JP5323496B2 - 機能性ナノ粒子、その製造方法及び使用方法 - Google Patents
機能性ナノ粒子、その製造方法及び使用方法 Download PDFInfo
- Publication number
- JP5323496B2 JP5323496B2 JP2008549006A JP2008549006A JP5323496B2 JP 5323496 B2 JP5323496 B2 JP 5323496B2 JP 2008549006 A JP2008549006 A JP 2008549006A JP 2008549006 A JP2008549006 A JP 2008549006A JP 5323496 B2 JP5323496 B2 JP 5323496B2
- Authority
- JP
- Japan
- Prior art keywords
- nanoparticles
- acid
- mmol
- functional groups
- complex
- 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.)
- Active
Links
- 239000002105 nanoparticle Substances 0.000 title claims description 53
- 238000000034 method Methods 0.000 title description 14
- 125000000524 functional group Chemical group 0.000 claims description 45
- 239000011230 binding agent Substances 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 18
- 229910017052 cobalt Inorganic materials 0.000 claims description 17
- 239000010941 cobalt Substances 0.000 claims description 17
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 17
- 229910000859 α-Fe Inorganic materials 0.000 claims description 14
- -1 methacryloyl Chemical group 0.000 claims description 13
- 229920000642 polymer Polymers 0.000 claims description 12
- 229920000858 Cyclodextrin Polymers 0.000 claims description 11
- 102000004169 proteins and genes Human genes 0.000 claims description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 239000006185 dispersion Substances 0.000 claims description 8
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 8
- 229910052700 potassium Inorganic materials 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 229920000962 poly(amidoamine) Polymers 0.000 claims description 6
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical group O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 6
- QUBISUNNAAPTOD-UHFFFAOYSA-N 12-amino-n-hydroxydodecanamide Chemical compound NCCCCCCCCCCCC(=O)NO QUBISUNNAAPTOD-UHFFFAOYSA-N 0.000 claims description 5
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 229910045601 alloy Inorganic materials 0.000 claims description 4
- 239000000956 alloy Substances 0.000 claims description 4
- 229960000304 folic acid Drugs 0.000 claims description 4
- 235000019152 folic acid Nutrition 0.000 claims description 4
- 239000011724 folic acid Substances 0.000 claims description 4
- 229910044991 metal oxide Inorganic materials 0.000 claims description 4
- 150000004706 metal oxides Chemical class 0.000 claims description 4
- YSOJQXZDWZMHPM-UHFFFAOYSA-N OCCCCCCCCCCCCOP(O)=O Chemical compound OCCCCCCCCCCCCOP(O)=O YSOJQXZDWZMHPM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229940097362 cyclodextrins Drugs 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims description 3
- 229910003321 CoFe Inorganic materials 0.000 claims description 2
- 229910002548 FeFe Inorganic materials 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 229910052748 manganese Inorganic materials 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 238000001226 reprecipitation Methods 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
- 238000005119 centrifugation Methods 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000003223 protective agent Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 55
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 239000000047 product Substances 0.000 description 32
- 230000015572 biosynthetic process Effects 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 238000003786 synthesis reaction Methods 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 238000004611 spectroscopical analysis Methods 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 13
- ZDHCZVWCTKTBRY-UHFFFAOYSA-N 12-hydroxylauric acid Chemical compound OCCCCCCCCCCCC(O)=O ZDHCZVWCTKTBRY-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 12
- 229910001873 dinitrogen Inorganic materials 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 230000003068 static effect Effects 0.000 description 12
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000003480 eluent Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 8
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- PBLZLIFKVPJDCO-UHFFFAOYSA-N 12-aminododecanoic acid Chemical compound NCCCCCCCCCCCC(O)=O PBLZLIFKVPJDCO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- RDXXXMKZHHUPJK-UHFFFAOYSA-N ethyl 12-hydroxydodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCO RDXXXMKZHHUPJK-UHFFFAOYSA-N 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 229920001222 biopolymer Polymers 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- ILRSCQWREDREME-UHFFFAOYSA-N dodecanamide Chemical compound CCCCCCCCCCCC(N)=O ILRSCQWREDREME-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000007306 functionalization reaction Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000005192 partition Methods 0.000 description 4
- 238000010183 spectrum analysis Methods 0.000 description 4
- WYKAHXSDDLPGAB-UHFFFAOYSA-N 12-amino-2-[(2-methylpropan-2-yl)oxycarbonyl]dodecanoic acid Chemical compound CC(C)(C)OC(=O)C(C(O)=O)CCCCCCCCCCN WYKAHXSDDLPGAB-UHFFFAOYSA-N 0.000 description 3
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 150000002894 organic compounds Chemical class 0.000 description 3
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- ZTMLAFCUUHCORH-UHFFFAOYSA-N 12-amino-2-[(2-methylpropan-2-yl)oxycarbonyl]dodecanoate dicyclohexylazanium Chemical compound CC(C)(C)OC(=O)C(CCCCCCCCCCN)C(=O)[O-].C1CCC(CC1)[NH2+]C2CCCCC2 ZTMLAFCUUHCORH-UHFFFAOYSA-N 0.000 description 2
- XPNBRSQMEFLWOU-UHFFFAOYSA-N 12-amino-n-phenylmethoxydodecanamide Chemical compound NCCCCCCCCCCCC(=O)NOCC1=CC=CC=C1 XPNBRSQMEFLWOU-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- NSKURDBFMVZRKB-UHFFFAOYSA-N ClO.NCCCCCCCCCCCCO Chemical compound ClO.NCCCCCCCCCCCCO NSKURDBFMVZRKB-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- DYFVMVODIGRODW-UHFFFAOYSA-N ethyl 12-bromododecanoate Chemical compound CCOC(=O)CCCCCCCCCCCBr DYFVMVODIGRODW-UHFFFAOYSA-N 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229910000314 transition metal oxide Inorganic materials 0.000 description 2
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SYXCACKKFONCRD-UHFFFAOYSA-N 12-(hydroxyamino)-12-oxododecanoic acid Chemical compound ONC(=O)CCCCCCCCCCC(O)=O SYXCACKKFONCRD-UHFFFAOYSA-N 0.000 description 1
- WTFDVZBZBFUOFV-UHFFFAOYSA-N 12-bromododecyl benzoate Chemical compound BrCCCCCCCCCCCCOC(=O)C1=CC=CC=C1 WTFDVZBZBFUOFV-UHFFFAOYSA-N 0.000 description 1
- VJOPNKODAZUCRH-UHFFFAOYSA-N 12-ethoxy-12-oxododecanoic acid Chemical compound CCOC(=O)CCCCCCCCCCC(O)=O VJOPNKODAZUCRH-UHFFFAOYSA-N 0.000 description 1
- QDHWEQVVRFFGKU-UHFFFAOYSA-N 12-hydroxydodecyl dihydrogen phosphate Chemical compound OCCCCCCCCCCCCOP(O)(O)=O QDHWEQVVRFFGKU-UHFFFAOYSA-N 0.000 description 1
- FQNLLSKGZYYFMQ-UHFFFAOYSA-N 12-phenylmethoxydodecyl dihydrogen phosphate Chemical compound OP(O)(=O)OCCCCCCCCCCCCOCC1=CC=CC=C1 FQNLLSKGZYYFMQ-UHFFFAOYSA-N 0.000 description 1
- GSFNQBFZFXUTBN-UHFFFAOYSA-N 2-chlorothiophene Chemical compound ClC1=CC=CS1 GSFNQBFZFXUTBN-UHFFFAOYSA-N 0.000 description 1
- YWBDZPWYYUZJHV-UHFFFAOYSA-N 2-hydroxydodecanamide Chemical compound CCCCCCCCCCC(O)C(N)=O YWBDZPWYYUZJHV-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- VPCWSYMMXNORBE-UHFFFAOYSA-N C1=CC=C(C=C1)CONC(=O)CCCCCCCCCCCOC(=O)N Chemical compound C1=CC=C(C=C1)CONC(=O)CCCCCCCCCCCOC(=O)N VPCWSYMMXNORBE-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- QJYYMNOTJXIOBP-UHFFFAOYSA-N Et ester-Tridecanoic acid Natural products CCCCCCCCCCCCC(=O)OCC QJYYMNOTJXIOBP-UHFFFAOYSA-N 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- JWIPGAFCGUDKEY-UHFFFAOYSA-L O[Cr](Cl)(=O)=O.C1=CC=NC=C1 Chemical compound O[Cr](Cl)(=O)=O.C1=CC=NC=C1 JWIPGAFCGUDKEY-UHFFFAOYSA-L 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000007824 aliphatic compounds Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- YVIGPQSYEAOLAD-UHFFFAOYSA-L disodium;dodecyl phosphate Chemical compound [Na+].[Na+].CCCCCCCCCCCCOP([O-])([O-])=O YVIGPQSYEAOLAD-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- CNRDTAOOANTPCG-UHFFFAOYSA-N dodecyl carbamate Chemical compound CCCCCCCCCCCCOC(N)=O CNRDTAOOANTPCG-UHFFFAOYSA-N 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000002082 metal nanoparticle Substances 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- WWNWRSUYUPQUCQ-UHFFFAOYSA-N o-benzylhydroxylamine;hypochlorous acid Chemical compound ClO.NOCC1=CC=CC=C1 WWNWRSUYUPQUCQ-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000000913 palmityl 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])C([H])([H])C([H])([H])[H] 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 239000012209 synthetic fiber Substances 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
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
- C01G51/00—Compounds of cobalt
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
- B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
- C01G53/00—Compounds of nickel
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Nanotechnology (AREA)
- Manufacturing & Machinery (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compounds Of Iron (AREA)
- Catalysts (AREA)
- Medicinal Preparation (AREA)
- Inorganic Compounds Of Heavy Metals (AREA)
Description
Aronoff, Y. G. et al. J. Am. Chem. Soc. 1997, 119, 259-262. Heimer, T. A. D'Arcangelis et al. Langmuir, 2002, 18, 5205-5212 Yee, C. et al. Langmuir, 1999, 15, 711 1 -71 15 Folkers, J. et al. Langmuir, 1995, 71 , 813-824
さらに、遊離状態の単純な脂肪鎖は、生理活性分子が通常有する官能基と、相互に作用し合うということがまったくない。
nは2乃至20の整数であり、
R1は、OH、NH2、COOH、COOR3からなる一群から選択されるものであり、
R2はCONHOH、CONHOR3、PO(OH)2、PO(OH)(OR3)、COOH、COOR3、SH、SR3から選択されるものである。
R3はアルカリ金属で、好ましくはK、Na若しくはLiであり、又は有機的な保護試薬である。
a)アミン類を外部の官能基として備える機能化されたナノ粒子は、先に定義した分子、重合体又はタンパク質であって、カルボン酸、アルデヒド及びアクリルアミドのうちの一つを官能基として有するものと結合してもよい。
b)カルボン酸を外部の官能基として備える機能化されたナノ粒子は、バイオポリマー、タンパク質又は分子(シクロデキストリン、葉酸、抗体、薬剤)であって、今度はアルコール、アミン及びチオールのうちの一つを官能基として有するものと結合してもよい。
例えば、ω−ヒドロキシ、ω−カルボキシ及びω−アミノ−カルボン酸;ω−ヒドロキシ、ω−カルボキシ及びω−アミノ−ヒドロキサム酸;ω−ヒドロキシ、ω−カルボキシ及びω−アミノ−リン酸;ω−ヒドロキシ、ω−カルボキシ及びω−アミノ−チオール(ω-hydroxy-, ω-carboxy- and ω-amino- carboxylic acids; ω-hydroxy-, ω- carboxy- and ω-amino- hydroxamic acids; ω-hydroxy-, ω-carboxy- and ω-amino- phosphoric acids; ω-hydroxy-, ω-carboxy- and ω-amino-thiols)のような単純な2の官能基を有する結合剤とナノ粒子との機能化である。それに引き続き、2の官能基を有する粒子と、分子、タンパク質又は重合体と、2の官能基を有する結合剤とを結合させる。
結合剤を交換する手段によって、結合剤を伴う分子、重合体又は変性されたタンパク質と、機能化されたナノ粒子とを結合させる。
2の官能基を有する結合剤の混合物とナノ粒子との機能化以外は製造工程Aと同様である。
2の官能基を有する結合剤の混合物とナノ粒子との機能化以外は製造工程Bと同様である。
適合した2の官能基を有する結合剤と結合させた前述の分子、重合体又はタンパク質と、ナノ粒子とを直接機能化するものである。
適合した2の官能基を有する結合剤と既に結合させた分子、重合体又はタンパク質と、異なる2の官能基を有する結合剤との混合物と、ナノ粒子とを機能化するものである。
「12−アミノ−N−ヒドロキシドデカンアミド(12-amino-N-hvdroxy dodecanamide)の合成」
磁石アンカーと、有孔隔壁と、アルゴン用の蛇口とを備えた250mlの二口フラスコで、市場で入手可能な12−アミノ−ドデカン酸(5.2g、25.8mmol)をジオキサン(20ml)に溶解させ、Boc2O(6.5ml、28mmol)を添加する。
1H-NMR (400 MHz, CD3OD): 1.35 (s, 9H), 1.40-1.60 (m, 18H), 2.35 (t, J=7.0 Hz, 2H), 3.00 (t, J=6.6 Hz, 2H), 4.80 (brs, 1 H).
13C-NMR (100.2 MHz, CD3OD): 24.9, 26.7, 27.7, 29.1, 29.3, 29.4 (2CH2), 29.48, 29.5, 29.8, 33.8, 40.2, 78.6, 157.3, 176.4.
MS: 315 (M+)
12−アミノ−(tert−ブトキシカルボニル)ドデカン酸(12-amino-(tert-butoxycarbonyl)dodecanoic acid)のジシクロへキシルアンモニウム塩(dicyclohexyl ammonium salt)(9.1g、18.4mmol)を、磁石アンカーと、有孔隔壁と、アルゴン用の蛇口とを備えた100mlの二口フラスコに入れ、ピリジン(1.50ml、15.2mmol)とジクロロメタン(18ml)とを添加する。
1H-NMR (400 MHz, CDCI3): 1.05-1.10 (m, 16H), 1.40 (s, 9H), 1.40-1.55 (m, 2H), 2.00 (brs, 2H), 3.00-3.10 (m, 2H), 4.80 (brs, 1 H), 4.90 (s, 2H), 7.25-7.35 (m, 5H), 9.25 (brs, 1H).
13C-NMR (75.3 MHz, CDCI3): 25.2, 26.4, 28.1, 28.8, 28.9, 29.1, 29.2, 29.7, 32.7, 40.3, 77.5, 78.6, 128.0, 128.7 (2ArCH), 135.3, 155.8, 170.1
MS: 420 (M+)
tert−ブチル12−(ベンジルオキシアミノ)−12−オキソドデシルカルバミン酸塩(tert-butyl 12-(benzyloxy amino)- 12-oxododecyl carbamate)(3.14g、7.5mmol)が入った不活性ガス雰囲気の一口フラスコにクロロホルム(30ml)を添加する。
1H-NMR (400 MHz, CDCI3): 1.00-1.40 (m, 16H), 1.45-1.55 (brs, 2H), 2.00 (brs, 2H), 2.45 (brs, 2H), 4.80-5.00 (brm, 5H), 7.20-7.40 (m, 5H).
13C-NMR (75.3 MHz, CDCI3): 25.3, 26.5, 28.9, 29.0, 29.1, 29.2, 29.24, 32.7, 32.9, 41.5, 77.5, 128.2, 129.0 (2ArCH), 135.7, 170.7.
MS: 320 (M+)
Parr反応器で水素によって水素付加を行う。Pd−C120mg、12−アミノ−N−(ベンジルオキシ)ドデカンアミド(12-amino-N-(benzyloxy)dodecanamide)(1.0g、2.4mmol)と、エタノール(40ml)を反応器に入れる。三角フラスコによってエタノール中で生成物を50℃に加熱するのが良策である。
1H-NMR (400 MHz, CDCI3): 1.10-1.60 (m, 18H), 2.0 (brt, 2H), 2.70-2.75 (m, 4H), 6.80 (brs, 1 H), 7.40 (brs, 1 H).
13C-NMR (75.3 MHz, CDCI3): Interval CH225.9-33.0, 41.8, 169.8.
MS: 230 (M+).
「12−アミノドデシルホスホン酸水素カリウム(potassium hydrogen-12-aminododecyl phosphonate)の合成」
還流冷却器、磁石アンカーを備える100mlの二口フラスコに、静的な窒素ガス源下、12−アミノ−1−ドデカノールクロロハイドレート(12-amino-1 -dodecanol chlorohydrate)(3.34g、14.1mmol)を秤量して入れ、ピリジン(40ml)、IPr2Net(2.45ml、14.1mmol)及びBoC2O(3.24ml、14.1mmol)を添加する。これを70℃で60時間攪拌したままにしておき、ロータリーエバポレーターと高真空ポンプによって濃縮し、生成物をシリカゲルのカラムクロマトグラフィーで、石油エーテル/酢酸エチルで1/1の溶離液によって精製することにより、ter−ブチル12−ヒドロキシドデシルカルバメート(Synthesis of ter-butyl 12-hydroxy dodecylcarbamate)3.1gが収率73%で白色の固体として単離される。融点は78℃。
1H-NMR (400 MHz, CDCI3): 1.20-1.30 (brs, 20H), 1.40 (brs, 9H), 3.15 (brs, 2H), 3.6 (t, J=8.5Hz, 2H), 4.4 (brs, 1 H).
13C-NMR (75.3 MHz, CDCI3): 24.8, 26.7, 27.6, 29.0, 29.2 (2CH2), 29.5, 29.6, 29.7, 29.73, 33.7, 40.1, 78.9, 157.1
MS: 301 (M+)
還流冷却器、磁石アンカーを備える250mlの二口フラスコで、静的な窒素ガス源下、ter−ブチル12−ヒドロキシドデシルカルバメート(ter-butyl 12-hydroxy dodecylcarbamate)(3.07g、10.2mmol)をジクロロメタン(75ml)に溶解させる。PPh3(2.94g、11.2ml)及びNBS(2.42g、10.7mmol)を添加。この混合物を還流させた状態で24時間攪拌させる。これをロータリーエバポレーターと高真空ポンプによって濃縮し、生成物をシリカゲルのカラムクロマトグラフィーで、石油エーテル/酢酸エチルで3/1の溶離液によって精製することにより、ter−ブチル12−ブロモドデシルカルバメート(ter-butyl 12-bromo dodecylcarbamate)2.9gが収率78%で低融点の白色の固体として単離される。融点は42〜44℃。
1H-NMR (400 MHz, CDCI3): 1.10-1.20 (brs, 20H), 1.35 (brs, 9H), 3.05 (brs, 2H), 3.60 (t, J=6.0 Hz, 2H), 4.80 (brs, 1H).
13C-NMR (100.4 MHz, CDCI3): 26.4, 27.8, 28.1, 28.4, 28.9, 29.1, 29.15, 29.2, 29.7, 32.5, 33.4, 40.2, 78.2, 155.2
MS: 363 (M+).
還流冷却器を備える一口フラスコにter−ブチル12−ブロモドデシルカルバメート(ter-butyl 12-bromo dodecylcarbamate)(2.39g、6.6mmol)を秤量し、リン酸トリエチル(2.25ml、13.1mmol)を添加。反応混合物を150℃にして、静的な窒素ガス源下、攪拌させる。18時間後、一口フラスコに高真空ポンプを接続して揮発性生成物を除去し、その結果生じた不透明な油状物質を直接シリカゲルによるカラムクロマトグラフィーに入れる。石油エーテル/酢酸エチルが1/1の混合液で溶出させ、0.4gのter−ブチル12−(ジエトキシホスホリル)ドデシルカルバメート(ter-butyl 12-(diethoxyphosphoryl)dodecylcarbamate)が無色の油状物質として単離される(収率=14%)。
1H-NMR (400 MHz, CDCI3): 1.20-1.45 (m+t, J=7.0 Hz, 35H), 1.55-1.60 (bm, 2H), 3.05 (brq, 2H), 3.90-4.15 (m, 4H).
13C-NMR (75.3 MHz, CDCI3): 15.6, 24.9-29.8 (10CH2+ t-Bu), 40.0, 61.2, 65.2, 78.3, 155.6.
MS: 421 (M+).
還流冷却器を備える一口フラスコにter−ブチル12−(ジエトキシホスホリル)ドデシルカルバメート(ter-butyl 12-(diethoxyphosphoryl)dodecylcarbamate)(0.35g、8.3mmol)を秤量し、濃塩酸(1.5ml)を添加。温度を100℃とし、静的な窒素ガス源下で攪拌する。18時間後、高真空ポンプで濃縮し、うす茶色でゴム状の固体を得る。
1H-NMR (400 MHz, CDCI3): 広域信号: (1.0-1.80, m), brs 2.80, brs 3.40.
13C-NMR (100.4 MHz, CDCI3): 23.0-28.8 (重複信号), 31.2, 33.4.
MS: 265 (M+).
「12−ヒドロキシドデシルホスホン酸水素カリウム(potassium hydrogen-12-hydroxy dodecylphosphonate)の合成」
静的な窒素ガス源下、100mlの二口フラスコで、12−ブロモ−ドデカノール(5.0g、18.9mmol)を秤量し、ピリジン(25ml)を添加し、氷と塩とによる外部浴によって温度を0℃にする。
IR: 2926, 2853, 1716, 1269, 1109.
1H-NMR (400 MHz, CDCI3): 1.10-1.60 (m, 16 H), 1.60-1.80 (m, 4H), 3.55 (t, J=6.8 Hz, 2H), 4.25 (t, J=6.8 Hz, 2H), 7.30-7.35 (m, 3H), 8.00-8.05 (m, 2H) ppm.
13C-NMR (75.3 MHz, CDCI3): 25.8, 26.6, 28.5, 28.6-29.3 (6CH2), 32.4, 44.8, 64.8, 128.0, 129.3, 130.3, 132.5, 166.3.
MS: 369 (M+).
還流冷却器を備える一口フラスコに安息香酸12−ブロモドデシル(12-Bromododecyl benzoate)(4.25g、11.5mmol)を秤量し、亜リン酸トリエチル(4.11ml、24mmol)を添加。反応混合物を150℃にして、静的な窒素ガス源下で攪拌させる。24時間後、一口フラスコに高真空ポンプを接続して揮発性生成物を除去し、その結果生じた不透明な油状物質を直接シリカゲルによるカラムクロマトグラフィーに入れる。酢酸エチル/石油エーテルが1/1の混合溶離液で溶出させ、4.0g(収率=82%)の安息香酸12−ジエトキシホスホリル(12-Diethoxyphosphoryl benzoate)が無色の油状物質として単離される。
1H-NMR (400 MHz, CDCI3): 1.30 (t, J= 7.0 Hz, 6H), 1.40-1.80 (m, 22 H), 3.95-4.05 (m, 4H), 4.25 (t, J=6.0 Hz, 2H), 7.40-7.65 (m, 3H), 8.00-8.05 (m, 2H) ppm.
13C-NMR (75.3 MHz, CDCI3): 16.0, 22.6, 24.2-34.1 (10CH2), 61.0, 65.3, 128.2, 129.4, 131 .4, 167.1.
MS: 426 (M+).
還流冷却器を備える一口フラスコに安息香酸12−ジエトキシホスホリル(12-Diethoxyphosphoryl benzoate)(4.0g、9.3mmol)を秤量し、濃塩酸(10ml)を添加。混合物の温度を100℃とし、静的な窒素ガス源下で攪拌させる。72時間後、酢酸エチル(80ml)と蒸留水(40ml)を添加する。
1H-NMR (400 MHz, D2O): 1.10-1.90 (m, 22H), 3.40 (brs, 2H).
13C-NMR (75.3 MHz, D2O): 24.5, 25.3, 29.0-29.3 (7CH2), 30.5, 31.7, 61.9.
MS: 266 (M+).
1H-NMR (400 MHz, CD3OD): 1.20-1.85 (m, 22H), 3.50 (t, J=6.8Hz, 2H)
13C-NMR (75.3 MHz, CD3OD): 22.9, 25.7, 29.1 -29.5 (7CH2), 30.7 (d, J=12Hz), 61 .8
MS: 265 (M"), 39 (K+)
「13−エトキシ−13−オキサトリデシルホスホン酸水素カリウム(potassium hydrogen-13-ethoxy-13-oxatridecyl phosphonate)の合成」
還流冷却器、磁石アンカーを備える100mlの二口フラスコに、静的な窒素ガス源下、12−ヒドロキシドデカン酸(12-hydroxy-dodecanoic acid)(5.0g、23.2mmol)を秤量して入れ、エタノール(20ml)及び塩化アセチル(1.62mmol、0.09ml、0.1eq.)を添加する。
1H-NMR (400 MHz, CDCI3):1.05-1.25 (m, 17H), 1.40-1.60 (m, 4H), 2.17 (t, J=7.2Hz, 2H), 2.34 (s, 1 H), 3.49 (t, J=6.8 Hz, 2H), 4.01 (1, J=7.2 Hz, 2H).
13C-NMR (75.3 MHz, CDCI3): 14.0, 24.7, 25.6, 28.9, 29.0, 29.2, 29.2, 29.3, 29.4, 32.6, 34.2, 59.98, 62.6, 173.8.
MS: 234 (M+)
還流冷却器、磁石アンカーを備える100mlの二口フラスコで、静的な窒素ガス源下、12−ヒドロキシドデカン酸エチル(ethyl 12-hydroxydodecanoate)(1.65g、6.7mmol)をジクロロメタン(20ml)に溶解させる。
1H-NMR (400 MHz, CDCI3): 1.20-1.45 (m, 15H), 1.55-1.65 (m, 4H), 1.80-1.90 (m, 2H), 2.30 (t, J=7.0Hz, 2H), 3.40 (t, J=7.1 Hz, 2H), 4.10 (1, J=7.2Hz, 2H).
13C-NMR (75.3 MHz, CDCI3): 14.2, 24.9, 28.1, 28.7, 29.1, 29.3 (2CH2), 29.4, 32.8, 33.9, 34.3, 61.1, 173.8.
MS: 296 (M+)
還流冷却器を備える一口フラスコに、12−ブロモドデカン酸エチル(ethyl 12-bromododecanoate)(1.8g、7.37mmol)を秤量し、リン酸トリエチル(2.6ml、15mmol)を添加する。
1H-NMR (400 MHz, CDCI3): 1.05-1.15 (m, 25H), 1.40-1.80 (m, 4H), 2.0-2.1 (m, 2H), 4.00 (brs, 6H).
13C-NMR (75.3 MHz, CDCI3): 14.0, 15.9, 16.2 (d, J=5.6 Hz), 22.1, 22.2, 24.7, 26.2, 26.8, 29.0, 29.1, 29.2, 30.3 (d, J=16.1 Hz), 34.1, 59.9, 61.1 1 (d, J=6.4 Hz), 63.7(d, J=5.6 Hz), 173.6.
MS: 364 (M+)
還流冷却器を備える一口フラスコに、(ジエトキシホスホリル)トリデカン酸エチル(ethyl (diethoxyphosphoryl)tridecanoate)(1.3g、3.6mmol)を秤量し、濃塩酸(2ml)を添加する。
1H-NMR (400 MHz, D2O): 1.00-1.40 (m, 20H), 2.0 (t, J=7.6 Hz, 2H).
13C-NMR (100.3 MHz, D2O): 23.5, 24.4, 26.1, 28.7, 28.9, 31.3, 37.87 (CH2 として識別可能な信号のみ)
MS (m/z): 278/2= 139 (M+)
「12−(ヒドロキシアミノ)−12−オキソドデカン酸エチル(ethyl 12-(hvdroxyamino)-12-oxododecanoate)の合成」
1H-NMR δ, ppm (400 MHz, CDCl3): 1.05-1.25 (m, 17H), 1.40-1.60(m, 4H), 2.17 (t, J=7.2 Hz, 2H), 2.34 (s, 1H), 3.49 (t, J=6.8 Hz, 2H), 4.01 (1, J=7.2 Hz, 2H).
13C-NMRδ, ppm (100.6 MHz, CDCl3): 14.0, 24.7, 25.6, 28.9, 29.0, 29.2, 29.2, 29.3, 29.4, 32.6, 34.2, 59.98, 62.6, 173.8.
IR, cm-1: 3423, 2928, 2855, 1737.
MS : 245 (M+1)+
1H-NMR δ, ppm (400 MHz, CDCl3): 1.26 (m, 15H), 1.61(m, 4H), 2.28 (t, J=7.6 Hz, 2H), 2.35 (t, J=7.4 Hz, 2H), 4.12 (q, J=7.1 Hz, 2H).
13C-NMR δ, ppm (100.6 MHz, CD3OD): 14.5, 26.0, 30.1-30.5, 34.9, 35.0, 61.3, 175.4, 177.5.
IR, cm-1: 2916, 2850, 1739, 1714, 1473, 1432.
MS : 259 (M+1)+
1H-NMR δ, ppm (400 MHz, CD3OD): 1.27 (m, 15H), 1.60(m, 4H), 2.08 (t, J=7.4 Hz, 2H), 2.30 (t, J=7.2 Hz, 2H), 4.11 (q, J=7.1 Hz, 2H).
13C-NMR δ, ppm (100.6 MHz, CD3OD): 14.5, 25.9, 26.5, 30.0-30.4, 33.1, 35.0, 61.3, 173.4, 175.4.
IR, cm-1: 3421, 2922, 2848, 1735, 1636, 1469, 1421.
MS : 274 (M+1)+
「コバルトフェライト/12−ヒドロキシドデシルホスホン酸 ナノ粒子錯体(Cobalt ferrite/12-hvdroxydodecyl phosphonate acid nanoparticle complexes)(図1の1.2)」
ジエチレングリコール中に重量で3%の、例えば直径5nmのコバルトフェライトであるナノ粒子を含む分散液10gに、軽く加熱したEtOH20gに加えて溶かした12−ヒドロキシドデシルホスホン酸(12-hydroxydodecyl phosphonate acid)0.3gを添加し、全量を常温で2時間攪拌し続ける。
「コバルトフェライト/12−アミノ−N−ヒドロキシドデカンアミド ナノ粒子錯体(Cobalt ferhte/12-Amino-N-hydroxydodecanamide nanoparticle complexes)(図1の1.2)」
ジエチレングリコール中に重量で3%の、例えば直径5nmのコバルトフェライトであるナノ粒子を含む分散液10gに、沸騰水20gに加えて溶かした12−アミノ−N−ヒドロキシドデカンアミド(12- amino-N-hydroxydodecanamide)0.21gを添加し、全量を常温で2時間攪拌し続ける。
[実施例8]
「エチレンジアミノ二酢酸-ビサクリロイルピペラジン(ethylendiamino diacetic acid-bisacryloil piperazine)からなるポリアミドアミン(PAA)で機能化されたナノ粒子化合物の合成(図1の1.2.1)」
ジエチレングリコール中に重量で0.1%の、ヒドロキサミック12−アミノドデカン酸(hydroxamic 12-aminododecanoic acid)で機能化した例えば直径5nmのコバルトフェライトであるナノ粒子を含む水性の分散液10gに、重合体0.02gを含む溶液10gを添加する。
「機能化されたナノ粒子/シクロデキストリンの化合物の合成」
a)移植された生成物におけるシクロデキストリンを直接固定する手順(図1の1.2.1)
ジエチレングリコール中に重量で0.1%の、例えば直径5nmのコバルトフェライトであるナノ粒子を含む分散液10gに、軽く加熱したEtOH20gにハイドロキサミック12−ヒドロキシドデカン酸(hydroxamic 12-hydroxydodecanoic acid)0.21gを加えて溶かした溶液を添加し、全量を60℃で1時間攪拌し続ける。
b)官能基を有する結合剤におけるシクロデキストリンの直接固定と、その後のコバルトフェライトへの移植の手順(図1の1.4)
Claims (10)
- ナノ粒子形状の金属酸化物、鉄、コバルト又はこれらの合金と、一般式(I):
R 1 -(CH 2 ) n -R 2
[ここで、
nは、2〜20の整数であり、
R 1 は、NH 2 、COOH、COOR 3 からなる一群から選択され、
R 2 は、CONHOH、PO(OH) 2 、PO(OH)(OR 3 )、SHから選択され、
R 3 はアルカリ金属又は有機的な保護試薬である]で示される2の官能基を有する化合物とからなる錯体。 - 前記ナノ粒子形状の金属酸化物が、式:MIIMIII 2O4(ここで、MIIはCo、Ni、FeII、Zn、Mnであり、MIIIはFeIII、Co、Alである)で示される化合物である、請求項1に記載の錯体。
- 前記酸化物は、コバルト・フェライトであるCoFe2O4、磁鉄鉱であるFeFe2O4及び磁赤鉄鉱であるFe2O3からなる一群から選択される、請求項2に記載の錯体。
- 前記アルカリ金属は、K、Na又はLiからなる一群から選択される、請求項1に記載の錯体。
- コバルトフェライトのナノ粒子/12−ヒドロキシドデシルホスホネート酸;コバルトフェライトのナノ粒子/12−アミノ−N−ヒドロキシドデカンアミド;エチレンジアミノ二酢酸−ビスアクリロイルピペラジンからなるポリアミドアミン(PAA)で官能化されたナノ粒子からなる、請求項1に記載の錯体。
- 前記ナノ粒子の分散液を有機溶媒中で結合剤と反応させ、該分散液を低温で数時間攪拌し続け、得られた生成物を沈殿させ、次いで、遠心分離により分離し、溶媒中での再分散及び再沈殿により精製させる、請求項1〜5のいずれか1項に記載の錯体の製造方法。
- 2の官能基を有する誘導体を有し、前記2の官能基を有する誘導体の外部の官能基が分子、タンパク質又は重合体に結合される、請求項1〜5のいずれか1項に記載の錯体からなる化合物。
- 前記分子は、シクロデキストリン、葉酸、抗体、ポリアミドアミンから選択される、請求項7に記載の化合物。
- コバルトフェライト/12−ヒドロキシドデシルホスホネート酸と、カルボキシメチル化シクロデキストリンとの結合からなる、請求項8に記載の化合物。
- コバルトフェライト/コバルトフェライト酸/12−アミノ−N−ヒドロキシドデカンアミドと、カルボキシメチル化シクロデキストリンとからなる、請求項9に記載の化合物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT000006A ITFI20060006A1 (it) | 2006-01-04 | 2006-01-04 | Nanoparticelle funzionalizzate, loro produzione ed uso |
ITFI2006A000006 | 2006-01-04 | ||
PCT/EP2007/050036 WO2007077240A2 (en) | 2006-01-04 | 2007-01-03 | Functionalised nanoparticles, their production and use |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2009522200A JP2009522200A (ja) | 2009-06-11 |
JP2009522200A5 JP2009522200A5 (ja) | 2013-03-21 |
JP5323496B2 true JP5323496B2 (ja) | 2013-10-23 |
Family
ID=36950411
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008549006A Active JP5323496B2 (ja) | 2006-01-04 | 2007-01-03 | 機能性ナノ粒子、その製造方法及び使用方法 |
Country Status (16)
Country | Link |
---|---|
US (1) | US8816107B2 (ja) |
EP (1) | EP1979365B1 (ja) |
JP (1) | JP5323496B2 (ja) |
KR (1) | KR101354123B1 (ja) |
CN (1) | CN101365709A (ja) |
AU (1) | AU2007204067B2 (ja) |
BR (1) | BRPI0706359A2 (ja) |
CA (1) | CA2636326C (ja) |
ES (1) | ES2390837T3 (ja) |
IT (1) | ITFI20060006A1 (ja) |
MX (1) | MX2008008707A (ja) |
NZ (1) | NZ570216A (ja) |
PL (1) | PL1979365T3 (ja) |
RU (1) | RU2437890C2 (ja) |
WO (1) | WO2007077240A2 (ja) |
ZA (1) | ZA200806727B (ja) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8501159B2 (en) | 2006-12-18 | 2013-08-06 | Colorobbia Italia S.P.A. | Magnetic nanoparticles for the application in hyperthermia, preparation thereof and use in constructs having a pharmacological application |
FR2921838A1 (fr) * | 2007-10-05 | 2009-04-10 | Guerbet Sa | Nouveau procede de preparation de nanoparticules recouvertes d'une couche stabilisatrice gem-bisphosphonate couplee a des ligands de biodistribution hydrophile |
ITFI20070285A1 (it) * | 2007-12-19 | 2009-06-20 | Colorobbia Italiana Spa | Nanosfere con superficie esterna in metalli nobili. |
ITFI20080117A1 (it) * | 2008-06-26 | 2009-12-27 | Colorobbia Italiana Spa | Uso di cobalto ferriti come agenti di contrasto per risonanza magnetica. |
US9205155B2 (en) | 2009-10-30 | 2015-12-08 | General Electric Company | Treating water insoluble nanoparticles with hydrophilic alpha-hydroxyphosphonic acid conjugates, the so modified nanoparticles and their use as contrast agents |
JP5639371B2 (ja) * | 2010-03-10 | 2014-12-10 | ゼネラル株式会社 | 水性磁性分散体および磁性インクジェットインク |
US10475559B1 (en) * | 2012-09-25 | 2019-11-12 | Maxim Integrated Products, Inc. | Controlling the morphology in metal loaded paste material |
CN103588820B (zh) * | 2013-09-11 | 2016-04-27 | 南京大学 | 一种叶酸-镍配位聚合物纳米管及其制备方法与应用 |
EP3084483A1 (en) * | 2013-12-19 | 2016-10-26 | 3M Innovative Properties Company | Articles comprising self-assembled layers comprising nanoparticles with a phosphorous surface treatment |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2279560A (en) * | 1940-05-08 | 1942-04-14 | Du Pont | Viscous hydrocarbon oil |
US3367959A (en) * | 1964-09-28 | 1968-02-06 | Diamond Shamrock Corp | Esters of amidoximes and hydroxamic acids |
US5318838A (en) * | 1988-01-22 | 1994-06-07 | Fuji Photo Film Co., Ltd. | Magnetic recording medium comprising ferromagnetic particles, binder resins and phenyl phosphonic acid |
JP2806578B2 (ja) * | 1989-12-11 | 1998-09-30 | 日本ゼオン株式会社 | 磁気記録媒体 |
CA2242647A1 (en) * | 1996-01-10 | 1997-07-17 | Amersham Health As | Contrast media |
ES2319733T3 (es) * | 2000-07-28 | 2009-05-12 | Ausmelt Limited | Preparacion de hidroxamato graso. |
DE10063090A1 (de) | 2000-12-18 | 2002-06-20 | Henkel Kgaa | Nanoskaliges ZnO in Hygiene-Produkten |
US6812268B2 (en) | 2001-11-01 | 2004-11-02 | Science Applications International Corporation | Methods for material fabrication utilizing the polymerization of nanoparticles |
US20030180780A1 (en) | 2002-03-19 | 2003-09-25 | Jun Feng | Stabilized inorganic particles |
US20040242729A1 (en) | 2003-05-30 | 2004-12-02 | 3M Innovative Properties Company | Stabilized particle dispersions containing surface-modified inorganic nanoparticles |
TWI265948B (en) * | 2004-02-17 | 2006-11-11 | Walsin Lihwa Corp | Clay mixture of aluminum compound and clay and preparation method thereof |
JP4485442B2 (ja) * | 2004-10-01 | 2010-06-23 | コリア インスティテュート オブ サイエンス アンド テクノロジー | 均一な粒度を有する親水性金属酸化物ナノ粒子及びその製造方法 |
EP1846421A4 (en) | 2005-01-20 | 2009-10-28 | Agency Science Tech & Res | WATER-SOLUBLE NANOPARTICLE WITH FUNCTIONALIZED SURFACE FOR BIOCONJUGATION BY UNIVERSAL SILANE COUPLING |
-
2006
- 2006-01-04 IT IT000006A patent/ITFI20060006A1/it unknown
-
2007
- 2007-01-03 PL PL07700240T patent/PL1979365T3/pl unknown
- 2007-01-03 BR BRPI0706359-8A patent/BRPI0706359A2/pt not_active Application Discontinuation
- 2007-01-03 AU AU2007204067A patent/AU2007204067B2/en active Active
- 2007-01-03 WO PCT/EP2007/050036 patent/WO2007077240A2/en active Application Filing
- 2007-01-03 US US12/087,304 patent/US8816107B2/en active Active
- 2007-01-03 RU RU2008131958/04A patent/RU2437890C2/ru active
- 2007-01-03 JP JP2008549006A patent/JP5323496B2/ja active Active
- 2007-01-03 CN CNA2007800019720A patent/CN101365709A/zh active Pending
- 2007-01-03 MX MX2008008707A patent/MX2008008707A/es active IP Right Grant
- 2007-01-03 KR KR1020087019077A patent/KR101354123B1/ko active IP Right Grant
- 2007-01-03 EP EP07700240A patent/EP1979365B1/en active Active
- 2007-01-03 NZ NZ570216A patent/NZ570216A/en unknown
- 2007-01-03 ES ES07700240T patent/ES2390837T3/es active Active
- 2007-01-03 CA CA2636326A patent/CA2636326C/en active Active
-
2008
- 2008-08-01 ZA ZA200806727A patent/ZA200806727B/xx unknown
Also Published As
Publication number | Publication date |
---|---|
RU2008131958A (ru) | 2010-02-10 |
CA2636326A1 (en) | 2007-07-12 |
US8816107B2 (en) | 2014-08-26 |
ZA200806727B (en) | 2009-05-27 |
AU2007204067B2 (en) | 2012-10-25 |
MX2008008707A (es) | 2008-10-29 |
ES2390837T3 (es) | 2012-11-16 |
PL1979365T3 (pl) | 2012-12-31 |
BRPI0706359A2 (pt) | 2011-03-22 |
EP1979365A2 (en) | 2008-10-15 |
EP1979365B1 (en) | 2012-07-11 |
WO2007077240A2 (en) | 2007-07-12 |
ITFI20060006A1 (it) | 2007-07-05 |
KR101354123B1 (ko) | 2014-01-24 |
AU2007204067A1 (en) | 2007-07-12 |
NZ570216A (en) | 2010-07-30 |
WO2007077240A3 (en) | 2007-11-01 |
RU2437890C2 (ru) | 2011-12-27 |
CA2636326C (en) | 2014-04-08 |
JP2009522200A (ja) | 2009-06-11 |
CN101365709A (zh) | 2009-02-11 |
KR20080112194A (ko) | 2008-12-24 |
US20090054555A1 (en) | 2009-02-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5323496B2 (ja) | 機能性ナノ粒子、その製造方法及び使用方法 | |
JP5632287B2 (ja) | 親水性生体内分布リガンドにカップリングされたgem−ビスホスホネート安定化層で覆われるナノ粒子を調製する新規な方法 | |
Rutledge et al. | Thiol− ene induced diphosphonic acid functionalization of superparamagnetic iron oxide nanoparticles | |
KR20170059491A (ko) | 진단 영상화용 나노입자 조영제 | |
EP3125949B1 (en) | Dendronized metallic oxide nanoparticles, a process for preparing the same and their uses | |
US5495042A (en) | Non-alkaline purification of aminophosphonic acids | |
WO2011006453A1 (zh) | 基于季戊四醇的复合脂质、其中间体、制备方法和用途 | |
JP5640191B2 (ja) | 無機骨格を有する高分子修飾ハイブリッドナノ粒子及びその合成方法 | |
Lopez et al. | Highly efficient coordination of Hg 2+ and Pb 2+ metals in water with squaramide-coated Fe 3 O 4 nanoparticles | |
Sayin et al. | Preparation of calix [4] arene-based sporopollenin and examination of its dichromate sorption ability | |
JP3660282B2 (ja) | ハイドロゲル化剤 | |
RU2699071C1 (ru) | Новый полиэтиленгликольсодержащий глицеролипид | |
Bruce et al. | Synthesis of Organosilicon Ligands for Europium (III) and Gadolinium (III) as Potential Imaging Agents | |
Alami et al. | Functionalization of graphene oxide surfaces with phosphorus dendrimer and dendron | |
WO2015065168A1 (en) | Oligo-ethylene glycol based phosphonate surface modification reagents and use thereof | |
KR100413532B1 (ko) | 폴리아민이 말단에 치환된 덴드리머 및 그 제조방법 | |
Li | Design and Synthesis of Ceragenins-Cationic Steroid Antimicrobial Compounds, Structural Improvement and Synthesis of Cyclopentenone Prostaglandins and Modification and Synthesis of Derivatives of Ribityllumazines: Potential Antigens for Activation of MAIT Cells | |
WO2011131912A1 (fr) | Nano-objets magneto-optiques pour la detection des cancers | |
WO2016088137A2 (en) | A novel process for the synthesis of boron enriched magnetic nanoparticles | |
KR20200125501A (ko) | 금 나노클러스터와 이의 제조방법 및 이를 포함하는 광학 센서 | |
Crasmareanu et al. | Hybrid Materials Obtained with Iron Oxides | |
Achalkumar et al. | Synthesis of nitrilotriacetic acid terminated tethers for the binding of His-tagged proteins to lipid bilayers and to gold | |
JPH0680977A (ja) | 磁性流体 | |
JP2014181219A (ja) | 人工シデロフォア錯体が修飾された微粒子、および当該微粒子が被着したセンサー用基板 | |
Stiti et al. | Grafting of 4-aminomethylbenzensulfonamide-lipoic acid conjugate on gold nanoparticles |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20091224 |
|
RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7421 Effective date: 20110405 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121012 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130115 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130122 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20130131 |
|
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: 20130628 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130717 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5323496 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |