請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32773完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃義侑 | |
| dc.contributor.author | Chin-Hsiung Hsieh | en |
| dc.contributor.author | 謝錦雄 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:15:15Z | - |
| dc.date.available | 2011-07-28 | |
| dc.date.copyright | 2006-07-28 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-25 | |
| dc.identifier.citation | [1] Cao, A., 1993. Preventing a genetic disease. World Health. 6：26-27.
[2]林東燦，民82˙β-海洋性貧血的傳統治療˙醫學繼續教育˙. 3 (6)：741-745。 [3] Dyson, S., Davis, V., Rahman, R., 1993. Thalassaemia: Establishing basic awareness… part 1. Health Visitor. 66 (10)：360-361. [4]行政院衛生署/長庚醫訊.19(12),財團法人長庚紀念醫院出版 [5] Martin, M. B., Butler, R. B., 1993. Understanding the basics of β thalassemia major. Pediatric Nursing. 19 (2)：143-145. [6] B.W. Barry, 2001. Novel mechanisms and devices to enable successful transdermal drug delivery, European Journal of Pharmaceutical Sciences.14：101–114 [7] Zemel, R., Dickman, R., Tamary, H., Bukh, J., Zaizov, R., Turkaspa, R., 1998. Viremia, genetic heterogeneity, and immunity to hepatitis G/GB-C virus in multiply transfused patients with thalassemia. Transfusion. 38 (3)：301-306. [8] Cazzola, M., Borgna-Pignatti, C., Locatelli, F., Ponchio, L., Beguin, Y., De Stefano, P., 1997. A moderate transfusion regimen may reduce iron loading in β -thalassemia major without producing excessive expansion of erythropoiesis. Transfusion. 37 (2)：135-140 [9] Stanley L. Schrier and Emanuele Angelucci, 2005. New strategies in the treatment of the thalassemias, Annu. Rev. Med.. 56:157–71 [10] Chien, Y. W., Faaps, F., Faprs, 1993. Development of biomedical technology for noninvasive systemic delivery of peptide-based therapeutic agents: (Ⅱ)TIPS-facilitated transdermal delivery of insulin pharmacokinetics and pharmacodynamics studies. Biomedical Engineering Applications, Basis & Communications. 5 (2)：212-233. [11] Chien, Y. W., 1987. “Transdermal Controlled Systemic Medications”, Marcel Dekker, New York. [12] Hadgraft, J. and Guy, R.H. 1989. Transdennal Drug Delivery: Developmental Issues and Research Initiatives. Marcel Dekker, New York. [13] Singh, S., Singh J., 1993. Transdermal drug delivery by passive diffusion and iontophoresis. A Review, Medicinal Research Reviews. 13 (5)：569-621. [14] Barry, B. W., 1991. Lipid-protein-partitioning theory of skin penetration enhancement. Journal of Controlled Release. 15：237-248. [15] Illel, B., Schaefer, H., Wepierre, J., Doucet, O., 1991. Follicles play an important role in percutaneous absorption. Journal of Pharmaceutical Sciences. 80：424-427. [16] Rolf, D., 1988. Chemical and physical methods of enhancing transdermal drug delivery. Pharmaceutical Science & Technology Today. 130-140. [17] Walker, R. B., Smith, E. W., 1996. The role of percutaneous penetration enhancers. Advanced Drug Delivery Reviews. 18：295-301. [18] Barry B.W., 2004. Breaching the skin’s barrier to drugs, Nature Biotechnology 22 (2)：165-166 [19] Barry, B.W., Williams, A.C., 1995. Permeation enhancement through skin. In: Swarbrick, J., Boylan, J.C. (Eds.). Encyclopedia of Pharmaceutical Technology. Marcel Dekker, New York.11：449-493. . [20] Barry B.W., 1983.Dermatological Formulations: Percutaneous Absorption, Marcel Dekker, New York [21] Adrian C. Williams, Brian W. Barry, 2004.Penetration enhancers, Advanced Drug Delivery Reviews 56：603-618 [22] Aungst B.J., inSmith E.W. and Maibach H.I. (Eds.),1995.Percutaneous penetration enhancers, CRC Press, Boca Raon Chap. 9.1：277 [23] Golden GM, McKie JE, Potts RO., 1987.Role of stratum corneum lipid fluidity in transdermal drug flux. J Pharm Sci 76：25-28 [24] Ongpipattanakul B, Burnette R, Potts RO, 1991. Francoeur ML: Evidence that oleic acid exists in a separate phase within stratum corneum lipids. Pharm Res 8：350-354 [25]Meidan V, Walmsley A, Iriwin W., 1995. Phonophoreis it a reality? Inter J Pharm Sci.118:129 [26]Danial G, Agnes K, Matthew J., 1996.Physical enhancement of dermatologic drug delivery:Iontophoresis and phonophoresis., J Am Dermtol.34:337 [27]Nancy N Byl., 1995. The use of ultrasound as enhancer for transcutanous drug delivery:Phonophoresis, Phys Ther.75(6):539 [28]Mitragotri S, Edwards D, Blankschtein D,et al. ,1995.A mechanistic study of ultrasonically enhanced transdermal drug delivery, J Pharm Sci.84(6):879 [29]Mitragotri S,Blankchein D,Langer R., 1996.Transdermal drug delivery using low-frequency sonophoresis.Pharm Res.13(3):411 [30] Tezel A., Sens A. and Mitragotri S., 2002.Investigations of the role of cavitation in low-frequency sonophoresis using acoustic spectroscopy. J. Pharm. Sci.91： 444–453. [31] Kost, J., Katz, N., Shapiro, D., Herrmann, T., Kellog, S., Warner, N. and Custer, L., 2003.Ultrasound skin permeations pretreatment to accelerate the onset of topical anesthesia. Proceedings of the Controlled Release Society 30th Annual Meeting held July 19-23, Glascow, Scotland, UK [32] Tezel A., Sens A.and Mitragotri S., 2003.A theoretical description of transdermal transport of hydrophilic solutes induced by low-frequency sonophoresis. J. Pharm. Sci. 92：381-393. [33] Suslick K.S., 1989. Ultrasound: It’s Chemical, Physical and Biological Effects. VCH Publishers, New York. [34] Pankaj Karande, Amit Jain & Samir Mitragotri, 2004. Discovery of transdermal penetration enhancers by high-throughput screening, Nature biotechnology.22 (2)： 192-197 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32773 | - |
| dc.description.abstract | 海洋性貧血病人需長期接受輸血以維持生命，長期輸血容易導致病人體內三價鐵離子含量過高而產生鐵中毒的現象，鐵中毒慣例上採用deferoxamine mesylate(Desferal○R, DFO)皮下注射或以連續式點滴以螯合治療，病患容易因為疼痛而產生排斥感，使治療效果不佳，因此我們希望能夠改變藥物劑型，嘗試以經皮給藥的方式來取代注射治療，本實驗的目的即是評估將DFO製成貼劑貼在皮膚上給藥的可行性，將選擇基質式經皮吸收系統，設計DFO 貼片。此貼片希望能夠以一定傳送速率讓藥穿過皮膚到達循環系統，而達全身性治療效果。
實驗中以正在開發中的新材質，探討藥物在其中的釋放情形，以水膠和感壓膠分別開發為同相及異相的藥物經皮吸收貼劑，並在異相的感壓膠貼片中加入tween80當做結晶抑制劑使用，但因貼片基質中只能負荷一定量之承載藥物，且藥物在穿透皮膚時，會遇到角質層的障礙，因而降低藥物穿透皮膚的量，在加入oleic acid後對藥物穿透量有明顯的促進，以連續波超音波處理鼠皮後可以增進藥物的穿透量，而針對超音波導入效果的相關參數還有待進一步測試。 | zh_TW |
| dc.description.abstract | The ultimate goal of this study is to help thalassemia major patients, who chronically require blood transfusions to keep alive. However, such long-term transfusions will lead to the accumulation of trivalent iron and bring about an iron overload condition. To treat iron overload, the patients usually receive intravenous or subcutaneous infusion of deferoxamine mesylate (DFO) regularly. The high costs of the drug, pump, and infusion materials, as well as the side effects, limit its acceptability and utility. For this reason, we hope to be able to change the method of delivering DFO. We want to replace the traditional injection method with transdermal drug delivery system. The preliminary goal of this study is to estimate the feasibility of designing and fabricating a DFO patch by using the single-layer drug-in-adhesive transdermal drug delivery system. We expect it can enable the drug to penetrate the skin at a stable rate and reach the circulation system successfully to allow the concentration of drug reach the therapeutic window.
In this research, we develop the pressure sensitive adhesives and hydrogels as the drug reservoirs and observe the release profile of DFO in the adhesives in order to develop and design transdermal patches. Because drug matrices can only contain a certain amount loading drug, the area of the designed patch is too large. The existence of Tween 80 in our pressure sensitive adhesives will enhance DFO penetrating through nude mice skin.When adding oleic acid to be penetration enhancer, the penetrating effect of DFO is enhanced. The synergistic effect of tween 80 and oleic acid in our pressure sensitive adhesives seems not very well with the ratio one to one. The pretreatment of nude mice skin with ultrasound enhance DFO penetrating through skin. But the parameters of the sonophoresis in nude mice are needed further research and development. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:15:15Z (GMT). No. of bitstreams: 1 ntu-95-R93548023-1.pdf: 3254535 bytes, checksum: e33567569b739fd1ec05742fcbd33f40 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄
目錄 I 圖表目錄 Ⅳ 中文摘要 Ⅵ 英文摘要 Ⅶ 第一章 緒論 1 1-1 前言 1 1-2 研究動機與目的 3 第二章 文獻回顧 4 2-1 海洋性貧血 4 2-1-1 生理與病理變化 4 2-1-2 α型海洋性貧血 5 2-1-3 β型海洋性貧血 6 2-1-4 治療方法 8 2-2 藥物經皮吸收系統 11 2-2-1 皮膚組織結構 15 2-2-2 藥物經皮途徑 19 2-3 促進藥物經皮吸收方法 22 2-3-1 化學滲透促進劑 25 2-3-2超音波導入 27 第三章 實驗材料與方法 31 3-1 試藥與原料 31 3-2 儀器 32 3-3 試藥配製 33 3-4 藥物濃度之分析方法 33 3-5 豬皮之前處理 34 3-6 DFO溶液於豬皮之穿透實驗 35 3-7 貼片之製備 35 3-8 貼片之水溶液藥物釋放實驗 36 3-9 貼片之體外藥物釋放實驗 37 第四章 結果與討論 38 4-1 藥物濃度之分析 38 4-2 DFO溶液鼠皮穿透實驗 40 4-3 感壓膠貼片測試 41 4-3-1 感壓膠釋放實驗 43 4-3-2 感壓膠DFO貼片製作分析 44 4-3-3 感壓膠貼片鼠皮穿透實驗 45 4-4 水膠貼片測試 47 4-4-1水膠貼片之水溶液溶離測試 48 4-4-2水膠貼片鼠皮穿透實驗 49 4-4-3以超音波前處理鼠皮之水膠貼片穿透實驗 50 4-5藥物貼片其他形式 52 第五章 結論 53 第六章 參考文獻 54 圖表目錄 圖2-1 不同釋放劑型血中藥物濃度變化比較 12 圖2-2 藥物經皮吸收過程 15 圖2-3 皮膚結構圖 18 圖2-4 藥物穿透皮膚巨觀路徑圖 21 圖2-5 藥物穿透皮膚微觀路徑 21 圖2-6 滲透促進劑對角質的作用機制 24 圖2-7 滲透促進劑對角質的作用機制 24 圖2-8空化效應增強角質層的滲透三種可能型態 29 圖4-1 UV光譜圖（A）DFO溶液（B）豬皮溶液 57 圖4-2 DFO + Fe3+ → FO 之結構式 58 圖4-3 FO全光譜吸收圖 59 圖4-4 鐵標準液全光譜吸收圖 59 圖4-5 FO標準曲線 60 圖4-6 感壓膠水溶液溶離測試圖 61 圖4-7 Lidocaine hydrochloride 感壓膠貼片水溶液釋放圖 62 圖4-8 Lidocaine 感壓膠貼片水溶液釋放圖 63 圖4-9 Lidocaine hydrochloride standard curve 64 圖4-10 Lidocaine standard curve 65 圖4-11 DFO 溶液對豬皮之滲透曲線 66 圖4-12 DFO溶液對鼠皮穿透曲線 67 圖4-13 DFO藥物貼片實物圖 68 圖4-14 含不同滲透促進劑的藥物貼片(5% DFO) 69 圖4-15 感壓膠貼片鼠皮穿透實驗 70 圖4-16 DFO水膠貼片水溶液溶離測試 71 圖4-17 三種水膠鼠皮穿透實驗比較圖 72 圖4-18 DFO溶液對以超音波前處理之鼠皮穿透測試 73 圖4-19 DFO溶液對以超音波前處理之鼠皮穿透測試 74 圖4-20 水膠1對以超音波前處理之鼠皮穿透測試 75 圖4-21 以超音波處理後的鼠皮水膠穿透與DFO溶液比較圖 76 圖4-22 以超音波處理鼠皮之滲透效果綜合比較圖 77 圖4-23 DFO溶液在海綿結構中之藥物滲透曲線圖 78 圖4-24 不同形式之經皮吸收藥物貼片 79 | |
| dc.language.iso | zh-TW | |
| dc.subject | 經皮吸收藥物系統 | zh_TW |
| dc.subject | 超音波導入 | zh_TW |
| dc.subject | 海洋性貧血 | zh_TW |
| dc.subject | 滲透促進劑 | zh_TW |
| dc.subject | Desferal | zh_TW |
| dc.subject | sonophoresis | en |
| dc.subject | thalassemia | en |
| dc.subject | Desferal | en |
| dc.subject | transdermal drug delivery system | en |
| dc.subject | chemical enhancer | en |
| dc.title | 海洋性貧血經皮吸收藥物系統開發 | zh_TW |
| dc.title | The Development of Transdermal Drug Delivery System for Beta-Thalassaemia Major | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鍾次文,楊台鴻,劉得任 | |
| dc.subject.keyword | 海洋性貧血,Desferal,經皮吸收藥物系統,滲透促進劑,超音波導入, | zh_TW |
| dc.subject.keyword | thalassemia,Desferal,transdermal drug delivery system,chemical enhancer,sonophoresis, | en |
| dc.relation.page | 79 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-25 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| 顯示於系所單位： | 醫學工程學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-95-1.pdf 未授權公開取用 | 3.18 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。