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研究生: 李承穎
Cheng-Ying Lee
論文名稱: 超音波結合微氣泡敷料促進人類毛髮生長效果之研究
Evaluation of human hair growth enhancements with ultrasound-mediated microbubbles dressing
指導教授: 廖愛禾
Ai-Ho Liao
口試委員: 江建平
沈哲州
劉浩澧
學位類別: 碩士
Master
系所名稱: 應用科技學院 - 醫學工程研究所
Graduate Institute of Biomedical Engineering
論文出版年: 2018
畢業學年度: 106
語文別: 中文
論文頁數: 93
中文關鍵詞: 雄性禿超音波超音波對比劑Minoxidil毛髮生長穴蝕效應
外文關鍵詞: Androgenetic alopecia, Ultrasound, Ultrasound contrast agents, Minoxidil, Hair follicle, Cavitation
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  • 治療雄性禿目前主要外用藥為敏諾西代(Minoxidil),研究指出,微氣泡結合超音波作用後能以穴蝕效應,增加皮膚的通透度提升傳輸藥量,但微氣泡為液體,較難於皮膚表面使用;本研究研發一款微氣泡敷料結合超音波導入儀,針對雄性禿患者進行16週的治療,探討微氣泡敷料結合超音波後塗抹敏諾西代對於治療效果及可行性進行驗證。
    本研究一開始以超音波對微氣泡打破效率以及施打超音波後溫度檢測找出臨床超音波導入儀最佳參數,在染劑滲透豬皮的實驗中找出最適合超音波導入儀能量的微氣泡濃度。經由濃度與粒徑分析得知蛋白微氣泡對比劑平均粒徑大小為1.87±0.02 µm,平均濃度為4.72±2.3 ( x108 bubbles/mL),超聲波治療儀最佳參數為Duty cycle = 0.5,Tempo = 10,強度70%,施打時間2分鐘,最佳化微氣泡使用濃度為10倍稀釋。
    體外模擬豬皮染劑滲透實驗組別分別為: (1) 自然靜置(Control)、(2) 超音波(US)、(3) 微氣泡敷料(US+MBs),(2)、(3)組別又分為兩款敷料組別分別為Dressing I與Dressing II。根據實驗結果得知,Dressing I中US組與US+MBs組滲透深度相差約41.46%,Dressing II中US組與US+MBs組滲透深度相差約13.89%。
    人體試驗中招募48位年齡介於20到65歲的雄性禿患者(48位男性),其中23名完成16週的療程,實驗組別分別為先以: (1) 超音波(Control)、(2) 超音波結合微氣泡敷料(US+MBs)進行治療後塗抹敏諾西代,根據皮膚科醫師進行差異性評分結果,US+MBs組平均差異分數高於Control組,微觀影像量化的結果,Control組治療前後差異約增加了5倍,而MBs組治療前後差異約增加了9倍,綜合以上結果超音波結合微氣泡敷料之方法能加強敏諾西代之局部治療雄性禿之效果。


    Minoxidil (Mx) is a conventional drug for treating androgenetic alopecia (AGA), preventing hair loss, and promoting hair growth. In previous study in the literature, transdermal drug delivery (TDD) has been demonstrated by ultrasound (US)-mediated microbubbles (MBs) cavitation, but MBs are difficult to apply on the skin surface. In the present study, a new MBs dressing was developed for TDD in clinical trials. At first, the US mediated MBs destruction and temperature changes were detected to obtain the optimal parameters of clinical sonophoresis. The optimal MBs concentration was obtained through in vitro penetration experiments of pig skin. The average diameter of the MBs was 1.87±0.02 μm, the average concentration was 4.72 ± 2.3 ( x108 bubbles/mL), the optimal parameter of sonophoresis was set by the following conditions: Duty cycle = 0.5, Tempo = 10, the intensity is 70%, the application time is 2 minutes, and the 10 fold diluted MBs is the optimal concentration.
    The in vitro penetration experiments of pig skin were divided into the following three groups: (1) control, (2) US alone (US), (3) US combined with MBs dressing (US+MBs). Dressing I and Dressing II were both evaluated for MBs dressing. According to the experimental results, the penetration depth of model drug in US+MBs group is 41.46% significant than US group by using dressing I and is 13.89% significant than US group by using dressing II, respectively.
    In clinical trial, 48 AGA patients (age 20-65 years) were evaluated and 23 patients finished the 4-month treatments. The experimental groups were divided as: (1) US alone (control) and (2) US combined with MBs dressing (US+MBs). The hair grading was evaluated by dermatologists; the hair growth in US+MBs group was more obvious than in control group. In microscopic examination, the hair growth in US+MBs group and US group increase 9 times and 5 times hairs, respectively. US-mediated MBs cavitation on dressing can apply in human to enhance TDD and the efficacy of local minoxidil treatment in AGA patients.

    中文摘要 I ABSTRACT II 誌 謝 IV 目錄 VII 圖目錄 XI 表目錄 XIII 第 1 章 、緒論 1 1.1 皮膚結構生理學 1 1.1.1 表皮層 (Epidermis) 3 1.1.2 真皮層 (Dermis) 5 1.1.3 皮下組織 (Hypodermis) 6 1.1.4 皮膚附屬器官-毛囊 (Hair follicle) 6 1.2 超音波簡介 8 1.2.1 診斷型超音波 9 1.2.2 治療型超音波 10 1.3 超音波微氣泡對比劑 11 1.4 超音波結合微氣泡藥物傳輸機制 12 1.5 穴蝕效應 (CAVITATION) 13 1.5.1 穩態穴蝕效應(Stable cavitation) 14 1.5.2 慣性穴蝕效應 (Inertial cavitation) 14 1.6 雄性禿 ( ANDROGENETIC ALOPECIA) 15 1.6.1 雄性禿病症及原因 15 1.6.2 雄性禿治療方式 17 1.7 研究動機 18 第 2 章 、材料與方法 19 2.1 研究架構 19 2.2 藥品與設備 20 2.2.1 藥品 20 2.2.2 設備 21 2.3 白蛋白微氣泡敷料製作 22 2.3.1 濃度與粒徑分析 22 2.4 超聲波治療儀參數設定 23 2.4.1 打破效率 23 2.4.2 溫度檢測 24 2.4.3 打破效率結果量化 24 2.5 敷料測試 26 2.5.1 敷料吸附微泡測試 26 2.5.2 掃描式電子顯微鏡拍攝 27 2.6 豬皮染劑滲透實驗 27 2.6.1 微氣泡濃度變化分析 28 2.6.2 不同敷料影響穿透深度變化之分析 28 2.7 人體試驗 29 2.7.1 受試者基本資料 30 2.7.2 油水檢測 30 2.7.3 拉髮測試 31 2.7.4 巨觀與微觀分析 31 2.7.5 頭皮脂肪超音波影像 31 2.8 影像處理 33 2.8.1 灰階及二值化轉換 34 2.8.2 型態濾波 37 2.8.3 邊緣偵測 40 2.8.4 毛髮微觀量化 42 2.8.5 頭骨邊界判別 42 2.8.6 頭皮脂肪厚度量化 44 第 3 章 、實驗結果 46 3.1 白蛋白微氣泡對比劑濃度與粒徑分析 46 3.2 超聲波治療儀參數設定 47 3.2.1 打破效率 47 3.2.2 溫度檢測 49 3.3 敷料測試 50 3.3.1 敷料吸附微泡測試 50 3.3.2 掃描式電子顯微鏡拍攝 51 3.4 豬皮染劑滲透實驗 52 3.4.1 微氣泡濃度變化分析 52 3.4.2 不同敷料影響穿透深度變化之分析 53 3.5 人體試驗 55 3.5.1 受試者基本資料 55 3.5.2 油水檢測 57 3.5.3 拉髮測試 59 3.5.4 巨觀與微觀分析 60 3.5.5 頭皮脂肪厚度量化 65 第 4 章 、討論 66 第 5 章 、結論 71 參考文獻 72 附件–人體試驗計畫同意函 77

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