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研究生:吳勇毅
論文名稱:不同方法製備幾丁聚醣膠粒之膨潤及其控制釋放特性
論文名稱(外文):The preparation of chitosan beads, their pH-sensitivity and the controlled release of amoxicillin from the chitosan bead
指導教授:張克亮
學位類別:碩士
校院名稱:國立海洋大學
系所名稱:食品科學系
學門:農業科學學門
學類:食品科學類
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:1
中文關鍵詞:幾丁聚醣顆粒
外文關鍵詞:chitosanamoxicillinbead
相關次數:
  • 被引用被引用:9
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  • 下載下載:171
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中 文 摘 要
幾丁聚醣因具有生物可分解性、生物相容性及低毒性等特性,再加上其在藥物控製釋放上有延緩藥物釋放、生物附著及促進吸收等效果,因此這幾年來被拿來當作藥物載體之新素材。本研究之目的,為利用市售之幾丁聚醣(去乙醯度為83.9%,分子量為202kDa)利用不同方法來製造幾丁聚醣顆粒,並探討其膨潤性與控制釋放特性之關係。
利用凝聚法、胺基酸成膠法所製得之幾丁聚醣顆粒,在酸性環境下會快速溶解,而利用戊二醛來交聯固定之幾丁聚醣顆粒在酸性環境則不會有溶解現象。而在鹼性環境下,幾丁聚醣顆粒皆沒有溶解的現象發生。利用胺基酸成膠法所製得之幾丁聚醣顆粒,不論是在酸、鹼環境下,或是利用烘乾法、凍乾法所製得之顆粒,都和利用凝聚法所製得之顆粒有相近的表現。利用凍乾法所製得之幾丁聚醣顆粒比烘乾法所製得之幾丁聚醣顆粒在酸性環境下更容易溶解,這主要是因為凍乾之樣品孔隙多,使得溶液能直接進入顆粒內部,進而加速幾丁聚醣顆粒之溶解。
經過戊二醛交聯反應後的幾丁聚醣顆粒,會因為交聯之戊二醛濃度而在膨潤率上有不同的表現,較高濃度交聯出來之顆粒質地較硬、脆,故膨潤率是以低濃度之幾丁聚醣顆粒有較高之膨潤率。而在酸性環境下之膨潤率也比在弱鹼性環境下高,這是因為幾丁聚醣分子上之胺基,在酸性環境下會帶有正電,進而相互排斥,使得幾丁聚醣分子間距加大,故幾丁聚醣顆粒在酸性環境下之膨潤率會較在弱鹼性大。
在膨潤率的比較上,架橋法—烘乾品在酸性環境下的膨潤率約是在弱鹼性環境下的2.5倍;架橋法—凍乾品在酸性環境下的膨潤率約是在弱鹼性環境下的1.8倍。而弱鹼環境下,凝聚法和胺基酸成膠法之烘乾品膨潤率約是架橋法的3~4倍;而凍乾品則是和2.5%之架橋法差不多。
利用凝聚法、胺基酸成膠法、2.5%和5.0%戊二醛架橋法所製備之幾丁聚醣顆粒,對於阿莫斯西林(Amoxicillin)之包覆率分別是84%、82%、76%和74%。在24小時的釋放實驗中,酸性環境下最大釋出量為幾丁聚醣顆粒完全溶解之100%,架橋法之凍乾品約有95%左右,而架橋法之烘乾品則約有將近75%左右;鹼性環境下總釋放率在凍乾品部份約有95%,而烘乾品則介於44%~68%之間。凍乾品之幾丁聚醣顆粒膨潤性質對於釋放效果沒有太大之影響,烘乾品之膨潤性及顆粒表面之完整性會影響到釋放之速率。
Abstract
Chitosan is a biodegrabale, biocompatible, non-toxic polysaccharide. It has a potential to become an ingredient for novel drug delivery systems because it can delay the release of drug compounds and enhance drug absorption. The objectives of this study were to prepare chitosan beads using commercial chitosan (with degree of deacetylation of 83.9 % and molecular weight of 202 kDa), to investigate their pH-sensitivity, and to measure the release behavior of amoxicillin from the chitosan beads.
Coagulated and glycine-gelled chitosan beads dissolved in acidic environment quickly. On the contrary, the cross-linked samples slowly erosed. Chitosan beads did not dissolve in weak basic environment. The glycine-gelled chitosan bead showed similar behavior to the coagulated samples both in dry state and when they were dissolved in acidic or weak basic environment. Freeze-dried chitosan beads dissolved faster than air-dried samples in acidic environment. That was because freeze-dried chitosan beads had more porous structure that test solution could diffuse into them and resulted in a faster dissolution of the beads.
The glutaraldehyde concentration affected the swelling ratio of glutaraldehyde-cross-linked chitosan beads. Higher glutaraldehyde concentration made the chitosan beads hard and brittle, while chitosan beads cross-linked with lower glutaraldehyde concentration had higher swelling ratio. Swelling in acidic environment was higher than swelling in weak basic environment. This might be due to that the amino groups in chitosan molecule became protonated in acidic solution. The cationic chitosan molecules would lead to higher intermolecular repulsive forces between molecules. Consequently, chitosan beads had higher swelling ratio in acidic environment.
The swelling ratio in acidic solution of cross-linked and air-dried gel beads were about 2.5 times that of the samples in weak basic solution. Cross-linked and freeze-dried samples swelled about 1.8 times (in acidic solution) as high as those in weak basic solution. In weak basic solution, the swelling ratio of coagulated and glycine-gelled chitosan beads swelled about 3~4 times that of the cross-linked and air-dried samples.
The total amount of amoxicillin loaded on coagulated, glycine-gelled, 2.5% and 5.0% glutaraldehyde-cross-linked chitosan beads was 84%, 82%, 76% and 74% respectively. During the 24 hr release test in acidic environment the maximum amount of amoxicillin released from coagulated beads was 100%. That of the cross-linked and freeze-dried samples was 95%, and that of the cross-linked and air-dried samples was about 75%. In weak basic environment, freeze-dried samples released about 95% of loaded amoxicillin, while the air-dried samples released about 44~68%. The swelling ratio and its surface structure would affect amoxicillin release from air-dried chitosan bead.
一、前言---------------------------------------------------------------------------1
二、文獻整理---------------------------------------------------------------------3
2.1 幾丁質與幾丁聚醣-------------------------------------------------------3
2.1.1 幾丁質與幾丁聚醣的由來-----------------------------------------3
2.1.2 幾丁質之種類--------------------------------------------------------3
2.1.3 幾丁質與幾丁聚醣的結構-----------------------------------------4
2.1.4 幾丁質與幾丁聚醣的分佈-----------------------------------------5
2.1.5 幾丁質與幾丁聚醣之溶解性質-----------------------------------6
2.2 幾丁聚醣在醫藥方面的應用-------------------------------------------7
2.2.1 幾丁聚醣在控制釋放載體的形式--------------------------------9
2.2.2幾丁聚醣顆粒、膠囊之種類---------------------------------------9
2.2.3影響幾丁聚醣顆粒釋放之機制------------------------------------10
2.3 控制釋放------------------------------------------------------------------11
2.3.1 控制釋放之目的----------------------------------------------------11
2.3.2 控制釋放之型式----------------------------------------------------12
2.3.3載體之藥物釋出機制-----------------------------------------------13
2.4 阿莫斯西林(Amoxicillin)-------------------------------------------15
2.4.1 阿莫斯西林的功效--------------------------------------------------15
2.4.2 阿莫斯西林的特性--------------------------------------------------15
三、實驗材料與方法------------------------------------------------------------17
3.1 材料-------------------------------------------------------------------------17
3.2 化學藥品-------------------------------------------------------------------17
3.3 去乙醯度之測定----------------------------------------------------------17
3.3.1 膠體滴定法-----------------------------------------------------------18
3.3.2 紅外線光譜分析法--------------------------------------------------18
3.4 幾丁聚醣分子量之測定-------------------------------------------------19
3.5 Amoxicillin之測定--------------------------------------------------------20
3.6 實驗方法-------------------------------------------------------------------21
3.6.1 幾丁聚醣顆粒之製作法--------------------------------------------21
3.6.1.1 凝聚法(coagulation)----------------------------------------21
3.6.1.2 架橋法(cross-linking)--------------------------------------22
3.6.1.3 胺基酸鍵結法---------------------------------------------------22
3.6.2 幾丁聚醣顆粒粒徑之測定-----------------------------------------23
3.6.3 幾丁聚醣顆粒膨潤率實驗-----------------------------------------23
3.6.4 包覆率實驗-----------------------------------------------------------23
3.6.4.1包覆率測定------------------------------------------------------24
3.6.5 釋放率測定-----------------------------------------------------------24
四、實驗流程----------------------------------------------------------------------26
五、結果與討論-------------------------------------------------------------------30
5.1 幾丁聚醣顆粒-------------------------------------------------------------30
5.1.1乾燥法對幾丁聚醣顆粒粒徑之影響------------------------------30
5.1.1.1 烘乾法對丁聚醣顆粒之影響---------------------------------30
5.1.1.2 凍乾法對幾丁聚醣顆粒之影響------------------------------31
5.1.1.3 乾燥法對幾丁聚醣顆粒外觀之影響------------------------31
5.2 幾丁聚醣顆粒之pH敏感性--------------------------------------------32
5.2.1 酸性環境下幾丁聚醣顆粒之膨潤率-----------------------------32
5.2.1.1 凝聚法和胺基酸成膠法---------------------------------------32
5.2.1.2 不同濃度的架橋法---------------------------------------------33
5.2.2 弱鹼性環境下幾丁聚醣顆粒之膨潤率--------------------------34
5.2.2.1 凝聚法和胺基酸成膠法---------------------------------------34
5.2.2.2 不同濃度的架橋法---------------------------------------------35
5.2.3 幾丁聚醣顆粒之pH敏感性整理---------------------------------36
5.3 Amoxicillin之釋放-------------------------------------------------37
5.3.1 Amoxicillin之包覆率-----------------------------------------37
5.3.2 Amoxicillin之釋放速率--------------------------------------38
5.3.2.1 Amoxicillin於酸性環境下之釋放速率---------------38
5.3.2.2 Amoxicillin於弱鹼性環境下之釋放速率------------39
5.3.3 Amoxicillin之釋放現象與幾通聚醣顆粒結構之關係---39
六、結論----------------------------------------------------------------------41
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