静脉注射重组Ⅲ型人源化胶原蛋白的一般毒理学研究OA

OBJECTIVE:To evaluate safety of recombinant humanized Type Ⅲ collagen and to provide reference data for safe clinical use.METHODS:The maximum tolerated dose method was adopted in the acute toxicity test.ICR mice aged 3-5 weeks were administered the recombinant collagen via tail vein injection at the maximum dosage of 2 000 mg/kg for a single administration.After administration,the toxic reaction in these mice was closely observed.In the long-term toxicity test,120 SD rats aged 6 weeks were selected and divided into high-dose(130 mg/kg),medium-dose(65 mg/kg),low-dose(32.5 mg/kg)groups and a control group,with 30 rats in each group.The drug was continuously administered for 28 days,followed by a 28-day recovery period.The main inspection indicators included animal ophthalmology,body weight,feed consumption,hematological indexes,serum biochemistry,blood coagulation,urine indexes,histopathology,etc.RESULTS:In the acute toxicity test,the maximum tolerated dose was greater than 2 000 mg/kg,equivalent to 1 503.76 times the clinically proposed dosage,and no obvious toxic and side effects.In the 28-day repeated dose toxicity test,the no-observed-adverse-effect level(NOAEL)of recombinant humanized Type Ⅲ collagen administered via tail vein injection in SD rats was 130 mg/kg,corresponding to 97.74 times the proposed clinical dose for adults.CONCLUSION:Under the conditions of this experiment,recombinant type Ⅲ humanized collagen did not show obvious toxic reactions.