A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.     

脂蛋白残粒RLP-c检测的临床意义

目的 探讨脂蛋白残粒RLP-c作为新的脂质指标的临床意义。方法 采用免疫分离法测定正常对照组(NC)、冠心病组(CHD)和2型糖尿病组(T2DM)的RLP-c水平,并比较RLP-c与其他脂质指标的相关性。结果 CHD组和T2DM组RLP-c水平明显高于NC组(P<0.01),其水平与甘油三脂(TG)和极低密度脂蛋白胆固醇(VLDL-c)高度相关(P<0.01)。结论 RLP-c可用于对动脉粥样硬化的危险性评估。     

静脉输液加药后的微粒变化

本文对我院急诊病人常用的供静脉给药的22种药物、42组配伍情况,制成静脉加药输液,在超净工作台条件下,用KF—4型微粒计数器,测定了168次微粒数,结果显示输液加药后微粒虽有增加,但均在药典规定范围内。输液中加1种、2种、3种药物后所产生的微粒数分别为x_1=5.52(n_1=16);x_2=8.17(n_2=18)、x_3=10.25(n_3=8),经统计处理,三组间无显著差异(P<0.05)。本文对产生微粒的药物、注射器、操作环境等因素进行了分析。     

无皂乳液聚合法合成均一性聚苯乙烯微球

研究了聚苯乙烯微球的合成过程中，离子强度、聚合时间对粒径的影响及其稳定性，实验结果表明：适当改变离子强度、聚合时间可以得到不同粒径的聚苯乙烯微球，且粒子稳定性较好。     

高频等离子体化学气相淀积法制备TiO2超细粒子

利用ＴｉＣｌ４＋Ｏ２体系，在高频等离子体化学气相淀积反应器中合成了纯度高、粒度细的ＴｉＯ２粒子。考察了工艺条件对ＴｉＯ２粒子物性的影响；探讨了ＴｉＯ２粒子晶型控制的方法，金红石型质量分数可通过工艺条件控制；探讨了ＴｉＯ２粒子晶型控制的方法。金红石型质量分数可通过工艺条件控制，减少ＴｉＯ２单体浓度可提高金红石型质量分数；也可通过在原料ＴｉＣｌ４中添加ＡｌＣｌ３等晶型转化剂，使可转化为单一金红石型Ｔｉ     

接枝环氧树脂水分散液的合成、分离与表征

控制不同的反应条件,采用甲基丙烯酸、苯乙烯与环氧树脂在丙二醇丁醚/正丁醇溶剂中接枝共聚,合成了粒径在87～104nm范围的环氧树脂水分散液。通过环己烷/乙醇和丙酮两步萃取,对接枝共聚产物进行分离,用FTIR表征,并估算了接枝共聚物的组成。实验结果表明,所制备的粒径为纳米级的环氧树脂水分散液,具有良好的机械稳定性、冻融稳定性及贮存稳定性。ξ电位测定表明,产物在pH>8的条件下更为稳定。     

棉织布与无纺布尘埃粒子数及抗渗液性能比较研究

目的比较棉织布与无纺布制作的手术衣和手术洞巾等在手术铺巾时空气中的尘埃粒子数及术中抗渗液性能，为有效控制外科切口感染和预防医患交叉感染提供参考。方法将棉织布与无纺布制作的手术布类各备15包，包内内容均相同，经灭菌处理。应用尘埃粒子计数仪测定两组铺巾时、铺巾后及收巾时空气中的尘埃粒子数，同时在手术过程中观察其抗渗液性能。结果无纺布组在铺巾时、铺巾后及收巾时产生的尘埃粒子数显著少于棉织布组（P〈0．05，P〈0．01）；其抗渗液率为100％，而棉织布组为0。结论无纺布抗渗液性能优，可减少手术环境中的尘埃粒子数，从而控制外科切口感染；其阻隔防护效能对患者和医护人员具有双重保护作用。     

小柴胡汤口服液药效作用的研究

观察了小柴胡汤口服液的主要药理作用。研究表明,小柴胡汤口服液有显著抑制角叉菜胶诱发的大鼠踝关节水肿(p<0.05),保护四氯化碳所致的大鼠急性肝功能损害,有极显著降低血清SGPT及LDH的作用(P<0.01)。对家兔发热反应也有较好的抑制作用。此外,小柴胡汤口服液对小鼠兔疫反应也有一定的增强作用,可促进小鼠碳粒廓清速率,提高血清溶血素水平及增强鸡红细胞所致的迟发性过敏反应。     

大气细菌粒子浓度的时间分布特征及最佳采样时间的研究

用ＭＦ－４５型和ＨＴＫ－２０１型空气微生物采样器分别在北京、天津和沈阳三地观测了不同季节和一天中大气细菌粒子的浓度及其变化。结果表明：京、津二地春季大气细菌粒子浓度高，分别为２０５３个／ｍ３和２５５６个／ｍ３；夏季低，分别为９９５个／ｍ３和１０６４个／ｍ３。沈阳秋季大气细菌粒子浓度高，为１０１０８个／ｍ３；冬季低，为１２９４个／ｍ３。一天中，大气细菌粒子浓度呈双峰型变化，６：００～７：００和１８：００时大气细菌粒子浓度高，１１：００～１３：００和１：００～２：００时大气细菌粒子浓度低。根据大气细菌粒子浓度的季节变化和一天中大气细菌粒子浓度的时间分布特征，经过京、津、沈三地一天中分别１２次、８次、６次和４次不同采样时间组合的大气细菌粒子浓度的数理统计分析，大气细菌粒子浓度的监测拟集中在一年冬、春、夏、秋四季的中间月份，即１月、４月、７月、１０月进行；一天中采样８次的时间序列可为７：００、１０：００、１３：００、１６：００、１９：００、２２：００、１：００、４：００一天采样４次的时间序列可为５：００、１１：００、１７：００、２３：００。白天采样４次的时间序列可为春、秋季６：００、９：００、１２：００、１５：００?     

Estimated Functional Diameter of Alveolar Septal Microvessels at the Zone I-II Border

Objective : To measure the functional diameter of alveolar septal microvessels under conditions in which the pulmonary arterial pressure and the lung inflation pressure are equal, at 25 cm H₂O (zone I-II border), and to compare these results with those obtained when inflation pressure exceeded arterial pressure by 5 or 10 cm H₂O (zone I). Methods : We perfused isolated rat lungs (P_A 25, P_PA 25, P_LA 0 cm H₂O) with fluorescent latex particles of specific diameters (0.49, 1.05, 2.0, 4.0, or 10 μm) and then prepared samples for histology. Using a confocal, laser-scanning fluorescence microscope, we measured latex particle densities within the septal plane of individual alveoli. We compared these particle densities with those in arterioles supplying the septa and calculated the density ratio. We fit curves produced by the Verniory equation to these ratios to estimate the septal microvessel functional diameter. Results : Particle densities in septa ranged from 0.06 ± 0.02 particles per μm² ‘for 0.49-μm-diameter particles to 0.007 ± 0.004 particles per μm² for 4.0-μm-diameter particles. The 10-μm particles did not enter septa. Calculations based on these data suggest a septal microvessel functional diameter of 6–8 μm. Conclusions : In a previous study, conducted at the same value of P_inflat, but with P_PA set at 15 or 20 (5 or 10 cm H₂O into zone I), we estimated the capillary diameter to be 1.7 μm. Thus, the septal capillary diameter seems to increase by three- to fourfold as P_PA is raised to equal P_inflat.