• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

药用级糖中的纳米颗粒杂质及其对基于光散射的蛋白质制剂分析的干扰。

Nanoparticulate Impurities in Pharmaceutical-Grade Sugars and their Interference with Light Scattering-Based Analysis of Protein Formulations.

作者信息

Weinbuch Daniel, Cheung Jason K, Ketelaars Jurgen, Filipe Vasco, Hawe Andrea, den Engelsman John, Jiskoot Wim

机构信息

Coriolis Pharma, Am Klopferspitz 19, 82152, Martinsried-Munich, Germany.

出版信息

Pharm Res. 2015 Jul;32(7):2419-27. doi: 10.1007/s11095-015-1634-1. Epub 2015 Jan 30.

DOI:10.1007/s11095-015-1634-1
PMID:25630820
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4452213/
Abstract

PURPOSE

In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products.

METHODS

Different sugars as well as sucrose of various purity grades, suppliers and lots were analyzed by DLS and NTA before and (only for sucrose) after treatment by ultrafiltration and diafiltration. Furthermore, Fourier transform infrared (FTIR) microscopy, scanning electron microscopy coupled energy-dispersive X-ray spectroscopy (SEM-EDX), and fluorescence spectroscopy were employed.

RESULTS

The intensity of the interference signal differed between sugar types, sucrose of various purity grades, suppliers, and batches of the same supplier. The interference signal could be successfully eliminated from a sucrose solution by ultrafiltration (0.02 μm pore size). Nanoparticles, apparently composed of dextrans, ash components and aromatic colorants that were not completely removed during the sugar refinement process, were found responsible for the interference and were successfully purified from sucrose solutions.

CONCLUSIONS

The interference signal of sugar-containing solutions in DLS and NTA is due to the presence of nanoparticulate impurities. The nanoparticles present in sucrose were identified as agglomerates of various impurities originating from raw materials.

摘要

目的

在本研究中，我们调查了含糖溶液在动态光散射（DLS）和纳米颗粒跟踪分析（NTA）中产生干扰信号（100 - 200纳米）的根本原因及其对生物制药产品中颗粒分析的影响。

方法

通过DLS和NTA对不同糖类以及不同纯度等级、供应商和批次的蔗糖进行分析，在超滤和渗滤处理之前（仅对蔗糖进行处理之后）进行分析。此外，还采用了傅里叶变换红外（FTIR）显微镜、扫描电子显微镜联用能量色散X射线光谱仪（SEM - EDX）和荧光光谱法。

结果

干扰信号的强度在不同糖类、不同纯度等级的蔗糖、不同供应商以及同一供应商的不同批次之间存在差异。通过超滤（孔径0.02μm）可以成功地从蔗糖溶液中消除干扰信号。发现纳米颗粒显然由葡聚糖、灰分成分和在糖精制过程中未完全去除的芳香族色素组成，这些纳米颗粒是干扰的原因，并已成功地从蔗糖溶液中纯化出来。

结论

含糖溶液在DLS和NTA中的干扰信号是由于存在纳米颗粒杂质。蔗糖中存在的纳米颗粒被鉴定为源自原材料的各种杂质的聚集体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/67fce3bf171e/11095_2015_1634_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/e06fb7c9ddf1/11095_2015_1634_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/25b585732902/11095_2015_1634_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/109364f31c9f/11095_2015_1634_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/70235e95c298/11095_2015_1634_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/67fce3bf171e/11095_2015_1634_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/e06fb7c9ddf1/11095_2015_1634_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/25b585732902/11095_2015_1634_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/109364f31c9f/11095_2015_1634_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/70235e95c298/11095_2015_1634_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d6b/4452213/67fce3bf171e/11095_2015_1634_Fig5_HTML.jpg

相似文献

1
Nanoparticulate Impurities in Pharmaceutical-Grade Sugars and their Interference with Light Scattering-Based Analysis of Protein Formulations.药用级糖中的纳米颗粒杂质及其对基于光散射的蛋白质制剂分析的干扰。
Pharm Res. 2015 Jul;32(7):2419-27. doi: 10.1007/s11095-015-1634-1. Epub 2015 Jan 30.
2
Effects of Impurities from Sugar Excipient on Filtrate Flux during Ultrafiltration and Diafiltration Process.糖辅料中的杂质对超滤和渗滤过程中滤液通量的影响
Membranes (Basel). 2021 Oct 11;11(10):775. doi: 10.3390/membranes11100775.
3
Nanoparticulate Impurities Isolated from Pharmaceutical-Grade Sucrose Are a Potential Threat to Protein Stability.纳米颗粒杂质从药用级蔗糖中分离出来，可能对蛋白质稳定性构成威胁。
Pharm Res. 2017 Dec;34(12):2910-2921. doi: 10.1007/s11095-017-2274-4. Epub 2017 Oct 24.
4
Influence of Nano-Particulate Impurities and β-glucans on the Stability of Protein-Based Formulations.纳米颗粒杂质和β-葡聚糖对蛋白质制剂稳定性的影响。
Curr Drug Deliv. 2025;22(6):659-665. doi: 10.2174/0115672018290111240119115306.
5
Interference from Proteins and Surfactants on Particle Size Distributions Measured by Nanoparticle Tracking Analysis (NTA).蛋白质和表面活性剂对纳米颗粒跟踪分析（NTA）测量的粒度分布的干扰。
Pharm Res. 2017 Apr;34(4):800-808. doi: 10.1007/s11095-017-2109-3. Epub 2017 Feb 2.
6
Stable sugar-based protein formulations by supercritical fluid drying.通过超临界流体干燥制备稳定的糖基化蛋白质制剂。
Int J Pharm. 2008 Jan 4;346(1-2):102-8. doi: 10.1016/j.ijpharm.2007.06.013. Epub 2007 Jun 19.
7
Comparison of particle size methodology and assessment of nanoparticle tracking analysis (NTA) as a tool for live monitoring of crystallisation pathways.比较粒径测定方法并评估纳米颗粒跟踪分析（NTA）作为实时监测结晶途径的工具。
Eur J Pharm Biopharm. 2018 Sep;130:314-326. doi: 10.1016/j.ejpb.2018.07.012. Epub 2018 Jul 18.
8
Practical Considerations for Detection and Characterization of Sub-Micron Particles in Protein Solutions by Nanoparticle Tracking Analysis.通过纳米颗粒跟踪分析检测和表征蛋白质溶液中亚微米颗粒的实际考虑因素
PDA J Pharm Sci Technol. 2015 May-Jun;69(3):427-39. doi: 10.5731/pdajpst.2015.01051.
9
Particle Sizing of Nanoparticle Adjuvant Formulations by Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA).通过动态光散射（DLS）和纳米颗粒跟踪分析（NTA）对纳米颗粒佐剂制剂进行粒度分析。
Methods Mol Biol. 2017;1494:239-252. doi: 10.1007/978-1-4939-6445-1_17.
10
Novel Mechanism of Glass Delamination in Type 1A Borosilicate Vials Containing Frozen Protein Formulations.含冷冻蛋白质制剂的1A型硼硅玻璃小瓶中玻璃分层的新机制
PDA J Pharm Sci Technol. 2013 Jul-Aug;67(4):323-35. doi: 10.5731/pdajpst.2013.00925.

引用本文的文献

1
Impact of Excipient Extraction and Buffer Exchange on Recombinant Monoclonal Antibody Stability.赋形剂提取和缓冲液交换对重组单克隆抗体稳定性的影响。
Mol Pharm. 2024 Apr 1;21(4):1872-1883. doi: 10.1021/acs.molpharmaceut.3c01157. Epub 2024 Feb 29.
2
Influence of Nano-Particulate Impurities and β-glucans on the Stability of Protein-Based Formulations.纳米颗粒杂质和β-葡聚糖对蛋白质制剂稳定性的影响。
Curr Drug Deliv. 2025;22(6):659-665. doi: 10.2174/0115672018290111240119115306.
3
Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering.

本文引用的文献

1
Formulation and stability of cytokine therapeutics.细胞因子疗法的配方与稳定性
J Pharm Sci. 2015 Feb;104(2):307-26. doi: 10.1002/jps.24243. Epub 2014 Dec 9.
2
Liquid formulation for antibody drugs.抗体药物的液体制剂
Biochim Biophys Acta. 2014 Nov;1844(11):2041-2052. doi: 10.1016/j.bbapap.2014.07.016. Epub 2014 Aug 13.
3
Immunogenicity of therapeutic proteins: influence of aggregation.治疗性蛋白质的免疫原性：聚集的影响。
多角动态光散射法评估和筛选生物制药。
AAPS PharmSciTech. 2023 Mar 22;24(4):84. doi: 10.1208/s12249-023-02529-4.
4
Detection of innate immune response modulating impurities (IIRMI) in therapeutic peptides and proteins: Impact of excipients.治疗性肽和蛋白质中先天免疫反应调节杂质（IIRMI）的检测：赋形剂的影响。
Front Immunol. 2022 Sep 6;13:970499. doi: 10.3389/fimmu.2022.970499. eCollection 2022.
5
Effects of Impurities from Sugar Excipient on Filtrate Flux during Ultrafiltration and Diafiltration Process.糖辅料中的杂质对超滤和渗滤过程中滤液通量的影响
Membranes (Basel). 2021 Oct 11;11(10):775. doi: 10.3390/membranes11100775.
6
Impact of crystalline and amorphous matrices on successful spray drying of siRNA polyplexes for inhalation of nano-in-microparticles.结晶和无定形基质对用于吸入纳米包载微粒的siRNA多聚体喷雾干燥成功的影响。
Adv Ther (Weinh). 2021 May 7;4(6). doi: 10.1002/adtp.202100073. eCollection 2021 Jun.
7
Excipients for the lyoprotection of MAPKAP kinase 2 inhibitory peptide nano-polyplexes.用于 MAPKAP 激酶 2 抑制肽纳米多聚物的冷冻保护剂。
J Control Release. 2018 Jul 28;282:110-119. doi: 10.1016/j.jconrel.2018.04.045. Epub 2018 Apr 27.
8
Submicron Protein Particle Characterization using Resistive Pulse Sensing and Conventional Light Scattering Based Approaches.使用电阻脉冲传感和基于常规光散射的方法对亚微米蛋白颗粒进行特性分析。
Pharm Res. 2018 Feb 8;35(3):58. doi: 10.1007/s11095-017-2306-0.
9
Nanoparticulate Impurities Isolated from Pharmaceutical-Grade Sucrose Are a Potential Threat to Protein Stability.纳米颗粒杂质从药用级蔗糖中分离出来，可能对蛋白质稳定性构成威胁。
Pharm Res. 2017 Dec;34(12):2910-2921. doi: 10.1007/s11095-017-2274-4. Epub 2017 Oct 24.
J Immunotoxicol. 2014 Apr-Jun;11(2):99-109. doi: 10.3109/1547691X.2013.821564. Epub 2013 Aug 6.
4
Immunogenicity of different stressed IgG monoclonal antibody formulations in immune tolerant transgenic mice.不同应激 IgG 单克隆抗体配方在免疫耐受转基因小鼠中的免疫原性。
MAbs. 2012 Nov-Dec;4(6):740-52. doi: 10.4161/mabs.22066. Epub 2012 Sep 5.
5
Taylor dispersion analysis compared to dynamic light scattering for the size analysis of therapeutic peptides and proteins and their aggregates.泰勒分散分析与动态光散射在治疗性肽和蛋白质及其聚集体的粒径分析中的比较。
Pharm Res. 2011 Sep;28(9):2302-10. doi: 10.1007/s11095-011-0460-3. Epub 2011 May 11.
6
Strategies for the assessment of protein aggregates in pharmaceutical biotech product development.在药物生物技术产品开发中评估蛋白质聚集体的策略。
Pharm Res. 2011 Apr;28(4):920-33. doi: 10.1007/s11095-010-0297-1. Epub 2010 Oct 23.
7
Quality of original and biosimilar epoetin products.原研和生物类似物重组人促红素产品的质量。
Pharm Res. 2011 Feb;28(2):386-93. doi: 10.1007/s11095-010-0288-2. Epub 2010 Oct 1.
8
Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates.纳米颗粒跟踪分析（NTA）的纳米视野法在纳米颗粒和蛋白聚集体测量中的批判性评估。
Pharm Res. 2010 May;27(5):796-810. doi: 10.1007/s11095-010-0073-2. Epub 2010 Mar 4.
9
Immunological mechanism underlying the immune response to recombinant human protein therapeutics.重组人蛋白治疗药物免疫应答的免疫机制。
Trends Pharmacol Sci. 2010 Feb;31(2):53-9. doi: 10.1016/j.tips.2009.11.001. Epub 2009 Dec 4.
10
Dynamic light scattering as a relative tool for assessing the molecular integrity and stability of monoclonal antibodies.动态光散射作为评估单克隆抗体分子完整性和稳定性的相关工具。
Biotechnol Genet Eng Rev. 2007;24:117-28. doi: 10.1080/02648725.2007.10648095.