【作者】 蔡巍；

【导师】 杜洪光；

【作者基本信息】 北京化工大学 ， 应用化学， 2007， 硕士

【摘要】 左炔诺孕酮(levonorgestrel)是国际上应用广泛的一种口服避孕药。目前国际和国内市场上主要以单一的左炔诺孕酮避孕药和以左炔诺孕酮为主药的复方避孕药为主，有片剂、滴丸剂和埋植剂等，未见国内外有左炔诺孕酮贴剂上市。左炔诺孕酮具有药理作用强(避孕剂量为20～25μg／d)，分子量适宜(312.45)，而且具有一定的水溶性及亲脂性(油水分配系数logPo／w=3.48)的特点，适于制成透皮贴剂。本论文对左炔诺孕酮的部分理化性质进行了测定；对左炔诺孕酮经豚鼠皮肤的渗透性进行了研究；并考察了3种常用的促渗剂单独使用对左炔诺孕酮经皮渗透的作用。进行了左炔诺孕酮透皮贴剂处方设计、分析方法学研究、质量标准研究和制剂性能研究等。处方设计采用正交设计实验对系统中的促渗剂、压敏胶和药量等进行选择。实验结果表明，左炔诺孕酮经皮给药制剂的最佳处方为：主药量为3％；促渗剂选用肉豆蔻酸异丙酯(IPM)，含量为5％：RS100含量为15％；压敏胶含量为60％；背衬材料为聚酯膜。建立了左炔诺孕酮的鉴别方法——紫外分光光度法；贴剂含量、有关物质的HPLC分析法等。对左炔诺孕酮贴剂质量标准包括制剂的性状、制剂含量均匀度、制剂有关物质检查、释放度、体外透皮和粘附性等进行了研究。综上所述，左炔诺孕酮透皮贴剂具有良好的性能，能维持3天的恒定药物释放，对皮肤无强烈刺激，是一种安全、有效的新剂型。更多还原

【Abstract】 Levonorgestrel is a very pouplar oral prophylactic in the world. In nowadays, the prophylactic is single or compound of levonorgestrel in the markets, and the dosage forms of it available on the market are tablet, dripping pills and implant. However, at present, marketed transdermal therapeutic patches was not found.Levonorgestrel has a strong pharmaco dynamic effect (contraceptive dose is 20～25μg/d). It has a compatible molecular weight (312．45) and a surely octanol/water partition coefficient (logPo/w = 3．48) .So it is adapted to be made as transdermal therapeutic systems (TTS).In this thesis, some physicochemical properties and the transdermal delivery across Guinea pig skin in vitro of levonorgestrel with 3 kinds of penetration enhancers used alone were studied. For the successful development, a series of systematic studies were conducted. The prescription of levonorgestrel TTS were designed. Pharmaceutical analysis methodology, quality standard and the properties of preparations were studied.In order to obtain the optimal drug delivery, the main ingredients, pressure sensitive adhesives (PSA) and permeation enhancers were chosen through orthogonal tests. The results show crylic acid PSA and single permeation enhancers of IPM can make a remarked synergistic enhancement of levonorgestrel permeating through Guinea pig skin. Finally, based on the extensive development studies, a prototype of levonorgestrel TTS is prepared with 3% levonorgestrel, 5% IPM, 15% RS100, 60% crylic acid PSA, and mylar films.The method of UV was used as distinguished. The method of HPLC has been developed to determine the content and relative substances of levonorgestrel TTS.Quality measures included sample size and shape, homogeneity, detection of relative substances, release rates, penatration rates and adhesiveness.The results above studies indicate that levonorgestrel-TTS is capable of 3 days continuous delivery of Ievonorgestrel with a stable permeation rate and has not any skin irritation. So it is a safe and effective transdermal therapeutic system.更多还原