Influence of methylation process on the degree of quaternization of N-trimethyl chitosan chloride
Influence of methylation process on the degree of quaternization of N-trimethyl chitosan chloride
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DOI：
10.1016/s0939-6411(03)00151-6
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发表时间：
2004-01-01
影响因子：
4.9
通讯作者：
Junginger, HE
中科院分区：
文献类型：
--
作者：
Polnok, A;Borchard, G;Junginger, HE
N-三甲基壳聚糖氯(TMC)是一种可溶性的壳聚糖衍生物，对多肽和蛋白质类药物的粘膜转运具有有效的促进作用。以壳聚糖为原料，在碱性条件下高温还原甲基化合成了TMC。甲基化过程的步骤数和过程中使用的碱基影响伯氨基的季胺化程度以及3-和6-羟基的甲基化程度。H-1-核磁共振谱表明，与二甲氨基吡啶相比，氢氧化钠为碱时，TMC的季铵化程度更高。随着反应步数的增加，TMC的季胺化程度和O-甲基化程度增加。O-甲基化导致TMC的溶解度降低。采用一步加成、两步加成和控制混合反应的碱性环境，可制得季铵化程度高、O-甲基化度低的TMC。(C)2003爱思唯尔B.V.保留所有权利。
N-Trimethyl chitosan chloride (TMC) is a soluble chitosan derivative that shows effective enhancing properties for peptide and protein drug transport across mucosal membranes. TMC was synthesized by reductive methylation of chitosan in an alkaline environment at elevated temperature. The number of methylation process steps and the base used in the process was demonstrated to affect the degree of quaternization of the primary amino group and methylation of 3- and 6-hydroxyl groups. H-1-Nuclear magnetic resonance spectra showed that the degree of quaternization of TMC was higher when using sodium hydroxide as the base compared to using dimethyl amino pyridine. The degrees of quaternization as well as O-methylation of TMC increased with the number of reaction steps. O-Methylation resulted in decreased solubility of TMC. The high degree of quaternization of TMC with a low degree of O-methylation was prepared by employing one reaction step with two subsequent addition steps and a controlled alkaline environment of the mixture reaction. (C) 2003 Elsevier B.V. All rights reserved.