中科大功能高分子课件4.pptVIP

4Drug Delivery Systems;基金委-董建华处长 高分子研究进展与国家自然科学基金近况 12月25日下午2:30，地点: 18层大楼1楼 院士系列学术报告: 颜德岳；江明；曹镛 高分子研究进展与国家自然科学基金近况 12月27日上午8:30，地点: 18层大楼1楼 ;Content; 定义：药物控制释放是指在较长的时间内（至少12h），按照预定速度向全身或某一特定器官连续释放一种或多种药物，并且在一段固定时间内，使药物在血浆和组织中的浓度能稳定某一适当水平（该浓度是使治疗作用尽可能大而副作用尽可能小的最佳水平）。而传统的给药方式（口服或注射）往往使血液中药物大幅度波动，即有时超过有效治疗指数而带来副作用，有时未达到有效治疗范围而失去疗效。 与传统的给药方式相比，药物控制释放具有以下潜在的优点： （1）可连续保持药物浓度在一个理想的疗效范围; （2）由于可靶向释放药物到某一特定细胞或组织而减少毒副作用; （3）可能减少所需药物剂量; （4）减少给药频率; （5）对于蛋白质和多肽药物，其体内半衰期短，可方便地进行药物释放而不至于失去药物活性。;药物控释的途径： 经口(ingestion): 口服经胃肠道、消化道等；体腔内粘膜给药（眼内、口腔、舌下、鼻腔、直肠等） 注射(injection):动脉注射及静脉点滴给药；皮下及肌肉注射 透皮(transdermal) 发展阶段： 1950’s，传统型药物制剂 1950-70’s，缓释型药物制剂 1970’s，控释型药物制剂 1980’s，靶向型、智能型药物制剂;;Mechanisms of Polymer-based Drug Delivery Systems; In some cases (a, reservoir systems), the drug is surrounded by a polymer membrane, such as a capsule or microcapsule. Fig. a: reservoir systems; b, matrix systems. In other cases (b, matrix systems), the drug is uniformly distributed through the system. In both cases, diffusion of the drug through the polymer backbone or pores in the polymer membrane is the rate-limiting mechanism. ; Release rates from membranes are determined by the steady-state Fick’s Law diffusion equation:;Non-biodegradable polymer “Norplant” commodity: the silicone capsule containing contraceptives that are released by diffusion through polymer for 5 years. (Mr ＜400)---reservoir system (membrane-controlled diffusion); Ethylene-vinyl acetate (EVA), PSt, Ethyl-cellulose, Hydrogels (PVA)----matrix system (interconnecting pores); Biodegradable polymer PLGA system: combination of diffusion and polymer matrix degradation.; The osmotically controlled release system involves a tablet containing an osmotic agent surrounded by a semipermeable membrane (permeable to water but impermeable to salt or drug). The membrane contains a single laser-drilled hole. The external solvent, water, enters the tablet through the membrane at a constant rate and drives the drug out through the la