盐酸阿比朵尔微乳的制备及其质量评价

目的:研制阿比朵尔微乳并对其质量进行评价。方法:选用肉豆蔻酸异丙酯作为油相,蓖麻油聚氧乙烯醚-40、聚山梨酯-20和聚山梨酯80-司班20(质量比为49∶51)分别作为表面活性剂,乙醇、正丁醇和异丙醇作为助表面活性剂。再通过滴定法制备伪三元相图的基础上,根据相图优选处方,分别考察微乳制剂的稳定性、形态粒径;用高效液相色谱(HPLC)法测定微乳中阿比朵尔的含量。结果:以蓖麻油聚氧乙烯醚-40为表面活性剂和乙醇作为助表面活性剂形成微乳系统。阿比朵尔微乳稳定,透射电镜下呈圆球形,分布均匀,平均粒径为28.4nm,呈Gauss分布。用RP-HPLC法测定回收率为100.18%,RSD为0.51%(n=6)。结论:采用微乳作为药物载体制备口服阿比朵尔微乳,为开发阿比朵尔微乳新型口服制剂提供了依据;HPLC检测方法可靠,重复性好。     

尼莫地平微乳的制备及质量评价

目的:研究尼莫地平微乳的制备和质量评价.方法:考察尼莫地平在不同油相、乳化剂和助乳化剂中的平衡溶解度,并通过滴定法绘制伪三元相图,确定最优的Km值和处方,分别考察载药微乳的外观、稳定性、形态和粒径大小.用高效液相色谱法测定微乳中尼莫地平的包封率和载药量.结果:尼莫地平微乳为澄清或略带乳光的淡黄色液体,稳定,透射电镜下呈圆球形,分布均匀.平均粒径18.2 nm,呈Gauss分布.微乳经0.9%氯化钠注射液和5%葡萄糖注射液稀释50倍后,外观、pH值、载药量、粒径均无明显变化,高效液相色谱法测定包封率为97.62%,载药量为0.402 g·L-1.结论:微乳能提高尼莫地平的溶解度,微乳制剂质量稳定,易于制备.     

青藤碱微乳的相图研究及质量控制

目的:研究青藤碱微乳的处方、制备,并建立其含量测定方法。方法:通过滴定法绘制伪三元相图,根据相图优选处方,并初步考察青藤碱微乳的稳定性、粒径分布和理化性质。用HPLC法测定微乳中青藤碱的含量。结果:青藤碱微乳稳定,平均粒径为35.67nm,多分散指数0.237。HPLC线性关系良好,平均回收率为99.33%,RSD为0.91%(n=9)。结论:该处方设计合理,制剂稳定,易于制备。含量测定方法可靠,重复性好。     

苦杏仁苷自微乳的制备及理化性质的研究

目的 制备苦杏仁苷自微乳,并进行初步质量评价研究。方法 通过平衡溶解度的测定和伪三元相图的绘制筛选苦杏仁苷的最佳处方,并对苦杏仁苷自微乳的粒径、多分散系数、稳定性进行评价。结果 苦杏仁苷自微乳的最优处方为Peceol/MCT(1︰1)-乳化剂OP-1,2-丙二醇=45%︰40%︰15%,载药量为6 mg·mL^-1。所得苦杏仁苷自微乳平均粒径为(113.3±0.8)nm,多分散系数为(0.171±0.007),离心稳定性良好。结论 优选处方稳定可行,制备的苦杏仁苷自微乳粒径均匀,稳定性良好。     

星点设计-效应面法优化依托泊苷自微乳化释药系统

目的 研制稳定的依托泊苷自微乳制剂并评价其质量.方法 通过溶解度试验、处方配比、三元相图的绘制及星点设计-效应面法的优化,以粒径、溶解度和zeta电位为指标,筛选各组分的最佳组合和处方配比,并对依托泊苷自微乳的理化性质和体外溶出进行测定.结果 依托泊苷自微乳最佳处方为:依托泊苷(2.0％)、Capryol 90(15.1％)、Cremophor RH40(30.4％)、Transcutol HP(52.5％),平均粒径为18.31 nm,自乳化时间＜1min,乳化后载药量＞ 25 mg· mL-1.结论 制备的依托泊苷自微乳稳定性好,载药量高.     

丹皮酚自微乳处方设计研究

目的 研究丹皮酚自微乳的处方设计.方法 采用测定溶解度,绘制伪三元相图和星点设计法筛选及优化处方.结果 以油酸乙酯(EO)为油相、聚氧乙烯辛基苯基醚(OP-10)为乳化剂、二乙二醇单乙基醚(HP)为助乳化剂,比例为24.47％∶50.35％∶25.18％时能形成稳定的丹皮酚自微乳.结论 丹皮酚自微乳处方设计方法简单,结果可靠,性质稳定.     

肝靶向去甲斑蝥素微乳的研究

目的考察去甲斑蝥素(NCTD)微乳的形态、粒径分布及生物安全性，研究去甲斑蝥素微乳及其注射液在小鼠体内的组织分布、药代动力学和体外药效学。方法用气相法测定小鼠体内去甲斑蝥素含量。数据用3P87处理，得到各主要药代动力学参数。采用体外细胞毒性和体内全身急性毒性试验方法，评价去甲斑蝥素微乳的抗肿瘤活性及其生物安全性。结果微乳平均粒径为(44±9) nm。血浆中成分及制剂中辅料不干扰去甲斑蝥素测定。小鼠静脉注射去甲斑蝥素微乳及其去甲斑蝥素注射液后的药-时曲线均符合二室模型。去甲斑蝥素微乳的药代动力学研究表明，在同剂量条件下，NCTD微乳可在体内较长时间保持较高浓度，即可在一定程度上延长体内循环时间；微乳及注射液的AUC，MRT，T_1/2分别为(29.7±0.9)，(9.25±0.09) mg·h·L^-1，(110±11)，(86.7±0.8)，(103±12)，(42±4) h，NCTD微乳改变NCTD注射剂在小鼠体内的药时曲线和血药浓度的高低，其消除T_1/2和MRT比其注射剂分别增加了2.48和1.27倍，AUC增加了3.21倍；NCTD微乳在肝、肾中的靶向指数分别为0.43和0.12。去甲斑蝥素微乳的生物安全性与其市售注射液比较无显著性差异。结论去甲斑蝥素微乳较去甲斑蝥素注射液增强了药物的肝靶向性，降低了肾脏分布，在一定程度上延长药物在小鼠体内的循环时间。     

苦参碱口服微乳的制备及含量测定

目的制备苦参碱口服微乳,并对微乳进行含量测定和理化性质考察。方法通过滴定法绘制伪三元相图,考察不同因素对微乳区域的影响,筛选合适的微乳处方;采用稀释法和染色法鉴别微乳的类型。结果确定了油酸乙酯-cremophor EL-无水乙醇-蒸馏水的苦参碱微乳,所制备微乳为O/W型;理化性质:pH值为8.23、平均粒径为61.3 nm、黏度为0.022 mPa.s、电导率为0.183 2 S.m-1z、eta电位为-3.72 mV;HPLC法测定微乳中苦参碱的平均质量浓度为39.94 g.L-1。结论所制备的苦参碱微乳粒径较小,分布均匀,理化性质稳定,为进一步研究奠定了基础。     

o/w型、w/o型葛根素口服微乳的制备及质量评价

目的研制o/w型、w/o型葛根素口服微乳制剂并进行质量评价。方法通过相图研究进行处方筛选,并考察最大载药量。对制备的o/w型、w/o型微乳的性质进行考察。结果得到空白微乳的最终处方(重量比)为:o/w型微乳:RH∶1,2-丙二醇∶EO∶水=12.6∶6.3∶2.1∶79.0;w/o型微乳:PC∶无水乙醇∶EO∶水=45∶22.5∶27.5∶5。葛根素含量均为30 mg.mL-1,平均粒径分别为23.4和46.2 nm。结论o/w型、w/o型微乳均能显著提高葛根素溶解度,且制备简单,质量稳定。     

葛根素自微乳的制备及其质量控制

目的制备葛根素自微乳给药系统并建立其质量评价方法。方法以乳化剂OP-10、CremophorRH40、Transcutol P制备葛根素自微乳给药系统,考察其外观、Zeta电位、粒径分布及稳定性;采用高效液相色谱法建立葛根素自微乳的质量评价方法。结果所得自微乳稳定性良好,平均粒径为32．31nm,电动电势为-19．98mV（／Z=3）。葛根素的HPLC分析线性范围为0．213—3．195μg;平均回收率为100．25％（n=9）,RSD=0．49％。结论本制剂制备工艺简便,质量稳定可控,符合良好的身微乳制剂的要求。     

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.     

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.