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研究生:林利澤
研究生(外文):LIN,LI-ZE
論文名稱:製備摻雜鈰或銪之碳酸鈣聲動力介質顆粒於體態雕塑之研究
論文名稱(外文):Preparation of Ce-doped or Eu-doped CaCO3 as Sonodynamic Particles Applied on Body Sculpture
指導教授:林峯輝施並裕
指導教授(外文):LIN,FENG-HUEISHIH,PING-YU
口試委員:林峯輝施並裕陳景欣吳造中
口試委員(外文):LIN,FENG-HUEISHIH,PING-YUCHEN,JING-XINWU,ZAO-ZHONG
口試日期:2019-07-05
學位類別:碩士
校院名稱:國立聯合大學
系所名稱:材料科學工程學系碩士班
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2019
畢業學年度:107
語文別:中文
論文頁數:92
中文關鍵詞:體態雕塑超音波碳酸鈣活性氧化物
外文關鍵詞:Body sculptureUltrasoundCalcium carbonateCeriumEuropiumReactive oxygen species
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  局部肥胖對於我們身體的危害影響之大,此類族群的人罹患心臟病或糖尿病的風險明顯提升。體態雕塑方式包含運動、抽脂、低強度超音波、高強度聚焦超音波等,但這些方法都有各自的缺點及潛在因素。因此我們提出一種微創局部雕塑的方法,將降解性聲敏感材料施打至脂肪組織間,藉由超音波作用激發微米顆粒,並在局部釋放出ROS,使脂肪細胞凋亡,且藉由高鈣環境抑制脂肪細胞成熟,進而達到體態雕塑之目的。
  本研究利用含有硝酸鈣及硝酸鈰或硝酸銪的混合液與碳酸鈉溶液合成,製備出摻雜鈰和摻雜銪之碳酸鈣,藉由縮小電子躍遷之能隙大小,僅憑著使用低能量超音波即可達到局部雕塑的效果。材料分析方面,材料尺寸約為2 μm,且於水中具有良好的分散性,材料除了主體元素外,也偵測到摻雜之元素,鈰和銪的存在。細胞實驗結果顯示,摻雜鈰和摻雜銪之碳酸鈣材料具有良好的生物相容性,且在高鈣環境能抑制脂肪細胞成熟,當材料配合超音波作用下,能在脂肪細胞中產生更多的ROS自由基,且對細胞有顯著的損傷。動物實驗方面,驗證了材料配合超音波作用下,減緩體重及腰圍上升之趨勢,其效果對脂肪細胞造成顯著損傷及抑制脂肪細胞成長,並且對動物無造成明顯發炎等其他不良反應。因此聲敏感材料在超音波作用下,有潛力作為局部體態雕塑的新技術。

  Due to local fat may significantly increase risk of heart disease or diabetes, and even lead to other illnesses. In order to ameliorate local fat, body sculptures became an emerging market for regulating and inhibiting local fat. Body sculptures include exercise, liposuction, low-intensity ultrasound, high-intensity focused ultrasound, etc., but these methods exist some side-effects or potential shortcomings. Therefore, we proposed a semi-invasive method for local body sculpture. In this study, we created the degradable and sonodynamic calcium carbonate-based microparticle for injecting into local adipose tissues, and the microparticle would be excited by ultrasonic energy. The acoustic sensitive microparticle would transform ultrasonic energy into ROS release in local area, and ROS attack would induce adipotic cell apoptosis. Moreover, the degradable calcium carbonate-based microparticle might result in high calcium environment to inhibit pre-adipotic cell maturation.
  The cerium-doped and europium-doped calcium carbonate have been successfully synthesized and served as sonosensitizers with biocompatible, biodegradable and micron-sized properties. Cerium and europium could reduce the energy gap of the electronic transition, thereupon, low-power ultrasonic energy was enough to activate the mechanism for achieving the goal of local body sculpture. In terms of material analysis, the EDS evaluation presented cerium and europium elements had been doped into calcium carbonate micropaticles, and the paticle size was about 2 μm with excellent dispersibility in water. For in-vitro cell experiment part, the data showed that cerium-doped and cerium-doped calcium carbonate had good biocompatibility, and the differentiation induction results demonstrated the high-calcium condition would inhibit adipototic maturation. Under ultrasonic activation, however, the cerium-doped and europium-doped calcium carbonate microparticles represented sonodynamic effects to generate large amounts of ROS for damaging local adipotic cells. For in-vivo animal experiments, the data verified the strategy could successfully achieve the goal of local body sculpture without any harmful side-effects or shortcomings. Consequently, the cerium-doped and europium-doped calcium carbonate sonodynamic microparticles combining with low-power ultrasonic energy have potentials to be a new technology for local body sculpture.

口試委員會審定書 ii
謝誌 iii
中文摘要 iv
英文摘要 v
目錄 vii
圖目錄 x
表目錄 xii
公式目錄 xiii
縮寫目錄 xiv
第 1 章 緒論 1
1.1 前言 1
1.2 局部肥胖 3
1.3 體態雕塑處理方法 4
1.3.1 運動 4
1.3.2 抽脂(Liposuction) 4
1.3.3 低強度超音波(Low intensity ultrasound) 4
1.3.4 高強度聚焦超音波(High intensity focused ultrasound) 5
1.4 研究目的 5
第 2 章 理論基礎 7
2.1 聲動力作用 7
2.2 超音波 8
2.2.1 空化作用 9
2.2.2 超音波誘發凋亡機制 10
2.3 聲敏感材料 11
2.4 材料-摻雜鈰或銪之碳酸鈣 12
2.4.1 主體材料-碳酸鈣(CaCO3) 12
2.4.2 鈣離子(Ca2+) 12
2.4.3 稀土元素-鈰或銪之摻雜 13
2.5 細胞吞噬作用(Phagocytosis) 14
第 3 章 實驗方法與步驟 15
3.1 實驗儀器 15
3.2 實驗藥品 16
3.3 實驗架構 18
3.4 材料製備 19
3.5 材料分析 20
3.5.1 X光繞射分析儀(XRD, X-ray Diffraction) 20
3.5.2 掃描式電子顯微鏡(SEM, Scanning Electron Microscope) 21
3.5.3 穿透式電子顯微鏡(TEM, Transmission Electron Microscope) 21
3.5.4 奈米粒徑量測儀(Zetasizer) 22
3.5.5 能量散射光譜儀(EDS, Energy Dispersive Spectrometer) 23
3.6 生物相容性試驗 24
3.6.1 細胞株培養 24
3.6.2 材料萃取液之製備 24
3.6.3 WST-1細胞活性測試 25
3.7 超音波裝置 27
3.7.1 超音波裝置 27
3.7.2 超音波參數選擇 28
3.7.3 慣性空化作用的測定 28
3.8 體外測試(In virto study) 30
3.8.1 細胞株培養 30
3.8.2 細胞分化測試 30
3.8.3 鈣離子抑制分化測試 32
3.8.4 ROS的生成 33
3.8.5 WST-1細胞活性測試 35
3.8.6 Live/Dead分析 36
3.9 動物實驗(In vivo study) 38
3.9.1 動物模型的建立 38
3.9.2 安全性測試 40
3.10 統計方法 41
第 4 章 結果與討論 42
4.1 材料性質分析 42
4.1.1 X光繞射分析 42
4.1.2 微結構分析 44
4.1.3 材料粒徑分析 46
4.1.4 材料組成分析 48
4.1.5 超音波參數之評估 50
4.2 生物相容性分析 52
4.3 體外測試 53
4.3.1 細胞分化測試 53
4.3.2 鈣離子抑制分化測試 55
4.3.3 ROS 的生成 56
4.3.4 WST-1 細胞活性測試 58
4.3.5 Live/Dead 分析 59
4.4 動物實驗 62
4.4.1 體重變化 62
4.4.2 腰圍變化 63
4.4.3 皮下脂肪率 64
4.4.4 體溫變化 66
4.4.5 組織切片 67
4.4.6 血液分析 70
第 5 章 結論 72
參考文獻 73


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