环孢素A-pH敏感性纳米粒与研究.docVIP

中文摘要 本文主要研究了口服环孢素A-pH敏感性纳米粒的处方组成、制备工艺、体外药剂学性质、体内药动学与过敏性反应；以及对纳米粒冷冻干燥后的药剂学性质、体内药动学与过敏反应研究。 基于提高环孢素A口服相对生物利用度以及降低上市制剂过敏性反应的目的，本文做了以下的研究。以肠溶包衣材料优特奇S100（Eudragit S100）162.1%（P﹤0.01），冻干纳米粒为130.1%（P﹤0.01），均能够显著提高环孢素A口服相对生物利用度。胶体纳米粒的AUC略高于冻干纳米粒的AUC，但二者之间的差别没有统计学意义（P＞0.05）。 此外，以新山地明为对照，分别对两种纳米粒制剂进行了豚鼠过敏性实验比较，实验证明，由于处方中使用泊洛沙姆188替代新山地明中的Cremophor EL做乳化剂，两种纳米粒的过敏性反应明显低于新山地明。 关键词：环孢素A，pH敏感性纳米粒，冷冻干燥，冻干保护剂，相对生物利用度，药物动力学，过敏反应 作 者：杨志强 指导教师：张学农  Development and Study of a new pH-sensitive Cyclosporine A nanoparticles Abstract The main purpose of this paper was to develop a new pH-sensitive Cyclosporine A -loaded nanoparticles and its freeze-drying formulation, investigate on the physico-chemical characteristics, pharmacokinetics as well as hypersensitivity reaction of them. In order to improve the bioavailability of lipophilic Cyclosporine A(CyA) and lessen the hypersensitivity reaction of its commercial preparation, a new pH-sensitive CyA nanoparticles consisting of enteric dissolved material Eudragit? S100 (CyA-NP) was prepared with quasi-emulsion solvent diffusion technique. The particle size, polydispersity index and encapsulation efficiency were introduced as indexes to optimize the compositions and conditions for the process in orthogonal design experiments; the morphological characteristic, size distribution, encapsulation efficiency and in vitro released characteristic from vehicles of CyA were studied individually. The results showed that the CyA-NP looked round and regular under transmission electron microscopy; the particle size was 44.8±3.2nm, and distributed between 20 and 82nm; a polydispersity index of 0.59±0.11 and a maximum encapsulation efficiency up to (99.7±0.1)%; the signification pH-dependant release profiles were revealed when the medium pH was above 6.0. It was found in the influencing facter tests that high temperature and high light can cause the aggregation of CyA-NP, which indicated it should be tightly preserved from light and stored at low temperat