臺灣博碩士論文加值系統

隨著現代人生活飲食習慣變遷，心血管疾病在全世界都已成為主要死亡因素。過去通常用冠狀動脈繞道手術與經皮冠狀動脈腔內氣球擴張術進行治療，但在心臟血管支架被發明後，就成為醫學界的主流。而裸金屬血管支架容易發生血管再狹窄的現象，需要配合防止細胞增生的藥物，防止支架內血栓的發生。現代最新的版本則是塗藥血管支架，將藥物部署在血管支架表面，只在患部精準投藥，減少過去口服藥物的全身性副作用。但如果直接在金屬表面部署藥物，在置入人體後，藥物很快就會被血流完全沖走，導致藥物快速釋放，減少實際作用時間。為了控制釋放時間，藥物通常會與聚合物混合，形成固體塗層。最初使用無法在體內分解的聚合物，藥物利用擴散的方式釋放，但一輩子留在體內的聚合物有機會發生問題；所以現在多使用生物可分解的聚合物，如聚乳酸(Poly-lactic acid, PLA)/聚乳酸-甘醇酸(Poly-lactide-co-glycolide, PLGA)，藥物隨著聚合物的水解逐漸釋放，副作用也較小。
血管支架主要的塗藥方式為dip coating或spray coating，但這兩者都是大範圍面積塗佈，對於價格昂貴的塗藥血管支架藥物來說是一大浪費。最新的塗藥方法是噴墨式塗藥，利用微型壓電噴嘴極小的液滴直徑，以及精準的支架表面路徑規劃，可以將塗佈每根支架所需的藥物量降得更低。
本研究首先測試多種非毒化物有機溶劑對PLA的溶解度，嘗試找出適合的溶劑，因為多數研究為追求溶解度，使用毒性極高的氯化溶劑，如氯仿。接下來調整脈波控制器參數以拉長可穩定工作的噴塗間隔，因為這與生產流程息息相關。最後，嘗試多種參數與噴塗時間的組合，並以掃描式電子顯微鏡表面照片進行分析與佐證，嘗試歸納出參數對噴塗表面結果的影響。本研究之成果旨在驗證血管支架噴墨式塗層參數與噴塗表面的關係，有助於未來進一步發展。

Due to the changes in modern lifestyles, cardiovascular disease has become a major cause of death all over the world. In the past, coronary artery bypass surgery and percutaneous transluminal coronary angioplasty were usually used for treatment, but after the invention of coronary stents, it has become the mainstream in the medical field. Bare metal vascular stents are prone to vascular restenosis, and drugs to prevent cell proliferation are required to prevent in-stent thrombosis. Then the drug-eluting stent is invented. The drug is deployed on the surface of the vascular stent, and the drug is accurately applied only to the lesion, reducing the systemic side effects of oral drugs in the past. However, if the drug is directly deployed on the metal surface, after being placed in the human body, the drug will be completely washed away by the bloodstream, resulting in rapid release of the drug and reducing the actual effective time. In order to control the release time, the drug is usually mixed with a polymer to form a solid coating. In the past, polymers that cannot be decomposed in the body were used, and the drugs were released by diffusion, but the polymers that remained in the body for a lifetime may have problems; therefore, biodegradable polymers such as PLA(Poly-lactic acid)/PLGA(Poly-lactide-co-glycolide) are used now, and the drugs release along with hydrolysis of the polymer, and the side effects are smaller.
The main coating methods of vascular stents are dip coating or spray coating, but both of these apply coating in a large area, which is a big waste for the expensive drugs for vascular stents. The latest coating method is inkjet coating, which utililyzes the micro droplet diameter of the piezoelectric nozzle and the precise path planning of the stent surface to reduce the amount of drug required to coat each stent.
In this study, first, the solubility of a variety of non-toxic organic solvents to PLA is tested, for finding a suitable solvent, because most studies pursue solubility and use highly toxic chlorinated solvents, such as chloroform. Next, the parameters of pulse wave generator are adjusted to extend the spray interval that can work stably, because this is closely related to the production process. Finally, a combination of various parameters and spraying time are tested, and SEM stent surface photos are analyzed, for summarizing the influence of the parameters on the coated surface results. The results of this study are intended to verify the relationship between the parameters of the inkjet coating of the vascular stent and the sprayed surface, which will help further development in the future.

誌謝 i
摘要 ii
Abstract iii
目錄 v
圖目錄 vii
表目錄 x
第一章　緒論 1
1.1. 前言 1
1.2. 研究目的 3
1.3. 研究內容 4
第二章　文獻探討 5
2.1. 微型壓電噴嘴 5
2.2. 聚乳酸(Poly-lactic acid, PLA) 8
2.3. 聚乳酸-甘醇酸(Poly-lactide-co-glycolide, PLGA) 11
第三章　藥物載具自動塗佈系統 14
3.1. 精密移動控制機構 14
3.2. 光學影像定位機構 15
3.3. 藥物塗佈控制機構 16
3.3.1. 微型玻璃噴嘴 16
3.3.2. 脈波控制器 17
3.3.3. 精密壓力調節裝置 18
3.4. 系統軟體介面 19
第四章　研究方法 20
4.1. 溶液準備 20
4.1.1. 實驗藥品 20
4.1.2. 漢森溶解度參數(Hansen solubility parameter, HSP) 21
4.1.3. 溶解度實驗 22
4.1.4. 溶液處理 23
4.2. 塗藥支架設計、模擬、製造 23
4.3. 噴塗間隔測試 26
4.4. 噴塗參數測試 27
4.5. 噴塗時間測試 28
4.6. 支架擴張測試 28
4.7. 塗層厚度量測 30
第五章　結果與討論 31
5.1. 溶解度實驗 31
5.2. 噴塗間隔測試 33
5.3. 噴塗參數測試 35
5.3.1. 溶液濃度 35
5.3.2. 脈波參數 36
5.4. 儲藥槽式血管支架 39
5.5. 噴塗時間測試 41
5.6. 支架擴張測試 46
5.7. 塗層厚度量測 49
第六章　結論與未來展望 51
6.1. 結論 51
6.2. 未來展望 52
參考文獻 53

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