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ウレタン架橋をした固体のポリ(2-メトキシエチルアクリレート) 血管治療用医療材料の研究 (本文)

田澤, 俊介 慶應義塾大学

2022.07.27

概要

医療の現場では,ステント,人工関節,銀歯などさまざまな器具が体内に埋め込まれて使用されている.そしてそれらの器具は,金属,セラミックなど幅広い種類の材料から成り立っている.その中でもポリマーは,金属やセラミックなどの材料と比較して,柔軟性や成形性が高いという利点を有する材料である.この性質より,カテーテルやステント,人工血管など血管の治療で用いる器具に,ポリマー材料は多く利用されている.血管は,骨や歯などの部位と比較して,柔らかく変形しやすい部位である.さらに,血管には,動脈のような太いものから毛細血管のような細いものまでさまざまな太さの管が存在する.そのため,血管に埋め込む材料には,大きな変形に耐える柔軟性やさまざまなサイズの作製に対応した成形性が必要であるため,成形性の高いポリマーはきわめて有用である.しかし,一般的なポリマー材料は,我々の人体にもともと備わっているものではないため,体内で異物として認識され,さまざまな問題を引き起こしてきた.特に人工血管やステントなどの血液に接触する医療器具においては,Figure1.1のように人工血管の壁面に血液成分の血小板の凝固体である血栓が付着,および堆積してしまい,最終的に血管を塞栓してしまう問題が生じていた.そして,血栓による血流の阻害により人体に障害が残るばかりでなく,心筋梗塞や脳梗塞等,最悪の場合死に至る病につながる恐れもある.そのため,血液付着箇所に用いる医療器具の開発のためには,血栓が付着せず,体内における副作用が生じない材料の開発が,極めて重要な課題となっている.

参考文献

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第2章

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37. Koberstein, J. T.; Stein, R. S., Small-angle X-ray-scattering studies of microdomain structure in segmented polyurethane elastomers. Journal of Polymer Science Part B-Polymer Physics, 1983, 21, (8), 1439-1472.

38. Nozaki, S.; Masuda, S.; Kamitani, K.; Kojio, K.; Takahara, A.; Kuwarnura, G.; Hasegawa, D.; Moorthi, K.; Mita, K.; Yamasaki, S., Superior properties of polyurethane elastomers synthesized with aliphatic diisocyanate bearing a symmetric structure. Macromolecules, 2017, 50, (3), 1008-1015.

39. Xiang, D.; He, J.; Cui, T.; Liu, L.; Shi, Q. S.; Ma, L. C.; Liang, Y., Multiphase structure and electromechanical behaviors of aliphatic polyurethane elastomers. Macromolecules, 2018, 51, (16), 6369-6379.

40. Gaina, C.; Ursache, O.; Gaina, V.; Varganici, C. D., Thermally reversible cross-linked poly(ether- urethane)s. Express Polymer Letters, 2013, 7, (7), 636-650.

41. Carré, C.; Bonnet, L.; Avérous, L., Original biobased nonisocyanate polyurethanes: solvent- and catalyst-free synthesis, thermal properties and rheological behaviour. Rsc Advances, 2014, 4, (96), 54018-54025.

42. Murakami, D.; Mawatari, N.; Sonoda, T.; Kashiwazaki, A.; Tanaka, M., Effect of the molecular weight of poly(2-methoxyethyl acrylate) on interfacial structure and blood compatibility. Langmuir, 2019, 35, (7), 2808-2813.

43. Kobayashi, S.; Wakui, M.; Iwata, Y.; Tanaka, M., Poly(ω-methoxyalkyl acrylate)s: Nonthrombogenic polymer family with tunable protein adsorption. Biomacromolecules, 2017, 18, (12), 4214-4223.

44. Koguchi, R.; Jankova, K.; Tanabe, N.; Amino, Y.; Hayasaka, Y.; Kobayashi, D.; Miyajima, T.; Yamamoto, K.; Tanaka, M., Controlling the hydration structure with a small amount of fluorine to produce blood compatible fluorinated poly(2-methoxyethyl acrylate). Biomacromolecules, 2019, 20, (6), 2265-2275.

45. Xue, L.; Greisler, H. P., Biomaterials in the development and future of vascular grafts. Journal of Vascular Surgery, 2003, 37, (0741-5214 (Print)), 472-480.

46. Fang, Z.; Xiao, Y.; Geng, X.; Jia, L.; Xing, Y.; Ye, L.; Gu, Y.; Zhang, A.-y.; Feng, Z.-g., Fabrication of heparinized small diameter TPU/PCL bi-layered artificial blood vessels and in vivo assessment in a rabbit carotid artery replacement model. Biomaterials Advances, 2022, 133, 112628.

第3章

1. Chen, Y. L.; Kushner, A. M.; Williams, G. A.; Guan, Z. B., Multiphase design of autonomic self-healing thermoplastic elastomers. Nature Chemistry, 2012, 4, (6), 467-472.

2. Cordier, P.; Tournilhac, F.; Soulie-Ziakovic, C.; Leibler, L., Self-healing and thermoreversible rubber from supramolecular assembly. Nature, 2008, 451, (7181), 977-980.

3. Yan, M.; Tang, J.; Xie, H.-L.; Ni, B.; Zhang, H.-L.; Chen, E.-Q., Self-healing and phase behavior of liquid crystalline elastomer based on a block copolymer constituted of a side-chain liquid crystalline polymer and a hydrogen bonding block. Journal of Materials Chemistry C, 2015, 3, (33), 8526-8534.

4. Chan, B. Q. Y.; Liow, S. S.; Loh, X. J., Organic–inorganic shape memory thermoplastic polyurethane based on polycaprolactone and polydimethylsiloxane. Rsc Advances, 2016, 6, (41), 34946-34954.

5. Tazawa, S.; Maeda, T.; Nakayama, M.; Hotta, A., Synthesis of thermoplastic poly(2-methoxyethyl acrylate)-based polyurethane by RAFT and condensation polymerization. Macromolecular Rapid Communications, 2020, 41, (19), 2000346.

6. Tazawa, S.; Maeda, T.; Hotta, A., Mechanical, thermal, and microstructural analyses of thermoplastic poly(2-methoxyethyl acrylate)-based polyurethane by RAFT and polyaddition. Materials Advances, 2021, 2, (5), 1657-1664.

7. Aoki, D.; Ajiro, H., Design of polyurethane composed of only hard main chain with oligo(ethylene glycol) units as side chain simultaneously achieved high biocompatible and mechanical properties. Macromolecules, 2017, 50, (17), 6529-6538.

8. Nozaki, S.; Masuda, S.; Kamitani, K.; Kojio, K.; Takahara, A.; Kuwarnura, G.; Hasegawa, D.; Moorthi, K.; Mita, K.; Yamasaki, S., Superior properties of polyurethane elastomers synthesized with aliphatic diisocyanate bearing a symmetric structure. Macromolecules, 2017, 50, (3), 1008-1015.

9. Stefanović, I. S.; Spirkova, M.; Poreba, R.; Steinhart, M.; Ostojic, S.; Tesevic, V.; Pergal, M. V., Study of the properties of urethane-siloxane copolymers based on poly(propylene oxide)-b- poly(dimethylsiloxane)-b-poly(propylene oxide) soft segments. Industrial & Engineering Chemistry Research, 2016, 55, (14), 3960-3973.

10. Gaina, C.; Ursache, O.; Gaina, V.; Varganici, C. D., Thermally reversible cross-linked poly(ether- urethane)s. Express Polymer Letters, 2013, 7, (7), 636-650.

11. Fu, D.; Pu, W.; Wang, Z.; Lu, X.; Sun, S.; Yu, C.; Xia, H., A facile dynamic crosslinked healable poly(oxime-urethane) elastomer with high elastic recovery and recyclability. Journal of Materials Chemistry A, 2018, 6, (37), 18154-18164.

12. Rahmawati, R.; Nozaki, S.; Kojio, K.; Takahara, A.; Shinohara, N.; Yamasaki, S., Microphase-separated structure and mechanical properties of cycloaliphatic diisocyanate-based thiourethane elastomers. Polymer Journal, 2019, 51, (2), 265-273.

13. Sudo, A.; Hamaguchi, T.; Aoyagi, N.; Endo, T., RAFT-approach to well-defined telechelic vinyl polymers with hydroxyl terminals as polymeric diol-type building blocks for polyurethanes. Journal of Polymer Science Part a-Polymer Chemistry, 2013, 51, (2), 318-326.

14. Liu, X. L.; Yang, B.; Hou, Z. S.; Zhang, N.; Gao, Y. Y., A mild method for surface-grafting MPC onto poly(ester-urethane) based on aliphatic diurethane diisocyanate with high grafting efficiency. Materials Science & Engineering C-Materials for Biological Applications, 2019, 104, 109952.

15. Ye, S.; Morita, S.; Li, G. F.; Noda, H.; Tanaka, M.; Uosaki, K.; Osawa, M., Structural changes in poly(2- methoxyethyl acrylate) thin films induced by absorption of bisphenol A. An infrared and sum frequency generation (SFG) study. Macromolecules, 2003, 36, (15), 5694-5703.

16. Morita, S.; Tanaka, M.; Ozaki, Y., Time-resolved in situ ATR-IR observations of the process of sorption of water into a poly(2-methoxyethyl acrylate) film. Langmuir, 2007, 23, (7), 3750-3761.

17. Tang, C. Y. Y.; Kwon, Y. N.; Leckie, J. O., Effect of membrane chemistry and coating layer on physiochemical properties of thin film composite polyamide RO and NF membranes I. FTIR and XPS characterization of polyamide and coating layer chemistry. Desalination, 2009, 242, (1-3), 149-167.

18. Fukumaru, T.; Fujigaya, T.; Nakashima, N., Extremely high thermal resistive poly(p-phenylene benzobisoxazole) with desired shape and form from a newly synthesized soluble precursor. Macromolecules, 2012, 45, (10), 4247-4253.

19. Xu, Z. C.; Wang, X. Y.; Huang, H., Thermoplastic polyurethane-urea elastomers with superior mechanical and thermal properties prepared from alicyclic diisocyanate and diamine. Journal of Applied Polymer Science, 2020, 137, (48), 49575.

20. Xiang, D.; Liu, M.; Chen, G. L.; Zhang, T.; Liu, L.; Liang, Y. R., Optimization of mechanical and dielectric properties of poly(urethane urea)-based dielectric elastomers via the control of microstructure. Rsc Advances, 2017, 7, (88), 55610-55619.

21. Kojio, K.; Fukumaru, T.; Furukawa, M., Highly softened polyurethane elastomer synthesized with novel 1,2-bis(isocyanate)ethoxyethane. Macromolecules, 2004, 37, (9), 3287-3291.

22. Jena, K. K.; Chattopadhyay, D. K.; Raju, K., Synthesis and characterization of hyperbranched polyurethane-urea coatings. European Polymer Journal, 2007, 43, (5), 1825-1837.

23. Burattini, S.; Greenland, B. W.; Merino, D. H.; Weng, W.; Seppala, J.; Colquhoun, H. M.; Hayes, W.; Mackay, M. E.; Hamley, I. W.; Rowan, S. J., A healable supramolecular polymer blend based on aromatic π−π stacking and hydrogen-bonding interactions. Journal of the American Chemical Society, 2010, 132, (34), 12051-12058.

24. Babra, T. S.; Wood, M.; Godleman, J. S.; Salimi, S.; Warriner, C.; Bazin, N.; Siviour, C. R.; Hamley, I. W.; Hayes, W.; Greenland, B. W., Fluoride-responsive debond on demand adhesives: Manipulating polymer crystallinity and hydrogen bonding to optimise adhesion strength at low bonding temperatures. European Polymer Journal, 2019, 119, 260-271.

25. Adhikari, R.; Gunatillake, P. A.; Meijs, G. F.; McCarthy, S. J., The effect of diisocyanate isomer composition on properties and morphology of polyurethanes based on 4,4′-dicyclohexyl methane diisocyanate and mixed macrodiols (PDMS–PHMO). Journal of Applied Polymer Science, 1999, 73, (4), 573-582.

26. Higaki, Y.; Kiyoshima, Y.; Suzuki, K.; Kabayama, H.; Ohta, N.; Seo, Y.; Takahara, A., Elastomers built up through the π–π stacking association of polycyclic planar aromatic diimides. Rsc Advances, 2017, 7, (73), 46195-46200.

27. Kobayashi, S.; Wakui, M.; Iwata, Y.; Tanaka, M., Poly(ω-methoxyalkyl acrylate)s: Nonthrombogenic polymer family with tunable protein adsorption. Biomacromolecules, 2017, 18, (12), 4214-4223.

28. Koguchi, R.; Jankova, K.; Tanabe, N.; Amino, Y.; Hayasaka, Y.; Kobayashi, D.; Miyajima, T.; Yamamoto, K.; Tanaka, M., Controlling the hydration structure with a small amount of fluorine to produce blood compatible fluorinated poly(2-methoxyethyl acrylate). Biomacromolecules, 2019, 20, (6), 2265-2275.

29. Jankova, K.; Javakhishvili, I.; Kobayashi, S.; Koguchi, R.; Murakami, D.; Sonoda, T.; Tanaka, M., Hydration states and blood compatibility of hydrogen-bonded supramolecular poly(2-methoxyethyl acrylate). ACS Applied Bio Materials, 2019, 2, (10), 4154-4161.

30. Sato, K.; Kobayashi, S.; Kusakari, M.; Watahiki, S.; Oikawa, M.; Hoshiba, T.; Tanaka, M., The relationship between water structure and blood compatibility in poly(2-methoxyethyl acrylate) (PMEA) analogues. Macromolecular Bioscience, 2015, 15, (9), 1296-1303.

第4章

1. Arevalo-Alquichire, S.; Morales-Gonzalez, M.; Navas-Gomez, K.; Diaz, L. E.; Gomez-Tejedor, J. A.; Serrano, M. A.; Valero, M. F., Influence of polyol/crosslinker blend composition on phase separation and thermo-mechanical properties of polyurethane thin films. Polymers, 2020, 12, (3), 666.

2. Fukushima, K.; Honda, K.; Inoue, Y.; Tanaka, M., Synthesis of antithrombotic poly(carbonate- urethane)s through a sequential process of ring-opening polymerization and polyaddition facilitated by organocatalysts. European Polymer Journal, 2017, 95, 728-736.

3. Stefanović, I. S.; Spirkova, M.; Poreba, R.; Steinhart, M.; Ostojic, S.; Tesevic, V.; Pergal, M. V., Study of the properties of urethane-siloxane copolymers based on poly(propylene oxide)-b- poly(dimethylsiloxane)-b-poly(propylene oxide) soft segments. Industrial & Engineering Chemistry Research, 2016, 55, (14), 3960-3973.

4. Liu, X. L.; Yang, B.; Hou, Z. S.; Zhang, N.; Gao, Y. Y., A mild method for surface-grafting MPC onto poly(ester-urethane) based on aliphatic diurethane diisocyanate with high grafting efficiency. Materials Science & Engineering C-Materials for Biological Applications, 2019, 104, 109952.

5. Song, L.; Wei, W.; Farooq, M. A.; Xiong, H., Quasi-living copolymerization of aryl isocyanates and epoxides. ACS Macro Letters, 2020, 9, (11), 1542-1546.

6. Gudeangadi, P. G.; Sakamoto, T.; Shichibu, Y.; Konishi, K.; Nakano, T., Chiral polyurethane synthesis leading to π-stacked 2/1-helical polymer and cyclic compounds. ACS Macro Letters, 2015, 4, (9), 901- 906.

7. Lambeth, R. H.; Baranoski, M. H.; Savage, A. M.; Morgan, B. F.; Beyer, F. L.; Mantooth, B. A.; Zander, N. E., Synthesis and characterization of segmented polyurethanes containing trisaminocyclopropenium carbocations. ACS Macro Letters, 2018, 7, (7), 846-851.

8. Jia, Y. C.; Ying, H. Z.; Zhang, Y. F.; He, H.; Cheng, J. J., Reconfigurable poly(urea-urethane) thermoset based on hindered urea bonds with triple-shape-memory performance. Macromolecular Chemistry and Physics, 2019, 220, (12), 1900148.

9. Nozaki, S.; Masuda, S.; Kamitani, K.; Kojio, K.; Takahara, A.; Kuwarnura, G.; Hasegawa, D.; Moorthi, K.; Mita, K.; Yamasaki, S., Superior properties of polyurethane elastomers synthesized with aliphatic diisocyanate bearing a symmetric structure. Macromolecules, 2017, 50, (3), 1008-1015.

10. Zheng, N.; Fang, Z. Z.; Zou, W. K.; Zhao, Q.; Xie, T., Thermoset shape-memory polyurethane with intrinsic plasticity enabled by transcarbamoylation. Angewandte Chemie-International Edition, 2016, 55, (38), 11421-11425.

11. Couthouis, J.; Keul, H.; Moller, M., Telechelic poly(methyl acrylate)s as constituents for multiblock poly(urethane urea)s. Macromolecular Chemistry and Physics, 2016, 217, (1), 72-84.

12. Sudo, A.; Hamaguchi, T.; Aoyagi, N.; Endo, T., RAFT-approach to well-defined telechelic vinyl polymers with hydroxyl terminals as polymeric diol-type building blocks for polyurethanes. Journal of Polymer Science Part a-Polymer Chemistry, 2013, 51, (2), 318-326.

13. Tazawa, S.; Maeda, T.; Nakayama, M.; Hotta, A., Synthesis of thermoplastic poly(2-methoxyethyl acrylate)-based polyurethane by RAFT and condensation polymerization. Macromolecular Rapid Communications, 2020, 41, (19), 2000346.

14. Tazawa, S.; Maeda, T.; Hotta, A., Mechanical, thermal, and microstructural analyses of thermoplastic poly(2-methoxyethyl acrylate)-based polyurethane by RAFT and polyaddition. Materials Advances, 2021, 2, (5), 1657-1664.

15. Ye, S.; Morita, S.; Li, G. F.; Noda, H.; Tanaka, M.; Uosaki, K.; Osawa, M., Structural changes in poly(2- methoxyethyl acrylate) thin films induced by absorption of bisphenol A. An infrared and sum frequency generation (SFG) study. Macromolecules, 2003, 36, (15), 5694-5703.

16. Tang, C. Y. Y.; Kwon, Y. N.; Leckie, J. O., Effect of membrane chemistry and coating layer on physiochemical properties of thin film composite polyamide RO and NF membranes I. FTIR and XPS characterization of polyamide and coating layer chemistry. Desalination, 2009, 242, (1-3), 149-167.

17. Xu, Z. C.; Wang, X. Y.; Huang, H., Thermoplastic polyurethane-urea elastomers with superior mechanical and thermal properties prepared from alicyclic diisocyanate and diamine. Journal of Applied Polymer Science, 2020, 137, (48), 49575.

18. Xiang, D.; Liu, M.; Chen, G. L.; Zhang, T.; Liu, L.; Liang, Y. R., Optimization of mechanical and dielectric properties of poly(urethane urea)-based dielectric elastomers via the control of microstructure. Rsc Advances, 2017, 7, (88), 55610-55619.

19. Stefanović, I. S.; Dzunuzovic, J. V.; Dzunuzovic, E. S.; Dapcevic, A.; Seslija, S. I.; Balanc, B. D.; Dobrzynska-Mizera, M., Composition-property relationship of polyurethane networks based on polycaprolactone diol. Polymer Bulletin, 2021, 78, 7103-7128.

20. Inukai, S.; Kurokawa, N.; Hotta, A., Annealing and saponification of electrospun cellulose-acetate nanofibers used as reinforcement materials for composites. Composites Part a-Applied Science and Manufacturing, 2018, 113, 158-165.

21. Aoki, D.; Ajiro, H., Design of polyurethane composed of only hard main chain with oligo(ethylene glycol) units as side chain simultaneously achieved high biocompatible and mechanical properties. Macromolecules, 2017, 50, (17), 6529-6538.

22. Jena, K. K.; Chattopadhyay, D. K.; Raju, K., Synthesis and characterization of hyperbranched polyurethane-urea coatings. European Polymer Journal, 2007, 43, (5), 1825-1837.

23. Ha, H.; Park, J.; Ha, K.; Freeman, B. D.; Ellison, C. J., Synthesis and gas permeability of highly elastic poly(dimethylsiloxane)/graphene oxide composite elastomers using telechelic polymers. Polymer, 2016, 93, 53-60.

24. Creusen, G.; Roshanasan, A.; Garcia Lopez, J.; Peneva, K.; Walther, A., Bottom-up design of model network elastomers and hydrogels from precise star polymers. Polymer Chemistry, 2019, 10, (27), 3740- 3750.

25. Haraguchi, K.; Ebato, M.; Takehisa, T., Polymer-clay nanocomposites exhibiting abnormal necking phenomena accompanied by extremely large reversible elongations and excellent transparency. Advanced Materials, 2006, 18, (17), 2250-2254.

26. Tanaka, M.; Mochizuki, A., Effect of water structure on blood compatibility— thermal analysis of water in poly(meth)acrylate. Journal of Biomedical Materials Research Part A, 2004, 68A, (4), 684-695.

27. Murakami, D.; Mawatari, N.; Sonoda, T.; Kashiwazaki, A.; Tanaka, M., Effect of the molecular weight of poly(2-methoxyethyl acrylate) on interfacial structure and blood compatibility. Langmuir, 2019, 35, (7), 2808-2813.

28. Kobayashi, S.; Wakui, M.; Iwata, Y.; Tanaka, M., Poly(ω-methoxyalkyl acrylate)s: Nonthrombogenic polymer family with tunable protein adsorption. Biomacromolecules, 2017, 18, (12), 4214-4223.

29. Jankova, K.; Javakhishvili, I.; Kobayashi, S.; Koguchi, R.; Murakami, D.; Sonoda, T.; Tanaka, M., Hydration states and blood compatibility of hydrogen-bonded supramolecular poly(2-methoxyethyl acrylate). ACS Applied Bio Materials, 2019, 2, (10), 4154-4161.

30. Xue, L.; Greisler, H. P., Biomaterials in the development and future of vascular grafts. Journal of Vascular Surgery, 2003, 37, (0741-5214 (Print)), 472-480.

31. Fang, Z.; Xiao, Y.; Geng, X.; Jia, L.; Xing, Y.; Ye, L.; Gu, Y.; Zhang, A.-y.; Feng, Z.-g., Fabrication of heparinized small diameter TPU/PCL bi-layered artificial blood vessels and in vivo assessment in a rabbit carotid artery replacement model. Biomaterials Advances, 2022, 133, 112628.

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