本研究主要使用擁有兩個末端位置碳碳雙鍵之雙馬來醯亞胺(N,N’-bismaleimide-4,4’-diphenylmethane, BMI) 與擁有一個CH2及兩個NH基之巴比妥酸 (Barbituric acid,BTA) 進行聚合反應，形成STOBA 溶液，再添加不同比例之Jeffamine ( M1000 , JF) 或L –半胱胺酸 (L-Cystene) 進行親水性改質，形成親水性之JF-STOBA或Cys-STOBA 樣品。
本研究使用不同BMI/BTA莫爾比 (4/1、3/1及2/1)，分別添加不同比例之安定劑50% JF、30% JF、20% JF、10% Cys合成樣品，其中以NMP合成之BMI/BTA 3/1-50% JF、30% JF、20% JF、10% Cys與BMI/BTA 2/1-20% JF、10% Cys 樣品最穩定。在低pH值時， BTA或COO-提供的負電荷會愈少，︱︱值減少，粒徑上升；在高pH值時，︱︱值減少，JF的立體障礙以及STOBA-Cys樣品表面帶相同電荷增加產法靜電斥力，使粒徑維持不變。STOBA-JF樣品之分子量大小為含有50% JF分子量最大，其次為30% JF，20% JF分子量最低。
由於在細胞毒系測試中所有樣品皆無細胞毒性，因此此一具有酸鹼應答特性之樣品具有相當大的潛力應用於藥物載體中。

This work studied the polymerization reaction of the two terminal -C=C- groups of N,N-bismaleimide-4,4-diphenylmethane (BMI) with one CH2 group and two NH groups of Barbituric acid (BTA). The experimental steps were divided into two parts. First, BMI and BTA was polymerized to STOBA solution. Second, using different proportions of Jeffamine (M1000,JF) or L-cystene (L-Cys) to modify STOBA solution. JF-STOBA or Cys-STOBA became a hydrophilic structure.
This work used different BMI/BTA molar ration 4/1、3/1及2/1, by adding different proportions of stabilier separately : 50% JF、30% JF、20% JF、10% Cys to synthesis samples. BMI/BTA 3/1-50% JF、30% JF、20% JF、10% Cys與BMI/BTA 2/1 20% JF、10% Cys samples polymerized by NMP solvent were more stable. At low pH value, BTA or COO - would provide less negative charges,︱︱value reduce；at high pH value,︱︱value reduce. Because of JF provided steric stabilization and Cys provided electrostatic stabilization, particles size keep the same. The molecular weight of STOBA-JF samples were 50% JF largest, followed by 30% JF, 20% JF was the lowest.
Since all samples in the cytotoxic experiment were non cytotoxicity. As a result, these pH- responsive samples have great potential in the applications of drug carrier.

【1】 葉明功；胡接燊；洪伯達，奈米藥品在臨床上的運用.藥學雜誌2012，28(2)，21-25
【2】 T. Pascal, R. Mercier, and B. Sillion, "New semi-interpenetrating polymeric networks from linear polyimides and thermosetting bismaleimides. 1: Synthesis and characterization of starting components," Polymer, vol. 30, pp. 739-744, 1989.
【3】 C. S. Wang and C. H. Lin, "Synthesis and properties of phosphorus containing copoly (bismaleimide)," Polymer, vol. 40, pp. 5665-5673, 1999.
【4】 R. H. Pater, “Thermosetting Polyimides: A Review”, SAMPE J , 1994.
【5】 P. Mison and B. Sillion, "Thermosetting oligomers containing maleimides and nadimides end-groups," in Progress in Polyimide Chemistry I, ed:Springer, pp. 137-179,1999.
【6】 Z. D. Xiang and F. R. Jones, "Thermal degradation of an end-capped bismaleimide resin matrix (PMR-15) composite reinforced with pan-based carbon fibres," Composites science and technology, vol. 47, pp. 209-215,1993.
【7】 A. von. Baeyer, “Untersuchungen uber die Harsauregrouppe”, Ann. Chem. Pharm. vol.127 , pp. 199, 1863.
【8】 G. B. Kauffman, "Adolf von Baeyer and the Naming of Barbituric Acid,"Journal of Chemical Education, vol. 57, 1980.
【9】 K. T. Mahmudov, M. N. Kopylovich, A. M. Maharramov, M. M. Kurbanova, A. V. Gurbanov, and A. J. L. Pombeiro, "Barbituric acids as a useful tool for the construction of coordination and supramolecular compounds,"Coordination Chemistry Reviews, vol. 265, pp. 1-37, 2014.
【10】 曾昭瓊, 有機化學. 第四版上冊, 北京: 高等教育出版社2005.
【11】 J.-P. Pan, G.-Y. Shiau, S.-S. Lin, and K.-M. Chen, "Effect of Barbituric acid on the Self-Polymerization Reaction of Bismaleimides," Journal of Applied Polymer Science, vol. 45, pp. 103-109, 1992.
【12】 C.-S. Chern, H.-L. Su, J.-M. Hsu, J.-P. Pan, and T.-H. Wang, " Understanding hyperbranched polymerization mechanisms," Society of Plastics Engineers, 2011.
【13】 L. R. Dix, J. R. Ebdon, N. J. Flint, P. Hodge, and R. O'Dell, "Chain extension and crosslinking of telechelic oligomers—I. Michael additions of bisamines to bismaleimides and bis (acetylene ketone) s," European polymer journal, vol. 31, pp. 647-652, 1995.
【14】 M. Sava and C. Grigoras, "Bismaleimide monomers and polymers with ester and ether units. Synthesis and properties," Journal of Macromolecular Science, Part A: Pure and Applied Chemistry, vol. 42, pp. 1095-1108, 2005.
【15】 Z. Shen, J. Schlup, and L. Fan, "Synthesis and characterization of leather impregnated with bismaleimide (BMI)–Jeffamine® resins," Journal of applied polymer science, vol. 69, pp. 1019-1027, 1998.
【16】 E.D. Bergman, D. Ginsburg, R. Pappo, “The Michael reaction”, Organic Reaction, 1959.
【17】 M. E. Jung, "Stabilized nucleophiles with electron deficient alkenes and alkynes," Comprehensive organic synthesis, vol. 4, p. 1, 1991.
【18】 S. Tokura, S.-i. Nishimura, and N. Nishi, "Studies on chitin IX. Specific binding of calcium ions by carboxymethyl-chitin," Polymer journal, vol. 15, pp. 597-602, 1983.
【19】 J. Pavlinec and N. Moszner, "Photocured polymer networks based on multifunctional β‐ketoesters and acrylates," Journal of applied polymer science, vol. 65, pp. 165-178, 1997.
【20】 J. Crivello, D. Conlon, and S. Rice, "Bismaleimide-bisvinylether copolymers: A new class of thermosetting resins," Polymer Bulletin, vol. 13, pp. 409-415, 1985.
【21】 I. M. Brown and T. C. Sandreczki, "Cross-linking reactions in maleimide and bis (maleimide) polymers. An ESR study," Macromolecules, vol. 23, pp. 94-100, 1990.
【22】 L. G. Wade, Organic Chemistry 5th Ed. Mechanism supplements origina, 2002.
【23】 Tsubokawa, N.; Shibata, N.; Sone, Y., "Radical polymerization of methyl methacrylate initiated by an enolizable ketone–carbon black system. " Journal of Polymer Science: Polymer Chemistry Edition ,vol.21, pp. 425-433, 1983.
【24】 Su, H. L.; Hsu, J. M.; Pan, J. P.; Wang, T. H.; Yu, F. E.; Chern, C. S., "Kinetic and structural studies of the polymerization of N, N′‐bismaleimide‐4, 4′‐diphenylmethane with barbituric acid. " Polymer Engineering & Science ,vol. 51,pp. 1188-1197, 2011.
【25】 張基隆、胡祐甄、黃姿菁、鄭筱翎、謝寶萱，生物化學，初版，台灣：華杏出版有限公司2013.
【26】 蔡偉博，奈米凝膠在藥物傳輸的應用.化工2015，62(1)，84-91
【27】 Peppas NA. " Hydrogels in medicine and pharmacy " CRC Press, 1988, Chapter 1.
【28】 Hoffman AS. "Hydrogels for biomedical applications " Advanced Drug Reviews, vol. 43, pp. 3-12, 2002.
【29】 Zhang Z, Wu D, Chu C. "Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels" Biomaterials, vol. 25, pp. 3793 – 3805, 2004.
【30】 LiuW, Zhang B, LuWW, Li X, Zhu D, Yao KD., Wang Q, Zhao C, Wang C. "A rapid temperature-responsive sol-gel reversible poly (N-isopropylacrylamide) -g-methylcellulose copolymer hydrogel" Biomaterials, vol. 25, pp. 3005 – 3012, 2004.
【31】 Gerlach G, Guenther M, Suchaneck G, Sorber J, Arndt KF, Richter A. "Application of sensitive hydrogels in chemical and pH sensor", Macromol. Symp, vol. 210, pp. 403-410, 2004.
【32】 Schild HG. Progress in Polymer Science , vol.17, pp. 163-249, 1992.
【33】 Qiu Y, Park K. "Environment-sensitive hydrogels for drug delivery" , Advance Drug Delivery Reviews.vol. 53, pp. 321-339, 2001.
【34】 Anzai J, Ueno A, Sasaki H, Shimokawa K, Osa T, "Photocontrolled permeation of alkali cation through poly(vinyl chloride) crown ether membrane", Makromol. Chem. Rapid Commun., vol. 4, pp. 731-734, 1983.
【35】 Ishihara K, Shinohara I. "Photoinduced permeation control of proteinsusing amphiphilic azoaromatic polymer membrane", J. Polym. Sci. Polym. Lett. Ed., vol. 22, pp. 515-518, 1984.
【36】 Murdan S. "Electro-responsive drug delivery from hydrogels ", Journal of Controlled Release, vol. 92, pp. 1-17, 2003.
【37】 Tomer R, Dimitrijevic D, Florence AT. "Electrically controlled release of macromolecules from cross-linked hyaluronic acid hydrogels ", Journal of Controlled Release , vol. 33, pp. 405-413, 1995.
【38】 Wu H J, Interrante L V. Macromolecules,vol.25, pp. 1840, 1992.
【39】 Soppimath KS, Kulkarni AR, Aminabhavi TM. "Chemically modified polyacrylamide-g-guar gum-based crosslinked anionic microgels as pH-sensitive drug delivery systems: preparation and characterization. " Journal of Controlled Release. vol. 75, pp. 331-345, 2001.
【40】 García-González N, Kellaway IW, Blanco-Fuente H, Anguiano-Igea S, Delgado-Charro B, Otero-Espinar FJ, Blanco-Méndez J. "Design and evaluation of buccoadhesive metoclopramide hydrogels composed of poly(acrylic acid) crosslinked with sucrose. " International Journal of Pharmaceutics. vol.100, pp. 65-70, 1993.
【41】 朱涵葳，2014，海藻酸鈉與凱索尼酸複合水膠之黏彈性質和細胞相容性研究，國立台灣科技大學，碩士論文
【42】 王冠斐、賴山強，膠體中的物理簡介.物理雙月刊2001，13 (4)，482-487
【43】 Á. V. Delgado, "Interfacial electrokinetics and electrophoresis", Marcel Dekker Inc., 2002.
【44】 張有義，郭蘭生編著 D. J. shaw 原著，”膠體及界面化學入門( Introduction to colloid and surface chemistry)”, 高立圖書有限公司, 2004.
【45】 Levine, S., Problems of stability in hydrophobic colloidal solutions I. On the interaction of two colloidal metallic particles. General discussion and applications. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, vol. 170, pp. 145, 1939.
【46】 吳哲宇，2011，粒徑及界面電位探討－聚苯胺及其衍生物，國立東華大學，碩士論文
【47】 施正雄，儀器分析原理與應用，五南圖書出版股份有限公司，2012
【48】 Garrett, R. H., Grisham, " Biochemistry ", Saunders College Publishing, C. M. p.81-p.91, 2nd ,1999
【49】 W.O. Baker, Ind. Eng. Chem., 41 (1949) 511.
【50】 H. Staudinger, E. Husemann, Ber.,vol. 68, pp.1618 , 1935.
【51】 M.J. Murray, M.J. Snowden, Adv. " Colloid Interface Sci ",vol. 54, pp.73, 1995.
【52】 Brian R. Saundersa, Brian Vincent, " Microgel particles as model colloids: theory, properties and applications ", Advances in Colloid and Interface Science, vol.80, pp.1-25,1999.