CN1322330C - 钴胺素的分析方法 - Google Patents
钴胺素的分析方法 Download PDFInfo
- Publication number
- CN1322330C CN1322330C CNB2004100055424A CN200410005542A CN1322330C CN 1322330 C CN1322330 C CN 1322330C CN B2004100055424 A CNB2004100055424 A CN B2004100055424A CN 200410005542 A CN200410005542 A CN 200410005542A CN 1322330 C CN1322330 C CN 1322330C
- Authority
- CN
- China
- Prior art keywords
- cobalamin
- transcobalamin
- conjunction
- analytical approach
- holo
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims description 66
- 239000003153 chemical reaction reagent Substances 0.000 title description 2
- 102000011409 Transcobalamins Human genes 0.000 claims abstract description 125
- 108010023603 Transcobalamins Proteins 0.000 claims abstract description 125
- 239000003446 ligand Substances 0.000 claims abstract description 59
- 230000009870 specific binding Effects 0.000 claims abstract description 20
- 210000001124 body fluid Anatomy 0.000 claims abstract description 16
- 239000010839 body fluid Substances 0.000 claims abstract description 16
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims abstract 25
- 230000027455 binding Effects 0.000 claims description 63
- 238000013459 approach Methods 0.000 claims description 48
- 108010006591 Apoenzymes Proteins 0.000 claims description 38
- 238000004458 analytical method Methods 0.000 claims description 34
- 210000002966 serum Anatomy 0.000 claims description 27
- 210000002381 plasma Anatomy 0.000 claims description 18
- 239000002245 particle Substances 0.000 claims description 17
- 230000009260 cross reactivity Effects 0.000 claims description 9
- 210000004369 blood Anatomy 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000003346 cobalamin group Chemical group 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 210000000582 semen Anatomy 0.000 claims description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 3
- 108010001857 Cell Surface Receptors Proteins 0.000 claims description 3
- 108020004414 DNA Proteins 0.000 claims description 3
- 210000004381 amniotic fluid Anatomy 0.000 claims description 3
- 238000004737 colorimetric analysis Methods 0.000 claims description 3
- 230000002860 competitive effect Effects 0.000 claims description 3
- 102000006240 membrane receptors Human genes 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- 102000015636 Oligopeptides Human genes 0.000 claims description 2
- 108010038807 Oligopeptides Proteins 0.000 claims description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 2
- 238000001952 enzyme assay Methods 0.000 claims description 2
- 230000003053 immunization Effects 0.000 claims description 2
- 238000002649 immunization Methods 0.000 claims description 2
- WUPRCGRRQUZFAB-YOAOAAAGSA-N corrin Chemical compound N1C2CC\C1=C\C(CC1)=NC1=CC(CC1)=NC1=CC1=NC2CC1 WUPRCGRRQUZFAB-YOAOAAAGSA-N 0.000 claims 2
- 102100040423 Transcobalamin-2 Human genes 0.000 abstract description 117
- 238000003556 assay Methods 0.000 abstract description 4
- ASARMUCNOOHMLO-WLORSUFZSA-L cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2s)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O ASARMUCNOOHMLO-WLORSUFZSA-L 0.000 description 175
- 150000001875 compounds Chemical class 0.000 description 34
- 239000000370 acceptor Substances 0.000 description 17
- 238000000926 separation method Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 15
- 239000012634 fragment Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 10
- 239000006249 magnetic particle Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 108090001008 Avidin Proteins 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 230000035945 sensitivity Effects 0.000 description 8
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 239000012491 analyte Substances 0.000 description 7
- 239000007790 solid phase Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 229940029329 intrinsic factor Drugs 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000002503 metabolic effect Effects 0.000 description 6
- 101710124862 Transcobalamin-2 Proteins 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 229960002685 biotin Drugs 0.000 description 5
- 235000020958 biotin Nutrition 0.000 description 5
- 239000011616 biotin Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 108010088751 Albumins Proteins 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 238000013016 damping Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 208000005577 Gastroenteritis Diseases 0.000 description 3
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 102100040396 Transcobalamin-1 Human genes 0.000 description 3
- 208000007502 anemia Diseases 0.000 description 3
- 238000011088 calibration curve Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- WUPRCGRRQUZFAB-DEGKJRJSSA-N corrin Chemical group N1C2CC\C1=C\C(CC/1)=N\C\1=C/C(CC\1)=N/C/1=C\C1=NC2CC1 WUPRCGRRQUZFAB-DEGKJRJSSA-N 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000012797 qualification Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 102100034613 Annexin A2 Human genes 0.000 description 2
- 108090000668 Annexin A2 Proteins 0.000 description 2
- 108090000669 Annexin A4 Proteins 0.000 description 2
- 102100034612 Annexin A4 Human genes 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001597008 Nomeidae Species 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
- 238000007413 biotinylation Methods 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000005515 coenzyme Substances 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 230000005415 magnetization Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000012543 microbiological analysis Methods 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 239000003488 releasing hormone Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- -1 thin plate Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MZFOKIKEPGUZEN-AGCMQPJKSA-N (R)-methylmalonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)[C@@H](C(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MZFOKIKEPGUZEN-AGCMQPJKSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- JNGRENQDBKMCCR-UHFFFAOYSA-N 2-(3-amino-6-iminoxanthen-9-yl)benzoic acid;hydrochloride Chemical compound [Cl-].C=12C=CC(=[NH2+])C=C2OC2=CC(N)=CC=C2C=1C1=CC=CC=C1C(O)=O JNGRENQDBKMCCR-UHFFFAOYSA-N 0.000 description 1
- IYZPEGVSBUNMBE-UHFFFAOYSA-N 2-[[5-[1-[3-[[carboxylatomethyl(carboxymethyl)azaniumyl]methyl]-4-hydroxy-5-methylphenyl]-3-oxo-2-benzofuran-1-yl]-2-hydroxy-3-methylphenyl]methyl-(carboxymethyl)azaniumyl]acetate Chemical compound OC(=O)CN(CC(O)=O)CC1=C(O)C(C)=CC(C2(C3=CC=CC=C3C(=O)O2)C=2C=C(CN(CC(O)=O)CC(O)=O)C(O)=C(C)C=2)=C1 IYZPEGVSBUNMBE-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- GUQQBLRVXOUDTN-XOHPMCGNSA-N 3-[dimethyl-[3-[[(4r)-4-[(3r,5s,7r,8r,9s,10s,12s,13r,14s,17r)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]propyl]azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CC(O)CS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 GUQQBLRVXOUDTN-XOHPMCGNSA-N 0.000 description 1
- PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 206010002065 Anaemia megaloblastic Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- PQMOXTJVIYEOQL-UHFFFAOYSA-N Cumarin Natural products CC(C)=CCC1=C(O)C(C(=O)C(C)CC)=C(O)C2=C1OC(=O)C=C2CCC PQMOXTJVIYEOQL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108010025076 Holoenzymes Proteins 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 208000000682 Megaloblastic Anemia Diseases 0.000 description 1
- FSOGIJPGPZWNGO-UHFFFAOYSA-N Meomammein Natural products CCC(C)C(=O)C1=C(O)C(CC=C(C)C)=C(O)C2=C1OC(=O)C=C2CCC FSOGIJPGPZWNGO-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 108010053210 Phycocyanin Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000235342 Saccharomycetes Species 0.000 description 1
- 108010032838 Sialoglycoproteins Proteins 0.000 description 1
- 102000007365 Sialoglycoproteins Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000011358 absorbing material Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 208000012873 acute gastroenteritis Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000000987 azo dye Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical group [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- SYELZBGXAIXKHU-UHFFFAOYSA-N dodecyldimethylamine N-oxide Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-] SYELZBGXAIXKHU-UHFFFAOYSA-N 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 210000001842 enterocyte Anatomy 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000002500 ions Chemical group 0.000 description 1
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000002935 megaloblast Anatomy 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000000272 myelencephalon Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 230000008884 pinocytosis Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000005234 proximal tubule cell Anatomy 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910021487 silica fume Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000004206 stomach function Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- VNOYUJKHFWYWIR-ITIYDSSPSA-N succinyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 VNOYUJKHFWYWIR-ITIYDSSPSA-N 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 229940046001 vitamin b complex Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Images
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
- G01N33/82—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving vitamins or their receptors
-
- 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
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/54326—Magnetic particles
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Lubrication Of Internal Combustion Engines (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Liquid Developers In Electrophotography (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
- Cable Accessories (AREA)
- Glass Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Devices For Conveying Motion By Means Of Endless Flexible Members (AREA)
- Mechanical Treatment Of Semiconductor (AREA)
- Measuring And Recording Apparatus For Diagnosis (AREA)
- Polyamides (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Analysing Materials By The Use Of Radiation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9820473.8 | 1998-09-18 | ||
| GBGB9820473.8A GB9820473D0 (en) | 1998-09-18 | 1998-09-18 | Assay |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB998110396A Division CN1148580C (zh) | 1998-09-18 | 1999-09-20 | 钴胺素的分析方法和试剂盒 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1530659A CN1530659A (zh) | 2004-09-22 |
| CN1322330C true CN1322330C (zh) | 2007-06-20 |
Family
ID=10839158
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100055424A Expired - Fee Related CN1322330C (zh) | 1998-09-18 | 1999-09-20 | 钴胺素的分析方法 |
| CNB998110396A Expired - Fee Related CN1148580C (zh) | 1998-09-18 | 1999-09-20 | 钴胺素的分析方法和试剂盒 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB998110396A Expired - Fee Related CN1148580C (zh) | 1998-09-18 | 1999-09-20 | 钴胺素的分析方法和试剂盒 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US7279283B1 (enExample) |
| EP (2) | EP1114323B1 (enExample) |
| JP (1) | JP4394285B2 (enExample) |
| KR (2) | KR100646305B1 (enExample) |
| CN (2) | CN1322330C (enExample) |
| AT (2) | ATE283490T1 (enExample) |
| AU (1) | AU761498B2 (enExample) |
| BR (1) | BR9913770A (enExample) |
| CA (1) | CA2344193C (enExample) |
| CY (1) | CY1106688T1 (enExample) |
| CZ (2) | CZ298310B6 (enExample) |
| DE (2) | DE69922225T2 (enExample) |
| DK (1) | DK1443328T3 (enExample) |
| ES (2) | ES2287607T3 (enExample) |
| GB (1) | GB9820473D0 (enExample) |
| HU (1) | HU228077B1 (enExample) |
| MX (1) | MXPA01002591A (enExample) |
| NO (2) | NO327771B1 (enExample) |
| NZ (1) | NZ510766A (enExample) |
| PL (2) | PL198095B1 (enExample) |
| PT (2) | PT1114323E (enExample) |
| WO (1) | WO2000017659A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0016460D0 (en) * | 2000-07-04 | 2000-08-23 | Axis Shield Asa | Assay |
| GB0109925D0 (en) * | 2001-04-23 | 2001-06-13 | Axis Shield Asa | Method |
| TR201903607T4 (tr) | 2012-11-06 | 2019-04-22 | Hyundai Motor Co Ltd | Yüksek oranda ısıl dirençli, ses soğurumlu ve perdelemeli malzemenin üretilmesine yönelik yöntem. |
| CN104198598B (zh) * | 2014-07-15 | 2016-03-16 | 汤臣倍健股份有限公司 | 一种维生素b12的测定方法 |
| CN106841017B (zh) * | 2017-01-22 | 2019-05-07 | 耐斯检测技术服务有限公司 | 一种评价辐照或热处理对钴胺素-蛋白结合体影响的方法 |
| CN106693443A (zh) * | 2017-01-23 | 2017-05-24 | 北京美正生物科技有限公司 | 一种维生素b12适配体亲和柱及其制备方法和用途 |
| CN118126173A (zh) * | 2019-08-09 | 2024-06-04 | 美国西门子医学诊断股份有限公司 | 抗猪tcn1单克隆抗体及其生产和使用方法 |
| CN116457657B (zh) * | 2020-12-18 | 2025-03-11 | 中外制药株式会社 | 基于动态分析的相对fu比的测定方法 |
| CN113189252A (zh) * | 2021-04-19 | 2021-07-30 | 中国医学科学院北京协和医院 | 一种总钴胺素和氰钴胺的检测方法及其检测试剂盒和应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4680273A (en) * | 1985-07-29 | 1987-07-14 | Victor Herbert | Assay for vitamin B12 deficiency |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4273757A (en) * | 1977-06-02 | 1981-06-16 | Yissum Research Development Company | Determination of transcobalamins |
| US4332785A (en) * | 1980-04-09 | 1982-06-01 | University Patents, Inc. | Immunoassay for measurement of reticulocytes, and immunoreactive reagents for use therein |
| DE3262956D1 (en) * | 1981-06-22 | 1985-05-15 | Technicon Instr | Labelled vitamin b12 derivatives, their preparation and use |
| US5374560A (en) * | 1989-04-03 | 1994-12-20 | The University Of Colorado, Inc. | Method for screening and distinguishing between cobalamin and folic acid deficiency based on assay for cystathionine and 2-methylcitric acid |
| US5457055A (en) * | 1986-11-20 | 1995-10-10 | The University Of Colorado Foundation | Diagnostic method for cobalamin deficiency |
| DE3900650A1 (de) * | 1989-01-11 | 1990-07-12 | Boehringer Mannheim Gmbh | Vitamin-b12-bestimmung |
| US5310656A (en) | 1989-06-26 | 1994-05-10 | Tritech Partners | Vitamin B12 assay |
| WO1991000519A1 (en) * | 1989-06-26 | 1991-01-10 | Triton Diagnostics, Inc. | Vitamin b12 assay |
| US5506109A (en) | 1989-06-26 | 1996-04-09 | Bayer Corporation | Vitamin B12 assay |
| KR950701390A (ko) * | 1992-05-08 | 1995-03-23 | 에이. 찰스 모간 2세 | 비타민 B12/ 트랜스코발라민 II 수용체에 대한 항-수용체 제제(Anti-receptor agents to the vitamin B12/ transcobalamin II receptor) |
| CA2266412A1 (en) * | 1996-09-18 | 1998-03-26 | William J. Sarill | Compositions containing cobalamin and amino acids |
-
1998
- 1998-09-18 GB GBGB9820473.8A patent/GB9820473D0/en not_active Ceased
-
1999
- 1999-09-20 HU HU0103532A patent/HU228077B1/hu not_active IP Right Cessation
- 1999-09-20 AT AT99947642T patent/ATE283490T1/de active
- 1999-09-20 CA CA002344193A patent/CA2344193C/en not_active Expired - Lifetime
- 1999-09-20 JP JP2000571269A patent/JP4394285B2/ja not_active Expired - Lifetime
- 1999-09-20 MX MXPA01002591A patent/MXPA01002591A/es not_active IP Right Cessation
- 1999-09-20 DE DE69922225T patent/DE69922225T2/de not_active Expired - Lifetime
- 1999-09-20 CN CNB2004100055424A patent/CN1322330C/zh not_active Expired - Fee Related
- 1999-09-20 EP EP99947642A patent/EP1114323B1/en not_active Expired - Lifetime
- 1999-09-20 ES ES04009702T patent/ES2287607T3/es not_active Expired - Lifetime
- 1999-09-20 AU AU61026/99A patent/AU761498B2/en not_active Ceased
- 1999-09-20 KR KR1020047014817A patent/KR100646305B1/ko not_active Expired - Lifetime
- 1999-09-20 CN CNB998110396A patent/CN1148580C/zh not_active Expired - Fee Related
- 1999-09-20 WO PCT/GB1999/003127 patent/WO2000017659A1/en not_active Ceased
- 1999-09-20 EP EP04009702A patent/EP1443328B1/en not_active Expired - Lifetime
- 1999-09-20 DK DK04009702T patent/DK1443328T3/da active
- 1999-09-20 BR BR9913770-4A patent/BR9913770A/pt not_active IP Right Cessation
- 1999-09-20 PL PL347104A patent/PL198095B1/pl unknown
- 1999-09-20 CZ CZ20010975A patent/CZ298310B6/cs not_active IP Right Cessation
- 1999-09-20 ES ES99947642T patent/ES2234299T3/es not_active Expired - Lifetime
- 1999-09-20 PT PT99947642T patent/PT1114323E/pt unknown
- 1999-09-20 DE DE69936154T patent/DE69936154T2/de not_active Expired - Lifetime
- 1999-09-20 PT PT04009702T patent/PT1443328E/pt unknown
- 1999-09-20 CZ CZ20023143A patent/CZ298381B6/cs not_active IP Right Cessation
- 1999-09-20 KR KR1020017003485A patent/KR100781014B1/ko not_active Expired - Lifetime
- 1999-09-20 AT AT04009702T patent/ATE363076T1/de active
- 1999-09-20 NZ NZ510766A patent/NZ510766A/en not_active IP Right Cessation
- 1999-09-20 PL PL382436A patent/PL201360B1/pl unknown
-
2000
- 2000-10-04 US US09/679,043 patent/US7279283B1/en not_active Expired - Lifetime
-
2001
- 2001-03-16 NO NO20011353A patent/NO327771B1/no not_active IP Right Cessation
-
2007
- 2007-07-02 CY CY20071100864T patent/CY1106688T1/el unknown
-
2008
- 2008-08-21 NO NO20083610A patent/NO331074B1/no not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4680273A (en) * | 1985-07-29 | 1987-07-14 | Victor Herbert | Assay for vitamin B12 deficiency |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10732111B2 (en) | Automated immunoanalyzer system for performing diagnostic assays for allergies and autoimmune diseases | |
| US6143510A (en) | Measuring method using whole blood sample | |
| CN1322330C (zh) | 钴胺素的分析方法 | |
| JPH09504094A (ja) | 磁性ラテックス粒子および非磁性粒子を用いて免疫物質をアッセイする方法 | |
| AU682478B2 (en) | Two-site immunoassay for an antibody with chemiluminescent label and biotin bound ligand | |
| EP1257830B1 (en) | Assay for measuring holo-transcobalamin and folate | |
| US7344849B2 (en) | Assay | |
| AU2003203209B2 (en) | Cobalamin assay | |
| NZ525253A (en) | Cobalamin assay | |
| ZA200101937B (en) | Cobalamin assay. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |