臺灣博碩士論文加值系統

人工關節置換手術已經逐漸增加被用來減緩疼痛及改善人體關節的機動性，並增進其生活品質。雖然人工關節置換術通常可以解除痛苦，而且可以恢復關節的部份功能， 仍然被視為最後的方法。在藥物，關節注射，休息或其他手術都失敗後才會進行人工關節置換手術。其中也必須注意人工關節感染的問題。
在台灣已經發現人工關節的感染率很高。因為手術並沒有在一個標準的人類排氣系統下完成。於是對全台灣人工關節感染做全面的調查，結果發現台灣的感染率遠高於美國，因此發展有效且便宜的預防人工關節感染對台灣有急迫性的須要。
預防人工關節感染的方法有環繞操作抗菌預防法和一個層流外科手術環境的使用，而手術伴隨引起的感染會導致發病及不健全，進而需要更多的醫療費用。
本研究利用不同比例及濃度的可生物裂解polylactide-co-polyglycolide(PLGA)共高分子材料塗布於含抗生素的不同人工關節表面上，測試抗生素釋放情形。
在有抗生素藥物的結晶面金屬片上包覆PLGA(85:15)釋放並抑制菌種可以達到3天以上;而包覆PLGA(50:50)可以達到5天以上。另外在有抗生素藥物的噴砂面金屬片上包覆15% PLGA(85:15)與5%及15% PLGA(50:50)藥物釋放時間都可以達到7天以上。
一般金屬片浸泡抗生素釋放時間卻最多只能達到兩小時，而有包覆PLGA的金屬片很明顯可以延長控制抗生素釋放的時間。

Prosthetic-joint replacement is used increasingly to alleviate pain and to improve mobility for damaged joints. Infections associated with prosthetic joints cause significant morbidity and account for a substantial proportion of health care expenditures. It is not surprising to find a lot of infected artificial joints in our country because none of the surgeries were done in a standard Humane Exhaust System. Rate of deep infection after artificial joint implantation in Taiwan was higher than US.
Biodegradable polymers in several forms offer promising results for drug delivery or release in several prospects. Biodegradable polylactide-co-polyglycolide (PLGA) polymer of different concentration and copolymeric ratio encapsulate the antibiotics loaded artificial stem surface will be tested for its long term and controllable drug release anti-infective effect.
PLGA (85:15) encapsulating the antibiotics loaded Co-Cr-Mo bead disc, the antibiotics can be released and inhibit more than 3 days. PLGA (50:50) encapsulating the antibiotics loaded Co-Cr-Mo bead disc,the antibiotics can be released more than 5 days. However, PLGA (85:15 or 50:50) encapsulating the antibiotics loaded Sand blasting disc can release more than 7 days. However, the antibiotics loaded metals can release within 2 hour, PLGA coating can prolong the time of Antibiotics release.

中文摘要………………………………………………………………I
Abstract………………………………………………………………II
誌謝……………………………………………………………………III
目錄……………………………………………………………………IV
表目錄…………………………………………………………………VI
圖目錄…………………………………………………………………VII
第一章 緒論…………………………………………………………1
1.1微生物 ……………………………………………………………4
1.1.1細菌的分類…………………………………………………4
1.1.2細菌的生長…………………………………………………5
1.1.3 Escherichia coli(大腸桿菌)……………………………6
1.1.4 Staphylococcus aureus (金黃色葡萄球菌)……………6
1.1.5 Staphylococcus epidermidis (表皮葡萄球菌)…………8
1.2 抗生素………………………………………………………………9
1.2.1 抗生素的定義………………………………………………9
1.2.2抗生素的分類 ……………………………………………10
1.2.3 抗微生物作用效力的測定 ………………………………13
1.2.4 影響抗微生物作用效力的因素 …………………………14
1.2.5 Vancomycin（萬古黴素）…………………………………15
1.2.6 Gentamycin(健地黴素) …………………………………16
1.2.7 Cefazolin(西華樂林)……………………………………17
1.3 生物可分解性材料………………………………………………18
1.3.1 生物醫學上的應用 ………………………………………19
1.3.2生物可分解性材料物理化學性質介紹 …………………21
1.3.3 PLA與PGA聚合物在藥物傳輸的發展 …………………23
1.4 研究的方向及探討的問題………………………………………24
1.5 研究的問題………………………………………………………28
第二章 實驗方法……………………………………………………29
2.1 定性研究…………………………………………………………29
2.1.1 細菌培養方法……………………………………………30
2.1.2過夜菌液之培養…………………………………………31
2.2 定量研究…………………………………………………………32
2.3 PLGA包覆……………………………………………………33
2.3.1 兩種不同比例的PLGA……………………………………34
第三章 結果…………………………………………………………36
第四章 討論…………………………………………………………50
第五章 未來發展……………………………………………………55
第六章 參考文獻……………………………………………………56













表目錄

表1-1 台灣與美國人工關節置換感染率[12]………………………3
表2-1 抗生素濃度[45]………………………………………………29
表3-1 抗生素分別對菌株的抑菌圈…………………………………37
表3-2 金屬片加上抗生素在1及2小時後的抑菌效果……………38
























圖目錄
圖1-1 細菌的生長時期………………………………………………5
圖2-1 將菌株接種在培養皿…………………………………………31
圖2-2 鋪有鐵氟龍薄片的空白玻璃培養皿…………………………33
圖2-3 金屬片在鋪有鐵氟龍薄片的空白玻璃培養皿………………34
圖2-4 PLGA(50:50) …………………………………………………34
圖2-5 PLGA(85:15) …………………………………………………35
圖3-1 Gentamycin對S.A的抑菌情形 ……………………………36
圖3-2 結晶面金屬片掃描式電子顯微鏡
Scanning Electron Microscope(SEM)………………………39
圖3-3 噴砂面金屬片掃描式電子顯微鏡
Scanning Electron Microscope(SEM)………………………39
圖3-4 結晶面金屬片PLGA 包覆與時間關係………………………40
圖3-5 (a)結晶面金屬片上殘留的PLGA
(b)清洗乾淨的結晶面金屬片………………………………41
圖3-6 丙酮和金屬片有無泡過的PLGA-丙酮的抑菌效果…………41
圖3-7 結晶面金屬片PLGA包覆與時間關係(沒加抗生素)…………42
圖3-8 氧化鋁噴砂面 時間與包覆的關係(沒加抗生素) …………43
圖3-9 PLGA 包覆與濃度關係(沒加抗生素)…………………………44
圖3-10 PLGA 包覆在結晶面金屬片…………………………………44
圖3-11包覆的PLGA破裂 ……………………………………………45
圖3-12 PLGA 包覆在結晶面，抗生素釋放總抑菌時間……………45
圖3-13 包覆PLGA85:15 (15%)，PBS及金屬片抑菌情形…………46
圖3-14 包覆 PLGA50:50 (5%)，PBS及金屬片抑菌情形…………47
圖3-15 包覆 PLGA50:50 (15%)，PBS及金屬片抑菌情形…………48
圖3-16金屬片包覆PLGA 85:15(15%)與50:50(5%和15%)…………49
圖4-1 經過PBS溶液洗提(a)2天 (b)4天 (c)6天…………………52
圖4-2 經過PBS溶液洗提1~7天金屬片的外觀……………………52
圖4-3 金相顯微鏡:包覆PLGA在噴砂面金屬片上………………….54

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