复方妥布霉素滴眼液的制备

为避免地塞米松在湿热灭菌过程中晶型改变科妥布霉素妥热分解。分别采用干热法和无菌过滤的灭菌工艺制备了复方妥布霉素滴眼液,制得的混悬液具有良好的稳定性。     

妥布霉素地塞米松眼膏联合茶树油清洁湿巾治疗蠕形螨睑缘炎

目的：探讨妥布霉素地塞米松眼膏联合缘螨净茶树油清洁湿巾治疗蠕形螨睑缘炎的治疗效果。

方法：前瞻性临床研究。选取蠕形螨睑缘炎患者72例,随机分为3组,试验组给予妥布霉素地塞米松眼膏联合缘螨净茶树油清洁湿巾治疗,对照1组给予妥布霉素地塞米松眼膏联合茶树油眼膏治疗,对照2组给予茶树油眼膏治疗。治疗30d后,对患者进行症状评分、拔睫毛螨虫计数及裂隙灯下观察临床体征评分。比较三组治疗前后数据。

结果：三组治疗前后蠕形螨计数均有差异(P<0.01),症状总评分差值有差异(F=20.05,P<0.01),体征总评分差值有差异(F=8.10,P<0.01)。

结论：妥布霉素地塞米松眼膏联合缘螨净茶树油清洁湿巾治疗蠕形螨睑缘炎疗效显著,茶树油清洁湿巾具有便携、易保存、不易变质的特点。     

妥布霉素玻璃酸钠滴眼液在超声乳化白内障摘出术后的应用

目的评价妥布霉素玻璃酸钠滴眼液在超声乳化白内障摘出术后应用的临床有效性和安全性。方法随机、双盲筛选出白内障患者121例（121眼）施行超声乳化白内障摘出联合人工晶状体植入术，分为试验组和对照组，试验组术后滴用妥布霉素玻璃酸钠滴眼液，对照组术后滴用妥布霉素地塞米松滴眼液，分别于术后第1d、用药后第3、7、14d观察眼部症状和体征，并进行统计学分析。结果两组术后泪膜破裂时间、结膜充血、睫状充血、房水闪辉等比较，差异有统计学意义（P〈0．05）；角膜内皮细胞计数、视力、眼压等比较差异无统计学意义（P〉0．05）。结论对部分手术创伤小，反应轻的超声乳化白内障摘出术后的患者可以使用妥布霉素玻璃酸钠滴眼液。     

HPLC梯度洗脱法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质

摘 要 目的： 建立HPLC梯度法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质。方法: 采用HPLC法,色谱柱：Inertsil ph苯基柱（250 mm×4.6 mm,5 μm）;流动相A：0.25%醋酸溶液 乙腈（80∶20）;流动相B：乙腈;流速：2.0 ml·min^-1,进行线性梯度洗脱;检测波长：244 nm;柱温：30℃;进样量：20 μl。结果: 主成分与各杂质峰分离度良好。氯替泼诺浓度在0.001~1.02 mg·mL^-1（r=0.999 9）范围内与峰面积线性关系良好,平均回收率为99.9%,RSD为0.9%（n=9）。结论:该方法灵敏准确,色谱峰分离完全,可用于氯替泼诺妥布霉素混悬滴眼液的质量控制。     

单组分妥布霉素产生菌的选育

目的 提高妥布霉素产生菌的发酵单位。方法 以黑暗链霉菌UVS－51为出发菌株，采用UV和NTG为诱变剂，结合耐受妥布霉素，运用固体循环诱变筛选高产菌株。结果 获得两株高产稳定变株NS－81和NT－26，这两株菌的授瓶发酵效价分别比出发菌株提高53％和77％。经薄层层析检验，该两变株的产物仍为单一的氨甲酰妥布霉素。结论 出发菌株经UV和NTG诱变处理后结合耐自身代谢物的驯育，正变率显著提高。通过引入循环诱变筛选的思路，大大缩短的实验周期有交待 提高了诱变育种的工作效率，能在较短时间内选育到理想变株，因此，循环诱变筛选法是一种较好的选育方法。     

Prediction of the Distribution Volumes of Cefazolin and Tobramycin in Obese Children Based on Physiological Pharmacokinetic Concepts

So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children. Serum concentration–time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80%. Volume of distribution at steady state (V _ss) per total body weight of tobramycin was significantly less than that for normal-weight children (P < 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children. The equation to express the difference of V_ss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children. The V _ss value (liter) for tobramycin was predicted by using the equation 0.261 · {ideal body weight (kg) + 0.4 · [total body weight (kg) – ideal body weight (kg)]}. The V _ss value of cefazolin was predicted to be 0.3 · (predicted V _ss of tobramycin) + 0.052 · total body weight (kg). A good correlation between the predicted and the observed V _ss values was obtained.     

Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week

Summary Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p>0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p>0.05), and elimination half-life averaged 8.6 and 7.1 h (p>0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants 1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p<0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p<0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants 1.5 kg birth weight.supported by Lilly Research Laboratories, Indianapolis, USA     

眼用妥布霉素羧甲基壳聚糖微球的制备及体外释放性能研究

目的 制备眼用妥布霉素羧甲基壳聚糖微球,并评价其体外释药性能。方法 采用乳化-交联固化法制备妥布霉素羧甲基壳聚糖微球,并以微球的收率、粒径分布和包封率作为评价指标,使用Box-Behnken实验设计优化得到妥布霉素羧甲基壳聚糖微球的最优处方。通过马尔文激光粒度仪测定了微球的粒径分布,扫描电镜观察其微观结构,考察微球在人工泪液中的释药性能。结果 优化得到微球的处方组成：羧甲基壳聚糖质量浓度为3.5%,甲醛质量浓度为1.5%,Span-80质量浓度为0.8%;妥布霉素羧甲基壳聚糖微球的平均粒径为（12.3±0.4）μm,呈圆整球状分布,无聚集;体外释药前期较快,后期较为缓慢,药物释放符合Higuchi释药模型。结论 通过使用Box-Behnken实验设计优化制备得到妥布霉素羧甲基壳聚糖微球,制备工艺简易,重现性良好,具有较好的缓释性能,可进一步进行实验研究。     

Selective digestive tract decontamination in critically ill patients

Introduction: Selective decontamination of the digestive tract (SDD) has been proposed to prevent endogenous and exogenous infections and to reduce mortality in critically ill patients. Although the efficacy of SDD has been confirmed by randomized controlled trials (RCTs) and systematic reviews, SDD has been the subject of intense controversy, based mainly on an insufficient evidence of efficacy and on concerns about resistance.

Areas covered: This article reviews the philosophy, the current evidence on the efficacy of SDD and the issue of emergence of resistance. All SDD RCTs were searched using Embase and Medline, with no restriction of language, gender or age. Personal archives were also explored, including abstracts from major scientific meetings; references in papers and published meta-analyses on SDD were crosschecked. Up-to-date evidence of the impact of SDD on carriage, infections and mortality is presented, and the efficacy of SDD in selected patient groups was investigated, along with the problem of the emergence of resistance.

Expert opinion: SDD significantly reduces the number of infections of the lower respiratory tract and bloodstream, multiple organ failure and mortality. It also controls resistance, particularly when the full protocol of parenteral and enteral antimicrobials is used.