乳膏剂基质的因素大小为凡士林占油相的比例>乳化剂用量>表面活性剂的HLB值>乳化温度。结论:所选因素可为后续进行处方、工艺筛选提供参考。     

伪三元相图法研究芦丁自微乳化释药系统的制备工艺

摘 要 目的：应用伪三元相图法优化芦丁自微乳化释药体系的处方构成。 方法: 对油相、乳化剂、助乳化剂通过溶解度试验进行初步筛选,应用水滴定法绘制伪三元相图,考察不同配方的相图行为,确定芦丁的最佳自微乳处方构成。 结果: 优化的芦丁自微乳化释药系统的处方组成为油酸 聚氧乙烯40氢化蓖麻油 无水乙醇,质量比为23∶36∶12,制备的自微乳和载药微乳澄清透明。 结论:由伪三元相图法筛选的处方制备而成的自微乳化释药系统能显著提高芦丁的溶解度。     

罗红霉素自乳化制剂的制备及体外评价

目的制备罗红霉素自乳化制剂,并初步探讨其体外质量评价。方法通过测定药物在不同油相中的溶解度,确定油相与各种乳化剂(助乳化剂)的配伍对自乳化效率的影响;通过绘制伪三相图,筛选罗红霉素自乳化制剂的最佳处方;考察该制剂水稀释液的微乳外观、粒径和乳化时间。结果自乳化制剂处方为罗红霉素:肉豆蔻酸异丙酯:Tween80(甘油)为3∶3∶4,该制剂稀释50倍后仍为澄清透明液体,粒径约75nm,呈正态分布,乳化时间约10min。结论罗红霉素自乳化制剂制备简单,质量稳定,能显著提高药物的溶解度。     

水飞蓟素自微乳的制备

制备了水飞蓟素自微乳.通过测定水飞蓟素溶解度及绘制伪三相图,以成乳后的粒径、自乳化时间和色泽为指标,筛选处方中油相、乳化剂、助乳化剂.结果表明,含5%水飞蓟素、油相为MCT、乳化剂为CremophorRH40、助乳化剂为1,2-丙二醇,四者比例为0.5:5:3.6:0.9时可获得较好的自乳化效果.制品平均粒径为68.6nm,自微乳化可在3min内完全,在0.1mol/L盐酸中10～15min完全溶出.     

4-氨基-2-三氟甲基苯基维甲酸酯自微乳胶囊的研制

目的制备4-氨基-2-三氟甲基苯基维甲酸酯固体自乳化制剂,以解决该药水溶性差的问题,提高药物胃中溶出度和口服生物利用度。方法通过伪三元相图法考察不同乳化剂、助乳化剂和油相形成微乳的能力和区域,制备自微乳。然后采用mix-ture design方法进行处方优化,并对其乳化后粒径、制剂综合评分和载药量进行考察。结果制备出的最佳处方(含HS1570%,PEG400 10%,油酸乙酯20%)自乳化后粒径在30 nm左右,体外溶出10 min即可溶出80%以上。结论该处方制备出的ATPR固体自微乳可用于提高其溶出速度。     

松萝酸自微乳的处方优化及质量评价

目的:制备松萝酸自微乳,优化其处方,评价其质量。方法:采用乳化法,以中链甘油三酯-单亚油酸甘油酯(1∶1,m/m)为油相,聚氧乙烯氢化蓖麻油为乳化剂,二乙二醇单乙基醚为助乳化剂,制备松萝酸自微乳。在溶解度试验和伪三元相图的基础上,以自乳化时间(t)、透光率(T)、药物平衡溶解度(S)、5 min和60 min时药物的累积溶出度(Q_(5 min)、Q_(60 min))作为评价指标,采用星点设计-响应面法优化微乳处方中油相占比和乳化剂-助乳化剂质量比(K_m)。同时对最优处方进行验证试验,并对其形态、粒径、载药量、溶出度等进行考察。结果:最优处方中油相占比为25%、K_m为2.0,即处方中混合油相、乳化剂、助乳化剂的质量比分别为25%、50%、25%;最优处方所制松萝酸自微乳的t、T、S、Q_(5 min)、Q_(60 min)分别为1.96 min、87.67%、5.67 mg/g、66.58%、76.73%(RSD均小于3%,n=3),与预测值的相对误差均小于4%(n=3)。松萝酸自微乳经水稀释后为球形乳滴,乳化后平均粒径为39.4 nm,平均载药量为4.55 mg/g,在p H 6.8磷酸盐缓冲液中Q_(90 min)为99.58%(n=3)。结论:所制松萝酸自微乳的质量符合相关要求。关键词松萝酸;自微乳;伪三元相图;星点设计-响应面法;质量评价     

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.     

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.     

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.     

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.     

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.