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Frontiers of Chemical Science and Engineering 2013年第3期7卷 322-328页

作者： Liang ZHU Jingkang WANG Tianjin Key Laboratory of Marine Resources and Chemistry College of Marine Science and Engineering Yianjin University of Sciencc & Technology Tianjin 300457 China School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China

A simple and direct method without a deriva- tion step for routine analysis of tobramycin has been developed. This method used reversed-phase ion-pair high performance liquid chromatography （HPLC） with a refractive index （RI） detector and a C18 column which is stable at pH above 1.00. The presence of *** ] trifluoroacetic acid （TFA） in the mobile phase improved the protonation of tobramycin and the formation of ionpairs, and thus reduced its hydrophility. This unique separation-detection combination showed good linearity with correlation coefficients 0.9996 in the concentration range of *** 1. The quantitation limit and detection limit were determined to be 0.23 *** ~ and 0.071 mg. mL ~, respectively. tobramycin was recovered in 98.00%, 98.84% and 99.64% for tobramycin solutions at concentrations of 2.25 ***^-1, *** 1 and 0.75 *** ＇, respectively. The relative standard deviations for six spiked samples ranged from 0.20% to 2.40%, indicating a good reproducibility of this method.

关键词： tobramycin aminoglycoside refractive index detector high-performance liquid chromatography ionpairing

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Anti-bacterial mechanism of baicalin-tobramycin combination on carbapenem-resistant Pseudomonas aeruginosa

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World Journal of Clinical Cases 2023年第17期11卷 4026-4034页

作者： Li-Min Jin Hui Shen Xing-Ying Che Ye Jin Chun-Mei Yuan Neng-Hua Zhang Laboratory Department Jiaxing Hospital of Traditional Chinese MedicineJiaxing 314001Zhejiang ProvinceChina

BACKGROUND Pseudomonas aeruginosa(***)is an important cause of nosocomial infections,and contributes to high morbidity and mortality,especially in intensive care *** is considered a'critical'category bacterial pathogen by the World Health Organization to encourage an urgent need for research and development of new antibiotics against its *** To investigate the effectiveness of baicalin combined with tobramycin therapy as a potential treatment method for carbapenem-resistant ***(CRPA)*** Polymerase chain reaction(PCR)and RT-PCR were used to detect the expression levels of drug-resistant genes(including VIM,IMP and OprD2)and biofilmrelated genes(including algD,pslA and lasR)in CRPA that confer resistance to tobramycin,baicalin and tobramycin combined with baicalin(0,1/8,1/4,1/2 and 1MIC).RESULTS There was a correlation between biofilm formation and the expression of biofilmrelated *** addition,VIM,IMP,OprD2,algD,pslA and lasR that confer biofilm production under different concentrations in CRPA were significantly *** synergistic effect of baicalin combined with tobramycin was a significant down-regulation of VIM,IMP,algD,pslA and *** Baicalin combined with tobramycin therapy can be an effective treatment method for patients with CRPA infection.

关键词： Baicalin Pseudomonas aeruginosa tobramycin Carbapenem-resistant Pseudomonas aeruginosa Therapy

Improved reversed phase liquid chromatographic method with pulsed electrochemical detection for tobramycin in bulk and pharmaceutical formulation

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Journal of Pharmaceutical Analysis 2013年第3期3卷 161-167页

作者： Vicky Manyanga Ehab Elkady Jos Hoogmartens Erwin Adams Laboratory for Pharmaceutical Analysis Faculteit Farmaceutische Wetenschappen KU LeuvenO&N2 PB 923 Herestraat 49 B-3000 Leuven Belgium Pharmaceutical Chemistry Department Faculty of Pharmacy Cairo University Kasr El-Aini St.Cairo 11562 Egypt

tobramycin is one of the aminoglycoside antibiotics that lack a UV absorbing chromophore. However, the application of pulsed electrochemical detection （PED） has been used successfully for the analysis of this and similar antibiotics. This work describes an improved liquid chromatographic （LC） method combined with PED, which is able to separate much more impurities than before. Using a Discovery C-18 RP column （250 mm × 4.6 mm i.d., 5 μm）, isocratic elution was carried out with a mobile phase, containing sodium sulfate （35 g/L）, sodium octanesulphonic acid （1 g/L）, tetrahydrofuran （14mL/L） and 0.2 M phosphate buffer pH 3.0 （50 mL/L）. Using these experimental conditions, the limit of quantification （LOQ, S/N= 10） was 5 ng. The linearity was examined in the range LOQ-60 μg/mL and the coefficient of determination was 0.998. The method also proved to be repeatable and the recovery was close to 100%. The influence of the different chromatographic parameters on the separation was investigated by means of an experimental design. The proposed method is useful in quality control of tobramycin drug substances and drug products.

关键词： Liquidchromatography-Pulsed electrochemicaldetection tobramycin Aminoglycosideantibiotics

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托普霉素tobramycin的研究概况

微生物学杂志 1989年第3期9卷 64-68页

作者：修凤华大连制药厂研究所

托普霉素硫酸盐(商品名Nebcin)作为氨基糖苷类抗生素之一,已广泛地应用于治疗敏感菌引起的败血症,脑膜炎的中枢神经感染,新生儿的脓毒症等。因此引起医学界的重视。

关键词：托普霉素 tobramycin 美国礼莱公司黑暗链霉菌琼脂斜面脓毒症培养基组分气生菌丝抗菌活性产生菌

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Evaluation of assays for aminoglycosides in serum:a comparison of accuracy and precision based on external quality assessment

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中国药理学与毒理学杂志 2019年第10期 815-816页

作者： LI Meng-ya CHEN Chao-yang LEI Li-li Zhao Xia ZHOU Ying CUI Yi-min Peking University First Hospital Peking University First Hospitall

OBJECTIVE To compare the accuracy and precision of commercial assay techniques in the measurement of gentamicin, tobramycin, and amikacin in serum. METHODS Human plasma samples were spiked with known concentrations of amikacin, gentamicin, and tobramycin and provided to worldwide laboratories. The methods participating in the study include Enzyme multiplied immunoassay technique(EMIT), fluorescence polarization immunoassay(FPIA), Kinetic interaction of microparticle in solution(KIMS), particle enhanced turbidimetric inhibition immunoassay(PETINIA), Cloned Enzyme Donor Immunoassay(CEDIA), Quantitative Microsphere System(QMS), Chemiluminescence, Vitros and so *** accuracy and precision were compared between assays and between drugs. RESULTS 273 results of amikacin, 534 results of gentamycin and 207 results of tobramycin measurements were analyzed. Satisfactory rate was 83.88%, 86.27%, 93.72% for amikacin, gentamycin, and tobramycin. Significant differences in both accuracy and precision between techniques were present for all drugs. Coefficients of variation ranged from 1.06%to 15.61%, from 2.88% to 25.16% and from 1.84% to26.97%, for amikacin, gentamycin, and tobramycin,respectively. The percentage difference ranged from-7.46% to 6.57%, from-20.78% to 18.68% and from-33.22% to 41.52%, for amikacin, gentamycin, and tobramycin, respectively. Detection limits were from 0 to 2.76 and 0.12 to 1.04 for amikacin and gentamicin. CONCLUSION All assays performed to a satisfactory standard for measurement, but significant differences in both accuracy and precision between techniques were present for all drugs. All assays need more accuracy and precision of therapeutic drug measurements.

关键词： aminoglycosides immunoassays TDM amikacin gentamicin tobramycin

The Effects of Antibiotics, Metals, and Biotic Interactions on the Assembly of Taxonomically Diverse Single and Mixed Species Biofilms

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Advances in Microbiology 2020年第12期10卷 623-646页

作者： Roshan Angoshtari Kim T. Scribner Terence L. Marsh Department of Microbiology and Molecular Genetics Michigan State University East Lansing MI USA Department of Fisheries and Wildlife Michigan State University East Lansing MI USA

To better understand the assembly of the sturgeon egg microbiome, we purified six bacterial isolates from eggs and characterized their ability to form biofilms under the stress of tobramycin, with and without exogenous protein. In experiments with single species biofilms, tobramycin reduced the metabolic activity of all isolates and increased biofilm biomass of three. The addition of exogenous protein to the assay countered the inhibition of biofilm and metabolic activity by tobramycin of Pseudomonas sp., Brevundimonas sp., Flavobacterium columnare and mixed biofilms of Pseudomonas-F. columnare and Brevundimonas-Hydrogenophaga. Two of the isolates (Pseudomonas spp.) that produced antimicrobial activity, were effective at reducing biofilm formation by Brevundimonas, but enhanced biofilm formation in other isolates. Increasing concentrations of Mg2+ had no effect on biofilm formation but Ca2+ enhanced biofilm formation of Pseudomonas aeruginosa PA01 (positive control) and Brevundimonas. Biofilm assembly by these two bacteria was inhibited by low concentrations of Ni2+. Mixed biofilms of Brevundimonas and Hydrogenophage consistently produced more robust biofilm than the strains in isolation, suggesting synergism. Established Brevundimonas biofilm appeared adept at recruiting pelagic Acidovorax and Hydrogenophaga into biofilm, suggesting that it plays an important role in the selection of species into the microbiome.

关键词： Biofilm Assembly Antimicrobial Resistance tobramycin Metabolic Activity Metal Resistance

Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins

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Journal of Biomaterials and Nanobiotechnology 2013年第4期4卷 343-350页

作者： Mirjam Lilja Jan H.Sorensen Torben C.Sorensen Maria Astrand Philip Procter Hartwig Steckel Maria Stromme Division for Nanotechnology and Functional Materials Department of Engineering SciencesThe Angstrom LaboratoryUppsala UniversityUppsalaSweden Sandvik Coromant AB StockholmSweden Department of Pharmaceutics and Biopharmaceutics Christian Albrecht University KielKielGermany Stryker Trauma GmbH SchonkirchenGermany Stryker Trauma AG SelzachSwitzerland School of Engineering and Design Brunel UniversityUxbridgeUK

This work investigates the impact of biomechanical wear and abrasion on the antibiotic release profiles of hydroxyapatite (HA) coated fixation pins during their insertion into synthetic bone. Stainless steel fixation pins are coated with crystalline TiO2 by cathodic arc evaporation forming the bioactive layer for biomimetic deposition of tobramycin containing HA. tobramycin is either introduced by co-precipitation during HA formation or by adsorption-loading after HA deposition. The samples containing antibiotics are inserted into bone mimicking polyethylene foam after which the drug release is monitored using high performance liquid chromatography. This analysis shows that HA coating wear and delamination significantly decrease the amount of drug released during initial burst, but only marginally influence the sustained release period. Spalled coating fragments are found to remain within the synthetic bone material structure. The presence of HA within this structure supports the assumption that the local release of tobramycin is not only expected to eliminate bacteria growth directly at the pin interface but as well at some distance from the implant. Furthermore, no negative effect of gamma sterilization could be observed on the drug release profile. Overall, the observed results demonstrate the feasibility of a multifunctional implant coating that is simultaneously able to locally deliver clinically relevant doses of antibiotics and an HA coating capable of promoting osteoconduction. This is a potentially promising step toward orthopaedic devices that combine good fixation with the ability to treat and prevent post-surgical infections.

关键词： Hydroxyapatite Fixation Pin tobramycin Coating Wear Drug Release Gamma Sterilization

氧氟沙星、环丙沙星和妥布霉素人眼局部滴眼的前房穿透性研究

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氧氟沙星、环丙沙星和妥布霉素人眼局部滴眼的前房穿透性研究

作者：章征浙江大学

学位级别：硕士

抗生素是预防和治疗眼内炎的重要手段，而局部点用抗生素滴眼液是其中一条途径。目前国内在眼部感染的局部治疗方面主要使用氧氟沙星、环丙沙星为代表的喹喏酮类滴眼液和以妥布霉素为代表的氨基糖甙类滴眼液。妥布霉素对一些葡萄球菌和... 详细信息

抗生素是预防和治疗眼内炎的重要手段，而局部点用抗生素滴眼液是其中一条途径。目前国内在眼部感染的局部治疗方面主要使用氧氟沙星、环丙沙星为代表的喹喏酮类滴眼液和以妥布霉素为代表的氨基糖甙类滴眼液。妥布霉素对一些葡萄球菌和多种革兰氏阴性菌有抗菌活性，对金黄色葡萄球菌、表皮葡萄球菌、一些革兰氏阴性菌和大多数厌氧菌无效。而氧氟沙星、环丙沙星等喹喏酮类药物对多种革兰氏阳性和阴性菌具有广谱抗菌活性，它们通过阻断DNA消旋酶而抑制微生物的DNA合成。相对于其他药物，在治疗剂量下，喹喏酮类对角膜上皮毒性最低，对角膜内皮、视网膜基本无毒性，且前房穿透性较好，适合于作为眼内感染的预防和治疗药物。至今国外对喹喏酮类药物局部使用后人眼的药物动力学研究均为单个时间点的取样，缺少连续的观察过程。而国内在此方面尚无报道。因此，本次研究旨在探究国内抗眼部感染最常用的三种抗生素眼药水：氧氟沙星、环丙沙星、妥布霉素，在给药后不同时间点的前房药物浓度，比较三种药物的生物利用度，从而为预防和治疗细菌性眼内炎中的局部用药提供依据。对象和方法一、研究对象在门诊预约准备行白内障超声乳化术的老年性白内障患者中选取125人，每人一眼，入组患者无其他眼部疾患、无糖尿病，无抗生素过敏史，且同时未接受其他口服或局部使用的抗生素治疗。二、研究药物 0.3％氧氟沙星，0.3％环丙沙星，0.3％妥布霉素。三、研究方法 1、分组方法将患者随机分为三大组，氧氟沙星组(女性21例，男性21例，年龄71.6±9.8岁)，环丙沙星组(女性21例，男性20例，年龄72.9±9.0岁)，妥布霉素组(女性21例，男性21例，年龄70.5±11.2岁)，三组患者年龄均数经q检验比较，P均大于0.05，差异无显著性。每大组再随机分为五小组，每组8人或9人，分别在最后一次给药后不同时间点时抽取前房水。 2、给药及样品的采集根据所在的大组，患者术前分别局部使用氧氟沙星或环丙沙星或妥布霉素，均给药6 次，每次间隔15分钟，每次一滴。根据患者所在的小组，手术者分别在最后一次给药后 7．5、15、30、60或 120分钟时抽取前房水。手术时，从前房抽取房水***，立即保存于－20C，至分析时取出。 3、药物分析方法－均采用高效液相仪，氧氟沙星和环丙沙星房水最低检测限：*** n g／ml。妥布霉素的房水最低检测限：0．05 u g／ml。 4、统计方法计算各时间点的药物浓度平均值，SPSS统计软件进行秩和检验。 5、整个研究过程采用双盲法，且给药、手术、药物分析和数据统计由不同人担任。结果在末次给药后7．5、15、30、60、120分钟，氧氟沙星的前房平均浓度依次为2．32土1．33、 2．59if．34、3．23士1．60、2．94土1．41、1．73土0．64 u g／ml，在 30分钟处达到前房最高浓度 3．23上1．60 u g／ml。在同样五个时间点下，环丙沙星的前房平均浓度依次为 0．27土0．16。 0．51土0．19、0．37士0．24、0．45士0．26、0．4410．25 u g／ml，在 15分钟处达到前房最高平均浓度 0．51J．19 u g加。在同一时间点，氧氟沙星平均浓度均显著高于环丙沙星，SPSS 统计软件做秩和检验，P均小于0．01。使用梯形面积法计算两种药物的 AUC，氧氟沙星为 294．71u g·min／ml，环丙沙星为 48．55 u g·min砌l，两者面积之比约为 6，故此给药模式下氧氟沙星的前房生物利用度高出环丙沙星5倍。在各时间点，前房水中的妥布霉素均未被高效液相仪检测出，故其浓度必低于最低检测限 0．05 u g ／ml。结论本研究采用频繁点眼，获得较高的前房氧氟沙星和环丙沙星药物浓度，参考以往文献中氧氟沙星、环丙沙星和

关键词： Aqueous humor Ofloxacin Ciprofloxacin tobramycin

A potential CSPG4-specific immunomodulatory agent inhibits glioma growth through regulating Treg cells

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A potential CSPG4-specific immunomodulatory agent inhibits g...