ICP-MS法测定药用辅料蔗糖中元素杂质的含量

目的：建立ICP-MS 法测定药用辅料蔗糖中砷（As）、镉（Cd）、汞（Hg）、铅（Pb）、钴（Co）、镍（Ni）、钒（V）、锂（Li）、锑（Sb）、铜（Cu） 等10 种元素的含量,评估其风险。方法：将药用辅料蔗糖溶解在0.1%HNO₃溶液中,采用ICP-MS 法,设定测定模式为STD模式,通过优化仪器参数,测定蔗糖中⁷⁵As、¹¹¹Cd、²⁰²Hg、²⁰⁸Pb、⁵⁹Co、⁶⁰Ni、⁵¹V、⁷Li、¹²¹Sb、⁶³Cu 等10 种元素的含量。结果：As、Cd、Pd、Co、Ni、V、Li、Sb、Cu等10种元素在0~100 ng·mL^-1范围内线性良好（r=不低于0.99）;Hg在0~2 ng·mL^-1范围内线性良好（r=0.999 1）。10种元素的平均回收率在99.8%~100.0%,RSD小于5%（n=6）。结论：方法易操作、准确度高,可用于药用辅料蔗糖中10 种元素杂质的含量测定。通过结果可见,药用辅料蔗糖中含上述十种元素量远低于ICH Q3D中规定值,风险较小,修订标准时可不再单独考虑重金属项。     

肠炎宁颗粒辅料优化工艺研究

目的：通过优化肠炎宁颗粒辅料种类,改善药品口感,使其更易为患者接受,提高临床用药顺应性,增加患者服药依从性。方法：通过对肠炎宁颗粒不同辅料组合进行分组实验,优化辅料加入方式,从而调节本品口感。结果：优化后以糊精、乳糖、三氯蔗糖作为矫味剂,适当减少乳糖的用量。选用矫味剂三氯蔗糖调节本品口感,辅料调整后,其颗粒的装量为每袋2 g。结论：调整辅料后生产工艺更易于控制,增加了本品的甜味并掩盖苦味,改善本品的口感,使其嗅觉、味觉让儿童患者更易接受,而不增加辅料服用总量,可提高临床用药依从性。     

医院中成药口服液、颗粒剂中蔗糖等辅料的相关调查分析

目的：通过调查医院中成药中口服液、颗粒剂两类剂型辅料使用的相关情况,以引起患者和生产厂家重视药品中添加的辅料,便于临床用药。方法：调查分析医院中成药中88种口服液、80种颗粒剂两类剂型辅料的使用情况及药物是否为甜味等的相关情况。结果：部分厂家对此重视,在其外包装和说明书上都进行了标注,但仍有许多厂家没意识到。88种口服液中有48种未标明辅料,占54.55%,含辅料最多的是蔗糖,占27.27%;80种颗粒剂中有48种未标明辅料,占60.00%,含辅料最多的是蔗糖,占25.00%。结论：药剂中添加辅料和在说明书中的填写等有待进一步完善、规范,以便临床用药。     

浅谈生物制品生产用原辅材料的质量控制

目前,生物制品的安全性和有效性正在引起社会公众的更广泛关注,而生物制品制造过程中所使用的原辅材料的质量对制品的安全性和稳定性有着直接的影响。因此,加强对此类原辅材料的质量控制对提高生物制品的质量将起到重要作用。     

药用辅料蔗糖中亚硫酸盐检测方法的建立

目的：建立适宜的蔗糖中亚硫酸盐测定法,提高现行药典标准。方法：采用IonPac AS11-HC 阴离子分析柱并配加IonPac AG11-HC保护柱,柱温 25 ℃,以10.0 mmol·L^-1的KOH作为淋洗液,流速1.0 mL·min^-1,检测器为电导检测器,检测器温度30 ℃,抑制器为自动再生抑制模式,抑制电流40 mA,进样量 25 μL。结果：离子色谱法测定亚硫酸钠质量浓度在1~20 μg·mL^-1范围内线性良好, 回归方程为Y=0.0434X-0.0211,r=0.9993,精密度RSD为0.5%,稳定性RSD为1.5%,回收率范围为 93.5%~99.3%,检出限0.1 μg·mL^-1,定量限0.25 μg·mL^-1。8批样品中1号、2号、3号及5号样品结果分别为8.1、9.8、12. 0及10.4 μg·g^-1,其余各批样品均为未检出亚硫酸盐。结论：所建方法可行、准确,可用于测定蔗糖中亚硫酸盐的含量。     

注射用辅料类过敏反应的非临床评价方法

近年来注射剂的安全性问题引起了社会各界的广泛关注,注射用辅料引发的类过敏反应是导致注射剂临床使用安全隐患的主要原因之一,而目前尚未建立完善的可用于评价注射用辅料类过敏反应的非临床研究方法。对近年来国内外在该方面的研究进展做一综述,旨在为注射用辅料类过敏反应非临床评价方法的发展提供一些帮助和启示。     

止嗽颗粒成型辅料的筛选与工艺研究

目的:优选止嗽颗粒的成型辅料。方法:考察不同辅料对止嗽颗粒成型性、吸湿性和临界相对湿度的影响,并用综合评分法筛选出制备止嗽颗粒的最优辅料及处方组成。结果:制备止嗽颗粒的最优辅料为乳糖;最佳处方组成为4份喷雾粉与6份乳糖混合制粒。结论:本法所制颗粒成型性、溶解性好,且不易吸湿,较为理想。     

脂多糖激活补体诱导内皮细胞释放黏附分子和凋亡

目的在细胞水平上研究脂多糖(lipopolysaccharide,LPS)激活血清补体对内皮细胞的作用和影响。方法研究LPS激活血清补体的作用方式和特点,观察LPS激活补体对内皮细胞表达黏附分子和凋亡的影响。采用ELISA检测内皮细胞释放P-selectin、E-selectin和ICAM-1的变化,化学发光法检测Caspase-3/7活化情况,SRB法检测LPS激活补体对内皮细胞生长的影响。结果 LPS能够激活血清补体,这种激活呈现量效、时效性。LPS激活血清补体可诱导内皮细胞瞬时明显释放P-selectin,E-selectin和ICAM-1表达也明显上调,同时可导致Caspase-3/7活化。在本实验条件下,LPS激活血清补体对内皮细胞生长未产生抑制。结论 LPS激活血清补体可损伤内皮细胞,导致内皮细胞明显表达黏附分子以及发生凋亡。     

Variability of biological effects of silicas: different degrees of activation of the fifth component of complement by amorphous silicas

A biogenic and a pyrogenic amorphous silica were incubated in normal human plasma and compared on a per unit surface basis for their ability to split C5 molecules and yield small C5a peptides. Since C5a peptides induce selective chemotactic attraction of polymorphonuclear leukocytes (PMN), measurement of PMN-induced chemotaxis was used as an index of C5 activation. Though to a lesser extent than the crystalline forms, amorphous silicas can promote the cleavage of C5 protein and generation of C5a-like fragment. The biogenic silica, which differs from the pyrogenic variety in particle shape, level of contaminants, and degree of surface hydrophilicity, besides specific surface, induced a greater response. Both silicas activated C5 through a process which seems to involve multiple events similar to those induced by crystalline silica. C5 molecules are adsorbed and hydroxyl radicals are generated through Haber Weiss cycles catalyzed by the redox-active iron present at the particle surface either as trace impurities or chelated from plasma by silanol groups. In turn, these radicals convert native C5 to an oxidized C5-like form C5(H2O2). Finally, C5(H2O2) is cleaved by protease enzymatic action of plasma kallikrein activated by the same silica dusts, yielding a product, C5a(H2O2), having the same functional characteristic as C5a.     

Non-specific adsorption of complement proteins affects complement activation pathways of gold nanomaterials

The complement system is a key humoral component of innate immunity, serving as the first line of defense against intruders, including foreign synthetic nanomaterials. Although gold nanomaterials (AuNMs) are widely used in nanomedicine, their immunological response is not well understood. Using AuNMs of three shapes commonly used in biomedical applications: spherical gold nanoparticles, gold nanostars and gold nanorods, we demonstrated that AuNMs activated whole complement system, leading to the formation of SC5b-9 complex. All three complement pathways were simultaneously activated by all the AuNMs. Recognition molecules of the complement system interacted with all AuNMs in vitro, except for l-ficolin, but the correlation between these interactions and corresponding complement pathway activation was only observed in the classical and alternative pathways. We also observed the mediating role of complement activation in cellular uptake of all AuNMs by human U937 promonocytic cells, which expresses complement receptors. Taken together, our results highlighted the potential immunological challenges for clinical applications of AuNMs that were often overlooked.     

Surface plasmon resonance in monitoring of complement activation on biomaterials

When artificial materials come into contact with blood, various biological responses are induced. For successful development of biomaterials used in biomedical devices that will be exposed to blood, understanding and control of these interactions are essential. Surface plasmon resonance (SPR) spectroscopy is one of the surface-sensitive optical methods to monitor biological interactions. SPR enables real-time and in situ analysis of interfacial events associated with biomaterials research. In this review, we describe an SPR biosensor and its application to monitor complement activation onto biomaterials surface. We also discuss the effect of surface properties of the material on complement activation.     

应用补体活化体外模型评价姜黄素脂质体

目的建立补体活化体外模型,评价姜黄素脂质体补体激活能力。方法使用混合的人血清作为标准反应血清,用人IgG和zymosan A激活标准反应血清中的补体成分后得到标准阳性对照血清,在标准反应血清中加入姜黄素脂质体进行补体激活反应,并检测SC5b-9含量。结果姜黄素脂质体组SC5b-9浓度与NC组相比,增加了约330%。结论使用补体活化体外模型可以评价姜黄素脂质体补体激活能力和比较不同批次姜黄素脂质体补体激活能力的差异。     

Advances in assay of complement function and activation

The main function of the complement system is pattern recognition of danger. Typical exogenous danger signals are pathogen associated molecular patterns inducing a protective inflammatory response. Other examples are exposure to foreign surfaces of biomedical materials including nanoparticles, which principally induce the same inflammatory response. If a surface is “foreign” to the host, it induces complement activation. Development of monoclonal antibodies to neoepitopes on complement activation products introduced an entirely new set of methods for assay of complement activation. Activation of complement by a surface occurs by impairment of the fine balance of the control system, e.g. by preferred binding of factor B at the expense of factor H. Sensitive methods to detect complement activation on surfaces and in the fluid phase are a prerequisite for investigation of the biocompatibility of artificial materials. This information can be used to develop new materials with enhanced biocompatibility. Here we review available methods to study human and animal complement function and activation in vitro and in vivo.     

鸭跖草的抗补体活性成分及其作用靶点(英文)

采用抗补体活性导向分离法从中药鸭跖草中分离鉴定了24个化合物, 活性测试结果显示6个化合物对补体系统的经典途径和旁路途径显示出不同程度的抑制作用 (CH500.12-1.44 mM, AP500.28-7.05 mM)。作用靶点研究显示喹诺酸作用于补体系统的C1q, C2, C3, C4, C5 和 C9组分; β-谷甾醇作用于C3 和 C4组分; (+)-儿茶素-3-O-β-D-(2-肉桂酰基)-葡萄糖苷、对甲基苯酚和6-甲氧基-3-甲基-1,2,4-苯三酚均作用于C1q, C2, C3, C5 和C9组分。     

关于生物制品残余DNA质量控制问题

随着生物医药技术的飞速发展,越来越多的哺乳动物细胞,尤其是连续传代细胞系用于生产疫苗和治疗性生物制品。重组蛋白制品的用量随着临床治疗效果的需求越来越大,由微克级上升到了毫克甚至克级,需要长期反复用药的生物制品也越来越多。同时疫苗的使用者为健康人群,而且很多疫苗使用人群也扩大到婴幼儿,这使得药品监管部门不得不更加重视疫苗等生物制品的安全性,其中细胞残余DNA的质量控制一直是人们关注的热点。本文就不同时期国内外对于DNA残留问题的看法、DNA残留量质控标准的制定、DNA残留量检测方法等研究进展作一综述,并提出残余DNA问题未来需要进一步开展的工作。     

补体旁路激活对内皮细胞纤溶功能的影响

<正>补体对机体防御和免疫功能有重要的作用,然而其过度激活会造成炎症和损伤[1]。旁路激活是补体激活的一条重要途径,很多疾病的发生与补体的旁路激活密切相关[2]。激活的补体会对内皮细胞产生作用和影响。内皮细胞具有多种重要的分泌调节功能,而补体旁路激活对内皮细胞纤溶功能影响的研究极少见报道。为进一步探讨炎症相关病征中补体激活与凝血功能异常的相关性,本文开展了补体旁路激活对内皮细胞纤溶功能影响的研究。     

不同病原菌致社区获得性肺炎患者中性粒细胞表面补体受体的变化

目的 探讨不同病原菌致社区获得性肺炎（CAP）患者中性粒细胞表面补体受体（CR）1、3含量的变化.方法 59例CAP患者通过流式细胞仪测定CR的含量,同时检测患者C反应蛋白、红细胞沉降率、白细胞计数（WBC）等水平变化情况.结果 59例CAP患者中肺炎链球菌肺炎13例,A型流感病毒肺炎13例,非典型肺炎5例（支原体肺炎3例,衣原体肺炎1例,军团菌肺炎1例）,还有28例病原不明.CR1在链球菌肺炎和病原体不明肺炎中的相对含量分别为：（19.4±9.8）、（19.3±8.8）,较A型病毒性肺炎显著升高（t=6.13、5.09,均P〈0.01）.结论 CAP患者中性粒细胞表面CR1含量是一种可以提示细菌或病毒感染的有效预测因子,可作为一种快速简便的协助临床诊疗的观察指标.     

黄芩炮制品生物检定法实验研究

目的研究黄芩炮制品对敏感菌株的剂量效应曲线,建立生物检定质量评价方法。方法利用黄芩炮制品提取液对敏感菌的抑菌圈直径大小和质量浓度的对数建立标准曲线,根据量效曲线测定不同产地、不同批号黄芩炮制品的相对效价。采用《中国药典》2010年版HPLC方法进行含量测定,比较生物检定法和药典方法是否一致。结果当黄芩炮制品的质量浓度在0.204 8～0.976 6g·mL-1范围内时,黄芩炮制品的对数剂量和反应效应呈线性关系,且相关性好(r=0.997 5);生物检定法和HPLC作为质控指标得出质量评价结果不完全相同。结论采用生物检定法建立黄芩炮制品质量控制方法是可行的、合理的。