目的 建立国家一类新药甘露特钠首批国家标准物质,对标准物质的寡糖结构进行确证。方法 采用液质联用、核磁共振等方法确证待标物的结构。液相色谱采用GE Superdex 30 Increase 10/300GL色谱柱对寡糖进行分离,采用负离子模式进行质谱检测;采用一维、二维核磁共振技术,对聚甘露糖醛酸、聚古罗糖醛酸及待标物进行结构分析。结果 通过对质谱、光谱的分析,确证了甘露特钠待标品是以2~10糖组成的寡糖混合物,分子骨架以甘露糖醛酸为主,与理论结构一致。结论 本研究建立了甘露特钠结构确证方法,并对甘露特钠首批对照品的相对分子质量、分子结构进行了确证。
Abstract
OBJECTIVE To establish the first batch of national reference substance (RS) for the first-class new drug sodium oligomannate in China, and confirm the structure of the RS. METHODS Structure of the candidate was confirmed by liquid chromatography-mass spectrometry, nuclear magnetic resonance and other methods. GE Superdex 30 Increase 10/300GL column was used to separate oligosaccharides by liquid chromatography, and negative ion mode for mass spectrometry detection was used; one-dimensional and two-dimensional nuclear magnetic resonance techniques were used to analyze the structures of polymannuronic acid, polyguluronic acid and the sodium oligomannate RS . RESULTS Through the analysis of mass spectrometry and spectrum, it was confirmed that the sodium oligomannate RS is an oligosaccharide mixture composed of 2-10 saccharides, and the molecular backbone is mainly mannuronic acid, which is consistent with the theoretical structure. CONCLUSIONS In this study, the structure confirmation methods of sodium oligomannate are established, and the molecular weight and molecular structure of the first batch of national RS of sodium oligomannate are confirmed.
关键词
甘露特钠 /
高分辨质谱 /
核磁共振 /
结构鉴定 /
国家对照品 /
甘露糖醛酸 /
古罗糖醛酸
{{custom_keyword}} /
Key words
sodium oligomannate /
high resolution mass spectrometry /
nuclear magnetic resonance /
structure identification /
national standard /
mannuronic acid /
guluronic acid
{{custom_keyword}} /
中图分类号：
R282
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] SYED Y Y. Sodium oligomannte:first approval[J]. Drugs, 2020, 80(4):441-444. DOI: 10.1007/s40265-020-01268-1.
[2] SYED Y Y. Correction to: sodium oligomannate: first approval[J]. Drugs, 2020, 80(4):445-446. DOI: 10.1007/s40265-020-01274-3.
[3] WANG X Y, SUN G Q, FENG T, et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer′s disease progression[J]. Cell Res, 2019, 29(10):787-803. DOI: 10.1038/s41422-019-0216-x.
[4] ITZHAKI R F. Hypothesis: does the apparent protective action of green valley′s drug GV971 against cognitive decline result from antiviral action against herpes simplex virus type 1 in brain[J]. J Alzheimers Dis, 2020, 76(1):85-87. DOI: 10.3233/JAD-200210
[5] KLOSE J, GRIEHL C, ROSSNER S, et al. Natural products from plants and algae for treatment of alzheimer’s disease: a review[J]. Biomolecules, 2022, 12(5):694. DOI: 10.3390/biom12050694. PMID: 35625622; PMCID: PMC9139049.
[6] WANG Y, CHEN X T, LI Z H, et al. Analysis of monosaccharide composition and monosaccharide ratio in propylene glycol alginate sodium sulphate drugs by high performance anion exchange chromatography-pulsed amperometric detection[J]. Acta Pharm Sin (药学学报), 2021, 56(9):2346-2351.
[7] WANG Y,LI J,LI Y Y, et al. SAX-HPLC for 1, 6-anhydro derivatives quantification of enoxaparin sodium[J]. Chin Pharm J (中国药学杂志), 2014, 49(16):1461-1466.
[8] WANG Y,FAN H H. Quality control strategies and research progress in quality control technology of polysaccharide biochemical drugs[J]. Chin Pharm J (中国药学杂志), 2021, 56(1):8-12.
[9] LUO H, HE Y L, HAN Z R, et al. Structural analysis of chondroitin sulfate from shark cartilage by LC-MS analysis of enzyme-digested and deuterated PMP-Labeled products[J]. Chin J Mar Drugs (中国海洋药物), 2020, 39(3):51-57.
[10] DU H,YANG H Y,LIU G B, et al. Application of tandem mass spectrometry for glycopeptides structures representation[J]. J Henan Univ Technol(Nat Sci Ed)[河南工业大学学报(自然科学版)], 2022, 43(1):121-130, 138.
[11] LI L Y, ZHANG F M, ZAIA J, et al. Top-down approach for the direct characterization of low molecular weight heparins using LC-FT-MS[J]. Anal Chem, 2012, 84(20):8822-8829.
[12] LIU J, FENG Y F, LIU Y, et al. Application of nuclear magnetic resonance in development of first batch of traditional Chinese medicine chemical reference substances[J]. Mod Chin Med (中国现代中药), 2022, 24(2):298-303.
[13] GU X Y, BAI G H, LIU L, et al. Research progress on structural characterization of sea cucumber polysaccharide[J]. Chin J Mar Drugs (中国海洋药物), 2023, 42(1):68-75.
[14] GRASDALEN H, LARSON B, SMIDSROD O. A P.M.R. study of the composition and sequence of urinate residue in alginates[J]. Carbohydr Res, 1979, 68:23-31.
[15] TAKO M, KIYUNA S, SHUNTOKU U, et al. Isolation and characterization of alginic acid from commercially cultured Nemacystus decipiens (Itomozuku)[J]. Biosci Biotechnol Biochem, 2001, 65(3):654-657.
[16] RIKI S, SHUNTOKU U, SHINKICHI T, et al. Isolation and characterization of alginate from Hizikia fusiformis and preparation of its oligosaccharides[J]. J Appl Glycosci, 2007, 54:85-90.
[17] SALOMONSEN T, JENSEN H M, STENBAK D, et al. Chemometric prediction of alginate monomer composition: a comparative spectroscopic study using IR, Raman, NIR and NMR[J]. Carbohydr Polym, 2008, 72:730-739.
[18] XUE Y T, REN L, LI S, et al. Study on quality control of sulfated polysaccharide drug, propyleneglycol alginate sodium sulfate (PSS)[J]. Carbohydr Polym, 2016, 144:330-337.
[19] BERATTO A, AGURTO C, FREER J, et al. Chemical characterization and determination of the anti-oxidant capacity of two brown algae with respect to sampling season and morphological structure using infrared spectroscopy and multivariate analyses[J]. Appl Spectrosc, 2017, 71(10):2263-2277. DOI: 10.1177/0003702817715654.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
青岛海洋科学与技术试点国家实验室海洋药物与生物制品功能实验室开放性课题资助(LMDBKF201806);中国食品药品检定研究院学科带头人培养基金资助(2021X6)
{{custom_fund}}
PDF(3097 KB)
