臺灣博碩士論文加值系統

本研究是以UV光聚合法製備聚乙烯醇 / 聚甲基丙烯酸-2-羥基乙酯 (PVA / poly HEMA)的水膠薄膜，再進ㄧ步進行聚乙烯醇交聯戊二醛的改質反應，最後，討論不同比例的PVA / HEMA和聚乙烯醇交聯戊二醛前後的物性測試，如FT-IR和元素分析的變化、熱性質、機械性質、親疏水性和膨潤性。最後，討論水膠膜交聯戊二醛後之溶質透過。
由拉力測試可知，PVA / poly HEMA水膠膜之抗拉強度和伸長率均隨PVA增加而變大，而聚乙烯醇交聯戊二醛後的機械性更好。
由TGA可知，聚乙烯醇交聯戊二醛後的熱穩定性變好，溫度約上升20-100℃；由DSC可知聚乙烯醇和聚甲基丙烯酸-2-羥基乙酯並不相容，且熔點並無明顯的改變，溫度約為220℃。
　　由親水性結果可知接觸角隨聚乙烯醇增加而變小，而聚乙烯醇交聯戊二醛後則角度變大；由膨潤性結果可知含水率隨甲基丙烯酸-2-羥基乙酯增加而變大。
　　由溶質透過可知在37℃下討論creatinine、5-fluorouracil (5-FU)和vitamin B12的滲透實驗，滲透係數隨溶質分子量增加而變小並隨HEMA增加而變大。

Interpenetrating network membranes of poly (2-hydroxylethyl meth- acrylate) (poly HEMA) and poly (vinyl alcohol) (PVA) in various ratios were prepared by UV radiation and treated with glutaraldehyde (GA). From the spectral change of FTIR, the hydroxyl groups disappeared and an acetal ring and ether linkage were formed for the reaction between the hydroxyl groups of PVA and GA. From the stress-strain curve, it was found that the tensile strength and elongation increased with PVA content on the PVA / poly (HEMA) membranes. After crosslinking with GA, the membranes became brittle, whereas the thermal stability increased about 20-100℃. Two glass transition temperature were found for the PVA / poly (HEMA) membranes. It means that PVA and poly (HEMA) are incompatible in this study. Due to the hydrophilicity of poly (HEMA), the water content in the membranes increased with increasing the content of poly (HEMA) in the membranes. After treatment with GA, the contact angle on the PVA / poly (HEMA) membranes decreased. The permeation of creatinine, 5-fluorouracil (5-FU) and vitamin B12 through at 37℃ were conducted. The permeability increased with increasing poly (HEMA) content in the membranes.

致謝................................................................Ⅴ
中文摘要.............................................................Ⅵ
Abstract............................................................Ⅶ
目錄..............................................................Ⅷ-Ⅹ
圖目錄...........................................................XI-XⅣ
表目錄..............................................................XV
ㄧ、前言...........................................................1-2
二、文獻回顧........................................................3-5
2.1聚乙烯醇 (poly vinyl alcohol, PVA)相關研究........................3-4
2.2甲基丙烯酸-2-羥基乙酯 (2-hydroxylethyl methacrylate, HEMA)相關研究...4
2.3 UV光改質相關研究..................................................5
三、理論背景.......................................................6-17
3.1薄膜簡介.........................................................6-9
3.2水膠簡介.......................................................10-13
3.3生醫材料的表面改質..............................................13-17
3.4藥物釋放..........................................................17
四、材料與方法....................................................18-30
4.1材料..........................................................18-20
4.2儀器設備..........................................................21
4.3實驗流程..........................................................22
4.4實驗方法.......................................................23-30
4.4.1製備PVA / poly HEMA水膠膜 (PH膜)與PVA / poly HEMA交聯GA後水膠膜 (GPH膜)..............................................................23-24
4.4.2薄膜性質測試.................................................24-27
4.4.3溶質透過.....................................................27-30
五、結果與討論....................................................31-35
5.1組成與結構.....................................................31-32
5.2機械性質.......................................................32-33
5.3親疏水性..........................................................33
5.4膨潤性...........................................................33
5.5熱性質...........................................................34
5.6溶質透過..........................................................35
六、結論.............................................................36
七、參考資料......................................................37-42
八、附錄..........................................................69-73

圖 目 錄
Figure 3-1. Schematic drawing of the three basic types of membrane...7
Figure 3-2.膜過濾程序之分類圖譜........................................7
Figure 3-3. Schematic of crosslinking of homopolymers...............10
Figure 3-4. Schematic of the crosslinking of interpenetrating....16-17
Figure 3-5. (a)經皮吸收貼片, (b)口服緩慢製劑, (c)傳統錠劑, (d)注射......17
Figure 4-1. PVA結構式...............................................19
Figure 4-2. HEMA結構式..............................................19
Figure 4-3. BEE結構式...............................................19
Figure 4-4. GA結構式................................................19
Figure 4-5. Creatinine結構式........................................20
Figure 4-6. 5-FU結構式..............................................20
Figure 4-7. Vitamin B12結構式.......................................20
Figure 4-8. Stress-strain curve.....................................25
Figure 4-9.接觸角定義................................................26
Figure 4-10. Set-up of the diffusion cell...........................29
Figure 5-1. FT-IR spectra of various PVA / HEMA (PH) hydorgel membranes. (a)PH73, (b)PH82, (c)PH91, (d)PVA........................43
Figure 5-2. FT-IR spectra of various PVA / HEMA crosslinked GA (GPH)hydorgel membranes. (a)GPH73, (b)GPH91, (c)GPVA.....................44
Figure 5-3. FT-IR spectra of PH and GPH hydorgel membranes. (a)PH73, (b)GPH73, (c)PVA, (d)GAV............................................45
Figure 5-4. Stress-strain curve of various PVA / HEMA (PH) hydrogel membranes. (a)PH73, (b)PH82, (c)PH91, (d)PVA........................46
Figure 5-5. Stress-strain curve of various PVA / HEMA crosslinked GA (GPH) hydrogel membranes. (a)GPH73, (b)GPH82, (c)GPH91, (d)GPVA.....47
Figure 5-6. Stress-strain curve of PH and GPH hydrogel membranes. (a)GPH73, (b)PH73, (c)PVA, (d)GPVA.....................................48
Figure 5-7. DSC curve of various PVA / HEMA (PH) hydrogel membranes. (a)PVA, (b)PH91, (c)PH82, (d)PH73
(third scan, non-sealed sample pan).................................49
Figure 5-8. Tg of various PH hydrogel membranes. (a)PVA, (b)PH91, (c)PH82, (d)PH73.......................................................50
Figure 5-9. DSC curve of various PVA / poly HEMA crosslinked GA (GPH) hydrogel membranes. (a)GPVA, (b)PH91, (c)PH82, (d)PH73.
(third scan, non-sealed sample pan) ................................51
Figure 5-10. Tg of various GPH hydrogel membranes...................52
Figure 5-11. TGA curve of various PVA / HEMA (PH) hydrogel membranes. (■)PVA, (◆)PH91, (▲)PH82, (▼)PH73................................53
Figure 5-12. TGA curve of various PVA / HEMA crosslinked (GPH) hydrogel membranes. (■)GPVA, (◆)GPH91, (▲)GPH82, (▼)GPH73........54
Figure 5-13. TGA curve of PH and GPH hydrogel membranes. (■)PVA, (◆)PH82, (▲)GPVA,(▼)GPH82............................................55
Figure 5-14. Permeation of creatinine through various GPH hydrogel membranes with (■)GPH73, (◆)GPH82, (▲)GPH91, (▼)GPVA.............56
Figure 5-15. Permeation of 5-FU through various GPH hydrogel membranes with (■)GPH73, (◆)GPH82, (▲)GPH91, (▼)GPVA.............57
Figure 5-16. Permeation of vitamin B12 through various GPH hydrogel membranes with (■)GPH73, (◆)GPH82, (▲)GPH91, (▼)GPVA.............58
Figure 5-17. Permeability of (■)creatinine, (◆)5-FU and (▲)vitamin B12 through various GPH hydrogel membranes..........................59
Figure 8-1. Schematic representation of the screening effect of the cross- linked structure of a cross-linked hydrogel on solute diffusion. The “blobs” around the macromolecular chains define a region available for diffusion (mesh). The characteristic length of this region, ξ, is the mesh size....................................69
Figure 8-2. Ten possibilities for surface modification: (a) crosslinked graft, (b) polymeric brush graft, (c) assembled monolayer, (d) chemical reaction of the surface molecules, (e) patterned over- layer on the surface, (f) biomolecule immobilized directly to a surface, (g) biomolecule immobilized to a surface via a tether, (h) surface etching, (i) ions implantted into the surface zone, (j) surface interpenetrating graft............................70
Figure 8-3. Swelling of a hydrophilic, glassy polymer by water. A typical chain between two cross-links originally in its unperturbed state (a) relaxes slowly as water is incorporated until thermodynamic equilibrium (solvated state, b). The end-to-end distance of a chain is increased by α, the linear expansion ratio.......................71
Figure 8-4. Crosslinked PVA formed by formed by reaction between PVA and GA..............................................................73

表 目 錄
Table 3-1.薄膜分類和比較..............................................6
Table 3-2.合成膜製備方法和比較.......................................8-9
Table 4-1.樣品組成說明 (g)...........................................23
Table 4-2.交聯反應液組成說明 (ml).....................................24
Table 4-3.藥品最大吸收波長與檢量線方程式...............................30
Table 5-1. Assignment of infrared bands solid residue of PVA / poly HEMA (PH) hydorgel membranes........................................60
Table 5-2. Assignment of infrared bands solid residue of PVA / poly HEMA crosslinked GA (GPH) hydorgel membranes........................61
Table 5-3. Elemental analysis of PVA and PVA crosslinked GA hydrogel membranes. (Means ± SD, n = 3) .....................................62
Table 5-4. Contact angle of PH and GPH hydrogel membranes.
(Means ± SD, n = 9-14)..............................................63
Table 5-5. Contact angle of PH and GPH hydrogel membranes.
(Means ± SD, n = 9-14)..............................................64
Table 5-6. Water content of GPH hydrogel membranes.
(Means ± SD, n = 3).................................................65
Table 5-7. Tg and Tm of PH and GPH hydrogel membranes...............66
Table 5-8. Degradation temperature of PH and GPH hydorgel membranes.67
Table 5-9. Permeability of different solute through various GPH hydrogel membranes (37℃). (Means ± SD, n = 3)......................68

1. C. S. Brazel and N. A. Peppas, “Mechanism of solute and drug transport in relaxing, swellable hydrophilic glassy polymer”, Polymer 40 (1999) 3383-3398.
2. Sigma-aldrich web site：http://www.sigmaaldrich.com/Brands/Aldrich.html
3. J. Brandrupp and E. H. Immergut, Editors, “Polymer handbook” (second edition), 高立圖書有限公司 (民68), pp. Ⅲ-147, 150, Ⅳ-244, 246.
4. J. M. Yang , W. Y. Su, T. L. Leu, and M. C. Yang, “Evaluation of chitosan/PVA blended hydrogel membranes”, Journal of Membrane Science 236 (2004) 39-51.
5. B. Sarti and M. Scandola, “Viscoelastic and thermal properties of collagen / poly(vinyl alcohol) blends”, Biomaterials 16 (1995) 785- 792.
6. W. Y. Chuang, T. H. Young, C. H. Yao, and W. Y. Chiu, “Properties of the poly (vinyl alcohol) / chitosan blend and its effect on the culture of fibroblast in vitro”, Biomaterials 20 (1999) 1479-1487.
7. S. J. Kim, C. K. Lee, Y. M. Lee, and I. Y. Kim, “Electrical/pH-sensitive swelling behavior of polyelectrolyte hydrogels prepared with hyaluronic acid-poly(vinyl alcohol) interpenetrating polymer networks”, Reactive & Functional Polymers 55 (2003) 291-298.
8. C. K. Yeom and K. H. Lee, “Pervaporation separation of water-acetic acid mixture through poly(vinyl alcohol) membranes crosslinked with glutaraldehyde”, Journal of Membrane Science 109 (1996) 257-265.
9. N. A. Peppas and S. L. Wright, “Drug diffusion and bindng in ioni- zable interpenetrating networks from poly(vinyl alcohol) and poly (acrylic acid)”, European Journal of Pharmaceutics and Biopharma- ceutics 46 (1998) 15-29.
10. P. R. Somani, R. Marimuthu, A.K. Viswanath, and S. Radhakrishnan, “Thermal degradation properties for solid polymer electrolyte (poly (vinyl alcohol) + phosphoric acid)/methylene blue composites”, Polymer Degradation and Stability 79 (2003) 77-83.
11. B. J. Holland and J. N. Hay, “The thermal degradation of poly(vinyl alcohol)”, Polymer 42 (2001) 6775-6783.
12. J. Gong, X. Li, C. L. Shao, B. Ding, D. R. Lee, and H. Y. Kim, “Photochromic and thermal properties of poly(vinyl alcohol)/ H6P2W18O62 hybrid membranes”, Materials Chemistry and Physics 79 (2003) 87-93.
13. C. C. Demerlis and D. R. Schoneker, “Review of the oral toxicity of polyvinyl alcohol (PVA)”, Food and Chemical Toxicology 41 (2003) 319-326.
14. Q. Liu, E. L. Hederg, Z. Liu, R. Bahulekar, R. K. Meszlenyi, and A. G. Mikos, “Preparation of macroporous poly (2-hydorxyethyl meth- acrylate) hydrogels by enhanced phase separation”, Biomaterials 21 (2000) 2163-2169.
15. M. Y. Arica, G. A. Oktem, and A. Denizli, “Novel hydrophobic ligand-containing hydrogel membrane matrix: preparation and application to γ-globulins adsorption”, Colloids and Surfaces B: Biointerfaces 21 (2001) 273-283.
16. O. Moradi, H. Modarress, and M. Noroozi, “Experimental study of albumin and lysozyme adsorption onto acrylic acid (AA) and 2-hydroxyethyl methacrylate (HEMA) surfaces”, Journal of Colloid and Interface Science 271 (2004) 16-19.
17.葉明熙，”水膠之生醫應用技術”，化工資訊與商情 (2004.07 No. 13), pp. 42-47.
18. Ottenbrite, Huang, and Park, “Hydrogels and Biodegradable Polymers for Bioapplications”, America Chemical Society (c1996), pp. 2-7.
19. Nickolaos A. Peppas, “Hydrogels in medicine and pharmacy”, (1987 by CRC Press, Inc), vol. Ⅰ, pp. 67, vol. Ⅲ, pp. 115.
20.佘勝雄，”利用二階段自由基共聚合製備酸鹼應答型水膠及性質探討”，中興大學 (91/8碩士論文), pp. 5-6.
21.林浩慈，”藉由鈷六十照射與UV光照射法以丙烯酸﹑異丙基丙烯醯胺與聚甲殼醣改質聚丙烯”，長庚大學 (92/7博士論文), pp. 90-92.
22.陳進隆和葉德惠，”聚合物實驗”，新科技書局 (民80), pp. 107-116.
23. J. M. Yang, Y. J. Jong, and D. Y. Hsu, “Preparation and properties of SBS-g-DMAEMA copolymer membrane by ultraviolet radiation”, J Biomed Mater Res, 35 (1997) 175-180.
24. J. M. Yang, Y. J. Jong, K. Y. Hsu, and C. H. Chang, “Preparation and characterization of heparin-containing SBS-g-DMAEMA copolymer membrane”, J Biomed Mater Res, 39 (1998) 86-91.
25. J. M. Yang, C. P. C. Chian, and K. Y. Hsu, “Oxygen permeation in SBS-g-DMAEMA copolymer membrane prepared by UV photo- grafting without degassing”, Journal of Membrane Science 153 (1999) 175-182.
26. J. M. Yang, M. C. Wang, Y. G. Hsu, and C. H. Chang, “Preparation of SBS-g-VP copolymer membrane by UV radiation without degassing”, J Appl Polym Sci 65 (1997) 109-116.
27. J. M. Yang, M. C. Wang, Y. G. Hsu, and C. H. Chang, “The properties of SBS-g-VP copolymer membrane prepared by UV photografting without degassing”, Journal of Membrane Science 128 (1997) 133-140.
28. J. M. Yang, M. C. Wang, Y. G. Hsu, C. H. Chang, and S. K. Lo, “Preparation of heparin containing SBS-g-VP copolymer membrane for biomaterial usage”, Journal of Membrane Science 138 (1998) 19-27
29. Marcel Mulder, “Basic Principles of Membrane Technology” (Second edition) (1997), pp. 38, 44-45, 71-83.
30.童國倫、呂坤宗、李雨霖和胡哲嘉，”奈米過濾的發展及其應用”，化工 第51卷第3期 (2004), pp. 26.
31.王大銘和賴君義，“分離用高分子膜製備方法簡介”，化工 第51卷第3期 (2004), pp. 52-57.
32. Budy D. Ratner and D. G. Castner, ”Surface modification of polymeric biomaterials”, Plenum Press, New York (1996), pp. 1-7.
33. S. Raut, and V. Athawale, “New interpenetrating elastomeric networks based on uralkyd / poly(butyl methacrylate)”, European Polymer Journal 36 (2000) 1379-1386.
34.蔡燕玲和陳暉，”生醫高分子於藥物傳輸之應用”，化工技術 第十卷第三期 (2002年3月號), pp. 210-222.
35. T-H. Young, N-K. Yao R-F. Chang and L-W. Chen, “Evaluation of asymmetric poly(vinyl alcohol) membranes for use in artificial islets”, Biomaterials 17 (1996) 2139-2145.
36. K. Burczak, E. Gamian and A. Kochman, “Long-term in vivo perfor- mance and biocompatibility of poly(vinyl alcohol) hydrogel macro- capsules for hybridtype artificial pancreas”, Biomaterials 17 (1996) 2351-2356.
37. L. F. Gudeman and N. A. Peppas, “pH-sensitive membranes from poly(vinyl alcohol) / poly(acrylic acid) interpenetrating networks”, Journal of Membrane Science 107 (1995) 239-248.
38. A. S. Hickey and N. A. Peppas, “Mesh size and diffusive characterristics of semicrystalline poly(vinyl alcohol) membranes prepared by freezing / thawing techniques”, Journal of Membrane Science 107 (1995) 229-237.
39. A. Amanda, A. Kulprathipanja, M. Toennesen and S. K. Mallapragada, “Semicrystalline poly(vinyl alcohol) ultrafiltration membranes for bioseparations”, Journal of Membrane Science 176 (2000) 87-95.
40.http://www.washburn.edu/cas/chemistry/sleung/porphyrin/vitamin.html
41.http://www.accuspeedy.com.tw/A16_search_items/003_renal_func/120_Creatinine.htm
42. http://www.cancer.org/docroot/CDG/content/CDG_fluorouracil.html
43. http://fda.tmu.edu.tw/cosmics/zcosmics-27.htm
44. Stephen L. Rosen, “Fundamental Principles of Polymeric Materials” (Second edition), Wiley c1993, pp. 82-83, 103-107.