EMA对药用辅料右旋糖酐新的安全性评价

欧洲药品局（EMA）于2018年11月发布了"人用药品辅料右旋糖酐的包装说明书资料"，该文件引用大量文献全面评价了右旋糖酐的安全性，特别指出含有右旋糖酐辅料的注射和吸入制剂的疫苗与药品，应在说明书中描述有关其过敏反应信息的新要求。介绍该文件的主要内容，期望对我国这类药品说明书的撰写和监管有所帮助。     

Exploring the ameliorative potential of Punica granatum in dextran sulfate sodium induced ulcerative colitis in mice

The present study was designed to investigate the ameliorative potential of Punica granatum in dextran sulfate sodium (DSS) induced ulcerative colitis. DSS (2%) was administered orally in drinking water for 7 days to induce ulcerative colitis. The extent and severity of ulceration was analysed macroscopically, histopathologically and using a disease activity index. Myeloperoxidase (MPO), a specific marker of inflammation; histamine, a marker of mast cell degranulation; superoxide anion generation and, lipid peroxides were analysed. Administration of DSS resulted in a significant development of ulceration in the colon along with a rise in histamine, MPO activity and oxidative stress. Treatment with Punica granatum extract and its ellagic acid rich fraction (100 mg/kg and 200 mg/kg p.o.) significantly attenuated DSS‐induced colonic inflammation along with attenuation of histamine, MPO and oxidative stress. The antiulcerative effect of Punica granatum extract and its ellagic acid rich fraction were comparable to sulphasalazine (100 mg/kg, p.o.) and sodium cromoglycate (40 mg/kg i.p). It is concluded that Punica granatum has a potential for ameliorating DSS‐induced colitis and its ellagic acid rich fraction may be responsible for this effect. Further, the antiulcerative effects may be attributed to mast cell stabilizing, antiinflammatory and antioxidant actions. Copyright © 2009 John Wiley & Sons, Ltd.     

~99m锝-葡聚糖淋巴系统显像剂研制及其初步临床应用

作者采用沉淀法对药用葡聚糖进行分级纯化,通过家兔实验筛选出合乎淋巴系统定向要求分子量(105000)的葡聚糖,并制成一步标记法的亚锡葡聚糖药盒,4℃贮存8个月,标记率大于95％。~(99)m锝-葡聚糖的体内外稳定性均佳。家兔研究表明:(1)淋巴结内聚集量最高,其他非靶器(除肝脏、肾脏外)均处于极低水平;(2)显像速度快、图像清晰,既显示淋巴结又显示淋巴管;(3)注射部位清除速度快,6.5h清除95％。安全试验表明:~(99)m锝-葡聚糖是一种毒性极低、非常安全的药物。临床试用100余例,均获满意图像,检查全过程1h内完成,检查结果与诊断基本相符,故~(99)m锝-葡聚糖是目前临床上比较理想的淋巴系统显像剂,可进一步推广应用。     

曲安奈德PLGA微球对兔上腭部创面瘢痕形成影响的实验研究

目的:探讨曲安奈德PLGA微球对创面瘢痕愈合中瘢痕生成的抑制作用,研究局部应用曲安奈德的最佳给药途径。方法:3组共24只兔的上腭部创面模型,分别应用曲安奈德PLGA微球以及曲安奈德悬浊液,在瘢痕形成不同时间后切取瘢痕标本进行HE、VG染色及酶组织化学染色并电镜观察其组织形态学改变来分析曲安奈德不同给药途径的差异。结果:三组兔上腭创面愈合时间不同,表面颜色、质地不一样。电镜、常规染色以及免疫组织化学染色皆说明曲安奈德PLGA微球有明显的瘢痕抑制作用,且效果高于曲安奈德悬浊液。结论:曲安奈德PLGA微球能抑制瘢痕的增殖过程,使瘢痕组织纤维化过程明显减轻。合并手术一次性给药治疗瘢痕有很好的临床价值。     

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。     

Demonstration of adherence properties of Porphyromonas gingivalis outer membrane vesicles using a new microassay

Vesicles made by Porphyromonas gingivalis possess several biological activities, including the ability to adhere to oral surfaces and to bacteria. In this study, a new and simple method was developed to measure the adherence capability of outer membrane vesicles from P. gingivalis . Vesicles were conjugated to fluorescent microspheres (0.7 μ) and added to wells of a Teflon-coated microscope slide previously covered with a variety of soluble ligands. After incubation and washes, the number of fluorescent microspheres per microscopic field were counted. Vesicle-coated microspheres attached best to gelatin (<200 per field), whereas other compounds (such as fibronectin, fibrinogen, collagen and laminin) provided moderate attachment, and no attachment was observed to bovine serum albumin. Adherence to any of the tested ligands was not observed when fluorescent micro-spheres were conjugated to bovine serum albumin or lipopolysaccharides from P. gingivalis. The adherence of vesicle-coated microspheres to ligands was not significantly affected when the pH of the reaction mixture was between 4 and 10. None of the tested carbohydrates lowered the attachment capability of vesicle-coated microspheres to substrates. When vesicle-coated microspheres were treated with trypsin and chymotrypsin or heated, this resulted in a significant loss of attachment, suggesting a possible involvement of proteinaceous molecules in the process. The present study confirms that vesicles of P. gingivalis are capable of attachment to various molecules and indicate their potential role in colonization.     

Channges in regional cerebral blood flow after hyperventilation in the pig with an induced focal cerebral contusion

Summary Changes in regional cerebral blood flow in anaesthetized pigs with an induced focal cerebral contusion were studied before and after two grades of hyperventilation. A reduction in arterial tension of CO₂ with 0.70mmHg and a further reduction of 0.55mmHg did not change the CO₂ reactivity. Reactivity in both injured and macroscopically normal regions was the same, revealing an average of 39.3% flow change per kPa change in CO₂ tension. Regions with low flow after the contusion had an equally big reduction apparently leading to hypoxia because global metabolic rate was unchanged.     

细胞标记用大粒径羧化彩色高分子微球的研制

制备一种普通光学显微镜下可见的细胞标记用大粒径彩色高分子微球。以苯乙烯及丙烯酰胺为原料，在体系中加入电解质，有机溶剂及油溶性染料，采用无乳化剂乳液聚合法制备彩色高分子微球，并通过酰肼化和羧化两步反应在微球表现衍生出羧基。     

Effects of IgM Allotype Suppression on Serum IgM Levels,B-1 and B-2 Cells,and Antibody Responses ir Allotype Heterozygous F1 Mice

IgM allotype heterozygous F1 mice were independently suppressed for Igh6a or Igh6b to evaluate the contribution of B-1 and B-2 cells to natural serum IgM levels and Ab responses. B-2 B cells expressing IgM of the suppressed allotype were evident in the spleens of suppressed mice 4 to 6 weeks after cessation of the suppression regimen, whereas B-1 B cells of the suppressed allotype were undetectable for up to 9 months. Although serum IgM of the suppressed allotype was initially depleted in mice suppressed for either allotype, by 7 months of age, there were detectable levels of IgM of the suppressed allotype in the serum; however, the levels were significantly below that found in nonsuppressed mice. When mice were immunized with either the T-independent or T-dependent form of phosphorylcholine, those suppressed for either allotype, and consequently depleted of B-1 B cells of that allotype, did not respond with phosphorylcholine-specific IgM of the suppressed allotype. In contrast, when mice were immunized with α1-3 dextran, the Igh6a allotype-suppressed mice were able to produce dextran-specific IgM of that allotype. These results show that allotype-bearing B-1 cells of both allotypes can be effectively suppressed by this suppression protocol and this produces long-lasting effects on B-1 cell levels and serum IgM of the suppressed allotype. These observations reflect the derivation of the majority of B-1 cells from fetal-neonatal precursors, which cannot be replaced by newly emerging B-2 cells of adult origin. Their ablation by antibody treatment results in permanent alterations to the adult B-cell repertoire.     

不同时间等容血液稀释对犬急性心肌梗塞左室功能的改善作用

在麻醉开胸纯氧呼吸状态下的犬急性心肌梗塞（ＡＭＩ）模型上，观察以右旋糖酐４０在不同时间（ＡＭＩ前１ｈ、２４ｈ和ＡＭＩ后３０ｍｉｎ）行等容血液稀释对犬ＡＭＩ６ｈ内左室功能（±ｄｐ／ｄｔｍａｘ、ＬＶＳＰ）的改善作用。结果表明：ＡＭＩ后３０ｍｉｎ行血液稀释可使＋ｄｐ／ｄｔ－ｍａｘ明显升高（Ｐ＜０．０５）；而ＡＭＩ前１ｈ、２４ｈ行血液稀释不仅使ＡＭＩ后＋ｄｐ／ｄｔ－ｍａｘ明显升高，ＬＶＳＰ与－ｄｐ／ｄｔｍａｘ也明显升高（Ｐ＜０．０５）。提示：①不同时间行等容血液稀释对犬ＡＭＩ后左室收缩功能均有改善作用；②提前稀释血液不仅改善左室收缩功能，也能改善左室舒张功能。