JP2012092326A - 蛍光ハイドロゲルおよびその製造方法、ならびにそれを用いた糖類測定用センサー - Google Patents
蛍光ハイドロゲルおよびその製造方法、ならびにそれを用いた糖類測定用センサー Download PDFInfo
- Publication number
- JP2012092326A JP2012092326A JP2011214500A JP2011214500A JP2012092326A JP 2012092326 A JP2012092326 A JP 2012092326A JP 2011214500 A JP2011214500 A JP 2011214500A JP 2011214500 A JP2011214500 A JP 2011214500A JP 2012092326 A JP2012092326 A JP 2012092326A
- Authority
- JP
- Japan
- Prior art keywords
- group
- chemical formula
- substituted
- carbon atoms
- hydrogen atom
- 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
- 239000000017 hydrogel Substances 0.000 title claims abstract description 132
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 23
- 150000001720 carbohydrates Chemical class 0.000 title abstract description 30
- 238000005259 measurement Methods 0.000 title abstract description 17
- 239000000126 substance Substances 0.000 claims abstract description 119
- 239000007864 aqueous solution Substances 0.000 claims description 86
- 239000000178 monomer Substances 0.000 claims description 77
- 125000004432 carbon atom Chemical group C* 0.000 claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical group NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 24
- 125000002947 alkylene group Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 238000002513 implantation Methods 0.000 claims description 13
- 230000000379 polymerizing effect Effects 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 10
- 125000000524 functional group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 210000001124 body fluid Anatomy 0.000 claims description 7
- 239000010839 body fluid Substances 0.000 claims description 7
- 150000001721 carbon Chemical class 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 230000005855 radiation Effects 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims description 5
- 230000005284 excitation Effects 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 5
- 230000001678 irradiating effect Effects 0.000 claims description 5
- 239000003999 initiator Substances 0.000 claims description 4
- 239000007870 radical polymerization initiator Substances 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 37
- 239000008103 glucose Substances 0.000 abstract description 37
- 238000001514 detection method Methods 0.000 abstract description 2
- -1 glucose Chemical class 0.000 description 185
- 238000000034 method Methods 0.000 description 51
- 229920001223 polyethylene glycol Polymers 0.000 description 37
- 239000002202 Polyethylene glycol Substances 0.000 description 35
- 238000006116 polymerization reaction Methods 0.000 description 34
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 31
- 239000003960 organic solvent Substances 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- 210000004369 blood Anatomy 0.000 description 21
- 239000008280 blood Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 239000000499 gel Substances 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000010894 electron beam technology Methods 0.000 description 8
- 239000012530 fluid Substances 0.000 description 8
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical group OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
- 239000003505 polymerization initiator Substances 0.000 description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- 238000004140 cleaning Methods 0.000 description 7
- 239000003431 cross linking reagent Substances 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 6
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical group CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 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 5
- 239000000203 mixture Substances 0.000 description 5
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 238000001179 sorption measurement Methods 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 238000001917 fluorescence detection Methods 0.000 description 4
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 229920000098 polyolefin Polymers 0.000 description 4
- 230000004043 responsiveness Effects 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 3
- 125000005577 anthracene group Chemical group 0.000 description 3
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 229920002545 silicone oil Polymers 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- KOMNUTZXSVSERR-UHFFFAOYSA-N 1,3,5-tris(prop-2-enyl)-1,3,5-triazinane-2,4,6-trione Chemical compound C=CCN1C(=O)N(CC=C)C(=O)N(CC=C)C1=O KOMNUTZXSVSERR-UHFFFAOYSA-N 0.000 description 2
- VLHMMJXEVIEYHI-UHFFFAOYSA-N 1-(9,10-dimethylanthracen-2-yl)ethanone Chemical compound C1=CC=CC2=C(C)C3=CC(C(=O)C)=CC=C3C(C)=C21 VLHMMJXEVIEYHI-UHFFFAOYSA-N 0.000 description 2
- ONCICIKBSHQJTB-UHFFFAOYSA-N 1-[4-(dimethylamino)phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=C(N(C)C)C=C1 ONCICIKBSHQJTB-UHFFFAOYSA-N 0.000 description 2
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VVBLNCFGVYUYGU-UHFFFAOYSA-N 4,4'-Bis(dimethylamino)benzophenone Chemical compound C1=CC(N(C)C)=CC=C1C(=O)C1=CC=C(N(C)C)C=C1 VVBLNCFGVYUYGU-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 description 2
- 239000004341 Octafluorocyclobutane Substances 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 244000028419 Styrax benzoin Species 0.000 description 2
- 235000000126 Styrax benzoin Nutrition 0.000 description 2
- 235000008411 Sumatra benzointree Nutrition 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000001412 amines Chemical class 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
- 125000000129 anionic group Chemical group 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229960002130 benzoin Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 238000007446 glucose tolerance test Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000003827 glycol group Chemical group 0.000 description 2
- 235000019382 gum benzoic Nutrition 0.000 description 2
- 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 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- GUAQVFRUPZBRJQ-UHFFFAOYSA-N n-(3-aminopropyl)-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NCCCN GUAQVFRUPZBRJQ-UHFFFAOYSA-N 0.000 description 2
- 238000007344 nucleophilic reaction Methods 0.000 description 2
- BCCOBQSFUDVTJQ-UHFFFAOYSA-N octafluorocyclobutane Chemical compound FC1(F)C(F)(F)C(F)(F)C1(F)F BCCOBQSFUDVTJQ-UHFFFAOYSA-N 0.000 description 2
- 235000019407 octafluorocyclobutane Nutrition 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000009958 sewing Methods 0.000 description 2
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SUEDCWGEKSLKOM-UHFFFAOYSA-N (2,6-dimethoxyphenyl)-diphenylphosphorylmethanone Chemical compound COC1=CC=CC(OC)=C1C(=O)P(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 SUEDCWGEKSLKOM-UHFFFAOYSA-N 0.000 description 1
- SQWIEBKHVLRDRG-UHFFFAOYSA-N (2,6-dimethylphenyl)-diphenylphosphorylmethanone Chemical compound CC1=CC=CC(C)=C1C(=O)P(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 SQWIEBKHVLRDRG-UHFFFAOYSA-N 0.000 description 1
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- GSRWBDHSNVWQLC-ZETCQYMHSA-N (2s)-6-amino-2-(prop-2-enoylamino)hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)C=C GSRWBDHSNVWQLC-ZETCQYMHSA-N 0.000 description 1
- OBDUMNZXAIUUTH-HWKANZROSA-N (e)-tetradec-2-ene Chemical group CCCCCCCCCCC\C=C\C OBDUMNZXAIUUTH-HWKANZROSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- 125000005923 1,2-dimethylpropyloxy group Chemical group 0.000 description 1
- MSAHTMIQULFMRG-UHFFFAOYSA-N 1,2-diphenyl-2-propan-2-yloxyethanone Chemical compound C=1C=CC=CC=1C(OC(C)C)C(=O)C1=CC=CC=C1 MSAHTMIQULFMRG-UHFFFAOYSA-N 0.000 description 1
- QWQFVUQPHUKAMY-UHFFFAOYSA-N 1,2-diphenyl-2-propoxyethanone Chemical compound C=1C=CC=CC=1C(OCCC)C(=O)C1=CC=CC=C1 QWQFVUQPHUKAMY-UHFFFAOYSA-N 0.000 description 1
- DKEGCUDAFWNSSO-UHFFFAOYSA-N 1,8-dibromooctane Chemical compound BrCCCCCCCCBr DKEGCUDAFWNSSO-UHFFFAOYSA-N 0.000 description 1
- UWFRVQVNYNPBEF-UHFFFAOYSA-N 1-(2,4-dimethylphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(C)C=C1C UWFRVQVNYNPBEF-UHFFFAOYSA-N 0.000 description 1
- HUDYANRNMZDQGA-UHFFFAOYSA-N 1-[4-(dimethylamino)phenyl]ethanone Chemical compound CN(C)C1=CC=C(C(C)=O)C=C1 HUDYANRNMZDQGA-UHFFFAOYSA-N 0.000 description 1
- FADLMGMYEZTIIY-UHFFFAOYSA-N 1-[9,10-bis(bromomethyl)anthracen-2-yl]ethanone Chemical compound C1=CC=CC2=C(CBr)C3=CC(C(=O)C)=CC=C3C(CBr)=C21 FADLMGMYEZTIIY-UHFFFAOYSA-N 0.000 description 1
- BLWDSCRXGNZAQH-UHFFFAOYSA-N 1-[9,10-bis(bromomethylidene)anthracen-2-yl]ethanone Chemical compound C1=CC=C2C(=CBr)C3=CC=C(C(=O)C)C=C3C(=CBr)C2=C1 BLWDSCRXGNZAQH-UHFFFAOYSA-N 0.000 description 1
- MGRRZBKEFOXFRI-UHFFFAOYSA-N 1-anthracen-1-ylethanone Chemical compound C1=CC=C2C=C3C(C(=O)C)=CC=CC3=CC2=C1 MGRRZBKEFOXFRI-UHFFFAOYSA-N 0.000 description 1
- DQFWGPPCMONVDS-UHFFFAOYSA-N 1-anthracen-2-ylethanone Chemical compound C1=CC=CC2=CC3=CC(C(=O)C)=CC=C3C=C21 DQFWGPPCMONVDS-UHFFFAOYSA-N 0.000 description 1
- ZFIVBGXETFWLQL-UHFFFAOYSA-N 1-diphenylphosphoryl-2-ethyl-2-methylhexan-1-one Chemical compound C=1C=CC=CC=1P(=O)(C(=O)C(C)(CC)CCCC)C1=CC=CC=C1 ZFIVBGXETFWLQL-UHFFFAOYSA-N 0.000 description 1
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- PIZHFBODNLEQBL-UHFFFAOYSA-N 2,2-diethoxy-1-phenylethanone Chemical compound CCOC(OCC)C(=O)C1=CC=CC=C1 PIZHFBODNLEQBL-UHFFFAOYSA-N 0.000 description 1
- IVIDDMGBRCPGLJ-UHFFFAOYSA-N 2,3-bis(oxiran-2-ylmethoxy)propan-1-ol Chemical compound C1OC1COC(CO)COCC1CO1 IVIDDMGBRCPGLJ-UHFFFAOYSA-N 0.000 description 1
- BJELTSYBAHKXRW-UHFFFAOYSA-N 2,4,6-triallyloxy-1,3,5-triazine Chemical compound C=CCOC1=NC(OCC=C)=NC(OCC=C)=N1 BJELTSYBAHKXRW-UHFFFAOYSA-N 0.000 description 1
- LCHAFMWSFCONOO-UHFFFAOYSA-N 2,4-dimethylthioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC(C)=CC(C)=C3SC2=C1 LCHAFMWSFCONOO-UHFFFAOYSA-N 0.000 description 1
- WMKRKJLHGIYASB-UHFFFAOYSA-N 2-[2-(bromomethyl)phenyl]-1,3,2-dioxaborinane Chemical compound BrCC1=CC=CC=C1B1OCCCO1 WMKRKJLHGIYASB-UHFFFAOYSA-N 0.000 description 1
- CCJAYIGMMRQRAO-UHFFFAOYSA-N 2-[4-[(2-hydroxyphenyl)methylideneamino]butyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCCCN=CC1=CC=CC=C1O CCJAYIGMMRQRAO-UHFFFAOYSA-N 0.000 description 1
- TXBCBTDQIULDIA-UHFFFAOYSA-N 2-[[3-hydroxy-2,2-bis(hydroxymethyl)propoxy]methyl]-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)(CO)COCC(CO)(CO)CO TXBCBTDQIULDIA-UHFFFAOYSA-N 0.000 description 1
- ZCDADJXRUCOCJE-UHFFFAOYSA-N 2-chlorothioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC(Cl)=CC=C3SC2=C1 ZCDADJXRUCOCJE-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- BQZJOQXSCSZQPS-UHFFFAOYSA-N 2-methoxy-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(OC)C(=O)C1=CC=CC=C1 BQZJOQXSCSZQPS-UHFFFAOYSA-N 0.000 description 1
- HFCUBKYHMMPGBY-UHFFFAOYSA-N 2-methoxyethyl prop-2-enoate Chemical compound COCCOC(=O)C=C HFCUBKYHMMPGBY-UHFFFAOYSA-N 0.000 description 1
- GQWNPIKWYPQUPI-UHFFFAOYSA-N 2-methylbut-3-enoic acid Chemical compound C=CC(C)C(O)=O GQWNPIKWYPQUPI-UHFFFAOYSA-N 0.000 description 1
- LPNSCOVIJFIXTJ-UHFFFAOYSA-N 2-methylidenebutanamide Chemical compound CCC(=C)C(N)=O LPNSCOVIJFIXTJ-UHFFFAOYSA-N 0.000 description 1
- 125000006607 3,3-dimethylbutyloxy group Chemical group 0.000 description 1
- FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 description 1
- DMQYPVOQAARSNF-UHFFFAOYSA-N 3-[2,3-bis(3-prop-2-enoyloxypropoxy)propoxy]propyl prop-2-enoate Chemical compound C=CC(=O)OCCCOCC(OCCCOC(=O)C=C)COCCCOC(=O)C=C DMQYPVOQAARSNF-UHFFFAOYSA-N 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 1
- OKISUZLXOYGIFP-UHFFFAOYSA-N 4,4'-dichlorobenzophenone Chemical compound C1=CC(Cl)=CC=C1C(=O)C1=CC=C(Cl)C=C1 OKISUZLXOYGIFP-UHFFFAOYSA-N 0.000 description 1
- LNYTUARMNSFFBE-UHFFFAOYSA-N 4-(diethylazaniumyl)benzoate Chemical compound CCN(CC)C1=CC=C(C(O)=O)C=C1 LNYTUARMNSFFBE-UHFFFAOYSA-N 0.000 description 1
- YDIYEOMDOWUDTJ-UHFFFAOYSA-N 4-(dimethylamino)benzoic acid Chemical compound CN(C)C1=CC=C(C(O)=O)C=C1 YDIYEOMDOWUDTJ-UHFFFAOYSA-N 0.000 description 1
- MAGFQRLKWCCTQJ-UHFFFAOYSA-N 4-ethenylbenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(C=C)C=C1 MAGFQRLKWCCTQJ-UHFFFAOYSA-N 0.000 description 1
- KFDVPJUYSDEJTH-UHFFFAOYSA-N 4-ethenylpyridine Chemical compound C=CC1=CC=NC=C1 KFDVPJUYSDEJTH-UHFFFAOYSA-N 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- 125000000439 4-methylpentoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LWMIRJUDVHHBEE-UHFFFAOYSA-N CC1=CC(C)=C(C(C(C=CC2=CC=CC=C22)=C2OP(O)=O)=O)C(C)=C1 Chemical compound CC1=CC(C)=C(C(C(C=CC2=CC=CC=C22)=C2OP(O)=O)=O)C(C)=C1 LWMIRJUDVHHBEE-UHFFFAOYSA-N 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 241001662443 Phemeranthus parviflorus Species 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 239000006087 Silane Coupling Agent Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- VBIIFPGSPJYLRR-UHFFFAOYSA-M Stearyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)C VBIIFPGSPJYLRR-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- LFOXEOLGJPJZAA-UHFFFAOYSA-N [(2,6-dimethoxybenzoyl)-(2,4,4-trimethylpentyl)phosphoryl]-(2,6-dimethoxyphenyl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)P(=O)(CC(C)CC(C)(C)C)C(=O)C1=C(OC)C=CC=C1OC LFOXEOLGJPJZAA-UHFFFAOYSA-N 0.000 description 1
- ALBJGICXDBJZGK-UHFFFAOYSA-N [1-[(1-acetyloxy-1-phenylethyl)diazenyl]-1-phenylethyl] acetate Chemical compound C=1C=CC=CC=1C(C)(OC(=O)C)N=NC(C)(OC(C)=O)C1=CC=CC=C1 ALBJGICXDBJZGK-UHFFFAOYSA-N 0.000 description 1
- URLYGBGJPQYXBN-UHFFFAOYSA-N [4-(hydroxymethyl)cyclohexyl]methyl prop-2-enoate Chemical compound OCC1CCC(COC(=O)C=C)CC1 URLYGBGJPQYXBN-UHFFFAOYSA-N 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- ORPDTKXFAPFHPD-UHFFFAOYSA-N anthracene;boric acid Chemical class OB(O)O.C1=CC=CC2=CC3=CC=CC=C3C=C21 ORPDTKXFAPFHPD-UHFFFAOYSA-N 0.000 description 1
- 210000000617 arm Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 229910052790 beryllium Inorganic materials 0.000 description 1
- ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- RTWRNNFUXCOKNO-UHFFFAOYSA-N diphenylphosphoryl-(2,3,6-trimethylphenyl)methanone Chemical compound CC1=CC=C(C)C(C(=O)P(=O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C RTWRNNFUXCOKNO-UHFFFAOYSA-N 0.000 description 1
- GFABLBCPAJSSTF-UHFFFAOYSA-N diphenylphosphoryl-(2,4,6-trichlorophenyl)methanone Chemical compound ClC1=CC(Cl)=CC(Cl)=C1C(=O)P(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 GFABLBCPAJSSTF-UHFFFAOYSA-N 0.000 description 1
- PODOEQVNFJSWIK-UHFFFAOYSA-N diphenylphosphoryl-(2,4,6-trimethoxyphenyl)methanone Chemical compound COC1=CC(OC)=CC(OC)=C1C(=O)P(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 PODOEQVNFJSWIK-UHFFFAOYSA-N 0.000 description 1
- VFHVQBAGLAREND-UHFFFAOYSA-N diphenylphosphoryl-(2,4,6-trimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C)=C1C(=O)P(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 VFHVQBAGLAREND-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- DOMLXBPXLNDFAB-UHFFFAOYSA-N ethoxyethane;methyl prop-2-enoate Chemical compound CCOCC.COC(=O)C=C DOMLXBPXLNDFAB-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- IMBKASBLAKCLEM-UHFFFAOYSA-L ferrous ammonium sulfate (anhydrous) Chemical compound [NH4+].[NH4+].[Fe+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O IMBKASBLAKCLEM-UHFFFAOYSA-L 0.000 description 1
- 229920001109 fluorescent polymer Polymers 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexamethylene diamine Natural products NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 125000002297 iodooxy group Chemical group IO[*] 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000005921 isopentoxy group Chemical group 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- ZBKFYXZXZJPWNQ-UHFFFAOYSA-N isothiocyanate group Chemical group [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000000344 low-energy electron-beam lithography Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 description 1
- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical compound CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 description 1
- RFZRLVGQBIINKQ-UHFFFAOYSA-N n-(2-aminoethyl)-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NCCN RFZRLVGQBIINKQ-UHFFFAOYSA-N 0.000 description 1
- HXJGFDIZSMWOGY-UHFFFAOYSA-N n-(2-azaniumylethyl)prop-2-enimidate Chemical compound NCCNC(=O)C=C HXJGFDIZSMWOGY-UHFFFAOYSA-N 0.000 description 1
- FZLUWDXMHJPGBS-UHFFFAOYSA-N n-(3-aminopropyl)prop-2-enamide Chemical compound NCCCNC(=O)C=C FZLUWDXMHJPGBS-UHFFFAOYSA-N 0.000 description 1
- UTSYWKJYFPPRAP-UHFFFAOYSA-N n-(butoxymethyl)prop-2-enamide Chemical compound CCCCOCNC(=O)C=C UTSYWKJYFPPRAP-UHFFFAOYSA-N 0.000 description 1
- GRJFFSRTVQFRLT-UHFFFAOYSA-N n-(trihydroxymethyl)prop-2-enamide Chemical compound OC(O)(O)NC(=O)C=C GRJFFSRTVQFRLT-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002004 n-butylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006610 n-decyloxy group Chemical group 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000006609 n-nonyloxy group Chemical group 0.000 description 1
- 125000006608 n-octyloxy group Chemical group 0.000 description 1
- 125000003935 n-pentoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004888 n-propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XFHJDMUEHUHAJW-UHFFFAOYSA-N n-tert-butylprop-2-enamide Chemical compound CC(C)(C)NC(=O)C=C XFHJDMUEHUHAJW-UHFFFAOYSA-N 0.000 description 1
- 125000005484 neopentoxy group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 125000005429 oxyalkyl group Chemical group 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 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
- 230000008569 process Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- OKDWPOPWOQICDL-UHFFFAOYSA-M sodium;(2-nonylphenyl) sulfate Chemical compound [Na+].CCCCCCCCCC1=CC=CC=C1OS([O-])(=O)=O OKDWPOPWOQICDL-UHFFFAOYSA-M 0.000 description 1
- ASJUTVUXOMPOQH-UHFFFAOYSA-M sodium;4-octylbenzenesulfonate Chemical compound [Na+].CCCCCCCCC1=CC=C(S([O-])(=O)=O)C=C1 ASJUTVUXOMPOQH-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- VPYJNCGUESNPMV-UHFFFAOYSA-N triallylamine Chemical compound C=CCN(CC=C)CC=C VPYJNCGUESNPMV-UHFFFAOYSA-N 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- CEYYIKYYFSTQRU-UHFFFAOYSA-M trimethyl(tetradecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)C CEYYIKYYFSTQRU-UHFFFAOYSA-M 0.000 description 1
- XHGIFBQQEGRTPB-UHFFFAOYSA-N tris(prop-2-enyl) phosphate Chemical compound C=CCOP(=O)(OCC=C)OCC=C XHGIFBQQEGRTPB-UHFFFAOYSA-N 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
- C08F220/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F290/00—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
- C08F290/02—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups on to polymers modified by introduction of unsaturated end groups
- C08F290/06—Polymers provided for in subclass C08G
- C08F290/062—Polyethers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N2021/7769—Measurement method of reaction-produced change in sensor
- G01N2021/7786—Fluorescence
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/80—Fluorescent dyes, e.g. rhodamine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Immunology (AREA)
- Optics & Photonics (AREA)
- Heart & Thoracic Surgery (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Surgery (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Emergency Medicine (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
【解決手段】下記化学式1で表される構造を有する蛍光ハイドロゲルおよびその製造方法、ならびにそれを用いた糖類測定用センサーである。
【選択図】なし
Description
Zは、同一または異なっていてもよく、−O−または−NR'−であり、この際R'は、水素原子または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Lは、単結合、−U5−、−U5−NR2−、−U5−O−、−U5−S−、−U5−SS−、−U5−NR2CO、−U5−CONR2−、−U5−OCO−、−U5−COO−、下記化学式7で表される基、および下記化学式8で表される基からなる群より選択される基であり、
本工程では、各種モノマーを水溶液の形態とし、該水溶液の状態で重合反応を行う。(a1)の工程と(a2)の工程との異なる点は、使用するモノマーが異なるところにある。上記化学式9で表されるモノマーを用いる(a1)の工程においては、本工程により上記化学式6で表される構造(ポリアルキレンオキサイド構造)が蛍光ハイドロゲルに導入され、本発明の蛍光ハイドロゲルが得られる。上記化学式10で表されるモノマーを用いる(a2)の工程においては、本工程と後述の化学式11で表される化合物を反応させる工程(b)とを行うことにより、上記化学式6で表される構造(ポリアルキレンオキサイド構造)が蛍光ハイドロゲルに導入され、本発明の蛍光ハイドロゲルが得られる。
本工程では、上記(a2)工程を行った場合に得られるハイドロゲル中の反応性官能基(上記化学式中の)と、下記化学式11で表される化合物中のJ2部分とを反応させ、蛍光ハイドロゲルにポリアルキレンオキサイド構造を導入する。
J2は、−O−U6−ハロゲン原子、−O−U6−CHO、−O−U6−SH、−O−U6−NH2、−O−U6−NHR5、−O−U6−COOH、−O−U6−COOR5、−O−U6−O−パラトルエンスルホニル基、−O−U6−イソチオシアネート基、−OCO−U6−イソチオシアネート基、−O−U6−マレイミド基、−O−U6−NHCO−U6−マレイミド基、−O−U6−CONH−U6−マレイミド基、−O−U6−OSO2R5、−O−U6−OCOR5、−O−U6−(OR5)2、−O−U6−COO−パラニトロフェニル基、−OCO−U6−COO−N−スクシンイミド基、または−O−U6−COO−N−スクシンイミド基を含む基であり、
この際、U6は置換されているかまたは非置換の炭素数1〜10の直鎖状または分枝状のアルキレン基であり、R5は水素原子または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
nは2〜5であり、mは1〜200である。
(A)9,10−ビス(ブロモメチル)−2−アセチルアントラセン(上記反応式1中のII)の合成
9,10−ジメチル−2−アセチルアントラセン(上記反応式1中のI)600mg、N−ブロモスクシンイミド800mg、および過酸化ベンゾイル5mgを、クロロホルム6mLと四塩化炭素20mLの混合物に加え、80℃で2時間、加熱還流を行った。溶媒を除去した後、残渣をメタノールで抽出し、780mgの目的物を得た。
上記(A)で得た生成物500mg、N−BOC−ヘキシルジアミン(上記反応式1中のIII) 1.125g、およびジイソプロピルエチルアミン 1.25mLを、N,N−ジメチルホルムアミド(DMF)10mLに溶解し、45℃で1時間攪拌して反応を行った。反応混合物はクロロホルム60mLで希釈し、水100mLで3回、飽和食塩水100mLで1回洗浄し、有機相を無水硫酸ナトリウムで乾燥した。乾燥剤を濾過後、濃縮し、クロロホルム/メタノール(体積比 95/5)混合溶媒を溶離液とするシリカゲルカラムクロマトグラフィーにて精製し、367mgの目的物を得た。
上記(B)で得た生成物200mg、2−(2−ブロモメチルフェニル)−1,3−ジオキサボリナン(上記反応式1中のV)700mgおよびN,N−ジイソプロピルエチルアミン0.35mLを、3mLのジメチルホルムアミドに溶解し、室温(25℃)で16時間攪拌した。溶媒除去後、メタノール/クロロホルムを溶離液とするシリカゲルカラムで精製し目的物194mgを得た。
上記(C)で得られた生成物100mgを、2mLのメタノールに溶解し、4N 塩酸2mLを加えて、室温(25℃)で10時間攪拌した。蒸発乾固後、ゲル濾過によって無機塩を除去し、目的物95mgを得た。
上記(D)で得られた生成物160mgを、0.5mLのDMFに溶解し、アクリロイル−(ポリエチレングリコール)−N−ヒドロキシスクシンイミドエステル(ポリエチレングリコール残基部分の分子量は3,400)1.22gの10mL 100mMリン酸緩衝液(pH=8.0)溶液に加え、室温(25℃)で20時間攪拌した。反応混合物をゲル濾過に供し、蛍光高分子画分を採取し、凍結乾燥後、目的物であるF−PEG−AAm 1.2gを得た。重クロロホルムを用いて測定した1H−NMRデータは下記表1の通りであり、ポリエチレングリコール(PEG)残基由来のピークと重なる水素のシグナルは確認されなかった。
ここでは、上記(a1)の方法により、蛍光ハイドロゲルの作製を行った。アクリルアミドの濃度が15質量%、およびN,N'−メチレンビスアクリルアミドの濃度が0.3質量%、ポリエチレングリコールメチルエーテルアクリレート(アルドリッチ社製、品番454990−250ML、平均分子量:480、以下、単に「PEGアクリレート」とも称する)の濃度が0、1、5、10質量%となるように、60mMリン酸緩衝液(pH7.4)にそれぞれ加えて溶解・混合し、計4種類の水溶液を調製した。ここで用いたPEGアクリレートは、上記化学式9のsが2、tが8〜9の混合物、R1がメチル基、R3が水素原子、Zが−O−、Lが単結合である化合物である。次に、4種類の水溶液を室温(25℃)でそれぞれ窒素バブリングを行った。
実施例2で得られた直径700μmの蛍光ハイドロゲル(PEGアクリレート 5質量%)を、グルコース濃度が0〜1000mg/dLの範囲となるように調製した60mMリン酸緩衝液中に浸漬し、蛍光実体顕微鏡により、各グルコース濃度における蛍光ハイドロゲルの蛍光強度について観察した。結果を図5に示す。
蛍光ハイドロゲルへのPEG構造導入の確認のため、実施例2の方法においてF−PEG−AAmを用いずに作製したハイドロゲルについてFT−IRの測定(図6の(c))を行った。FT−IR測定は、作製したハイドロゲルを凍結乾燥したのち、ATR法にて行った。コントロールとして、実施例2の方法において、F−PEG−AAmとPEGアクリレートとを用いずに作製したAAmゲルのみのFT−IRスペクトル(図6の(a))と、PEGアクリレートのみのFT−IRスペクトル(図6の(b))も測定した。
蛍光ハイドロゲルのタンパク質吸着抑制能の評価のため、実施例4にて作製した4種類の蛍光ハイドロゲル(PEGアクリレート 0、1、5、10質量%)を、1mg/mLのウシ血清アルブミン溶液に浸漬した。室温(25℃)で48時間浸漬を行った後、500mMの塩化ナトリウム溶液に浸漬し、蛍光ハイドロゲルに吸着したウシ血清アルブミンを溶出させた。この溶出液に対し、BCAアッセイを行うことで、ゲルに吸着していたウシ血清アルブミン量を求めた。結果を図7に示す。
実施例2で得られた直径700μmの蛍光ハイドロゲル(PEGアクリレート 5質量%)を長さ25mm程度にカットし、マウスの耳に埋めこんだ。このときの写真を図8の(a)に示す。次に、マウスの頚静脈から、グルコース溶液、およびインスリン溶液を投与し、マウスの血糖値を変化させたときの、蛍光ハイドロゲルの生体内における蛍光強度変化の観察結果を図8の(b)に示す。
実施例6と同様に蛍光ハイドロゲル(PEGアクリレート 5質量%)を埋め込んでから72日後、実施例6と同様の糖負荷試験を行った。蛍光ハイドロゲルを埋め込んでから72日後のマウスの写真を図9(a)に、糖負荷試験時の血糖値変化および埋め込まれていた蛍光ハイドロゲルの蛍光強度変化を図9(b)に示す。
実施例6および7と同様に蛍光ハイドロゲル(PEGアクリレート 5質量%)を埋め込んでから140日後、実施例6および7と同様の糖負荷試験を行った。蛍光ハイドロゲルを埋め込んでから140日後のマウスの写真を図10(a)に、糖負荷試験時の血糖値変化および埋め込まれていた蛍光ハイドロゲルの蛍光強度変化を図10(b)に示す。
12、24 水溶液柱、
21 マイクロ流路(微小流路)のインレット、
22 マイクロ流路(微小流路)のアウトレット、
23 マイクロ流路(微小流路)、
26、27 基板、
31 コア部の流体、
32 シェル部の流体、
33 インジェクション用ガラス管、
34 ポリジメチルシロキサン製ホルダー、
35 集束用ガラス管、
36 蛍光ハイドロゲル、
37 DI水。
Claims (8)
- 下記化学式1で表される構造を有する、蛍光ハイドロゲル:
X1およびX2は同一または異なっていてもよく、−COO−、−OCO−、−CH2NR−、−NR−、−NRCO−、−CONR−、−SO2NR−、−NRSO2−、−O−、−S−、−SS−、−NRCOO−、−OCONR−、および−CO−からなる群より選択される少なくとも1種の置換基を含んでいてもよい炭素数1〜30のアルキレン基であり、この際、Rは、水素原子、または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Z1、Z2、Z3およびZ4は同一または異なっていてもよく、−O−または−NR'−であり、この際R'は、水素原子または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Q、Q'、Q''、Q'''は同一または異なっていてもよく、水素原子、ヒドロキシ基、置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基、炭素数2〜11のアシル基、置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルコキシ基、ハロゲン原子を含む基、カルボキシル基、カルボン酸エステル基、カルボン酸アミド基、シアノ基、ニトロ基、アミノ基、または炭素数1〜10のアルキルアミノ基であり、QおよびQ'ならびにQ''およびQ'''の少なくとも一方は、互いに結合して芳香環または複素環を形成してもよく、
Y1およびY2は、同一または異なっていてもよく、置換されていてもよい2価の有機残基または単結合であり、この際、Y1およびY2の少なくとも一方が、下記化学式3または下記化学式4で表される構造を含んでいてもよく、
A1、A2、A3およびA4は同一または異なっていてもよく、水素原子またはメチル基であり、
U1、U2、U3およびU4は同一または異なっていてもよく、水素原子、または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
D1およびD2は同一または異なっていてもよく、下記化学式6で表される基であり、
L1およびL2は同一または異なっていてもよく、単結合、−U5−、−U5−NR2−、−U5−O−、−U5−S−、−U5−SS−、−U5−NR2CO−、−U5−CONR2−、−U5−OCO−、−U5−COO−、下記化学式7で表される基、および下記化学式8で表される基からなる群より選択される基であり、
p1とq1とのモル比(p1:q1)およびp2とq2とのモル比(p2:q2)は、1:50〜1:6,000であり、
p1とr1とのモル比(p1:r1)およびp2とr2とのモル比(p2:r2)は、1:5〜1:3,000である。 - 三次元架橋構造を有する、請求項1に記載の蛍光ハイドロゲル。
- (a1)下記化学式5で表される蛍光モノマーと、下記化学式9で表されるモノマーと、(メタ)アクリルアミド残基を含む重合性モノマーと、を含む水溶液を重合させる工程を含む、蛍光ハイドロゲルの製造方法:
X1およびX2は、同一または異なっていてもよく、−COO−、−OCO−、−CH2NR−、−NR−、−NRCO−、−CONR−、−SO2NR−、−NRSO2−、−O−、−S−、−SS−、−NRCOO−、−OCONR−、および−CO−からなる群より選択される少なくとも1種の置換基を含んでいてもよい炭素数1〜30の直鎖状または分枝状のアルキレン基であり、この際、Rは、水素原子、または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Z1およびZ2は同一または異なっていてもよく、−O−または−NR'−であり、この際R'は、水素原子または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Q、Q'、Q''、Q'''は同一または異なっていてもよく、水素原子、ヒドロキシ基、置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基、炭素数2〜11のアシル基、置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルコキシ基、ハロゲン原子を含む基、カルボキシル基、カルボン酸エステル基、カルボン酸アミド基、シアノ基、ニトロ基、アミノ基、または炭素数1〜10のアルキルアミノ基であり、QおよびQ'ならびにQ''およびQ'''の少なくとも一方は、互いに結合して芳香環または複素環を形成してもよく、
Y1およびY2は、同一または異なっていてもよく、置換されていてもよい2価の有機残基または単結合であり、この際、Y1およびY2の少なくとも一方が、下記化学式3または下記化学式4で表される構造を含んでいてもよく、
Zは、同一または異なっていてもよく、−O−または−NR'−であり、この際R'は、水素原子または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Lは、単結合、−U5−、−U5−NR2−、−U5−O−、−U5−S−、−U5−SS−、−U5−NR2CO、−U5−CONR2−、−U5−OCO−、−U5−COO−、下記化学式7で表される基、および下記化学式8で表される基からなる群より選択される基であり、
- (a2)下記化学式5で表される蛍光モノマー化合物と、下記化学式10で表されるモノマーと、(メタ)アクリルアミド残基を含む重合性モノマーと、を含む水溶液を重合させる工程と、
(b)下記化学式11で表される化合物を反応させる工程と、
を含む、蛍光ハイドロゲルの製造方法:
X1およびX2は、同一または異なっていてもよく、−COO−、−OCO−、−CH2NR−、−NR−、−NRCO−、−CONR−、−SO2NR−、−NRSO2−、−O−、−S−、−SS−、−NRCOO−、−OCONR−、および−CO−からなる群より選択される少なくとも1種の置換基を含んでいてもよい炭素数1〜30の直鎖状または分枝状のアルキレン基であり、この際、Rは、水素原子、または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Z1およびZ2は同一または異なっていてもよく、−O−または−NR'−であり、この際R'は、水素原子または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
Q、Q'、Q''、Q'''は同一または異なっていてもよく、水素原子、ヒドロキシ基、置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基、炭素数2〜11のアシル基、置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルコキシ基、ハロゲン原子を含む基、カルボキシル基、カルボン酸エステル基、カルボン酸アミド基、シアノ基、ニトロ基、アミノ基、または炭素数1〜10のアルキルアミノ基であり、QおよびQ'ならびにQ''およびQ'''の少なくとも一方は、互いに結合して芳香環または複素環を形成してもよく、
Y1およびY2は、同一または異なっていてもよく、置換されていてもよい2価の有機残基または単結合であり、この際、Y1およびY2の少なくとも一方が、下記化学式3または下記化学式4で表される構造を含んでいてもよく、
Gはその末端に反応性官能基を含む置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、R4は水素原子またはメチル基であり、
J2は、−O−U6−ハロゲン原子、−O−U6−CHO、−O−U6−SH、−O−U6−NH2、−O−U6−NHR5、−O−U6−COOH、−O−U6−COOR5、−O−U6−O−パラトルエンスルホニル基、−O−U6−イソチオシアネート基、−OCO−U6−イソチオシアネート基、−O−U6−マレイミド基、−O−U6−NHCO−U6−マレイミド基、−O−U6−CONH−U6−マレイミド基、−O−U6−OSO2R5、−O−U6−OCOR5、−O−U6−(OR5)2、−O−U6−COO−パラニトロフェニル基、−OCO−U6−COO−N−スクシンイミド基、または−O−U6−COO−N−スクシンイミド基を含む基であり、
この際、U6は置換されているかまたは非置換の炭素数1〜10の直鎖状または分枝状のアルキレン基であり、R5は水素原子または置換されているかもしくは非置換の炭素数1〜10の直鎖状もしくは分枝状のアルキル基であり、
nは2〜5であり、mは1〜200である。 - 前記水溶液を重合させる工程は、ラジカル重合開始剤を用いて前記水溶液を化学重合させるか、光重合開始剤を用いて前記水溶液を光重合させるか、または放射線を照射して前記水溶液を放射線重合させる、請求項3または4に記載の蛍光ハイドロゲルの製造方法。
- 請求項1もしくは2に記載の蛍光ハイドロゲル、または請求項3〜5のいずれか1項に記載の製造方法により得られる蛍光ハイドロゲルを含む、体内埋め込み用の糖類測定用センサー。
- 請求項1もしくは2に記載の蛍光ハイドロゲル、または請求項3〜5のいずれか1項に記載の製造方法により得られる蛍光ハイドロゲルを体内に埋込み、体内または体外より励起光を照射して、前記蛍光ハイドロゲルから発生する蛍光を計測する手段を有する、体内埋め込み用の糖類測定用センサー。
- 請求項1もしくは2に記載の蛍光ハイドロゲル、または請求項3〜5のいずれか1項に記載の製造方法により得られる蛍光ハイドロゲルを、体液が循環する経路の少なくとも一部に貼り付け、励起光を照射して前記蛍光ハイドロゲルから発生する蛍光を計測する手段を有する、糖類測定用センサー。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011214500A JP5901199B2 (ja) | 2010-09-30 | 2011-09-29 | 蛍光ハイドロゲルおよびその製造方法、ならびにそれを用いた糖類測定用センサー |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010222363 | 2010-09-30 | ||
JP2010222363 | 2010-09-30 | ||
JP2011214500A JP5901199B2 (ja) | 2010-09-30 | 2011-09-29 | 蛍光ハイドロゲルおよびその製造方法、ならびにそれを用いた糖類測定用センサー |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012092326A true JP2012092326A (ja) | 2012-05-17 |
JP5901199B2 JP5901199B2 (ja) | 2016-04-06 |
Family
ID=45892650
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011214500A Active JP5901199B2 (ja) | 2010-09-30 | 2011-09-29 | 蛍光ハイドロゲルおよびその製造方法、ならびにそれを用いた糖類測定用センサー |
Country Status (4)
Country | Link |
---|---|
US (1) | US8822722B2 (ja) |
EP (1) | EP2623530B1 (ja) |
JP (1) | JP5901199B2 (ja) |
WO (1) | WO2012043177A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014203831A (ja) * | 2013-04-01 | 2014-10-27 | テルモ株式会社 | 生体内物質検出装置 |
CN110606907A (zh) * | 2019-07-10 | 2019-12-24 | 山东省产品质量检验研究院 | 一种用于检测工业废水中重金属离子的荧光探针及其制备方法 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105219375B (zh) * | 2015-10-09 | 2017-06-06 | 闫东鹏 | 一种具有上转换发光可调的9‑乙酰基蒽共晶材料及其制备方法 |
JP6998042B2 (ja) * | 2017-01-19 | 2022-01-18 | 国立大学法人 東京大学 | グルコース検出用蛍光ゲル及びそれを用いた連続的グルコースモニタリング方法 |
CN110455759A (zh) * | 2019-08-14 | 2019-11-15 | 吉林大学 | 一种基于铜纳米颗粒的乐果检测试剂盒及检测乐果浓度的方法 |
CN110679591B (zh) * | 2019-10-28 | 2021-09-21 | 上海悦联生物科技有限公司 | 一种农药组合物及其制备方法 |
GB2616873A (en) | 2022-03-23 | 2023-09-27 | Ide8 Ltd | Superabsorbent Polymer based Biosensor Apparatus and Methods |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006111719A (ja) * | 2004-10-14 | 2006-04-27 | Terumo Corp | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー |
JP2010209339A (ja) * | 2010-04-19 | 2010-09-24 | Terumo Corp | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2883824B2 (ja) | 1993-11-07 | 1999-04-19 | 科学技術振興事業団 | ボロン酸基を有する発蛍光性化合物 |
GB2284809B (en) * | 1993-11-07 | 1998-04-29 | Japan Res Dev Corp | A fluorescent phenylboronic acid suitable for use in the detection of saccharides |
EP0862648B1 (en) | 1995-11-22 | 2004-10-06 | Medtronic MiniMed, Inc. | Detection of biological molecules using chemical amplification and optical sensors |
DK1307464T3 (da) | 2000-08-04 | 2013-03-18 | Senseonics Inc | Detektion af analytter i vandige miljøer |
US6800451B2 (en) * | 2001-01-05 | 2004-10-05 | Sensors For Medicine And Science, Inc. | Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone |
EP1619229B1 (en) | 2004-07-23 | 2007-04-11 | Terumo Kabushiki Kaisha | Saccharide-measuring fluorescent monomer, saccharide-measuring fluorescent sensor substance, and implantable, saccharide-measuring sensor |
JP4691345B2 (ja) | 2004-10-07 | 2011-06-01 | テルモ株式会社 | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー |
KR20060104140A (ko) | 2005-03-29 | 2006-10-09 | 문영백 | 무선구간의 거리측정장치 및 그 방법 |
TWI431100B (zh) * | 2006-11-30 | 2014-03-21 | Senseonics Inc | 抗氧化指示劑分子 |
-
2011
- 2011-09-07 EP EP11828738.2A patent/EP2623530B1/en active Active
- 2011-09-07 WO PCT/JP2011/070389 patent/WO2012043177A1/ja active Application Filing
- 2011-09-07 US US13/877,004 patent/US8822722B2/en active Active
- 2011-09-29 JP JP2011214500A patent/JP5901199B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006111719A (ja) * | 2004-10-14 | 2006-04-27 | Terumo Corp | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー |
JP2010209339A (ja) * | 2010-04-19 | 2010-09-24 | Terumo Corp | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014203831A (ja) * | 2013-04-01 | 2014-10-27 | テルモ株式会社 | 生体内物質検出装置 |
CN110606907A (zh) * | 2019-07-10 | 2019-12-24 | 山东省产品质量检验研究院 | 一种用于检测工业废水中重金属离子的荧光探针及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
EP2623530A1 (en) | 2013-08-07 |
EP2623530B1 (en) | 2015-03-04 |
US20130267800A1 (en) | 2013-10-10 |
WO2012043177A1 (ja) | 2012-04-05 |
EP2623530A4 (en) | 2014-07-23 |
US8822722B2 (en) | 2014-09-02 |
JP5901199B2 (ja) | 2016-04-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5901199B2 (ja) | 蛍光ハイドロゲルおよびその製造方法、ならびにそれを用いた糖類測定用センサー | |
JP6628780B2 (ja) | 酸素センサ | |
Guan et al. | Boronic acid-containing hydrogels: synthesis and their applications | |
JP5209424B2 (ja) | 消光剤前駆体組成物 | |
JP5943286B2 (ja) | 糖応答性ゲル及び薬剤投与デバイス | |
US7873398B2 (en) | Saccharide-measuring fluorescent monomer, saccharide-measuring fluorescent sensor substance, and implantable, saccharide-measuring sensor | |
JP2013519895A (ja) | グルコースセンサ用障壁層 | |
CN107759820A (zh) | 一种硅橡胶表面亲水改性的方法及应用方法 | |
WO2011101624A1 (en) | Indicator system for fibre optic sensor | |
JP4691345B2 (ja) | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー | |
JP5380174B2 (ja) | 蛍光ハイドロゲルビーズおよびそれを用いた体内埋め込み用の糖類測定用センサー | |
JP2011190403A (ja) | 蛍光ハイドロゲルファイバーおよびその製造方法、ならびにそれを用いた糖類測定用センサー | |
EP3774951B1 (en) | Boronic acid derivatives for diol-sensing hydrogels | |
JP2006036664A (ja) | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー | |
JP5700723B2 (ja) | 蛍光ハイドロビーズを用いた体内埋め込み用の糖類測定用センサー | |
JP2011001469A (ja) | 蛍光ハイドロゲルビーズの製造方法 | |
JP4520272B2 (ja) | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー | |
JP2010209339A (ja) | 糖類測定用蛍光モノマー化合物、糖類測定用蛍光センサー物質および体内埋め込み用の糖類測定用センサー | |
WO2015146897A1 (ja) | 医療用の高分子化合物、及びそれを用いた組成物、機器 | |
Ghazi et al. | Synthesis and Characterization of New Boronic Acid-Containing Hydrogels as Glucose-Sensitive Vehicle for Controlled Insulin Release | |
Koverzanova et al. | Possibility of using embolizing preparation derived from poly (2-hydroxyethyl methacrylate)(poly-HEMA) for chemoemobolization |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120928 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20130115 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130116 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140521 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140522 Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140522 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150714 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150901 |
|
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: 20160223 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160308 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5901199 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |