脱氧胆酰酪氨酸热敏凝胶剂对家兔避孕效果和阴道黏膜刺激性研究

Contraceptive Effect and Vaginal Mucosa Irritation of Deoxycholyltyosine Thermoreversible Gel

目的:验证脱氧胆酰酪氨酸热敏凝胶剂(DCTgel)对家兔避孕效果和阴道黏膜的刺激作用。方法:采用体外杀精试验、体内杀精试验和家兔避孕效果试验;按WHO方法评价阴道黏膜刺激性。结果:DCTgel体外杀精的ED50为0.026mg/ml;DCTgel(12.5mg、25mg)体内杀精效果与市售壬苯醇醚凝胶剂(N-9jelly,25mg)相同。家兔避孕试验表明,25mgDCTgel组与25mgN-9jelly组的避孕率相同,与基质对照组相比,有非常显著的差异(P<0.01)。阴道黏膜刺激试验结果表明,25mgN-9jelly组的总分值为6.8±0.6,25mgDCTgel为2.7±0.15,基质对照组为1.5±0.2,均在临床可接受范围。但光镜下显示,25mgN-9jelly对家兔阴道黏膜有中度刺激,但部分黏膜上皮发生点状溃疡,并伴有坏死或脱落;25mgDCTgel组仅对家兔阴道黏膜有轻度刺激,黏膜上皮完整,仅见部分黏膜上皮充血及炎症细胞浸润。结论:DCTgel与市售N-9jelly比较,避孕效果相似,而前者副作用较小,显示出具有一定的应用前景,可作为先导药物进一步进行临床前药效学研究。

Objective： To identify the contraceptive effect and possible vaginal mucosa irritation of deoxycholyltyosine thermo-reversible gel （DCT gel）. Methods： In vitro spermicidal test, in vivo spermicidal test and contraceptive effect test in rabbits were conducted. Vaginal mucosa irritation indices were assessed according to WHO criteria. Results： In vitro spermicidal test showed that 50% effective dose （EDso） of DCT gel was 0.026 mg/ml. The in vivo spermicidal effect of DCT gel group （12.5 mg and 25.0 mg） was comparable to that of N-9 jelly group （25.0 rag）. Contraceptive effect test showed that, the contraceptive rates of 25.00 mg DCT gel group and 25.00 mg N-9 jelly group were similar, significantly higher than blank control （P〈0.01）. Vaginal irritation test showed that, the score of N-9 jelly group （25.0 mg）, DCT gel group （25.0 mg） and blank control group were 6.8 ± 0.6, 2.7 ± 0.1 and 1.5 ± 0.2, respectively. All scores were within the clinical acceptable ranges, however, light microscopic examination showed that, in N-9 jelly group epithelial spot ulceration and necrosis were found, while in 25.0 mg DCT gel group epithelia were intact with occasional vascular congestion and leukocyte infiltration, indicating milder vaginal irritation. Conclusion： Compared with N-9 jelly, DCT gel has similar contraceptive effect but less side effect, suggesting DCT can be a promising precursor compound.