奥卡西平及其中间体的新合成方法

介绍了一种新的合成奥卡西平(OCBZ)及其中间体的方法:以5H-二苯并[b,f]氮杂卓-5-甲酰氯为原料,通过加成溴化、氨解、水解得到OCBZ,总收率可达62左右,OCBZ的摩尔分数大于99.0。考察了影响氨解反应的因素,优化条件为n(NH3)/n(10,11-二溴-5H-二苯并[b,f]氮杂卓-5-甲酰氯)=5,反应温度约20℃,反应时间约35h,10-溴-5H-二苯并[b,f]氮杂卓-5-甲酰胺收率大于98,摩尔分数大于98.0。结果表明,温度高时氨解反应主要易生成副产物10,11-二溴-5H-二苯并[b,f]氮杂卓。主要产物及副产物的结构均用元素分析和MS进行了确证。该文报道工作的新颖性,已为浙江省科技信息研究院2008年1月8日出具的第200833B210143号《科技查新报告》所证实。该工作已进行1t/a规模的中试,结果为:平均收率约61,产品摩尔分数大于99.1。     

Construction of Cu7S4@CuCo2O4 Yolk–Shell Microspheres Composite and Elucidation of Its Enhanced Photocatalytic Activity,Mechanism, and Pathway for Carbamazepine Degradation

Water pollution caused by the massive use of medicines has caused significant environmental problems. This work first reports the synthesis and characterization of the Cu₇S₄/CuCo₂O₄ (CS/CCO) yolk–shell microspheres via hydrothermal and annealing methods, and then investigates their photocatalytic performance in removing organic water pollutants. The 10-CS/CCO composite with yolk–shell microspheres exhibits the highest photodegradation rate of carbamazepine (CBZ), reaching 96.3% within 2 h. The 10-CS/CCO also demonstrates more than two times higher photodegradation rates than the pure (Cu₇S₄) CS and (CuCo₂O₄) CCO. This outstanding photocatalytic performance can be attributed to the unique yolk–shell structure and the Z-scheme charge transfer pathway, reducing multiple reflections of the acting light. These factors enhance the light absorption efficiency and efficiently transfer photoexcited charge carriers. In-depth, photocatalytic degradation pathways of CBZ are systematically evaluated via the identification of degradation intermediates with Fukui index calculation. The insights gained from this work can serve as a guideline for developing low-cost and efficient Z-scheme photocatalyst composites with the yolk–shell structure.     

Preliminary study on the development of nanoemulsions for carbamazepine intravenous delivery: an investigation of drug polymorphic transition

Carbamazepine (CBZ) is available on the pharmaceutical market as tablets, capsules, and oral suspensions, but not as a parenteral formulation for clinical use. Parenteral emulsions are a good alternative to poorly water-soluble drugs such as CBZ. In this way, four different emulsions containing 3 mg/mL of CBZ were developed, but during a period of storage, drug crystal precipitates appeared. To investigate this phenomenon, differential scanning calorimetry, infrared spectroscopy, and light microscopy were employed. The results suggested a polymorphic transition from β form to dehydrate form, resulting in drug precipitation, although the emulsions themselves remained stable for at least three months.     

外加电流阴极保护强化ACF激活PDS降解水中卡马西平

卡马西平是一种典型的持久性的有机药物污染物,采用一种新的外加电流阴极保护强化活性炭纤维(ACF)激活过硫酸盐(PDS)的高级氧化方法,实现对水中卡马西平的高效降解.考察该体系对比活性炭纤维激发过硫酸盐体系、阴极保护活性炭纤维电解体系、过硫酸盐体系、活性炭纤维吸附体系、电解体系等不同工艺对卡马西平的降解率,探究过硫酸盐初始浓度、电压、初始pH等因素对体系的影响,并通过活性炭纤维性质测定和自由基捕获探究其降解机制.结果显示,外加电流阴极保护增强活性炭纤维(ACF)激活过硫酸盐(PDS)体系对水中卡马西平的氧化降解率远高于其他5种处理工艺.在外加电流阴极保护强化活性炭纤维(ACF)激活过硫酸盐(PDS)体系中,过高的过硫酸盐浓度反而不利于卡马西平的降解,在一定条件下存在一个适宜的过硫酸盐浓度范围;电压的提高和初始pH为酸性(pH=3)更有利于对卡马西平的氧化降解.此外,该体系中活性炭纤维受到阴极电场保护,使用寿命大大延长.硫酸根自由基在体系去除卡马西平过程中起主导作用.     

Biotransformation of Sildenafil in the Male Rat: Evaluation of Drug Interactions with Testosterone and Carbamazepine

The biotransformation of sildenafil to its major circulating metabolite, UK-103,320, was studied in male rat liver microsomes. The conversion of sildenafil to UK-103,320 by rat microsomes followed Michaelis–Menten kinetics, for which the parameters were V_max?=?1.96 μM/minand K_m?=?27.31 μM. Using substrates of CYP3A4 of testosterone and carbamazepine, the active sites on CYP3A4 responsible for metabolizing sildenafil were also evaluated. Sildenafil biotransformation was inhibited in the individual presence of testosterone and carbamazepine. The results showed drug interaction was observed in the sildenafil-testosterone and sildenafil-carbamazepine. Although testosterone and carbamazepine can inhibit sildenafil demethylation in concentration- and incubation time-dependent manners, sildenafil did not inhibit testosterone hydroxylation or carbamazepine epoxidation. These results may be explained by a model in which multiple substrates or ligands can concurrently bind to the active site of a single CYP3A4 molecule. However, the contribution of separate allosteric sites and conformational heterogeneity to the atypical kinetics of CYP3A4 cannot be ruled out in this study.     

Optimization of hot melt extrusion parameters for sphericity and hardness of polymeric face-cut pellets

The aim of this study was to formulate face-cut, melt-extruded pellets, and to optimize hot melt process parameters to obtain maximized sphericity and hardness by utilizing Soluplus^® as a polymeric carrier and carbamazepine (CBZ) as a model drug. Thermal gravimetric analysis (TGA) was used to detect thermal stability of CBZ. The Box–Behnken design for response surface methodology was developed using three factors, processing temperature (?°C), feeding rate (%), and screw speed (rpm), which resulted in 17 experimental runs. The influence of these factors on pellet sphericity and mechanical characteristics was assessed and evaluated for each experimental run. Pellets with optimal sphericity and mechanical properties were chosen for further characterization. This included differential scanning calorimetry, drug release, hardness friability index (HFI), flowability, bulk density, tapped density, Carr’s index, and fourier transform infrared radiation (FTIR) spectroscopy. TGA data showed no drug degradation upon heating to 190?°C. Hot melt extrusion processing conditions were found to have a significant effect on the pellet shape and hardness profile. Pellets with maximum sphericity and hardness exhibited no crystalline peak after extrusion. The rate of drug release was affected mainly by pellet size, where smaller pellets released the drug faster. All optimized formulations were found to be of superior hardness and not friable. The flow properties of optimized pellets were excellent with high bulk and tapped density.     

一种新型卡马西平共晶的合成及表征

以卡马西平（CBZ）作为药物活性成分（API）,以没食子酸甲酯（MTG）作为共晶形成物（CCF）,在室温条件下制得一种新的药物共晶CBZ-MTG。通过X-射线单晶衍射测得了其晶体结构,并进行了红外光谱、X-射线粉末衍射、热重分析和差示扫描量热的表征。此外,利用HPLC测得其溶解性质并测试了稳定性,其共晶在溶解性,稳定性和生物利用度上都有了明显的改观。各种结构性质的表征,为其在药物领域的应用提供了基础数据和理论基础,为卡马西平-没食子酸甲酯共晶化合物作为药物应用及在制剂领域提供了新的选择。     

A Comparison of Anticonvulsants in the Treatment of Impulsive Aggression.

This study compared the behavioral effects of 3 anticonvulsants in impulsive aggressive men. In a double-blind, placebo-controlled, parallel groups design, participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n = 7), carbamazepine (n = 7), valproate (n = 7), or placebo (n = 8). The efficacy measure was the average aggression score, a global severity index from the Overt Aggression Scale (J. M. Silver & S. C. Yudofsky, 1991). Analysis showed a significant reduction in impulsive aggression during all 3 anticonvulsant conditions compared with placebo. However, the treatment effect during carbamazepine administration was slightly delayed compared with phenytoin and valproate. These findings suggest that increased use of anticonvulsants could make a significant impact in the control of impulsive aggression in both mental health and criminal justice settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adsorption of Carbamazepine in Fixed Bed Columns: Experimental and Modeling Studies

The adsorption of carbamazepine was evaluated on activated carbon in fixed bed columns. The effect of various parameters on breakthrough curves like carbamazepine initial concentrations (1.2, 1.6, and 2.5 mg/L), bed depths (0.4, 0.6, and 0.8 cm) and volumetric flow rates (1.0, 2.0, and 3.0 mL/min) was investigated. The breakthrough time increased with increase of bed depth, and decreased with increase of initial concentration and volumetric flow rate. In order to predict the theoretical breakthrough curves and to determine model parameters, BDST, Thomas, Yoon-Nelson and Clark models were applied to the experimental adsorption processes under the operational conditions described above. The Thomas and Yoon-Nelson models were in good agreement with the experimental data.