高效液相色谱法测定脂质体中硝酸益康唑的含量及其理化性质的考察

目的:高效液相色谱法测定硝酸益康唑脂质体中药物的含量并考察其理化性质.方法:建立了用色谱预处理柱除磷脂测定脂质体中药物含量的HPLC法,并用此法测定了硝酸益康唑的溶解度和分配系数.结果:此法可以除去大部分磷脂,具有较好的专属性、回收率和精密度;硝酸益康唑在水,生理盐水,20%PEG生理盐水中的溶解度分别为(879.4±42.9),(361.6±23.8),(3006.5±60.4)mg·L,油/水,表皮/水和真皮/水分配系数为45.4,4.82×105和5.31×105.结论:此法适于测定硝酸益康唑脂质体中药物含量;硝酸益康唑对表皮和真皮有较强的亲和力,适于皮肤给药.     

硝酸益康唑纳米乳滴眼剂的制备及理化性质研究

目的:制备硝酸益康唑(ECZ)纳米乳并对其性质进行考察。方法:在制备三元相图的基础上,优选硝酸益康唑纳米乳的最佳处方及制备工艺,并通过形态观察、ξ电位的测定、稳定性的考察等研究了硝酸益康唑的性质。结果:硝酸益康唑纳米乳的最佳处方工艺组合为聚氧乙烯40氢化蓖麻油(PEG-40氢化蓖麻油)/辛酸/癸酸三甘酯(M-812)/水,ξ电位为1.968 mV,平均粒径为64.06 nm。稳定性考察表明纳米乳在强光及高温加速试验中均较稳定。结论:硝酸益康唑纳米乳增加了益康唑的溶解度,而且剂型稳定,HPLC法检测方便。     

硝酸益康唑脂质体凝胶的释放和经皮渗透性研究

目的：比较自制硝酸益康唑脂质体凝胶与市售硝酸益康唑霜剂的离体皮肤渗透性,探讨脂质体作为硝酸益康唑的载体对皮肤的渗透机制。方法：测定硝酸益康唑脂质体的体外释放百分率,采用双室渗透池作为离体皮肤的渗透试验装置,测定硝酸益康唑在接受液内的累计渗透百分数和在皮肤内的滞留百分数。结果：硝酸益康唑脂质体的体外释放速度较慢,其凝胶和霜剂透过皮肤进入接受液中的药物量都很少,累计渗透百分数均小于硝酸益康唑给药量的5%;其凝胶制剂的皮肤层内的滞留百分数（26%）高于其霜剂在皮肤层内的滞留百分数（11%）,2种不同制剂的经皮渗透性均符合Higuchi方程。结论：脂质体有促进药物进入皮肤的能力,而药物进入血循环的量并不增加。     

天蛭方对阴虚阳亢兼瘀血阻络证型高血压血液流变学的影响

目的:探讨天蛭方对阴虚阳亢兼瘀血阻络证型高血压血液流变学的影响。方法:选择张家口建国医院内科收治的原发性高血压患者150例作为研究对象,依照随机数字表法分为对照组(给予厄贝沙坦治疗)和观察组(在对照组基础上联合天蛭方治疗),每组75例。比较2组治疗前后全血黏度、全血还原黏度、血浆黏度、红细胞比容(hematocrit, HCT)、红细胞沉降率(erythrocyte sedimentation rate, ESR)、红细胞聚集指数(erythrocyte aggregation index, EAI)、红细胞变形指数(erythrocyte deformed index, EDI)及血小板聚集率(platelet aggregation, PAG)等血液流变学指标变化情况。结果:治疗后观察组全血黏度高中低切[(5.03±0.25) mPa·s、(5. 12±0.74) mPa·s、(9.26±1.31) mPa·s]、全血还原黏度高中低切[(7.33±1.03) mPa·s、(8.27±1.58) mPa·s、(13.76±3. 16) mPa·s]、血浆黏度[(1.52±0.11)mPa·s]、HCT(40.11%±3.58%)、ESR[(31.37±5.72)mm·h^(-1)]、PAG(50.33%±10.25%)水平均较治疗前明显降低(P<0.01),且低于对照组全血黏度高中低切[(5.94±1.07) mPa·s、(6. 12±1.50)mPa·s、(10.44±1.45)mPa·s]、全血还原黏度高中低切[(8.02±1.24)mPa·s、(9.29±1.42)mP·s、(10.44±1.45) mPa·s]、血浆黏度[(1.71±0.27) mPa·s]、HCT (45.62%±4.34%)、ESR [(34.67±4. 73) mm·h^(-1)]、PAG(55.61%±7.57%)水平,P<0.01。结论:在厄贝沙坦降压基础上联用天蛭方治疗阴虚阳亢兼瘀血阻络证型原发性高血压,可明显改善患者的血流变状况,使患者在预防心脑血管事件、阻止靶器官损害方面获益。     

HPLC测定清洁验证中残留物硝酸益康唑的含量

目的建立清洁验证中硝酸益康唑含量测定的高效液相色谱法(HPLC)。方法检测波长:235 nm;柱温:30℃;流动相:乙酸铵溶液(2%)-乙腈-甲醇(38:30:32);擦拭溶剂:乙醇。结果硝酸益康唑在5.80~232.07μg/ml范围内线性关系良好,r=1.0000。平均回收率为99%,RSD为0.3%(n=6)。结论本方法简便、快速、准确,可以用于硝酸益康唑清洁验证中残留物硝酸益康唑的定量分析。     

RP—HPLC测定硝酸益康唑脂质体凝胶中硝酸益康唑的含量

目的：建立一种反相高效液相色谱法检测硝酸益康唑脂质体凝胶中药物含量的方法。方法：以ODS为固定相,甲醇－水（80：20）为流动相,检测波长为230nm,硝酸咪康唑为内标。结果：硝酸益康唑在4－120ug.mL^-1(r=0.99998,n=7)浓度范围内呈线性关系,硝酸益康唑的平均回收率为98．0％－100．3％;RSD为0．24％－1．43％（n=5)。结论：此方法简便,快速、准确,可消防辅料的影响。     

阿苯达唑纳米脂质体冻干粉的制备及性质考察

目的:制备阿苯达唑纳米脂质体冻干粉并对其性质进行考察。方法:利用冷冻干燥法制备阿苯达唑纳米脂质体冻干粉,以粒径、包封率联合外观、再分散性为指标,采用单因素试验联合正交试验筛选冻干处方工艺。考察冻干前、后脂质体的形态学变化、粒径、Zeta电位、水分含量、4℃下12个月的稳定性。结果:采用外加冻干保护剂的总量为10%,其中葡萄糖-海藻糖-甘露醇配比为1.0∶1.0∶3.0,以速冻的方式,于-35℃冰箱预冻18 h,冷冻干燥48 h获得冻干粉。与冻干前比较,冻干后脂质体形态未发生明显变化,可见清晰的磷脂双分子层膜结构;冻干前、后脂质体的粒径分别为(208.63±1.04)、(223.04±2.02)nm,Zeta电位分别为(-15.6±0.04)、(-19.4±0.06)m V,包封率分别为(94.62±0.49)%、(91.10±0.46)%(n=3);与脂质体比较,脂质体冻干粉在4℃下12个月较稳定。结论:成功制得阿苯达唑纳米脂质体冻干粉,其稳定性优于阿苯达唑纳米脂质体,冻干工艺可行。     

唑来膦酸阳离子脂质体的制备及其体外特性表征

目的制备唑来膦酸阳离子脂质体,并对其体外特性进行表征。方法采用薄膜分散法制备唑来膦酸阳离子脂质体,以包封率、载药量、平均粒径、Zeta电位为评价指标,对处方及工艺进行单因素考察,并对其体外特性进行表征。结果确定处方工艺为DPPC与DC-Chol比例为3∶1,PBS水化体积10 m L,旋转蒸发时间60 min,超声均化5 min,制备得到的阳离子脂质体的平均粒径、聚分散指数、包封率、载药量和Zeta电位分别为(106.76±1.94)nm,0.262±0.027,(38.54±0.99)%,(3.42±0.27)%,+(42.37±2.60)m V,唑来膦酸阳离子脂质体体外释药具有缓释靶向特性,药物释放曲线符合Weibull方程模型。结论采用薄膜分散法制备的唑来膦酸阳离子脂质体具有较高的稳定性,为其药动学和药效学研究奠定了基础。     

HPLC法测定派瑞松乳膏中曲安奈德和硝酸益康唑的含量

目的 HPLC法测定派瑞松乳膏中曲安奈德和硝酸益康唑的含量。方法色谱柱为Dionex C18(200 mm×4.6 mm,5μm);流动相为质量分数为0.5%的三乙铵溶液(乙酸调节pH为3.0)(A)-乙腈(B),线性梯度洗脱;流速为1.0 mL·min-1;柱温为30℃;检测波长为235 nm。结果曲安奈德和硝酸益康唑在13.57⁴2.28 mg·L-1和131.342.28 mg·L-1和131.3⁴25.4 mg·L-1内,两者峰面积线性良好,R分别为0.999 8和0.999 0。平均回收率分别为99.8%和100.4%,RSD分别为0.99%和0.86%(n=9)。结论 HPLC法可用于派瑞松乳膏中曲安奈德和硝酸益康唑的含量测定。     

HPLC法测定复方莪术油栓的含量

目的:建立复方莪术油栓中硝酸益康唑和牻牛儿酮的含量测定方法.方法:采用高效液相色谱法.结果:硝酸益康唑在0.02058～0.205 8 mg·mL-1范围内,牻牛儿酮峰在0.00799～0.079 92 mg·mL-1范围内,线性关系良好;平均回收率分别为97.9%和98.7%,RSD分别为1.5%与1.2%(n＝9).结论:所建方法简便、准确,适用于复方莪术油栓中硝酸益康唑和牻牛儿酮的含量测定.     

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.