一种可吸收止血纤丝的有效性和安全性评价

Evaluation of self-prepared absorbable hemostatic cellulose fibrils

目的:评估可吸收止血纤丝的有效性和安全性。方法:采用自主研发专利技术制备得到一种可吸收止血纤丝,与已上市产品速即纱进行比较,通过大体观察和傅里叶红外光谱法表征其物理形态及分子结构;电位滴定法测定纤丝的羧基含量,酸碱度计测定酸碱度值,铜乙二胺法测定相对分子质量;倒置显微镜观察纤丝与血液接触后的表现;琼脂扩散法评价纤丝的细胞毒性。建立大鼠髂外动脉出血模型和背部肌肉渗血模型,通过止血时间和血液质量考察纤丝的止血有效性,通过观察拍照、免疫器官称重、血液学和凝血功能检测及组织病理学检查分析纤丝的降解吸收情况和安全性。结果:纤丝和速即纱具有相似的分子结构。与原料再生纤维素相比,纤丝和速即纱在1727 cm–1附近均出现了典型的羧基–COOH伸缩振动吸收峰。两种材料羧基含量约为20%,酸碱度值约为3,与氧化前相比表现出明显的酸性。纤丝经氧化后的相对分子质量为4466±79,与速即纱接近(P>0.05)。纤丝与速即纱接触血液后体积膨胀,可吸收自身质量数十倍的血液。琼脂扩散实验表明纤丝无细胞毒性。动物实验结果显示,纤丝可在2 min内完成止血,止血时间和吸收血液质量与速即纱差异无统计学意义(均P>0.05)。纤丝植入肌肉渗血部位后1周即可降解,植入纤丝对动物的外观体征、体重、摄食、胸腺、脾脏、淋巴结及血液学、凝血功能等均无明显影响,组织病理学检查未见明显异常。结论:本研究自主研发的可吸收止血纤丝具有较好的生物安全性和有效性。

Objective:To evaluate the effectiveness and safety of self-prepared absorbable hemostatic fibrils.Methods:A kind of absorbable hemostatic fibrils were prepared by self-developed patent technique.The physical form and molecular structure of the fibrils and a marketed product Surgicel■were characterized by general observation and infrared spectroscopy;the carboxyl content,pH value and relative molecular mass of fibrils were determined by potentiometric titration method,pH meter and copper ethylenediamine method,respectively.The behavior of the fibrils and Surgicel■in contact with blood was observed by inverted microscope,the cytotoxicity was evaluated by agarose diffusion cell assay in vitro.The external iliac artery hemorrhage model and the back muscle infiltration model in rats were established.The hemostatic effectiveness of the fibrils was investigated by hemostasis time and blood weight,and the degradation and biosafety of fibrils were investigated by observation photography,immune organ weighing,hematology and coagulation index measuring,and histopathological examination.Results:The fibrils and Surgicel■had similar molecular structures.Compared with the raw material regenerated cellulose,the typical carboxyl stretching vibration absorption peak of-COOH appeared near 1727 cm^(-1) in both fibrils and Surgicel■.The carboxyl content of the two materials was about 20%,and the pH value was about 3.The relative molecular mass of the fibers after oxidation was 4466±79,which was close to that of Surgicel■(P>0.05).After contacting with blood,the volume of fibrils and Surgicel■expanded,and absorbed blood of dozens of times as their own weight.The results of agar diffusion test showed that the fibrils had no cytotoxicity.The results of animal experiments showed that the hemostasis completed within 2 min,and there was no significant difference in blood weight and speed of hemostasis between two products(both P>0.05).The fibrils could be degraded 1 week after being implanted to the bleeding sites of the muscle.There were no pathological effects on the appearance,body weight,food intake,immunological tissue thymus,spleen,lymph nodes,hematology and coagulation indexes of the rats,and no obvious abnormality found in the histopathological examination.Conclusion:The prepared absorbable hemostatic fibrils have excellent biological safety and effectiveness.