肾炎灵片生殖毒性试验

Reproductive Toxicity Test of Shenyanling Tablet

目的:研究江苏康缘药业股份有限公司提供的治疗肾小球疾病纯中药制剂肾炎灵片的生殖毒性。该剂是对传统中药组方创新和剂型改造,为其临床应用和新药审批提供安全性资料。方法:①雄性大鼠生殖毒性试验:成年雄性大鼠连续灌服肾炎灵片剂2个月,与正常雌性大鼠1∶1合笼。雌鼠第2天起做阴道涂片,见到精子日为妊娠第1天(D1),于妊娠第19天(D19)剖杀,记录孕鼠数、胎仔数、活胎数、死胎数、吸收胎仔数及胎鼠的外观检查(性别、体质量、尾长、胎盘质量等)。将1/2胎鼠用茜苏红骨骼染色检查骨骼有否畸形;其余1/2胎鼠用Bouin氏液固定,观察内脏发育情况。②雌性大鼠生殖毒性试验:成年雌鼠连续灌服肾炎灵片剂14d,14d后与正常雄鼠1:1合笼交配,第2天起做阴道涂片,见到精子日为D1。妊娠后继续灌药,其中10只孕鼠再灌药第13天停药,D19剖杀,观察指标同上;另10只孕鼠连续给药至整个妊娠期(21d)和哺乳期(21d),观察其受孕、分娩、哺乳和仔鼠存活情况。结果:高剂量6.25g/kg和低剂量1.25g/kg的上述雌、雄大鼠生殖毒性试验结果,分别与雌、雄大鼠对照组比较,孕鼠数、胎仔数、活胎数、死胎数、吸收胎仔数及胎仔内脏等各项观察指标均无明显差异,哺乳和仔鼠存活也无明显差异。结论:在本实验条件下,肾炎灵片剂的生殖毒性试验为阴性。

Objective： To study the repro＇dnctive toxicity of Shenyanling tablet, a components innovation and dosage form reforming of traditional Chinese medicine, provided by Jiangsu Kangyuan pharmaceutical limited company for the treatment of renal glomerular disease, and to provide safety evidences for its clinical application and new drug approval. Methods： （1） Reproductive toxicity test of male rats. Adult male SD rats were treated with Shenyanling tablets by intragastric administration for 2 months, and then mated with female rats （male： female, 1：1）. The female rats were checked with Vaginal smear the second morning, and the day with the presence of sperm was denoted the first day of gestation （D1）. Female rats were dissected on D19, and the numbers of pregnant rats, litter size, living fetus, dead fetus and absorbed fetus, as well as the external appearance of fetus were checked, including gender, body weight, length of tail, and weight of placenta. Skeleton malformation was examined using Qiansuhong dyeing, and the development of internal organs was observed by Bouins-fixing of fetus. （2） Reproductive toxicity test of female rats. Adult female rats were treated with Shenyanling tablets by intragastric administration for 14 days, and then mated with male rats （male： female, 1：1）. Vaginal smear was performed the second morning, and the day with the presence of sperm was denoted the first day of gestation （D 1）. 10 pregnant rats were treated with Shenyanling for 13 days and dissected on D 19, with the same observation indexes as mentioned above. Another 10 pregnant rats were treated with Shenyanling during the whole period of gestation （21 days） and lactation （21 days）. The additional parameters were detected, including the status of conceiving, parturition, lactation, and the survival of fetus. Results： All data collected from the two study groups of Shenyanling treatment （the high dosage group with 6.25 g/kg and the low dosage group with 1.25 g/kg） were compared with the control groups, and the differences among all the observation indexes mentioned above showed no statistical significance. Conclusions： The reproductive toxicity of Shenyanling is negative under the experiment condition of this study.