海洋性貧血經皮吸收藥物系統開發

The Development of Transdermal Drug Delivery System for Beta-Thalassaemia Major

謝錦雄(Chin-Hsiung Hsieh)

指導教授 ： 黃義侑

國立臺灣大學/工學院/醫學工程學研究所/碩士(2006年)

https://doi.org/10.6342/NTU.2006.02225

摘要

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。

關鍵字

海洋性貧血 ； Desferal ； 經皮吸收藥物系統 ； 滲透促進劑 ； 超音波導入

並列摘要

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.

並列關鍵字

thalassemia ； Desferal ； transdermal drug delivery system ； chemical enhancer ； sonophoresis

參考文獻

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