坤灵丸对雌性大鼠生育力及胚胎-胎仔发育影响的研究

目的 评价坤灵丸对雌性大鼠的生育力及胚胎发育的影响。方法 在生育力及早期胚胎发育毒性研究中，每组25只雌性SD大鼠从交配前14 d开始，每天ig给予1次坤灵丸（0.875、1.750、3.500 g制剂/kg）或去离子水至妊娠第7天，评价雌鼠症状、体质量、摄食量、生殖能力和早期胚胎发育情况；在胚胎-胎仔发育毒性研究中，每组25只雌性SD大鼠从妊娠第6~15天每天ig给予坤灵丸（0.875、1.750、3.500 g制剂/kg）或去离子水1次，评价妊娠母鼠的症状、体质量、摄食量、生殖能力及胎仔的体质量、性别和外观、内脏、骨胳发育的畸形或变异。结果 在生育力及早期胚胎发育毒性研究和胚胎-胎仔发育毒性研究中，坤灵丸给药剂量达到3.500 g/kg时未产生任何药物相关的母体毒性和胚胎毒性。结论 本试验条件下，雌鼠生育力及胚胎发育毒性的安全剂量为3.500 g/kg，按照体质量计算，该剂量相当于人用最大临床使用剂量的43.2倍。

Effects of Kunling Pills on fertility and embryo-fetal development in femal rats

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).