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。     

氟比洛芬酯注射液消除瑞芬太尼全身麻醉患者术后苏醒期躁动的临床观察

疼痛是全麻患者术后躁动的主要原因。瑞芬太尼是一种短效阿片类药物,半衰期短,术后苏醒迅速。瑞芬太尼的超短效作用使患者术后急需镇痛药物。氟比洛芬酯注射液（凯芬）是非甾体类静脉注射靶向镇痛药物,具有作用持久,疗效确切的优点。本研究旨在观察氟比洛芬酯注射液消除瑞芬太尼全麻患者术后苏醒期躁动的效果。     

氟比洛芬聚丙烯酸树脂RL/RS固体分散体的制备

目的制备氟比洛芬固体分散体并考察其体外释药特性。方法以氟比洛芬为主药,分别以聚丙烯酸树脂Eudragit RL、RS及RL/RS混合物为载体,卵磷脂为乳化剂,以溶剂法制备固体分散体。以体外溶出半衰期t1/2为指标,优选固体分散体的最佳制备方法。结果氟比洛芬固体分散体的最佳处方比例为:药物∶载体=1∶9,RL∶RS=2∶1,卵磷脂浓度为0.2%。固体分散体体外溶出测定采用小杯法,测定波长为247 nm,分别采用紫外分光光度法和差示扫描热量法进行定量、定性分析。结论制备所得氟比洛芬固体分散体体外溶出缓慢、平稳、完全,达到提高生物利用度、12 h给药1次的缓释设计目的,可进一步制成其他剂型。     

HPLC法拆分氟比洛芬对映体

建立氟比洛芬手性药物的高效液相色谱拆分方法。方法:手性流动相添加剂HPLC法:利用C18柱,以羟丙基-β-环糊精作为手性流动相添加剂,调节有机修饰剂甲醇的比例和添加不同量的三乙胺对氟比洛芬进行拆分;手性固定相HPLC法:利用Chiral-pakAD手性柱,以正己烷-乙腈为流动相基本成分,调整两者不同比例和添加不同量的三乙胺,对氟比洛芬进行拆分。结果:手性流动相添加剂法:使用C18柱对氟比洛芬对映异构体进行拆分,调节流动相中有机修饰剂甲醇浓度、手性流动相添加剂羟丙基环糊精浓度、峰型修饰剂三乙胺的浓度等都不能使氟比洛芬对映体达到基线分离,只能部分分离。手性固定相法:氟比洛芬对映体在Chiral-pakAD手性柱上能达到较好的分离。在正己烷-乙腈流动相系统中,正己烷体积含量为90%,三乙胺体积含量为0.05%的条件下,氟比洛芬对映体得到了较好的分离,分离度为10.0。结论:建立的手性固定相法能有效拆分氟比洛芬对映体而手性流动相添加剂法不能拆分氟比洛芬对映体。     

氟比洛芬透皮贴剂的质量控制及体外透皮试验

目的:建立氟比洛芬贴剂的质量控制方法,并考察其体外透皮效果.方法:以HPLC法测定氟比洛芬的含量,并测定黏附性能、含量均匀度等指标;同时对其小鼠离体皮肤透皮特性进行了测试.结果:建立的HPLC法可用来测定氟比洛芬的含量,在0.1～100 mg·L-1范围内线性关系良好,该贴剂具有良好的黏附性能,24 h内累积渗透量为979.9 μg.结论:建立的方法可用于氟比洛芬贴剂的质量控制,其体外透皮效果良好.     

洛索洛芬钠大鼠在体肠吸收动力学研究

目的:研究洛索洛芬钠大鼠在体肠吸收动力学,为剂型设计提供依据。方法:采用大鼠在体肠灌流方法,采用高效液相色谱法-紫外检测器测定洛索洛芬含量,取麻醉后大鼠的十二指肠、空肠、回肠和结肠段作为受试肠段建立在体肠灌流模型,计算洛索洛芬的吸收速率常数和吸收百分率。结果:洛索洛芬在大鼠各肠段吸收百分率和吸收速率常数均无显著性差异(P>0.05),无特异吸收部位。洛索洛芬在不同质量浓度及pH范围内的肠吸收速率常数基本不变。结论:洛索洛芬大鼠肠吸收为一级动力学过程,各肠段均有吸收,吸收机制为被动扩散,适合制成缓控释制剂。     

氟比洛芬酯脂微球注射液对老年癌痛镇痛作用的临床分析

目的观察氟比洛芬酯脂微球载体注射液(商品名凯纷)治疗老年癌痛的疗效和副作用。方法 47例不能耐受阿片类药物或阿片类药物效果不佳的癌性疼痛患在2周的时间内者每天静脉注射50～100 mg氟比洛芬酯脂微球载体注射液,分别就其疗效、生活质量改善情况以及不良反应等方面进行全面评价。结果氟比洛芬酯脂微球载体注射液治疗老年癌痛的有效率为87.23%(PR+CR),生活质量改善情况治疗前后差异有统计学意义(P<0.05)。但未见一般非甾体类药物常见腹痛、消化道出血等副作用;也未见便秘、恶心、呕吐、嗜睡、血压下降等阿片类药物常见不良反应。结论氟比洛芬酩脂微球载体注射液治疗老年癌痛疗效可靠,生活质量可得到改善,氟比洛芬酯脂微球载体注射液不良反应发生率较低,为临床止痛药物的选择提供了一个新途径。     

氟比洛芬酯超前镇痛对甲状腺手术患者镇痛效果及血浆细胞因子的影响

<正>氟比洛芬酯为新型非甾体类靶向镇痛药,目前国内外对氟比洛芬酯用于甲状腺手术镇痛仅停留于临床镇痛效果评估,关于细胞因子水平变化的报道少见。本研究旨在观察氟比洛芬酯对甲状腺手术患者行超前镇痛的效果,及其对术后细胞因子改变的影响。1资料与方法1.1一般资料:选择美国麻醉学家学会(ASA)Ⅰ～Ⅱ级择期行甲状腺切除术患者80例,随机分成对照组和试验组(氟比洛芬酯脂组)。2组年龄、体质量、手术时间比较差异     

GC-MS与稳定的同位素技术相结合评价大鼠中舒洛芬的代谢手性转化

舒洛芬［（±）－α－4－（2-噻嗯基羰基）苯乙酸）是肝芳丙酸型的非自体抗炎药，具有手性碳原子，因此以对映体形式存在，除甲氧茶丙酸外，服用外消旋混合物。为了研究循环系统对映体的转化，作者新近发展了稳定的同位素一标记假外消旋体一非对映体方法学，它可评价每个对映体的药动学，包括给予外消旋混合物后的手性转化的测定。本文报道了Wistar大鼠中舒洛芬对映体的药动学和分离鼠肝细胞中舒洛芬的手性转化。同位素合成物为外消旋舒洛芬SP一办SP－d7。本标记外消旋舒治芬SP心其对映体为（S）－SP一小（R）－SP王向，（S）－SPdx…     

洛索洛芬钠双层缓释片的研制和体外释放特性研究

目的：研制洛索洛芬钠双层缓释片并考察其体外释药特性。方法：以两种不同处方作湿法制粒,压制双层片,用高效液相色谱法测定洛索洛芬钠的释放度.结果与结论：洛索洛芬钠双层缓释片的释药曲线可用Higuchi方程或Peppas方程拟合,可维持12h持续释放达到设计要求.     

Supramolecular chiro-biomedical assays and enantioselective HPLC analyses for evaluation of profens as non-steroidal anti-inflammatory drugs, potential anticancer agents and common xenobiotics

The permanent world-wide increase in therapeutic administration of racemic profens as easy available non-prescribed analgesic drugs and a common first-choice anti-inflammatory agents was recently linked with renewed interest in their beneficial use, also as enantiopure formulations, to treat and/or prevent a variety of human malignancies including its four major types as colorectal, breast, lung, and prostate cancer. This underlies the continuous need of selecting perfectly suited chiral separation methods of profens capable to determine nanolevels of a distomer in presence of the eutomer in a variety of complex biological and environmental media. Thus, current improvements for direct enantiomeric separations of profens by well defined supramolecular-based chiral HPLC and recently developed monolithic, combinatorial, bimodal and polymeric chiral stationary phases employing a modern supramolecular chirality concepts has been outlined in this review. The use of diverse supramolecular approaches for chiral HPLC as an easy accessible tool enabling fast development of nanoscale enantioselective, high-throughput and gradient screening procedures for in situ monitoring of stereoselective ADME properties of profens in range of anticancer drug discovery technologies has been also addressed.     

Bovine serum albumin adsorbed on eremomycin and grafted on silica as new mixed-binary chiral sorbent for improved enantioseparation of drugs

A new silica-based, mixed-binary chiral sorbent grafted with the macrocyclic antibiotic eremomycin and bovine serum albumin (BSA) was obtained. The sorbent-filled high-performance liquid chromatography column was capable of enantioseparation of racemic drugs, such as profens, in reversed-phase-chromatography mode. The mixed-binary eremomycin-BSA-sorbent showed better capability for profens enantioseparation as compared with a sorbent containing eremomycin only. BSA grafted onto the sorbent surface significantly reduced retention times of other proteins from the analyte solution, and free proteins (including BSA) injected as analytes were not retained on the column, and subsequently eluted with a dead volume. The drastic difference observed in the binding of profens and other proteins using the sorbent was tested for determination and enantioseparation of profens in artificial-urine solutions.     

Simultaneously Improving the Mechanical Properties, Dissolution Performance, and Hygroscopicity of Ibuprofen and Flurbiprofen by Cocrystallization with Nicotinamide

Purpose

To be fully exploitable in both formulation and manufacturing, a drug cocrystal needs to demonstrate simultaneous improvement of multiple key pharmaceutical properties over the pure drug crystal. The present work was aimed at investigating such feasibility with two model profen-nicotinamide cocrystals.

Methods

Phase pure 1:1 ibuprofen-nicotinamide and flurbiprofen-nicotinamide cocrystals were prepared from solutions through rapid solvent removal using rotary evaporation,and characterized by DSC, PXRD, FTIR, phase solubility measurements, equilibrium moisture sorption analysis, dissolution testing and tabletability analysis.

Results

Temperature-composition phase diagrams constructed from DSC data for each profen and nicotinamide crystal revealed the characteristic melting point of the 1:1 cocrystal as well as the eutectic temperatures and compositions. Both cocrystals exhibited higher intrinsic dissolution rates than the corresponding profens. The cocrystals also sorbed less moisture and displayed considerably better tabletability than the individual profens and nicotinamide.

Conclusions

Phase behaviors of 1:1 profen-nicotinamide cocrystal systems were delineated by constructing their temperature-composition phase diagrams. Cocrystallization with nicotinamide can simultaneously improve tableting behavior, hygroscopicity, and dissolution performance of ibuprofen and flurbiprofen. This could pave the way for further development of such cocrystal systems into consistent, stable, efficacious and readily manufacturable drug products.     

Stereoselective internal acyl migration of 1beta-O-acyl glucuronides of enantiomeric 2-phenylpropionic acids

Internal acyl migration reactions of 1beta-O-acyl glucuronides of 2-arylpropionic acids (profens) are of interest because of their possible role in covalent binding to serum proteins and consequent allergic reactions. The stereoselective degradation of 1beta-O-acyl glucuronides of enantiomeric 2-phenylpropionic acids (PAs), the basic structures of profens, in phosphate buffer (pH 7.4) at 37 degrees C, has been investigated using HPLC. Apparent first-order degradation of 1beta-O-acyl glucuronide and the sequential appearance of 2-, 3- and 4-O-acyl isomers were observed for each enantiomer. Acyl migration was observed to predominate over hydrolysis as in the other profen glucuronides. All the positional isomers and anomers were characterized using NMR and HPLC-NMR. The overall degradation half-life of (R)- and (S)-PA glucuronides was 1.8 and 3.3 h, respectively. These results suggest that (R)-PA glucuronide could be more susceptible to covalent binding to proteins via acyl migration than the corresponding antipode. The lability of the (R)-diastereomer over the antipode is consistent with previous reports on other profen glucuronides. Thus, the diastereomeric PA glucuronides are considered to be the best model compounds for the computation of structural physicochemical parameters to control the stereoselective internal acyl migration of profen glucuronides because PA has the simplest chemical structure of all the profens.     

Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes

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Different in vitro activity of flurbiprofen and its enantiomers on human articular cartilage

The 2-arylpropionic acid derivatives or 'profens' are an important group of non-steroidal anti-inflammatory drugs that have been used for the symptomatic treatment of various forms of arthritis. These compounds are chiral and the majority of them are still marketed as racemate although it is known that the (S)- form is the principal effective in the cyclooxygenase inhibition. However, recent findings suggest that certain pharmacological effect of 2-arylpropionic acids cannot be attributed exclusively to the (S)-(+) enantiomer. To obtain further insights into the pharmacological effect of profens, the present study investigated the influence of racemic and pure enantiomers of flurbiprofen on the production of nitric oxide and glycosaminoglycans, key molecules involved in cartilage destruction. The culture of human articular cartilage stimulated by interleukin-1beta (IL-1beta), which plays an important role in the degradation of cartilage, has been established, as a profit experimental model, for reproducing the mechanisms involved in the pathophysiology of arthritic diseases. Our results show that mainly (S)-(+)-flurbiprofen decreases, at therapeutically concentrations, the IL-1beta induced cartilage destruction.     

Drug users' participation in addiction care: different groups do different things

This study allocated 201 (nearly) daily users of heroin and/or crack into four groups, depending on their addiction care participation. Earlier studies have compared treatment groups and nontreatment groups. In this study the treatment group is divided into three categories: (1) drug users in contact with only treatment agencies--i.e., methadone maintenance, clinical and ambulant drug treatment; (2) drugs users in contact with only care agencies--i.e., day and night shelters and drug consumption rooms, which have no explicit aims to change patterns of drug use; and (3) drug users in contact with both treatment and care agencies. This allocation intro three different groups fits the notion of harm reduction, one of the policy aims in The Netherlands. The fourth group consists of drug users in contact with neither treatment nor care agencies. The results show that it is useful to distinguish these four categories, instead of two. The four groups are different from each other with respect to some of their characteristics (e.g. debt situation, prostitution, homelessness) and their drug use (e.g. drug use in public, use of crack, and use of other drugs). A much clearer distinction can be made between the "care" group and the "treatment and care" group. Treatment and care agencies can thus better match their services to their clients or patients.     

The role of drugs in crime: insights from a group of incoming prisoners

The present study was designed to evaluate whether drug dependence is associated with any specific perception of the role of drugs in crime. In the summers of 1997 and 1998, face-to-face interviews were conducted with members of a group of incoming prisoners at the Cuyahoga County Jail in Cleveland. Ohio. "Incoming prisoners" denotes persons whose criminal cases had been adjudicated and who were of their way to one of Ohio's prisons. Respondents were asked whether they themselves perceived that drugs had been a factor in the crimes for which they had been arrested. Those respondents classified as dependent on at least one illicit drug tended to answer affirmatively. This sub-group was also more likely than their non-dependent counterparts to admit to using drugs in the two days following the commission of their crimes. Specifically, these respondents viewed the need to obtain drugs for personal use as one of their main motives for participating in crime.     

波士顿矩阵理论在医院药品战略管理中的应用研究

目的:通过对比研究H1医院和H2医院的药品销售数据,供H1医院领导决策参考。方法:调查和统计H1医院和H2医院2003~2007年的药品销售总额及化学药品(包括生物制品)、中成药和中草药的销售额,应用波士顿矩阵进行相对市场占有率、市场增长率等的分析评价。结果:H1医院的化学药品、中成药业务为明星类业务;中草药业务为瘦狗类业务。结论:对H1医院的化学药品、中成药业务采取增长战略,促使其转变为金牛类业务;对中草药业务采取收缩战略,积极寻找出路,合理控制库存。     

Old and new antiepileptic drugs for the treatment of idiopathic generalized epilepsies

Generalized epilepsies are a large group of epilepsies with different clinical aspects and prognosis. Many antiepileptic drugs are available for the treatment of these seizures. This paper reviews the evidence relating to the treatment of this group of epilepsies. Historically, the great majority of patients have been treated with "old" anticonvulsant drugs. Over recent years, there has been a marked improvement in the pharmacological armamentarium of physicians. Today, "new" antiepileptic drugs, such as lamotrigine, levetiracetam, topiramate and zonisamide are useful tools in the treatment of pharmacoresistant epilepsies.