新型布洛芬衍生物的合成及其抗炎活性

以布洛芬为原料,依次与草酰氯和氨基酸(2a~2d)反应制得中间体布洛芬衍生物(3a~3d);3与可缓慢释放H2S的5-对羟基苯基-1,2-二硫杂环戊烯-3-硫酮(4)经酯化反应,合成了4个新型的S-(+)-布洛芬衍生物(5a~5d)。α-溴乙酰氯与4经酯化反应制得5-(4-α-溴乙酰氧基)-苯基-1,2-二硫杂环戊烯-3-硫酮(6);6与1经偶联反应合成了一个新型的S-(+)-布洛芬衍生物(7),5和7的结构经1H NMR,IR和HR-MS表征。二甲苯致小鼠耳肿胀试验结果表明:5a,5c,5d和7均有较强的抗炎活性。     

离子色谱法分析布洛芬片剂中的布洛芬含量

研究离子色谱法分析布洛芬片剂中的布洛芬含量的分析方法。用碳酸钠 碳酸氢钠溶液作为淋洗液 ,并以此淋洗液作为提取液 ,提取布洛芬片剂中的布洛芬 ,用紫外检测器在波长 2 1 5nm下检测 ,回收率在 96%～ 98%之间 ,RSD等于 0 .92 % ,方法简单快速。     

S-布洛芬磁性分子印迹膜的吸附及拆分性能

以S-布洛芬为模板分子、3-氨丙基三乙氧基硅烷为功能单体、正硅酸乙酯为交联剂,采用溶胶凝胶法成功制备了对S-布洛芬具有特异选择识别功能的磁性分子印迹聚合物,并且分别采用红外(IR)光谱、扫描电镜(SEM)、X射线粉末衍射(XRD)对其结构进行了表征.通过紫外(UV)光谱研究了其对S-布洛芬的吸附性能,并且建立了高效液相色谱(HPLC)手性流动相法研究其对布洛芬的拆分.结果表明,该磁性分子印迹聚合物具有良好的磁响应性,在外加磁场下可实现快速分离;S-布洛芬分子印迹复合膜对S-布洛芬具有较好的选择结合性,其结合量达到68.3mg/g;每100mg复合膜可使外消旋布洛芬的分离度增加2.1%.     

布洛芬合成绿色化进展

对亲一代消炎止痛药物布洛芬的合成方法作了论述，重点介绍了被誉为典型“ 清洁生产”的Boots/Hoechst-Celanese（BHC）方法及布洛芬合成中的绿色化进展 ，特别对催化剂环境友好分离回收方法和对异丁基苯乙烯手性羰化合成布洛芬的研 究进展作了评述及展望。     

以阴离子手性模板合成螺旋形貌的介孔分子筛

本文首次以具有手性的药物分子布洛芬(Ibuprfen, 2-(4-异丁基苯基)丙酸)为模板剂, 以3-氨丙基-3-乙氧基硅烷为共模板剂, 合成了具有新颖螺旋形貌的介孔分子筛, 并用XRD, FTIR, TEM 和SEM对其结构进行了表征.     

布洛芬高分子前体药物及纳米微球的合成和表征

将非甾体消炎药布洛芬以共价键连接到舍双键的甲基丙烯酸-2-羟基乙酯(HEMA)上,制成含布洛芬药物的单体,进而通过自聚或共聚,合成了含布洛芬的高分子药物;采用乳液聚合方法制备了高分子药物蚋米微球。研究了影响聚合反应的有关因素,并对所合成的产物用^1H-NMR,GPC和TEM等检测手段进行了表征。     

超高效液相色谱法同时测定布洛芬注射液中布洛芬和精氨酸的含量

建立了一种同时测定布洛芬注射液中布洛芬和精氨酸含量的超高效液相色谱方法。精氨酸与衍生化试剂2,4-二硝基氟苯(DNFB)反应后,与布洛芬同时在超高效液相色谱-二极管阵列检测器(UPLC-PDA)上检测。采用BEH C18色谱柱(50 mm×2.1 mm, 1.7 μm),以乙腈-0.05 mol/L磷酸二氢钾缓冲液(pH 2.5)为流动相进行梯度洗脱,流速为0.4 mL/min,柱温为30 ℃,检测波长分别为357 nm(精氨酸衍生物)和220 nm(布洛芬)。结果表明,布洛芬与精氨酸分别在2.0～100.5 mg/L和1.7～84.5 mg/L范围内呈良好的线性关系,相关系数(r)均为0.9997;平均回收率分别为99.8%和99.6%,相对标准偏差(RSDs)分别为0.37%和0.25%;定量限(信噪比（S/N）=10)分别为0.1 ng和0.2 ng;检出限(S/N=3)分别为0.03 ng和0.05 ng。本方法快速、准确,重复性好,可较全面地评价布洛芬注射液的质量。     

离子色谱法分析布洛芬片剂的布洛芬含量

研究离子色谱分析布洛芬片剂中的布洛芬含量的分析方法。用碳酸钠-碳酸氢钠溶液作为淋洗液，并以此淋洗液作为提取液，提取布洛芬片剂中的布洛芬，用紫外检测器在波长215nm下检测。回收率在96%-98%之间，RSD等于0.92%，方法简单快速。     

微流控芯片非接触电导法测定药品中的精氨酸布洛芬含量

建立了微流控芯片非接触电导检测快速测定精氨酸布洛芬含量的方法。考察了缓冲液种类和浓度、添加剂、分离电压以及进样时间等因素对分离检测的影响。优化条件为:20 mmol/L Tris-20 mmol/L H3BO3(p H 8.6)为缓冲溶液、不加添加剂、分离电压2.0 k V、进样时间10.0 s,在45.0 s内可实现精氨酸布洛芬的快速分离测定。结果表明,布洛芬和精氨酸在80.0~1.00×103mg/L范围内线性关系良好,相关系数(r)分别为0.998和0.997,检出限(S/N=3)为60 mg/L,相对标准偏差分别为1.9%和1.8%,加标回收率分别为97.9%~103%和97.3%~102%。该方法快速、简便,为精氨酸布洛芬非甾体抗炎药物的分析和质量控制提供了一种新方法。     

淀粉基荧光微球的制备及其布洛芬包载和释药性能

以淀粉为原料,用乙酸酐酰化后,将异硫氰酸荧光素（FITC）接枝到淀粉醋酸酯大分子链上,以自组装的方法制备出包载布洛芬的淀粉基荧光微球,同时考察了淀粉基荧光纳米微球对布洛芬的控制释放性能。 荧光淀粉酯的用量、布洛芬的加入量及丙酮与水的体积比可影响载药微球的包封率和药物释放速度。 研究结果表明,当荧光淀粉酯用量为200 mg、布洛芬的量为60 mg、水和丙酮体积分别为50和20 mL时所合成的载药微球包封率最高,为69.5%,其药物体外释放也最快,48 h可释放62.7%。 用扫描电子显微镜和激光共聚焦显微镜(CLSM)对包药微球的体外释放过程进行了表征。     

Flexible porous metal-organic frameworks for a controlled drug delivery

Flexible nanoporous chromium or iron terephtalates (BDC) MIL-53(Cr, Fe) or M(OH)[BDC] have been used as matrices for the adsorption and in vitro drug delivery of Ibuprofen (or alpha- p-isobutylphenylpropionic acid). Both MIL-53(Cr) and MIL-53(Fe) solids adsorb around 20 wt % of Ibuprofen (Ibuprofen/dehydrated MIL-53 molar ratio = 0.22(1)), indicating that the amount of inserted drug does not depend on the metal (Cr, Fe) constitutive of the hybrid framework. Structural and spectroscopic characterizations are provided for the solid filled with Ibuprofen. In each case, the very slow and complete delivery of Ibuprofen was achieved under physiological conditions after 3 weeks with a predictable zero-order kinetics, which highlights the unique properties of flexible hybrid solids for adapting their pore opening to optimize the drug-matrix interactions.     

Nanosizing drug particles in supercritical fluid processing

The supercritical fluid-processing technique, rapid expansion of a supercritical solution into a liquid solvent (RESOLV), was applied to the nanosizing of water-insoluble drug particles. Selected for demonstration were antiinflammatory drugs Ibuprofen and Naproxen, for which CO2 and CO2-cosolvent systems were used. The RESOLV process produces exclusively nanoscale (less than 100 nm) Ibuprofen and Naproxen particles suspended in aqueous solutions, and the aqueous suspensions of the drug nanoparticles are protected from particle agglomeration and precipitation by using common polymeric and oligomeric stabilization agents.     

Annealed Ti/Zn-TiO2 nanocomposites tested as photoanodes for the degradation of Ibuprofen

Ti/Zn-TiO₂ electrodes were successfully prepared by the co-deposition method, on a titanium substrate, using an acidic zinc sulphate solution with TiO₂ nanoparticles in suspension. After electrodeposition, samples were heated in air at 450?°C for 6?h. The X-ray diffraction analysis of the deposits point to the metal matrix modification from Zn to ZnO. In addition, the scanning electron microscopy results indicate that the films have a high surface area with a rich morphology, due to the appearance of ZnO needle-shaped grains. The voltammograms recorded, in Na₂SO₄ solution, for these electrodes under illumination at λ?=?365?nm confirmed the films photoactivity. Photoelectrochemical degradation of Ibuprofen (Ibu) was achieved with the Zn-TiO₂ electrodes after thermal treatment. UV–Vis spectrometry, high-performance liquid chromatography (HPLC), chemical oxygen demand (COD) and total organic carbon (TOC) measurements were performed and data demonstrated that Ibuprofen was efficiently degraded. Absorbance at 220?nm, COD and TOC removals of 35%, 34% and 23%, respectively, were obtained after a 3 h period.     

新型手性氨基醇的合成及其对布洛芬对映异构体的手性识别

5-叔丁基-2-二甲氨基苯甲醛与L-苯甘氨酸经酯化、格氏反应途径的产物二齿手性氨基醇经缩合、还原反应,得到新型三齿手性氨基醇(2S)-2-(5-叔丁基-2-二甲氨基)苯甲氨基-1,1,2-三苯基乙醇,运用1H NMR考察了该新型三齿手性氨基醇作为主体对客体布洛芬消旋体的手性识别能力。     

Ibuprofen-loaded PCL meshes manufactured using rapid tooling for ocular orbital repair

This study investigated the manufacture of resorbable polycaprolactone/ibuprofen (PCL/IBP) meshes by injection molding for application in ocular orbital repair. The pore dimension sizes used demonstrate that micro-porous meshes can be manufactured by injection molding using a prototype mold. The mechanical properties were observed to be dependent on the material composition and morphology. Lower stiffness, strength and elongation at failure were observed for the 8 mm pore sized samples. The PCL/Ibuprofen meshes initially showed a fast drug release but after 3 days the release was slow and controlled. The cytotoxicity test results of the PCL/Ibuprofen meshes indicated that the large initial quantity of Ibuprofen released was too high and resulted in cell toxicity. However, after this initial release, the PCL/Ibuprofen meshes showed a good interaction with the cells seeded on their surface. The presence of a low concentration of Ibuprofen does not negatively influence cell viability in culture.     

Determination of the plasticizer N-butylbenzenesulfonamide and the pharmaceutical Ibuprofen in wastewater using solid phase microextraction (SPME)

A rapid, inexpensive and solvent-free method for the simultaneous determination of the polyamide plasticizer N-butylbenzenesulfonamide (NBBS) and the widely used pharmaceutical Ibuprofen by solid phase microextraction (SPME) combined with gas chromatography/mass spectrometry (GC/MSD) in wastewater samples was developed. Besides the optimized analytical conditions, results of investigations with varying analytical parameters are reported. Problems, which may occur during the analytical procedure (e.g. salt deposits, adsorption phenomena, carry-over), are discussed. For the determination of Ibuprofen, it is important to carry out the extraction under acidic conditions with sufficiently buffered samples; the GC/MSD system must be very clean and well maintained. SPME allows an extraction of Ibuprofen without derivatization of its carboxylic group. For quantification in complex matrices, the standard addition technique is necessary. Limit of detection and limit of determination are 0.1 μg/L for both analytes. NBBS and Ibuprofen were detected in several raw and treated wastewater samples from municipal wastewater treatment plants in the range from < 0.1 to 3.5 μg/L.     

Determination of the plasticizer N-butylbenzenesulfonamide and the pharmaceutical Ibuprofen in wastewater using solid phase microextraction (SPME)

A rapid, inexpensive and solvent-free method for the simultaneous determination of the polyamide plasticizer N-butylbenzenesulfonamide (NBBS) and the widely used pharmaceutical Ibuprofen by solid phase microextraction (SPME) combined with gas chromatography/mass spectrometry (GC/MSD) in wastewater samples was developed. Besides the optimized analytical conditions, results of investigations with varying analytical parameters are reported. Problems, which may occur during the analytical procedure (e.g. salt deposits, adsorption phenomena, carry-over), are discussed. For the determination of Ibuprofen, it is important to carry out the extraction under acidic conditions with sufficiently buffered samples; the GC/MSD system must be very clean and well maintained. SPME allows an extraction of Ibuprofen without derivatization of its carboxylic group. For quantification in complex matrices, the standard addition technique is necessary. Limit of detection and limit of determination are 0.1 μg/L for both analytes. NBBS and Ibuprofen were detected in several raw and treated wastewater samples from municipal wastewater treatment plants in the range from < 0.1 to 3.5 μg/L. Received: 13 March 1998 / Revised: 16 June 1998 / Accepted: 19 June 1998     

PHOTOLYTIC DEGRADATION OF IBUPROFEN. TOXICITY OF THE ISOLATED PHOTOPRODUCTS ON FIBROBLASTS and ERYTHROCYTES

The photodegradation of Ibuprofen, a widely used non-steroidal anti-inflammatory drug (NSAID), was examined. Several photoproducts (I-VI) were isolated and identified on the basis of their IR-¹H-NMR- and ¹³C-NMR- spectra. The chemical structures were confirmed by unambiguous alternative synthesis from available reagents. The most significant primary photochemical process was the cleavage of the C-C bond a to the carboxy group. Subsequent secondary processes (hydrogen abstraction, dimerization, incorporation of methanol, or reaction with oxygen) might account for the formation of the different photoproducts. The cytotoxic effects were assayed using the red-blood cell lysis test and the enzyme leakage (LDH and GOT) from cultured fibroblasts. Compound V [l-(4 isobutylphenyl)-ethanol] was found to be toxic for both system at concentrations greater than 1 mM while compound IV [l-(4 isobutylphenyl acetophenone)] was toxic for fibroblasts but not for erythrocytes at the same concentration. Ibuprofen and the other photocompounds were apparently non-toxic. The significance of these results is discussed in connection with the possible in vivo phototoxicity of Ibuprofen.     

Topical administration of ibuprofen in man. Simultaneous determination of the drug and its metabolites in urine by high resolution gas chromatography

A selective and sensitive high resolution gas chromatography assay for simultaneous determination of Ibuprofen and its major metabolites in urine is described. Biological samples were collected from healthy volunteers after a single topical administration of the drug in gel form. The chromatographic system, developed on a WCOT OV-1 glass capillary column, ensured a clear separation of Ibuprofen and its metabolites and their quantitative evaluation.     

Determination of Ibuprofen in human plasma by high-performance liquid chromatography: validation and application in pharmacokinetic study

A specific method for the simultaneous determination of S-(+)Ibuprofen and R-(-)Ibuprofen enantiomers in human plasma is described. Adopting a high-performance liquid chromatographic (HPLC) system with spectrofluorometer detector, the compounds were extracted from plasma in alcohol medium and were separated on C18 column, using a solution of acetonitrile-water-acetic acid-triethylamine as mobile phase. The limit of quantitation was 0.1 microg/mL for both compounds. The method was validated by intra-day assays at three concentration levels and was used in a kinetic study in healthy volunteers. During the study we carried out inter-day assays to confirm the feasibility of the method.