JP2017179098A - Piperidine 2-carboxylic acid residue-containing copolymer - Google Patents
Piperidine 2-carboxylic acid residue-containing copolymer Download PDFInfo
- Publication number
- JP2017179098A JP2017179098A JP2016067649A JP2016067649A JP2017179098A JP 2017179098 A JP2017179098 A JP 2017179098A JP 2016067649 A JP2016067649 A JP 2016067649A JP 2016067649 A JP2016067649 A JP 2016067649A JP 2017179098 A JP2017179098 A JP 2017179098A
- Authority
- JP
- Japan
- Prior art keywords
- ethylenically unsaturated
- unsaturated monomer
- acrylate
- meth
- carboxylic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229920001577 copolymer Polymers 0.000 title claims abstract description 27
- HXEACLLIILLPRG-PTQBSOBMSA-N piperidine-2-carboxylic acid Chemical group O[13C](=O)C1CCCCN1 HXEACLLIILLPRG-PTQBSOBMSA-N 0.000 title 1
- 239000000178 monomer Substances 0.000 claims abstract description 86
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 229920000642 polymer Polymers 0.000 claims abstract description 13
- 239000000560 biocompatible material Substances 0.000 claims abstract description 10
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical group OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 40
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 6
- 239000000758 substrate Substances 0.000 abstract description 16
- 230000007062 hydrolysis Effects 0.000 abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 7
- 125000000539 amino acid group Chemical group 0.000 abstract description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 42
- -1 methacrylic acid serine ester Chemical class 0.000 description 25
- 239000002904 solvent Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000000034 method Methods 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000011248 coating agent Substances 0.000 description 10
- 238000000576 coating method Methods 0.000 description 10
- 229920005989 resin Polymers 0.000 description 10
- 239000011347 resin Substances 0.000 description 10
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000007514 bases Chemical class 0.000 description 9
- 238000006116 polymerization reaction Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000003586 protic polar solvent Substances 0.000 description 9
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000001179 sorption measurement Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000003505 polymerization initiator Substances 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 239000012433 hydrogen halide Substances 0.000 description 4
- 229910000039 hydrogen halide Inorganic materials 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
- ZSZRUEAFVQITHH-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CC(=C)C(=O)OCCOP([O-])(=O)OCC[N+](C)(C)C ZSZRUEAFVQITHH-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 239000008199 coating composition Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000000909 electrodialysis Methods 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000139 polyethylene terephthalate Polymers 0.000 description 3
- 239000005020 polyethylene terephthalate Substances 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 150000003926 acrylamides Chemical class 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229920002678 cellulose Chemical class 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 239000012460 protein solution Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000010526 radical polymerization reaction Methods 0.000 description 2
- 238000001226 reprecipitation Methods 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 2
- 125000003011 styrenyl group Chemical group [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- MJYFYGVCLHNRKB-UHFFFAOYSA-N 1,1,2-trifluoroethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(F)(F)CF MJYFYGVCLHNRKB-UHFFFAOYSA-N 0.000 description 1
- JWTGRKUQJXIWCV-UHFFFAOYSA-N 1,2,3-trihydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(O)C(O)CO JWTGRKUQJXIWCV-UHFFFAOYSA-N 0.000 description 1
- ZRZHXNCATOYMJH-UHFFFAOYSA-N 1-(chloromethyl)-4-ethenylbenzene Chemical compound ClCC1=CC=C(C=C)C=C1 ZRZHXNCATOYMJH-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- STFXXRRQKFUYEU-UHFFFAOYSA-N 16-methylheptadecyl prop-2-enoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)C=C STFXXRRQKFUYEU-UHFFFAOYSA-N 0.000 description 1
- YKTNISGZEGZHIS-UHFFFAOYSA-N 2-$l^{1}-oxidanyloxy-2-methylpropane Chemical group CC(C)(C)O[O] YKTNISGZEGZHIS-UHFFFAOYSA-N 0.000 description 1
- PITLEXLWAKFCAI-UHFFFAOYSA-N 2-(2-hydroxyethoxy)-1-phenoxyethanol;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.OCCOCC(O)OC1=CC=CC=C1 PITLEXLWAKFCAI-UHFFFAOYSA-N 0.000 description 1
- IAMASUILMZETHW-UHFFFAOYSA-N 2-(2-hydroxyethoxy)-1-phenoxyethanol;prop-2-enoic acid Chemical compound OC(=O)C=C.OCCOCC(O)OC1=CC=CC=C1 IAMASUILMZETHW-UHFFFAOYSA-N 0.000 description 1
- OLQFXOWPTQTLDP-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOCCO OLQFXOWPTQTLDP-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- KANYKVYWMZPGSL-UHFFFAOYSA-N 2-(hydroxymethyl)-2-methylpropane-1,3-diol;prop-2-enoic acid Chemical compound OC(=O)C=C.OC(=O)C=C.OC(=O)C=C.OCC(C)(CO)CO KANYKVYWMZPGSL-UHFFFAOYSA-N 0.000 description 1
- RGADKZXRWFOTFV-UHFFFAOYSA-N 2-(hydroxymethyl)-2-methylpropane-1,3-diol;prop-2-enoic acid Chemical compound OC(=O)C=C.OC(=O)C=C.OCC(C)(CO)CO RGADKZXRWFOTFV-UHFFFAOYSA-N 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- PFHOSZAOXCYAGJ-UHFFFAOYSA-N 2-[(2-cyano-4-methoxy-4-methylpentan-2-yl)diazenyl]-4-methoxy-2,4-dimethylpentanenitrile Chemical compound COC(C)(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)(C)OC PFHOSZAOXCYAGJ-UHFFFAOYSA-N 0.000 description 1
- VLTSFMBMFCXCKB-UHFFFAOYSA-N 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]-1-phenoxyethanol;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.OCCOCCOCCOCC(O)OC1=CC=CC=C1 VLTSFMBMFCXCKB-UHFFFAOYSA-N 0.000 description 1
- TVFJLSWPPLFHKR-UHFFFAOYSA-N 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]-1-phenoxyethanol;prop-2-enoic acid Chemical compound OC(=O)C=C.OCCOCCOCCOCC(O)OC1=CC=CC=C1 TVFJLSWPPLFHKR-UHFFFAOYSA-N 0.000 description 1
- XMIYEVCXHOOJMF-UHFFFAOYSA-N 2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]-1-phenoxyethanol;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.OCCOCCOCCOCCOCCOCC(O)OC1=CC=CC=C1 XMIYEVCXHOOJMF-UHFFFAOYSA-N 0.000 description 1
- ADRHDZXSVIPHAF-UHFFFAOYSA-N 2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]-1-phenoxyethanol;prop-2-enoic acid Chemical compound OC(=O)C=C.OCCOCCOCCOCCOCCOCC(O)OC1=CC=CC=C1 ADRHDZXSVIPHAF-UHFFFAOYSA-N 0.000 description 1
- TXHZNLCKXHJYNX-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl 2-methylprop-2-enoate Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCOCCOC(=O)C(C)=C TXHZNLCKXHJYNX-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- RCEJCSULJQNRQQ-UHFFFAOYSA-N 2-methylbutanenitrile Chemical compound CCC(C)C#N RCEJCSULJQNRQQ-UHFFFAOYSA-N 0.000 description 1
- CEXQWAAGPPNOQF-UHFFFAOYSA-N 2-phenoxyethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOC1=CC=CC=C1 CEXQWAAGPPNOQF-UHFFFAOYSA-N 0.000 description 1
- RZVINYQDSSQUKO-UHFFFAOYSA-N 2-phenoxyethyl prop-2-enoate Chemical compound C=CC(=O)OCCOC1=CC=CC=C1 RZVINYQDSSQUKO-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- DOYKFSOCSXVQAN-UHFFFAOYSA-N 3-[diethoxy(methyl)silyl]propyl 2-methylprop-2-enoate Chemical compound CCO[Si](C)(OCC)CCCOC(=O)C(C)=C DOYKFSOCSXVQAN-UHFFFAOYSA-N 0.000 description 1
- LZMNXXQIQIHFGC-UHFFFAOYSA-N 3-[dimethoxy(methyl)silyl]propyl 2-methylprop-2-enoate Chemical compound CO[Si](C)(OC)CCCOC(=O)C(C)=C LZMNXXQIQIHFGC-UHFFFAOYSA-N 0.000 description 1
- MCDBEBOBROAQSH-UHFFFAOYSA-N 3-[dimethoxy(methyl)silyl]propyl prop-2-enoate Chemical compound CO[Si](C)(OC)CCCOC(=O)C=C MCDBEBOBROAQSH-UHFFFAOYSA-N 0.000 description 1
- RUROFEVDCUGKHD-UHFFFAOYSA-N 3-bromoprop-1-enylbenzene Chemical compound BrCC=CC1=CC=CC=C1 RUROFEVDCUGKHD-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- IWTYTFSSTWXZFU-UHFFFAOYSA-N 3-chloroprop-1-enylbenzene Chemical compound ClCC=CC1=CC=CC=C1 IWTYTFSSTWXZFU-UHFFFAOYSA-N 0.000 description 1
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 description 1
- JIGUICYYOYEXFS-UHFFFAOYSA-N 3-tert-butylbenzene-1,2-diol Chemical compound CC(C)(C)C1=CC=CC(O)=C1O JIGUICYYOYEXFS-UHFFFAOYSA-N 0.000 description 1
- ZJWCURYIRDLMTM-UHFFFAOYSA-N 3-tributoxysilylpropyl 2-methylprop-2-enoate Chemical compound CCCCO[Si](OCCCC)(OCCCC)CCCOC(=O)C(C)=C ZJWCURYIRDLMTM-UHFFFAOYSA-N 0.000 description 1
- URDOJQUSEUXVRP-UHFFFAOYSA-N 3-triethoxysilylpropyl 2-methylprop-2-enoate Chemical compound CCO[Si](OCC)(OCC)CCCOC(=O)C(C)=C URDOJQUSEUXVRP-UHFFFAOYSA-N 0.000 description 1
- XDQWJFXZTAWJST-UHFFFAOYSA-N 3-triethoxysilylpropyl prop-2-enoate Chemical compound CCO[Si](OCC)(OCC)CCCOC(=O)C=C XDQWJFXZTAWJST-UHFFFAOYSA-N 0.000 description 1
- XDLMVUHYZWKMMD-UHFFFAOYSA-N 3-trimethoxysilylpropyl 2-methylprop-2-enoate Chemical compound CO[Si](OC)(OC)CCCOC(=O)C(C)=C XDLMVUHYZWKMMD-UHFFFAOYSA-N 0.000 description 1
- YENIUOKSTSIUOR-UHFFFAOYSA-N 4-bromobut-1-enylbenzene Chemical compound BrCCC=CC1=CC=CC=C1 YENIUOKSTSIUOR-UHFFFAOYSA-N 0.000 description 1
- HIPMXTORBGIBCC-UHFFFAOYSA-N 4-chlorobut-1-enylbenzene Chemical compound ClCCC=CC1=CC=CC=C1 HIPMXTORBGIBCC-UHFFFAOYSA-N 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- NDWUBGAGUCISDV-UHFFFAOYSA-N 4-hydroxybutyl prop-2-enoate Chemical compound OCCCCOC(=O)C=C NDWUBGAGUCISDV-UHFFFAOYSA-N 0.000 description 1
- TZRQBRODRXBKDJ-UHFFFAOYSA-N 5-bromopent-1-enylbenzene Chemical compound BrCCCC=CC1=CC=CC=C1 TZRQBRODRXBKDJ-UHFFFAOYSA-N 0.000 description 1
- CDINNLUJIQAPRY-UHFFFAOYSA-N 5-chloropent-1-enylbenzene Chemical compound ClCCCC=CC1=CC=CC=C1 CDINNLUJIQAPRY-UHFFFAOYSA-N 0.000 description 1
- HXQXSNNOGXXMLU-UHFFFAOYSA-N 6-bromohex-1-enylbenzene Chemical compound BrCCCCC=CC1=CC=CC=C1 HXQXSNNOGXXMLU-UHFFFAOYSA-N 0.000 description 1
- OISKVOSLHIGZCY-UHFFFAOYSA-N 6-chlorohex-1-enylbenzene Chemical compound ClCCCCC=CC1=CC=CC=C1 OISKVOSLHIGZCY-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- RBUWQEHTCBTJBF-UHFFFAOYSA-N CCCC(=C)C(=O)N(NCC)NCC Chemical compound CCCC(=C)C(=O)N(NCC)NCC RBUWQEHTCBTJBF-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical group CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical group C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920002396 Polyurea Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 1
- LXEKPEMOWBOYRF-UHFFFAOYSA-N [2-[(1-azaniumyl-1-imino-2-methylpropan-2-yl)diazenyl]-2-methylpropanimidoyl]azanium;dichloride Chemical compound Cl.Cl.NC(=N)C(C)(C)N=NC(C)(C)C(N)=N LXEKPEMOWBOYRF-UHFFFAOYSA-N 0.000 description 1
- DBPBBEWGTZWSRJ-UHFFFAOYSA-N [4-(2-methylprop-2-enoyloxy)-1-(trimethylazaniumyl)butan-2-yl] hydrogen phosphate Chemical compound CC(=C)C(=O)OCCC(C[N+](C)(C)C)OP(O)([O-])=O DBPBBEWGTZWSRJ-UHFFFAOYSA-N 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000005370 alkoxysilyl group Chemical group 0.000 description 1
- 125000002521 alkyl halide group Chemical group 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 1
- 239000002216 antistatic agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- AOJOEFVRHOZDFN-UHFFFAOYSA-N benzyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC1=CC=CC=C1 AOJOEFVRHOZDFN-UHFFFAOYSA-N 0.000 description 1
- GCTPMLUUWLLESL-UHFFFAOYSA-N benzyl prop-2-enoate Chemical compound C=CC(=O)OCC1=CC=CC=C1 GCTPMLUUWLLESL-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- SHZIWNPUGXLXDT-UHFFFAOYSA-N caproic acid ethyl ester Natural products CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- OIWOHHBRDFKZNC-UHFFFAOYSA-N cyclohexyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC1CCCCC1 OIWOHHBRDFKZNC-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000012674 dispersion polymerization Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 238000007720 emulsion polymerization reaction Methods 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000008394 flocculating agent Substances 0.000 description 1
- 238000010528 free radical solution polymerization reaction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- PBOSTUDLECTMNL-UHFFFAOYSA-N lauryl acrylate Chemical compound CCCCCCCCCCCCOC(=O)C=C PBOSTUDLECTMNL-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- VHRYZQNGTZXDNX-UHFFFAOYSA-N methacryloyl chloride Chemical compound CC(=C)C(Cl)=O VHRYZQNGTZXDNX-UHFFFAOYSA-N 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- GZPVGWXZCDJAGP-UHFFFAOYSA-N n,n-bis(butoxymethyl)prop-2-enamide Chemical compound CCCCOCN(C(=O)C=C)COCCCC GZPVGWXZCDJAGP-UHFFFAOYSA-N 0.000 description 1
- YOPHLFVSHAHNMB-UHFFFAOYSA-N n,n-bis(ethoxymethyl)prop-2-enamide Chemical compound CCOCN(C(=O)C=C)COCC YOPHLFVSHAHNMB-UHFFFAOYSA-N 0.000 description 1
- FKUCXJWFJBFVHQ-UHFFFAOYSA-N n,n-bis(methoxymethyl)prop-2-enamide Chemical compound COCN(COC)C(=O)C=C FKUCXJWFJBFVHQ-UHFFFAOYSA-N 0.000 description 1
- DFENKTCEEGOWLB-UHFFFAOYSA-N n,n-bis(methylamino)-2-methylidenepentanamide Chemical compound CCCC(=C)C(=O)N(NC)NC DFENKTCEEGOWLB-UHFFFAOYSA-N 0.000 description 1
- BDGYUEIEAPRCRS-UHFFFAOYSA-N n,n-bis(pentoxymethyl)prop-2-enamide Chemical compound CCCCCOCN(C(=O)C=C)COCCCCC BDGYUEIEAPRCRS-UHFFFAOYSA-N 0.000 description 1
- FEAREGDDZJVSTE-UHFFFAOYSA-N n,n-bis(propoxymethyl)prop-2-enamide Chemical compound CCCOCN(C(=O)C=C)COCCC FEAREGDDZJVSTE-UHFFFAOYSA-N 0.000 description 1
- OVHHHVAVHBHXAK-UHFFFAOYSA-N n,n-diethylprop-2-enamide Chemical compound CCN(CC)C(=O)C=C OVHHHVAVHBHXAK-UHFFFAOYSA-N 0.000 description 1
- CWXODBOOPJEYLA-UHFFFAOYSA-N n-(ethoxymethyl)-n-(methoxymethyl)-2-methylprop-2-enamide Chemical compound CCOCN(COC)C(=O)C(C)=C CWXODBOOPJEYLA-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical group CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- WRAQQYDMVSCOTE-UHFFFAOYSA-N phenyl prop-2-enoate Chemical compound C=CC(=O)OC1=CC=CC=C1 WRAQQYDMVSCOTE-UHFFFAOYSA-N 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002492 poly(sulfone) Chemical class 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 239000004417 polycarbonate Chemical class 0.000 description 1
- 229920000515 polycarbonate Chemical class 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920005591 polysilicon Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- MFSZVOKHTMONOW-UHFFFAOYSA-M potassium;pyrrolidine-2-carboxylate Chemical compound [K+].[O-]C(=O)C1CCCN1 MFSZVOKHTMONOW-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- NHARPDSAXCBDDR-UHFFFAOYSA-N propyl 2-methylprop-2-enoate Chemical compound CCCOC(=O)C(C)=C NHARPDSAXCBDDR-UHFFFAOYSA-N 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011342 resin composition Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- CUTQWXGMRNLXQC-UHFFFAOYSA-M sodium;pyrrolidine-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1CCCN1 CUTQWXGMRNLXQC-UHFFFAOYSA-M 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- SJMYWORNLPSJQO-UHFFFAOYSA-N tert-butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C)(C)C SJMYWORNLPSJQO-UHFFFAOYSA-N 0.000 description 1
- GJBRNHKUVLOCEB-UHFFFAOYSA-N tert-butyl benzenecarboperoxoate Chemical compound CC(C)(C)OOC(=O)C1=CC=CC=C1 GJBRNHKUVLOCEB-UHFFFAOYSA-N 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- HQYALQRYBUJWDH-UHFFFAOYSA-N trimethoxy(propyl)silane Chemical compound CCC[Si](OC)(OC)OC HQYALQRYBUJWDH-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
- Polymerisation Methods In General (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
Description
本発明は、１分子中にスチレン骨格ならびにピロリジン-２-カルボン酸残基を有する両性エチレン性不飽和単量体（ａ）およびアルキル基含有エチレン性不飽和単量体（ｂ）を含有するエチレン性不飽和単量体（ｃ）の共重合体に関する。さらに該共重合体を含有してなる生体適合性樹脂組成物に関する。 The present invention relates to an ethylene containing an amphoteric ethylenically unsaturated monomer (a) having a styrene skeleton and a pyrrolidine-2-carboxylic acid residue in one molecule and an alkyl group-containing ethylenically unsaturated monomer (b). The present invention relates to a copolymer of the polymerizable unsaturated monomer (c). Furthermore, it is related with the biocompatible resin composition formed by containing this copolymer.
近年、バイオテクノロジーの急速な発展により、医療ならびにヘルスケアデバイスと生体成分が接触する界面において、優れた生体適合性を発現する両性高分子が注目されている。両性高分子の原料と単量体の開発も活発に検討されており、２−メタクリロイルオキシエチルホスホコリンを代表とするベタイン基含有両性高分子やアミノ酸残基含有両性高分子が開発されている。
特許文献１では、２−メタクリロイルオキシエチルホスホコリンを共重合して得られるホスホベタイン型の高分子材料が開示されている。しかしながら、２−メタクリロリルオキシエチルホスホコリンは、合成工程が多く、純度を高めることが困難であり、生成した結晶も短時間で潮解するという欠点を有する。したがって単量体の取り扱いが難しく、単量体ならびにその重合体は非常に高価である。特許文献２ではアミノ酸残基を有する両性単量体であるメタクリル酸セリンエステルとそれを共重合してなる両性高分子が開示されている。これについても合成工程が複雑であるため、安価かつ高純度、高収率で単量体を得る事は困難である。
また、上述のエチレン性不飽和単量体は、その単量体から製造される高分子の親水基が容易に加水分解される恐れがあり、材料の長期耐久性に課題が残る。
In recent years, due to the rapid development of biotechnology, amphoteric polymers that exhibit excellent biocompatibility are attracting attention at the interface where medical and health care devices are in contact with biological components. The development of amphoteric polymer materials and monomers is also being actively studied, and betaine group-containing amphoteric polymers such as 2-methacryloyloxyethylphosphocholine and amino acid residue-containing amphoteric polymers have been developed.
Patent Document 1 discloses a phosphobetaine-type polymer material obtained by copolymerizing 2-methacryloyloxyethylphosphocholine. However, 2-methacryloyloxyethyl phosphocholine has many synthetic steps, and it is difficult to increase purity, and the produced crystals have the disadvantage of being deliquescent in a short time. Therefore, it is difficult to handle the monomer, and the monomer and its polymer are very expensive. Patent Document 2 discloses an amphoteric polymer obtained by copolymerizing methacrylic acid serine ester which is an amphoteric monomer having an amino acid residue. Also in this case, since the synthesis process is complicated, it is difficult to obtain a monomer with low cost, high purity, and high yield.
Moreover, the above-mentioned ethylenically unsaturated monomer has a possibility that the hydrophilic group of the polymer produced from the monomer may be easily hydrolyzed, and there remains a problem in the long-term durability of the material.
本発明の目的は、耐加水分解性、生体適合性、フィルム基材への密着性に優れるアミノ酸残基含有共重合体を提供する事にある。 An object of the present invention is to provide an amino acid residue-containing copolymer having excellent hydrolysis resistance, biocompatibility, and adhesion to a film substrate.
すなわち、本発明は、一般式（１）で表されるエチレン性不飽和単量体（ａ）およびアルキル基含有エチレン性不飽和単量体（ｂ）を含むエチレン性不飽和単量体（ｃ）の共重合体である、ピロリジン２−カルボン酸残基含有共重合体に関する。一般式（１）：
（Ｒは、直鎖又は分岐アルキレン基を示す）
That is, the present invention relates to an ethylenically unsaturated monomer (c) including the ethylenically unsaturated monomer (a) represented by the general formula (1) and the alkyl group-containing ethylenically unsaturated monomer (b). ) Is a pyrrolidine 2-carboxylic acid residue-containing copolymer. General formula (1):
(R represents a linear or branched alkylene group)
また、本発明は、エチレン性不飽和単量体（ｃ）１００重量％中、一般式（１）で表される両性エチレン性不飽和単量体（ａ）が５〜９０重量％含まれる事を特徴とする請求項１記載のピロリジン２−カルボン酸残基含有共重合体に関する。 In addition, the present invention includes 5 to 90% by weight of the amphoteric ethylenically unsaturated monomer (a) represented by the general formula (1) in 100% by weight of the ethylenically unsaturated monomer (c). The pyrrolidine 2-carboxylic acid residue-containing copolymer according to claim 1.
また、本発明は、前記ピロリジン２−カルボン酸残基含有共重合体を含有する生体適合性材料に関する。 The present invention also relates to a biocompatible material containing the pyrrolidine 2-carboxylic acid residue-containing copolymer.
また、本発明は、基材上に、前記生体適合性材料から形成された被膜を有する積層体に関する。 The present invention also relates to a laminate having a coating film formed from the biocompatible material on a substrate.
また、本発明は、ピロリジン２−カルボン酸と一般式（２）で表されるエチレン性不飽和単量体を反応させ、一般式（１）で表されるエチレン性不飽和単量体（ａ）を得た後、エチレン性不飽和単量体（ａ）とアルキル基含有エチレン性不飽和単量体（ｂ）を含有するエチレン性不飽和単量体（ｃ）を共重合するピロリジン２−カルボン酸残基含有共重合体の製造方法に関する。
一般式（１）：
（Ｒは、直鎖又は分岐アルキレン基を示す）
一般式（２）：
（Ｒは、直鎖又は分岐アルキレン基、
Ｘは、ＣｌまたはＢｒを示す）
Moreover, this invention makes the ethylenically unsaturated monomer represented by General formula (1) react with the pyrrolidine 2-carboxylic acid and the ethylenically unsaturated monomer represented by General formula (2) (a ), And then copolymerizing the ethylenically unsaturated monomer (c) containing the ethylenically unsaturated monomer (a) and the alkyl group-containing ethylenically unsaturated monomer (b). The present invention relates to a method for producing a carboxylic acid residue-containing copolymer.
General formula (1):
(R represents a linear or branched alkylene group)
General formula (2):
(R is a linear or branched alkylene group,
X represents Cl or Br)
本発明は、一般式（１）で表される両性エチレン性不飽和単量体（a）とアルキル基含有エチレン性不飽和単量体（ｂ）を含むエチレン性不飽和単量体をラジカル重合してなるピロリジン２−カルボン酸残基含有共重合体である。この共重合体は、生体適合性、耐加水分解性に優れており、各種基材への密着性、耐水性も良好な事から、耐久性が求められる医療ならびにヘルスケアデバイスへの利用が期待できる。また、両性エチレン性不飽和単量体（a）は、芳香族骨格からなる疎水性部位とピロリジン２−カルボン酸残基からなる親水性部位を１分子中に有しているため、疎水性相互作用による吸着機能に優れ、水系の各種分散剤への展開も期待できる。保湿剤、増粘剤、凝集剤、帯電防止剤、キレート剤等、両性高分子が使用されている幅広い分野にも応用する事ができる。 The present invention radically polymerizes an ethylenically unsaturated monomer including the amphoteric ethylenically unsaturated monomer (a) represented by the general formula (1) and an alkyl group-containing ethylenically unsaturated monomer (b). A pyrrolidine 2-carboxylic acid residue-containing copolymer. This copolymer is excellent in biocompatibility and hydrolysis resistance, and has good adhesion to various substrates and water resistance, so it is expected to be used in medical and healthcare devices that require durability. it can. In addition, since the amphoteric ethylenically unsaturated monomer (a) has in one molecule a hydrophobic site consisting of an aromatic skeleton and a hydrophilic site consisting of a pyrrolidine 2-carboxylic acid residue, It has an excellent adsorption function due to its action, and can be expected to be applied to various aqueous dispersants. It can also be applied to a wide range of fields where amphoteric polymers are used, such as humectants, thickeners, flocculants, antistatic agents, chelating agents, and the like.
エチレン性不飽和単量体（ａ）は、下記一般式（１）で示されるものである。
一般式（１）：
Ｒは、直鎖又は分岐アルキレン基を示し、
直鎖又は分岐アルキレン基としては、メチレン基、エチレン基、プロピレン基、ブチレン基、トリメチレン基、テトラメチレン基、ヘキサメチレン基、オクタメチレン、または、１，２−シクロヘキセン基、１，３−シクロヘキセン基、１，４−シクロヘキセン基、２−メチルプロペン基等が挙げられる。好ましくは炭素数が１〜６のアルキレン基である。
The ethylenically unsaturated monomer (a) is represented by the following general formula (1).
General formula (1):
R represents a linear or branched alkylene group,
Examples of the linear or branched alkylene group include a methylene group, an ethylene group, a propylene group, a butylene group, a trimethylene group, a tetramethylene group, a hexamethylene group, an octamethylene group, a 1,2-cyclohexene group, and a 1,3-cyclohexene group. 1,4-cyclohexene group, 2-methylpropene group and the like. Preferably it is a C1-C6 alkylene group.
一般式（１）で表される両性エチレン性不飽和単量体の好ましい製造方法としては、アミノ酸であるピロリジン２−カルボン酸と塩基性化合物、またはピロリジン２−カルボン酸塩をあらかじめプロトン性溶媒中に溶解させた後、一般式（２）で表されるエチレン性不飽和単量体を添加して反応させて得る（第一の工程）方法が好ましい。 As a preferable production method of the amphoteric ethylenically unsaturated monomer represented by the general formula (1), an amino acid pyrrolidine 2-carboxylic acid and a basic compound, or pyrrolidine 2-carboxylate is previously contained in a protic solvent. The method obtained by adding the ethylenically unsaturated monomer represented by the general formula (2) and reacting them after being dissolved in (the first step) is preferable.
一般式（２）：
（Ｒは、直鎖又は分岐アルキレン基、Ｘは、ＣｌまたはＢｒを示す）
General formula (2):
(R represents a linear or branched alkylene group, X represents Cl or Br)
第一の工程の詳細について説明する。まず、反応溶媒中にピロリジン２−カルボン酸と塩基性化合物、またはあらかじめ塩になっているピロリジン２−カルボン酸塩を加熱しながら溶媒に溶解させる。原料に使用するピロリジン２−カルボン酸は光学異性体を有するため、Ｌ体とＤ体が存在するが、生体への安全性の観点から合成にはＬ体を使用する事が好ましい。ピロリジン２−カルボン酸およびその塩は、非プロトン性溶媒にはほとんど溶解しないため、反応溶媒には、プロトン性溶媒を使用する事が好ましい。 Details of the first step will be described. First, pyrrolidine 2-carboxylic acid and a basic compound or a pyrrolidine 2-carboxylate salt that has been converted into a salt in a reaction solvent are dissolved in the solvent while heating. Since pyrrolidine 2-carboxylic acid used as a raw material has an optical isomer, there are L-form and D-form, but it is preferable to use L-form for synthesis from the viewpoint of safety to living bodies. Since pyrrolidine 2-carboxylic acid and its salt are hardly dissolved in an aprotic solvent, it is preferable to use a protic solvent as a reaction solvent.
溶媒には、反応を阻害しない溶媒であれば任意のものを使用する事ができる。使用できるプロトン性溶媒としては、メタノール、エタノール、１−プロパノール、２−プロパノール等のアルコール類、水等が挙げられる。 Any solvent can be used as long as it does not inhibit the reaction. Examples of protic solvents that can be used include alcohols such as methanol, ethanol, 1-propanol, and 2-propanol, and water.
続いて、一般式（２）で表されるエチレン性不飽和単量体を添加する。一般式（２）で表されるエチレン性不飽和単量体のハロゲン基とピロリジン２−カルボン酸骨格中の二級アミノ基との間で求核置換反応が起こり、アミノ基が三級化されて目的物が生成する。反応の際、同時にハロゲン化水素も副生成物として発生するが、溶媒中の塩基と反応してハロゲン塩を形成するため、ハロゲン化水素は捕捉される。ハロゲン塩が溶媒に対して不溶な場合、反応の進行に伴って塩が生成、析出してくるのを確認する事ができる。 Subsequently, an ethylenically unsaturated monomer represented by the general formula (2) is added. A nucleophilic substitution reaction occurs between the halogen group of the ethylenically unsaturated monomer represented by the general formula (2) and the secondary amino group in the pyrrolidine 2-carboxylic acid skeleton, and the amino group is tertiaryized. The target product is generated. During the reaction, hydrogen halide is also generated as a by-product at the same time, but the hydrogen halide is trapped because it reacts with the base in the solvent to form a halogen salt. When the halogen salt is insoluble in the solvent, it can be confirmed that the salt is produced and precipitated as the reaction proceeds.
上記のプロトン性溶媒の中でも、ピロリジン-２-カルボン酸塩の溶解性に優れ、塩の除去が容易な点から、プロトン性溶媒にはアルコール溶媒を使用する事が好ましく、さらに安全性の観点から、プロトン性溶媒には、エタノールを使用する事がさらに好ましい。 Among the above protic solvents, it is preferable to use an alcohol solvent as the protic solvent from the viewpoint of excellent solubility of pyrrolidine-2-carboxylate and easy salt removal, and from the viewpoint of safety. More preferably, ethanol is used as the protic solvent.
本発明で使用する塩基性化合物は、上述のハロゲン化水素を捕捉できるものであれば任意のものを使用する事ができる。塩基性化合物としては、例えば、
ピリジン、トリエチルアミンなどの各種アミン類；
水酸化ナトリウム、水酸化カリウム、水酸化カルシウムなどの各種水酸化物；
等が挙がられる。
As the basic compound used in the present invention, any compound can be used as long as it can capture the above-described hydrogen halide. Examples of basic compounds include:
Various amines such as pyridine and triethylamine;
Various hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide;
And so on.
上記の塩基性化合物の中でも、プロトン性溶媒に溶解しやすい点、ハロゲン化水素との反応により生成するハロゲン化合物塩の除去が容易である点（プロトン溶媒中での析出）を考慮すると、塩基性化合物には水酸化物を使用する事が好ましく、水酸化カリウムを使用する事がさらに好ましい。 Among the basic compounds described above, in view of the point of being easily dissolved in a protic solvent and the point of easy removal of the halogen compound salt produced by the reaction with hydrogen halide (precipitation in a proton solvent) The compound is preferably a hydroxide, and more preferably potassium hydroxide.
ピロリジン２−カルボン酸塩は、ピロリジン２−カルボン酸と塩基性化合物をあらかじめ反応させたアミノ酸塩である。ピロリジン２−カルボン酸塩としては、例えば、ピロリジン２−カルボン酸ナトリウム、ピロリジン２−カルボン酸カリウム等が挙げられる。 Pyrrolidine 2-carboxylate is an amino acid salt obtained by reacting pyrrolidine 2-carboxylic acid with a basic compound in advance. Examples of the pyrrolidine 2-carboxylate include sodium pyrrolidine 2-carboxylate and potassium pyrrolidine 2-carboxylate.
一般式（２）で表されるエチレン性不飽和単量体は、１分子中にスチレン骨格とハロゲン化アルキル基を有している。
Ｒは、炭素数１以上の直鎖又は分岐アルキレン基を示し、直鎖又は分岐アルキレン基としては、メチレン基、エチレン基、プロピレン基、ブチレン基、トリメチレン基、テトラメチレン基、ヘキサメチレン基、オクタメチレン、または、１，２−シクロヘキセン基、１，３−シクロヘキセン基、１，４−シクロヘキセン基、２−メチルプロペン基等が挙げられる。好ましくは炭素数が１〜６のアルキレン基である。
一般式（２）で表されるエチレン性不飽和単量体の好ましい例としては、クロロメチルスチレン、クロロエチルスチレン、クロロプロピルスチレン、クロロブチルスチレン、ブロモメチルスチレン、ブロモエチルスチレン、ブロモプロピルスチレン、ブロモブチルスチレン等が挙げられる。これらは、オルト体、メタ体、パラ体等の構造異性体を含んでいても構わない。
The ethylenically unsaturated monomer represented by the general formula (2) has a styrene skeleton and an alkyl halide group in one molecule.
R represents a linear or branched alkylene group having 1 or more carbon atoms, and examples of the linear or branched alkylene group include a methylene group, an ethylene group, a propylene group, a butylene group, a trimethylene group, a tetramethylene group, a hexamethylene group, an octane group, Examples include methylene, 1,2-cyclohexene group, 1,3-cyclohexene group, 1,4-cyclohexene group, 2-methylpropene group and the like. Preferably it is a C1-C6 alkylene group.
Preferred examples of the ethylenically unsaturated monomer represented by the general formula (2) include chloromethyl styrene, chloroethyl styrene, chloropropyl styrene, chlorobutyl styrene, bromomethyl styrene, bromoethyl styrene, bromopropyl styrene, Examples include bromobutyl styrene. These may contain structural isomers such as ortho, meta, and para isomers.
反応温度は５℃から８０℃の範囲で行う事が好ましい。上記反応温度に限定されるわけではないが、反応温度が５℃未満であると、反応が進行しない恐れがある。一方で８０℃を超えた場合、ハロゲン基が、二級アミノ基以外の官能基と反応する副反応の割合が高くなり、収率の低下を招く恐れがある。また、エチレン性不飽和基が重合してしまう恐れもある。 The reaction temperature is preferably 5 to 80 ° C. Although it is not necessarily limited to the said reaction temperature, there exists a possibility that reaction may not advance that reaction temperature is less than 5 degreeC. On the other hand, when it exceeds 80 degreeC, the ratio of the side reaction which a halogen group reacts with functional groups other than a secondary amino group may become high, and there exists a possibility of causing the fall of a yield. Further, there is a possibility that the ethylenically unsaturated group is polymerized.
反応時間は、２〜２０時間である事が好ましい。上記反応温度に限定されるわけではないが、２時間未満であると、反応が十分に進行せず、収率が下がる恐れがある。一方、２０時間以上であると、エチレン性不飽和基の重合が起こり、収率が低下する恐れがある。 The reaction time is preferably 2 to 20 hours. Although it is not necessarily limited to the said reaction temperature, when it is less than 2 hours, reaction may not fully advance and there exists a possibility that a yield may fall. On the other hand, when it is 20 hours or more, polymerization of the ethylenically unsaturated group occurs and the yield may be lowered.
上述の反応の際に、原料もしくは目的物の重合を防ぐために、重合禁止剤を適量併用する事ができる。 In the above reaction, an appropriate amount of a polymerization inhibitor can be used in combination in order to prevent polymerization of the raw material or the target product.
重合禁止剤としては、メトキシフェノールやハイドロキノン、ｔ−ブチルカテコールなどが挙げられる。 Examples of the polymerization inhibitor include methoxyphenol, hydroquinone, t-butylcatechol and the like.
反応の進行ならびに終点は、薄層クロマトグラフィー（展開溶媒はクロロホルム・メタノール混合溶媒。重量比でクロロホルム：メタノール＝３：１）により確認した。 The progress and end point of the reaction were confirmed by thin layer chromatography (developing solvent: chloroform / methanol mixed solvent, chloroform: methanol = 3: 1 by weight).
次に生成したハロゲン塩を脱塩処理する第２の工程について説明する。脱塩処理の方法としては、電気透析により分離する方法や、溶媒に対して不溶なハロゲン塩を析出させて濾別する方法等が挙げられる。またこれらの方法を組み合わせる事も可能である。 Next, the 2nd process of desalting the produced | generated halogen salt is demonstrated. Examples of the desalting treatment include a method of separating by electrodialysis, a method of depositing a halogen salt insoluble in a solvent, and filtering. It is also possible to combine these methods.
電気透析で分離する方法は、一般的に知られるアミノ酸と食塩の分離と同様の要領で分離する事ができる。本発明で製造する両性エチレン性不飽和単量体は、アミノ酸に類似した両性構造を有している。したがって、当電点付近で電気透析をかける事でハロゲン化物の塩に由来するイオンを除去する事ができる。 The method of separation by electrodialysis can be performed in the same manner as the separation of generally known amino acids and sodium chloride. The amphoteric ethylenically unsaturated monomer produced in the present invention has an amphoteric structure similar to an amino acid. Therefore, by applying electrodialysis in the vicinity of the current point, ions derived from halide salts can be removed.
溶媒に対して不溶なハロゲン化物塩を析出させて濾別する方法は、最適な塩基性化合物、プロトン性溶媒を選択する事で、比較的簡単な設備で容易に脱塩処理をおこなう事ができる。例えば、塩基性化合物に水酸化カリウム、プロトン性溶媒にエタノールを使用した場合、反応前の段階では容易に塩基性化合物が溶媒に溶解する一方、反応後にはハロゲン化物の塩がほとんど溶解せずに析出するため、簡単な濾別だけで脱塩処理が可能である。 The method of precipitating a halide salt that is insoluble in the solvent and filtering it out can be easily desalted with relatively simple equipment by selecting the most suitable basic compound and protic solvent. . For example, when potassium hydroxide is used as the basic compound and ethanol is used as the protic solvent, the basic compound is easily dissolved in the solvent before the reaction, while the halide salt is hardly dissolved after the reaction. Since it precipitates, it can be desalted by simple filtration.
得られたピロリジン-２-カルボン酸残基含有エチレン性不飽和単量体は、再沈殿や再結晶の工程により純度を上げる事ができる。再沈殿や再結晶の際に使用する溶剤には任意の溶剤を使用する事ができるが、除去のしやすさを考慮すると、低沸点の溶剤を使用する事が好ましい。使用できる溶剤としては、アセトン、メチルエチルケトン、メチルイソブチルケトン等のケトン系溶剤；酢酸エチル、酢酸プロピル等のエステル系溶剤；ジエチルエーテル等のエーテル系溶剤；ヘキサン等の炭化水素系溶剤等が挙げられる。 The purity of the obtained pyrrolidine-2-carboxylic acid residue-containing ethylenically unsaturated monomer can be increased by a reprecipitation or recrystallization process. Although any solvent can be used as the solvent used for reprecipitation or recrystallization, it is preferable to use a solvent having a low boiling point in view of ease of removal. Examples of the solvent that can be used include ketone solvents such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; ester solvents such as ethyl acetate and propyl acetate; ether solvents such as diethyl ether; hydrocarbon solvents such as hexane.
アルキル基含有エチレン性不飽和単量体（ｂ）としては、メチルメタクリレート、エチルメタクリレート、プロピルメタクリレート、ｎ−ブチルメタクリレート、ｔーブチルメタクリレート、ペンチル（メタ）アクリレート、ヘプチル（メタ）アクリレート、ヘキシル（メタ）アクリレート、２−エチルヘキシル（メタ）アクリレート、オクチル（メタ）アクリレート、ノニル（メタ）アクリレート、デシル（メタ）アクリレート、ウンデシル（メタ）アクリレート、ドデシル（メタ）アクリレート、トリデシル（メタ）アクリレート、テトラデシル（メタ）アクリレート等の直鎖または分岐アルキル基含有エチレン性不飽和単量体；
シクロヘキシル（メタ）アクリレート、イソボニル（メタ）アクリレート等の脂環式ア
ルキル基含有エチレン性不飽和単量体；
等が挙げられる。
Examples of the alkyl group-containing ethylenically unsaturated monomer (b) include methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, pentyl (meth) acrylate, heptyl (meth) acrylate, hexyl (meta) ) Acrylate, 2-ethylhexyl (meth) acrylate, octyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, undecyl (meth) acrylate, dodecyl (meth) acrylate, tridecyl (meth) acrylate, tetradecyl (meth) ) Ethylenically unsaturated monomers containing linear or branched alkyl groups such as acrylates;
Alicyclic alkyl group-containing ethylenically unsaturated monomers such as cyclohexyl (meth) acrylate and isobornyl (meth) acrylate;
Etc.
次に両性基含有エチレン性不飽和単量体（ａ）とアルキル基含有エチレン性不飽和単量体（ｂ）を含むエチレン性不飽和単量体から製造される共重合体について説明する。本発明のピロリジン-２-カルボン酸残基含有共重合体は、上述の工程で得られた両性基含有エチレン性不飽和単量体（ａ）とアルキル基含有エチレン性不飽和単量体（ｂ）を含むその他のエチレン性不飽和単量体とをラジカル重合により、共重合して得る事ができる。重合方法としては、溶液重合や乳化重合、分散重合など任意の方法が使用できる。 Next, a copolymer produced from an ethylenically unsaturated monomer including the amphoteric group-containing ethylenically unsaturated monomer (a) and the alkyl group-containing ethylenically unsaturated monomer (b) will be described. The pyrrolidine-2-carboxylic acid residue-containing copolymer of the present invention comprises an amphoteric group-containing ethylenically unsaturated monomer (a) and an alkyl group-containing ethylenically unsaturated monomer (b ) And other ethylenically unsaturated monomers can be obtained by copolymerization by radical polymerization. As the polymerization method, any method such as solution polymerization, emulsion polymerization, and dispersion polymerization can be used.
本発明で使用する両性基含有エチレン性不飽和単量体（ａ）は、その他のエチレン性不飽和単量体との共重合性に優れ、親水基として耐加水分解性にも優れる。また、ピロリジン-２-カルボン酸残基が水相に向かって配向するため、水の構造を乱さない両性基の性質から、生体分子の吸着抑制能（生体適合性）を発現する。このピロリジン-２-カルボン酸残基含有エチレン性不飽和単量体にアルキル基含有エチレン性不飽和単量体（ｂ）を共重合する事で樹脂に柔軟性や疎水性が付与され、フィルム基材との密着性が向上し、高耐久性の生体適合性材料を得る事ができる。 The amphoteric group-containing ethylenically unsaturated monomer (a) used in the present invention is excellent in copolymerizability with other ethylenically unsaturated monomers and is also excellent in hydrolysis resistance as a hydrophilic group. In addition, since the pyrrolidine-2-carboxylic acid residue is oriented toward the aqueous phase, it exhibits the ability to suppress the adsorption of biomolecules (biocompatibility) from the nature of the amphoteric group that does not disturb the structure of water. By copolymerizing this pyrrolidine-2-carboxylic acid residue-containing ethylenically unsaturated monomer with an alkyl group-containing ethylenically unsaturated monomer (b), flexibility and hydrophobicity are imparted to the resin. Adhesion with the material is improved, and a highly durable biocompatible material can be obtained.
両性エチレン性不飽和単量体（a）は、エチレン性不飽和単量体全体に対して、５〜９０％含有する事が好ましい。５％以上であると、生体分子の吸着抑制の効果に優れる。一方で、９０％以下であると、樹脂の耐水性が向上し、水中に溶出しにくくなるため生体分子の吸着抑制効果に優れる。また、上記範囲であると基材密着性も向上する。 The amphoteric ethylenically unsaturated monomer (a) is preferably contained in an amount of 5 to 90% based on the entire ethylenically unsaturated monomer. When it is 5% or more, the effect of suppressing the adsorption of biomolecules is excellent. On the other hand, if it is 90% or less, the water resistance of the resin is improved, and it becomes difficult to elute in water, so that the effect of suppressing the adsorption of biomolecules is excellent. Moreover, substrate adhesiveness also improves that it is the said range.
アルキル基含有エチレン性不飽和単量体（ｂ）は、共重合体に柔軟性、基材密着性、耐水性を付与し、共重合体の生体適合性の耐久性を向上させる。 The alkyl group-containing ethylenically unsaturated monomer (b) imparts flexibility, substrate adhesion and water resistance to the copolymer, and improves the biocompatibility durability of the copolymer.
アルキル基含有エチレン性不飽和単量体（ｂ）はエチレン性不飽和単量体全体に対して、１０〜９５％含有する事が好ましい。この範囲で、アルキル基含有エチレン性不飽和単量体（ｂ）を含有する事で、樹脂の柔軟性およびフィルム界面との疎水性相互作用が向上するため、フィルム基材への密着性が良化する。 The alkyl group-containing ethylenically unsaturated monomer (b) is preferably contained in an amount of 10 to 95% based on the entire ethylenically unsaturated monomer. Within this range, the inclusion of the alkyl group-containing ethylenically unsaturated monomer (b) improves the flexibility of the resin and the hydrophobic interaction with the film interface, and therefore the adhesion to the film substrate is good. Turn into.
エチレン性不飽和単量体（ｃ）に含まれていても良い他の共重合可能なエチレン性不飽和単量体としては、
ベンジルアクリレート、ベンジルメタクリレート、フェノキシエチルアクリレート、フェノキシエチルメタクリレート、フェノキシジエチレングリコールアクリレート、フェノキシジエチレングリコールメタクリレート、フェノキシテトラエチレングリコールアクリレート、フェノキシテトラエチレングリコールメタクリレート、フェノキシヘキサエチレングリコールアクリレート、フェノキシヘキサエチレングリコールメタクリレート、フェニルアクリレート、フェニルメタクリレート等の芳香族エチレン性不飽和単量体；
トリフルオロエチル（メタ）アクリレート、ヘプタデカフルオロデシル（メタ）アクリレート等のフッ素化アルキル基含有エチレン性不飽和単量体；
アセトアセトキシ（メタ）アクリレート等のケト基含有エチレン性不飽和単量体；
（メタ）アクリルアミド、Ｎ−メトキシメチル−（メタ）アクリルアミド、Ｎ−エトキシメチル−（メタ）アクリルアミド、Ｎ−プロポキシメチル−（メタ）アクリルアミド、Ｎ−ブトキシメチル−（メタ）アクリルアミド、Ｎ−ペントキシメチル−（メタ）アクリルアミド、Ｎ，Ｎ−ジ（メトキシメチル）アクリルアミド、Ｎ−エトキシメチル−Ｎ−メトキシメチルメタアクリルアミド、Ｎ，Ｎ−ジ（エトキシメチル）アクリルアミド、Ｎ−エトキシメチル−Ｎ−プロポキシメチルメタアクリルアミド、Ｎ，Ｎ−ジ（プロポキシメチル）アクリルアミド、Ｎ−ブトキシメチル−Ｎ−（プロポキシメチル）メタアクリルアミド、Ｎ，Ｎ−ジ（ブトキシメチル）アクリルアミド、Ｎ−ブトキシメチル−Ｎ−（メトキシメチル）メタアクリルアミド、Ｎ，Ｎ−ジ（ペントキシメチル）アクリルアミド、Ｎ−メトキシメチル−Ｎ−（ペントキシメチル）メタアクリルアミド、Ｎ，Ｎ−ジメチルアミノプロピルアクリルアミド、Ｎ，Ｎ−ジエチルアミノプロピルアクリルアミド、Ｎ，Ｎ−ジメチルアクリルアミド、Ｎ，Ｎ−ジエチルアクリルアミド等のアミド基含有エチレン性不飽和単量体；
ポリエチレングリコールモノ（メタ）アクリレート（日油社製、ブレンマーＰＥ−９０、２００、３５０、３５０Ｇ、ＡＥ−９０、２００、４００等）ポリエチレングリコール・ポリプロピレングリコールモノ（メタ）アクリレート（日油社製、ブレンマー５０ＰＥＰ−３００、７０ＰＥＰ−３５０等）、メトキシポリエチレングリコールモノ（メタ）アクリレート（日油社製、ブレンマーＰＭＥ−４００、５５０、１０００、４０００等）等のポリエチレンオキサイド基含有エチレン性不飽和単量体；２−ヒドロキシエチル（メタ）アクリレート、２−ヒドロキシプロピル（メタ）アクリレート、４−ヒドロキシブチル（メタ）アクリレート、グリセロールモノ（メタ）アクリレート等のヒドロキシル基含有エチレン性不飽和単量体；
As other copolymerizable ethylenically unsaturated monomers which may be contained in the ethylenically unsaturated monomer (c),
Benzyl acrylate, benzyl methacrylate, phenoxyethyl acrylate, phenoxyethyl methacrylate, phenoxydiethylene glycol acrylate, phenoxydiethylene glycol methacrylate, phenoxytetraethylene glycol acrylate, phenoxytetraethylene glycol methacrylate, phenoxyhexaethylene glycol acrylate, phenoxyhexaethylene glycol methacrylate, phenyl acrylate, phenyl Aromatic ethylenically unsaturated monomers such as methacrylate;
Fluorinated alkyl group-containing ethylenically unsaturated monomers such as trifluoroethyl (meth) acrylate and heptadecafluorodecyl (meth) acrylate;
Keto group-containing ethylenically unsaturated monomers such as acetoacetoxy (meth) acrylate;
(Meth) acrylamide, N-methoxymethyl- (meth) acrylamide, N-ethoxymethyl- (meth) acrylamide, N-propoxymethyl- (meth) acrylamide, N-butoxymethyl- (meth) acrylamide, N-pentoxymethyl -(Meth) acrylamide, N, N-di (methoxymethyl) acrylamide, N-ethoxymethyl-N-methoxymethylmethacrylamide, N, N-di (ethoxymethyl) acrylamide, N-ethoxymethyl-N-propoxymethylmeta Acrylamide, N, N-di (propoxymethyl) acrylamide, N-butoxymethyl-N- (propoxymethyl) methacrylamide, N, N-di (butoxymethyl) acrylamide, N-butoxymethyl-N- (methoxymethyl) meta Acrylic net N, N-di (pentoxymethyl) acrylamide, N-methoxymethyl-N- (pentoxymethyl) methacrylamide, N, N-dimethylaminopropylacrylamide, N, N-diethylaminopropylacrylamide, N, N-dimethyl Amide group-containing ethylenically unsaturated monomers such as acrylamide and N, N-diethylacrylamide;
Polyethylene glycol mono (meth) acrylate (manufactured by NOF Corporation, Blemmer PE-90, 200, 350, 350G, AE-90, 200, 400, etc.) polyethylene glycol / polypropylene glycol mono (meth) acrylate (manufactured by NOF Corporation, Blemmer Polyethylene oxide group-containing ethylenically unsaturated monomers such as 50PEP-300, 70PEP-350, etc.), methoxypolyethylene glycol mono (meth) acrylate (manufactured by NOF Corporation, BLEMMER PME-400, 550, 1000, 4000, etc.); Hydroxyl group-containing ethylenically unsaturated monomers such as 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate, glycerol mono (meth) acrylate;
アクリル酸、メタクリル酸等のカルボキシル基含有エチレン性不飽和単量体； Carboxyl group-containing ethylenically unsaturated monomers such as acrylic acid and methacrylic acid;
アリル（メタ）アクリレート、１−メチルアリル（メタ）アクリレート、２−メチルアリル（メタ）アクリレート、１−ブテニル（メタ）アクリレート、２−ブテニル（メタ）アクリレート、３−ブテニル（メタ）アクリレート、１，３−メチル−３−ブテニル（メタ）アクリレート、ｏ−アリルフェニル（メタ）アクリレート、２−（アリルオキシ）エチル（メタ）アクリレート、アリルラクチル（メタ）アクリレート、シトロネリル（メタ）アクリレート、ゲラニル（メタ）アクリレート、ロジニル（メタ）アクリレート、シンナミル（メタ）アクリレート、２−（２’−ビニロキシエトキシ）エチル（メタ）アクリレート、エチレングリコールジ（メタ）アクリレート、トリエチレングリコール（メタ）アクリレート、テトラエチレングリコール（メタ）アクリレート、トリメチロールプロパントリ（メタ）アクリレート、ペンタエリスリトールトリ（メタ）アクリレート、１，１，１−トリスヒドロキシメチルエタンジアクリレート、１，１，１−トリスヒドロキシメチルエタントリアクリレート、１，１，１−トリスヒドロキシメチルプロパントリアクリレート等の２個以上のエチレン性不飽和基を有するエチレン性不飽和単量体；
グリシジル（メタ）アクリレート、３，４−エポキシシクロヘキシル（メタ）アクリレート等のエポキシ基含有エチレン性不飽和単量体；
γ−メタクリロキシプロピルトリメトキシシラン、γ−メタクリロキシプロピルトリエトキシシラン、γ−メタクリロキシプロピルトリブトキシシラン、γ−メタクリロキシプロピルメチルジメトキシシラン、γ−メタクリロキシプロピルメチルジエトキシシラン、γ−アクリロキシプロピルトリメトキシシラン、γ−アクリロキシプロピルトリエトキシシラン、γ−アクリロキシプロピルメチルジメトキシシラン、γ−メタクリロキシメチルトリメトキシシラン、γ−アクリロキシメチルトリメトキシシラン等のアルコキシシリル基含有エチレン性不飽和単量体が挙げられるが、特にこれらに限定されるものではない。これらは１種類または２種以上を併用して用いることができる
Allyl (meth) acrylate, 1-methylallyl (meth) acrylate, 2-methylallyl (meth) acrylate, 1-butenyl (meth) acrylate, 2-butenyl (meth) acrylate, 3-butenyl (meth) acrylate, 1,3- Methyl-3-butenyl (meth) acrylate, o-allylphenyl (meth) acrylate, 2- (allyloxy) ethyl (meth) acrylate, allyl lactyl (meth) acrylate, citronellyl (meth) acrylate, geranyl (meth) acrylate, rosinyl ( (Meth) acrylate, cinnamyl (meth) acrylate, 2- (2′-vinyloxyethoxy) ethyl (meth) acrylate, ethylene glycol di (meth) acrylate, triethylene glycol (meth) acrylate, tetraethylene glycol Recall (meth) acrylate, trimethylolpropane tri (meth) acrylate, pentaerythritol tri (meth) acrylate, 1,1,1-trishydroxymethylethane diacrylate, 1,1,1-trishydroxymethylethane triacrylate, 1 Ethylenically unsaturated monomers having two or more ethylenically unsaturated groups, such as 1,1-trishydroxymethylpropane triacrylate;
Epoxy group-containing ethylenically unsaturated monomers such as glycidyl (meth) acrylate and 3,4-epoxycyclohexyl (meth) acrylate;
γ-methacryloxypropyltrimethoxysilane, γ-methacryloxypropyltriethoxysilane, γ-methacryloxypropyltributoxysilane, γ-methacryloxypropylmethyldimethoxysilane, γ-methacryloxypropylmethyldiethoxysilane, γ-acryloxy Alkoxysilyl group-containing ethylenic unsaturation such as propyltrimethoxysilane, γ-acryloxypropyltriethoxysilane, γ-acryloxypropylmethyldimethoxysilane, γ-methacryloxymethyltrimethoxysilane, γ-acryloxymethyltrimethoxysilane Although a monomer is mentioned, it is not specifically limited to these. These can be used alone or in combination of two or more.
重合開始剤としては、溶媒に溶解し、ラジカル重合を開始する能力を有するものであれば特に制限はなく、公知の油溶性重合開始剤や水溶性重合開始剤を使用することができる。 The polymerization initiator is not particularly limited as long as it has the ability to dissolve in a solvent and start radical polymerization, and known oil-soluble polymerization initiators and water-soluble polymerization initiators can be used.
油溶性重合開始剤としては特に限定されず、例えば、ベンゾイルパーオキサイド、ｔｅｒｔ−ブチルパーオキシベンゾエート、ｔｅｒｔ−ブチルハイドロパーオキサイド、ｔｅｒｔ−ブチルパーオキシ（２−エチルヘキサノエート）、ｔｅｒｔ−ブチルパーオキシ−３，５，５−トリメチルヘキサノエート、ジ−ｔｅｒｔ−ブチルパーオキサイドなどの有機過酸化物；
２，２’−アゾビスイソブチロニトリル、２，２’−アゾビス−２，４−ジメチルバレロニトリル、２，２’−アゾビス（４−メトキシ−２，４−ジメチルバレロニトリル）、１，１’−アゾビス−シクロヘキサン−１−カルボニトリルなどのアゾビス化合物を挙げることができる。これらは１種類または２種類以上を混合して使用することができる。
The oil-soluble polymerization initiator is not particularly limited, and examples thereof include benzoyl peroxide, tert-butyl peroxybenzoate, tert-butyl hydroperoxide, tert-butyl peroxy (2-ethylhexanoate), and tert-butyl peroxide. Organic peroxides such as oxy-3,5,5-trimethylhexanoate, di-tert-butyl peroxide;
2,2′-azobisisobutyronitrile, 2,2′-azobis-2,4-dimethylvaleronitrile, 2,2′-azobis (4-methoxy-2,4-dimethylvaleronitrile), 1,1 Mention may be made of azobis compounds such as' -azobis-cyclohexane-1-carbonitrile. These can be used alone or in combination of two or more.
水溶性重合開始剤としては特に限定されず、例えば、過硫酸アンモニウム、過硫酸カリウム、過酸化水素、２，２’−アゾビス（２−メチルプロピオンアミジン）ジハイドロクロライドなど、従来既知のものを好適に使用することができる。 The water-soluble polymerization initiator is not particularly limited, and for example, conventionally known ones such as ammonium persulfate, potassium persulfate, hydrogen peroxide, 2,2′-azobis (2-methylpropionamidine) dihydrochloride are preferably used. Can be used.
重合時に使用する溶媒としては、両性エチレン性不飽和単量体（ａ）を溶解するものであれば、任意のものを使用する事ができるが、重合後の除去を考慮すると、水、アルコール溶剤を使用する事が好ましい。また、ピロリジン-２-カルボン酸残基含有エチレン性不飽和単量体を得る際に使用したアルコール溶剤は、そのまま重合工程に進む場合には、反応系から除去せずに重合時の溶剤としても使用する事も可能である。 As the solvent used in the polymerization, any solvent can be used as long as it dissolves the amphoteric ethylenically unsaturated monomer (a). It is preferable to use In addition, the alcohol solvent used in obtaining the ethylenically unsaturated monomer containing pyrrolidine-2-carboxylic acid residue may be used as a solvent for polymerization without being removed from the reaction system when proceeding to the polymerization step as it is. It is also possible to use it.
本発明のピロリジン-２-カルボン酸残基含有共重合体は、生体適合性材料として好適に使用できる。また、生体適合性材料は、生体適合性に悪影響を及ぼさない範囲で、他の樹脂、添加剤、溶剤などが含まれていても構わない。 The pyrrolidine-2-carboxylic acid residue-containing copolymer of the present invention can be suitably used as a biocompatible material. In addition, the biocompatible material may contain other resins, additives, solvents, and the like as long as the biocompatibility is not adversely affected.
本発明の生体適合性材料を用いて、基材上に被膜を形成することができる。被膜を形成する方法は、特に限定されず、例えば、基材に、塗布、スプレー、蒸着をした後に、熱乾燥させて被膜を形成する方法、重合前のモノマー組成物と重合開始剤とを混合した液体を基材に塗布した後、熱や光でモノマー組成物を重合させ、被膜を形成する方法などが挙げられる。 A coating can be formed on a substrate using the biocompatible material of the present invention. The method for forming the coating is not particularly limited. For example, after coating, spraying, and vapor-depositing on a substrate, the coating is thermally dried to form the coating, and the monomer composition before polymerization and the polymerization initiator are mixed. For example, a method of forming a film by applying the liquid to the substrate and then polymerizing the monomer composition with heat or light.
本発明のピロリジン２−カルボン酸残基含有共重合体は金属やガラス等の極性基材は勿論の事、ポリエチレンテレフタレート（ＰＥＴ）やポリプロピレン（ＰＰ）などの非極性フィルム基材への密着性に優れる。 The pyrrolidine 2-carboxylic acid residue-containing copolymer of the present invention is not only for polar substrates such as metals and glass, but also for adhesion to nonpolar film substrates such as polyethylene terephthalate (PET) and polypropylene (PP). Excellent.
基材を構成する素材としては、例えば、ポリエチレン、ポリプロピレン、ポリエチレンテレフタレート、ポリスチレン、ポリ塩化ビニル、ナイロン、ポリウレタン、ポリウレア、ポリ乳酸、ポリグリコール酸、ポリビニルアルコール、ポリ酢酸ビニル、ポリ(メタ)アクリル酸、ポリ(メタ)アクリル酸誘導体、ポリアクリロニトリル、ポリ(メタ)アクリルアミド、ポリ(メタ)アクリルアミド誘導体、ポリスルホン、ポリカーボネート、セルロース、セルロース誘導体、ポリシリコーン、ガラス、セラミック、金属などが挙げられる。これらの素材は、それぞれ単独でまたは２種以上を組合せて用いることができる。 Examples of the material constituting the substrate include polyethylene, polypropylene, polyethylene terephthalate, polystyrene, polyvinyl chloride, nylon, polyurethane, polyurea, polylactic acid, polyglycolic acid, polyvinyl alcohol, polyvinyl acetate, and poly (meth) acrylic acid. , Poly (meth) acrylic acid derivatives, polyacrylonitrile, poly (meth) acrylamides, poly (meth) acrylamide derivatives, polysulfones, polycarbonates, celluloses, cellulose derivatives, polysilicones, glasses, ceramics, metals and the like. These materials can be used alone or in combination of two or more.
以下に、実施例により本発明をさらに具体的に説明するが、以下の実施例は本発明の権利範囲を何ら制限するものではない。なお、実施例における「部」は「重量部」、「％」は「重量％」を表す。 EXAMPLES The present invention will be described more specifically with reference to the following examples. However, the following examples do not limit the scope of rights of the present invention. In the examples, “part” represents “part by weight” and “%” represents “% by weight”.
＜エチレン性不飽和単量体（ａ）の製造＞
[製造例１]
撹拌機および温度計、還流器、滴下ロートを備えた反応容器に、ピロリジン−２−カルボン酸３７．７部、水酸化カリウム１８．４部、エタノール１０６．０部を仕込んだ。撹拌しながら７０度まで昇温して原料を溶解させた。溶解後、温度を４０℃まで冷却した。滴下ロートから、４−クロロメチルスチレン５０．０部を１時間かけて滴下した。反応温度を４０℃に維持して６時間反応させた。反応後、溶液を濾過して副生成物の塩化カリウムの結晶を除去し、濾液を分取した。この濾液に酢酸エチルを少しずつ加え、冷却して再結晶をおこなった。再度、得られた結晶をエタノールに溶解させ、酢酸エチルで再結晶下後、室温で２４時間、減圧乾燥して目的物であるエチレン性不飽和単量体の白色結晶を得た。収率は８０．０％であった。
得られた生成物について、1Ｈ−ＮＭＲおよび元素分析をおこなった。
[1Ｈ−ＮＭＲ］
ＮＭＲスペクトルは、日本電子製ＥＣＸ−４００Ｐ（４００ＭＨｚ）を使用して測定した。測定時の重溶媒には重クロロホルム（ＣＤＣｌ3）を用いた。
[元素分析]
元素分析は、パーキンエルマー社製、２４００ＣＨＮを使用して測定した。
[1Ｈ−ＮＭＲスペクトル]
（δ値）１．８８−２．０１（２Ｈ）、２．２３−２．３４（２Ｈ）、２．８３−２．９０（１Ｈ）、３．６４−３．７０（１Ｈ）、３．７７−３．８１（１Ｈ）、４．１３−４．１９（１Ｈ），４．３０−４.３４（１Ｈ）、５．２８−５．３０（１Ｈ）、５．７２−５．７７（１Ｈ）、６．６４−６．７１（１Ｈ）、７．２７−７．３４（４Ｈ）
[元素分析]
Ｃ１４Ｈ１７Ｎ１として
理論値（％）：Ｈ=８．６０ Ｃ=８４．３７ Ｎ= ７．０３
実測値（％）：Ｈ=８．５４ Ｃ=８４．４２ Ｎ= ７．０４
上記の結果から、生成物が次式で表されるエチレン性不飽和単量体であると同定した。
<Production of ethylenically unsaturated monomer (a)>
[Production Example 1]
A reaction vessel equipped with a stirrer, a thermometer, a reflux condenser, and a dropping funnel was charged with 37.7 parts of pyrrolidine-2-carboxylic acid, 18.4 parts of potassium hydroxide, and 106.0 parts of ethanol. The temperature was raised to 70 degrees with stirring to dissolve the raw material. After dissolution, the temperature was cooled to 40 ° C. From the dropping funnel, 50.0 parts of 4-chloromethylstyrene was dropped over 1 hour. The reaction temperature was maintained at 40 ° C. for 6 hours. After the reaction, the solution was filtered to remove crystals of by-product potassium chloride, and the filtrate was separated. Ethyl acetate was added little by little to the filtrate, followed by cooling and recrystallization. The obtained crystals were dissolved again in ethanol, recrystallized with ethyl acetate, and then dried under reduced pressure at room temperature for 24 hours to obtain white crystals of the target ethylenically unsaturated monomer. The yield was 80.0%.
The obtained product was subjected to 1 H-NMR and elemental analysis.
[ 1 H-NMR]
The NMR spectrum was measured using ECX-400P (400 MHz) manufactured by JEOL. Deuterated chloroform (CDCl 3 ) was used as a heavy solvent for the measurement.
[Elemental analysis]
Elemental analysis was performed using 2400CHN manufactured by PerkinElmer.
[ 1 H-NMR spectrum]
(Δ value) 1.88-2.01 (2H), 2.23-2.34 (2H), 2.83-2.90 (1H), 3.64-3.70 (1H), 3. 77-3.81 (1H), 4.13-4.19 (1H), 4.30-4.34 (1H), 5.28-5.30 (1H), 5.72-5.77 ( 1H), 6.64-6.71 (1H), 7.27-7.34 (4H)
[Elemental analysis]
Theoretical value (%) as C14H17N1: H = 8.60 C = 84.37 N = 7.03
Actual value (%): H = 8.54 C = 84.42 N = 7.04
From the above results, the product was identified as an ethylenically unsaturated monomer represented by the following formula.
化学式（３）
[製造例２]
還流器および撹拌機を備えた反応容器に、４−ヒドロキシブチルアクリレート１３８．０重量部、ピリジン７６．０重量部を仕込んだ。氷冷しながら、メタクリル酸クロリド１００．０重量部を１時間かけて滴下した。４時間反応させた後、ピリジン塩酸塩をろ過で取り除き、４-(アクリロイルオキシ)ブチルメタクリレートを１３０．０重量部得た。還流器および撹拌機を備えた反応容器に前記で得た４-(アクリロイルオキシ)ブチルメタクリレート１００．０重量部、ピロリジン-2-カルボン酸５１．５重量部、エタノール１５１．５重量部を仕込んだ。撹拌しながら昇温した後、７０℃で５時間反応させた。反応終了後、減圧乾燥によりエタノールを除去し、アセトンで再結晶をおこない目的物を得た。収率は８５％であった。得られた生成物について、1Ｈ−ＮＭＲおよび元素分析をおこなった。
[1Ｈ−ＮＭＲスペクトル]
（δ値）１．６０(４Ｈ)、１．９０−１．９８（５Ｈ）、２．３１（２Ｈ）、２．８９（３Ｈ）、３．２９（１Ｈ）、３．５２（３Ｈ）、３．７３（１Ｈ）、３．８１（１Ｈ）、４．１２（４Ｈ）、５．６１（１Ｈ）、６．１４（１Ｈ）
[元素分析]
Ｃ１６Ｈ２５Ｎ１として
理論値（％）：H=１０．８９ C=８３．０６ N= ６．０５
実測値（％）：H=１０．７５ C=８３．２８ N= ５．９７
上記の結果から、生成物が次式で表されるエチレン性不飽和単量体であると同定した。
[Production Example 2]
A reaction vessel equipped with a refluxing apparatus and a stirrer was charged with 138.0 parts by weight of 4-hydroxybutyl acrylate and 76.0 parts by weight of pyridine. While cooling with ice, 100.0 parts by weight of methacrylic acid chloride was added dropwise over 1 hour. After reacting for 4 hours, pyridine hydrochloride was removed by filtration to obtain 130.0 parts by weight of 4- (acryloyloxy) butyl methacrylate. A reaction vessel equipped with a reflux and a stirrer was charged with 100.0 parts by weight of 4- (acryloyloxy) butyl methacrylate obtained above, 51.5 parts by weight of pyrrolidine-2-carboxylic acid, and 151.5 parts by weight of ethanol. . After raising the temperature with stirring, the reaction was carried out at 70 ° C. for 5 hours. After completion of the reaction, ethanol was removed by drying under reduced pressure, and recrystallization was performed with acetone to obtain the desired product. The yield was 85%. The obtained product was subjected to 1 H-NMR and elemental analysis.
[ 1 H-NMR spectrum]
(Δ value) 1.60 (4H), 1.90-1.98 (5H), 2.31 (2H), 2.89 (3H), 3.29 (1H), 3.52 (3H), 3.73 (1H), 3.81 (1H), 4.12 (4H), 5.61 (1H), 6.14 (1H)
[Elemental analysis]
Theoretical value (%) as C16H25N1: H = 10.89 C = 83.06 N = 6.05
Actual value (%): H = 10.75 C = 83.28 N = 5.97
From the above results, the product was identified as an ethylenically unsaturated monomer represented by the following formula.
化学式（４）
Chemical formula (4)
＜ピロリジン２−カルボン酸残基含有共重合体の製造＞
[実施例１]
還流器および撹拌機を備えた反応容器に実施例１で得た両性イオン型エチレン性不飽和単量体３０．０重量部、ブチルメタクリレート７０．０重量部、エタノール１５０．０重量部を仕込んだ。撹拌しながら７０℃に昇温し、窒素置換後、開始剤のアゾビスイソブチルニトリルを５．０重量部添加し、還流条件下で１５時間反応させた。冷却後、目的のピロリジン-２-カルボン酸残基含有重合体を得た。重量平均分子量は３０８００であった。得られた重合体をジエチルエーテルで再沈し、真空乾燥して溶剤を除去し、共重合体の固体を得た。
<Production of pyrrolidine 2-carboxylic acid residue-containing copolymer>
[Example 1]
A reaction vessel equipped with a reflux and a stirrer was charged with 30.0 parts by weight of the zwitterionic ethylenically unsaturated monomer obtained in Example 1, 70.0 parts by weight of butyl methacrylate, and 150.0 parts by weight of ethanol. . The temperature was raised to 70 ° C. with stirring, and after substitution with nitrogen, 5.0 parts by weight of azobisisobutylnitrile as an initiator was added and reacted for 15 hours under reflux conditions. After cooling, the desired pyrrolidine-2-carboxylic acid residue-containing polymer was obtained. The weight average molecular weight was 30800. The obtained polymer was reprecipitated with diethyl ether and vacuum-dried to remove the solvent to obtain a copolymer solid.
[重量平均分子量]
重量平均分子量は、ＧＰＣ（ゲルパーミエーションクロマトグラフィー）測定によるポリスチレン換算の値の事をさす。装置：ＨＬＣ−８３２０−ＧＰシステム（東ソー社製）
カラム；ＴＳＫｇｅｌ ＳｕｐｅｒＨＭ−Ｍ
溶出溶媒;ジメチルホルムアミド
標準物質；ポリスチレン
流速；０．６ｍＬ／分、試料溶液使用量；１０μＬ、カラム温度；４０℃。
[Weight average molecular weight]
The weight average molecular weight refers to a value in terms of polystyrene measured by GPC (gel permeation chromatography). Apparatus: HLC-8320-GP system (manufactured by Tosoh Corporation)
Column; TSKgel SuperHM-M
Elution solvent; dimethylformamide standard; polystyrene flow rate; 0.6 mL / min, sample solution usage; 10 μL, column temperature; 40 ° C.
[実施例２〜８および比較例１〜７]
実施例１と同様に表１に示す配合組成で重合体を調製した。得られた重合体を洗浄して減圧乾燥し、共重合体の固体を得た。
[Examples 2-8 and Comparative Examples 1-7]
A polymer was prepared in the same manner as in Example 1 with the composition shown in Table 1. The obtained polymer was washed and dried under reduced pressure to obtain a copolymer solid.
表１に記載の略称を下記に示す。
・ＭＰＣ：２−メタクリロリルオキシエチルホスホコリン
・ＣＭＢ：Ｎ−メタクリロイルオキシエチル−Ｎ，Ｎ−ジメチルアンモニウム−α−Ｎ−メチルカルボキシベタイン
・ＭＭＡ：メチルメタクリレート
・ＢＭＡ：Ｎ−ブチルメタクリレート
・ＥＡ：エチルアクリレート
・ＩＳＴＡ：イソステアリルアクリレート
・ＢＡ：Ｎ−ブチルアクリレート
・ＬＡ：ラウリルアクリレート
・ＣＨＭＡ：シクロヘキシルメタクリレート
・Ｓｔ：スチレン
・ＨＥＡ：２−ヒドロキシエチルアクリレート
・ＰＭＥ−２００：メトキシポリエチレングリコールモノメタクリレート（エチレンオキサイド鎖付加モル数ｎ＝４)
・ＡＩＢＮ：２,２-アゾビス（２−メチルブチロニトリル）
Abbreviations listed in Table 1 are shown below.
MPC: 2-methacryloyloxyethylphosphocholine CMB: N-methacryloyloxyethyl-N, N-dimethylammonium-α-N-methylcarboxybetaine MMA: methyl methacrylate BMA: N-butyl methacrylate EA: Ethyl acrylate, ISTA: Isostearyl acrylate, BA: N-butyl acrylate, LA: Lauryl acrylate, CHMA: Cyclohexyl methacrylate, St: Styrene, HEA: 2-hydroxyethyl acrylate, PME-200: Methoxypolyethylene glycol monomethacrylate (ethylene oxide) Number of moles of chain addition n = 4)
AIBN: 2,2-azobis (2-methylbutyronitrile)
＜生体適合性材料（塗工用組成物）の調製＞
実施例１で得た樹脂１００部を、ｐＨ４およびｐＨ９の緩衝液１L中で、４０℃・２週間振とうした（加水分解の促進）。その後、水洗浄しながら濾過物を回収し、濾過物を真空乾燥した。この固形樹脂を２０．０部、溶剤としてエタノール８０．０部を混合、溶解して、固形分２０．０％の生体適合評価用の塗工用組成物を調製した。緩衝液は下記の方法で調製した。
ｐＨ４緩衝液（０．１ｍol/L水酸化ナトリウム溶液４ｍＬとフタル酸水素カリウム１０．２ｇを超純水で１０００ｍＬに希釈して調製）
ｐＨ９緩衝液（０．１ｍol/L水酸化ナトリウム溶液２１３ｍＬとホウ酸３．１ｇを超純水で１０００mLに希釈して調製）
<Preparation of biocompatible material (coating composition)>
100 parts of the resin obtained in Example 1 was shaken in 1 L of pH 4 and pH 9 buffer solution at 40 ° C. for 2 weeks (acceleration of hydrolysis). Thereafter, the filtrate was collected while washing with water, and the filtrate was vacuum dried. 20.0 parts of this solid resin and 80.0 parts of ethanol as a solvent were mixed and dissolved to prepare a coating composition for biocompatibility evaluation having a solid content of 20.0%. The buffer solution was prepared by the following method.
pH 4 buffer solution (prepared by diluting 4 mL of 0.1 mol / L sodium hydroxide solution and 10.2 g of potassium hydrogen phthalate to 1000 mL with ultrapure water)
pH 9 buffer (prepared by diluting 213 mL of 0.1 mol / L sodium hydroxide solution and 3.1 g of boric acid to 1000 mL with ultrapure water)
＜評価用被膜の調製＞
処理ＯＰＰ基材に実施例１〜８ならびに比較例１〜７の樹脂を含む塗工用組成物をバーコータ―（Ｎｏ.０９）で塗工した。塗工物をオーブンで８０℃・５分乾燥し、さらに４０℃で２４時間、減圧乾燥をおこない評価用被膜を得た。
<Preparation of coating film for evaluation>
A coating composition containing the resins of Examples 1 to 8 and Comparative Examples 1 to 7 was applied to the treated OPP substrate with a bar coater (No. 09). The coated product was dried in an oven at 80 ° C. for 5 minutes, and further dried under reduced pressure at 40 ° C. for 24 hours to obtain a coating film for evaluation.
＜生体適合性（タンパク質吸着抑制）の評価＞
２４ウェルプレートに上述の塗工物の試験片（直径１４ｍｍ）を入れて底面に固定した。次にリン酸緩衝生理食塩水（以下ＰＢＳ溶液と呼ぶ）を２ｍｌ加え、２４時間静置した。続いて１％タンパク質溶液（フィブリノゲンのＰＢＳ希釈溶液）を０．７ｍｌ添加し３７℃のインキュベータで２４時間静置した。その後、ウェルのタンパク質溶液を除去し、ＰＢＳ溶液で１０回洗浄した。さらにウェルを入れ替えてＰＢＳ溶液で５回洗浄した。ＰＢＳ溶液を除去後、１％ドデシル硫酸ナトリウム水溶液を１ｍｌ加えて１時間静置し、吸着しているタンパク質を溶出させ、ＢＣＡ法（ビスコンシン酸試薬を用いたタンパク定量）で定量した。吸着量が少ないほど、生体適合性、耐加水分解性に優れる。
<Evaluation of biocompatibility (protein adsorption suppression)>
The test piece (14 mm in diameter) of the above-mentioned coated product was put in a 24-well plate and fixed to the bottom surface. Next, 2 ml of phosphate buffered saline (hereinafter referred to as PBS solution) was added and allowed to stand for 24 hours. Subsequently, 0.7 ml of 1% protein solution (diluted solution of fibrinogen in PBS) was added and allowed to stand in a 37 ° C. incubator for 24 hours. Thereafter, the protein solution in the wells was removed and washed 10 times with PBS solution. Further, the wells were replaced and washed 5 times with PBS solution. After removing the PBS solution, 1 ml of 1% sodium dodecyl sulfate aqueous solution was added and allowed to stand for 1 hour to elute the adsorbed protein, and quantified by the BCA method (protein quantification using a bisconsin acid reagent). The smaller the amount of adsorption, the better the biocompatibility and hydrolysis resistance.
＜基材密着性＞
上述の評価用塗膜にセロハンテープ（ニチバン社製１８ｍｍ幅）を貼り付け、垂直方向に剥離試験をおこない、樹脂被膜の剥がれた面積の割合から基材密着性について評価した。
評価基準は以下の通りである。（実用可能レベルは○以上）
◎；剥がれがない
○；剥がれがややある（１０％未満）
△；剥がれがある（１０％以上、５０％未満）
×；剥がれがかなりある（５０％以上）
<Base material adhesion>
A cellophane tape (18 mm width manufactured by Nichiban Co., Ltd.) was applied to the above-described evaluation coating film, a peeling test was performed in the vertical direction, and the substrate adhesion was evaluated from the ratio of the area where the resin coating film was peeled off.
The evaluation criteria are as follows. (Practical level is more than ○)
◎: No peeling ○: Some peeling (less than 10%)
Δ: Peeling (10% or more, less than 50%)
×: There is considerable peeling (50% or more)
表２の結果から、実施例１〜８のピロリジン２−カルボン酸残基含有共重合体を含有した樹脂被膜は、比較例１〜３および７の樹脂被膜と比較して、タンパク質の吸着量が著しく少なく、加水分解促進試験後も生体適合性に優れる事が確認された。また、比較例４から６に対しては、フィルム基材への密着性で優れている事が確認された。
From the results of Table 2, the resin film containing the pyrrolidine 2-carboxylic acid residue-containing copolymer of Examples 1 to 8 has a protein adsorption amount as compared with the resin films of Comparative Examples 1 to 3 and 7. It was confirmed that the biocompatibility was extremely small even after the hydrolysis acceleration test. Moreover, with respect to Comparative Examples 4 to 6, it was confirmed that the adhesiveness to the film substrate was excellent.
Claims (5)
一般式（１）：
（Ｒは、直鎖又は分岐アルキレン基を示す）
A copolymer of the ethylenically unsaturated monomer (c) including the ethylenically unsaturated monomer (a) represented by the general formula (1) and the alkyl group-containing ethylenically unsaturated monomer (b); A pyrrolidine 2-carboxylic acid residue-containing copolymer.
General formula (1):
(R represents a linear or branched alkylene group)
一般式（１）：
（Ｒは、直鎖又は分岐アルキレン基を示す）
一般式（２）：
（Ｒは、直鎖又は分岐アルキレン基、Ｘは、ＣｌまたはＢｒを示す）
After reacting the pyrrolidine 2-carboxylic acid with the ethylenically unsaturated monomer represented by the general formula (2) to obtain the ethylenically unsaturated monomer (a) represented by the general formula (1), A pyrrolidine 2-carboxylic acid residue-containing copolymer copolymerizing an ethylenically unsaturated monomer (c) containing an ethylenically unsaturated monomer (a) and an alkyl group-containing ethylenically unsaturated monomer (b) A method for producing a polymer.
General formula (1):
(R represents a linear or branched alkylene group)
General formula (2):
(R represents a linear or branched alkylene group, X represents Cl or Br)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016067649A JP6651944B2 (en) | 2016-03-30 | 2016-03-30 | Pyrrolidine 2-carboxylic acid residue-containing copolymer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016067649A JP6651944B2 (en) | 2016-03-30 | 2016-03-30 | Pyrrolidine 2-carboxylic acid residue-containing copolymer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017179098A true JP2017179098A (en) | 2017-10-05 |
| JP6651944B2 JP6651944B2 (en) | 2020-02-19 |
Family
ID=60003771
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016067649A Active JP6651944B2 (en) | 2016-03-30 | 2016-03-30 | Pyrrolidine 2-carboxylic acid residue-containing copolymer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6651944B2 (en) |
-
2016
- 2016-03-30 JP JP2016067649A patent/JP6651944B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP6651944B2 (en) | 2020-02-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9932499B2 (en) | UV-curable composition and pressure sensitive adhesive having breathability derived therefrom, as well as method for manufacturing the same | |
| KR101819640B1 (en) | Physically crosslinkable adhesive copolymer | |
| JP6805488B2 (en) | Monomer composition for polymers for medical devices and polymers for medical devices | |
| US20050027079A1 (en) | Aqueous multistage emulsion polymer composition | |
| JP6064766B2 (en) | Zwitterionic ethylenically unsaturated monomer and method for producing the same. | |
| JP2011072851A (en) | Scale inhibitor containing amino group-containing copolymer | |
| JP2016108559A (en) | Curable composition and film | |
| JP6775225B2 (en) | Materials for medical devices and medical devices made from them | |
| TW201829697A (en) | Resin composition for adhesive and adhesive sheet | |
| JP6651944B2 (en) | Pyrrolidine 2-carboxylic acid residue-containing copolymer | |
| JP6868235B2 (en) | Polymers for medical devices, materials for medical devices and medical devices using them | |
| Monge et al. | Polymerization of phosphorus-containing (Meth) acrylate Monomers | |
| JP2015214614A (en) | Block polymer and production method thereof | |
| JP2003192728A (en) | Vinyl polymerizable monomer having tertiary hydroxyl group | |
| JP6890883B2 (en) | Photoreactive polymer | |
| JP2804978B2 (en) | Modifier for polymer, method for producing the same, and method for modifying polymer using the same | |
| JP2000169510A (en) | Aqueous resin dispersion | |
| JP2004331637A (en) | Bifunctional cross-linking agent monomer, method for producing the same and cross-linked polymer | |
| JPWO2018221564A1 (en) | Adhesive and structure | |
| JP2019023319A (en) | Block polymer and method for producing the same | |
| US11220567B2 (en) | Hydrophobically modified acrylic rheology modifiers having high carbon number hydrophobes | |
| JP6024891B2 (en) | Phosphorylcholine group-containing (meth) acrylate compound, production method thereof, and polymer thereof | |
| JP6667825B2 (en) | Polymer for medical device, material for medical device, and medical device using the same | |
| JP6484927B2 (en) | Block polymer and method for producing the same | |
| JP4829428B2 (en) | Method for producing aqueous metal-containing resin composition and coating resin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190109 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20191219 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20191224 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200106 |
|
| R151 | Written notification of patent or utility model registration |
Ref document number: 6651944 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R151 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |