诺氟沙星阴道用温度敏感原位凝胶的制备及体外释放度研究

摘 要 目的：制备诺氟沙星阴道用温度敏感原位凝胶,并考察其体外药物释放行为。方法: 以泊洛沙姆为基质,采用冷溶法制备诺氟沙星阴道用温度敏感原位凝胶,考察泊洛沙姆407与泊洛沙姆188的用量对胶凝相变温度的影响,采用星点设计 效应面法优化其处方,并考察其体外药物释放行为。结果: 在一定浓度范围内,随着泊洛沙姆407用量的增大胶凝化温度逐渐降低,随着泊洛沙姆188用量的增大胶凝化温度逐渐升高,通过优化得到诺氟沙星阴道用温度敏感原位凝胶的最佳处方为：泊洛沙姆407的浓度为20.6%（w/v）,泊洛沙姆188的浓度为5.7%（w/v）,在温度为36.5 ℃以上可发生胶凝。药物在温度敏感原位凝胶中呈持续缓慢释放,6 h药物的累积释放度为87.5%±5.4%。结论: 诺氟沙星阴道用温度敏感原位凝胶具有很好的温度敏感性,可以延缓药物释放,有望开发成为一种新型阴道给药制剂。     

正交试验优选甲硝唑阴道用温敏凝胶的处方工艺

摘 要 目的：优选甲硝唑温敏凝胶的处方工艺。方法: 以胶凝温度和24 h累积释放度为评价指标,采用正交试验考察泊洛沙姆407（P407）、泊洛沙姆188（P188）、海藻酸钠和聚乙二醇4000（PEG4000）用量4个因素,筛选温敏凝胶的最佳处方。采用HPLC法测定甲硝唑温敏凝胶的体外释放度,并与市售普通凝胶剂进行比较。结果: 温敏凝胶最佳处方组成为： 20% P407,18% P188,0.1%海藻酸钠,1.5% PEG4000。制得的甲硝唑温敏凝胶累积释放度高,胶凝温度适宜。与市售凝胶相比,阴道滞留性明显提高。结论:该处方设计合理,制备工艺可行。     

温控型胰岛素液体肛门栓药剂学研究

目的 温控型胰岛素液体肛门栓药剂学性质的研究。 方法 采用正交试验法,以形成凝胶时间、胶凝强度、生物黏附力、黏度、胶凝温度作为评价指标,对处方中的泊洛沙姆407和泊洛沙姆188的比例、壳聚糖质量分数和pH值3个因素进行考察,确定最优处方工艺;测定最优处方液体栓剂的胶凝强度、生物黏附力、黏度、胶凝温度。 结果 泊洛沙姆407:泊洛沙姆188(15:25),壳聚糖质量分数0.4%,pH值为5±0.2。 结论 经验证结果良好,液体栓剂强度及生物黏附力良好。     

星点设计-效应面法优化贝美前列素眼用温度敏感原位凝胶的处方工艺

目的 使用星点设计-效应面法探讨贝美前列素眼用温度敏感原位凝胶的处方组成，并考察其体外释放度。方法 以泊洛沙姆407和188为凝胶基质，用星点设计-效应面法筛选出最佳处方得到合适的胶凝温度，高效液相色谱法测定贝美前列素眼用凝胶的含量，并以无膜溶出模型考察其体外释放度。结果 处方以1%吐温80，0.03%贝美前列素（w/v）、21%泊洛沙姆407（w/v）和2%泊洛沙姆188（w/v）组成能达到最适胶凝温度。体外释放度的考察结果显示药物的释放与时间呈线性关系。结论 本实验制备的贝美前列素眼用温度敏感原位凝胶具有理想的胶凝温度，能够使药物更加持久地附在给药部位，具有给药方便等优点，是一种值得开发并推广使用的眼用制剂。     

N-三甲基壳聚糖包覆司帕沙星纳米脂质体原位凝胶的研制及体外释药研究

摘 要 目的：制备眼用N-三甲基壳聚糖（TMC）包覆的司帕沙星（SL）纳米脂质体原位凝胶（ISG）,并考察其体外释放度。方法: 采用pH梯度法制备SL脂质体,经高压均质至纳米级,用TMC包衣。以胶凝温度为指标,优选ISG基质泊洛沙姆407的最佳浓度,采用冷法制备TMC包覆SL纳米脂质体ISG。对TMC包覆SL纳米脂质体ISG中脂质体的形态、粒径、Zeta电位及包封率进行考察;以TMC包覆SL纳米脂质体为对照,采用无膜溶出模型考察其体外释药特性。结果: 泊洛沙姆407的最佳浓度为25%,在人工泪液中的胶凝温度为23.6 ℃,稀释后的胶凝温度为33.5 ℃。TMC包覆SL纳米脂质体ISG中脂质体形态圆整,平均粒径为（96.8±1.5）nm,Zeta电位为（46.2±1.4）mV,包封率为（76.6±2.4）%,与TMC包覆SL纳米脂质体相比无明显变化。TMC包覆SL纳米脂质体ISG药物释放和凝胶溶蚀均为符合零级动力学特征,且与TMC包覆SL纳米脂质体相比,缓释性更为显著。结论:TMC包覆SL纳米脂质体ISG胶凝温度理想,并可延缓药物释放。     

复方甲硫酸新斯的明眼用原位凝胶的处方工艺研究

目的 筛选用于治疗近视的复方甲硫酸新斯的明眼用原位凝胶处方。方法 温度敏感型凝胶以泊洛沙姆P407和泊洛沙姆P188为基质;离子敏感型凝胶以去乙酰结冷胶为基质;pH敏感型凝胶以卡波姆P934、卡波姆P940和羟丙基甲基纤维素为基质,以胶凝的黏度与成分的相溶性为考察指标,筛选最佳基质处方。采用美国药典溶出度测定法第三法的改良法,作缓释制剂的释放度考察。结果 以温度敏感型的泊洛沙姆P407 24%和P188 10%合用的基质制备复方甲硫酸新斯的明眼用原位凝胶最为适合。结论 本法制备眼用原位凝胶的工艺可行,并具有较好的缓释效果。     

眼用即型凝胶基质的成胶性研究

目的:研究眼用原位凝胶基质的成胶性,并建立温度敏感型、离子敏感型和pH敏感型眼用原位凝胶的基质处方。方法:使用人工泪液,模拟眼部生理条件综合考虑黏度、突跃点等因素来考察各类基质处方的成胶性并筛选基质处方。结果:眼部生理条件下,0.02%卡波姆P934、0.02%卡波姆P940和0.5%羟丙基甲基纤维素(HPMC)-K4M合用、0.45%的去乙酰结冷胶、24%泊洛沙姆P407与10%泊洛沙姆P188合用等三种情况下有合适的成胶性。结论:pH敏感型、离子敏感型、温度敏感型眼用原位凝胶的适用基质处方分别为0.02%卡波姆P934+0.02%卡波姆P940+0.5%羟丙基甲基纤维素(HPMC)-K4M合用、0.45%的去乙酰结冷胶、24%泊洛沙姆P407+10%泊洛沙姆P188合用。     

左氧氟沙星与曲安奈德双载药温敏泪道凝胶的制备及评价

摘 要 目的：制备左氧氟沙星和曲安奈德温敏型双载药泪道凝胶,以期用于泪道阻塞性疾病防治。 方法: 以泊洛沙姆407为基质,泊洛沙姆188为凝胶增强剂,以人工泪液稀释前后的胶凝温度为考察指标,确定合适的凝胶基质处方。再以盐酸左氧氟沙星和醋酸曲安奈德为主药,制备温敏型双载药泪道凝胶,测定凝胶的含药量,并考察凝胶体外溶蚀行为。建立泪道阻塞动物模型,进一步考察凝胶对泪道炎症的作用。 结果: 最佳凝胶基质组成为：泊洛沙姆188浓度为10%,泊洛沙姆407浓度为18%。所制得的温敏型双载药泪道凝胶中,盐酸左氧氟沙星的标示含量为（97.4±0.72）%,醋酸曲安奈德的标示含量为（92.98±0.85）%,体外溶蚀行为持续缓慢,在阻塞局部具有显著的抗炎作用。 结论: 成功制得温敏型双载药泪道凝胶。     

美沙拉嗪温敏液体栓的制备及体外性质考察

摘 要 目的： 研制美沙拉嗪温敏液体栓,并对其体外性质进行考察。方法: 以泊洛沙姆407和188为温敏材料,采用冷法制备美沙拉嗪温敏液体栓;以胶凝温度为评价指标,筛选出两种材料的最佳配比;对美沙拉嗪温敏液体栓的胶凝强度、生物黏附力等性质进行考察,并对其体外溶蚀行为及释药特性进行研究。结果: 泊洛沙姆407及188的最佳配比为20%∶2.5%,此时胶凝温度为（36.9±0.2）℃,胶凝强度为（115.1±3.2 ）s,生物黏附力为（130.7±5.8）×10² dyne·cm^-2;体外释药特性及凝胶溶蚀特性均符合一级动力学特征,且两者相关性良好,显示美沙拉嗪液体栓具有较好的缓释性。结论:美沙拉嗪温敏液体栓制备工艺简单,且具有较好的胶凝性、生物黏附性及缓释性。     

氨来呫诺鼻用温敏凝胶喷雾剂处方优化及质量控制

摘 要 目的： 研制氨来呫诺鼻用温敏凝胶喷雾剂,建立其质量控制方法。方法: 采用冷法工艺制备氨来呫诺鼻用温敏凝胶喷雾剂,以泊洛沙姆407和泊洛沙姆188为基质,并以胶凝温度与成胶前黏度为考察指标,采用星点设计 效应面法对两种基质的用量进行考察;采用HPLC法测定氨来呫诺的含量,参照《中国药典》2010年版相关规定,对氨来呫诺鼻用温敏凝胶喷雾剂的外观、pH、黏度、含量、装量、每瓶总喷次和每喷主药含量进行测定。结果: 泊洛沙姆407和泊洛沙姆188的最佳配比为17.0%和0.9%;凝胶中氨来呫诺含量测定的平均回收率为98.8%,RSD为1.7%（n = 9）;制备的3批样品各项质量指标均符合规定。结论:氨来呫诺鼻用温敏凝胶喷雾剂处方和制备工艺合理可行,质量可控,可进一步研究开发。     

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.