臺灣博碩士論文加值系統

精油普遍用於化妝品及保養品，其中又以茶樹精油為廣泛用於芳香療法的精油之一。其源自於澳洲茶樹具有抑制微生物、消炎作用，但是在高濃度時會引起皮膚刺激作用，因此本研究將探討茶樹精油的安全、有效劑量及主要成分中導致皮膚刺激反應之相關性。以實證醫學方式搜尋茶樹精油之臨床試驗文獻不多，且Jadad評值偏低，因此將進行後續基礎實驗。
首先取蒸餾萃取茶樹精油 (天然精油)，及市售品以氣相層析質譜儀檢測其主要成分，其品質均符合ISO 4730之成分規範。繼而進行抑制金黃色葡萄球菌活性及皮膚局部使用之安全性探討。12個標準品、天然精油及市售品檢測抑制金黃色葡萄球菌活性。結果顯示：以terpinolene (MIC 6.25%, MBC 100%)、α-terpinene (MIC 6.25%, MBC 25%)及α-terpineol (MIC 10%, MBC 40%)之抗菌效果最佳。再以主要抗菌之成分調配人工配方精油，抗菌作用提高，且較天然精油強，但仍不及某廠商市售品之效果。
皮膚接觸毒性檢測，是利用neomycin建立皮膚刺激反應標準。天然茶樹精油及主要毒性成分1,8-cineole 與活性成分terpinen-4-ol檢測結果顯示：天然茶樹精油2%以上即產生顯著之皮膚刺激毒性，而1,8-cineole及terpinen-4-ol則無顯著毒性。另外，連續28天塗抹2%茶樹精油於Wistar大鼠皮膚，觀察血清中GOT、GPT、BUN及creatinine之變化，相對於溶媒組，其無顯著影響肝腎功能。
綜合實證醫學及基礎研究對於茶樹精油應用於痤瘡治療之功效與安全性之探討結果：茶樹精油確實能有效抑制金黃色葡萄球菌，並有抗發炎之機轉，而達成治療痤瘡之效果；且若低濃度塗抹局部皮膚使用而非口服，亦不會對身體造成毒性。

Tea tree oil (TTO) is one of the essential oils that are popularly used in cosmetics and mending agents. TTO, the essential oil of Melaleuca alternifolia, is used in aromatherapy and has been investigated as antimicrobial and anti-inflammatory agents. However, TTOs can cause skin irritation at high concentrations. In this study, we explored the safety and efficient dosage of TTO and investigated the mechanism of TTO-induced skin irritation between with its components. The clinical trial literatures with randomized and double blinding design were very rare and Jadad score very low. Therefore, we executed following animal experimental research.
Tea tree oils were extracted by hydrodistillation and five brands commercial TTOs were purchased in Taiwan market. All compositions fit with International Standard 4730 guideline for TTO. In the followings, we established anti-Staphylococcal activity and safety evaluation for skin irritations of TTOs in rats. The antibacterial effects of 12 kinds of TTO’s components, extracted and commercial TTOs were measured by agar well diffusion method. Terpinolene (MIC 6.25%, MBC 100%), α-terpinene (MIC 6.25%, MBC 25%), and α-terpineol (MIC 10%, MBC 40%) were the major components in TTOs and exhibited most potent antibacterial activity. According to the above results, we designed the formulated TTOs. Formulated TTOs were more effect than extracted TTO but not as well as commercial one.
Allergic contact dermatitis model was established by neomycin irritations. The extracted TTO showed significant skin irritation at more than 2%/site, 1,8-cineole and terpinen-4-ol no significant dermal toxicity. Continued smear 2%/site TTO on Wistar rats skin for 28 days, GOT, GPT, BUN and creatinine of rats in serum did not significantly changed. We suggested TTO did not damage in the function of liver and kidney under 2%/site smear on skin for 28 days.
According to efficacy and safety literature review of evidence-based medicine and experimental research of TTO for acne treatment, TTOs were ability for Staphylococcus aureus inhibition and anti-inflammatory activity. Topical used with low dose of TTOs rather than oral administration will not cause harm to health.

目錄……………………………………………………………… i
附圖目錄………………………………………………………… iv
附表目錄………………………………………………………… v
縮寫表…………………………………………………………… vi
中文摘要………………………………………………………… 1
英文摘要………………………………………………………… 2
第一章緒論………………………………………………… 4
第一節研究背景…………………………………………… 4
第二節痤瘡之病因………………………………………… 10
第三節澳洲茶樹簡介……………………………………… 14
第四節澳洲茶樹精油……………………………………… 15
第五節研究目的…………………………………………… 17
本實驗之流程圖…………………………………… 19
第二章茶樹精油之品質管制……………………………… 20
第一節前言………………………………………………… 20
第二節實驗部分…………………………………………… 20
一、材料及設備………………………………………… 20
二、茶樹精油之製備…………………………………… 21
1. 水蒸氣蒸餾………………………………………… 21
2. 精油含量測定………………………………………… 21
三、茶樹精油之氣相層析質譜儀圖譜與指標成分之定
量…………………………………………………… 22
1. 利用GC-MS分析茶樹精油及其標準品…………… 22
2. 氣相層析質譜儀之條件…………………………… 22
3. 檢品配製…………………………………………… 23
第三節氣相層析質譜儀指紋圖譜分析指標成分結果…… 25
一、澳洲茶樹各部位之精油萃取結果與產率………… 25
二、茶樹精油之成分分析結果………………………… 25
第四節討論………………………………………………… 30
第三章茶樹精油之抗痤瘡療效評估……………………… 33
第一節前言………………………………………………… 33
第二節茶樹精油作用之實證醫學探討…………………… 34
一、茶樹精油用於痤瘡治療之系統評價……………… 34
1. 文獻來源…………………………………………… 34
2. 文獻之納入標準…………………………………… 34
3. 納入文獻之質量評值方法………………………… 35
二、茶樹精油作用之實證醫學探討結果……………… 35
ii
1. 茶樹精油用於痤瘡治療之系統評價結果………… 35
2. 茶樹精油用於痤瘡治療之基礎研究文獻回顧…… 36
(1) 茶樹精油之抗細菌活性…………………………… 36
(2) 茶樹精油之抗真菌活性…………………………… 38
(3) 茶樹精油之抗病毒活性…………………………… 38
(4) 茶樹精油之抗原蟲活性…………………………… 38
(5) 茶樹精油之抗發炎反應…………………………… 38
(6) 結論………………………………………………… 39
第三節實驗部份…………………………………………… 42
一、實驗材料…………………………………………… 42
1. 試驗菌株…………………………………………… 42
2. 試藥………………………………………………… 42
3. 人工配方茶樹精油…………………………………… 42
4. 儀器設備…………………………………………… 42
二、實驗方法…………………………………………… 42
1. 培養液及培養基之製備…………………………… 42
2. 瓊脂井化擴散法(agar well diffusion method)…… 43
三、茶樹精油抑制金黃色葡萄球菌活性結果………… 44
1. 茶樹精油之主成分抑制金黃色葡萄球菌活性…… 44
2. 市售品及萃取茶樹精油抑制金黃色葡萄球菌活性45
3. 茶樹精油各主要成分比例調整後對金黃色葡萄球菌
之活性……………………………………………… 47
四、討論………………………………………………… 47
第四章茶樹精油之安全性評估…………………………… 49
第一節前言………………………………………………… 49
第二節茶樹精油安全性之實證醫學探討………………… 50
一、茶樹精油安全性之系統評價……………………… 50
1. 文獻來源…………………………………………… 50
2. 文獻之納入標準…………………………………… 50
3. 納入文獻之質量評值方法………………………… 50
二、茶樹精油安全性之實證醫學探討結果…………… 50
1. 茶樹精油安全性之系統評價結果………………… 50
2. 茶樹精油不良反應之文獻回顧…………………… 53
第三節實驗部份…………………………………………… 58
一、單一劑量皮膚毒性試驗…………………………… 58
1. 實驗材料…………………………………………… 59
1.1 實驗動物…………………………………………… 59
1.2 試藥………………………………………………… 59
iii
1.3 實驗儀器…………………………………………… 59
2. 實驗方法…………………………………………… 59
3. 單一劑量皮膚毒性試驗結果……………………… 61
3.1 單一劑量皮膚毒性試驗正對照組Neomycin 評估量
表之建立…………………………………………… 61
3.2 Terpinen-4-ol與1,8-cineole之單一劑量皮膚急性毒
性試驗結果………………………………………… 62
3.3 茶樹精油單一劑量皮膚毒性試驗結果…………… 63
3.4 市售茶樹精油之單一劑量皮膚急性毒性試驗結果63
二、塗抹茶樹精油28 天之肝腎毒性評估……………… 65
1. 試驗材料…………………………………………… 66
1.1 實驗動物…………………………………………… 66
1.2 試藥………………………………………………… 66
1.3 實驗儀器…………………………………………… 66
2. 實驗方法…………………………………………… 66
3. 塗抹茶樹精油28 天之肝腎毒性評估結果………… 66
三、討論………………………………………………… 70
第五章結論………………………………………………… 71
第六章參考文獻…………………………………………… 72
iv
附圖目錄
圖一、痤瘡致病之規則系統…………………………… 10
圖二、不同類型痤瘡之治療方式……………………… 13
圖三、澳洲茶樹之外觀(A)樹型與(B)葉枝……………… 15
圖四、水蒸氣蒸餾萃取裝置……………………………… 21
圖五、茶樹精油含量測定之裝置………………………… 22
圖六、樣品TTO-A之GC-MS指紋圖譜………………… 27
圖七、樣品TTO-B之GC-MS指紋圖譜………………… 27
圖八、樣品TTO-C 之GC-MS 指紋圖譜………………… 28
圖九、樣品TTO-D 之GC-MS 指紋圖譜………………… 28
圖十、樣品TTO-E 之GC-MS 指紋圖譜………………… 29
圖十一、樣品TTO-F 之GC-MS 指紋圖譜………………… 29
圖十二、植物二次代謝物生合成主要途徑………………… 31
圖十三、瓊脂井化擴散法及精油於平板培養基之抑菌圈外
觀…………………………………………………… 44
圖十四、蒸餾萃取茶樹精油及市售品之金黃色葡萄球菌抑
制…… ……… …… …… ……… …… …… …… 46
圖十五、1,8-Cineole (eucalyptol)在大鼠及人體內之代謝52
圖十六、單一劑量皮膚毒性試驗操作圖…… …… …… 60
圖十七、Neomycin單一劑量皮膚毒性試驗評估…………… 61
圖十八、長期塗抹TTO-A之後大鼠血清血清肝腎功能生化
數值……………………………………………… 68
v
附表目錄
表一、植物萃取物與抗痘相關之科學論文……………… 6
表二、常用於抗痘化�菻~之植物萃取物的毒性研究及其
使用濃度或劑量………………………………… 8
表三、茶樹精油之組成………………………………… 16
表四、茶樹精油成分之性質…………………………… 17
表五、十二種購得茶樹精油成分標準品之名稱及其
GC-MS滯留時間………………………………… 24
表六、市售五種茶樹精油之品牌及樣品代號…………… 24
表七、蒸餾萃取與市售之茶樹精油成分含量分析…… 26
表八、茶樹精油及組成之Rideal-Walker coefficient…… 34
表九、Jadad Score Calculation…………………………… 35
表十、茶樹精油用於痤瘡治療之文獻摘要及Jadad評分36
表十一、茶樹精油之抗細菌活性………………………… 40
表十二、茶樹精油之抗真菌活性………………………… 41
表十三、蒸餾萃取及人工配方茶樹精油之組成…………… 43
表十四、茶樹精油主成分之金黃色葡萄球菌抑菌圈直徑比
及MIC、MBC……………………………………… 45
表十五、茶樹精油與人工配方精油DF1, DF2 之抑菌圈直徑
比…………………………………………………… 46
表十六、茶樹精油之不良反應相關文獻回顧……………… 51
表十七、精油植物主成分及潛在之接觸性過敏原……… 54
表十八、茶樹精油成分造成之毒性………………………… 56
表十九、皮膚紅腫評分表(Draize-FHSA scoring System)… 58
表二十、Neomycin單一劑量皮膚刺激試驗紅腫比較……… 61
表二十一、Neomycin紅腫程度評分比較表………………… 62
表二十二、Terpinen-4-ol與1,8-cineole之單一劑量皮膚急性毒
性試驗…………………………………………… 62
表二十三、茶樹精油單一劑量皮膚刺激試驗紅腫比較……… 64
表二十四、茶樹精油之皮膚毒性利用Draize-FHSA scoring
Sys t em分析…………………………………… 64
表二十五、市售品茶樹精油之單一劑量皮膚急性毒性試驗評
分表……………………………………………… 64
表二十六、雌性Wistar大鼠血中肝腎功能之生化檢驗參考值67

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