盐酸罗哌卡因温敏凝胶注射剂的制备及其含量测定

目的 制备盐酸罗哌卡因温敏凝胶注射剂,并建立其含量测定方法。方法 采用泊洛沙姆作为温敏材料,以冷法制备,利用反相高效液相色谱法测定其中药物的含量。结果 温敏凝胶注射剂中辅料泊洛沙姆P407与P188的质量比为28:1,盐酸罗哌卡因含量为2%,相变温度为37℃。盐酸罗哌卡因在2.03~48.72 μg/ml范围内线性关系良好(r=0.999 8),精密度和重复性良好,低、中、高浓度盐酸罗哌卡因的回收率分别为(99.58±0.20)%、(97.80±0.35)%、(103.60±0.63)%,n=3,3批样品中盐酸罗哌卡因的平均含量分别为标示量的(98.92±0.35)%、(99.18±0.38)%、(98.72±0.62)%,n=3。结论 采用泊洛沙姆为基质制备的盐酸罗哌卡因温敏凝胶注射剂质量可控,是一种很有开发前景的新型止痛剂。     

黄体酮热熔压敏胶透皮贴剂的制备及其体外释药性能研究

目的 制备黄体酮热熔压敏胶透皮贴剂并考察其体外释药性能。 方法 采用苯乙烯-异戊二烯-苯乙烯热塑性弹性体热熔压敏胶为骨架材料,以大鼠离体皮肤为渗透屏障,采用改良Freeze扩散池,用HPLC法测定接收液浓度,筛选促渗剂的种类、浓度和涂布厚度,确定贴剂处方。 结果 促渗剂选择肉豆蔻酸异丙酯(IPM),含量为2%;选择涂布厚度为300 μm,得到累积渗透曲线为Q=6.172 1 t-5.457 7(r=0.998 8);24 h药物累积渗透量为144.17 μg/cm²;稳态渗透速率为(6.17±0.49) μg/(cm²·h)。 结论 制备的黄体酮热熔压敏胶透皮贴剂中的有效成分黄体酮体外经皮渗透良好,具有较好的临床应用前景。     

两种盐酸特拉唑嗪片的人体生物等效性研究

目的 评价单剂量口服国产和进口盐酸特拉唑嗪片的人体生物等效性。 方法 采用单中心、随机、开放、双周期交叉试验设计,21名受试者在不同周期分别空腹口服国产和进口盐酸特拉唑嗪片2 mg,于给药前0 h及给药后60 h内不同时间点采集静脉血4 ml,采用液-质联用(LC-MS/MS)法测定受试者血浆中特拉唑嗪的浓度。 结果 国产和进口盐酸特拉唑嗪片的t_1/2分别为(13.2±2.39)和(12.5±1.93) h;t_max分别为(1.01±0.83)和(1.08±0.69) h;C_max分别为(40.1±10.6)和(37.3±9.57) ng/ml;AUC_0-∞分别为(428±82.1)和(426±85.2) ng·h/ml。国产盐酸特拉唑嗪片的相对生物利用度为(101.2±14.7)%。国产与进口盐酸特拉唑嗪片AUC_0-t和C_max几何均值比的90%置信区间(CI)均落在80%~125%之间。 结论 国产和进口盐酸特拉唑嗪片具有生物等效性。     

不同介质制备制霉素搽剂的稳定性考察及医院调剂管理

目的 建立一种测定制霉素搽剂含量的高效液相色谱法，考察不同介质制备的制霉素搽剂稳定性。方法 使用0.9%氯化钠注射液、2.5%碳酸氢钠溶液、开塞露、纯甘油等制备制霉素搽剂，各搽剂分为2组，分别在(25.0±0.5)℃及(5.0±0.5)℃下保存，于第0，7，14，21，28d测定制霉素含量，考察各搽剂药物含量稳定性。结果 4周内0.9%氯化钠、开塞露、纯甘油3种介质制备的制霉素搽剂含量变化不明显，测定结果分别为(102.2±1.3)%与(102.7±1.3)%，(102.0±1.9)%与(103.1±1.3)%，(99.9±3.3)%与(101.5±2.0)%；2.5%碳酸氢钠制备的制霉素搽剂含量变化显著，第0天测定结果为(85.2±2.1)%与(84.3±1.26)%，第28天测定结果为(59.2±1.7)%与(65.1±2.4)%。结论 使用0.9%氯化钠、开塞露、纯甘油3种介质制备的制霉素搽剂4周内含量变化不明显，必要时3种介质可相互替代，而制霉素在2.5%碳酸氢钠中不稳定，2.5%碳酸氢钠不能作为调剂介质使用。     

高效液相色谱法测定新保肾片中芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚的含量

目的 建立新保肾片中芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚的含量测定方法,为生产质量提供保障。方法 采用高效液相色谱法测定,色谱柱为Lichrospher-C₁₈柱(250 mm ×4.6 mm,5 μm),流动相为甲醇:0.1%磷酸溶液(7030),流速为1.0 ml/min,柱温为35 ℃,检测波长为254 nm。结果 芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚分别在2.30~18.4 μg/ml(r=1.0)、2.930~23.44 μg/ml(r=1.0)、5.00~40.0 μg/ml(r=1.0)、14.870~118.96 μg/ml (r=0.999 8)、7.410~59.28 μg/ml(r=0.999 9)范围内有良好的线性关系,平均回收率分别为100.16%、102.91%、99.76%、100.32%、100.44%,RSD分别为1.58%、1.27%、1.67%、1.33%、1.03%(n=9)。结论 该方法准确易行,便于质量控制。     

高效液相色谱法测定麻杏口服液中盐酸麻黄碱及盐酸伪麻黄碱的含量

目的 建立HPLC法测定麻杏口服液中盐酸麻黄碱及盐酸伪麻黄碱的含量。 方法 采用Phenomenex Hydro-RP (250 mm×4.6 mm,4 μm)色谱柱,以乙腈(A)-0.1%磷酸溶液(含0.1%三乙胺)(B)为流动相,梯度洗脱(0~20 min,3%→10% A),流速:1.0 ml/min,检测波长:210 nm,进样量:20 μl。 结果 盐酸麻黄碱在0.99~39.6 μg/ml范围内线性关系良好,r=0.999 9, 平均回收率为101.5%,RSD为1.77%(n=6);盐酸伪麻黄碱在1.09~43.6 μg/ml范围内线性关系良好,r= 0.999 9,平均回收率为100.8%, RSD为 1.96%(n=6)。 结论 本法简便、可靠、准确,可用于该制剂的质量控制。     

应用高效液相色谱法测定猫人参中积雪草酸的含量

目的 建立猫人参药材中积雪草酸的含量测定方法。 方法 采用高效液相色谱法,色谱柱为Agilent HC-C₁₈柱(4.6 mm×250 mm,5.0 μm),流动相为乙腈(30 mmol/L)-醋酸铵水溶液(35:65),流速1.0 ml/min,柱温25 ℃,紫外检测波长210 nm,进样量25 μl,运行时间35 min。 结果 积雪草酸与周围干扰峰达到基线分离,线性范围25.3~506.0 μg/ml, r=0.999 6;日内及日间精密度均<3% (n=5),平均回收率为99.4%(RSD=1.9%, n=6),猫人参中积雪草酸的含量为0.751 mg/g。 结论 该法简便快捷、测定结果准确、实用性强,可用于猫人参药材中积雪草酸的含量测定。     

瘤内注射用替加氟温敏凝胶的处方筛选及体外释放研究

摘 要 目的：筛选瘤内注射用替加氟温敏凝胶的最佳处方并考察其体外释放特征。方法: 通过细胞毒性试验确定药物剂量,以聚丙交酯-乙交酯-聚乙二醇-聚丙交酯-乙交酯（PLGA-PEG-PLGA）、羟丙基甲基纤维素（HPMC）为基质制备凝胶。以体外释放度为指标,考察不同浓度PLGA-PEG-PLGA和HPMC等因素对凝胶的影响,并以胶凝温度、黏度、pH等评价凝胶质量。结果: 凝胶剂的最佳处方为：25% PLGA-PEG-PLGA,1% HPMC,替加氟剂量为1 mg·mL^-1。制得凝胶的平均胶凝温度为36.7℃,平均黏度为7 550 mPa·s,平均pH 为7.2。结论:所制备的瘤内注射用替加氟温敏凝胶具有温敏特性和明显的缓释作用,为后续的临床研究提供了试验依据。     

依托泊苷壳聚糖胶束的制备及壳聚糖促进依托泊苷肠吸收作用的研究

目的 制备依托泊苷壳聚糖胶束,并研究壳聚糖对依托泊苷肠吸收的促进作用。方法 用透析法制备依托泊苷壳聚糖胶束,建立依托泊苷HPLC含量测定方法,测定了其包封率与载药量;采用大鼠在体肠循环实验,研究不同剂量壳聚糖对依托泊苷全肠段和各个肠段吸收的影响。结果 壳聚糖胶束平均粒径为139.5 nm,多分散系数为0.569;依托泊苷标准曲线为A=8 436.8C-4 963.8,r=1.000 0,日内、日间精密度符合要求;包封率为（47.3±2.84）%,载药量为（1.10±1.27）%;随着壳聚糖浓度的增加,依托泊苷在全肠段的单位面积吸收量有不同程度的增加;壳聚糖对依托泊苷的吸收促进作用存在着肠道特异性,作用大小顺序：回肠 >空肠 >十二指肠。结论 在十二指肠、空肠和回肠,壳聚糖都不同程度促进了药物的吸收,且在空肠和回肠有显著性的影响。     

早产儿肺功能发育与脑损伤关系的初步探讨

目的 探讨早产儿肺功能发育与脑损伤之间的关系。方法 2012年6月至2014年6月入住安徽医科大学第三附属医院新生儿科早产儿,除外肺部感染、需吸氧及机械通气等影响肺功能疾病的早产儿。依据临床表现及头颅MRI结果,分为脑损伤组及非脑损伤组,矫正胎龄40周时行潮气呼吸肺功能检测,比较两组早产儿肺功能的特点及差异。结果 符合入选标准共55例,其中脑损伤组22例(男性12例,女性10例),非脑损伤者33例(男性19例,女性14例)。脑损伤组早产儿呼吸频率[(51.4±6.3)次/min比(42.8±5.8) 次/min,t=5.19]、每分钟通气量[(431.0±84.4)mL/min比(344.3±64.5) mL/min,t=4.31,P<0.05]明显高于非脑损伤组,达峰时间比[(28.1±4.3)%比(35.4±7.2)%,t=-4.27]、达峰容积比[(32.8±2.3)%比(39.9±3.8)%,t=-9.42]、呼气峰流速[(58.7±11.7)mL/s比(67.7±13.7) mL/s,t=-2.54]及75%、50%、25%潮气量时呼气流速[(51.7±8.4)mL/s比(61.6±12.8) mL/s,t=-3.19;(34.4±4.9)mL/s比(47.4±7.4) mL/s,t=-7.23;(31.5±4.0)mL/s比(40.7±7.3) mL/s,t=-6.24,P均<0.05]均明显低于非脑损伤组。结论 脑损伤组早产儿肺功能发育较非脑损伤组早产儿更为不成熟。     

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.     

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.     

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.     

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.