【摘要】 本研究将两种不同用途的凝胶产品通过腹腔注射和皮下植入的方式,分别对其亚慢性全身毒性和局部植入反应进行评价。全身毒性试验结果显示:在给药期间,试验组和对照组动物体重增长无明显差异;试验终期血液学和临床血液生化指标均无临床意义差异;大体病理学和组织病理学检查均未见由试验材料导致的脏器改变和组织病理学异常。局部植入的病理学观察发现:凝胶A植入早期有轻微炎症反应,植入后期有轻度组织反应。凝胶B植入早期有轻微炎症反应,植入后14d包囊结构消失。本研究结果表明:凝胶产品的不同特性决定了其在动物体内不同的降解代谢过程,从而决定了其在临床上不同的应用范围。同时,本文对亚慢性全身毒性和局部植入反应两种评价方法在风险管理中的应用进行了比较,以期对生物安全评价选项提供参考。更多还原

【Abstract】 According to the requirements of ISO10993-11:2006 and ISO10993-6:2007 standards,we used SD rats for evaluating the subchronic systemic toxicity and local implantation response of two kinds of sodium hyaluronan gels with different application.The results of 90d subchronic toxicity study by intraperitoneal route showed that the animals of the tested group and control group grew normally.There were no differences in the increases of the body weight,haematological index and clinical biochemistry indexes.The examination of gross pathology and histopathology revealed no abnormal changes caused by the test substance during the process.But there was different degree test article residual in the body of the animals at the end of the experiment.It was observed in the local subcutaneous implantation that at the early stage,gel A had mild inflammatory response,cysts were seen clearly,and new blood capillaries were visible at local area.Later,the wall got thinner and dense with little tissue reaction.Gel B also had mild inflammatory response earlier,but it totally disappeared after 14 days of implantation.It can be concluded that the gel products with different characteristics decided its degradation and metabolic process in the body of the test animals and therefore the areas of application of the products clinically.Meanwhile,we compared the evaluation method of subchronic systemic toxicity and local implantation response in risk assessment,providing reference for the choice of biological safe testing.更多还原