辅酶Q10亚微乳注射剂的制备及其性质研究

目的对静脉注射用辅酶Q10亚微乳剂的处方工艺进行研究,并对其体外理化性质进行考察。方法以乳剂粒径、稳定常数为评价指标,采用正交设计对制剂处方进行优化,用高压均质法制备辅酶Q10亚微乳。结果按照优化的处方工艺制备的辅酶Q10亚微乳平均粒径为(176.4±15.2)nm,zeta电位为(-35.93±8.13)mV,40℃下考察6个月,理化性质稳定。结论该处方工艺可行,所制备的辅酶Q10静脉注射亚微乳剂具有较高稳定性,解决了辅酶Q10的水溶性问题。     

姜黄素自微乳化释药系统的制备与评价

目的研制姜黄素自微乳化释药系统(Cur-SMEDDS)并对其理化性能、稳定性等进行评价。方法通过溶解度实验和伪三元相图筛选SMEDDS组分;采用星点设计和效应面法优化处方研制Cur-SMEDDS,并对其形态、粒径、理化参数及稳定性进行考察。结果优化后Cur-SMEDDS的处方为油相MCT∶乳化剂Cremophor RH40∶助乳化剂甘油=22.5∶49.3∶28.2,其平均载药量为1.0%,澄清度好,微乳粒子形态主要为圆球形,平均粒径为40.83 nm,稳定性良好。结论所制制剂理化性质稳定,制备工艺简单,质量稳定,容易控制。     

辅酶Q10自微乳化释药系统的制备及稳定性研究

筛选辅酶Q10自微乳化释药系统(CoQ10-SMEDDS)的处方并考察其稳定性。通过溶解度实验筛选油相、表面活性剂和助表面活性剂;绘制三元相图,以乳化时间、乳化效果和乳滴粒径大小为指标,确定最佳处方及配比;考察CoQ10-SMEDDS在各处理条件下的稳定性。CoQ10-SMEDDS最佳处方配比为油酸乙酯∶Cremo-phor EL∶PEG400为18∶35∶7,自乳化形成平均粒径为30.9 nm的微乳。所制备的CoQ10-SMEDDS对CoQ10的溶解度大,自乳化效果好,乳滴粒径小,稳定性高。     

尼莫地平自微乳化释药系统的研制

目的:研制尼莫地平(nimodipine,NM)自微乳化释药系统(SMEDDS).方法:以溶解度,相容性试验、自乳化效率及伪三元相图法筛选最佳油相、表面活性剂及助表面活性剂;以星点设计-效应面法优化处方;对NM-SMEDDS分散后粒径、体外溶出度及初步稳定性进行考察.结果:经处方筛选和星点效应面法优化得出最佳处方为:Captex200P,Cremophor EL,Labrosol 分别为油相,乳化剂和助乳化剂,比例为30:47:23;NM-SMEDDS的粒径分别为33.8±3.42 nm,1h累积溶出百分率为98.83％,约为市售片剂的3.84倍;经高温(60℃)、低温(4℃)、强光(4 500±500) Lx考察10 d,除强光可引起NM含量降低外,其他各项指标均无明显变化.结论:该处方及工艺筛选、优化法简便可行,容易控制,制备得到的NM-SMEDDS体外溶出度显著增加,稳定性较好,为进一步研发尼莫地平新制剂提供了理论和试验基础.     

银杏酮酯口服自微乳化给药系统的制备

研究制备银杏酮酯口服自微乳化给药系统。采用平衡溶解度方法筛选乳化剂与助乳化剂; 采用伪三元相图法制备微乳; 采用正交法优化处方组成; 并考察自微乳化制剂的乳化效率、溶出度、稳定性与药动学研究等。结果表明, 由肉豆蔻酸异丙酯IPM、聚氧乙烯蓖麻油Cremophor EL、丙二醇与银杏酮酯组成的自微乳化给药系统遇水可自发形成粒径为20～50 nm的稳定微乳。自微乳化给药系统的乳化效率与溶出快, 且制剂稳定性高, 能提高生物利用度。制备的银杏酮酯口服自微乳化给药系统稳定有效。     

辅酶Q_(10)亚微乳的制备及理化性质考察

目的:制备辅酶Q10亚微乳,并考察其稳定性及理化性质。方法:设计正交试验优选辅酶Q10亚微乳的处方及制备工艺并制备乳剂,以高效液相色谱法测定其含量及包封率,考察其粒径、ζ电位、pH值及稳定性等。结果:辅酶Q10亚微乳的最佳处方工艺为大豆油∶中碳链甘油三酸酯=1∶2,大豆磷脂∶泊洛沙姆188=3∶1,高速剪切乳化时间10min,制备温度60℃。所制备的乳剂包封率3批样品平均值为98.07%,ζ电位为—28.4mV,平均粒径为168nm。该制剂贮存时应避免光照和冻融,在4℃条件下稳定性较好。结论:所制备的辅酶Q10亚微乳满足静脉注射用制剂要求。     

硫普罗宁眼用原位凝胶的研制

目的筛选硫普罗宁温度敏感型眼用原位凝胶最优处方,提高药物在角膜前的滞留时间。方法以胶凝温度、凝胶溶蚀量、体外药物释放度、离体角膜透过性为考察指标,设计和优化处方;以家兔为受试动物,考察硫普罗宁在角膜的滞留时间、刺激性及稳定性。结果含有质量分数0.2%透明质酸钠的硫普罗宁原位凝胶具有适宜的胶凝温度和一定的缓释作用,其角膜表观透过系数为15.43 cm.s-1,角膜前滞留时间为130 min;刺激性、稳定性符合眼用制剂要求。结论硫普罗宁眼用原位凝胶延长了药物在眼部的作用时间,达到了缓释的目的。     

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。     

星点设计效应面法优化非洛地平自微乳给药系统

目的 设计非洛地平自微乳给药系统，并进行体外评价。方法 测定非洛地平的溶解度，考察油相与乳化剂的相容性，绘制伪三元相图，初步设计自微乳处方；运用星点设计效应面法优化自微乳处方；评价自乳化性能和体外溶出行为。结果 非洛地平自微乳处方：油相LABRAFIL M 1944CS为4.4 g，乳化剂Cremophor EL35为5.5 g，助乳化剂PEG400为1.1 g，非洛地平1.0 g；自乳化效率高，乳液澄明稳定，平均粒径为30.4 nm，PDI为0.16；水中溶出很快，5 min内平均溶出度>85%，30 min达99%，24 h后乳滴依然稳定。结论 星点设计-效应面法优化的非洛地平自微乳，自乳化性能高，乳液稳定，显著提高非洛地平的体外溶出度。     

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。     

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.