高纯度庆大霉素C1a游离碱制备工艺研究

目的 探索用大孔吸附树脂层析法及盐析结晶法精制纯化硫酸依替米星起始物料-庆大霉素C1a成品(HPLC纯度91%~93%)，从而减少由起始物料引入依替米星杂质的水平。方法 以庆大霉素C1a吸附量和庆大霉素C1a纯度为指标，考察大孔吸附树脂纯化庆大霉素C1a的吸附性能和洗脱参数；以盐析后庆大霉素C1a样品纯度和盐析收率为指标，考察盐析工艺最佳温度、溶剂、酸的添加量及酸的种类。结果 获得较优的树脂NM200，获得较优的解析液pH值为2.0和流速0.5BV/h。经过优化后，纯化收率从65%提高至74%。通过盐析结晶条件筛选和优化，确定室温先加溶剂后加硫酸(pH6.5)和甲醇与乙醇1:2的条件较优，优化后获得的庆大霉素C1a纯度达到98.2%，收率大于93%。研究了多种无机酸盐析结晶的情况，发现磷酸、硫酸和碳酸条件下能析出白色固体。结论 通过比较大孔吸附树脂和盐析结晶的纯化连接，组合纯化后获得的庆大霉素C1a游离碱纯度大于99.0%，比纯化前样品提高6%以上，收率大于70%。     

Is gentamicin safe and effective for severe community-acquired pneumonia? An 8-year retrospective cohort study

Gram-negative bacilli are the causative organisms in a significant proportion of patients with severe community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU). Clinical guidelines recommend broad-spectrum antimicrobials for empirical treatment despite alarming global trends in antimicrobial resistance. In this study, we aimed to assess the safety and efficacy of gentamicin, an aminoglycoside with potent bactericidal activity, for empirical Gram-negative coverage of severe CAP in patients admitted to the ICU. A retrospective cohort study was performed at a university teaching hospital where the severe CAP guideline recommends penicillin, azithromycin and gentamicin as empirical cover. Ceftriaxone plus azithromycin is used as an alternative. Adults with radiologically-confirmed severe CAP were included, comparing those who received gentamicin in the first 72?h of admission with those who did not. Participants were identified using ICD-10 codes for bacterial pneumonia and data manually extracted from electronic medical records. Of 148 patients admitted with severe pneumonia, 117 were given at least one dose of gentamicin whereas the remaining 31 were not. The two groups were well matched in terms of demographics, co-morbidities and disease severity. There were no significant differences between the gentamicin and no-gentamicin groups in the incidence of acute kidney injury [60/117 (51%) vs. 16/31 (52%), respectively], hospital mortality [20/117 (17%) vs. 7/31 (23%)] and secondary outcomes including relapse and length of hospital stay. In conclusion, gentamicin is safe and has similar outcomes to alternative Gram-negative antimicrobial regimens for empirical coverage in severe CAP patients admitted to the ICU.     

对中国药典2015年版硫酸庆大霉素原料及其注射液标准中存在问题的探讨

中国药典2015年版中对硫酸庆大霉素原料和注射液标准进行了修订,其中在有关物质检查项下二者的限度数值相同。但由于原料和注射液中硫酸庆大霉素有关物质含量的含义和量纲(单位)不同,使得可能出现合格原料生产出不合格注射液的尴尬局面。本文从庆大霉素含量表征的特点入手,通过阐述原料和其制剂有关物质含量表述方式和量纲(单位)方面的差异,并以量效统一化研究为基础,讨论可以确保两标准限度间相互匹配的解决方案,从而为该品种的合理修订提供理论支撑。     

庆大霉素-藻酸钙三维缓释微球的药物释放研究

目的研制庆大霉素一藻酸钙三维缓释微球并调控其庆大霉素的释放。使其达到长期局部抗菌的效果。方法制作不同浓度T、S、U组庆大霉素-藻酸钙缓释凝珠,与庆大霉素-骨水泥颗粒Y组进行庆大霉索释放情况比较。通过不同时间点抽取浸泡液,送紫外分光光度法（UV）及金黄色葡萄球菌（SA）培养检测,由此计算出各组包封率、释放率,绘制庆大霉素释放曲线。结果4组样品（微生物法）的包封率及30d药物释放率分别为：U组（53．99％、36．31％）,S组（39．62％、27．55％）。T组（34．20％、30．83％）,Y组（100．00％、48．49％）。U组的包封率较高,30d释放庆大霉素的总量较大,更接近Y组。4组间差异有统计学意义（P〈0．01）。U、Y组庆大霉素的释放明显高于S、T组的释放。各组30d内庆大霉素的浓度几乎都能超过金黄色葡萄球菌的最低抑菌浓度（MIC）．即〉2μg／mI。结论U组载药缓释凝珠30d内的庆大霉索释放较为理想。可作为BMSCs的三维培养支架。     

胰岛素山莨菪碱联合庆大霉素湿敷治疗压疮的观察

目的：探讨胰岛素山茛菪碱联合庆大霉素湿敷治疗压疮的效果。方法：将62例Ⅱ～Ⅳ期压疮患者随机分为研究组和对照组。研究组采用胰岛素、山莨菪碱联合庆大霉素湿敷治疗，对照组用0．5％碘伏棉球直接涂抹治疗。结果：研究组在平均治愈天数、治愈率及有效率方面与对照组比较差异有显著性（P〈0．05），研究组疗效优于对照组，同时缩短了愈合时间。结论：胰岛素、山莨菪碱联合庆大霉素湿敷治疗压疮效果较好，缩短了压疮愈合时间，提高了压疮的治愈率。     

庆大霉素C组分和有关物质测定的HPLC-柱后衍生化法与脉冲安培电化学法的比较研究

摘 要 目的： 参考《欧洲药典》的HPLC 脉冲安培电化学法建立高效液相色谱 柱后衍生化法测定庆大霉素C组分含量及其有关物质, 同时与电化学法进行比较研究。方法: 采用亲水性HydrosphereC₁₈（250 mm×4.6 mm,5 μm）色谱柱,以含0.7%三氟乙酸及0.025%五氟丙酸的50 mmol·L^-1氢氧化钠溶液（pH2.6）-乙腈（98.5∶1.5）为流动相。衍生化法反应温度30℃,荧光激发波长340 nm,发射波长430 nm。电化学法采用脉冲安培检测器,金电极为工作电极,四电位波形工作模式。结果:两种方法测定的庆大霉素C组分（C_1a, C₂, C_2a和C₁）分别在5.82～233.00,6.92～277.00,4.00～160.00和6.23～249.00 μg·mL^-1的浓度范围内线性关系良好（r均≥0.999 3）,检测限和定量限范围分别为0.92～3.28 ng和1.37～5.19 ng。结论: 两种方法的检测结果无明显差异。     

Gentamicin affects melanogenesis in normal human melanocytes

Background: Aminoglycoside antibiotics, including gentamicin, despite their ability to induce adverse effects on pigmented tissues, remain valuable and sometimes indispensable for the treatment of various infections. It is known that gentamicin binds to melanin biopolymers, but the relation between this drug affinity to melanin and its toxicity is not well documented. The aim of this work was to examine the impact of gentamicin on viability and melanogenesis in HEMa-LP (light pigmented) and HEMn-DP (dark pigmented) normal human melanocytes.

Methodology/principal findings: The effect of gentamicin on cell viability was determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay; melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that gentamicin induces concentration-dependent loss in melanocytes viability. The application of antibiotic in concentration of 10?mM causes higher reduction in viability of the light pigmented melanocytes (by about 74%) when compared with the dark pigmented ones (by about 62%). The value of the concentration of a drug that produces loss in cell viability by 50% (EC₅₀) for both cell lines was found to be ～7.5?mM. It has been shown that gentamicin causes inhibition of tyrosinase activity and reduces melanin content in light pigmented melanocytes significantly more than in the dark pigmented cells.

Conclusion/significance: We have found that gentamicin modulates melanization process in melanocytes in vitro, what may explain the potential role of melanin biopolymer in the mechanisms of undesirable toxic effects of this drug in vivo, as a result of its accumulation in pigmented tissues. We have also stated that the melanogenesis process in light pigmented melanocytes is more sensitive to the inhibitory effect of gentamicin than in the dark pigmented cells.     

Simplified conditions for storing and cryopreservation of dental pulp stem cells

ObjectivesThis study aimed to simplify the collection, isolation and cryopreservation procedure of human dental pulp stem cells (DPSCs) to ease the establishment of dental stem cell banking.DesignExtracted third molars were collected and stored either in growth medium or in gentamicin-saline (480 μg/ml) for 6, 9 or 12 h. DPSCs were isolated and subjected to cryopreservation by a controlled-rate or rapid freezing method in 5 or 10% DMSO. Flow cytometry and growth pattern of DPSCs before and after cryopreservation were conducted.ResultsRate of contamination by which the extracted teeth were stored in control and gentamicin-saline were 9.1% (N = 33) and 2.3% (N = 43), respectively. Successful cell isolation rate of teeth preserved in gentamicin-saline at 6 h (92.9%) was comparable to those of growth media group (90.3%). At 9 and 12 h, the rates dropped significantly to 75% and 54%, respectively. Cryopreservation by controlled-rate freezing either in 5 or 10% DMSO resulted in a significantly higher percentage of viable cells than by rapid freezing. Cells conserved by controlled-rate freezing in 5% DMSO showed a pattern of growth similar to control unfrozen cells; 10% DMSO significantly deteriorated the growth pattern of the cells. After thawing, DPSCs conserved by controlled-rate freezing still expressed stemness characteristics, although hematopoietic stem cell markers were slightly increased.ConclusionGentamicin-saline was effective in preserving human teeth for DPSC isolation. Controlled-rate freezing in 5% DMSO gave the highest rate of cell viability. This study simplifies the storage conditions and proposes a simple method for cryopreservation of DPSCs.     

阿霉素与庆大霉素治疗三叉神经痛的早期疗效对比研究

目的：比较不同浓度阿霉素及庆大霉素用于三叉神经痛的治疗效果。方法：50例三叉神经痛患者随机分为3组，分别用0．2％、0．5％阿霉素及庆大霉素行外周神经阻滞。观察治疗前、治疗后1天、3天、1周、2周、1月、2月、3月时的疼痛缓解情况及治疗过程中出现的不良反应。结果：0．2％阿霉素组除治疗后第1天外其余各时间点数字评分(NRS)均较治疗前降低，而其它两组治疗后各时间点NRS均明显下降。0.5％阿霉素组在治疗后1天、2周、1月、2月、3月时的NRS值明显低于0．2％阿霉素组，治疗后1月、2月时明显低于庆大霉素组。0．5％阿霉素组有效率明显高于0．2％阿霉素及庆大霉素组。结论：0.5％阿霉素对三叉神经痛的治疗效果较好，庆大霉素可用于病情不太严重的患者。     

含庆大霉素冲洗液预防输尿管镜碎石术后感染

目的探讨在手术中应用含有庆大霉素的冲洗液以预防输尿管镜碎石术后感染的临床效果。方法采用前瞻性、随机对照研究。2003年7月-2006年6月116例具有输尿管镜碎石术后感染高危因素患者被随机分为庆大霉素组(GP)和对照组(CP),GP组在术中使用含有庆大霉素的冲洗液。术后随访2周,期间出现临床感染征象者考虑为术后感染。结果116例患者最终有109例完成手术,其中GP组58例,CP组51例。在所有完成手术患者中,13例临床诊断为术后感染(占11.9%),其中GP组3例(3/58,5.2%),CP组10例(10/51,19.6%),两者间差异有统计学意义(χ~2=5.3342,P=0.0209)。13例诊断为术后感染的患者中有8例分离到病原菌,1例为血培养阳性;其中革兰阳性菌2例(占15.4%),革兰阴性菌5例(占38.5%),1例为白念珠菌(占7.7%),另5例细菌培养阴性(占38.5%)。结论输尿管镜碎石术后感染仍以革兰阴性菌较为常见,在采取适当保护措施后发生血流感染概率较低。术中使用的冲洗液中加入庆大霉素后,可以减少术后感染的发生。