目的 評價坤靈丸對雌性大鼠的生育力及胚胎發(fā)育的影響。方法 在生育力及早期胚胎發(fā)育毒性研究中，每組25只雌性SD大鼠從交配前14 d開始，每天ig給予1次坤靈丸（0.875、1.750、3.500 g制劑/kg）或去離子水至妊娠第7天，評價雌鼠癥狀、體質(zhì)量、攝食量、生殖能力和早期胚胎發(fā)育情況；在胚胎-胎仔發(fā)育毒性研究中，每組25只雌性SD大鼠從妊娠第6~15天每天ig給予坤靈丸（0.875、1.750、3.500 g制劑/kg）或去離子水1次，評價妊娠母鼠的癥狀、體質(zhì)量、攝食量、生殖能力及胎仔的體質(zhì)量、性別和外觀、內(nèi)臟、骨胳發(fā)育的畸形或變異。結(jié)果 在生育力及早期胚胎發(fā)育毒性研究和胚胎-胎仔發(fā)育毒性研究中，坤靈丸給藥劑量達(dá)到3.500 g/kg時未產(chǎn)生任何藥物相關(guān)的母體毒性和胚胎毒性。結(jié)論 本試驗條件下，雌鼠生育力及胚胎發(fā)育毒性的安全劑量為3.500 g/kg，按照體質(zhì)量計算，該劑量相當(dāng)于人用最大臨床使用劑量的43.2倍。

Objective To evaluate the effects of Kunling Pills on fertility and embryo-fetal development (EFD) in female rats.Methods In fertility and early embryonic development toxicity studies, 25 femal SD rats per group were ig administrated daily with deionized water or Kunling Pills (preparation 0.875, 1.750, and 3.500 g/kg) respectively two weeks before mating until gestational day (GD) 7. The clinical signs, body weight and body weight gain, food consumption, reproductive performance, and early embryonic development were evaluated. In EFD studies, 25 femal SD rats per group were ig administrated daily with deionized water or Kunling Pills (preparation 0.875, 1.750, and 3.500 g/kg) respectively from GD 6 to 15. Confirmed pregnant dams were evaluated for clinical signs, body weight and body weight gain, food consumption, and reproductive performance. The body weight, gender and external, visceral, and skeletal malformations/variations of fetuses were examined.Results There were no maternal toxicity and embryotoxicity at dose up to 3.500 g/kg/d in the rat fertility and early embryonic development studies and EFD studies.Conclusion Under the condition of the experiment, the no observable adverse effect level (NOAEL) for maternal fertility and embryo-fetal development was preparation 3.500 g/kg (43.2 times of the maximum recommended human daily dose based on weight).

國家科技重大新藥創(chuàng)制項目（2015ZX09501004）