The optimal technical parameters for potassium permanganate oxidation in the extraction and purification of heparin sodium were studied. The amount of potassium permanganate, oxidation temperature, pH vaule and oxidation time were selected for single-factor experiments. Furthermore, orthogonal experiments were used to optimize the decolorization conditions of heparin with potassium permanganate. The quality indicators for oxidized heparin such as decolorization rate, anti-factor IIa activity, yield and weight average molecular weight were investigated, and the structure of disaccharides was analyzed. Results show that the optimal conditions for the oxidation decolorization with potassium permanganate were as follows: the amount of added potassium permanganate was 1.6%, the oxidation temperature was 75 ℃, pH vaule was 9.0, the oxidation time was 4 h. The structure analysis of disaccharides showed that the content of ΔGlyser prepared by oxidation decolorization with potassium permanganate was lower, and the product quality was more stable.
胡立娜1,3,张 惠1,3,赵一凡1,许忠良2,郄正刚1,李志敏1,3. 高锰酸钾氧化脱色技术在肝素制备中的应用研究[J]. 煤炭与化工, 2025, 48(7): 135-140.
Hu Lina1,3, Zhang Hui1,3, Zhao Yifan1, Xu Zhongliang2, Qie Zhenggang1, Li Zhimin1,3. Study on the application of potassium permanganate decolorization technology in the preparation of heparin. CCI, 2025, 48(7): 135-140.
1 ] Linhardt, Robert, J. claude s. hudson award address in carbohyd-
rate chemistry. heparin: structure and activity[ J ]. Journal of Medicinal Chemistry, 2003, 46( 13 ): 2 551 - 2 564.
[ 2 ] Lennart Thunberg and Gudrun Bockstrom and Ulf Lindahl. Furt-
her characterization of the antithrombin - binding sequence in heparin[ J ]. Carbohydrate Research, 1982( 53 ): 441 - 450.
[ 3 ] Martins, S. I. F. S. , Jongen, W. M. F. , Boekel, M. A. J. S. V. A review of maillard reaction in food and implications to kinetic modelling[ J ]. Trends in Food Science & Technology, 2000,11( 9 - 10 ): 364 - 373.
[ 4 ] 任红媛,何 泼,李红心. 猪小肠粘膜中肝素钠提取与精制工艺研究[ J ]. 食品研究与开发,2007,28( 1 ):4 - 5.
[ 5 ] 曲 涛,高福凯,苗 伟,等. 一种肝素钠的制备方法:CN,103755838A[ P ]. 2014.
[ 6 ] Lormeau J C, Petitou M, Choay J. LOW MOLECULAR WEIGHT HEPARINS OF REGULAR STRUCTURE, THEIR PREPARATION AND THEIR BIOLOGICAL USES: AU19880014663[ P ]. 2003.
[ 7 ] 刘力波,田志鹏,李志敏. 牛源肝素钠的工艺研究与结构分析[ J ]. 农产品加工,2023( 6 ):77 - 80.
[ 8 ] R Ishiwatari, S Morinaga. A study of formation mechanism of sedi-
mentary humic substances-i. characterization of synthetic humic substances ( melanoidins ) by alkaline potassium permanganate oxidation[ J ]. Organic Geochemistry, 1986, 9( 1 ): 11 - 23.
[ 9 ] 李 宁,张静岩,任风芝,等. 依诺肝素钠树脂脱色工艺研究[ J ]. 化学与生物工程,2017,34( 7 ):3 - 5.
[ 10 ] 陈群英. 生色底物法测定低分子肝素抗FⅩa以及抗FⅡa效价的方法研究[ J ]. 中国医药工业,2019,50( 8 )5 - 8.
[ 11 ] Griffin C C, Linhardt R J, Gorp C L V, et al.Isolation and charact-
erization of heparan sulfate from crude porcine intestinal mucosal peptidoglycan heparin[ J ]. Carbohydrate Research, 1995, 276( 1 ): 183 - 197.
[ 12 ] Halal S.L.M., Colussi R., Pinto V.Z., et al. Structure, morphology and functionality of acetylated and oxidised barley starches[ J ]. Food Chem., 2015( 168 ): 247 - 256.
[ 13 ] Rosenberg, R. D.The purification and mechanism of action of hu-
man antithrombin - heparin cofactor[ J ]. Journal of Biological Chemistry, 1973( 248 ): 289 - 293.
[ 14 ] Damus P S, Hicks M, Rosenberg R D. Heparin a generalized view of its anticoagulant action[ J ]. Nature, 1973( 246 ): 159 - 162.
[ 15 ] Beccati D, Roy S, Yu F, et al. Identification of a novel structure in heparin generated by potassium permanganate oxidation[ J ]. Carbohydrate polymers, 2010, 82( 3 ): 699 - 705.
[ 16 ] Mourier P A J, Guichard O Y, Fréderic Herman,et al.Heparin sodium compliance to USP monograph: Structural elucidation of an atypical 2.18ppm NMR signal[ J ]. Journal of Pharmaceutical & Biomedical Analysis, 2012( 67 - 68 ): 169 - 174
[ 17 ] Mourier P A J, Agut C, Souaifi - Amara H, et al. Analytical and statistical comparability of generic enoxaparins from the US market with the originator product[ J ]. Journal of Pharmaceutical and Biomedical Analysis, 2015( 115 ): 431 - 442.