人血白蛋白中不溶性微粒的检测及制品质量考察趋势分析

目的:考察目前市售国内外人血白蛋白制品中不溶性微粒的含量情况并与自检结果进行对比。方法:随机抽取来自国内外企业的规格为200 g.L-1,每瓶50 mL的人血白蛋白共53批,以GWF-8JA型微粒检测仪按2010年版中国药典三部附录第一法光阻法对抽检样品进行不溶性微粒质量考察。每批供试品取1瓶,分别检测供试品中≥10μm和≥25μm 2个通道的微粒总数,将所得结果与自检数据进行趋势比对,并将2个粒径通道所测得的结果按微粒数的多少分成A、B、C、D、E 5个级别并计算符合各个级别的人血白蛋白的批次数。结果:53批人血白蛋白全部符合2010年版中国药典三部的相关规定,抽验的人血白蛋白样品中有80%以上的制品的不溶性微粒结果能够达到A级水平,各批次的检验结果与企业自检结果具有一致性。结论:随机抽样结果表明80%以上的人血白蛋白不溶性微粒结果远低于国家相关标准规定,制品质量控制良好,实验室间结果趋势一致。     

光阻法检测人血白蛋白、静注人免疫球蛋白中的不溶性微粒

目的对人血白蛋白、静注人免疫球蛋白中的不溶性微粒进行检查研究。方法按照《中国药典》2010年版三部中不溶性微粒检查法-光阻法进行检测。结果样品不经稀释,即可用于检测。液体制剂混匀后静置2min即可消除气泡,冻干制剂则需静置2~4h方可脱气。10μm粒子的回收率为98.5%,25μm粒子的回收率为100.1%。共检测人血白蛋白130批、静注人免疫球蛋白（pH 4）103批、冻干静注人免疫球蛋白（pH 4）44批,均符合规定。结论《中国药典》2010年版三部附录中的＂不溶性微粒检查法＂可用于人血白蛋白、静注人免疫球蛋白的检测,抽检的样品均能达到新版药典的要求。     

重组人血白蛋白的研究进展

<正>人血白蛋白(Humanserumalbumin,HSA)是人体血浆中含量最丰富的蛋白质,约占到血浆蛋白总量的60%。HSA能维持血液动力学平衡和血管内渗透压,吸收组织中多余液体到血液循环中,使动脉压升高,广泛应用于失血创伤烧伤引起的休克,脑水肿及损伤引起的颅压升高,肝硬化及肾病引起的水肿或腹水,低蛋白血症的防治和新生     

人血白蛋白中细菌内毒素检查法的应用

人血白蛋白中细菌内毒素检查法的应用张雪萍浙江省血液制品所温州３２５０００热原质检查是药品生产中一项重要的质量指标．许多国家越来越多地选用灵敏方便的细菌内毒素检查法替代传统的家兔法．本文总结了用鲎试剂检查人血白蛋白半成品的经验，以家兔法实验结果为依据，...     

人血白蛋白的临床合理应用

目的 探讨人血白蛋白在临床中的应用指征和基本原则.方法 系用循证医学方法,基于国内外指南、药品说明书、临床试验等临床证据对人血白蛋白的临床应用作一总结和综述.结果 人血白蛋白在增加血容量和维持血浆胶体渗透压、运输小分子物质及解毒、营养供给方面有明确的适应证.结论 临床应用人血白蛋白应把握适应证,避免滥用,促进规范用药.     

人血白蛋白制品铝残留量的追踪研究

目的:通过对我国人血白蛋白制品在执行2005年版中国药典前后的铝残留量状况的追踪分析,并与进口人血白蛋白比较,以提高国内人血白蛋白制品的质量。方法:采用原子吸收分光光度法检测人血白蛋白制品中的铝残留量。结果:国内压滤法生产的人血白蛋白制品合格率为98.6%以上,离心法为96.8%,比执行前的合格率平均提高了56.2%。结论:在执行2005年版中国药典仅仅一年的时间内,国内生产厂家通过对工艺的优化改进,人血白蛋白制品铝残留量的控制基本符合标准。     

人血白蛋白引起过敏性休克1例

1临床资料患者,男,60岁,因左侧腰腹痛14d,考虑左肾盂肿瘤,于2009年12月18日入院。入院体查：体温36．8℃,脉搏68次·min-1,呼吸20次·min-1,血压110／78mmHg,左季肋区轻压痛,余无异常。CI＂示左肾盂内巨大占位性病变累及输尿管上段,诊断为“左肾盂癌”。既往无药物过敏史。患者于2009年12月23日全麻下行腹腔镜下左肾盂癌根治性切除术＋膀胱袖式切除术＋膀胱造瘘术,     

人血白蛋白不良反应分析

目的：了解人血白蛋白文献报道中的不良反应情况。方法：检索CHKI收载的1994年1月—2006年10月国内公开发表的医药学期刊中所有关于人血白蛋白不良反应文献共计36篇，对其报道的病例进行统计分析。结果：人血白蛋白在临床存在不合理应用现象。人血白蛋白引起的不良反应多出现在药物输注过程中，不良反应类型主要为全身过敏反应和心脏损害。结论：临床应用人血白蛋白应严格遵循适应证，给药速度应适当，才能保证人血白蛋白安全、合理的应用。     

人血白蛋白的不良反应分析

目的:分析人血白蛋白的不良反应,促进合理用药.方法:对1996-2004年国内公开报道及重庆市涪陵中心医院ADR中心收集到的人血白蛋白不良反应病例进行分析.结果:人血白蛋白的不良反应主要有过敏样反应、热原样反应、精神障碍、肾功能损害、喉头水肿、消化道出血等.结论:应重视人血白蛋白的不良反应,加大产品质量检测力度,临床慎重使用,以减少其不良反应的发生.     

人血白蛋白临床应用进展

人血白蛋白（HSA）为单链多肽,有585个氨基酸残基组成,分子量为66458。人血白蛋白是血浆中含量最多的的蛋白质,主要功能是维持人体胶体渗透和维系血液中蛋白水平。另外由于人血白蛋白在体液环境中带有200个以上的负电荷,可以作为体内很多小分子的载体蛋白。其主要的适应证有：出血性休克、外伤性休克、烧伤、成人呼吸窘迫综合征（ ARDS）、肝硬化伴有腹水及水肿、恶性肿瘤以及在其他疾病方面其特殊的应用［1］。     

人血白蛋白的蛋白质含量测定能力验证结果与分析

目的：对全国血液制品批签发授权药检机构及相关生产企业或单位实验室的人血白蛋白蛋白质含量检测能力进行评价。方法：选择符合要求的人血白蛋白产品作为原料进行合并、除菌、分装。制备后按照《中国药典》2015年版三部蛋白质含量（凯式定氮）测定,组织协作标定后确立指定值。均一性和稳定性监测合格后按能力验证要求发放样品。以多中心协作标定结果作为评价参加者能力验证结果的依据。结果：能力验证样品确立的指定值及其参考范围为（193.30±5.08） g·L^-1,参加本次能力验证的药检机构或企业实验室共13家,10家实验室结果为优秀,1家实验室为合格,2家实验室为不满意。整体满意率为84.6%,优秀率76.9%,不合格率15.4%。结论：国内血液制品的7家批签发授权药检机构能力验证结果均为优秀,部分企业实验室能力验证结果为满意,但也有个别实验室测定结果出现偏差,参加者应调查并改进。     

重组人血清白蛋白突变体干扰素2b融合蛋白的纯化

在成功构建人血清白蛋白突变体干扰素α2b融合蛋白(rmHSA-IFN-α2b)毕赤酵母工程菌株PicZαA/rmHSA-IFN-α2b/X33的基础上,建立了发酵分泌表达rmHSA-IFN-α2b的纯化工艺。对工程菌进行9 L罐高密度发酵后,离心收集发酵液上清,rmHSA-IFN-α2b的表达量为421 mg/L。对发酵液上清,依次进行3步纯化。第一步采用SP sepharose FF除去大部分色素和部分杂蛋白。第二步采用Blue sepharose FF根据亲和作用原理除去部分杂质。第三步采用Q sepharose FF除去溶剂和其他杂质以及类毒素。最终得到高纯度、有活性的rmHSA-IFN-α2b。通过HPLC检测和SDS-PAGE检测,最终产品的纯度都大于95%;通过活性检测,rmHSA-IFN-α2b的比活为1.5×106IU/mg。纯化总收率为25.3%。连续重复纯化6批,结果稳定。该工艺简单稳定,容易放大,适合规模化生产。简单高效纯化工艺的建立,为rmHSA-IFN-α2b后续研究奠定了坚实的基础。     

凯氏定氮法测定人血白蛋白中蛋白质含量的不确定度评价

目的：对凯氏定氮法测定人血白蛋白中蛋白质含量的不确定度进行评价。方法：建立不确定度计算模型,对测定中的各影响因素进行考察。结果：量化了各不确定度分量并计算出合成不确定度为0．62％,取k=2,得扩展不确定度为1．2％,人血白蛋白中蛋白质含量为（104．7±1．2）％。结论：测定总氮时样品的稀释和量取以及实际消耗硫酸滴定液体积、测量重复性、硫酸滴定液的浓度标定和稀释是凯氏定氮法测定人血白蛋白含量不确定度的主要因素,通过分析上述不确定度分量对试验进行优化,可使测定结果更加可靠。     

Human Serum Albumin as a Probe for Protein Adsorption to Nanopartides: Relevance to Biodistribution

Abstract

A range of poloxamers and poloxamines were adsorbed to biodegradable poly(lactide-coglycolide) (PLGA) and non-biodegradable polystyrene (PS) particulate systems in order to alter their surface characteristics and produce potential drug targeting systems. Human serum albumin (HSA) was chosen as a model protein to investigate protein adsorption to the above systems and was quantified by two techniques. I¹²⁵ radiolabelled HSA proved to be a useful probe for determining protein adsorption but was limited by a modification that occurred on storage. Also, HSA eluted from the particle surface was quantified by densitometry following it's development on an SDS-PAGE gel. Both techniques produced similar results. For cleaned coated PS particles it was found that the PEO chain length and the molecular structure of the block copolymer were important in preventing protein adsorption. The presence of excess block copolymer in the uncleaned preparations resulted in further suppression of HSA adsorption, which was thought to be due to their detergent properties. Due to the different results obtained with similarly coated PLGA particles, it was concluded that the block copolymers adsorb onto the surface of me PLGA particles in a different conformation to those adsorbed onto PS particles. Correlating in vivo biodistribution in terms of the prevention of protein (opsonin) adsorption was of only limited success and it was concluded that adsorption data for a single model protein can only be used with caution to predict the in vivo behaviour of colloidal targeting systems.     

Protein Aggregates in Inhaled Biologics: Challenges and Considerations

Pulmonary delivery is the main route of administration for treatment of local lung diseases. Recently, the interest in delivery of proteins through the pulmonary route for treatment of lung diseases has significantly increased, especially after Covid-19 pandemic. The development of an inhalable protein combines the challenges of inhaled as well as biologic products since protein stability may be compromised during manufacture or delivery. For instance, spray drying is the most common technology for manufacture of inhalable biological particles, however, it imposes shear and thermal stresses which may cause protein unfolding and aggregation post drying. Therefore, protein aggregation should be evaluated for inhaled biologics as it could impact the safety and/or efficacy of the product. While there is extensive knowledge and regulatory guidance on acceptable limits of particles, which inherently include insoluble protein aggregates, in injectable proteins, there is no comparable knowledge for inhaled ones. Moreover, the poor correlation between in vitro setup for analytical testing and the in vivo lung environment limits the predictability of protein aggregation post inhalation. Thus, the purpose of this article is to highlight the major challenges facing the development of inhaled proteins compared to parenteral ones, and to share future thoughts to resolve them.     

人血白蛋白的激光拉曼光谱法测定

建立了激光拉曼光谱法测定人血白蛋白溶液。采用一元线性回归法及偏最小二乘法建立定量分析模型,人血白蛋白在48.8～243 g/L(4.88%～24.30%)浓度范围内线性关系良好。两种方法的r均为0.999 7,交叉验证均方差(RMSECV)为0.385和0.153。     

Viral Infectivity of Albumin and Plasma Protein Fraction

Original research, reviews, and case reports discussing viral infectivity of blood- and plasma-derived products were reviewed to determine the potential viral infectivity of human serum albumin (HSA) and plasma protein fraction (PPF). Data concerning viral infectivity, viral screening and inactivation procedures, and viral outbreaks associated with blood and plasma products were extracted and evaluated for pertinence to HSA and PPF. The starting material used for fractionation, the manufacturing process, postmanufacturing handling, and immunocompetence of HSA or PPF recipients were assessed to determine risk of symptomatic viral disease after transfusion. Both HSA and PPF are manufactured with pasteurization procedures that have led to an excellent viral safety record based on 50 years of clinical use. One outbreak of hepatitis B was associated with PPF as a result of an unreliable manufacturing process that has been corrected. The pasteurization process is effective in eradicating known viral pathogens when good manufacturing practices are followed. Continued surveillance of such products is warranted for viruses not included in routine screening procedures and for those that are resistant to current inactivation methods.     

Interaction of Citrinin with Human Serum Albumin

Citrinin (CIT) is a mycotoxin produced by several Aspergillus, Penicillium, and Monascus species. CIT occurs worldwide in different foods and drinks and causes health problems for humans and animals. Human serum albumin (HSA) is the most abundant plasma protein in human circulation. Albumin forms stable complexes with many drugs and xenobiotics; therefore, HSA commonly plays important role in the pharmacokinetics or toxicokinetics of numerous compounds. However, the interaction of CIT with HSA is poorly characterized yet. In this study, the complex formation of CIT with HSA was investigated using fluorescence spectroscopy and ultrafiltration techniques. For the deeper understanding of the interaction, thermodynamic, and molecular modeling studies were performed as well. Our results suggest that CIT forms stable complex with HSA (logK ~ 5.3) and its primary binding site is located in subdomain IIA (Sudlow’s Site I). In vitro cell experiments also recommend that CIT-HSA interaction may have biological relevance. Finally, the complex formations of CIT with bovine, porcine, and rat serum albumin were investigated, in order to test the potential species differences of CIT-albumin interactions.     

重组人血清白蛋白的药学应用研究进展

综述了重组人血清白蛋白的性质、结构和功能,及常用表达系统.重点介绍了重组人血清白蛋白在药学上的应用.人血清白蛋白是人血浆中最丰富的蛋白质,具有许多重要的生理特性,用途广泛.