疏水壳聚糖的制备及其凝血效果研究

Preparation of Hydrophobic Chitosan and Its Hemostatic Effect

摘要:

为增强壳聚糖的止血效果，采用酰基化方法在壳聚糖氨基上连接长链烷基以形成疏水性壳聚糖。该制备工艺中采用单因素设计对反应过程中的温度、浓度进行筛选，以疏水壳聚糖的黏度、取代度以及凝血效果作为评价指标，通过梯度设计筛选得到最优工艺条件：温度55℃，壳聚糖浓度1%（g/ml），月桂酸酐浓度0.3%（g/ml）。采用红外、核磁等方法对其进行表征，表明合成了疏水壳聚糖。由体外凝血实验发现，疏水壳聚糖的止血效果与其取代度在一定范围内呈正相关性，当其取代度小于9%时，1%（g/ml）的疏水壳聚糖乙酸溶液止血效果不理想；当超过15%时，相同质量浓度的疏水壳聚糖乙酸溶液呈凝胶状态，无法与血液充分混合，严重影响其止血效果。通过该实验发现取代度为9%-15%的疏水壳聚糖与血液混合后，且疏水壳聚糖的浓度不小于0.75%（g/ml）时，具有良好的凝血效果。又通过小鼠在体肝脏止血实验发现疏水壳聚糖粉末能够迅速止血，且效果显著优于壳聚糖。因此，由该方法合成的疏水壳聚糖作为止血材料时，能够显著改善壳聚糖的止血效果，达到快速止血，有望开发为新型止血材料。

Abstract:

To enhance the hemostatic effect of chitosan, a long chain alkyl group was connected to the amino group of chitosan by acylation to form hydrophobic chitosan. Single factor experiments were used to optimize the temperature and the concentration in the reaction process. The viscosity, degree of substitution and coagulation effect of hydrophobic chitosan were used as evaluation indexes. The optimum conditions were as follows: the temperature 55 ℃, 1% (g / ml) chitosan, 0.3% (g/ml) lauric acid anhydride. Its properties were characterized by IR, NMR and contact angle. It showed that hydrophobic chitosan was synthesized. The results of coagulation experiments showed that the hemostatic effect of hydrophobic chitosan was positively correlated with its degree of substitution in a certain range. When the degree of substitution was less than 9%, the hemostatic effect of 1% (g/ml) hydrophobic chitosan acetic acid solution was not ideal. When the degree of substitution was higher 15%, the same concentration of hydrophobic chitosan acetic acid solution was in a gel state and could not be fully mixed with the blood, and seriously affected the hemostatic effect. It was found that the hydrophobic chitosan with a degree of substitution 9% -15% has a good coagulation effect after mixed with blood and the concentration of hydrophobic chitosan was not less than 0.75% (g/ml). The mouse liver hemostasis experiment showed that hydrophobic chitosan powder could quickly stop bleeding and the effect was significantly better than that of chitosan. Therefore, the hydrophobic chitosan synthesized can significantly improve the hemostatic effect of chitosan. It is expected to be developed into a new quickly hemostatic material in the future.