黄体酮凝胶剂的刺激性和子宫内膜转化实验研究

Irritation test and endometrial transformation experiment of progesterone gel on rabbits after vaginal delivery

目的:研究黄体酮凝胶剂阴道给药后的刺激性及其对子宫内膜Mcphail指数的影响,初步考察药效,探讨黄体酮凝胶剂的制剂可行性。方法:选取雌性未孕未产普通家兔20只,随机分成空白对照组,空白基质组,低、中、高剂量组,每组各4只。除空白对照组和空白基质组外,其余各组分别给予不同剂量黄体酮凝胶剂,考察黄体酮凝胶剂单次和多次给药后的阴道刺激性。在此基础上,采用子宫内膜转化实验检测黄体酮凝胶剂对家兔子宫的作用。结果:单次或多次给药后,与空白对照组相比,各组家兔均未出现明显的红斑、分泌物渗出。病理切片结果表明,单次或多次给药后,各组病理结果无明显差异。药效学结果表明,经过23 d给药,空白基质组,低、中、高剂量组,阳性对照组的Mcphail分级结果分别为(0.25±0.46)、(1.00±0.61)、(1.75±0.50)、(2.25±0.50)、(3.20±0.27);子宫病理切片结果显示低、中、高剂量组子宫逐渐由增生期向分泌期转变。结论:黄体酮凝胶剂单次或多次给药后,对家兔阴道和子宫无明显刺激性,Mcphail分级显示黄体酮凝胶剂具有一定的孕激素活性,能促进家兔子宫内膜发育,表明该剂型具有一定的制备可行性。

Objective： To study vaginal irritation and effect on the lining of the uterus after vaginal delivered progesterone gel, and investigate the practicability of progesterone gel preparation. Methods： A total of 20 female rabbits were randomly divided into five groups： blank control group, blank matrix group, low dose group, middle dose group, and high dose group. Then the irritation of progesterone vaginal gel was studied after a single dose and multiple doses. The results were scored according to vaginal irritation grading standard tables and classification criteria for vaginal irritation after observation. Furthermore, initial pharmacodynamics of progesterone gel was studied. The vagina and uterus of every rabbit was detected as well as the results were measured by transforming activity of each rabbit. Results： Compared with the blank control group, after a single dose and multiple doses, the rabbits in each group showed no obvious erythema and exudate. Biopsy results showed that there was no significant difference between rabbits in each group. In the initial pharmacodynamical study, the Mcphail indexes in blank matrix group, low, middle, high dose group and positive control group were （0.25 ± 0.46）, （1.00 ± 0.61）, （1.75 ± 0.50）, （2.25 ± 0.50）, （3.20 ± 0.27） respectively after 23 d treatments. Uterine pathological results showed the uterus changes from the proliferative phase to the secretory phase were all observed in the low, middle and high dose group. Conclusion： No significant vaginal and uterus irritation was observed in rabbits after vaginal delivery of progesterone gel with single or multiple doses. Furthermore, progesterone gel has certain progesterone activity, which shows that this formulation is feasible.