JP4902162B2 - COMPOSITE MATERIAL MOLDED AND MANUFACTURING METHOD - Google Patents
COMPOSITE MATERIAL MOLDED AND MANUFACTURING METHOD Download PDFInfo
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- JP4902162B2 JP4902162B2 JP2005277702A JP2005277702A JP4902162B2 JP 4902162 B2 JP4902162 B2 JP 4902162B2 JP 2005277702 A JP2005277702 A JP 2005277702A JP 2005277702 A JP2005277702 A JP 2005277702A JP 4902162 B2 JP4902162 B2 JP 4902162B2
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- phosphorylcholine
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- polyethylene
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- 239000002131 composite material Substances 0.000 title claims description 40
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- 239000002245 particle Substances 0.000 claims description 56
- -1 polyethylene Polymers 0.000 claims description 44
- 239000004698 Polyethylene Substances 0.000 claims description 43
- 229920000573 polyethylene Polymers 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 29
- 238000000465 moulding Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 11
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical group FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- 238000003856 thermoforming Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 230000000704 physical effect Effects 0.000 claims description 3
- 239000000047 product Substances 0.000 description 44
- 238000000034 method Methods 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 10
- 229920000642 polymer Polymers 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000003825 pressing Methods 0.000 description 4
- NJNWCIAPVGRBHO-UHFFFAOYSA-N 2-hydroxyethyl-dimethyl-[(oxo-$l^{5}-phosphanylidyne)methyl]azanium Chemical group OCC[N+](C)(C)C#P=O NJNWCIAPVGRBHO-UHFFFAOYSA-N 0.000 description 3
- BGRPBGWHJMMIKL-UHFFFAOYSA-O FC(C(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F Chemical compound FC(C(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F BGRPBGWHJMMIKL-UHFFFAOYSA-O 0.000 description 3
- IUULUALVQOANRW-UHFFFAOYSA-O FC(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F Chemical compound FC(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F IUULUALVQOANRW-UHFFFAOYSA-O 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229920000098 polyolefin Polymers 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- JJUBFBTUBACDHW-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanol Chemical compound OCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F JJUBFBTUBACDHW-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- ZXHFAJOIPYRNBU-UHFFFAOYSA-O FC(C(C(C(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F Chemical compound FC(C(C(C(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F ZXHFAJOIPYRNBU-UHFFFAOYSA-O 0.000 description 2
- JUQYTKQJWUAZSF-UHFFFAOYSA-O FC(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F Chemical compound FC(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F JUQYTKQJWUAZSF-UHFFFAOYSA-O 0.000 description 2
- 208000034699 Vitreous floaters Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000560 biocompatible material Substances 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 229920005672 polyolefin resin Polymers 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000009864 tensile test Methods 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- UFOVZASHPZGDNP-UHFFFAOYSA-O 2-[hydroxy(methoxy)phosphoryl]oxyethyl-trimethylazanium Chemical compound COP(O)(=O)OCC[N+](C)(C)C UFOVZASHPZGDNP-UHFFFAOYSA-O 0.000 description 1
- GRJRKPMIRMSBNK-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctan-1-ol Chemical compound OCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F GRJRKPMIRMSBNK-UHFFFAOYSA-N 0.000 description 1
- FLXYIZWPNQYPIT-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-henicosafluorododecan-1-ol Chemical compound OCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F FLXYIZWPNQYPIT-UHFFFAOYSA-N 0.000 description 1
- PKZMNAHODCQIOH-UHFFFAOYSA-N FC(C(C(C(C(C(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)OC(C[N+](C)(C)C)=P(=O)CC Chemical compound FC(C(C(C(C(C(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)OC(C[N+](C)(C)C)=P(=O)CC PKZMNAHODCQIOH-UHFFFAOYSA-N 0.000 description 1
- UYXDBSUBGGBPGO-UHFFFAOYSA-O FC(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F Chemical compound FC(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F UYXDBSUBGGBPGO-UHFFFAOYSA-O 0.000 description 1
- SFTTWCSEGLDPBZ-UHFFFAOYSA-O FC(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F Chemical compound FC(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(CCP(=O)=C(O)C[N+](C)(C)C)F SFTTWCSEGLDPBZ-UHFFFAOYSA-O 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007930 Oxalis acetosella Species 0.000 description 1
- 235000008098 Oxalis acetosella Nutrition 0.000 description 1
- 230000003373 anti-fouling effect Effects 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- URAZVWXGWMBUGJ-UHFFFAOYSA-N di(propan-2-yl)azanium;chloride Chemical compound [Cl-].CC(C)[NH2+]C(C)C URAZVWXGWMBUGJ-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 238000007561 laser diffraction method Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000000790 scattering method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Compositions Of Macromolecular Compounds (AREA)
Description
本発明は、生体適合性に優れ、医療用具やセンサー、化粧品容器、生化学関係の分析容器等に利用可能な、ホスホリルコリン類似基含有構成単位を有する化合物を配合した複合材料成形物及びその製造方法に関する。 The present invention provides a composite material molded with a compound having a phosphorylcholine-like group-containing structural unit, which is excellent in biocompatibility and can be used in medical devices, sensors, cosmetic containers, biochemical-related analysis containers, and the like, and a method for producing the same About.
ホスホリルコリン類似基含有化合物は、生体膜に由来するリン脂質類似構造に起因して、血液成分不活性化、生体物質非吸着性等の生体適合性に優れること、また防汚性、保湿性等において優れた性質を有することが知られている。そして、これらの機能を生かした生体関連材料の開発を目的としたホスホリルコリン類似基含有重合体の合成及びその用途に関する研究開発が活発に行われており、ホスホリルコリン類似基含有重合体を含む素材の検討もいくつかなされている。
ホスホリルコリン類似基含有化合物と、通常の樹脂とを用いた生体適合性成形物としては、例えば、特許文献１及び非特許文献１に、樹脂成形物基材の表面に生体適合性を有するホスホリルコリン類似基含有重合体等をコーティングする方法が提案されている。
しかし、上記コーティングする方法は、生体適合性材料と基材との密着力が十分でなく、生体適合性材料が基材から剥離したり、溶出する恐れがある。加えて、基材へのコーティング工程という作業工程が追加で必要となり、実際の製造においては作業コストに大きく影響する。
Phosphorylcholine-like group-containing compounds are superior in biocompatibility such as inactivation of blood components and non-adsorption of biological substances due to the phospholipid-like structure derived from biological membranes, and in antifouling properties, moisture retention, etc. It is known to have excellent properties. Research and development related to the synthesis and use of phosphorylcholine-like group-containing polymers for the purpose of developing bio-related materials that make use of these functions has been actively conducted. Some have been made too.
Examples of the biocompatible molded article using a phosphorylcholine-like group-containing compound and a normal resin include, for example, Patent Document 1 and Non-Patent Document 1, and a phosphorylcholine-like group having biocompatibility on the surface of a resin molded article substrate. A method for coating a containing polymer or the like has been proposed.
However, the coating method does not have sufficient adhesion between the biocompatible material and the substrate, and the biocompatible material may be peeled off or eluted from the substrate. In addition, an additional work process called a coating process on the base material is required, which greatly affects the work cost in actual production.
そこで、このような問題を解消するために、ホスホリルコリン類似基含有化合物を機械的特性に優れる他の重合体にブレンドして利用する技術が検討されている。
例えば、特許文献２には、ホスホリルコリン類似基含有重合体と種々の重合体とのブレンドに関する技術が開示されており、ホスホリルコリン類似基含有重合体とポリオレフィンをそれぞれ粉体状で混合しプレス成型する方法が開示されている。
しかし、ホスホリルコリン類似基含有重合体は、極性が非常に高いため、極性の小さなポリオレフィンへは表面にホスホリルコリン基が生態適合性を発現するに十分な量となるまで添加することが困難であり、前記プレス成型方法では、重合体の分子レベルでの混合が進行しないため、十分な力学的強度を有するブレンド成型物が得られない。
また、特許文献３には、ホスホリルコリン類似基含有重合体とポリオレフィン複合材料とを有機溶媒に溶解してブレンドした後、成型する方法が開示されている。
しかし、該方法では、有機溶媒を使用するために、製造設備に局所排気能力の付与など大きな制約を受ける。また、成型体中に該有機溶媒が残留する可能性がある。更に、ブレンドしたホスホリルコリン基には、表面配向性がないために成型体の表面上においてホスホリルコリン基の機能を発現させるためには、ホスホリルコリン類似基含有重合体を多量にブレンドする必要がある。
For example, Patent Document 2 discloses a technique relating to a blend of a phosphorylcholine-like group-containing polymer and various polymers, and a method of mixing and pressing each of the phosphorylcholine-like group-containing polymer and polyolefin in powder form. Is disclosed.
However, since the phosphorylcholine-like group-containing polymer has a very high polarity, it is difficult to add to a polyolefin with a small polarity until the phosphorylcholine group has a sufficient amount to express biocompatibility on the surface. In the press molding method, since the mixing of the polymer at the molecular level does not proceed, a blend molded product having sufficient mechanical strength cannot be obtained.
Patent Document 3 discloses a method in which a phosphorylcholine-like group-containing polymer and a polyolefin composite material are dissolved in an organic solvent, blended, and then molded.
However, in this method, since an organic solvent is used, there are significant restrictions such as giving a local exhaust capacity to the production facility. In addition, the organic solvent may remain in the molded body. Further, since the blended phosphorylcholine group does not have surface orientation, it is necessary to blend a large amount of the phosphorylcholine-like group-containing polymer in order to express the function of the phosphorylcholine group on the surface of the molded body.
本発明の課題は、ホスホリルコリン類似基含有化合物に基づく生体適合性を有するとともに、ポリエチレンの適度な強度を有する複合材料成形物を提供することにある。
本発明の別の課題は、ホスホリルコリン類似基含有化合物に基づく生体適合性を有するとともに、ポリエチレンの適度な強度を有する複合材料成形物を、簡易な工程により、また、ホスホリルコリン類似基含有化合物の割合を低減しても所望の生体適合性を付与することができる複合材料成形物の製造方法を提供することにある。
Object of the present invention has a biocompatibility that is based on phosphorylcholine-like group-containing compound, to provide a composite molded product having a moderate strength of poly ethylene.
Another object of the present invention, the proportion of which has a biocompatible based on phosphorylcholine-like group-containing compound, a composite material molded product having a moderate strength of poly ethylene, by a simple process, also, phosphorylcholine-like group-containing compound An object of the present invention is to provide a method for producing a composite material molded product that can impart desired biocompatibility even when the amount of the material is reduced.
本発明者らは、上記課題を解決するために鋭意検討した結果、特定のフッ化炭素基を有するホスホリルコリン類似基含有化合物と特定平均粒子径のポリオレフィン系樹脂粒子とを用い、混合後、加熱・加圧成形することにより、生体適合性に優れ、力学的強度に優れた性質を有する複合材料成形物が得られるとの知見を得て、本発明を完成するに至った。 As a result of intensive studies to solve the above problems, the present inventors have used a phosphorylcholine-like group-containing compound having a specific fluorocarbon group and a polyolefin-based resin particle having a specific average particle size, mixed, heated and heated. Obtaining the knowledge that a composite material molded product having excellent biocompatibility and excellent mechanical strength can be obtained by pressure molding, the present invention has been completed.
本発明によれば、式(１)で表されるフッ化炭素鎖を含むホスホリルコリン類似基含有化合物（以下、化合物(PC)と略すことがある）と、平均粒径１〜１０μmのポリエチレン粒子とを、質量比で１：１〜２０で含む複合材料を１００〜１８０℃で加熱・加圧成形して得た複合材料成形物であって、上記複合材料を１００〜１８０℃で加熱・加圧してフィルム状に成形した際の該フィルムの破断強度が１０ＭＰａ以上１７ＭＰａ以下、破断伸びが２０％以上７５％以下及び表面接触角値が５°以上３０°以下の物性を有する複合材料成形物が提供される。
また本発明によれば、上記化合物(PC)と、平均粒径１〜１０μmのポリエチレン粒子とを、質量比で１：１〜２０で含む複合材料を混合する工程(a)と、工程(a)で得られた混合物を１００〜１８０℃で加圧・加熱成形する工程(b)とを含むことを特徴とする上記複合材料成形物の製造方法が提供される。
According to the present invention, a phosphorylcholine-like group-containing compound containing a fluorocarbon chain represented by formula (1) (hereinafter sometimes abbreviated as compound (PC)) and polyethylene particles having an average particle diameter of 1 to 10 μm A composite material obtained by heating and pressure- molding a composite material containing a child at a mass ratio of 1: 1 to 20 at 100 to 180 ° C., wherein the composite material is heated at 100 to 180 ° C. Composite material molded article having physical properties such that the film has a breaking strength of 10 MPa to 17 MPa, a breaking elongation of 20% to 75%, and a surface contact angle value of 5 ° to 30 ° when pressed into a film . Is provided.
According to the invention, the step (a) of mixing the composite material containing the compound (PC) and polyethylene particles having an average particle diameter of 1 to 10 μm in a mass ratio of 1: 1 to 20 and the step ( and a step (b) of pressing and thermoforming the mixture obtained in a) at 100 to 180 ° C. to provide a method for producing the above composite material molded product.
本発明の複合材料成形物は、化合物(PC)と特定粒径のポリエチレン粒子とを含む複合材料を特定方法等によって成形した、所定の物性を有する成形物であるので、例えば、血小板に対する活性がほとんど無く、生体適合性を有するとともに、適度な強度を有する。従って、本発明の複合材料成形物は、生化学容器等の分野への利用や、医療用具に好適である。
本発明の製造方法は、前記工程(a)及び工程(b)を含むので、本発明の複合材料成形物を容易に得ることができ、また、製造時において、化合物(PC)が得られる成形物の表面に濃縮されるため、化合物(PC)の使用量を十分に低減することができる。
Since composite molded product of the present invention, a composite material comprising a compound (PC) and poly ethylene particles of a particular particle size was molded by a particular method and the like, a molded product having a predetermined physical properties, for example, activity against platelet There is almost no, and it has biocompatibility and moderate strength. Therefore, the composite material molded product of the present invention is suitable for use in the field of biochemical containers and the like and for medical devices.
Since the production method of the present invention includes the step (a) and the step (b), the composite material molded product of the present invention can be easily obtained, and molding in which the compound (PC) is obtained at the time of production. Since it is concentrated on the surface of the product, the amount of compound (PC) used can be sufficiently reduced.
以下、本発明を更に詳細に説明する。
本発明の複合材料成形物は、上記式(1)で示される化合物(PC)と、特定平均粒径のポリエチレン粒子とを特定割合で含む複合材料を特定温度範囲で加熱・加圧成形して得たものであって、上記複合材料を１００〜１８０℃で加熱・加圧してフィルム状に成形した際の該フィルムの破断強度１０ＭＰａ以上、破断伸び２０％以上、表面接触角値３０°以下、好ましくは２５°以下である。
破断強度及び破断伸びの上限は特に限定されないが、破断強度の上限は通常１７ＭＰａ程度であり、破断伸びの上限は通常７５％程度である。また、表面接触角値の下限は特に限定されないが、通常５°程度である。
表面接触角値は、本発明の成形物表面における、化合物(PC)に係るホスホリルコリン類似基の割合の目安となり、該値が大きいほどホスホリルコリン類似基の成形物表面における割合が小さくなる。従って、表面接触角値が２７°を超える場合には、成形物の化合物(PC)に係る所望の効果が得られない恐れがある。
Hereinafter, the present invention will be described in more detail.
The composite material molded product of the present invention is obtained by heating and pressure-molding a composite material containing a compound (PC) represented by the above formula (1) and polyethylene particles having a specific average particle diameter in a specific ratio within a specific temperature range. It was obtained, and when the composite material was heated and pressed at 100 to 180 ° C. to form a film, the breaking strength of the film was 10 MPa or more, the breaking elongation was 20% or more, the surface contact angle value was 30 ° or less, Preferably it is 25 degrees or less.
The upper limits of breaking strength and breaking elongation are not particularly limited, but the upper limit of breaking strength is usually about 17 MPa, and the upper limit of breaking elongation is usually about 75%. The lower limit of the surface contact angle value is not particularly limited, but is usually about 5 °.
The surface contact angle value is a measure of the ratio of phosphorylcholine-like groups related to the compound (PC) on the surface of the molded article of the present invention, and the larger the value, the smaller the ratio of phosphorylcholine-like groups on the molded article surface. Therefore, when the surface contact angle value exceeds 27 °, there is a possibility that the desired effect relating to the compound (PC) of the molded product cannot be obtained.
上記式(1)において、Ｒ1、Ｒ2及びＲ3はメチル基を示す。lは５〜２０の整数、好ましくは７〜１７の整数を示す。ｍ及びnは１又は２を示す。ここで、lが４以下の整数の場合は、フッ化炭素鎖の性能を十分に発現することができず、したがって得られる成形物の表面接触角値が低くならない。一方、lが２１以上の整数の場合は、ポリオレフィン系樹脂粒子との相溶性が悪いため十分な強度を持つ成形物が得られ難い。また、ｍ又はｎが３以上の場合には製造が困難である。 In the above formula (1), R 1 , R 2 and R 3 represent a methyl group . l represents an integer of 5 to 20, preferably an integer of 7 to 17. m and n represent 1 or 2. Here, when l is an integer of 4 or less, the performance of the fluorocarbon chain cannot be sufficiently exhibited, and thus the surface contact angle value of the obtained molded product does not become low. On the other hand, when l is an integer of 21 or more, it is difficult to obtain a molded product having sufficient strength because of poor compatibility with polyolefin resin particles. Further, when m or n is 3 or more, the production is difficult.
化合物(PC)としては、例えば、２−(パーフルオロヘキシル)メチルホスホリルコリン、２−(パーフルオロヘキシル)エチルホスホリルコリン、２−(パーフルオロヘプチル)メチルホスホリルコリン、２−(パーフルオロヘプチル)エチルホスホリルコリン、２−(パーフルオロオクチル)メチルホスホリルコリン、２−(パーフルオロオクチル)エチルホスホリルコリン、２−(パーフルオロノニル)メチルホスホリルコリン、２−(パーフルオロノニル)エチルホスホリルコリン、２−(パーフルオロデシル)メチルホスホリルコリン、２−(パーフルオロデシル)エチルホスホリルコリン、２−(パーフルオロドデシル)メチルホスホリルコリン、２−(パーフルオロドデシル)エチルホスホリルコリン、２−(パーフルオロテトラデシル)メチルホスホリルコリン、２−(パーフルオロテトラデシル)エチルホスホリルコリン、２−(パーフルオロオクタデシル)メチルホスホリルコリン、２−(パーフルオロオクタデシル)エチルホスホリルコリン等を挙げることができる。中でも２−(パーフルオロオクチル)エチルホスホリルコリン、２−(パーフルオロデシル)エチルホスホリルコリン、２−(パーフルオロドデシル)エチルホスホリルコリンが原料の入手性、合成のし易さ及び生体適合性を付与する点から好ましい。これらを複合材料に配合する場合は、１種でも、また２種以上の混合物として配合することができる。
前記化合物(PC)は、例えば、特開２０００−３５５５９４号公報等の記載に準じて合成することができる。
Examples of the compound (PC) include 2- (perfluorohexyl) methyl phosphorylcholine, 2- (perfluorohexyl) ethyl phosphorylcholine, 2- (perfluoroheptyl) methyl phosphorylcholine, 2- (perfluoroheptyl) ethyl phosphorylcholine, 2 -(Perfluorooctyl) methyl phosphorylcholine, 2- (perfluorooctyl) ethyl phosphorylcholine, 2- (perfluorononyl) methyl phosphorylcholine, 2- (perfluorononyl) ethyl phosphorylcholine, 2- (perfluorodecyl) methyl phosphorylcholine, 2 -(Perfluorodecyl) ethyl phosphorylcholine, 2- (perfluorododecyl) methyl phosphorylcholine, 2- (perfluorododecyl) ethyl phosphorylcholine, 2- (perfluorotetradecyl) methyl phosphorylcholine, 2 It can be mentioned (perfluoro tetradecyl) ethyl phosphorylcholine, 2- (perfluoro octadecyl) methyl phosphorylcholine, 2- (perfluoro-octadecyl) ethyl phosphoryl choline. Among them, 2- (perfluorooctyl) ethyl phosphorylcholine, 2- (perfluorodecyl) ethyl phosphorylcholine, and 2- (perfluorododecyl) ethyl phosphorylcholine provide raw material availability, ease of synthesis, and biocompatibility. preferable. When these are blended in the composite material, they can be blended as one kind or as a mixture of two or more kinds.
The compound (PC) can be synthesized, for example, according to the description in JP-A No. 2000-355594.
前記複合材料に用いるポリエチレン粒子の分子量は、特に限定されないが、相溶性、力学的強度、成形性等の観点から、通常、数平均分子量で１０００〜１００００００の範囲、特に３０００〜５０００００の範囲が好ましい。 The molecular weight of the poly ethylene particles used in the composite material is not particularly limited, compatibility, mechanical strength, in view of formability and the like, usually in the range of 1,000 to 1,000,000 in number average molecular weight, in particular in the range of from 3,000 to 500,000 Is preferred.
ポリエチレン粒子の粒径は、相溶性の観点から、平均粒径１〜１０μmである。平均粒径が２０μｍを超える場合には、得られる成形物の機械的強度及び生体適合性が低下する恐れが高くなる。
ここで、平均粒径とは、レーザー回折・散乱法により測定される粒径の累積分布におけるメディアン系(中位系)と定義される。
The particle size of the poly ethylene particles, in view of compatibility, an average particle diameter of 1 to 10 [mu] m. When the average particle size exceeds 20 μm, the mechanical strength and biocompatibility of the resulting molded product are likely to be reduced.
Here, the average particle diameter is defined as a median system (medium system) in a cumulative distribution of particle diameters measured by a laser diffraction / scattering method.
前記ポリエチレン粒子としては市販品等を用いることができ、該市販品としては、例えば、Shamrock Technologies社製の商品名「Cera PURE H5-C」(ポリエチレン、平均粒径４〜５μｍ)、「Cera PURE H10-C」(ポリエチレン、平均粒径９〜１２μｍ)、「Cera PURE H20-Ｃ」(ポリエチレン、平均粒径１２〜２０μｍ)、「Tex PURE 100E」(ポリエチレン、平均粒径１８μｍ)、HONEYWELL INTERNATIONAL社製の商品名「ACumistA-6」(ポリエチレン、平均粒径６μｍ)、「ACumistA-12」(ポリエチレン、平均粒径１２μｍ)、「ACumistA-18」(ポリエチレン、平均粒径１８μｍ)、「ACumistB-6」(ポリエチレン、平均粒径６μｍ)、「ACumistB-9」(ポリエチレン、平均粒径９μｍ)、「ACumistB-12」(ポリエチレン、平均粒径１２μｍ)、「ACumist B-18」(ポリエチレン、平均粒径１８μｍ)、「ACumist C-5」(ポリエチレン、平均粒径５μｍ)、「ACumist C-12」(ポリエチレン、平均粒径１２μｍ)、「ACumist C-18」(ポリエチレン、平均粒径１８μｍ)、「ACumist D-5」(ポリエチレン、平均粒径５μｍ)、「ACumist D-9」(ポリエチレン、平均粒径９μｍ)、住友精化株式会社製の商品名「フローセンUF-1.5」(ポリエチレン、平均粒径１０〜２０μｍ)、「フローセンUF-4」(ポリエチレン、平均粒径１５〜２５μｍ)、「フロービーズLE1080」(ポリエチレン、平均粒径６μｍ)、「フロービーズLE-2080」(ポリエチレン、平均粒径１２μｍ)、「フロービーズHE-3040」(ポリエチレン、平均粒径１２μｍ)、「フロービーズCL-2080」(ポリエチレン、平均粒径１２μｍ)等が挙げられる。 A commercial item etc. can be used as said polyethylene particle, As this commercial item, for example, the brand name "Cera PURE H5-C" (polyethylene, average particle diameter of 4-5 micrometers) by Shamrock Technologies, "Cera PURE" “H10-C” (polyethylene, average particle size 9-12 μm), “Cera PURE H20-C” (polyethylene, average particle size 12-20 μm), “Tex PURE 100E” (polyethylene, average particle size 18 μm), HONEYWELL INTERNATIONAL “ACumistA-6” (polyethylene, average particle size 6 μm), “ACumistA-12” (polyethylene, average particle size 12 μm), “ACumistA-18” (polyethylene, average particle size 18 μm), “ACumistB-6” "(Polyethylene, average particle size 6μm)," ACumistB-9 "(polyethylene, average particle size 9μm)," ACumistB-12 "(polyethylene, average particle size 12μm)," ACumist B-18 "(polyethylene, average particle size) 18μm), “ACumist C-5” (polyethylene, average grain) 5 μm), “ACumist C-12” (polyethylene, average particle size 12 μm), “ACumist C-18” (polyethylene, average particle size 18 μm), “ACumist D-5” (polyethylene, average particle size 5 μm), “ACumist D-9 ”(polyethylene, average particle size 9 μm), trade name“ Flusen UF-1.5 ”(polyethylene, average particle size 10-20 μm),“ Flusen UF-4 ”(polyethylene, average particle size) manufactured by Sumitomo Seika Co., Ltd. "Flow beads LE1080" (polyethylene, average particle size 6 μm), "Flow beads LE-2080" (polyethylene, average particle size 12 µm), "Flow beads HE-3040" (polyethylene, average particle size 12 μm), “flow beads CL-2080” (polyethylene, average particle size 12 μm), and the like.
前記複合材料において、化合物(PC)とポリエチレン粒子との割合は、質量比で１：１〜２０、好ましくは１：５〜１０である。化合物(PC)１質量部に対するポリエチレン粒子の割合が１質量部未満の場合には、得られる成形物の機械的強度が低下する恐れがあり、一方、２０質量部を超える場合には、得られる成形物の生体適合性が低下する恐れがある。 In the composite material, the proportion of the compound (PC) and poly ethylene particles, 1 mass ratio: 1 to 20, preferably from 1: 5 to 10. If the proportion of the poly ethylene particles is less than 1 part by weight relative to compound (PC) 1 part by mass, there is a possibility that the mechanical strength of the molded product obtained is lowered, whereas, if it exceeds 20 parts by weight, obtained There is a risk that the biocompatibility of the molded product may be reduced.
本発明の成形物は、前記複合材料を成形することにより得られるが、その好ましい成形方法としては、以下に示す本発明の製造方法を参照して行うことができる。 The molded product of the present invention can be obtained by molding the composite material, and a preferable molding method can be performed with reference to the production method of the present invention described below.
本発明の複合材料成形物を製造するには、後述する工程(a)及び工程(b)を含む本発明の製造方法等により得ることができる。
本発明の製造方法は、上記化合物(PC)と、平均粒径１〜１０μmのポリエチレン粒子とを、質量比で１：１〜２０で含む複合材料を混合する工程(a)を含む。
工程(a)において、複合材料の混合は、例えば、乳鉢やミル等を用いて均一になるように混合することにより行うことができる。該混合においては、ポリエチレン粒子の摩擦熱による熱融着を防ぐために、複合材料の混合物温度が５０℃以下となるような環境で混合することが好ましい。
The composite material molded article of the present invention can be obtained by the production method of the present invention including the steps (a) and (b) described later.
Production method of the present invention, the compound (PC), and a poly ethylene particles having an average particle size. 1 to 10 [mu] m, 1 in weight ratio: comprising mixing a composite material comprising 1 to 20 with (a).
In the step (a), the composite material can be mixed by, for example, mixing uniformly using a mortar, a mill, or the like. In the mixing, in order to prevent thermal fusion due to frictional heat of poly ethylene particles, it is preferable that the mixture temperature of the composite material is mixed in an environment such that 50 ° C. or less.
本発明の製造方法は、上記工程(a)で得られた混合物を加圧・加熱成形する工程(b)を含む。
工程(b)において、加圧・加熱成形の条件は適宜選択することができる。該条件における加熱は、良好な成形性を容易に得る観点から、通常、１００〜１８０℃で３０秒〜1時間、特に、１２０〜１５０℃で３〜３０分間の条件により行うことが好ましい。加熱温度が１００℃未満では、ポリエチレン粒子の成形時の融着が不十分となり、得られる成形物の強度が低下する恐れがあり、１８０℃を超えると、短時間であっても化合物(PC)のホスホリルコリン類似基が劣化し、所望の生体適合性が得られない恐れがある。一方、加熱時間が３０秒間未満の場合は、ポリエチレン粒子の成形時の融着が不十分となり、得られる成形物の強度が低下する恐れがあり、１時間を超えるとポリエチレンと化合物(PC)とが相分離し、得られる成形物の表面における機能が十分に発現しない恐れがある。
The production method of the present invention includes a step (b) of pressing and thermoforming the mixture obtained in the step (a).
In the step (b), the conditions for pressing and thermoforming can be appropriately selected. From the viewpoint of easily obtaining good moldability, the heating under these conditions is usually preferably performed at 100 to 180 ° C. for 30 seconds to 1 hour, particularly at 120 to 150 ° C. for 3 to 30 minutes. The heating temperature is lower than 100 ° C., fusion during molding of poly ethylene particles is insufficient, there is a possibility that the strength of the molded product obtained is lowered, and when it exceeds 180 ° C., even for a short time compound (PC ) Of the phosphorylcholine-like group may deteriorate, and the desired biocompatibility may not be obtained. On the other hand, if the heating time is less than 30 seconds, fused in molding of poly ethylene particles is insufficient, there is a possibility that the strength of the molded product obtained is lowered, more than 1 hours and poly ethylene compound (PC ) And the functions on the surface of the resulting molded product may not be sufficiently developed.
工程(b)において成形は、公知のいずれの成形方法であっても良く、例えば、プレス成形法、押し出し成形法、射出成形法、ロール成形法等が挙げられ、成形時の圧力は成形物の形態、成形方法に応じて適宜選択することができる。
工程(b)における成形は、例えば、得られる成形物の形態に応じて適宜選択でき、該形態としては、フィルム状、糸状、棒状、メッシュ状、チューブ状、バッグ状等が挙げられる。
In the step (b), the molding may be any known molding method, for example, a press molding method, an extrusion molding method, an injection molding method, a roll molding method, and the like. It can select suitably according to a form and a shaping | molding method.
The molding in the step (b) can be appropriately selected according to, for example, the form of the molded product to be obtained, and examples of the form include a film shape, a thread shape, a rod shape, a mesh shape, a tube shape, and a bag shape.
本発明の複合材料成形物は、前述のとおり、生体適合性と機械的強度とをあわせ持つので、例えば、医療用具や、化粧品容器及び生化学関係の分析容器等のさまざまな分野の容器等として使用可能である。特に、生化学関係の分析容器等のディスポーザーブル用途の容器として好適である。 Since the composite material molded product of the present invention has both biocompatibility and mechanical strength as described above, for example, as a medical device, a container for various fields such as a cosmetic container and a biochemical-related analysis container, etc. It can be used. In particular, it is suitable as a disposable container such as a biochemical analysis container.
以下、合成例、実施例及び比較例により本発明を更に詳しく説明するが本発明はこれらに限定されない。
合成例１
300mlの四つ口フラスコに、１−ヘキサデカノール12.12g(0.05モル)、ジイソプロピルアミン5.05g(0.05モル)及びテトラヒドロフラン120mlを加えて撹拌しながら０℃に冷却した。２−クロロ−２−オキソ−１，３，２−ジオキサホスホラン7.14g (0.05モル)をテトラヒドロフラン25mlに溶解し、得られた溶液を、前記フラスコに滴下ロートを用いて滴下した。滴下終了後、反応混合物を昇温して室温で２時間反応を継続させた。副生成物として析出したジイソプロピルアミン塩酸塩を濾別した。濾液を耐圧びんに移し替え、アセトニトリル150mlとトリメチルアミン4.43g(0.075モル)を加えて密栓し、８０℃で５時間反応し、さらに室温で一晩反応させ、反応を終了させた。過剰のトリメチルアミンを留去し冷却後、析出した結晶を濾別し、エタノール及びジエチルエーテルを用いて再結晶を行い、さらに真空乾燥して目的とする生成物9.1gを得た。
EXAMPLES Hereinafter, although a synthesis example, an Example, and a comparative example demonstrate this invention further in detail, this invention is not limited to these.
Synthesis example 1
To a 300 ml four-necked flask, 12.12 g (0.05 mol) of 1-hexadecanol, 5.05 g (0.05 mol) of diisopropylamine and 120 ml of tetrahydrofuran were added and cooled to 0 ° C. with stirring. 2-Chloro-2-oxo-1,3,2-dioxaphosphorane (7.14 g, 0.05 mol) was dissolved in 25 ml of tetrahydrofuran, and the resulting solution was added dropwise to the flask using a dropping funnel. After completion of the dropwise addition, the reaction mixture was heated and the reaction was continued at room temperature for 2 hours. Diisopropylamine hydrochloride precipitated as a by-product was filtered off. The filtrate was transferred to a pressure bottle, 150 ml of acetonitrile and 4.43 g (0.075 mol) of trimethylamine were added and sealed, reacted at 80 ° C. for 5 hours, and further reacted at room temperature overnight to complete the reaction. Excess trimethylamine was distilled off, and after cooling, the precipitated crystals were separated by filtration, recrystallized using ethanol and diethyl ether, and further vacuum dried to obtain 9.1 g of the desired product.
得られた生成物を、1H−NMR及び31P−NMRにより測定した結果を以下に示す。これらの結果から得られた生成物は、１−ヘキサデシルホスホリルコリン(以下、C16-PCと略す)であることが判った。得られた生成物と、該生成物の分子内のフッ化炭素鎖数を表１に示す。
1H−NMR(CDCl3、内部標準TMS)：δ＝0.88(t，3H，CH3)、1.25(m，26H，(CH2)13)、1.57(m，2H，OCH2CH2)、3.40(s，9H，+N(CH3)3)、3.76−3.88(m，4H，CH2N+，CH2OP)、4.27(br，2H，POCH2)。
31P−NMR(CDCl3、外部標準H3PO4)：δ＝0.54
The results of measuring the obtained product by 1 H-NMR and 31 P-NMR are shown below. The product obtained from these results was found to be 1-hexadecylphosphorylcholine (hereinafter abbreviated as C16-PC). Table 1 shows the obtained product and the number of fluorocarbon chains in the molecule of the product.
1 H-NMR (CDCl 3 , internal standard TMS): δ = 0.88 (t, 3H, CH 3 ), 1.25 (m, 26 H, (CH 2 ) 13 ), 1.57 (m, 2H, OCH 2 CH 2 ), 3.40 (s, 9H, + N (CH 3) 3), 3.76-3.88 (m, 4H, CH 2 N +, CH 2 OP), 4.27 (br, 2H, POCH 2).
31 P-NMR (CDCl 3 , external standard H 3 PO 4 ): δ = 0.54
合成例２
300ml四つ口フラスコに２−(パーフルオロヘキシル)エタノール16.38g(0.045モル)、トリエチルアミン4.55g(0.045モル)及びテトラヒドロフラン120mlを加えて撹拌しながら０℃に冷却した。２−クロロ−２−オキソ−１，３，２−ジオキサホスホラン6.43g(0.045モル)をテトラヒドロフラン25mlに溶解し、得られた溶液を前記フラスコに滴下ロートを用いて滴下した。滴下終了後、反応混合物を昇温して室温で２時間反応を継続させた。副生成物として析出したトリエチルアミン塩酸塩を濾別した。濾液を耐圧びんに移し替え、アセトニトリル100mlとトリメチルアミン7.08g(0.12モル)とを加えて密栓し、８０℃で５時間反応させ、さらに室温で一晩反応させ、反応を終了させた。過剰のトリメチルアミンを留去し冷却後、析出した結晶を濾別し、さらにアセトン及びジエチルエーテルを用いて洗浄を行い、真空乾燥して生成物14.1gを得た。
Synthesis example 2
To a 300 ml four-necked flask, 16.38 g (0.045 mol) of 2- (perfluorohexyl) ethanol, 4.55 g (0.045 mol) of triethylamine and 120 ml of tetrahydrofuran were added and cooled to 0 ° C. with stirring. 6.43 g (0.045 mol) of 2-chloro-2-oxo-1,3,2-dioxaphosphorane was dissolved in 25 ml of tetrahydrofuran, and the resulting solution was added dropwise to the flask using a dropping funnel. After completion of the dropwise addition, the reaction mixture was heated and the reaction was continued at room temperature for 2 hours. Triethylamine hydrochloride precipitated as a by-product was filtered off. The filtrate was transferred to a pressure-resistant bottle, 100 ml of acetonitrile and 7.08 g (0.12 mol) of trimethylamine were added and sealed, reacted at 80 ° C. for 5 hours, and further reacted overnight at room temperature to complete the reaction. Excess trimethylamine was distilled off, and after cooling, the precipitated crystals were separated by filtration, further washed with acetone and diethyl ether, and dried under vacuum to obtain 14.1 g of product.
得られた生成物を、1H−NMR、19F−NMR及び31P−NMRにより測定した結果を以下に示す。これらの結果から得られた生成物は、２−(パーフルオロヘキシル)エチルホスホリルコリン(以下、CF6-PCと略す)であることが判った。得られた生成物と、該生成物の分子内のフッ化炭素鎖数を表１に示す。
1H−NMR(CD3OD、内部標準TMS)：δ＝2.59(m，2H，CF2CH2)、3.21(s，9H，+N(CH3)3)、3.63(t，2H，CH2N+)、4.19(m，2H，CH2OP)、4.27(br，2H，POCH2)。
19F−NMR(CD3OD、外部標準CF3COOH)：δ＝−81.46(3F，CF3)、−113.41(2F，CF2CH2)、−121.74(2F，CF2CF2CH2)、−122.74(2F，CF3CF2CF2CF2)、−123.53(2F，CF3CF2CF2)、−126.16(2F，CF3CF2)。
31P−NMR(CD3OD、外部標準H3PO4)：δ＝0.48。
The results of measuring the obtained product by 1 H-NMR, 19 F-NMR and 31 P-NMR are shown below. The product obtained from these results was found to be 2- (perfluorohexyl) ethyl phosphorylcholine (hereinafter abbreviated as CF6-PC). Table 1 shows the obtained product and the number of fluorocarbon chains in the molecule of the product.
1 H-NMR (CD 3 OD, internal standard TMS): δ = 2.59 (m, 2H, CF 2 CH 2 ), 3.21 (s, 9H, + N (CH 3 ) 3 ), 3.63 (t, 2H, CH 2 N + ), 4.19 (m, 2H, CH 2 OP), 4.27 (br, 2H, POCH 2 ).
19 F-NMR (CD 3 OD, external standard CF 3 COOH): δ = −81.46 (3F, CF 3 ), −113.41 (2F, CF 2 CH 2 ), −121.74 (2F, CF 2 CF 2 CH 2 ) , -122.74 (2F, CF 3 CF 2 CF 2 CF 2), - 123.53 (2F, CF 3 CF 2 CF 2), - 126.16 (2F, CF 3 CF 2).
31 P-NMR (CD 3 OD, external standard H 3 PO 4 ): δ = 0.48.
合成例３
300ml四つ口フラスコに２−(パーフルオロオクチル)エタノール23.2g(0.05モル)、トリエチルアミン5.06g(0.05モル)及びテトラヒドロフラン100mlを加えて撹拌しながら０℃に冷却した。２−クロロ−２−オキソ−１，３，２−ジオキサホスホラン7.14 g(0.05モル)をテトラヒドロフラン30mlに溶解し、得られた溶液を前記フラスコに滴下ロートを用いて滴下した。滴下終了後、反応混合物を昇温して室温で２時間反応を継続させた。副生成物として析出したトリエチルアミン塩酸塩を濾別した。濾液を耐圧びんに移し替え、アセトニトリル150ml及びトリメチルアミン7.08g(0.12モル)を加えて密栓し、８０℃で５時間反応させ、さらに室温で一晩反応させ、反応を終了させた。過剰のトリメチルアミンを留去し冷却後、析出した結晶を濾別し、アセトンとジエチルエーテルを用いて洗浄を行い、真空乾燥して生成物23.5gを得た。
Synthesis example 3
To a 300 ml four-necked flask, 23.2 g (0.05 mol) of 2- (perfluorooctyl) ethanol, 5.06 g (0.05 mol) of triethylamine and 100 ml of tetrahydrofuran were added and cooled to 0 ° C. with stirring. 2-Chloro-2-oxo-1,3,2-dioxaphosphorane (7.14 g, 0.05 mol) was dissolved in 30 ml of tetrahydrofuran, and the resulting solution was added dropwise to the flask using a dropping funnel. After completion of the dropwise addition, the reaction mixture was heated and the reaction was continued at room temperature for 2 hours. Triethylamine hydrochloride precipitated as a by-product was filtered off. The filtrate was transferred to a pressure-resistant bottle, 150 ml of acetonitrile and 7.08 g (0.12 mol) of trimethylamine were added and sealed, reacted at 80 ° C. for 5 hours, and further reacted overnight at room temperature to complete the reaction. Excess trimethylamine was distilled off, and after cooling, the precipitated crystals were separated by filtration, washed with acetone and diethyl ether, and dried under vacuum to obtain 23.5 g of product.
得られた生成物を合成例２と同様にNMR測定した結果を以下に示す。これらの結果から得られた生成物は、２−(パーフルオロオクチル)エチルホスホリルコリン(以下、CF8-PCと略す)であることが判った。得られた生成物と、該生成物の分子内のフッ化炭素鎖数を表１に示す。
1H−NMR(CD3OD、内部標準TMS)：δ＝2.59(m，2H，CF2CH2)、3.21(s，9H，+N(CH3)3)、3.63(t，2H，CH2N+)、4.19(m，2H，CH2OP)、4.27(br，2H，POCH2)。
19F−NMR(CD3OD、外部標準CF3COOH)：δ＝−81.40(3F，CF3)、−113.39(2F，CF2CH2)、−121.75(6F，(CF2)3CF2CH2)、−122.58(2F，CF3CF2CF2CF2)、−123.49(2F，CF3CF2CF2)、−126.11(2F，CF3CF2)。
31P−NMR(CD3OD、外部標準H3PO4)：δ＝0.47。
The results of NMR measurement of the obtained product in the same manner as in Synthesis Example 2 are shown below. The product obtained from these results was found to be 2- (perfluorooctyl) ethyl phosphorylcholine (hereinafter abbreviated as CF8-PC). Table 1 shows the obtained product and the number of fluorocarbon chains in the molecule of the product.
1 H-NMR (CD 3 OD, internal standard TMS): δ = 2.59 (m, 2H, CF 2 CH 2 ), 3.21 (s, 9H, + N (CH 3 ) 3 ), 3.63 (t, 2H, CH 2 N + ), 4.19 (m, 2H, CH 2 OP), 4.27 (br, 2H, POCH 2 ).
19 F-NMR (CD 3 OD, external standard CF 3 COOH): δ = −81.40 (3F, CF 3 ), −113.39 (2F, CF 2 CH 2 ), −121.75 (6F, (CF 2 ) 3 CF 2 CH 2 ), −122.58 (2F, CF 3 CF 2 CF 2 CF 2 ), −123.49 (2F, CF 3 CF 2 CF 2 ), −126.11 (2F, CF 3 CF 2 ).
31 P-NMR (CD 3 OD, external standard H 3 PO 4 ): δ = 0.47.
合成例４
２−(パーフルオロオクチル)エタノールの代わりに、２−(パーフルオロデシル)エタノールを用い、その他の原料仕込組成並びに反応条件を合成例３と同様にして生成物を得た。得られた生成物を合成例２と同様にNMR測定した結果を以下に示す。これらの結果から得られた生成物は、２−(パーフルオロデシル)エチルホスホリルコリン(以下、CF10-PCと略す)であることが判った。得られた生成物と、該生成物の分子内のフッ化炭素鎖数を表１に示す。
1H−NMR(CD3OD／CF3COOD＝８／２、内部標準TMS)：δ＝2.58(m，2H，CF2CH2)、3.22(s，9H，+N(CH3)3)、3.70(t，2H，CH2N+)、4.29(m，2H，CH2OP)、4.41(br，2H，POCH2)。
19F−NMR(CD3OD／CF3COOD＝８／２、外部標準CF3COOH)：−81.63(3F，CF3)、−113.60(2F，CF2CH2)、−121.73(6F，(CF2)3CF2CH2)、−122.71(2F，CF3CF2CF2CF2)、−123.63(2F，CF3CF2CF2)、−126.28(2F，CF3CF2)。
31P−NMR(CD3OD／CF3COOD＝８／２、外部標準H3PO4)：δ＝0.47。
Synthesis example 4
Instead of 2- (perfluorooctyl) ethanol, 2- (perfluorodecyl) ethanol was used, and the other raw material charging compositions and reaction conditions were the same as in Synthesis Example 3 to obtain a product. The results of NMR measurement of the obtained product in the same manner as in Synthesis Example 2 are shown below. The product obtained from these results was found to be 2- (perfluorodecyl) ethyl phosphorylcholine (hereinafter abbreviated as CF10-PC). Table 1 shows the obtained product and the number of fluorocarbon chains in the molecule of the product.
1 H-NMR (CD 3 OD / CF 3 COOD = 8/2, internal standard TMS): δ = 2.58 (m, 2H, CF 2 CH 2 ), 3.22 (s, 9H, + N (CH 3 ) 3 ) 3.70 (t, 2H, CH 2 N + ), 4.29 (m, 2H, CH 2 OP), 4.41 (br, 2H, POCH 2 ).
19 F-NMR (CD 3 OD / CF 3 COOD = 8/2, external standard CF 3 COOH): −81.63 (3F, CF 3 ), −113.60 (2F, CF 2 CH 2 ), −121.73 (6F, ( CF 2 ) 3 CF 2 CH 2 ), −122.71 (2F, CF 3 CF 2 CF 2 CF 2 ), −123.63 (2F, CF 3 CF 2 CF 2 ), −126.28 (2F, CF 3 CF 2 ).
31 P-NMR (CD 3 OD / CF 3 COOD = 8/2, external standard H 3 PO 4 ): δ = 0.47.
実施例１
0.50gのCF8-PCと1.00gの平均粒径６μｍポリエチレン粒子(商品名「フロービーズLE-1080」、住友精化株式会社製)とを、乳鉢で均一になるよう５分間、混合物の温度を５０℃以下に保持しながら混合して複合材料を調製した。得られた混合物をステンレス板で挟み、プレス機において、１２０℃、圧力２０ＭＰａで２０分間加熱・加圧成形を行った。ステンレス板を取り出し室温になるまで放置した後、厚さ０．１ｍｍの複合材料フィルムをステンレス板から剥離、回収した。
得られたフィルム適当に切り出した試験片について、以下に示す外観観察、表面引張試験、表面接触角値の測定及び血小板粘着試験を実施した。結果を表２に示す。
Example 1
Mix 0.50 g CF8-PC and 1.00 g polyethylene particles with an average particle diameter of 6 μm (trade name “Flow Beads LE-1080”, manufactured by Sumitomo Seika Co., Ltd.) for 5 minutes so that the mixture is uniform in a mortar. A composite material was prepared by mixing while maintaining the temperature at 50 ° C. or lower. The obtained mixture was sandwiched between stainless plates, and heated and pressure-molded at 120 ° C. and a pressure of 20 MPa for 20 minutes in a press machine. The stainless steel plate was taken out and allowed to reach room temperature, and then a 0.1 mm thick composite material film was peeled off and collected from the stainless steel plate.
About the obtained test piece appropriately cut out of the film, the following appearance observation, surface tension test, measurement of surface contact angle value and platelet adhesion test were performed. The results are shown in Table 2.
＜外観観察＞
得られたフィルム表面を目視で観察して、ほとんど均一でムラがないものを○、局所的に白濁し、分離状態が認められるものを×と評価した。
＜表面引張試験＞
得られたフィルムを約１〜２mm幅で切り出し、引張強度試験機(YAMADEN社製、RHEONER RE-3305)を用いて、JIS-K7161に準じて引張試験を行い、破断強度及び破断伸びを測定した。
＜表面接触角値の測定＞
エルマ社製の接触角測定器G-1を用いて水による液滴法で行った。
<Appearance observation>
The obtained film surface was visually observed and evaluated as ○ when the film was almost uniform and non-uniform, and x when it was locally clouded and a separated state was observed.
<Surface tensile test>
The obtained film was cut out with a width of about 1 to 2 mm, and a tensile test was performed according to JIS-K7161 using a tensile strength tester (manufactured by YAMADEN, RHEONER RE-3305) to measure the breaking strength and breaking elongation. .
<Measurement of surface contact angle value>
It was carried out by a water droplet method using a contact angle measuring device G-1 manufactured by Elma.
＜血小板粘着試験＞
得られたフィルムの試験片を、２４穴培養用プレートにセットした。このプレートにウサギ多血小板血漿(以下、PRPと略す)1.0mlを加え、室温で３時間インキュベートした。終了後、PRPを取り除き、1.5mlのPBSで３回洗浄した。洗浄終了後、2.5vol％のグルタルアルデヒドを含む1.5mlのPBSを加えて室温で３時間インキュベートすることにより粘着して血小板を固定化した。粘着した血小板は、金蒸着機を用いて金蒸着した。その後、試験片を走査型電子顕微鏡(JSM-5400、日本電子社製)で観察した。１視野(約20μｍ×20μｍ)中における血小板数を以下のように評価した。
血小板数０〜１０個；◎、血小板数１１〜２０個；○、血小板数２１〜３０個；△、血小板数３１個以上；×。
<Platelet adhesion test>
The obtained film test piece was set on a 24-well culture plate. To this plate, 1.0 ml of rabbit platelet-rich plasma (hereinafter abbreviated as PRP) was added and incubated at room temperature for 3 hours. After completion, PRP was removed and washed 3 times with 1.5 ml PBS. After washing, 1.5 ml of PBS containing 2.5 vol% glutaraldehyde was added and incubated at room temperature for 3 hours to adhere and immobilize platelets. Adhered platelets were gold deposited using a gold deposition machine. Thereafter, the test piece was observed with a scanning electron microscope (JSM-5400, manufactured by JEOL Ltd.). The number of platelets in one visual field (about 20 μm × 20 μm) was evaluated as follows.
0 to 10 platelets; 、, 11 to 20 platelets; ◯, 21 to 30 platelets; Δ, 31 or more platelets;
実施例２〜４及び比較例１
CF8-PCの代わりに表２に示すホスホリルコリン類似基(PC)含有化合物を用いた以外は実施例１と同様にして複合材料フィルムを得て、各種測定及び試験を実施した。結果を表２に示す。
Examples 2 to 4 and Comparative Example 1
A composite film was obtained in the same manner as in Example 1 except that the phosphorylcholine-like group (PC) -containing compound shown in Table 2 was used instead of CF8-PC, and various measurements and tests were performed. The results are shown in Table 2.
比較例２
ポリエチレン粒子として、平均粒径１８０μｍのポリエチレン粒子(商品名「フロービーズCL-2507」、住友精化株式会社製)を用いた以外は実施例１と同様にして複合材料フィルムを得て、各種測定及び試験を実施した。結果を表２に示す。
Comparative Example 2
A composite material film was obtained in the same manner as in Example 1 except that polyethylene particles having an average particle diameter of 180 μm (trade name “Flow Beads CL-2507”, manufactured by Sumitomo Seika Co., Ltd.) were used as polyethylene particles. And the test was performed. The results are shown in Table 2.
表２より、本発明の実施例１〜４は、破断強度と破断伸びで表される力学的強度と、表面接触角値と血小板粘着試験から表される表面の生体適合性を両立する点から優れているのに対して、比較例１及び２では力学的強度又は表面の生体適合性が劣ることが判った。
From Table 2, Examples 1-4 of this invention are from the point which balances the mechanical strength represented by breaking strength and breaking elongation, and the surface biocompatibility represented from a surface contact angle value and a platelet adhesion test. In contrast to Comparative Example 1 and 2, it was found that mechanical strength or surface biocompatibility was inferior.
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