左炔诺孕酮长效缓释埋植剂 Ⅰ.结构特征的研究和体内外药物释放的长期观察  

LONG ACTING LEVONORGESTREL RELEASING IMPLANTS I. MORPHOLOGICAL STUDY AND DRUG RELEASE EVALUATION

作　　者：宋存先[1] 杨菁[1] 孙洪范[1] 王彭延[1] 史瑞文[1] 施化莲[1] 崔秀敏[1] 

机构地区：[1]中国医学科学院中国协和医科大学生物医学工程研究所

出　　处：《中国生物医学工程学报》1999年第1期22-29,共8页Chinese Journal of Biomedical Engineering

摘　　要：用生物降解性聚己内酯（ＰＣＬ）为载体制备女性抗生育药物左炔诺孕酮（ＬＮＧ）的长效皮下埋植胶囊。除可降解外，该胶囊具有微孔结构，重要技术特征是在ＰＣＬ中加入固体水溶性大分子ＰｌｕｒｏｎｉｃＦ６８（Ｆ６８）作为致孔剂，研究了加入致孔剂的工艺和微孔形成的原理，用核磁共振和扫描电镜等方法证明在亲水介质中Ｆ６８很快溶出，形成多微孔结构。体外和动物体内药物释放的研究证明该埋植剂具有零级释放动力学，可在体内长期维持稳定的药物释放量，每根３ｃｍ长的埋植剂在体内每天释放约２１微克ＬＮＧ。Biodegradable poly(ε caprolactone, PCL) was used as matrix to formulate the levonorgestrel (LNG) releasing subdermally implantable capsule for long acting female contraception. In addition to its biodegradability, the capsules featured a porous wall structure. An solid water soluble polymer, Pluronic F68(F68), was added in the PCL matrix as pore creating reagent. The manufacturing technique and pore forming process were investigated. In vitro drug release studies revealed a Zero order kinetics of LNG release from the LNG containing capsules. A relatively constant LNG level was maintained in rats for 2 years after implantation of the capsules. An in vivo release rate of 21 μg/day from a single 3 cm length of capsule was established. It is hypothesized that implantation of 2 pieces of the 3 cm capsule would be able to provide effective contraception for 2 years in women.

关 键 词：生物降解 聚己内酯 皮下埋植 左炔诺孕酮 胶囊 

分 类 号：R979.21[医药卫生—药品] R318.08[医药卫生—药学]