非甾体抗炎新药联苯乙酸的合成

联苯经乙酰化制得乙酰联苯,再经Willgerodt反应和水解制得联苯乙酸。     

4-联苯乙酸的新法合成

以联苯为原料，经氯甲基化、氰基取代及酸水解制得4-联苯乙酸，并优化了各步反应条件，新工艺总收率72%。     

非甾体抗炎药联苯乙酸的简便合成方法

目的探索联苯乙酸的一种新的合成方法。方法以苯硼酸和对溴苯乙酸乙酯为起始原料,经偶联、皂化二步反应得目标化合物。结果化合物的结构经IR1、HNMR分析确证。结论合成路线较短,反应条件温和、易控制,二步总收率达78%,是合成该目标化合物的一种较为理想的方法。     

联苯乙酸的合成工艺研究

目的:改进非甾体抗炎药联苯乙酸合成工艺。方法:以联苯为原料,经酰化、缩合、水解反应制备。结果:酰化反应通过改变反应条件,使该步反应收率由文献方法的89%提高到90.2%,成品由文献方法的醋酸重结晶改为氨水-醋酸重结晶。结论:酰化反应中改变了其反应条件,提高了反应收率;成品改进了重结晶的方法,使杂质含量及杂质数量减少。     

新型非甾体抗炎镇痛药联苯乙酸的研究

联苯乙酸为一安全有效的非甾体抗炎药,临床上主要用于变形性关节炎、肩周炎、肌肉痛、软组织损伤、外伤性肿胀疼痛等的镇痛消炎。本文对该药的药理毒理、国外临床研究评价进行了综述。     

HPLC法测定联苯乙酸凝胶含量和有关物质

目的:建立测定联苯乙酸凝胶的含量和有关物质的方法。方法:采用高效液相色谱法。色谱柱为Kromasil C18,流动相为甲醇-0.1%冰醋酸(65:35),流速为1.0mL·min-1,检测波长为254nm。结果:联苯乙酸检测浓度线性范围为0.3～60μg·mL-1(r=0.9998),低、中、高浓度平均回收率分别为100.3%、101.2%、99.8%,RSD=0.24%(n=9);3批样品主药和有关物质含量均符合限度要求。结论:本方法简便快速、重复性好,可用于控制联苯乙酸凝胶的质量。     

联苯乙酸搽剂的制备与质量研究

目的制备联苯乙酸搽剂,建立其质量标准。方法以联苯乙酸与辅料制备联苯乙酸搽剂,采用紫外-可见光分光光度法测定联苯乙酸的含量。结果以254 nm为测定波长,线性方程为C=10.111A-0.074,相关系数r=0.9997,线性范围为3.45～10.35μg/ml,平均回收率为99.5%,RSD为0.92%（n=9）。结论本制剂制备简便,可行;采用紫外-可见光分光光度法测定联苯乙酸的含量,操作简单、快捷,结果可靠,易于质量控制。     

联苯乙酸搽剂的制备与质量研究

目的 制备联苯乙酸搽剂,建立其质量标准.方法 以联苯乙酸与辅料制备联苯乙酸搽剂,采用紫外-可见光分光光度法测定联苯乙酸的含量.结果 以254 nm为测定波长,线性方程为C＝10.111A-0.074,相关系数r=0.9997,线性范围为3.45～10.35 μg/ml,平均回收率为99.5%,RSD为 0.92%(n=9).结论 本制剂制备简便,可行;采用紫外-可见光分光光度法测定联苯乙酸的含量,操作简单、快捷,结果 可靠,易于质量控制.     

2—噻吩乙酸的合成

2-噻吩乙酸(1)是头孢噻吩的原料,国内一般由乙酰噻吩经Willgerodt反应,再水解得到。由于收率不高,且在较高温度和压力下进行,这无疑带来一定的困难,因此1的常压法合成有一定的实际意义。文献报道的常压合成法有的以伯胺代替Willgerodt法的浓氨水;也有噻吩与二羟基乙酸一步合成法以及噻吩用草酸酰氯乙     

抗真菌药联苯苄唑的合成

联苯苄唑(白霉唑,bifonazole,1),是西德 Bayer 研究中心合成的一种不含卤素的咪唑类抗真菌药,化学名为1-(ρ,α-二苯基苄基)咪唑,其抗菌谱与克霉唑和益康唑类似,但有很强的皮肤渗透性,在表皮深层药物浓度可达其对皮肤真菌体外最低抑菌浓度的几倍。一次涂布后,皮肤中有效浓度能     

Pharmacokinetics of felbinac after intravenous administration of felbinac trometamol in rats

1. Felbinac trometamol (trishydroxymethylaminomethane 4-biphenylacetate) is a new water-soluble salt of felbinac currently undergoing clinical evaluation as an intravenous (i.v.) formulation for the treatment of severe post-operative pain. This article reports the pharmacokinetics of felbinac after i.v. administration of felbinac trometamol in Sprague–Dawley rats.

2. The maximum plasma concentration (C₀) and area under the plasma concentration-time curve (AUC) of felbinac administered at doses of 3.36, 8.40 and 21.0?mg/kg felbinac trometamol increased linearly with dose.

3. Felbinac was highly protein bound (~95%) at plasma concentrations up to 75?μg/ml and extensively metabolized with only small amounts being excreted unchanged in urine (0.318%), feces (0.530%) and bile (0.465%).

4. 4′-Hydroxyfelbinac was the principal metabolite in urine, feces and bile together with felbinac glucuronide, 4′-hydroxyfelbinac glucuronide and sulfate. The majority of the administered dose was excreted in urine (63.6%) mostly as 4′-hydroxyfelbinac. Total drug in urine and feces accounted for about 72% of the dose.

5. It would appear that felbinac trometamol has the potential to replace lipid-based NSAID formulations and progress to clinical evaluation.

     

Pharmacokinetics of felbinac after intravenous administration of felbinac trometamol in rats

Felbinac trometamol (trishydroxymethylaminomethane 4-biphenylacetate) is a new water-soluble salt of felbinac currently undergoing clinical evaluation as an intravenous (i.v.) formulation for the treatment of severe post-operative pain. This article reports the pharmacokinetics of felbinac after i.v. administration of felbinac trometamol in Sprague-Dawley rats. The maximum plasma concentration (C(0)) and area under the plasma concentration-time curve (AUC) of felbinac administered at doses of 3.36, 8.40 and 21.0?mg/kg felbinac trometamol increased linearly with dose. Felbinac was highly protein bound (~95%) at plasma concentrations up to 75?μg/ml and extensively metabolized with only small amounts being excreted unchanged in urine (0.318%), feces (0.530%) and bile (0.465%). 4'-Hydroxyfelbinac was the principal metabolite in urine, feces and bile together with felbinac glucuronide, 4'-hydroxyfelbinac glucuronide and sulfate. The majority of the administered dose was excreted in urine (63.6%) mostly as 4'-hydroxyfelbinac. Total drug in urine and feces accounted for about 72% of the dose. It would appear that felbinac trometamol has the potential to replace lipid-based NSAID formulations and progress to clinical evaluation.     

联苯乙酸透皮贴剂的体外透皮性能研究

目的:研究促进渗透剂对联苯乙酸贴剂(BPAA-TTS)体外透皮性能的影响.方法:用高体豚鼠皮肤为透皮屏障,采用改进的Franz扩散池,通过体外渗透性实验对含有不同处方的BPAA-TTS进行了透皮性能的研究.结果:体外渗透曲线符合平方根方程(Q=k×t1/2),含10%乙醇和8%的1,2-丙二醇的复合促进渗透剂的BPAATTS具有良好的透皮性能.结论:将加入复合促进渗透剂的贴剂中的BPAA的透皮速率与不加促进渗透剂贴剂的透皮速率进行比较,贴剂中药物的透皮性能有明显提高.     

超声波作用下合成奥沙拉秦

目的:合成奥沙拉秦.方法:以水杨酸为原料,在超声波作用下合成目标化合物.结果与结论:总收率为31.2%,反应时问为4.5 h,与文献相比提高了产率,缩短了反应时间.     

苯胺洛芬注射液镇痛作用及镇痛部位研究

目的研究苯胺洛芬注射液对大鼠单足致炎急性炎症模型和大鼠单发性关节慢性病理性炎症模型的镇痛作用,并对其镇痛部位进行分析。方法通过角叉菜胶致大鼠单足致炎后的后肢压痛实验和完全弗氏佐剂致大鼠单发性关节炎性疼痛实验,测定致炎足和非致炎足痛阈值和屈伸关节评分。结果在大鼠急性炎症模型和慢性病理性炎症模型中,苯胺洛芬注射液25.2、75.6 mg·kg-1可提升致炎足的痛阈值,但对非致炎足的痛阈值无明显影响,致炎足和非致炎足痛阈值变化情况与氟比洛芬酯注射液相当,而喷他佐辛注射液对致炎足和非致炎足均有镇痛作用。结论苯胺洛芬注射液发挥镇痛作用的部位主要在外周,这与非甾体类抗炎镇痛药的作用部位相似。     

超声条件下选择性脱除Fmoc-Asn(Ac_3GlcNAc)-OH的O-乙酰基

目的寻找N-(9-芴甲氧羰基)-N'-(2-乙酰氨基-2-脱氧-3,4,6-三-O-乙酰基-β-D-吡喃葡萄糖基)-L-天冬酰胺(Fmoc-Asn(Ac3GlcNAc)-OH)选择性脱除O-乙酰保护基的方法。方法采用HPLC法对反应进行监测,考察超声条件下Fmoc-Asn(Ac3GlcNAc)-OH脱除保护基的反应,寻找选择性脱除O-乙酰保护基的方法。结果在碱试剂的条件下脱除O-乙酰保护基的反应有很多杂质产生。但在超声条件下,反应无杂质生成且产率较高。结论超声条件下,Fmoc-Asn(Ac3GlcNAc)-OH和Fmoc-Ser(Ac3GlcNAc)-OH选择性脱除O-乙酰基,收率高于90%。     

一类创新药苯胺洛芬注射液安全性药理研究

目的:研究一类创新药苯胺洛芬的安全性药理,为新药研发提供依据。方法:通过小鼠自发活动试验、协调力实验和戊巴比妥钠催眠实验来考察苯胺洛芬对中枢神经系统的影响;通过麻醉Bealge犬实验考察苯胺洛芬对呼吸系统和循环系统的影响;通过正常大鼠和胃溃疡大鼠来考察苯胺洛芬对胃黏膜的影响。结果:苯胺洛芬剂量为临床拟用剂量的18倍时(小鼠216 mg.kg-1、大鼠162 mg.kg-1、犬45 mg.kg-1)单次给药后会导致麻醉Beagle犬血压一过性升高、小鼠自主活动降低、协调能力降低、与戊巴比妥钠具有协同作用;其余各剂量组和各观察指标均未见异常。结论:苯胺洛芬在剂量为临床拟用剂量的18倍时对中枢神经系统和心血管系统具有明显的影响;苯胺洛芬在剂量为临床拟用剂量的6倍时对中枢神经系统、呼吸系统和心血管系统未见明显影响;各剂量组对大鼠胃黏膜均未见明显影响。     

Fluorous derivatization and fluorous-phase separation for fluorometric determination of naproxen and felbinac in human plasma

Fluorous derivatization followed by fluorous-phase liquid chromatographic (LC) separation exploits the affinity between perfluoroalkyl compounds for highly selective and quantitative isolation of various analytes. However, the applicability of this technique as a simple pretreatment for fluorometric determination in clinical settings has not been fully explored. Here we show the applicability of this technique to the clinical determination of non-steroidal anti-inflammatory drugs (NSAIDs) in human plasma. Naproxen and felbinac, widely used native-fluorescent NSAIDs with a carboxyl group, can have toxic effects at acute doses, and were therefore chosen as representative NSAIDs. Samples were precolumn derivatized with a non-fluorescent fluorous amine, which allowed highly selective retention of only derivatized substances in the fluorous LC column. Thus, subsequently, only the retained fluorous-labeled and fluorescent analytes were detected fluorometrically at appropriate retention times. The detection limits for these two drugs were less than 11fmol on column. Correlation curves were liner over the range of 0.04-10 and 5-250nmol/mL plasma for both two drugs (r>0.999) with good repeatability. Thus, this method offers a simple, sensitive, and selective solution for determination of NSAIDs in clinical settings.     

Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats

We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 microL min(-1) with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetateinduced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and 0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation.     

B超引导下改良塞丁格技术在PICC置管术中的临床应用

目的 探讨B超引导下改良塞丁格技术在PICC置管中的应用及效果.方法 选取200例拟行PICC患者,随机分为观察组和对照组,每组100例.对照组给予传统盲穿置管法,观察组给予B超引导下改良塞丁格技术置管法.比较两组患者置管成功率、穿刺点渗血率、穿刺点疼痛率、舒适度评分、机械性静脉炎发生率.结果 观察组和对照组一次置管成功率分别为89.0％(89/100)和75.0％(75/100),组间比较差异具有统计学意义(P＜0.05).观察组患者穿刺点渗血发生率、穿刺点疼痛发生率及舒适度评分分别为31.0％ (31/100)、4.0％(4/100)、(27.9±2.4)分,对照组分别为48.0％(48/100)、12.0％(12/100)、(20.5±3.0)分,组间比较差异具有统计学意义(P＜0.05).观察组患者机械性静脉炎发生率明显低于对照组(2.0％ vs 27.0％),组间比较差异具有统计学意义(P＜0.05).结论 采用B超引导下改良塞丁格技术进行PICC置管,可提高置管成功率、减少不良反应、降低机械性静脉炎,值得临床推广应用.