【作者】 吴纯洁；

【导师】 侯世祥；

【作者基本信息】 四川大学 ， 药剂学， 2005， 博士

【摘要】 开发理想的眼部给药及其新剂型的趋势是通过改善药物的生物药剂学特性和使药物按预想的途径更准确地进入靶区。目前，眼部给药系统存在的共性问题是由于结膜囊内泪液不停地分泌及从鼻泪管迅速排除、普通滴眼液在结膜囊内滞留时间很短、药物难透过角膜、眼内生物利用度很低等问题。所以增加药物与角膜的接触时间以及改善角膜通透性十分重要。 课题采用延长药物与角膜的接触时间的同时改善角膜渗透性的治疗内眼疾病设计思路。以葛根素为模型药物，制备pH敏感型眼用凝胶以期提高葛根素眼部生物利用度，并探讨冰片合理配方与使用的(?)依据，拟建立葛根素眼新型给药系统。为此，立题进行了相关内容的研究。 为制备pH敏感型葛根素眼用凝胶，解决目前葛根素增溶出现的药液颜色加深、稳定性与生物利用度不理想、难以与卡波姆(Carbopol)制成新型凝胶等问题。实验采用相溶解度、稳定性考察及离体角膜透过性等方法，考察了羟丙基-β-环糊精(HP-β-CD)对葛根素性质的影响。结果表明，在不同浓度HP-β-CD下，葛根素的相溶解曲线呈A_L型；不同浓度HP-β-CD均能提高葛根素的稳定性：离体角膜透过实验得出，随HP-β-CD浓度的增大而葛根素表观渗透系数减小，5％HP-β-CD表观渗透系数分别是15％HP-β-CD、10％HP-β-CD增溶的3.12、1.77倍。HP-β-CD不仅能增加了葛根素的溶解度与稳定性，且能增加葛根素离体角膜透过率。 在上述基础上，进行了pH敏感型葛根素眼用凝胶剂的处方设计与制备方更多还原

【Abstract】 The tendency of developing new dosage forms through ideal ocular administration is to improve the biopharmaceutical characters and to make drugs enter the target areas more accurately through expected paths. Nowadays, the common problems existing in the Ophthalmic drug delivery system include the short retention time of ordinary eye drops in conjunctival sac due to the fact that dacryma unceasingly excreted in conjunctival sac and is quickly removed through nasal canal, making the drugs difficult to permeate cornea and resulting in a low bioavailability in eyes. Another is the probability of producing pantosomatous adverse effect when the drugs get into gastrointestinal tract after expelling through the nasal canal. Consequently it is of great importance to increase the contact time between drugs and cornea.The consideration to prolong the corneal contact time and improve the corneal permeability of drugs curing the intraocular diseases was introduced in this investigation. Our investigation adopted puerarin as model medicine to prepare pH triggered ophthalmic Gelling for puerarin, in order to enhance the bioavailability of puerarin taken in ocular region. And we also investigated the bases of the proper formulation and practice of borneol, expecting to establish a new ophthalmic drug delivery system of puerarin. Accordingly, we did researches on relative aspects.We investigated hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility, stability and in vitro corneal permeation of puerarin for the purpose of preparing pH Triggered ophthalmic Gelling for puerarin and solving the problems such as color deepening in physic liquor, poor stability and bioavailability, its difficulties in preparing new gel with Carbopol, etc. when solubilizing puerarin.更多还原