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  • 學位論文

研究具有高熱穩定性之血液相容性雙離子型分子結構設計

Novel Zwitterionic Formulation Design with High Thermal Stability and Excellent Blood Compatibility

指導教授 : 張雍

摘要


過去十年來的研究發現,目前泛用型仿生雙離子材料並不能在高溫處理後,仍然能保持其完美的生物惰性,因此在其實際應用方面會受到瓶頸。為克服此一問題,本研究論文主要提出新的仿生雙離子型單體結構材料,並探討其熱穩定性,與其形成最佳化材料分子結構組成,來控制於各種不同生物環境中,包含人體血液、細胞組織液、菌體溶液等,對於各式血球、細胞以及細菌的生物惰性(Bio-inert)性質分析討論。 在材料系統的設計,本研究導入吡啶分子結構來提升雙離子分子官能基的熱穩定性質,因此設計開環反應來合成此單體結構。合成路徑之設計,以4-乙烯基吡啶 (4-vinylpyridine; 4VP)為前驅單體,透過 1,3-丙烷磺内酯(1,3-Propansulton; PPS)化合物來對4VP進行雙離子化反應,所形成之新結構單體為4-vinylpyridine propyl sulfobetaine;4VPPS。在材料性質研究方面,本論文針對4VPPS的化學與物理性質,進行系統性的分析與探討,同時針對4VPPS單體結構與其形成高分子網狀結構(水膠系統)進行熱性質分析與比較,進一步探討熱處理前後對於其物化性質與生物惰性的影響。 本論文的研究結果,重要發現與論述歸納如下:(1)利用開環反應將4VP離子化,合成新型雙離子4VPPS,其中的吡啶結構能鞏固材料的熱穩定性質,其高分子poly(4VPPS)熱裂解溫度可達340℃;(2) 4VPPS經過121℃的高溫加熱後,仍保有完美的抗沾黏特性,然而這種穩定性確無法在實現在傳統的抗沾黏材料上;(3)將4VPPS接枝到金屬材料表面如:手術刀、人工支架、生物晶片等,使得金屬材可承受高溫滅菌後仍可抵抗各種類型的生物沾黏;(4)新型雙離子4VPPS突破傳統抗沾黏材料不具有熱穩定性的特點,有利於熱塑、熱固型加工製成,在高溫塑型後保持完美的抗沾黏特性,因此應用實例不局限於高階精密醫材,更能實現在日常生活中,例如齒列矯正器,傷口包覆材等,醫材能個人化並且重複使用。因此對於新型雙離子4VPPS的未來應用是具有潛力與多元化的。

並列摘要


Over the past decade, numerous studies found that currently zwitterionic materials can not sustain its bio-inert property after a high temperature treatment. With this draw back its practical applications will be limited. In order to overcome this problem, this research aims to synthesize a new zwitterionic based monomer structure and to evaluate its capability of bio-inertness after a high temperature treatment. The bio-inertness was measured by exposing the samples with different biomolecules such as human blood cells, tissue cells, and bacteria. The molecular structure of pyridine was used to enhance the thermal stability of the zwitterionic functional groups. The ring opening reaction of 4-vinylpyridine (4VP) with 1,3-propanesultone (PPS) was utilized to synthesize the zwitterionic monomer 4VPPS. The chemical and physical properties of 4VPPS were evaluated. The thermal stability, bio-inertness, and other properties of 4VPPS in a cross-linked network structure (hydrogel state) were analyzed before and after heat treatment. The 4VPPS was found to be able to withstand the a temperature of 121°C for heat treatment and still maintain its bio-inertness from all biomolecules tested compared to other conventional bio-inert materials that showed degradation and fouling after heat treatment. Also the 4VPPS hydrogel was used to modify titanium and stainless steel and was found out that it can enhance their thermal stability and still maintain bio-inertness. This results show that 4VPPS have a great potential for modifying the surface of biomaterials and still exhibit bio-inertness after a high temperature sterilization process. Its high thermal stability can provide biomaterials such as scalpels, artificial stents, or biochips stability after sterilization. This novel structure of a zwitterionic monomer boasts its advantage of having a good thermal stability over other antifouling materials. It has a very good potential for thermoplastics and thermosetting polymers processing to be able to have a bio-inert property after shaping. In this way its application would not be limited to high-end precision medical materials, but it can be applied more on a much wider materials that we use more often such as dental aligners, wound dressing, and others. The potential applications of the zwitterionic 4VPPS in the future can be very diverse and potentially limitless.

參考文獻


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