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研究生:郭蟬瑄
研究生(外文):Chan-Hsuan Kuo
論文名稱:手持式液態藥物輸送系統於經皮穿透效能測試
論文名稱(外文):Estimation the transdermal drug delivery efficiency of the handheld liquid drug delivery system
指導教授:廖愛禾
指導教授(外文):Ai-Ho Liao
口試委員:沈哲州劉浩澧江建平
口試日期:2018-07-27
學位類別:碩士
校院名稱:國立臺灣科技大學
系所名稱:醫學工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:中文
論文頁數:50
中文關鍵詞:手持式液態藥物輸送系統經皮給藥黑色素熊果素
外文關鍵詞:Handheld liquid drug delivery systemTransdermal drug deliveryMelaninArbutin
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經皮穿透給藥常受限於表皮層內的角質層所形成之屏障,導致藥物穿透不易。本研究目的為測試手持式液態藥物輸送系統經皮輸送藥物效能,手持式液態藥物輸送系統是以氣體壓力產生動量,將液體藥物傳送穿透皮膚角質層來達到治療的效果。
其中主要是評估手持式液態藥物輸送系統氣壓、充氣時間與出水量、滲透深度之間的關係、經皮滲透累積量以及動物試驗之美白效果。經出水量測試得知當氣體壓力上升,出水量(ml/1000shots)隨之下降,在豬皮的藥物滲透模擬實驗中,當氣體壓力上升,滲透深度也隨之上升,80 psi為37.19±1.81 μm、100 psi為42.11±2.30 μm,而120 psi為46.71±0.48 μm。本研究也協助開發手持式液態藥物輸送系統第五代及第六代,第六代修改了電磁閥長度,因此第六代設備全長較第五代短,氣體在輸送過程中損耗較少並將外殼改成金屬材質,延長使用壽命。
在體外測試實驗中,不論是豬皮滲透方面或是藥物經皮滲透累積量相較於控制組都有顯著性差異(P<0.01)。豬皮滲透實驗中手持式液態藥物輸送系統相較於控制組提升了38%,在藥物經皮滲透累積量實驗中,則是提升63%的給藥效率,在動物實驗中,以手持式液態藥物輸送系統施打熊果素組別相較於控制組及單純靜置熊果素組,在治療期間,皮膚美白亮度測試中都有較高的數值。
由以上研究結果得知,手持式液態藥物輸送系統確實能克服皮膚角質層的屏障及增加藥物滲透能力;在相同參數下,手持式液態藥物輸送系統第六代效能較第五代佳。由動物實驗中證實,手持式液態藥物輸送系統搭載美白藥物熊果素相較於控制組抑制黑色素生成效果較明顯。證明手持式液態藥物輸送系統在經皮給藥具有很大的運用潛力。
Drug permeation through the skin is usually limited by the stratum corneum in epidermis. In this study, the efficacy of a hand-held liquid drug delivery system for transdermal drug delivery will be evaluated. GNT GoldMedTM handheld liquid drug delivery system is a needle-free and low pressure of gas-powered injection system which can be used for transdermal biomaterials or drugs delivery.
This study is mainly to assess the gas pressure, gas inflation time, flux and penetration depth of transdermal drug delivery by using this hand-held liquid drug delivery system. According to the results, the flux is decreasing with increasing pressure, and the penetration depth of pigskin is proportional to the increasing of the pressure. In addition, the study also evaluated the efficancy of the fifth and sixth generation handheld liquid drug delivery system. In sixth generation of handheld liquid drug delivery system, the length of the solenoid valve was changed, and the total length of the sixth generation is shorter than the fifth generation handheld liquid drug delivery system. The total lenghth might influence the delivery efficancy.
The in vitro experiments in pigskin show that the penetration depth in hand-held liquid drug delivery system group increased 38% as compare to control group. Franz diffusion experiments on isolated porcine skin found that hand-held liquid drug delivery system increased 63% arbutin delivery, as compared with control group and arbutin alone group.
Our results showed that hand-held liquid drug delivery system can penetrate stratum corneum and enhance the transdermal drug delivery. The performance of the sixth generation is better than the fifth generation handheld liquid drug delivery system under the same parameters. In small animal experiments, the hand-held liquid drug delivery system enhances the delivery of arbutin to inhibit melanogenesis without damaging the skin in mice.
中文摘要 i
ABSTRACT ii
誌 謝 iii
目錄 iv
圖目錄 vi
表目錄 viii
第1章 、緒論 1
1.1 皮膚結構 1
1.1.1 表皮層 (Epidermis) 2
1.1.2 真皮層 (Dermis) 3
1.1.3 皮下組織 (Subcutaneous tissue) 4
1.2 經皮輸藥吸收機制 5
1.3 藥物經皮傳輸方法(Transdermal drug delivery) 6
1.3.1 化學滲透促進劑 (Chemical penetration enhancers, CPE) 6
1.3.2 離子導入法 (Iontophoresis) 7
1.3.3 電穿孔(Electroporation) 8
1.3.4 超音波 (Ultrasound) 9
1.3.5 微針 (Microneedle) 11
1.3.6 無針注射(Needle-free injection) 13
1.4 手持式液態藥物輸送系統 14
1.5 黑色素形成機制 15
1.6 熊果素簡介 18
1.7 研究動機 19
第2章 、材料與方法 20
2.1 研究架構 20
2.2 藥品與設備 21
2.2.1 藥品 21
2.2.2 設備 22
2.3 手持式液態藥物輸送系統 23
2.4 手持式液態藥物輸送系統於不同氣壓出水量分析 24
2.5 染劑穿透豬皮之分析 24
2.5.1 手持式液態藥物輸送系統不同氣壓及強度 24
2.5.2 手持式液態藥物輸送系統及臨床用超音波導入儀 26
2.5.3 冷凍切片處理流程 26
2.6 豬皮模擬體外經皮穿透實驗 27
2.6.1 逆向高效能液相層析儀 28
2.6.2 豬皮內藥物含量分析 28
2.7 掃描式電子顯微鏡皮膚表面分析 28
2.8 小鼠表皮之美白試驗 29
2.8.1 Lab色度檢測 30
2.9 組織切片 31
2.9.1 蘇木素-伊紅染色(H&E染色) 31
2.9.2 Fontana-Masson染色 31
2.10 統計分析 32
第3章 、實驗結果 33
3.1 手持式液態藥物輸送系統於不同氣壓出水量分析結果 33
3.2 染劑於豬皮之穿透深度分析結果 33
3.2.1 手持式液態藥物輸送系統不同氣壓及強度 33
3.2.2 手持式液態藥物輸送系及臨床用超音波導入儀 35
3.3 熊果素經皮穿透之濃度分析 36
3.4 掃描式電子顯微鏡鼠皮表面分析 38
3.5 小鼠皮膚美白試驗之亮度分析 39
3.6 鼠皮組織切片染色之黑色素分析 39
第4章 、討論 43
第5章 、結論 45
參考文獻 46
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