研究以自組裝表面改質技術將雙離子型共聚物塗佈於醫療級丁基膠塞並控制其界面之生物惰性

Coating zwitterionic copolymer on medical butyl rubber stopper with self-assembly surface modification technology and controlling the bio-inert interface

張正翰(CHENG-HAN CHANG)

指導教授 ： 張雍

中原大學/工學院/化學工程學系/碩士(2022年)

https://doi.org/10.6840/cycu202201340

摘要

近年來因COVID-19疫情的影響，全球在疾病預防、診斷與治療的需求產生重大改變，其中建構高階疫苗注射系統的醫療器材逐漸受到重視。因應目前許多高階藥物以基因片段或蛋白質體為主，注射器中的包裝元件對於生物惰性的功能需求提升，才能強化藥物保存的穩定性。而醫療級丁基膠塞目前在注射器包材的使用為主要的元件，且會產生大量的生物分子吸附與沾黏，為克服這個問題，本研究主題擬設計與製備具生物惰性的醫療級丁基膠塞。本研究目的為探討自組裝雙離子化表面改質技術於醫療級丁基膠塞對於抵抗生物分子貼附與沾黏的影響。分別將磺基甜菜鹼甲基丙烯酸酯(sulfobetaine methacrylate, SBMA)、磺基甜菜鹼甲基丙烯醯胺(sulfobetaine methacry-lamide, SBAA)與甲基丙烯酸丁酯(butyl methacrylate, BMA)，透過調整單體比例以自由基聚合法製備出兩種雙離子型共聚物：poly(SBMA-co-BMA)以及poly(SBAA-co-BMA)。使用浸泡式塗佈方法來一步驟改質丁基膠塞表面，並控制膠塞界面的生物惰性功能。本研究採用表面接觸角量測儀、全反射式傅立葉紅外線光譜儀、雷射共軛聚焦掃描式顯微鏡等設備來鑑定與分析膠塞表面之物理性質、化學組成、與生物惰性。本研究的重要成果歸納如下：(1)成功合成出poly(SBMA-co-BMA)與poly(SBAA-co-BMA)，並證明雙離子共聚物可經由疏水作用力驅動自組裝塗佈於丁基膠塞表面之可行性；(2)poly(SBAA-co-BMA)在組成比例為SBAA：BMA = 30：70條件下，可於丁基膠塞表面形成抵抗70%人類纖維腫瘤細胞與80%大腸桿菌的生物分子貼附及沾黏，展現高度生物惰性能力；(3)使用SBAA結構體之共聚物進行丁基膠塞表面雙離子化改質後，其水合能力與高溫滅菌前後的抗生物沾黏能力都有相當顯著的提升，並展現高度熱穩定性質。

關鍵字：雙離子共聚物、丁基膠塞、自組裝塗佈法、生物惰性、熱穩定性質

關鍵字

雙離子共聚物 ； 丁基膠塞 ； 自組裝塗佈法 ； 生物惰性 ； 熱穩定性質

並列摘要

In recent years, due to the impact of the COVID-19 epidemic, the global demand for disease prevention, diagnosis and treatment has changed significantly, especially medical equipment for the construction of high-level vaccine injection systems has gradually received attention. In view of the fact that many high-level drugs are currently dominated by gene segments or proteinoplast, the functional requirements of the packaging elements in the syringe for biological inertness are increased, so as to enhance the stability of drug storage. The medical butyl rubber stopper is currently used as the main component in the syringe packaging material, and it will generate a large amount of biomolecule adsorption and adhesion. The purpose of this study was to investigate the effect of self-assembled zwitterionic surface modification technology on medical butyl rubber stopper and the resistance to biomolecular adsorption and adhesion. The sulfobetaine methacrylate (SBMA), sulfobetaine methacrylamide (SBAA) and butyl methacrylate (BMA) adjusting the monomer ratio were respectively prepared to poly(SBMA-co-BMA) and poly(SBAA-co-BMA) by radical polymerization. Dip-coating method was used to modify the surface of butyl rubber stoppers in one step and to control the bio-inert function of the rubber stopper interface. In this study, Contact angle measuring instrument, Fourier transform infrared spectroscopy (FT-IR), Confocal laser scanning microscopy (CLSM) and other equipment were used to identify and analyze the physical properties, chemical composition, and biological inertness of the rubber stopper surface. The important achievements of this study are summarized as follows：(1) poly(SBMA-co-BMA) and poly(SBAA-co-BMA) were successfully synthesized, and it was proved that the zwitterionic copolymers can be coated on isobutylene isoprene rubber by hydrophobic force-driven self-assembly.；(2) poly(SBAA-co-BMA) of the monomer ratio SBAA：BMA = 30：70 could be coated on the surface of the butyl rubber stopper and it resists 70% Human Fibrosarcoma Cell and 80 % Escherichia coli adsorption and adhesion, showing a high degree of biological inertness.；(3) After using the copolymer of SBAA structure to carry out zwitterionic modification on the surface of butyl rubber stopper, it kept up its hydration ability and resistance before and after high temperature sterilization. Showing that the antifouling ability is significantly improved, and it exhibits high thermal stability properties.

Keywords：Zwitterionic copolymer, Butyl rubber stopper, Self-assembly coating method, Biological inertness, Thermal stability properties

並列關鍵字

Zwitterionic copolymer ； Butyl rubber stopper ； Self-assembly coating method ； Biological inertness ； Thermal stability properties

參考文獻

Uncategorized References

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