Study On A Special Impurity In Carboxymethylated Chitosan And Synthesis Optimization

Carboxymethylation is one of the strategies to perform the chemical modification of chitosan for exploitation, whose product is nontoxic, with good water solubility and wide perspective. Chloracetic acid was usually used in the synthesis of carboxymethylated chitosan(CMC). It was the first time that our laboratory found that a impurity named diglycolic acid(DGA) was mixed within the CMC, which caused slight cell toxicity and interfered its clinical application.This thesis aimed to study the special impurity--DGA in CMC. A HPLC method has been established to analyze diglycolic acid based on its physical and chemical properties. In this thesis, the synthesis route was optimized considering the carboxylated degree and the quantity of diglycolic acid.A Waters HPLC system equipped with a Atlantis C-18(5μm,150mm×4.6mm.ID) column, set at a temperature of 30℃was used in this study. The mobile phase was composed of methanol and lOmmol·L-1 potassium dihydrogen phosphate(KDP) (pH 2.50) (3/97, v/v). The flow rate was 0.6 mL·min-1, the detected wavelength was 204 nm, and the extract was methanol/water (8/2, v/v).The final optimal route was as follows:rate of reactant's weight was w(chitosan):w(NaOH)=1:4, w(NaOH):w(ClCH2COOH)=1:1, and reacting temperature 50℃, reacting time 3 hours. The way for cleaning CMC was also optimized in this thesis.In this thesis, a special impurity—DGA was found for the first time in the synthesis of CMC, the specific HPLC analysis method was established, the synthesis route of CMC was optimized. All of these work offered the quality control index and the solid foundation based on which to further develop CMC.