摘要
Abstract
Objective To evaluate the effects of repeated-dose toxicity of the candidate drug HYH2002 injection in Sprague-Dawley(SD)rats,thereby providing a basis for its use in clinical trials.Methods A total of 120 SD rats(half male,half female)were randomly divided into four groups.Group 1(vehicle control)received the blank formulation solution.Groups 2,3,and 4 were administered HYH2002 injection at doses of 0.60,3.00,and 9.00 mg·kg-1,respectively.The test article was administered once daily via tail vein infusion for 2 weeks,followed by a 2-week recovery period.Parameters including clinical observations,body weight,food consumption,body temperature,ophthalmological examinations,hematology,coagulation parameters,clinical biochemistry,and urinalysis were assessed at scheduled intervals.Necropsy,gross observations,and histopathological examinations were conducted at the end of the dosing period and the recovery period.Results Animals in the 9.00 mg·kg-1 group exhibited decreases in body weight and food consumption.Hematological changes included decreases in red blood cell(RBC)count,hemoglobin(HGB),hematocrit(HCT),and lymphocyte count(Lymph),alongside increases in neutrophil count(Neut),mean corpuscular volume(MCV),and reticulocyte count(Retic).Clinical biochemistry showed a decrease in albumin(Alb).These changes were reversible after the 2-week recovery period.No test article-related adverse effects were observed in the 0.60 and 3.00 mg·kg-1groups.Under the conditions of this study,the no-observed-adverse-effect level(NOAEL)was determined to be 3.00 mg·kg-1,which is 50 times the effective dose(0.06 mg·kg-1)in a rat model of gastric ulcer.Conclusion HYH2002 injection demonstrates a favorable safety profile within the anticipated therapeutic dose range,suggesting a low risk for clinical trials.关键词
HYH2002注射液/大鼠/重复给药/毒性试验Key words
HYH2002 injection/rats/repeated dose toxicity/toxicological study分类
医药卫生
