关键词: 清疫胶囊, 毒性, 单次给药, 重复给药, 最大耐受量, 无毒反应剂量, 非临床安全性评价, 大鼠

Abstract: Objective To assess the safety of Qingyi capsules for clinical use by evaluating the acute toxicity in a single-dose administration test and the subchronic toxicity in a 4-week repeated-dose administration test in SD rats. Methods The maximum tolerated dose (MTD) and no observed adverse effect level (NOAEL) were determined via single-dose gavage toxicity tests and repeated-dose 4-week toxicity tests in SD rats before the toxicology and target organs were identified. The highest single dose for toxicity testing was 21g·kg^-1, and clinical observation, measurement of body weight changes, and pathological examination were conducted. For the 4-week repeated-dose toxicity test, the three doses were set at 1.5, 4.5 and 10.5 g·kg^-1, respectively, along with a vehicle control group. The examination indicators involved the rats’ external signs, body weight, food intake, ophthalmology, hematology, biochemistry, immune indicators, weight of major organs, gross necropsy, and histopathological examination. Results In the toxicity test, no death occurred, and no abnormality related to drug administration was observed in the gross pathological examination. There were no significant abnormalities in organ weights. In the repeated-dose toxicity test, food consumption was decreased and body weight gain retarded in the 10.5 g·kg^-1 dosing group, accompanied by reductions in red blood cell count, hemoglobin levels and an increase in reticulocyte count. These abnormalities were possibly associated with long-term high-dose administration of the test substance, and all the above changes were reversible after drug withdrawal. No abnormality related to the test substance was observed in the histopathological examination. Conclusion The MTD of Qingyi capsules in SD rats by single intragastric administration is 21 g·kg^-1 (equivalent to 183.12 g·kg^-1 of the crude drug). The NOAEL in the 4-week repeated-dose toxicity test in SD rats is 4.5 g·kg^-1(equivalent to 39.24 g·kg^-1 of the crude drug). Under the conditions used in this test, Qingyi capsules show no obvious toxicity in the tested animals. Long-term oral administration is safe within the intended dosages and courses of treatment.

Key words: Qingyi Capsules, Toxicity, Single-Dose, Repeated Administration, Maximum Tolerance Dose (MTD), No Observed Adverse Effect Level (NOAEL), Non-Clinical Safety Evaluation, Rats