JP6144208B2 - アスコルビン酸の影響抑制方法 - Google Patents
アスコルビン酸の影響抑制方法 Download PDFInfo
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- JP6144208B2 JP6144208B2 JP2013557533A JP2013557533A JP6144208B2 JP 6144208 B2 JP6144208 B2 JP 6144208B2 JP 2013557533 A JP2013557533 A JP 2013557533A JP 2013557533 A JP2013557533 A JP 2013557533A JP 6144208 B2 JP6144208 B2 JP 6144208B2
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims description 80
- 235000010323 ascorbic acid Nutrition 0.000 title claims description 40
- 229960005070 ascorbic acid Drugs 0.000 title claims description 40
- 239000011668 ascorbic acid Substances 0.000 title claims description 40
- 230000000694 effects Effects 0.000 title description 10
- 102000017011 Glycated Hemoglobin A Human genes 0.000 claims description 77
- 108091005995 glycated hemoglobin Proteins 0.000 claims description 77
- 239000003153 chemical reaction reagent Substances 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 239000000126 substance Substances 0.000 claims description 45
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 44
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 44
- 102000001554 Hemoglobins Human genes 0.000 claims description 39
- 108010054147 Hemoglobins Proteins 0.000 claims description 39
- 238000005259 measurement Methods 0.000 claims description 34
- 102000035195 Peptidases Human genes 0.000 claims description 30
- 108091005804 Peptidases Proteins 0.000 claims description 30
- 229910052811 halogen oxide Inorganic materials 0.000 claims description 29
- 102000004316 Oxidoreductases Human genes 0.000 claims description 25
- 108090000854 Oxidoreductases Proteins 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 20
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 claims description 7
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 claims description 7
- -1 first Proteins 0.000 description 84
- 150000001875 compounds Chemical class 0.000 description 45
- 125000004432 carbon atom Chemical group C* 0.000 description 38
- 210000000601 blood cell Anatomy 0.000 description 23
- 235000002639 sodium chloride Nutrition 0.000 description 21
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 15
- 125000003342 alkenyl group Chemical group 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 102000003992 Peroxidases Human genes 0.000 description 12
- 238000002835 absorbance Methods 0.000 description 12
- 108040007629 peroxidase activity proteins Proteins 0.000 description 12
- 239000012736 aqueous medium Substances 0.000 description 11
- 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 11
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 10
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 125000004079 stearyl 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])C([H])([H])C([H])([H])[H] 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
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- 238000011088 calibration curve Methods 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
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- 239000001230 potassium iodate Substances 0.000 description 8
- 235000006666 potassium iodate Nutrition 0.000 description 8
- 229940093930 potassium iodate Drugs 0.000 description 8
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 8
- CWLYDTVACYGEPD-UHFFFAOYSA-M sodium;2-[[3,7-bis(dimethylamino)phenothiazine-10-carbonyl]amino]acetate Chemical compound [Na+].C1=C(N(C)C)C=C2SC3=CC(N(C)C)=CC=C3N(C(=O)NCC([O-])=O)C2=C1 CWLYDTVACYGEPD-UHFFFAOYSA-M 0.000 description 8
- 238000003018 immunoassay Methods 0.000 description 7
- 238000000691 measurement method Methods 0.000 description 7
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- JLKDVMWYMMLWTI-UHFFFAOYSA-M potassium iodate Chemical compound [K+].[O-]I(=O)=O JLKDVMWYMMLWTI-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 5
- 239000004153 Potassium bromate Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- 125000001204 arachidyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000002960 margaryl 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])C([H])([H])[H] 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 125000001196 nonadecyl 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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000002958 pentadecyl 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])[H] 0.000 description 5
- 229940094037 potassium bromate Drugs 0.000 description 5
- 235000019396 potassium bromate Nutrition 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 4
- XWNSFEAWWGGSKJ-UHFFFAOYSA-N 4-acetyl-4-methylheptanedinitrile Chemical compound N#CCCC(C)(C(=O)C)CCC#N XWNSFEAWWGGSKJ-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 4
- 229920004896 Triton X-405 Polymers 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 150000005215 alkyl ethers Chemical class 0.000 description 4
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 4
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 4
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000003607 modifier Substances 0.000 description 4
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- 229950000688 phenothiazine Drugs 0.000 description 4
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- 238000002360 preparation method Methods 0.000 description 4
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 4
- 229940054269 sodium pyruvate Drugs 0.000 description 4
- 125000000547 substituted alkyl group Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 150000003973 alkyl amines Chemical class 0.000 description 3
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
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- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 238000004040 coloring Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 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 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 3
- PYHRZPFZZDCOPH-QXGOIDDHSA-N (S)-amphetamine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C[C@H](N)CC1=CC=CC=C1.C[C@H](N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-QXGOIDDHSA-N 0.000 description 2
- GKQHIYSTBXDYNQ-UHFFFAOYSA-M 1-dodecylpyridin-1-ium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+]1=CC=CC=C1 GKQHIYSTBXDYNQ-UHFFFAOYSA-M 0.000 description 2
- QZTKDVCDBIDYMD-UHFFFAOYSA-N 2,2'-[(2-amino-2-oxoethyl)imino]diacetic acid Chemical compound NC(=O)CN(CC(O)=O)CC(O)=O QZTKDVCDBIDYMD-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
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- JUIQOABNSLTJSW-UHFFFAOYSA-N 2-Methyl-4,5-dihydro-1,3-thiazole Chemical compound CC1=NCCS1 JUIQOABNSLTJSW-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 description 2
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- CMPVUVUNJQERIT-UHFFFAOYSA-N 2-isobutylthiazole Chemical compound CC(C)CC1=NC=CS1 CMPVUVUNJQERIT-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
- 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 2
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
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- PJWWRFATQTVXHA-UHFFFAOYSA-N Cyclohexylaminopropanesulfonic acid Chemical compound OS(=O)(=O)CCCNC1CCCCC1 PJWWRFATQTVXHA-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
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- DBXNUXBLKRLWFA-UHFFFAOYSA-N N-(2-acetamido)-2-aminoethanesulfonic acid Chemical compound NC(=O)CNCCS(O)(=O)=O DBXNUXBLKRLWFA-UHFFFAOYSA-N 0.000 description 2
- YNLCVAQJIKOXER-UHFFFAOYSA-N N-[tris(hydroxymethyl)methyl]-3-aminopropanesulfonic acid Chemical compound OCC(CO)(CO)NCCCS(O)(=O)=O YNLCVAQJIKOXER-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
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- 108010064719 Oxyhemoglobins Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108090001109 Thermolysin Proteins 0.000 description 2
- 239000002280 amphoteric surfactant Substances 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
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- 239000011697 sodium iodate Substances 0.000 description 1
- 235000015281 sodium iodate Nutrition 0.000 description 1
- 229940032753 sodium iodate Drugs 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000008054 sulfonate salts Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/54—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2523/00—Reactions characterised by treatment of reaction samples
- C12Q2523/10—Characterised by chemical treatment
- C12Q2523/113—Denaturating agents
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
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- Biotechnology (AREA)
- Biophysics (AREA)
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- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Emergency Medicine (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Description
[2] ハロゲン酸化物が、ヨウ素酸若しくはその塩、及び、臭素酸若しくはその塩からなる群より選ばれるハロゲン酸化物である、[1]記載の方法。
[3] 糖化ヘモグロビンが、ヘモグロビンA1cである[1]又は[2]記載の方法。
[5] ハロゲン酸化物が、ヨウ素酸若しくはその塩、及び、臭素酸若しくはその塩からなる群より選ばれるハロゲン酸化物である、[4]記載の試薬。
[6] 糖化ヘモグロビンが、ヘモグロビンA1cである[4]又は[5]記載の試薬。
[7] 試料中の糖化ヘモグロビンの測定におけるアスコルビン酸の影響を抑制するための[4]〜[6]のいずれかに記載の試薬。
本発明の、糖化ヘモグロビン含有試料中の糖化ヘモグロビンの測定におけるアスコルビン酸の影響抑制方法は、糖化ヘモグロビン含有試料にタンパク質分解酵素を作用させた後、生成した糖化ペプチドを糖化ペプチド酸化酵素と反応させ、生成した過酸化水素を測定することにより、試料中の糖化ヘモグロビンを測定する方法において、糖化ペプチドと糖化ペプチド酸化酵素との反応を、ハロゲン酸化物と、一般式(I)
本発明の、糖化ヘモグロビン含有試料中の糖化ヘモグロビン測定試薬は、タンパク質分解酵素、糖化ペプチド酸化酵素、ハロゲン酸化物、化合物(I)及び化合物(II)からなる群より選ばれる物質、及び、過酸化水素測定用試薬を含む試薬である。本発明の糖化ヘモグロビン測定試薬は、本発明のアスコルビン酸の影響抑制方法に使用される。
水性媒体としては、例えば脱イオン水、蒸留水、緩衝液等が挙げられ、緩衝液が好ましい。
第1試薬
Bis−Tris(pH6.8) 10mmol/L
C12py 1.2g/L
ヨウ素酸カリウム
化合物(I)又は化合物(II)
塩化カルシウム2水和物 16mmol/L
ピルビン酸ナトリウム 2g/L
アクチナーゼE 340kU/L
DMSO 0.2mL/L
DA−67 12.6μmol/L
第2試薬
MOPS(pH7.0) 50mmol/L
トリトンX−405 7.1g/L
ペルオキシダーゼ 80kU/L
FPOX−CET 2.5kU/L
第1試薬
Bis−Tris(pH6.8) 10mmol/L
C14TMA 0.6g/L
ヨウ素酸カリウム
化合物(I)又は化合物(II)
塩化カルシウム2水和物 16mmol/L
ピルビン酸ナトリウム 2g/L
アクチナーゼE 340kU/L
DMSO 0.2mL/L
DA−67 12.6μmol/L
第2試薬
MOPS(pH7.0) 50mmol/L
トリトンX−405 7.1g/L
ペルオキシダーゼ 80kU/L
FPOX−CET 2.5kU/L
第1試薬
Bis−Tris(pH6.8) 10mmol/L
C14TMA 0.6g/L
臭素酸カリウム
化合物(I)又は化合物(II)
塩化カルシウム2水和物 16mmol/L
ピルビン酸ナトリウム 2g/L
アクチナーゼE 340kU/L
DMSO 0.2mL/L
DA−67 12.6μmol/L
第2試薬
MOPS(pH7.0) 50mmol/L
トリトンX−405 7.1g/L
ペルオキシダーゼ 80kU/L
FPOX−CET 2.5kU/L
測定キットとして、総ヘモグロビン測定用キットであるネスコートヘモキット−N(シアンメトヘモグロビン法)(アルフレッサファーマ社製)を用いて、検体として、ネスコートヘモキット−Nに付属の標準液(ヘモグロビン濃度:15.3 g/dL)を用いて、ヘモグロビン濃度と吸光度との関係を示す検量線を作成した。
ラテックス免疫凝集法と、血球画分の総ヘモグロビン値とから、HbA1c濃度が2.97 μmol/L、7.80 μmol/Lと値付けされた2つの血球画分について、実施例1のキット1を用いて測定し、各血球画分に対する吸光度を測定した。当該血球画分の代わりに生理食塩水を用いて、生理食塩水に対するHbA1c濃度を測定した。当該血球画分に対するそれぞれの吸光度から、生理食塩水に対する吸光度を差し引いて算出した値を、当該血球画分に対するブランク補正吸光度とした。当該血球画分に対するブランク補正吸光度と、生理食塩水に対するブランク補正吸光度(0 Abs)とから、HbA1c濃度(μmol/L)と吸光度との間の関係を示す検量線を作成した。
各試料に対して、25℃、3,000 rpmで5分間遠心分離を行い、血球画分を得た。各血球画分について、ネスコートヘモキット−Nを用いて測定し、得られた測定値と(1)の検量線とから、各血球画分中のヘモグロビン濃度(μmol/L)を決定した。
各血球画分について、実施例1のキット1を用いて測定し、得られた測定値と(2)の検量線とから、各血球画分中のHbA1c濃度(μmol/L)を決定した。
上記(3)で決定した各血球画分におけるヘモグロビン濃度(μmol/L)と、上記(4)で決定した各血球画分におけるHbA1c濃度(μmol/L)とから、以下の式により、日本糖尿病学会(Japan Diabetes Society;JDS)値のHbA1c(%)を算出した。
上記(5)でのHbA1c(%)の決定に使用した血球画分と同一の血球画分を用いて、各血球画分中のHbA1c(%)を、デタミナーL HbA1c(協和メデックス社製)を用いる免疫測定法により、デタミナーL HbA1cの添付文書に記載の方法に従って決定した。
本発明の測定キットを用いる測定方法により、上記(5)で決定したHbA1c(%)と、免疫測定法を用いて、上記(6)で決定したHbA1c(%)とから、本発明の測定方法と免疫測定法との間の相関関係を検証し、相関係数を決定した。
ヒト血液を遠心分離して得られた血球画分について、総ヘモグロビン測定用キットであるネスコートヘモキット−N(シアンメトヘモグロビン法)(アルフレッサファーマ社製)を用いてヘモグロビン濃度を決定した後、当該血球画分を精製水で希釈すると共に、溶血させて、ヘモグロビン濃度6.4 mg/mLのヘモグロビン溶液を調製した。
実施例4の(2)の方法により、HbA1c濃度(μmol/L)と吸光度との間の関係を示す検量線を作成した。
上記(1)で調製したアスコルビン酸の影響確認用試料の各試料について、実施例1のキット1を用いて測定し、得られた測定値と(2)の検量線とから、各試料中のHbA1c濃度(μmol/L)を決定した。アスコルビン酸濃度が0 mg/dLであるアスコルビン酸の影響確認用試料におけるHbA1c濃度(μmol/L)を100としたときの、アスコルビン酸濃度が0.5 mg/dL、1 mg/dL、2 mg/dLであるアスコルビン酸の影響確認用試料の各試料中のHbA1c濃度(μmol/L)の相対値を決定した。
Claims (7)
- 糖化ヘモグロビン含有試料にタンパク質分解酵素を作用させた後、生成した糖化ペプチドを糖化ペプチド酸化酵素と反応させ、生成した過酸化水素を測定することにより、試料中の糖化ヘモグロビンを測定する方法において、糖化ペプチドと糖化ペプチド酸化酵素との反応を、ハロゲン酸化物と、一般式(I)
- ハロゲン酸化物が、ヨウ素酸若しくはその塩、及び、臭素酸若しくはその塩からなる群より選ばれるハロゲン酸化物である、請求項1記載の方法。
- 糖化ヘモグロビンが、ヘモグロビンA1cである請求項1又は2記載の方法。
- タンパク質分解酵素、糖化ペプチド酸化酵素、ハロゲン酸化物、過酸化水素測定用試薬、並びに、一般式(I)
- ハロゲン酸化物が、ヨウ素酸若しくはその塩、及び、臭素酸若しくはその塩からなる群より選ばれるハロゲン酸化物である、請求項4記載の試薬。
- 糖化ヘモグロビンが、ヘモグロビンA1cである請求項4又は5記載の試薬。
- 試料中の糖化ヘモグロビンの測定におけるアスコルビン酸の影響を抑制するための請求項4〜6のいずれかに記載の試薬。
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HK1202592A1 (en) | 2015-10-02 |
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Free format text: JAPANESE INTERMEDIATE CODE: R250 |
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |