蛇黄凝胶与蛇黄散体外释放与透皮特性比较研究

目的 比较蛇黄散与其改良剂型蛇黄凝胶的体外释放度与透皮特性。方法 分别采用微孔滤膜与离体小鼠鼠皮及改进的Franz扩散池进行体外释放与透皮试验,以HPLC法定量测定蛇黄凝胶与蛇黄散中君药—蛇鳞草中triphyllin A与大黄中大黄酸的量为指标,测定2种制剂的体外释放量(Qs)、释放率(Q)、透皮量(Ls)与透皮率(L),并采用3种方程对蛇黄凝胶的体外释放与透皮结果进行模拟拟合。结果 蛇黄凝胶中triphyllin A 24 h的Qs=72.188 5μg·cm^-2,Q=30.458 3%,Ls=52.086 7μg·cm^-2,L=21.976 8%,大黄酸24 h的Qs=15.220 0μg·cm^-2,Q=9.429 0%,Ls=13.545 6μg·cm^-2,L=8.3917%,蛇黄散中triphyllin A 24 h的Qs=45.239 5μg·cm^-2,Q=17.124 9%,Ls=27.043 4μg·cm^-2,L=10.237 0%,大黄酸2...     

氟比洛芬压敏胶分散型贴剂的制备及体外经皮渗透性考察

目的:研制氟比洛芬压敏胶分散型贴剂并考察其体外经皮渗透性。方法:将氟比洛芬及各种促渗剂直接溶于压敏胶中制备压敏胶分散性贴剂,采用卧式双室扩散池,研究其体外经皮渗透行为。结果:由Duro-Tak 87-9301型压敏胶制备的贴刺具有较好的稳态渗透速率。5%氯酮与10%豆蔻酸异丙酯合用对氟比洛芬促渗效果明显,经皮渗透速率为（3.35±0.53）μg·cm^-2·h^-1,促渗倍率达2.68倍。贴剂中氟比洛芬的含量由5%增加到10%,经皮渗透速率明显增大,含量增加到15%和20%时,渗透速率无明显变化。结论:所得处方中各因素的组合有利于氟比洛芬的经皮吸收。     

青藤碱凝胶剂的制备及体外渗透性能研究

目的：制备青藤碱凝胶剂，研究其透皮渗透性能。方法：以卡波姆980为辅料制备青藤碱凝胶剂．采用改良Franz扩散池，以离体大鼠皮肤为透皮屏障，用HPLC法测定青藤碱的累积渗透量。结果：实验结果表明，青藤碱凝胶剂体外透皮释药方程为Q=65.852 t=55．677（r=0．9919），10h累积渗透量为638μg／cm^2。结论：青藤碱凝胶剂为一种新颖的控释型外用制剂。凝胶剂中的青藤碱以一级动力学经皮渗透。     

雷公藤甲素微乳凝胶的制备及体外透皮性能考察

目的：制备雷公藤甲素微乳凝胶并考察其理化性质及体外透皮扩散特性。方法：以混合乳化剂Tween80/Labrasol 1：4,助乳化剂无水乙醇,油相：油酸/Gemseal402：3,水相,泊洛沙姆407制备雷公藤甲素微乳凝胶。测定微乳的外观形态、粒径分布、pH、稳定性等理化性质。采用改良的Franz扩散池法,比较雷公藤甲素微乳凝胶和乳膏的经皮渗透特性。结果：制备的微乳澄清透明,呈现轮廓分明分布均匀的球形,平均粒径（27.8±0.3） nm,且PdI（0.2±0.004）,稳定性等理化性质均较好。雷公藤甲素微乳凝胶和雷公藤甲素乳膏24h单位面积累积渗透量分别为（4.33±0.17）、（7.07±0.16） μg·cm^-2,2种剂型中雷公藤甲素的渗透行为均符合Higuchi方程,透皮速率分别为1.9871,0.9149 μg·cm^-2·h^-1。结论：雷公藤甲素微乳凝胶和乳膏均具有缓释释药效果。雷公藤甲素微乳凝胶显著提高了雷公藤甲素的经皮渗透量及透过速率,且较乳膏强,可为雷公藤甲素经皮给药制剂选择提供参考。     

睾酮凝胶体外透皮吸收的特征

目的建立睾酮凝胶剂体外透皮吸收试验方法并考察其体外经皮吸收特性。方法采用单室扩散池,大鼠皮肤作为试验材料,以乙醇-生理盐水（3：7,V/V）为接收液,恒温32℃,分别于设定时间取样,用HPLC法测定接受液中睾酮含量。结果累积渗透量Q（μg·cm^-2）对t（h）进行线性回归,方程为Q=108．7069t＋65．4318,r=0．9968,求算透皮速率常数J为108．7μg·cm^-2·h^-1。结论所建立的体外透皮吸收模型和方法可以较好评价睾酮凝胶剂的体外透皮吸收特性。     

余甘子软膏的制备及冰片促渗作用考察

目的:制备余甘子软膏并考察冰片对余甘子软膏经皮渗透的影响。方法:采用L₉(3⁴)正交试验,以耐寒试验、耐热试验、离心试验及感官评价为指标优选余甘子软膏的制备工艺,并进行皮肤刺激性考察;采用Franz扩散池法,以没食子酸、柯里拉京的体外透皮为指标,通过HPLC考察不同含量冰片对余甘子软膏的促渗作用;并对余甘子软膏经皮渗透及体外释放规律进行探究。结果:余甘子软膏的最佳处方为石蜡油0.5 g,凡士林1 g,羊毛脂5 g,硬脂酸3 g,纯净水1 g,丙三醇1 g,余甘子浸膏4 g;5%的冰片对余甘子软膏中没食子酸和柯里拉京的促渗效果最佳,24 h时的经皮累计渗透量分别为1.163 6,0.073 8 mg·cm^-2,经皮吸收速率为0.046 3,0.003 1 mg·cm^-2·h^-1,增渗倍数为1.738 0,1.822 5;24 h时余甘子软膏中没食子酸和柯里拉京的累计释放率分别为58.91%,45.47%;含5%冰片的余甘子软膏中没食子酸和柯里拉京的经皮渗透均符合一级方程,体外释放分别符合Higuchi方程、Hixson-Crowell方程;单次给药1,24 h后均无明显皮肤刺激性。结论:制得的余甘子软膏具有良好的性状及体外经皮渗透、体外释放性能,无明显皮肤刺激性。     

黄连解毒汤传统饮片汤剂与配方颗粒汤剂中黄芩苷的药动学的比较

目的:比较黄连解毒汤传统饮片汤剂与配方颗粒汤剂中黄芩苷药动学行为的一致性。方法:大鼠分别灌胃低、中、高剂量两种汤剂后,采用HPLC法测定血浆中黄芩苷含量,采用DASS 2.1.1软件计算相关药动学参数。结果:灌胃低、中、高剂量两种汤剂后,大鼠血浆中黄芩苷C_max分别为:0.25和0.27μg·ml^-1,0.30和0.31μg·ml^-1,0.40和0.45μg·ml^-1;AUC分别为:2.48和2.59μg·h·ml^-1,3.59和3.71μg·h·ml^-1,5.71和6.16μg·h·ml^-1;T_max为3.0和3.0 h,3.0和3.0 h,4.0和4.0 h;Vd分别为:（2 822.4±118.2）和（2 998.9±255.6）L·kg^-1,（3 102.6±176.3）和（3 405.3±213.8）L·kg^-1,（4 231.2±155.4）和（4 486.0±187.0）L·kg^-1;CL分别为:（2 923.3±215.6）和（2 767.5±184.6）L·h^-1·kg^-1,（4 921.7±225.4）和（4 040.8±246.7）L·h^-1·kg^-1,（5 255.9±189.7）和（4 868.7±260.4）L·h^-1·kg^-1;t_1/2分别为:（3.88±0.41）和（3.71±0.37）h,（4.19±0.36）和（3.73±0.51）h,（5.54±0.38）和（5.80±0.54）h。结论:两种汤剂中黄芩苷的药动学参数差异无统计学意义。     

奥扎格雷鼻用凝胶的制备与质量控制

目的:制备奥扎格雷鼻用凝胶并建立其质量控制方法。方法:以无毒、无刺激的壳聚糖为凝胶基质制成奥扎格雷凝胶剂,采用HPLC法测定其含量。结果:所制制剂为淡黄色、半透明状凝胶;奥扎格雷检测浓度的线性范围为10.46～83.68μg·ml^-1（r=0.999 9）,平均回收率为96.88%（RSD=1.10%）,3批样品经留样试验考察,质量稳定。结论:该制剂处方合理,制备工艺简便,含量测定准确,制剂质量稳定     

盐酸利多卡因脂质体凝胶剂的体外透皮扩散研究

目的 对盐酸利多卡因(lidocaine hydrochloricde,LDH)脂质体凝胶剂体外透皮量、皮肤层滞留量进行评价.方法 超声法制备LDH脂质体,再用卡波普为基质制成凝胶剂;以体外经皮渗透释药法,比较LDH脂质体凝胶剂及LDH凝胶剂中的经皮渗透规律.结果 平均包封率为(83.4±1.81)%;LDH 凝胶剂的渗透符合Higuchi方程,其中脂质体凝胶剂24h内药物渗透速率为770.32μ g·h-1,明显高于游离药物凝胶渗透率280.01μg·h-1.结论 载药脂质体凝胶剂可显著促进药物经皮吸收,为经皮吸收药物的理想载体.     

黄连膏体外透皮吸收及抗炎活性研究

目的：采用改良的Franz透皮扩散池考察黄连膏中主要活性成分的体外透皮吸收情况,同时对黄连膏的抗炎活性进行初步研究。方法：选用改良Franz透皮扩散池,接收液为30%乙醇生理盐水,以小鼠背部皮肤为透皮材料,采用紫外分光光度法及高效液相色谱法测定透皮接收液中盐酸小檗碱、芝麻酚、芝麻素及总生物碱的含量,计算透皮吸收动力学参数,考察黄连膏中抗炎活性成分的累计透过量及吸收规律;取30只SPF级小鼠,随机分为5组,即模型组、醋酸地塞米松乳膏组（100 mg·kg^-1）、黄连膏高剂量组0.075 g·g^-1（生药/膏）、黄连膏中剂量组0.15 g ·g^-1（生药/膏）、黄连膏低剂量组0.3g ·g^-1（生药/膏）,每组6只。阳性对照组为醋酸地塞米松乳膏组,进行2,4-二硝基氯苯（DNCB）致小鼠耳肿胀实验,观察黄连膏对炎症的抑制作用。结果：黄连膏中芝麻酚、盐酸小檗碱、芝麻素及总生物碱在24 h内的累积透过量分别为2.82,4.10,0.78,16.54 μg·cm^-2;稳态透皮速率（J_s）分别为0.125 2,0.181 4,0.034 2,0.745 7 μg·cm^-2·h^-1;与阳性对照组比较,黄连膏高剂量组显著抑制DNCB所致小鼠耳肿胀。结论：黄连膏具有良好的体外透皮性能及抗炎活性,24 h内单位面积累积透过量随药物中主要有效成分含量升高而增加,经皮渗透行为符合零级动力学方程。     

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.