医用羧甲基葡糖胺聚糖凝胶生物安全性评价  

Biosafety evaluation of medical injectable carboxymethyl glycosaminoglycan gel

作　　者：程琳[1] 李睿智 程鹏[1] 祝君梅[1] 李昕[1] 李东风 于欢 王世炜 史梦柔 陈斌[1] 高萍[1] Cheng Lin;Li Ruizhi;Cheng Peng;Zhu Junmei;Li Xin;Li Dongfeng;Yu Huan;Wang Shiwei;Shi Mengrou;Chen Bin;Gao Ping(Tianjin Institute of Pharmaceutical Science,Tianjin 300020,China;IMEIK Technology Development Co.,Ltd,Beijing 102200,China)

机构地区：[1]天津市医药科学研究所,300020 [2]爱美客技术发展股份有限公司,北京100022

出　　处：《国际生物医学工程杂志》2020年第2期106-112,共7页International Journal of Biomedical Engineering

摘　　要：目的评价医用羧甲基葡糖胺聚糖凝胶的生物安全性。方法采用鼠伤寒沙门氏菌回复突变实验(Ames实验)、体外染色体畸变实验和体外基因突变实验检测医用羧甲基葡糖胺聚糖凝胶的遗传毒性。以日本大耳白兔为受试动物,经耳缘静脉缓缓注入凝胶盐水浸提液(10 ml/kg),测其体温并计算体温升温值。以昆明种小鼠为受试动物,分别经腹腔注射和尾静脉注射凝胶盐水浸提液(50 ml/kg)和氯化钠注射液(对照),观察动物的毒性反应,记录动物的体质量变化。在抗凝兔血中分别加入凝胶盐水浸提液、氯化钠注射液与蒸馏水,检测溶血率。结果在活化和非活化条件下,凝胶盐水浸提液组和凝胶二甲基亚砜浸提液组4种菌株的回变菌落数均未达到相应阴性对照组的2倍;3个剂量组(凝胶培养基浸提液和1/2、1/4凝胶培养基浸提液组)中国仓鼠肺成纤维细胞的染色体畸变率均为0;3个剂量组小鼠淋巴瘤细胞L5178Y的大集落突变频率、小集落突变频率和总突变频率均无明显增长(均P>0.05)。注射凝胶盐水浸提液后,3只日本大耳白兔的体温升温值分别为0、0.3和0.2℃。注射凝胶盐水浸提液后24、48和72 h,各组小鼠均未见毒性反应症状,且随着注射后时间的延长,样品组和对照组小鼠体质量均有所增长,但差异均无统计学意义(均P>0.05)。溶血实验结果显示,医用羧甲基葡糖胺聚糖凝胶的溶血率为0.1%。结论医用羧甲基葡糖胺聚糖凝胶无诱发细菌突变、体外细胞染色体畸变及细胞基因突变的作用,亦无热原性、急性全身毒性和溶血性,表明其具有良好的生物安全性。Objective To evaluate the biosafety of medical injectable carboxymethyl glycosaminoglycan gel.Methods Ames test,chromosome aberration test in vitro and gene mutation test in vitro were used to detect the genotoxicity of the medical carboxymethyl glycosaminoglycan gel.The gel saline extract(50 ml/kg)was injected slowly through the marginal vein of the ear into Japanese big-eared rabbits.The body temperature was measured and the temperature rise was calculated.The gel saline extract(50 ml/kg)and normal saline(control)were injected intraperitoneally and intravenously into the Kunming mice,respectively.The toxicity response in mice was observed after injection,and bodyweight change was valued.The gel saline extract,normal saline and distilled water were added into the rabbit anti-clotting,to detect the rate of hemolysis.Results Under active and inactive conditions,the number of spontaneous revertants of the 4 strains of gel saline extract group and gel DMSO extract group did not reach 2 times of that of the corresponding negative control group.The rate of chromosome aberration of the three dose groups were 0.There was no significant increase in the large colony mutation frequency,small colony mutation frequency and total mutation frequency in three dose groups(all P>0.05).After injection of gel saline extract for 24,48 and 72 h,no toxic reaction was found in each group of mice.With the extension of time after injection,the body weight of mice in the sample group and the control group increased,but the difference was not statistically significant(P>0.05).After injection of gel saline extract,the temperature rise of 3 Japanese big-eared rabbits were 0.0,0.3 and 0.2℃respectively.The results of hemolysis test showed that the hemolysis rate of the polycarboxymethyl glucosamine gel was 0.1%.Conclusions No genetic toxicity changes were found in carboxymethyl glycosaminoglycan to induce gene mutation or chromosome damage in bacteria and cells,and no pyrogenicity,acute systemic toxicity and hemolysis were observed.These res

关 键 词：凝胶类 诱变力实验 生物安全性 羧甲基葡糖胺聚糖 

分 类 号：R318.08[医药卫生—生物医学工程]