臺灣博碩士論文加值系統

在本研究中奈米級聚酯微粒(直徑小於0.1微米)以o/w乳化方式製備。十二烷基硫酸鈉(SDS)、聚丙烯酸(PAA)、Pluronic F-68和聚乙烯醇(PVA)為所使用之界面活性劑。製備方法、聚乳酸組成、聚乳酸濃度、十二烷基硫酸鈉濃度、聚丙烯酸濃度、Pluronic F-68濃度和聚乙烯醇濃度、聚乳酸分子量、聚乙烯醇分子量，以及振盪機振盪時間對奈米微粒之平均粒徑大小和分佈均有影響。

丙酮和十二烷基硫酸鈉加入溶於二氯甲烷的聚乳酸中，並經超音波振盪20分鐘，所產生的高分子微粒溶液再滴入以均質機攪拌(25000 rpm)含有(8-14%) Pluronic F-68界面活性劑溶液中，經減壓濃縮除去溶劑後，奈米聚酯微粒平均粒徑大小為61-64 nm，其他界面活性劑組合，包括十二烷基硫酸鈉與PVA、PAA與SDS，其產生聚酯平均粒徑皆大於此。

聚乳酸接枝聚丙烯酸的高分子化合物，用於製備微粒，二甲基乙醯胺為使用之溶劑，己烷及4%異丙醇為所需之沉澱溶液，界面活性劑並未使用，所得微粒平均粒徑大小為700-1250 nm。

Nanoparticles (less than 0.1µm) of poly(lactic acid) (PLA) have been prepared by o/w emulsion method. Sodium dodecylsulfate (SDS), poly(acrylic acid) (PAA) and poly(vinyl alcohol) (PVA) have been used as surfactants. Preparation methods, compositions of PLA’s, concentrations of PLA’s, concentrations of surfactants(SDS, PAA, PVA and Pluronic F-68), molecular weights of PLA and PVA and sonication time influence average diameter and polydispersity of nanoparticles.

Acetone and SDS have been added to CH2CL2 solution containing PLA. After sonification of 20 minutes, this polymer solution has been dropwisely added to aqueous solution containing 8-14% Pluronic F-68 surfactant and stirring with homogenizer (25000 rpm). With rota-evaporator to remove solvent, polyester nanoparticles possessed average size between 61 and 64 nm. Other combinations of surfactants, such as : SDS and PVA, PAA and SDS, used in preparation of nanoparticles of polyester, resulted in much larger particles compared to above.

PLA grafted with PAA has been used as material for preparation of particles. Without using surfactant, and with dimethyl acetamide as solvent and with hexane containing 4% (v/v) isopropanol as precipitation solution, PLA particles have been prepared with a diameter between 700 and 1250 nm.

中文摘要…………………………………………………………………………….…i
英文摘要..................................................................................................................ii
誌謝………………………………………………………………………….……..iii
目錄…………………………………….……………………………………………..iv
表目錄………………………………….……………………………………...…..vii
圖目錄……………………………….……………………………………………viii
第一章 緒論……………………………..……………………….…….…..………1
1.1 前言……………………….……………………….………….……..……1
1.2 研究背景、動機及策略……………………………..………….…..……2
1.3 研究目的…………….……………………………….….………..………3
第二章 文獻回顧………………………..…………………….…...………………4
2.1 聚乳酸…………..……………….………………….…........................…4
2.1.1 聚乳酸的合成……………………….……………………...……..…5
2.1.2 聚乳酸的水解性及生物分解性………………………..…………..7
2.2奈米醫藥技術………………………………………..……………..……..8
2.2.1 奈米級顆粒在藥物輸遞的應用…………………………..……..8
2.2.2奈米級顆粒的製造方法………………………………………........8
2.2.2.1溶劑揮發法………………………………………………..….8
2.2.2.2自發性乳化/溶劑擴散法…….…………………..……..…..9
2.2.2.3超臨界流體製備奈米級顆粒……………………….…….…9
2.3動態光散射粒徑分析儀………………………………….…..…………10
2.3.1測量原理..……………...……………………………..…..……..10
2.3.2粒徑分佈的分散度(polydispersity)……..…………….…………11
2.3.3動態光散射粒徑分析儀的優缺點……….…………………….....11
第三章 實驗材料與方法………………………………………………………....12
3.1 實驗藥品…………………………………………………………….......12
3.2 實驗器材………………………………………………………………...14
3.3 實驗儀器與測試方法……………………………………………...…15
3.3.1 核磁共振光譜法……………………………………..…………...15
3.3.2 凝膠滲透層析法……………………………………………….….15
3.3.3 傅立葉轉換紅外線光譜法…………………………..……...……16
3.3.4 動態光散射粒徑分析儀………………………………………..….16
3.3.5 掃描式電子顯微法……………………………………..……..……16
3.3.6 穿透式電子顯微法…………………………………………….....17
3.4 實驗方法…………………………………………………………….18
3.4.1 藥品的純化……………………………………..…….…………...18
3.4.2 聚乳酸之合成………………………….………..……….……..…19
3.4.3 聚乳酸之純化…………………………………………………..….19
3.4.4 微粒之製備…………………………………………………………20
3.4.4.1 微粒製備方法一……………………………………………20
3.4.4.2 微粒製備方法二……………………………………………21
3.4.5 PLA-HEMA之合成………………………………………………..23
3.4.6 PLA-HEMA之純化…………………………………………..……..24
3.4.7 PLA-HEMA-g-PAA之合成………………………………………..24
3.4.8 PLA-HEMA-g-PAA之純化……………………………………..…25
3.4.9 PLA-HEMA-g-PAA微粒之製備…………………………….…….25
第四章 結果與討論…………………………………………………………………26
4.1 PLA、PLA-HEMA和PLA-HEMA-g-PAA產率…………...….26
4.2 1H NMR光譜分析……………….………..……………………………...28
4.2.1 PLA…………………………………………………………….…..28
4.2.2 PLA-HEMA…………………………………………………….….29
4.2.3 PLA-HEMA-g-PAA.............................................................................30
4.3 FTIR光譜分析………………………………………..…………………...31
4.3.1 PLA………………………………………………………………...31
4.3.2 PLA-HEMA……………………………………………………..…32
4.3.3 PLA-HEMA-g-PAA………………………………………………....33
4.4 GPC鑑定…………………………………………………………….……34
4.5粒徑大小及分佈…………………………………………………………...35
4.5.1微粒製備方法(一)……………………………………………..…….35
4.5.2微粒製備方法(二)……………..………………………………….…39
4.5.3不同界面活性劑……………………………………………..………43
4.5.4不同之合成聚乳酸…………………………………………………..48
4.5.5微粒製備方法(三)……………………………………………..…….50
第五章 結論…………………………………………………………………..…….52
參考文獻………………………………………………………………………….....53
附錄A NMR光譜圖…………………………………….………………………..….57
附錄B FTIR紅外線光譜……………..……………………………………………62
附錄C GPC圖譜……………………

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