JPWO2016159203A1 - ヘムタンパク質の保存液及びヘムタンパク質の安定化方法 - Google Patents
ヘムタンパク質の保存液及びヘムタンパク質の安定化方法 Download PDFInfo
- Publication number
- JPWO2016159203A1 JPWO2016159203A1 JP2017510166A JP2017510166A JPWO2016159203A1 JP WO2016159203 A1 JPWO2016159203 A1 JP WO2016159203A1 JP 2017510166 A JP2017510166 A JP 2017510166A JP 2017510166 A JP2017510166 A JP 2017510166A JP WO2016159203 A1 JPWO2016159203 A1 JP WO2016159203A1
- Authority
- JP
- Japan
- Prior art keywords
- heme protein
- acid
- salt
- disulfonic acid
- hemoprotein
- 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
- 102000008015 Hemeproteins Human genes 0.000 title claims abstract description 68
- 108010089792 Hemeproteins Proteins 0.000 title claims abstract description 68
- 238000000034 method Methods 0.000 title claims abstract description 42
- 239000003761 preservation solution Substances 0.000 title claims abstract description 26
- 230000000087 stabilizing effect Effects 0.000 title claims abstract description 22
- 239000002253 acid Substances 0.000 claims abstract description 67
- 150000003839 salts Chemical class 0.000 claims abstract description 44
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 14
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 14
- 239000000523 sample Substances 0.000 claims description 61
- 239000000243 solution Substances 0.000 claims description 25
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 24
- 239000013068 control sample Substances 0.000 claims description 21
- 238000005259 measurement Methods 0.000 claims description 20
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 claims description 11
- 230000001900 immune effect Effects 0.000 claims description 8
- 239000011550 stock solution Substances 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 claims description 5
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- OPUAWDUYWRUIIL-UHFFFAOYSA-N methanedisulfonic acid Chemical compound OS(=O)(=O)CS(O)(=O)=O OPUAWDUYWRUIIL-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- FUDAIDRKVVTJFF-UHFFFAOYSA-N butane-1,1-disulfonic acid Chemical compound CCCC(S(O)(=O)=O)S(O)(=O)=O FUDAIDRKVVTJFF-UHFFFAOYSA-N 0.000 claims description 2
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims description 2
- CAXRKYFRLOPCAB-UHFFFAOYSA-N propane-1,1-disulfonic acid Chemical compound CCC(S(O)(=O)=O)S(O)(=O)=O CAXRKYFRLOPCAB-UHFFFAOYSA-N 0.000 claims description 2
- 230000015556 catabolic process Effects 0.000 abstract description 13
- 238000006731 degradation reaction Methods 0.000 abstract description 13
- 230000036425 denaturation Effects 0.000 abstract description 13
- 238000004925 denaturation Methods 0.000 abstract description 13
- 150000003278 haem Chemical class 0.000 abstract description 5
- 102000001554 Hemoglobins Human genes 0.000 description 79
- 108010054147 Hemoglobins Proteins 0.000 description 79
- 239000000872 buffer Substances 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 230000000694 effects Effects 0.000 description 12
- 239000007995 HEPES buffer Substances 0.000 description 11
- 239000004816 latex Substances 0.000 description 11
- 229920000126 latex Polymers 0.000 description 11
- 230000002550 fecal effect Effects 0.000 description 9
- 238000009534 blood test Methods 0.000 description 8
- 238000003018 immunoassay Methods 0.000 description 7
- 238000000691 measurement method Methods 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 108010088751 Albumins Proteins 0.000 description 6
- 102000009027 Albumins Human genes 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 230000006641 stabilisation Effects 0.000 description 6
- 238000011105 stabilization Methods 0.000 description 6
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 5
- 210000003608 fece Anatomy 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000006173 Good's buffer Substances 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229910052723 transition metal Inorganic materials 0.000 description 4
- 150000003624 transition metals Chemical class 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000084 colloidal system Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229920001220 nitrocellulos Polymers 0.000 description 3
- 239000003223 protective agent Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 2
- INEWUCPYEUEQTN-UHFFFAOYSA-N 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(O)CNC1CCCCC1 INEWUCPYEUEQTN-UHFFFAOYSA-N 0.000 description 2
- NUFBIAUZAMHTSP-UHFFFAOYSA-N 3-(n-morpholino)-2-hydroxypropanesulfonic acid Chemical compound OS(=O)(=O)CC(O)CN1CCOCC1 NUFBIAUZAMHTSP-UHFFFAOYSA-N 0.000 description 2
- XCBLFURAFHFFJF-UHFFFAOYSA-N 3-[bis(2-hydroxyethyl)azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound OCCN(CCO)CC(O)CS(O)(=O)=O XCBLFURAFHFFJF-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- GIZQLVPDAOBAFN-UHFFFAOYSA-N HEPPSO Chemical compound OCCN1CCN(CC(O)CS(O)(=O)=O)CC1 GIZQLVPDAOBAFN-UHFFFAOYSA-N 0.000 description 2
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 2
- DBXNUXBLKRLWFA-UHFFFAOYSA-N N-(2-acetamido)-2-aminoethanesulfonic acid Chemical compound NC(=O)CNCCS(O)(=O)=O DBXNUXBLKRLWFA-UHFFFAOYSA-N 0.000 description 2
- MKWKNSIESPFAQN-UHFFFAOYSA-N N-cyclohexyl-2-aminoethanesulfonic acid Chemical compound OS(=O)(=O)CCNC1CCCCC1 MKWKNSIESPFAQN-UHFFFAOYSA-N 0.000 description 2
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- -1 alkali metal salts Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 2
- VERAMNDAEAQRGS-UHFFFAOYSA-N butane-1,4-disulfonic acid Chemical compound OS(=O)(=O)CCCCS(O)(=O)=O VERAMNDAEAQRGS-UHFFFAOYSA-N 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000007515 enzymatic degradation Effects 0.000 description 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 238000003317 immunochromatography Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- FITZJYAVATZPMJ-UHFFFAOYSA-N naphthalene-2,6-disulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=CC(S(=O)(=O)O)=CC=C21 FITZJYAVATZPMJ-UHFFFAOYSA-N 0.000 description 2
- 125000004957 naphthylene group Chemical group 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ZIRURAJAJIQZFG-UHFFFAOYSA-N 1-aminopropane-1-sulfonic acid Chemical compound CCC(N)S(O)(=O)=O ZIRURAJAJIQZFG-UHFFFAOYSA-N 0.000 description 1
- YZBGUDOBFPDWKS-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(OC(F)(F)F)C=C1 YZBGUDOBFPDWKS-UHFFFAOYSA-N 0.000 description 1
- AJTVSSFTXWNIRG-UHFFFAOYSA-N 2-[bis(2-hydroxyethyl)amino]ethanesulfonic acid Chemical compound OCC[NH+](CCO)CCS([O-])(=O)=O AJTVSSFTXWNIRG-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- HSXUNHYXJWDLDK-UHFFFAOYSA-N 2-hydroxypropane-1-sulfonic acid Chemical compound CC(O)CS(O)(=O)=O HSXUNHYXJWDLDK-UHFFFAOYSA-N 0.000 description 1
- RZQXOGQSPBYUKH-UHFFFAOYSA-N 3-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound OCC(CO)(CO)NCC(O)CS(O)(=O)=O RZQXOGQSPBYUKH-UHFFFAOYSA-N 0.000 description 1
- FWEOQOXTVHGIFQ-UHFFFAOYSA-N 8-anilinonaphthalene-1-sulfonic acid Chemical compound C=12C(S(=O)(=O)O)=CC=CC2=CC=CC=1NC1=CC=CC=C1 FWEOQOXTVHGIFQ-UHFFFAOYSA-N 0.000 description 1
- 239000007991 ACES buffer Substances 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108700016232 Arg(2)-Sar(4)- dermorphin (1-4) Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000008000 CHES buffer Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- PJWWRFATQTVXHA-UHFFFAOYSA-N Cyclohexylaminopropanesulfonic acid Chemical compound OS(=O)(=O)CCCNC1CCCCC1 PJWWRFATQTVXHA-UHFFFAOYSA-N 0.000 description 1
- 101000925662 Enterobacteria phage PRD1 Endolysin Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- OWXMKDGYPWMGEB-UHFFFAOYSA-N HEPPS Chemical compound OCCN1CCN(CCCS(O)(=O)=O)CC1 OWXMKDGYPWMGEB-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 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 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 1
- 102100030856 Myoglobin Human genes 0.000 description 1
- 108010062374 Myoglobin Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- 208000034953 Twin anemia-polycythemia sequence Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- MIAUJDCQDVWHEV-UHFFFAOYSA-N benzene-1,2-disulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1S(O)(=O)=O MIAUJDCQDVWHEV-UHFFFAOYSA-N 0.000 description 1
- WRUAHXANJKHFIL-UHFFFAOYSA-N benzene-1,3-disulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC(S(O)(=O)=O)=C1 WRUAHXANJKHFIL-UHFFFAOYSA-N 0.000 description 1
- OATNQHYJXLHTEW-UHFFFAOYSA-N benzene-1,4-disulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(S(O)(=O)=O)C=C1 OATNQHYJXLHTEW-UHFFFAOYSA-N 0.000 description 1
- 239000007998 bicine buffer Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000020805 dietary restrictions Nutrition 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- FEVYVSQHKFKUEZ-UHFFFAOYSA-N hexane-1,6-disulfonic acid Chemical compound OS(=O)(=O)CCCCCCS(O)(=O)=O FEVYVSQHKFKUEZ-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical compound OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000000951 immunodiffusion Effects 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- VILFVXYKHXVYAB-UHFFFAOYSA-N naphthalene-2,7-disulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(S(=O)(=O)O)=CC=C21 VILFVXYKHXVYAB-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- WAIFNKJFSAECAT-UHFFFAOYSA-N pentane-1,5-disulfonic acid Chemical compound OS(=O)(=O)CCCCCS(O)(=O)=O WAIFNKJFSAECAT-UHFFFAOYSA-N 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- MGNVWUDMMXZUDI-UHFFFAOYSA-N propane-1,3-disulfonic acid Chemical compound OS(=O)(=O)CCCS(O)(=O)=O MGNVWUDMMXZUDI-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/795—Porphyrin- or corrin-ring-containing peptides
- C07K14/805—Haemoglobins; Myoglobins
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
-
- 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
- G01N21/82—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 producing a precipitate or turbidity
- G01N2021/825—Agglutination
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
前記鎖式の炭化水素基が分岐状もしくは直鎖状の炭化水素基であり、かつ分岐状の前記鎖式の炭化水素基の主鎖もしくは直鎖状の前記鎖式の炭化水素基の炭素数が1乃至10のいずれかであるジスルホン酸又はその塩、
前記環式の炭化水素基がシクロアルキレン基もしくはアリール基であり、かつ前記環式の炭化水素基の炭素数が3乃至10のいずれかであるジスルホン酸又はその塩、並びに、
前記シクロアルキレン基もしくは前記アリール基が1個以上の置換された窒素原子を有するジスルホン酸又はその塩からなる群より選択される少なくとも1種である(1)に記載のヘムタンパク質の保存液。
0.3w/v%の牛血清アルブミン、NaOH、及び緩衝液として0.05mol/Lのリン酸緩衝液を含み、残部を純水とするpH7.0の溶液を調製した。この溶液に、添加物として1,2−EDSを表1に示す各濃度(0.01乃至0.2mol/L)となるように添加し、各濃度の溶液を調製した。この調製した各溶液10mLに溶血ヘモグロビンを600ng/mLとなるように添加し、試料とした。
すなわち、各試料のヘモグロビンの残存率は、対照試料におけるヘモグロビンの添加直後濃度を100%とする相対値である。本実施例における対照試料は、牛血清アルブミン及びNaOHを含むリン酸緩衝液(1,2−EDSを含まない)であり、対照試料の添加直後濃度は583ng/mLであった。結果を表1に示す。
リン酸緩衝液の代わりに、0.05mol/LのN−(2−ヒドロキシエチル)ピペラジン−N’−エタンスルホン酸(以下、HEPESという)を用いた点、表2に示す各濃度(0.005乃至0.2mol/L)となるように1,2−EDSを添加した点以外は、実施例1と同様にして試料を調製し、ヘモグロビン濃度を測定した。結果を表2に示す。なお、各試料の残存率は、対照試料(牛血清アルブミン及びNaOHを含むHEPES緩衝液(1,2−EDSを含まない))における添加直後濃度(576ng/mL)を100%とする相対値で示した。
リン酸緩衝液の代わりに、0.05mol/LのHEPES、0.05mol/Lのピペラジン−N,N’−ビス(2−エタンスルホン酸)(以下、PIPESという)、又は0.05mol/Lの2−モルホリノエタンスルホン酸(以下、MESという)を用いた点、1,2−EDSを表3に示す濃度となるように添加した点以外は、実施例1と同様にして試料を調製し、ヘモグロビン濃度を測定した。結果を表3に示す。なお、各試料の残存率は、対照試料(牛血清アルブミン及びNaOHを含むリン酸緩衝液(1,2−EDSを含まない))における添加直後濃度(583ng/mL)を100%とする相対値で示した。
1,2−EDSの代わりに、1,4−ブタンジスルホン酸(以下、1,4−BDSという)、又は2,6−ナフタレンジスルホン酸(以下、2,6−NDSという)、PIPESを表4に示す濃度となるように添加した点、及びリン酸緩衝液の代わりに、0.05mol/LのHEPESを用いた点以外は、実施例1と同様にして試料を調製し、ヘモグロビン濃度を測定した。結果を表4に示す。なお、各試料の残存率は、対照試料(牛血清アルブミン及びNaOHを含むリン酸緩衝液(ジスルホン酸を含まない))における添加直後濃度(548ng/mL)を100%とする相対値で示した。
1,2−EDSの代わりに8−アニリノ−1−ナフタレンスルホン酸(以下、ANSという)もしくは2−メルカプトエタンスルホン酸ナトリウム(以下、MESSという)を0.01mol/Lとなるように添加した点以外は、実施例1と同様にして試料を調製し、ヘモグロビン濃度を測定した。結果を表5に示す。なお、各試料の残存率は、対照試料(牛血清アルブミン及びNaOHを含むリン酸緩衝液(添加物を含まない))における添加直後濃度(583ng/mL)を100%とする相対値で示した。
Claims (10)
- ジスルホン酸又はその塩を含むヘムタンパク質の保存液。
- 前記ジスルホン酸又はその塩が、鎖式の炭化水素基又は環式の炭化水素基の少なくとも1つを有するジスルホン酸又はその塩であって、
前記鎖式の炭化水素基が分岐状もしくは直鎖状の炭化水素基であり、かつ分岐状の前記鎖式の炭化水素基の主鎖もしくは直鎖状の前記鎖式の炭化水素基の炭素数が1乃至10のいずれかであるジスルホン酸又はその塩、
前記環式の炭化水素基がシクロアルキレン基もしくはアリール基であり、かつ前記環式の炭化水素基の炭素数が3乃至10のいずれかであるジスルホン酸又はその塩、並びに、
前記シクロアルキレン基もしくは前記アリール基が1個以上の置換された窒素原子を有するジスルホン酸又はその塩からなる群より選択される少なくとも1種である請求項1に記載のヘムタンパク質の保存液。 - 前記ジスルホン酸又はその塩が、メタンジスルホン酸、エタンジスルホン酸、プロパンジスルホン酸、ブタンジスルホン酸、ナフタレンジスルホン酸、ピペラジン−N,N’−ビス(2−エタンスルホン酸)又はその塩からなる群より選択される少なくとも1種である請求項1又は2に記載のヘムタンパク質の保存液。
- 前記ジスルホン酸又はその塩の濃度が0.001mol/L以上0.3mol/L以下である請求項1乃至3のいずれか1項に記載のヘムタンパク質の保存液。
- N−(2−ヒドロキシエチル)ピペラジン−N’−エタンスルホン酸をさらに含む請求項1乃至4のいずれか1項に記載のヘムタンパク質の保存液。
- 標準試料又はコントロール試料として用いられる、ヘムタンパク質をさらに含む請求項1乃至5のいずれか1項に記載のヘムタンパク質の保存液。
- 免疫学的測定に用いられる請求項1乃至6のいずれか1項に記載のヘムタンパク質の保存液。
- ヘムタンパク質を含む試料中に、ジスルホン酸又はその塩を共存させるヘムタンパク質の安定化方法。
- 前記ジスルホン酸又はその塩の濃度が0.001mol/L以上0.3mol/L以下である請求項8記載のヘムタンパク質の安定化方法。
- ヘムタンパク質と抗ヘムタンパク質抗体とをジスルホン酸又はその塩の存在下で接触させる工程を含む、ヘムタンパク質の免疫学的測定方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015070667 | 2015-03-31 | ||
JP2015070667 | 2015-03-31 | ||
PCT/JP2016/060597 WO2016159203A1 (ja) | 2015-03-31 | 2016-03-31 | ヘムタンパク質の保存液及びヘムタンパク質の安定化方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2016159203A1 true JPWO2016159203A1 (ja) | 2018-02-01 |
JP6818675B2 JP6818675B2 (ja) | 2021-01-20 |
Family
ID=57007254
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017510166A Active JP6818675B2 (ja) | 2015-03-31 | 2016-03-31 | ヘムタンパク質の保存液及びヘムタンパク質の安定化方法 |
Country Status (10)
Country | Link |
---|---|
US (2) | US11125659B2 (ja) |
EP (1) | EP3279660B1 (ja) |
JP (1) | JP6818675B2 (ja) |
KR (1) | KR102646392B1 (ja) |
CN (1) | CN107615069B (ja) |
AU (1) | AU2016240847B2 (ja) |
ES (1) | ES2804551T3 (ja) |
HK (1) | HK1244539A1 (ja) |
SG (2) | SG11201708762QA (ja) |
WO (1) | WO2016159203A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112285337A (zh) * | 2020-10-15 | 2021-01-29 | 爱若维生物科技(苏州)有限公司 | 一种兽用血细胞分析仪用鞘液及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000258420A (ja) * | 1999-03-05 | 2000-09-22 | Azwell Inc | 溶液中のヒトヘモグロビンの安定化方法および安定化溶液 |
JP2001249132A (ja) * | 2000-03-06 | 2001-09-14 | Eiken Chem Co Ltd | ヘムタンパク質の安定化方法 |
JP2008545371A (ja) * | 2004-12-22 | 2008-12-18 | アンブレツクス・インコーポレイテツド | 非天然アミノ酸及びポリペプチドを含む組成物、非天然アミノ酸及びポリペプチドに関連する方法並び非天然アミノ酸及びポリペプチドその使用 |
JP2013257216A (ja) * | 2012-06-13 | 2013-12-26 | Godo Shusei Co Ltd | ヒトヘモグロビンの安定化方法 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0281251A3 (en) | 1987-02-04 | 1988-09-28 | International Immunoassay Laboratories, Inc. | A method for preparing a fecal sample composition for immunoassay testing |
JP2654181B2 (ja) | 1989-05-10 | 1997-09-17 | 日東電工株式会社 | ヒトヘモグロビンの検出方法 |
US5242832A (en) * | 1990-03-01 | 1993-09-07 | Toa Medical Electronics Co., Ltd. | Reagent for measurement of leukocytes and hemoglobin in blood |
JP2902095B2 (ja) | 1990-10-08 | 1999-06-07 | 日東電工株式会社 | ヒトヘモグロビンを含有する被検液の保存方法及びそれに用いる便溶解用緩衝液 |
JP2723713B2 (ja) | 1991-09-11 | 1998-03-09 | 東洋機械金属株式会社 | 射出成形機の制御方法 |
JPH07229902A (ja) | 1994-02-22 | 1995-08-29 | Eiken Chem Co Ltd | ヘモグロビンの安定化方法 |
JPH11118806A (ja) | 1997-10-13 | 1999-04-30 | Eiken Chem Co Ltd | ヘモグロビンの安定化方法 |
JP4039590B2 (ja) | 1998-01-30 | 2008-01-30 | 栄研化学株式会社 | ヘモグロビン試料の安定化 |
AU3590199A (en) * | 1998-05-01 | 1999-11-23 | Queen's University At Kingston | Method for diagnosing a vascular condition |
JP2003503676A (ja) * | 1999-06-01 | 2003-01-28 | プロティオーム・サイエンシィズ・ピーエルシー | インスリン抵抗性疾患に関する方法及び組成物 |
JP4502352B2 (ja) | 2001-06-29 | 2010-07-14 | 栄研化学株式会社 | ヘムタンパク質の安定化方法および保存溶液 |
JP3898947B2 (ja) | 2001-12-27 | 2007-03-28 | 栄研化学株式会社 | ヘムタンパク質の安定化方法およびこれに用いる保存溶液 |
CN100394187C (zh) * | 2002-06-14 | 2008-06-11 | 爱科来株式会社 | 使用磺酸化合物和硝基化合物的测定方法 |
JPWO2006059694A1 (ja) * | 2004-12-03 | 2008-06-05 | アークレイ株式会社 | 検査用具 |
JP5017614B2 (ja) * | 2007-02-13 | 2012-09-05 | 株式会社シノテスト | 試料中の測定対象物質の測定方法及び測定試薬、非特異的発色を抑制する方法、並びに非特異的発色抑制剤 |
JP5422108B2 (ja) | 2007-10-16 | 2014-02-19 | 栄研化学株式会社 | ヘムタンパク質の安定化方法及び保存溶液 |
WO2009065126A2 (en) * | 2007-11-16 | 2009-05-22 | Boston Protein Solutions | Excipients for protein stabilization |
JP2009222710A (ja) | 2008-02-19 | 2009-10-01 | Sanyo Chem Ind Ltd | ヘモグロビン安定化剤及びヘモグロビンの安定化方法 |
-
2016
- 2016-03-31 WO PCT/JP2016/060597 patent/WO2016159203A1/ja active Application Filing
- 2016-03-31 SG SG11201708762QA patent/SG11201708762QA/en unknown
- 2016-03-31 SG SG10201909108W patent/SG10201909108WA/en unknown
- 2016-03-31 US US15/563,088 patent/US11125659B2/en active Active
- 2016-03-31 ES ES16773083T patent/ES2804551T3/es active Active
- 2016-03-31 JP JP2017510166A patent/JP6818675B2/ja active Active
- 2016-03-31 EP EP16773083.7A patent/EP3279660B1/en active Active
- 2016-03-31 AU AU2016240847A patent/AU2016240847B2/en active Active
- 2016-03-31 CN CN201680030211.7A patent/CN107615069B/zh active Active
- 2016-03-31 KR KR1020177031398A patent/KR102646392B1/ko active IP Right Grant
-
2018
- 2018-03-21 HK HK18103932.5A patent/HK1244539A1/zh unknown
-
2021
- 2021-08-17 US US17/404,715 patent/US20210381935A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000258420A (ja) * | 1999-03-05 | 2000-09-22 | Azwell Inc | 溶液中のヒトヘモグロビンの安定化方法および安定化溶液 |
JP2001249132A (ja) * | 2000-03-06 | 2001-09-14 | Eiken Chem Co Ltd | ヘムタンパク質の安定化方法 |
JP2008545371A (ja) * | 2004-12-22 | 2008-12-18 | アンブレツクス・インコーポレイテツド | 非天然アミノ酸及びポリペプチドを含む組成物、非天然アミノ酸及びポリペプチドに関連する方法並び非天然アミノ酸及びポリペプチドその使用 |
JP2013257216A (ja) * | 2012-06-13 | 2013-12-26 | Godo Shusei Co Ltd | ヒトヘモグロビンの安定化方法 |
Also Published As
Publication number | Publication date |
---|---|
KR102646392B1 (ko) | 2024-03-11 |
CN107615069B (zh) | 2021-04-20 |
EP3279660A1 (en) | 2018-02-07 |
US20210381935A1 (en) | 2021-12-09 |
WO2016159203A1 (ja) | 2016-10-06 |
US11125659B2 (en) | 2021-09-21 |
SG10201909108WA (en) | 2019-11-28 |
EP3279660B1 (en) | 2020-04-29 |
EP3279660A4 (en) | 2018-09-05 |
AU2016240847A1 (en) | 2017-11-09 |
HK1244539A1 (zh) | 2018-08-10 |
JP6818675B2 (ja) | 2021-01-20 |
SG11201708762QA (en) | 2017-11-29 |
US20180172562A1 (en) | 2018-06-21 |
ES2804551T3 (es) | 2021-02-08 |
KR20170132845A (ko) | 2017-12-04 |
AU2016240847B2 (en) | 2021-07-29 |
CN107615069A (zh) | 2018-01-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6434843B2 (ja) | ヘムタンパク質の保存液及びヘムタンパク質の安定化方法 | |
EP2204648B1 (en) | Method of stabilizing hem protein and storage solution therefor | |
CN109633148B (zh) | Kl-6检测乳胶凝集试剂 | |
US9046517B2 (en) | Cystatin C adsorption inhibitor | |
JP7508494B2 (ja) | ヘモグロビンの測定試薬、測定キット及び測定方法 | |
US20210381935A1 (en) | Preservative solution for heme protein, and method for stabilizing heme protein | |
JP2023100882A (ja) | ヘモグロビンとハプトグロビンとの複合体を安定化する方法、及びヘモグロビンを含む検体を保存するための保存溶液 | |
KR20030022314A (ko) | 불용성담체입자를 사용하는 면역측정방법 및 그 시약 | |
KR102181485B1 (ko) | 면역학적 측정 방법 및 측정 시약 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190314 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190314 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200512 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200709 |
|
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: 20201216 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20201228 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6818675 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |