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研究生:王雅琪
研究生(外文):Ya-Chi Wang
論文名稱:以幾丁聚醣包覆四環素對藥物控制釋放之研究
論文名稱(外文):Controlled Release Characteristics of Tetracycline Loaded Chitosan Microspheres
指導教授:鍾次文王士豪王士豪引用關係
指導教授(外文):Tze-Wen ChungShyh-Hau Wang
學位類別:碩士
校院名稱:中原大學
系所名稱:醫學工程研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:116
中文關鍵詞:二次乳化法聚乳酸-甘醇酸共聚物改良式滴入法微小球四環素幾丁聚醣
外文關鍵詞:microspherestetracyclinechitosanmodified orificel-lactide-co-glycolide)Poly(ddouble emulsion
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本文以改良式滴入法應用各種製備條件製備符合治療牙周病所需之幾丁聚醣-四環素微小球,並以二次乳化法將聚乳酸-甘醇酸共聚物(PLGA 50:50),及褐藻酸(Alginate)乳化具有幾丁聚醣-四環素溶液之微小球,並探討微小球的特性。
結果顯示以乾式法製備,經戊二醛(濃度2.5%)交聯六十分鐘的條件為最佳,其包覆效率為67.4%±5.6%(n=3),釋放時間可達11天,仍能達到抑菌的最低有效濃度(1~2μg/ml),且無突釋(initial burst)的現象。經細菌抑菌測定試驗,確定微小球所釋出的四環素仍保有抑菌活性。
以濕式法製備之微小球,四環素於製備過程中即大量損失,包覆效率幾乎不超過50%,釋放結果也不理想,經改變不同條件如:戊二醛交聯時間增加及濃度提昇,也無法達到要求。
以二次乳化製備之聚乳酸-甘醇酸共聚物-幾丁聚醣微小球發現,外部水相中加入0.05%褐藻酸可有效的提昇包覆效率達19.6%±4.3%,且釋放時間達至9天。
In this study, we fabricated tetracycline (Tc) loaded chitosan microspheres by using different preparing process, conditions and methods for therapy of periodontal disease. Modified orifice and double emulsion method have been applied to fabricate chitosan microspheres. The results showed that pre-dried microspheres prior to cross-linking by 2.5% glutaraldehyde at 60 minutes would be the best conditions for microspheres, fabricated by modified orifice method. The encapsulation efficiency were 67.4%±5.6% (n=3) and could maintain 11 days of in-vitro release characteristics test. The efficacy of encapsulated Tc has been confirmed by bacteriostatic tests.
Double emulsion (w/o/w) technique can also fabricate Tc loaded alginate / poly(d,l-lactide-co-glycolide) / chitosan multilayered microspheres. They could also release Tc (in vitro test ) up to 9 days although the encapsulation efficiency was only 19.6%±4.3% (n=3).
Through the study, we found the best conditions for fabricating Tc loaded microspheres, which can be applied for therapy of periodontal disease, by modified orifice and double emulsion method.
目 錄
中文摘要………………………………………………………...………..I
英文文摘要……………………..……………………………...………..II
謝誌……………………..………………………………………………III
目錄…………………………………………………………………..…IV
圖索引………………………………………………………...………VIII
表索引……………………………………………………….…………XI
第一章 緒論
§1-1 前言……………………………………………………………...1
§1-2 微膠囊…………………………………………………………...2
§1-2-1 微膠囊簡介…………………………………………….2
§1-2-2 微膠囊的應用特性…………………………………….4
§1-2-3 微膠囊的製備技術…………………………………….5
§1-2-4 微膠囊內藥物釋放模式…………………………….…8
§1-3 幾丁聚醣………………………………………….…………….11
§1-3-1 幾丁聚醣簡介…………………………………….…...11
§1-3-2 幾丁質之構造…………………………………….…...12
§1-3-3 幾丁聚醣之應用………………………………….…...15


§1-4 牙周病與四環素……………………………………………….19
§1-4-1 牙周病簡介…………………………………………...19
§1-4-2 四環素的介紹…………………………………….…...21
§1-5聚乳酸與聚甘醇酸共聚物…………………………….………..25
§1-6 研究目的…………………………………………………….….27
第二章 實驗材料與方法
§2-1 實驗設備………………………………………….…….……….28
§2-2 實驗藥品…………………………………………………..…….30
§2-3 實驗方法……………………………………………………..….31
§2-3-1 溶液配製……………………...…………………..……31
§2-3-2 以相分離法製備濕式幾丁聚醣-四環素微小球…..….33
§2-3-3 以相分離法製備乾式幾丁聚醣-四環素微小球…..….35
§2-3-4 四環素包覆效率之計算方式……………………..…...37
§2-3-5 幾丁聚醣-四環素微小球生物體外釋放實驗……..….37
§2-3-6 PLGA乳化幾丁聚醣—四環素溶液之微小球製備…....38
§2-3-7 幾丁聚醣—四環素之乳化微小球包覆效率測定……...39
§2-3-8 幾丁聚醣-四環素之乳化微小球生物體外釋放實驗...39
§2-3-9 微小球粒徑測量…………………………………….....39
§2-3-10 掃描式電子顯微鏡之觀察………………………..….40
§2-3-11 幾丁聚醣膨潤度的測定……………………….…….40
第三章 結果與討論………………………………………...………41
§3-1 幾丁聚醣-四環素微小球結構形態分析……….…….………...42
§3-1-1 戊二醛交聯時間及濃度對微小球結構形態之影響.…43
§3-1-2 戊二醛對乾式微小球交聯後的表面形態分析…….....48
§3-2幾丁聚醣-四環素微小球包覆效率之研究………………..…….53
§3-2-1交聯時間對包覆效率之影響………………………..…53
§3-2-2 交聯劑濃度對包覆效率之影響…………………..…...55
§3-2-3 微小球粒徑大小對包覆效率之影響……………….....58
§3-2-4 交聯程序對微小球包覆效率之影響………..………...60
§3-3 幾丁聚醣-四環素微小球生物體外釋放之研究………..……...63
§3-3-1 交聯劑反應時間對生物體外釋放之影響………….....64
§3-3-2 交聯劑濃度對生物體外釋放之影響…………..……...66
§3-3-3 微小球粒徑對生物體外釋放之影響…………..……...69
§3-3-4 交聯程序對生物體外釋放之影響…………..………...71
§3-3-5 預先乾燥程序中交聯時間與交聯劑濃度對生物體外釋放之影響……………………….…………….……..….74
§3-4 幾丁聚醣-四環素微小球釋放行為之分析………………..…...78
§3-4-1 以model解釋釋放行為………………..………………78
§3-4-2 每日釋出四環素含量計算……………………..……...80
§3-5 四環素抑菌活性測試……………..…………………………….83
§3-6 以PLGA乳化幾丁聚醣-四環素溶液之微小球表面形態分析..85
§3-7 PLGA乳化微小球粒徑分析…………………………..………...86
§3-8 PLGA乳化幾丁聚醣-四環素之微小球包覆效率的分析……...90
§3-9 PLGA乳化幾丁聚醣-四環素之微小球生物體外釋放分析…...92
§3-10表面官能基分析-FTIR………………………..………………..94
第四章 結論………………………………………………….………96
第五章 未來展望……………………….………………….………..98
參考文獻………………………………………………….…….……..99
參考文獻[1]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, 1479-1487, 1999.[2]M.R. Kreitz, J.A. Domm, and E. Mathiowitz, Controlled delivery of therapeutics from microporous Membranes. II. In vitro degradation and release of heparin-loaded poly (D, L-lactide-co-glycolide), Biomaterials, 18, 1645-1651, 1997.[3]C. Thomas, and L. Daniel, Chitosan/Polyethylene glycol-alginate microcapsules for oral delivery of hirudin, Journal of Applied Polymer Science, 70, 2143-2153, 1998.[4]R.A. Seymour and P.A. Heasmen, Tetracyclines in the management of periodontal diseases, J. Clin. Periodontol., 22, 22-35, 1995.[5]徐新興、糜福龍, 海洋資源與化工技術-幾丁質與幾丁聚醣在化工領堿之應用,中國化學工程期刊,46(3),51-66,1999.[6]B.K. Green and L. Schechem, US, pat 2730457, 1956.[7]S.C. Khanna, M. Soliva, P. Speiser, Epoxy resin beads as a pharmaceutical dosage form, Method of prepartion, J. Pharm. Sci., 58, 1114-1117,1969.[8]M.N. Vranken and D.A . Claeys, US, pat 3523907, 1970.[9]鍾志鴻,以幾丁聚醣微小球包覆肝素之特性研究,中原大學醫學工程研究所碩士論文,2000。[10]王振熙,微膠囊與微膠囊包覆技術,第四十二卷第二期,化工。[11]T. Higuchi, Mechanism of substained action medication, Journal of Pharmaceutical Science, 52, 1145-1149, 1963.[12]V.C. Yang, Overview of drug delivery system. Albert B., Prescott Professor of Pharmaceuyical Sciences, 2000.[13]R. Muzzarelli, R. Tarsi, O. Filippini, E. Giovanetti, G. Biagini, and P.E.Varaldo, Antimicrobial properties of N-carboxybutyl chitosan, Antimicrobial Agents and Chemotherapy, 34, 2019-2023, 1990.[14]陳榮輝,幾丁質、幾丁聚醣的生產製造、檢測與應用,科學發展月刊,29(10),776-787,2001.[15]陳美惠、莊淑惠、吳志律,幾丁聚醣的物化特性,食品工業月刊,31(10),1-6,1999. [16]D. Knorr, Use of chitinous polymer in food, Food Technol. , 1, 85-89, 1984.[17]M.V. Deshpande, Enzymatic degradation of chtin&its biological application, J. Sci.&Ind. Res., 45, 273-277, 1986.[18]M. O‘brine and R.R. Colwell, A rapid test for chitinase activity that uses 4 - methylumbelliferyl - N - acetyl - b - D - glucosamine, Appl. and Envir. Microb., 53, 1718-1724, 1987.[19]I.G. Cosio, R A. Fisher, and D.A. Carroad, Bio-conversion of shellfish chitin waste:waste pretretment, enzyme production, process design, and economic analysis, J. Food Sci., 47, 901-905, 1982.[20]D.A. Carroad, and R.A. Tom, Bioconversion of shell- fish chitin waste:process conception and selection of microorganism., J. Food Sci , 43, 1158-1164, 1978.[21]D. Knorr, Dye binding properties of chitin and chitosan, J. Food. Sci., 48, 36-39, 1983.[22]M.V. Deshpande, Enzymatic degradation of chtin & its biological application, J. Sci. & Ind. Res., 45, 273-277, 1986.[23]S.H. Chiou, W.T. Wu, Y.Y. Huang, and T.W. Chung, Effects of the characteristics of chitosan on controlling drug release of chitosan coated PLLA microspheres, Journal of Microencapsulation, 18, 613-625, 2001.[24]S.R. Jameela, T.V. Kumary and A. Jayakrishnan, Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system, Journal of Controlled Releas, 52, 17-24, 1998.[25]X.Z. Shu, K.J. Zhu, A novel approach to prepare tripolyphosphate / chitosan complex beads for controlled release drug delivery, International Journal of Pharmaceutics, 201, 51-58, 2000. [26]E.B. Denkbas, M. Seyyal, and E. Piskin, Implantable 5-fluorouracil loaded chitosan scaffolds prepared by wet spinning, Journal of Membrane Science, 172, 33-38, 2000.[27]M. Eroglu, S. Irmak, A. Acar, and E.B. Denkbas, Design and evaluation of a mucoadhesive therapeutic agent deliver system for postoperative chemotherapy in superficial bladder cancer, International Journal of Pharmaceutics, 235, 51-59, 2002.[28]陳岱全,陳德輝,藥理學,合記圖書出版社,pp. 71-74,1978。[29]徐人英,藥物化學,合記圖書出版社,1975。[30]劉興華,趙國芳,楊筱蕙,醫護藥物學,華杏出版股份有限公司,pp. 432-434,1995。[31]R.Muzzarelli, G. Biagini, A. Pugnaloni et. al., Reconstruction of parodontal tissue with chitosan, Biomaterials, 10, 598-603, 1989.[32]J.M. Goodson, D. Holborow, R. Dunn, P. Hogan, and S. Dunham, Monolithic tetracycline-containing fibers for controlled delivery to periodontal pockets, Journal of periodontology, 54, 575-579, 1983.[33]E. Esposito, R. Cortesi, F. Cervellati, E. Menegatti, and C. Nastruzzi, Biodegradable microparticles for sustained delivery of tetracycline to the periodontal pocket : formulatory and drug release studies, J. Microencapsulation, 14 (2), 175-187, 1997.[34]E-R. Kenawy, G.L. Bolwin, K. Mansfield, J. Layman, D.G. Simpson, E.H. Sanders, and G.E Wnek, Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a bland, Journal of Controlled Release, 81, 57-64, 2002.[35]G. Quintero, J.T. Mellonig et. al., A six-month clinical evaluation of decalcified freeze-dried bone allograft in periodontal osseous defects, J. Periodontol, 53, 726, 1982.[36]C.L Meadow, M.F. Gher et. al., A comparison of polylactic acid granules and decalcified freeze-dried bone allograft in human periodontal osseous defects, J. Periodontol., 64, 103, 1993.[37]R.K. Kulkarni, E.G. Moore, A.F. Hegyelli, and F. Leonard, Biodegradable polylactic acid polymer, J. Biomed. Mater. Re., 5, 169, 1971.[38]D.K. Gilding, A.M. Reed, Biodegradadable polymers for use in surgery-Poly(glycolic acid)/poly(lactide acid)homo- and copolymers. 2. In vitro degradation, Polymer, 22, 494-498, 1981.[39]D.K. Gilding, Biocompat. Clin. Implant Mater., 2, 209, 1981.[40]C.M. Lehr, J.A. Bouwstra, E.H. Schacht, and H.E. Junginger, In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers, International Journal of Pharmaceutics, 78, 43-48, 1992.[41]Fwu-Long Mi et. al., The adsorption of copper(II) ion on chitosan-tripolyphosphate chelating resin, Chemistry, 57(1), 11-24, 1999.[42]Y.Y. Huang, T.W Chung, and T.W. Tzeng, A method using biodegradable polylactides/polyethylene glycol for drug release with reduced initial burst, International Journal of Pharmaceutics, 182, 93-100, 1999.[43]Y. Kawashima, T. Handa, A. Kasai, H. Takenaka, and S.Y. Lin, The effects of thickness and hardness of the coating film on the drug release rate of theophylline granules coated with chitosan-sodium tripolyphosphate complex, Chem. Pharm. Bull., 33 (6), 2469-2474, 1985.[44]R. H. Chen, M. L. Tsaih, Effect of preparation method and characteristics of chitosan on the mechanical and release properties of the prepared capsule", Journal of Applied Polymer Science, 66, 161-169,1997.[45]S. R. Jameela, P. G. Latha, and A. Jayakrishnan, Antitumour activity of mitoxantrone-loaded chitosan microspheres against ehrlich ascites carcinoma , J. Pharm. Pharmacol, 48, 685-688, 1996.[46]X.Z. Shu, K.J. Zhu, Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure, International Journal of Pharmaceutics, 233, 217-225, 2002.[47]S.R. Jameela, T.V. Kumary and A. Jayakrishnan, Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system, Journal of Controlled Release, 52, 17-24, 1998.[48]X.Q. Chen, Y.Y. Yang, L. Wang, T.S. Chung, Effects of inner water volume on the peculiar surface morphology of microspheres fabricated by double emulsion technique, J. Microencapsulation, 18(5), 637-649, 2001.[49]Y.Y. Yang, T.S. Chuang, and N.P. Ng, Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction/ evaporation method, Biomaterals, 22, 231-241, 2001.[50]A.J. Ribeiro, R.J. Neufeld, P. Arnaud, and J.C. Chaumeil, Microencapsulation of lipophilic drugs in chitosan-coated alginate microspheres, International Journal of Pharmaceutics, 187, 15-123, 1999.[51]Y. Murata, N. Sasaki, E. Miyamoto, and S.Kawashima, Use of floating alginate gel beads for stomach-specific drug delivery, European Journal of Pharmaceutics and Biopharmaceutics, 50, 221-226, 2000.
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1. 36 謝玉頤,「從認識體內的自由基探討適度運動與健康的正確理念」,國教世紀,第一八一卷,第11-14頁(1998)。
2. 35 劉福勳、張皓傑、黃耀德,「PDA在工地使用之優缺點」,營建管理季刊,第四十六卷,第60-62頁(2001)。
3. 39 藍忠孚、熊惠英、胡澤芷、葉佳禧,「台灣地區醫療機構品質管理系況分析」,醫療品質雜誌,第二卷,第一期,第5-12頁(2000)。
4. 37 簡文山,李友專,唐大鈿,胡俊弘,「建立台灣醫療資訊交換中心之藍圖」,醫療資訊雜誌,第六期,第54-66頁(1997)。
5. 33 項怡平,「飲食、營養與藥物間的交互作用」,大豐醫藥資訊,第一七二期,第4-5頁(2000)。
6. 22 高耀基,「電腦在醫療系統上應用二十年之檢討」,臨床醫學,第五卷,第一期,第65-70頁(1980)。
7. 19 邱啟潤,柯任桂,「健康相關的飲食與運動行為自我效能量表信度效度之評估」,護理研究,第八卷,第三期,第301-312頁(2000)。
8. 18 林俊龍,張顯洋,陳玉寧,「醫療資訊化與醫療管理品質」,醫療資訊雜誌,第九期,第83-92頁(1999)。
9. 15 李作英、王如華、徐姍姍、陳麗芳、張雪吟,「護理資訊化---個人數位處理器(可攜式)在臨床護理之運用」,護理雜誌,第四十五卷,第一期,第69-75頁(1998)。
10. 14 朱金洲,「中老年人之運動保健」,壢商學報,第100-104頁(1998)。
11. 13 石惠美,電腦資訊系統對護理績效和生產力的影響」,長庚護理,第三卷,第二期,第18-21頁(1993)。
12. 10 王文華,「NII遠距醫療會診先導系統發展之現況」,醫療資訊電腦化,第十卷,第31-32頁(1995)。
13. 26 許龍池,「飲食與運動對健康瘦身影響之研究」,樹德科技學報,第一卷,第267-273頁(1999)。
14. 25 陳美慧,何明泉,「產品迷你設計之研究-以PDA為例,工業設計」,第二十八卷,第二期(2000)。
 
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