葡萄糖酸依诺沙星溶液的稳定性研究

目的考察葡萄糖酸依诺沙星溶液的稳定性。方法采用紫外分光光度法测定溶液中葡萄糖酸依诺沙星含量,HPLC法测定有关物质含量,考察了不同pH值的葡萄糖酸依诺沙星溶液在光照及高温条件下的质量变化。结果葡萄糖酸依诺沙星溶液在光照下易变色pH值5.5～6.0溶液在高温、光照5d后即出现结晶。pH值3.0～4.0溶液在光照条件下含量下降较多,有关物质增加较多。pH在4.0～5.5之间的葡萄糖酸依诺沙星溶液稳定性较好。结论本品应遮光保存,液体制剂的pH值范围确定在4.0～5.5之间较好。     

微渗析技术研究依诺沙星眼用缓释凝胶剂兔眼内药动学

目的:研究依诺沙星家兔眼内药动学.方法:采用微渗析技术进行依诺沙星眼用缓释凝胶剂在体药动学的研究,数据经非隔室模型处理,以方差分析和双单侧t检验评价各参数.结果:眼用缓释凝胶剂的药动学参数为:AUC=(1.615±0.900)μg·h·mL-1,Cmax=(2.726±1.790)μg·mL-1,Tmax=(0.33±0.24)h,Ke=(0.270±0.140);滴眼液的药动学参数为:AUC=(0.414±0.210)μg·h·mL-1,Cmax=(0.689±0.890)μg·mL-1,Tmax=(0.25±0.10)h,Ke=(0.548±0.500).结论:眼用缓释凝胶剂明显提高了药物在眼内的生物利用度,并且延长了作用时间,达到了缓释制剂的设计要求.     

依诺沙星角膜透过性的研究

目的:研究依诺沙星(ENX)的角膜透过性,为其处方设计提供理论基础.方法:采用体外扩散实验考察在多种渗透促进剂条件下ENX的离体兔眼角膜透过性.结果:1%的泊洛沙姆F68和2%羟丙基-β-环糊精(HP-β-CD)分别使ENX的表观渗透系数增加1.65和2.05倍,与对照组呈现显著性差异(P<0.01),而0.5%乙二胺四乙酸二钠(EDTA)与0.05%月桂氮(艹卓)酮(Azone)未能显著增大ENX的表观渗透系数(P>0.05);所有渗透促进剂均未显著改变ENX透过角膜的滞后时间;0.05% Azone和1% F68对眼组织具有刺激性.结论:2% HP-β-CD能够显著增加ENX的表观渗透系数,且对角膜无明显刺激性.     

Periodontitis in Rats Induces Systemic Oxidative Stress That Is Controlled by Bone‐Targeted Antiresorptives

Background: Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease–induced oxidative stress during oral infection. Methods: Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis‐enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham‐infected rats. Results: Rats infected with the periodontal pathogens displayed a five‐fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone‐targeted antiresorptives bis‐enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis‐enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. Conclusion: To the best of the authors’ knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone‐targeted antiresorptives.     

反相高效液相色谱法测定依诺沙星胶囊的血药浓度

目的　建立测定人血清中依诺沙星的浓度高效液相色谱法。方法　选用Shim packCLC ODS柱 (15 0mm× 6mm ,i d ,5 μm) ,0 .1mol L- 1 柠檬酸—甲醇 (78∶2 2 )为流动相 ,流速 1.0ml·min- 1 ,室温 ,检测波长 2 6 6nm ,灵敏度 0 .0 4AUFS。结果　在 0 .0 5～ 10 .0 μg·ml- 1 范围内血药浓度与色谱峰高线性关系良好 ,r=0 .9999(n =7,P <0 .0 0 1) ,平均回收率为 99.83% ,日内RSD≤ 2 .5 4 % (n =3) ,日间RSD≤ 4 .13% (n =5 )。结论　本法简便、灵敏、经济、重现性好 ,可作为依诺沙星药代动力学研究时血药浓度的测定方法。     

Evaluation of transdermal iontophoresis of enoxacin from polymer formulations: in vitro skin permeation and in vivo microdialysis using Wistar rat as an animal model

Polymers were used in vehicles to form hydrogel matrices in this study to evaluate the in vitro permeation and in vivo microdialysis of enoxacin. The highest transdermal delivery determined by area under flux-time curve (AUC) and intracutaneous enoxacin concentration were observed in methylcellulose (MC) and polyvinylpyrrolidone (PVP) hydrogels, respectively. To avoid the pH shift in vehicles during iontophoresis, buffer species were added to formulations to increase the buffer capacity. As expected, the permeability of enoxacin of anodal iontophoresis was larger than that of cathodal iontophoresis. Combination of benzalkonium chloride, a cationic surfactant as an enhancer, and iontophoresis exerted an enhancing effect for anionic enoxacin at pH 10.0. However, no effect or a negative effect was detected for cationic enoxacin in deionized water or pH 5.0 buffer, due to the shielding of the negative charge in the skin. The skin residue of enoxacin was slightly increased after the incorporation of Azone in PVP hydrogel. The result of in vivo microdialysis was in accordance with that of in vitro study. The effect of Azone on the intracutaneous enoxacin was more significant for in vivo microdialysis than in the in vitro study indicating the clinical feasibility of Azone for iontophoretic delivery. Microdialysis can be considered as a useful technique to investigate the pharmacokinetics of transdermal iontophoresis in vivo.     

Dysprosium‐sensitized chemiluminescence system for the determination of enoxacin in pharmaceutical preparations and biological fluids with flow‐injection sampling

A novel trivalence dysprosium(Dy³⁺)‐sensitized chemiluminescence method was developed for the first time for the determination of enoxacin (ENX) using flow‐injection sampling based on the chemiluminescence (CL) associated with the reaction of the Dy³⁺‐cerium(Ce(IV))‐S₂O₃^2?‐ENX system and the Dy³⁺‐MnO₄^? S₂O₃^2?‐ENX system. The analytical conditions for CL emission were investigated and optimized. The relationship between the CL intensity of ENX and its concentration has good linearity, with a correlation coefficient of 0.9984–0.9994. The limit of detection (LOD, 3σ) was 0.20 ng/mL for the Dy³⁺‐ENX‐S₂O₃^2?‐Ce(IV)‐H₂SO₄ system and 0.22 ng/mL for the Dy³⁺‐ENX‐S₂O₃^2?‐MnO₄^?‐HNO₃ system. The relative standard deviation (RSD, n = 11) was 1.8% for 11 determinations of 60 ng/mL ENX. The proposed method was applied to the analysis of ENX in injections, serum and urine samples with a recovery of 98%–105%. A possible mechanism for this sensitized CL reaction is discussed by comparing the CL spectra with the fluorescence emission spectra. The proposed method represents a wide linear range, high sensitivity and accuracy, and can be used for the routine determination of ENX in pharmaceutical preparations and biological fluids. Copyright © 2009 John Wiley & Sons, Ltd.     

葡萄糖依诺沙星治疗男性泌尿生殖器感染的疗效观察

目的:评价葡萄糖依诺沙星治疗男性泌尿生殖器感染的疗效.方法:选择符合诊断标准的患者500例,随机分为两组(各250例),实验组应用为注射用葡萄糖依诺沙星,对照组应用为盐酸左氧氟沙星注射液.结果:实验组的痊愈率和有效率分别为85.49％,98.73％,对照组为63.54％,91.68％；实验组的细茵清除率100％,对照组为92.86％；实验组的不良事件发生率为7.6％,对照组为3.2％,均无显著性差异(P＞0.05).结论:葡萄糖依诺沙星在治疗男性泌尿生殖器感染中有较好的临床疗效和安全性.     

依诺沙星在前列腺中相对生物利用度

本文报道了豚鼠口服５０ｍｇ／ｋｇ依诺沙星后，血和前列腺组织中药物动力学及相对生物利用度的结果。采用微生物法测定生物样品的药物浓度，用３Ｐ８７实用药代动力学程序处理药物浓度，并自动算出各项动力学参数和Ｃ－Ｔ曲线图，主要参数ｔ＿（１／２ｋｅ），ｔ＿ｐ，Ｃ＿（ｍａｘ），ＡＵＣ，Ｃｌ和Ｖｄ在血液中分别为３．０２ｈ，１．４５５ｈ，３．３３μｇ／ｍｌ，１９．８８９μｇ·ｈ／ｍｌ，２．５１４Ｌ／ｋｇ·ｈ，１０．９５１Ｌ／ｋｇ和前列腺组织中分别为１．８６８ｈ，２．４９ｈ，５．７０１μｇ／ｍｌ，３３．１４μｇ·ｈ／ｍｌ，１．５０９Ｌ／ｋｇ·ｈ和４．０６６Ｌ／ｋｇ，前列腺组织药物浓度曲线下面积相对血液中生物利用度为１６６．６％，结果表明药物在前列腺组织中达峰时间为２．４９ｈ，峰浓度高，清除较慢，前列腺组织中浓度明显高于血液浓度。     

氧氟沙星、依诺沙星和诺氟沙星治疗伤寒疗效比较

用氧氟沙星(65例)0.6g/d,依诺沙星(57例)0.6g/d,诺氟沙星(65例)0.8-1.2g/d治疗伤寒。开始退热时间依次为2.6±1.0d,3.8±1.2d,5.3±1.8d,热退到正常时间4.4±1.4d,7.6±2.6d,10±3d,疗程7.5±1.1d,10.6±2.6d,13±3d,有效率依次为100％,90％,63％。结果提示:氧氟沙星疗效显著优于依诺沙星和诺氟沙星,是临床治疗伤寒的满意药物。