星点设计-效应面法优化O-羧甲基壳聚糖止血海绵

Optimization of the O-carboxymethyl chitosan hemostatic sponge by the central composite design-response surface methodology

目的:优化O-羧甲基壳聚糖止血海绵处方,制备O-羧甲基壳聚糖止血海绵。方法:建立兔耳缘动、静脉创伤出血模型,以O-羧甲基壳聚糖为载体,戊二醛为交联剂,氯化钙为凝血启动因子,以止血时间和出血量为优化指标,应用星点设计-效应面法筛选最佳处方;采用冷冻干燥技术制备O-羧甲基壳聚糖止血海绵;并验证最优处方的止血效果。结果:O-羧甲基壳聚糖止血海绵的最优处方为:O-羧甲基壳聚糖2.49%,戊二醛1.08%,氯化钙2.11%,三者质量比为10∶0.1∶5;制得的海绵疏松多孔,具有良好的韧性;其用于兔耳动、静脉出血模型的止血时间为(53.0±8.5)s,出血量为(0.151±0.020)g,止血效果与预测值吻合。结论:采用星点设计-效应面法筛选得到的优化处方合理,制得的O-羧甲基壳聚糖止血海绵具有显著的止血效果。

OBJECTIVE To optimize the formulation of O-carboxymethyl chitosan hemostatic sponge and to prepare the o- carboxymethyl chitosan hemostatic sponge. METHODS The rabbit ear vessels, bleeding wound model was established. O-car- boxymethyl chitosan, glutaraldehyde and CaC12 were selected as carrier, coagulant and hemostatic promoter, respectively. The hemostatic time and bleeding volume（weight） were selected as optimized indexes. The central composite design-response sur- face methodology was used to screen the optimized prescription. The freeze drying technology was used to prepare the O-car- boxymethyl chitosan hemostatic sponge, and its hemostatic effects were verified. RESULTS The optimized formulation of o- carboxymethyl chitosan hemostatic sponge was as follows： O-carboxymethyl chitosan 2. 49 %, glutaraldehyde 1.08 % and CaC12 2. 11%, respectively. The ratio of O-carboxymethyl chitosan, glutaraldehyde and CaCl2 was 10 ： 0. 1 ： 5. The gained sponges had porosity and good tenacity. Both the hemostatic time and bleeding volume （weight） in the rabbit ear vessels, bleeding wound model were （53. 0 ± 8.5） s and （0. 151 ± 0. 020）g, respectively. The hemostatic efficacy conformed to the predicted val- ue. CONCLUSION The optimized prescription with central composite design-response surface methodology was reasonable and the prepared O-carboxymethyl chitosan hemostatic sponge has the significant hemostatic efficacy.