(3.235.245.219) 您好!臺灣時間:2021/05/10 02:14
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:詹騏銘
研究生(外文):Chi-Ming Chan
論文名稱:聚乙烯醇與聚丙烯酸複合水膠薄膜在藥物釋放上之研究
論文名稱(外文):Drug Release Behavior of Hydrogel Membrane composites based on Poly(vinyl alcohol)/Poly(acrylic acid)
指導教授:林寬鋸
指導教授(外文):Kuan-Jiuh Lin
學位類別:碩士
校院名稱:國立中興大學
系所名稱:化學系所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:74
中文關鍵詞:聚乙烯醇聚丙烯酸水膠藥物釋放
外文關鍵詞:poly(vinyl alcohol)poly(acrylic acid)hydrogeldrug release
相關次數:
  • 被引用被引用:0
  • 點閱點閱:371
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
本論文中使用戊二醛(Glutaraldehyde)對聚乙烯醇(polyvinyl alcohol, PVA)/聚丙烯酸(polyacrylic acid, PAA)進行交聯反應製備化學水膠。藉由聚丙烯酸直鏈性高分子之摻入形成半互穿型聚合網絡(semi-Interpenetrating Polymer Networks, semi-IPNs),使得聚乙烯醇水膠具有酸鹼敏感之特性,可應用於胃道與腸道酸鹼環境不同之選擇性釋放,並以FT-IR、DSC、XRD等儀器鑑定所製備水膠之組成與物性。
在此論文中選用Acetaminophen此低分子量、水溶性良好之藥物作為model drug了解水膠薄膜對藥物在水中溶離速率的影響。發現在不同交聯度下,水膠在膨潤動力學以及藥物釋放行為產生改變,發現交聯度與膨潤程度、速率成反比關係,而藥物釋放的速率則與膨潤動力學表現相符合。此外,聚丙烯酸的摻混程度,則顯著地影響水膠在不同pH值環境下之膨潤程度,當聚丙烯酸含量越高,在酸性環境膨潤的表現越不明顯,也因此藥物釋放速率緩慢;當環境之pH升高至中性時,由於羧基轉為解離態之羧酸根,產生電荷排斥力使得高分子鏈舒張,交聯網目亦被撐大故膨潤速率增加,藥物釋放速率變快。在前180分鐘為零階動力釋放行為,在中性環境之釋放速率為酸性環境的2倍。
Smart hydrogel, the semi-interpenetration polymer network system (semi-IPNs) composed of pH-sensitive polyacrylic acid (PAA) trapped with polyvinyl alcohol (PVA) in the present of glutaraldehyde (GA) as the cross-linker, is prepared for application in drug delivery of Acetaminophen. The structure and properties of as-produced hydrogels were investigated by Fourier transform infrared (FT-IR) analysis, Differential Scanning Calorimetry (DSC), X-ray diffraction pattern (XRD). Swelling rate of PVA hydrogels is inversely proportional to the cross-linker density, indicating the drug release rate from such hydrogels is determined by a density of the net and is lowered by a increase in the PVA : GA mass ratio. The swelling behaviors of PVA/PAA hydrogels and drug release from the hydrogels in relation to pH were investigated. As in neutral environment, the swelling velocity was much improved by introducing PAA in comparison with non-PAA, which is due to the enhancement of the entanglement of this hydrogel network resulted from electrostatic repulsive interaction of carboxylic (COO-) group. It indicated that the PAA introduced hydrogel system provided a suitable release profile for drug delivery vehicle.
中英文摘要 ---------------------------------------------------------------------- i
目錄 ------------------------------------------------------------------------------ iii
圖目錄 --------------------------------------------------------------------------- vi
表目錄 ---------------------------------------------------------------------------- x
第一章
緒論 --------------------------------------------------------------- 1
第一節
前言 --------------------------------------------------------------- 1
第二節
藥物控釋 -------------------------------------------------------- 3
1.2.1 藥物控制釋放概述 ------------------------------------------------ 3
1.2.2 藥物控制釋放機制 ------------------------------------------------ 5
1.2.2.1 擴散控制系統 ------------------------------------------------ 5
1.2.2.2 化學控制系統 ------------------------------------------------ 6
1.2.2.3 水滲透控制系統 --------------------------------------------- 7
1.2.2.4 應答式系統 --------------------------------------------------- 8
1.2.2.5 微粒系統 ------------------------------------------------------ 9
第三節
水膠簡介 ------------------------------------------------------- 11
1.3.1 水膠之定義與分類 ----------------------------------------------- 11
1.3.2 水膠之性質與結構 ---------------------------------------------- 14
1.3.3 水膠之製備方法 ------------------------------------------------- 16
1.3.4 環境敏感型水膠 ------------------------------------------------- 18
1.3.4.1 溫度敏感型水膠 -------------------------------------------- 20
1.3.4.2 酸鹼敏感型水膠 -------------------------------------------- 22
1.3.4.3 葡萄糖敏感型水膠 ----------------------------------------- 24
第四節 研究動機 ------------------------------------------------------- 26
第二章
實驗部分 ------------------------------------------------------ 30
第一節
藥品與儀器----------------------------------------------------- 30
2.1.1 實驗藥品 ----------------------------------------------------------- 30
2.1.2 儀器與設備 -------------------------------------------------------- 31
第二節
實驗方法 ------------------------------------------------------- 32
2.2.1實驗流程 ------------------------------------------------------------ 32
2.2.2製備水膠薄膜 ------------------------------------------------------ 33
2.2.2.1 製備聚乙烯醇交聯水膠薄膜 ----------------------------- 33
2.2.2.2 製備聚乙烯醇/聚丙烯酸薄膜 ---------------------------- 34
2.2.2.3 製備半互穿型聚合網絡之聚乙烯醇/聚丙烯酸水膠 - 34
2.2.3 鑑定與分析方法 -------------------------------------------------- 35
2.2.3.1 紅外線光譜儀量測 ----------------------------------------- 35
2.2.3.2 X-Ray粉末繞射儀 ---------------------------------------- 35
2.2.3.3 熱示差掃描卡量計 ----------------------------------------- 35
2.2.3.4 場發射掃描式電子顯微鏡觀測 -------------------------- 35
2.2.3.5 膨潤性測試 -------------------------------------------------- 36
2.2.4 藥物釋放行為量測 ----------------------------------------------- 36
2.2.4.1 Acetaminophen檢量線之製作 ---------------------------- 36
2.2.4.2 藥物釋放行為之量測 -------------------------------------- 36
第三章
結果與討論 --------------------------------------------------- 38
第一節
聚乙烯醇交聯水膠薄膜------------------------------------ 38
3.1.1 聚乙烯醇交聯水膠之形貌探討 -------------------------------- 40
3.1.2 交聯劑對聚乙烯醇結晶性之探討 ----------------------------- 42
3.1.3 膨潤行為量測 ----------------------------------------------------- 47
3.1.4 藥物釋放行為 ----------------------------------------------------- 49
第二節
半互穿型聚合網絡之聚乙烯醇/聚丙烯酸水膠 --- 53
3.2.1 聚乙烯醇/聚丙烯酸薄膜之形貌探討 ------------------------- 53
3.2.2 聚乙烯醇/聚丙烯酸薄膜結晶性之探討 ---------------------- 56
3.2.3 聚乙烯醇/聚丙烯酸薄膜之膨潤量測 ------------------------- 59
3.2.4 半互穿型聚合網絡之聚乙烯醇/聚丙烯酸水膠 ------------- 61
3.2.5藥物釋放行為 ------------------------------------------------------ 65
第四章 結論與未來展望 ------------------------------------------- 70
參考文獻 ---------------------------------------------------------------------- 72

圖目錄
Fig.1-1 藥物濃度-時間示意圖 ------------------------------------------------- 3
Fig.1-2 擴散控制系統 ----------------------------------------------------------- 6
Fig.1-3 化學控制系統 ----------------------------------------------------------- 7
Fig.1-4 親水凝膠控釋系統 ----------------------------------------------------- 7
Fig.1-5 滲透泵控釋系統 -------------------------------------------------------- 8
Fig.1-6 高分子材料釋放藥物之機制 ----------------------------------------- 9
Fig.1-7 化學性與物理性之水膠示意圖 ------------------------------------ 12
Fig.1-8 水膠製備之交聯方法 ------------------------------------------------ 16
Fig.1-9 化學法製備水膠之示意圖 ------------------------------------------ 17
Fig.1-10 環境敏感型水膠之高分子結構 ----------------------------------- 21
Fig.1-11 PDEAEM於酸鹼敏感水膠的應用 -------------------------------- 23
Fig.1-12 酸鹼值對膨潤動力學的影響 -------------------------------------- 23
Fig.1-13 自主控制葡萄糖敏感型水膠薄膜系統示意圖 ----------------- 24
Fig.1-14 溶膠-凝膠相轉移之葡萄糖敏感水膠示意圖 ------------------- 25
Fig.1-15 Phenylboronic acid應用之葡萄糖敏感水膠 --------------------- 25
Fig.1-16 應用於消化道各環節之各種水膠及其形式 -------------------- 27
Fig.1-17 不同濃度的PAA/PVP所形成微球之SEM圖 ----------------- 29
Fig.2-1 實驗流程圖 ------------------------------------------------------------ 32
Fig.3-1 poly(vinyl alcohol-co-vinyl acetate)結構示意圖 ------------------ 39
Fig.3-2 聚乙烯醇水膠薄膜之光學影像 ------------------------------------ 40
Fig.3-3 聚乙烯醇水膠薄膜之SEM影像 ----------------------------------- 41
Fig.3-4 戊二醛交聯聚乙烯醇反應示意圖 --------------------------------- 43
Fig.3-5 聚乙烯醇水膠之紅外線吸收圖譜 --------------------------------- 43
Fig.3-6 聚乙烯醇水膠之XRD圖譜 ---------------------------------------- 44
Fig.3-7 聚乙烯醇水膠之DSC圖譜 ----------------------------------------- 45
Fig.3-8 交聯劑量與Tm值之關係圖 ---------------------------------------- 46
Fig.3-9 不同交聯度之聚乙烯醇水膠的膨潤行為 ------------------------ 47
Fig.3-10 交聯網目大小在水膠膨潤-收縮狀態之示意圖 ---------------- 48
Fig.3-11 不同交聯度之聚乙烯醇水膠的釋放行為曲線 ----------------- 50
Fig.3-12 Acetaminophen標準品之檢量線 ---------------------------------- 51
Fig.3-13 聚乙烯醇/聚丙烯酸薄膜之光學影像 ---------------------------- 54
Fig.3-14 聚乙烯醇/聚丙烯酸薄膜之SEM影像 -------------------------- 55
Fig.3-15 聚乙烯醇/聚丙烯酸薄膜之紅外線吸收圖譜 ------------------- 57
Fig.3-16 聚乙烯醇/聚丙烯酸薄膜之XRD圖譜 --------------------------- 58
Fig.3-17 不同比例聚丙烯酸薄膜於不同酸鹼環境之膨潤行為 -------- 60
Fig.3-18 聚乙烯醇/聚丙烯酸半互穿型聚合網絡示意圖 ---------------- 61
Fig.3-19 半互穿型聚合網絡之聚乙烯醇/聚丙烯酸水膠之影像 ------- 62
Fig.3-20 聚乙烯醇/聚丙烯酸交聯水膠之紅外線光譜圖 ---------------- 63
Fig.3-21 聚乙烯醇/聚丙烯酸交聯水膠之XRD圖 ------------------------ 64
Fig.3-22 相同交聯劑比例、不同聚丙烯酸含量的藥物釋放曲線 ------ 67
Fig.3-23 零階動力釋放行為趨勢線 ----------------------------------------- 68

表目錄
Table. 1-1 水膠的多種分類方式 --------------------------------------------- 13
Table. 1-2 用於合成水膠之親水性高分子 --------------------------------- 13
Table. 1-3 應用於藥物傳遞之環境敏感型水膠 --------------------------- 19
Table. 3-1 Acetaminophen於不同交聯劑量之水膠中的含量計算結果 52
Table. 3-2 各趨勢線之斜率與截距列表 ------------------------------------ 68
Table. 3-3 Acetaminophen於semi-IPN水膠中的含量計算結果 -------- 69
參考文獻
[1] Taylor, Francis et al., Polymers in Drug Delivery, 2006
[2] Materials for Biomedical Applications. 3.051J/20.340J, MIT OCW, 2006
[3] 李玉寶等編著, 奈米生醫材料, 2006
[4] Buddy Ratner, Allan Hoffman, Frederick Schoen, Jack Lemons, Biomaterials Science, 2004, 628-648.
[5] Langer R. , Science, 1990, 249, 1527-1533.
[6] Brunetti, P., Benedetti, M. M., Calabrese, G., and Reboldi, G. P., Int. J. Artif. Organs, 1991, 14, 216-226.
[7] Hsieh, D. S., Langer, R., and Folkman, J. Proc. Natl. Acad. Sci. USA, 1981, 78, 1863-1867.
[8] Kost, J., Leong, K., and Langer, R. Proc. Natl. Acad. Sci. USA, 1989, 86, 7663-7666.
[9] Mansoor Amiji et al., Nanotechnology for Cancer Therapy, 2006
[10] O. Wichterle, D. Lim, Nature, 1960, 185, 117.
[11] F. Lim, A.M. Sun, Science, 1980, 210, 908-910.
[12] I.V. Yannas, E. Lee, D.P. Orgill, Proc. Natl. Acad. Sci. USA, 1989, 86, 933-937.
[13] Hoffman, A.S., Adv. Drug Deliv. Rev. , 2002, 43, 3-12.
[14] Watanabe, T., Utsunomiya, M., Kurihara, S., Nonaka, T. J. Polym. Sci. A. 2001, 39, 1505-1514.
[15] Piyush Gupta, Kavita Vermani and Sanjay Garg, Drug Discov. Today 7, 2002, 10, 569-579.
[16] Nicholas A. Peppas, Shelia L. Wright, European Journal of Pharmaceutics and Biopharmaceutics, 1998, 46 15-29.
[17] Mehrdad Hamidi, Amir Azadi, Pedram Rafiei, Advanced Drug Delivery Reviews, 2008, 60 1638-1649.
[18] Lee, K.Y. and Mooney, D.J., Hydrogels for tissue engineering, 2001, Chem. Rev., 101, 1869.
[19] Ikada, Y. and Tsuji, H., Macromol. Rapid Commun, 2000, 21, 117.
[20] Zhao, Z. et al., Adv. Drug Delivery Rev., 2003, 55, 483.
[21] Bromberg, L.E. and Ron, E.S., Adv. Drug Delivety Rev, 1998, 31, 197.
[22] Bae, Y.H., Okano, T., and Kim, S.W., Pharm, Res, 1991, 8, 624.
[23] Bae, Y. H., Okano, T., and Kim, S.W., Pharm. Res., 1991, 8, 531.
[24] Okano, T. et al., J. Controlled Release,1990, 11, 255.
[25] Okuyama, Y. et al., J. B i ornate r. Sci., Polym. Ed., 1993, 4, 545.
[26] Nikolam A. Peppas and Robert E. Benner, Jr., Biomaterials, 1980, 1, 158-162.
[27] Hong Chen, You-Lo Hsieh, Journal of Polymer Science: Part A: Polymer Chemistry, 2004, 42, 6331-6339.
[28] Firestone, B.A. and Siegel, R.A., J. Appl. Polym. Sci., 1991, 43, 901.
[29] Ito, Y. et al., J. Controlled Release, 1989, 10, 195.
[30] Hassan, C.M., Doyle, F.L III, and Peppas, N.A., Macromolecules, 1997, 30, 6166.
[31] Heller, J. et al., J. Controlled Release, 1990, 13, 295.
[32] Brownlee, M. and Cerami, A., Science, 1979, 206, 1190.
[33] Kim, J.J. and Park, K., J. Controlled Release, 2001, 77, 39.
[34] Obaidat, A.A. and Park, K., Pharm, Res., 1996, 13, 989.
[35] Qiu, Y. and Park, K., CRC Press, Boca Raton, FL, 2002, 227.
[36] Katono, H. et al., J. Controlled Release, 1991, 16, 215.
[37] Jeong, B., Bae, Y.H., and Kim, S.W., J. Controlled Release, 2000, 63, 155.
[38] Sawahata, K. et al., J. Controlled Release, 1990, 14, 253.
[39] Kwon, IC. et al., J. Controlled Release, 1991, 17, 149.
[40] Kwon, I.C., Bae, YR., and Kim, S.W., Nature, 1991, 354, 291.
[41] Suzuki, A. and Tanaka, T., Nature, 1990, 346, 345.
[42] Mamada, A. et al., Macromolecules, 1990, 23, 1517.
[43] Yui, N., Okano, T., and Sakurai, Y., J. Controlled Release, 1993, 26, 141.
[44] Miyata, T., Asarni, N., and Uragami, T., Nature, 1999, 399, 766.
[45] Qiu, Y. and Park, K., Adv. Drug Delivery Rev., 2001, 53, 321.
[46] Shufen Zhang, Shimei Xu, Jinzong Yang, Materials Letters, 2008, 62, 3999-4002
[47] Kitano, S. et al., J. Controlled Release, 1992, 19, 161.
[48] Myung-Kwan Chun, Chong-Su Cho, Hoo-Kyun Choi, International Journal of Pharmaceutics, 2005, 288, 295-303.
[49] Herman S. Mansur, Carolina M. Sadahira, Adriana N. Souza, Alexandra A.P. Mansur, Materials Science and Engineering C,2008, 28, 539-548.
[50] 陳瑋呈 國立台灣科技大學 高分子工程研究所 碩士學位論文 2008
[51] Andrew T. Metters, Chien-Chi Lin, Advanced Drug Delivery Reviews, 2006, 58, 1379-1408.
[52] Nicholas A. Peppas, Shelia L. Wright, European Journal of Pharmaceutics and Biopharmaceutics,1998, 46, 15-29.
[53] Christie M. Hassan, and Nikolaos A. Peppas, Macromolecules, 2000, 33, 2472-2479
[54] D. L. Siegfried, D. A. Thomas and L. H. Sperling, J. Appl. Polym. Sci., 1981, 26, 177.
[55] R. M. Hodge, G. H. Edward, and G. P. Simon, Polymer, 1996, 37, 1371-1376.
[56] A. Higuchi, and T. Iijima, Polymer, 1985, 26, 1207-1211.
[57] Yuk, S.H., Cho, S.H., and Lee, S.H., Macromolecules, 1997, 30, 6856-6859.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔