基于QbD理念的氨来呫诺亲水凝胶骨架缓释片的制备

本文基于“质量源于设计”(Quality by Design, QbD)理念设计并优化了氨来呫诺(Amlexanox, AML)亲水凝胶骨架缓释片(简称为“AML缓释片”)的处方工艺。在风险评估的基础上结合单因素考察结果和鱼骨分析法确定潜在关键工艺参数(Critical process parameters, CPPs),采用Plackett-Burman设计对CPPs进行筛选,然后用Box-Behnken设计对CPPs进行优化,建立统计模型,对优化后的工艺进行验证并考察其体外释放行为。结果表明骨架材料用量、黏合剂用量和片剂硬度对片剂释放行为有显著影响,当三者分别为50%～55%、62.5%～100%(占干物料的量)、124～142N时制备的氨来呫诺亲水凝胶骨架缓释片能达到释放目标,即2、6、12、18、24 h的累积释放率分别为8%～10%、25%～30%、50%～55%、75%～80%、95%以上。基于QbD理念设计的氨来呫诺亲水凝胶骨架缓释片处方工艺稳定可行,符合制剂设计的释放要求,具有良好的商业前景。     

正交试验优选复方莪术散的提取工艺及其颗粒制备工艺研究

目的：优选复方莪术散颗粒的最佳提取与颗粒制备工艺，为该复方的开发利用提供试验依据。方法：采用正交试验法对复方莪术散进行提取，以淫羊藿苷的含量和收率综合评价为指标，通过L_{9（3^{4）正交试验设计对醇的用量、提取的时间和提取次数进行考察，优选复方莪术散的醇提取工艺，再以浸膏为原料，通过L9（34）正交试验设计考察稀释剂（可溶性淀粉）的比例及粘合剂（乙醇）的浓度和干燥温度，制备复方莪术散颗粒。结果：复方莪术散提取最佳工艺为A2B22C11D1，即处方药材加60%浓度的10倍剂量的乙醇，提取2次，每次1.5h为最优。最佳制备工艺为A3B2C2，即干浸膏∶淀粉的比例为1∶2.5，并以90%乙醇为湿润剂，采用湿法制粒的方法，干燥温度为60℃，所制得颗粒剂经检查符合相关要求。结论：本试验所得复方莪术散颗粒剂的提取与制备工艺合理、可行，为该复方的开发利用提供了试验依据。}}     

不同提取工艺对复方银杏通脉口服液质量指标的影响

目的：探讨不同提取工艺对复方银杏通脉口服液质量指标的影响。方法：采用微波提取、超声提取、醇与水回流提取3种工艺,通过正交试验法对复方银杏通脉口服液的处方进行提取,以总黄酮醇苷、二苯乙烯苷、丹酚酸B含量及干膏率作为考察指标,运用综合评分法进行质量指标的比较。结果：最佳工艺为醇与水回流提取,12倍量料液比,回流提取1 h,提取2次。结论：醇与水回流提取工艺优于微波提取及超声提取工艺,且该方法实际可行,成本可控,可实现大生产。     

星点设计-效应面法优选壮药盘龙止咳颗粒提取工艺的研究

目的：通过星点设计-效应面法优选壮药盘龙止咳颗粒的最佳提取工艺,为后续研发更有效、更稳定、更方便的新制剂提供依据。方法：采用高效液相色谱法进行含量测定,采用单因素试验、星点设计-效应面法考察乙醇浓度、溶剂倍量、提取时间及提取次数,以山奈酚-3-O-龙胆二糖苷与岩白菜素总含量及干膏率的综合评分为评价指标,优选出壮药盘龙止咳颗粒最佳提取参数。结果：壮药盘龙止咳颗粒的最佳提取工艺为加入12倍量浓度为50%的乙醇,每次提取50 min,提取2次。结论：通过星点设计-效应面法优选盘龙止咳颗粒的提取工艺,方法预测性良好,重复性良好,简便可靠,为改变服用剂型研究提供了可靠依据。     

肺复方联合顺铂对气阴两虚Lewis肺癌荷瘤小鼠的影响

目的：研究气阴两虚Lewis肺癌荷瘤模型小鼠的行为学特征、饮水量、摄食量、体质量及肺复方对上述指标及脏器指数的影响。方法：取C57BL/6J小鼠40只,将其随机分为空白组8只、造模组32只。造模组灌服热性中药水煎液合并烟熏制备气阴两虚模型（造模第一阶段,共14 d）,于第15天移植Lewis肺癌细胞（造模第二阶段,共14 d）,按性别、体质量分层随机分为模型组、顺铂组、肺复方组及顺铂+肺复方组（联用组）,连续进行药物干预14 d。以造模每阶段及药物干预第1天的体质量、饮水量和摄食量分别作为基础体质量、基础饮水量和基础摄食量。并于固定时间,每2 d记录动物饮水量和摄食量,每3 d记录动物体质量,药物干预结束后处理动物,测量、计算其去瘤体质量和肝、脾及胸腺的脏器指数。结果：造模第一阶段小鼠饮水量和摄食量减少,造模第二阶段小鼠体质量增加,气阴两虚Lewis肺癌荷瘤模型小鼠脾脏和肝脏指数升高,胸腺指数降低（P<0.05或P<0.01）。药物干预后各组小鼠活动量增加,肺复方组饮水量、体质量增加,顺铂组小鼠摄食量、体质量减少,脾脏指数、去瘤体质量降低,联用组小鼠饮水量增加、摄食量减少,脾脏、胸腺指数升高（P<0.05或P<0.01）。结论：气阴两虚Lewis肺癌荷瘤模型小鼠的饮水量和摄食量减少,体质量增加;肺复方可缓解模型动物口干少饮、形体羸瘦等症状,改善顺铂引起的不良反应,增加模型小鼠脾脏和胸腺指数;肺复方干预肺癌的作用机制可能与其增强机体免疫功能有关。     

基于遗传算法的碟型水下滑翔机结构优化

以结构质量和应力作为目标函数,结构变形为约束条件,设计碟型水下滑翔机结构优化流程,采用单参数和多参数敏感度分析方法完成关键结构参数的筛选。采用拉丁超立方试验设计方法完成了对设计空间的采样布点工作,利用样本点数据创建了滑翔机结构优化的Kriging代理模型,并对Kriging代理模型进行了联合训练,使模型的拟合达到非常高的可用精度。采用NSGA-2第二代非支配排序多目标遗传算法对滑翔机进行了结构优化求解,得到了优化的Pareto前沿面最优解。优化结果显示,结构质量和应力较优化前分别降低5.57%和14.91%,文中所提方法在滑翔机结构优化设计中具有可行性。     

正交试验优选前列舒康片提取工艺研究

目的：优选前列舒康片的提取工艺。方法：以浸膏得率、盐酸小檗碱和京尼平苷酸为评价指标，将溶剂倍数、溶剂种类、提取时间、浸泡时间等作为考察因素，通过正交试验优选出前列舒康片的提取工艺。结果：优选出前列舒康片中黄柏醇提工艺为黄柏粗粉加乙醇回流提取2次，第1次加7倍量60%乙醇提取1.5h，第2次加6倍量60%醇提取1h；车前子等药材水提工艺为加水煎煮2次，1次加8倍量水，浸泡1h，煎煮2h；第2次加6倍量水，煎煮1.5h。结论：通过正交试验优选出的前列舒康片提取工艺合理可行、重复性良好，可为前列舒康片的工艺研究提供参照。     

化瘀骨合片提取工艺的优化研究

目的：优化化瘀骨合片的提取工艺条件。方法：以牡荆苷含量、芍药苷含量和固形物质量为评价指标,在单因素试验的基础上设计正交试验,考察料液比、提取时间、提取次数对提取工艺的影响,优化提取工艺条件。结果：最佳工艺条件为全方药材加水提取3次,每次加12倍量水提取2h,该条件下牡荆苷的提取率为89.81%,芍药苷的提取率为86.08%。结论：优选的提取工艺稳定,指标成分的提取率高,工艺合理可行。     

坛紫菜氨基酸提取工艺影响条件的优化与分析

以坛紫菜（Porphyra haitanensis）为实验材料,采用盐酸水解法和浸提法,以日立L-8900型高速全自动氨基酸分析仪为测定仪器,分别研究了坛紫菜总氨基酸（TAA）和游离氨基酸（FAA）在提取过程中各条件的不同水平对提取结果的影响.实验结果表明：（1）利用正交设计L9（34）对影响TAA提取的4个条件（藻体质量、稀释倍数、干燥温度、空白值）在3个水平上进行优化实验,藻体质量、稀释倍数对测定结果影响显著,干燥温度影响不显著;通过实验筛选出各条件的最佳水平为：藻体质量为0.050 0g,稀释3倍,干燥温度为60℃.（2）利用正交设计L16（45）对影响FAA测定的5个条件（藻体质量、提取液、提取温度、提取时间、空白值）在4个水平上进行优化实验,结果表明藻体质量、提取液、提取温度、提取时间的不同水平对测定结果均有显著影响,其中藻体质量对结果的影响最大;通过实验筛选出各条件的最佳水平为：藻体质量为0.010 0 g,提取液为去离子水,提取温度为60℃,提取时间为4 h.     

益气逐瘀利水方基于信息熵的工艺优化研究

目的：优选益气逐瘀利水方的煎煮工艺参数。方法：以提取时间、提取次数和提取溶剂倍数为影响因素,以毛蕊异黄酮葡萄糖苷（CG）含量和干浸膏率的综合评分为评价指标,设计正交实验并结合熵权法优选益气逐瘀利水方的最佳煎煮工艺。结果：最佳煎煮工艺为加12倍量的水,煎煮3次,每次1 h。结论：本研究工艺稳定,可为益气逐瘀利水方质量标准的制定提供参考。     

Assessing the Validity of Seismo-Acoustic Predictor Equations for Obtaining Seabed and Sub-Surface Sediment Physical Properties

The interdependence between the seismo-acoustic properties of a marine sediment and its geotechnical/physical parameters has been known for many years, and it has been postulated that this should allow the extraction of geotechnical information from seismic data. Though in the literature many correlations have been published for the surficial layer, there is a lack of information for greater sediment depths. In this article, a desktop study on a synthetic seafloor model illustrates how the application of published near-surface prediction equations to subsurface sediments (up to several tens of meters burial depth) can lead to spurious predictions. To test this further, acoustic and geotechnical properties were measured on a number of sediment core samples, some of which were subjected to loading in acoustically-equipped consolidation cells (oedometers) to simulate greater burial depth conditions. For low effective pressures (representing small burial depths extending to around 10 meters subsurface), the general applicability of established relationships was confirmed: the prediction of porosity, bulk density, and mean grain size from acoustic velocity and impedance appears generally possible for the investigated sedimentary environments. As effective pressure increases through, the observed relationships deviate more and more from the established ones for the near-surface area. For the samples tested in this study, in some instances increasing pressure even resulted in decreasing velocities. There are several possible explanations for this abnormal behavior, including the presence of gas, overconsolidation, or bimodal grain size distribution. The results indicate that an appropriate depth correction must be introduced into the published prediction equations in order to obtain reliable estimates of physical sediment properties for greater subsurface depths.     

海上大直径钢管桩打桩过程中桩周土强度弱化研究

海上大直径钢管桩打桩过程中,桩周土体受到强烈扰动而发生强度弱化,掌握桩周土体强度弱化规律对于准确预测打桩过程、保证工程安全具有重要意义。为研究土体强度弱化规律,开展了环剪试验模拟打桩对桩周土体的扰动,测试土体强度随剪切速率的变化规律,建立了描述土体强度弱化规律的拟合公式,引入到打桩分析软件中。研究结果表明：土体的强度折减程度不仅与土体本身的性质有关还受到土体的埋深和剪切速率的影响,埋深越深土体强度折减程度越低,剪切速率越高土体强度折减越高,在打桩分析中可采用这里推荐的线性折减方法来模拟不同深度处土体强度的折减规律。     

Interannual Sea Level Variations and Annual Tides in the Northwestern Pacific

Specific properties of the interannual sea level variations and annual tides in the Northwestern Pacific were studied. Several tide stations were monitored. The monthly mean sea level for the year of 1995 was analyzed at each tide station. A seismic event in 1995, some tectonic activity around the subject area, and the Kuroshio (the oceanic western boundary current) may possibly contaminate results which would have occurred from the astronomical annual tide alone.     

Flow Cytometric Analysis of Coastal Lagoon Bacterioplankton and Picophytoplankton: Fixation and Storage Effects

The effect of different fixation and storage protocols on the flow cytometric (FCM) simultaneous analysis of bacterioplankton and phytoplankton in coastal seawater samples (Mediterranean coastal lagoons) was investigated. FCM measurements (cell number, fluorescence and scatter characteristics) were obtained through DAPI staining. Three fixatives [glutaraldehyde (GA), formaldehyde (FA) and paraformaldehyde (PFA)] and two storage (3 months duration) methods (5 °C and −196 °C) were tested. Two dominant populations were detected in studied samples: bacteria and eukaryotic picophytoplankton. Adding fixatives (2% final concentration) appears necessary to obtain FCM exhaustive counts of all the bacteria and phytoplanktonic cells. This was related to the permeation effect of fixatives which allowed a better DAPI staining of the cells. Maximum fluorescence, i.e. optimal staining of the cells was obtained with FA or PFA, and significant lower fluorescences with GA. Fixed samples stored at 5 °C induced rapid cell loss. Only storage in liquid nitrogen of samples fixed with FA or PFA, allows mid-term (≥4 months) preservation of bacteria or picophytoplankton cell numbers, and limited evolution of DAPI-induced fluorescence and scatter characteristics.     

Phylogenetic diversity and phenotypic characterization of cultivable bacterioplankton isolated from polar oceans

A set of 27 marine planktonic bacteria isolated from the polar regions was characterized by 16S rDNA sequencing and physiological and biochemical testing. More than half of these bacteria were positive for caseinase, gelatinase and 13-glucosidase, and could utilize glucose, maltose or malic acid as carbon source for cell growth. Twelve isolates expressed nitrate reduction activities. Except for one antarctic isolate BSwlO175 belonging to Actinobacteria phylum, these isolates were classified as γ-Proteobacteria, suggesting that γ-Proteobacteria dominated in cultivable marine bacterioplankton at both poles. Genus Pseudoalteromonas was the predominant group in the Chukchi Sea and the Bering Sea, and genus ShewaneUa dominated in cultivable bacterioplankton in the Prydz Bay. With sequence similarities above 97%, genus Psychrobacter was found at both poles. These 27 isolates were psychrotolerant, and significant 16S rDNA sequence similarities were found not only between arctic and antarctic marine bacteria （ 〉 99% ）, but also between polar marine bacteria and bacteria from other aquatic environments （ ≥ 98.8% ）, including temperate ocean, deep sea, pond and lake, suggesting that in the polar oceans less temperature-sensitive bacteria may be cosmopolitan and have a bipolar, even global, distribution at the species level.     

INFORMATION FOR AUTHORS

<正>Acta Oceanologica Sinica(AOS)is a comprehensive academic journal edited by the Editorial Committee of Acta Oceanologica Sinica and is designed to provide a forum for important research papers of the marine scientific community which reflect the information on a worldwide basis.The journal publishes scholarly papers on marine science and technology,including physics,chemistry,biology,     

Estimation of Sediment Properties during Benthic Impact Experiments

Sediment properties, such as water content and density, have been used to estimate the dry and wet weights, as well as the volume of sediment recovered and discharged, during benthic impact experiments conducted in the Pacific and Indian Oceans. The estimates show that the weights of dry (355-1332 t) and wet sediment (1651-4888 t) recovered during the experiments, are not only a function of the total duration and distance covered during the experiment, but also depend on water content and density of the sediment. Estimation of dry sediment and its volumetric ratio in the discharge, are key parameters for calculating the discharged volume. The estimated volume of wet sediment recovered (1427-4049 m 3 ) as well as discharged (2693-6951 m 3 ) during the experiments, provide important inputs to evaluate the sediment resettlement and migration. Using these estimates, the average depth of excavation on the seafloor, can also been calculated. However, the stages of sediment recovery and discharge are expressed differently in some of the experiments. In order to standardize these, different stages have been identified, and definitions of certain terms have been suggested, for use in the future. The methods of calculating different properties, as well as weight and volume of discharged sediment are described in the paper for use in other applications concerning deep-sea discharges.