本文選題：黃體酮　切入點：緩釋凝膠　出處：《大連理工大學》2016年碩士論文　論文類型：學位論文

【摘要】：正常的黃體功能對于維持妊娠和胚胎著床是必不可少的。輔助生殖技術(shù)中的控制性促排卵及卵泡抽吸會降低黃體期的激素水平,導致黃體功能不全、妊娠率下降、流產(chǎn)率增加,影響治療效果。所以黃體支持成為輔助生殖技術(shù)的常規(guī)治療。為了有效地提供黃體支持,降低全身副作用,提高患者的順應(yīng)性,本研究擬對一種黃體酮陰道緩釋凝膠的處方、制備工藝和質(zhì)量標準等進行研究。根據(jù)國外相關(guān)產(chǎn)品雪諾同@的文獻資料與輔料的性質(zhì)特點,初步確定黃體酮陰道緩釋凝膠的處方。以凝膠的微相結(jié)構(gòu)、體外釋放度和粘度為指標,優(yōu)化黃體酮緩釋凝膠的處方組成及制備工藝。制得的黃體酮陰道緩釋凝膠是一種含有8%(w/w)微粉化黃體酮的水包油型乳液分散在聚卡波菲基質(zhì)中的凝膠制劑,通過一個特殊的給藥裝置陰道給藥。其中聚卡波菲確保凝膠黏附到陰道上皮細胞,而該乳液形式提供油相儲庫,使黃體酮連續(xù)從油相釋放到水相進而進入陰道組織。采用混合剪切工藝可制備出均勻細膩的白色黃體酮緩釋凝膠。在釋放度對比測試中,自制樣品與國外樣品的釋放曲線的相似因子f2為74.82,大于50,表明兩者釋放行為無差異。參考《中國藥典(2015年版)》以及《新藥質(zhì)量研究技術(shù)指導原則》,我們對凝膠進行了質(zhì)量研究,建立了含量測定、有關(guān)物質(zhì)檢查和微生物限度檢查方法,確定了體外釋放度測定條件及檢測方法。建立了微生物檢查方法,采用平皿法對細菌、真菌和霉菌進行計數(shù)檢查。該方法回收在0.5-2.0范圍內(nèi),適用于黃體酮凝膠的微生物檢查。為建立黃體酮陰道緩釋凝膠質(zhì)量標準提供依據(jù)。最后,對黃體酮凝膠的穩(wěn)定性進行了初步研究。影響因素試驗表明黃體酮緩釋凝膠在高溫(60℃)、高濕(RH 90%±5%)和強光照射(4500 1x+500 1x)條件下,藥物穩(wěn)定,無新雜質(zhì)產(chǎn)生。但在高溫條件下,性狀輕微變化,凝膠略有變干,可能是部分水分揮發(fā)造成的。加速實驗結(jié)果表明,在30℃,RH65%的條件下放置2個月后,凝膠的性狀、含量及有關(guān)物質(zhì)均無顯著變化,各時間點的累計釋放率無明顯差異,后續(xù)穩(wěn)定性試驗仍在進行中。參照上述試驗結(jié)果和雪諾同@的保存條件,黃體酮緩釋凝膠適合于密封低于25℃環(huán)境保存。
[Abstract]:Normal luteal function is essential for maintaining pregnancy and embryo implantation. Controlled ovulation and follicular aspiration in assisted reproductive technology can reduce hormone levels in the luteal phase, leading to inadequate luteal function, decreased pregnancy and increased abortion. In order to effectively provide luteal support, reduce systemic side effects and improve patients' compliance, this study is intended to prescribe a progesterone vaginal sustained-release gel. The preparation process and quality standard were studied. According to the characteristics of the literature and excipients of Snow @, the formulation of progesterone vaginal sustained-release gel was preliminarily determined. The microphase structure of the gel was used. In vitro release and viscosity were used as indicators, The formulation and preparation of progesterone sustained-release gel were optimized. The prepared gel was a kind of water-in-oil emulsion containing 8w / w micro-powdered progesterone dispersed in the polyCarbofi matrix. Through a special drug delivery device, vaginal administration, in which Poly Carbofi ensures that the gel adheres to the vaginal epithelial cells, while the emulsion provides an oil reservoir, Progesterone was continuously released from oil phase to water phase and then into vaginal tissue. A uniform and fine white sustained release gel of progesterone could be prepared by mixed shear process. The similarity factor f _ 2 of the release curve between domestic and foreign samples is 74.82, which indicates that there is no difference in release behavior between the two. Referring to "Chinese Pharmacopoeia (2015)" and "Technical guiding principles for New Drug quality Research", we have studied the quality of gel. The methods of content determination, related substances examination and microbial limit test were established, and the conditions and methods of in vitro release were determined. The method of microbiological examination was established, and the bacteria were tested by plate method. The method is suitable for microbiological examination of progesterone gel. It provides the basis for establishing the quality standard of progesterone vaginal sustained-release gel. The stability of progesterone gel was preliminarily studied. The experimental results showed that under the conditions of high temperature (60 鈩，

本文編號：1565298