黄体酮凝胶剂的制备及药效测定

Preparation and pharmacodynamics determination of progesterone gels

目的:制备黄体酮凝胶剂,并初步考察黄体酮凝胶剂的药效。方法:进行黄体酮凝胶剂的处方优化,选用卡波姆-940为凝胶剂的基质,通过正交试验,以黏度、屈服值和触变性为指标,筛选天然黄体酮凝胶剂的最佳处方。在此基础上,采用兔子宫内膜转化实验考察兔子宫分级指数、子宫增重指数和子宫腺体数,以考察黄体酮凝胶剂的药效。结果:通过处方优化制备的黄体酮凝胶剂外观乳白色,粒径分布均匀,黏度适中。药效学结果表明,经过23 d给药,空白基质组,低、中、高剂量组兔体质量均有明显增加,子宫指数逐渐升高,子宫分级结果空白基质组,阳性对照组,低、中、高剂量组分别为(0.30±0.46)、(3.20±0.27)、(1.00±0.61)、(1.80±0.50)、(2.30±0.50),低、中、高剂量组较空白基质组子宫腺体数目增加,但增加不及阳性对照组显著。结论:黄体酮凝胶剂的制备方法可行,给药后黄体酮凝胶剂具有一定的孕激素活性,能促进兔子宫内膜发育,表明该剂型具有一定的可行性。

Objective： To prepare progesterone gel and study its pharmacodynamics. Methods： Carbomer-940 was chosen as gel matrix, and the best preparation method was optimized through single factor and orthogonal test with viscosity, yield value and thixotropy as indicators. And the initial pharmacodynamics of progesterone gel was studied. The uterus grading number, uterus weight index and gland amounts were all measured by endometrial transformation experiment in rabbits. Results： The best preparation method of progesterone gel was decided, and a good progesterone gel with milky appearance, uniform particle size distribution, and moderate viscosity was made. In the initial pharmacodynamical study, the weight of the rabbits in control matrix group, low, middle and high dose group increased, the uterus grading number in control matrix group, positive control group, low, middle and high dose group was （0.30 ±0.46）, （3.20 ±0.27）, （1.00 ± 0.61）, （1.80 ± 0.50）, （2.30 ± 0.50） respectively. The uterus index and grading number improved. The uterine gland amounts in low, middle and high dose group were more than that in control matrix group, but the increase was not significant compared with positive control group. Conclusion： The preparation method about progesterone gel is feasible with well product quality and high effect on uterus of rabbits, which indicates progesterone can be made into gel through our method.