关键词: 重组III型人源化胶原蛋白, 急性毒性, 长期毒性, 非临床安全性评价

Abstract: 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.

Key words: recombinant type III humanized collagen, acute toxicity test, long-term toxicity test, nonclinical safety evaluation