CN102260291B - 一种核黄素磷酸钠化合物及其制备 - Google Patents
一种核黄素磷酸钠化合物及其制备 Download PDFInfo
- Publication number
- CN102260291B CN102260291B CN201110110744A CN201110110744A CN102260291B CN 102260291 B CN102260291 B CN 102260291B CN 201110110744 A CN201110110744 A CN 201110110744A CN 201110110744 A CN201110110744 A CN 201110110744A CN 102260291 B CN102260291 B CN 102260291B
- Authority
- CN
- China
- Prior art keywords
- sodium phosphate
- crystalline compounds
- riboflavin sodium
- riboflavin
- compounds according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229950001574 riboflavin phosphate Drugs 0.000 title claims abstract description 128
- 150000001875 compounds Chemical class 0.000 title claims abstract description 94
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 title abstract description 99
- 239000013078 crystal Substances 0.000 claims abstract description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 87
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 81
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 44
- 235000019192 riboflavin Nutrition 0.000 claims description 44
- 239000002151 riboflavin Substances 0.000 claims description 44
- OHSHFZJLPYLRIP-BMZHGHOISA-M Riboflavin sodium phosphate Chemical compound [Na+].OP(=O)([O-])OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O OHSHFZJLPYLRIP-BMZHGHOISA-M 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 239000000243 solution Substances 0.000 claims description 32
- 235000019983 sodium metaphosphate Nutrition 0.000 claims description 31
- 238000003756 stirring Methods 0.000 claims description 31
- MOMKYJPSVWEWPM-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-methylphenyl)-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=NC(CCl)=CS1 MOMKYJPSVWEWPM-UHFFFAOYSA-N 0.000 claims description 30
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 29
- 239000007864 aqueous solution Substances 0.000 claims description 25
- 239000007787 solid Substances 0.000 claims description 24
- 239000002994 raw material Substances 0.000 claims description 18
- 239000012046 mixed solvent Substances 0.000 claims description 17
- 239000003960 organic solvent Substances 0.000 claims description 15
- 239000000725 suspension Substances 0.000 claims description 15
- 235000019441 ethanol Nutrition 0.000 claims description 14
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 13
- 238000005406 washing Methods 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 238000000967 suction filtration Methods 0.000 claims description 8
- 238000010792 warming Methods 0.000 claims description 8
- 229910017488 Cu K Inorganic materials 0.000 claims description 7
- 229910017541 Cu-K Inorganic materials 0.000 claims description 7
- 230000005260 alpha ray Effects 0.000 claims description 7
- 230000001105 regulatory effect Effects 0.000 claims description 7
- 239000012065 filter cake Substances 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- UGTZMIPZNRIWHX-UHFFFAOYSA-K sodium trimetaphosphate Chemical compound [Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 UGTZMIPZNRIWHX-UHFFFAOYSA-K 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 33
- 239000000843 powder Substances 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 239000003643 water by type Substances 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 239000011768 flavin mononucleotide Substances 0.000 description 7
- 238000012856 packing Methods 0.000 description 7
- 238000004088 simulation Methods 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000007791 liquid phase Substances 0.000 description 5
- 238000011046 pyrogen test Methods 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- -1 sodium phosphate compound Chemical class 0.000 description 5
- 238000013112 stability test Methods 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 238000002411 thermogravimetry Methods 0.000 description 4
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 3
- 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 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000008176 lyophilized powder Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000002510 pyrogen Substances 0.000 description 3
- 229960002477 riboflavin Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 229910019213 POCl3 Inorganic materials 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 2
- 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000008558 metabolic pathway by substance Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical compound CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 description 1
- WDNLGALUJVJFSM-VGOFMYFVSA-N CC(C)=C(C1CC1)/C=C(\C)/C(CN(C)NCC1(C2)OC1)NCC2=O Chemical compound CC(C)=C(C1CC1)/C=C(\C)/C(CN(C)NCC1(C2)OC1)NCC2=O WDNLGALUJVJFSM-VGOFMYFVSA-N 0.000 description 1
- 208000027219 Deficiency disease Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 239000004228 Riboflavin-5'-Phosphate Substances 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- CMNWUCGLNTVCSI-UHFFFAOYSA-J [Na+].[Na+].[Na+].[Na+].[Cl-].[O-]P([O-])([O-])=O Chemical compound [Na+].[Na+].[Na+].[Na+].[Cl-].[O-]P([O-])([O-])=O CMNWUCGLNTVCSI-UHFFFAOYSA-J 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- ALVPFGSHPUPROW-UHFFFAOYSA-N dipropyl disulfide Chemical compound CCCSSCCC ALVPFGSHPUPROW-UHFFFAOYSA-N 0.000 description 1
- GRWZHXKQBITJKP-UHFFFAOYSA-N dithionous acid Chemical compound OS(=O)S(O)=O GRWZHXKQBITJKP-UHFFFAOYSA-N 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 1
- 229940013640 flavin mononucleotide Drugs 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- YXJHJCDOUFKMBG-BMZHGHOISA-M riboflavin sodium Chemical compound [Na+].OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)[N-]C2=O YXJHJCDOUFKMBG-BMZHGHOISA-M 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical compound OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 1
- 229940103494 thiosalicylic acid Drugs 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (27)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110110744A CN102260291B (zh) | 2011-04-29 | 2011-04-29 | 一种核黄素磷酸钠化合物及其制备 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110110744A CN102260291B (zh) | 2011-04-29 | 2011-04-29 | 一种核黄素磷酸钠化合物及其制备 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102260291A CN102260291A (zh) | 2011-11-30 |
CN102260291B true CN102260291B (zh) | 2012-08-29 |
Family
ID=45007151
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201110110744A Active CN102260291B (zh) | 2011-04-29 | 2011-04-29 | 一种核黄素磷酸钠化合物及其制备 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102260291B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102617643B (zh) * | 2012-03-06 | 2013-04-10 | 黄金秀 | 一种核黄素磷酸钠化合物 |
CN104072540B (zh) * | 2014-05-22 | 2016-08-17 | 深圳朗欧医药集团有限公司 | 核黄素磷酸钠化合物及其制备方法 |
CN106674225B (zh) * | 2016-11-09 | 2019-04-02 | 珠海同源药业有限公司 | 一种核黄素磷酸钠化合物及其药物组合物 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0523582A1 (de) * | 1991-07-19 | 1993-01-20 | BASF Aktiengesellschaft | Verbessertes Verfahren zur Herstellung des Mononatriumsalzes von Riboflavin 5'-phosphat |
CN101601647A (zh) * | 2009-07-09 | 2009-12-16 | 周晓东 | 一种核黄素磷酸钠组合物注射液及制备方法 |
-
2011
- 2011-04-29 CN CN201110110744A patent/CN102260291B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0523582A1 (de) * | 1991-07-19 | 1993-01-20 | BASF Aktiengesellschaft | Verbessertes Verfahren zur Herstellung des Mononatriumsalzes von Riboflavin 5'-phosphat |
CN101601647A (zh) * | 2009-07-09 | 2009-12-16 | 周晓东 | 一种核黄素磷酸钠组合物注射液及制备方法 |
Non-Patent Citations (1)
Title |
---|
代金玲.核黄素5’-(二氢磷酸酯)单钠盐合成工艺研究.《天津药学》.2007,第19卷(第4期),1-13. * |
Also Published As
Publication number | Publication date |
---|---|
CN102260291A (zh) | 2011-11-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104744462B (zh) | 吡咯并喹啉醌的钠盐结晶、其制法、功能性食品和医药 | |
CN103119044B (zh) | 吡咯并喹啉醌的钙盐 | |
CN100488968C (zh) | 药用磷酸肌酸二钠盐六水合物及其制备方法 | |
CN109134459B (zh) | 吡咯喹啉醌二钠盐晶体及其制备方法 | |
JPH03501970A (ja) | S‐アデノシル‐l‐メチオニン(sam)のアシル化タウリン誘導体との親油性塩 | |
CN103304476B (zh) | 一种布洛芬-烟酰胺共晶的制备方法 | |
CN105753904B (zh) | 一种磷酸特地唑胺的精制方法 | |
CN102260291B (zh) | 一种核黄素磷酸钠化合物及其制备 | |
CN103619842A (zh) | 吡咯并喹啉醌二钠盐的结晶及其制造方法 | |
CN102596952A (zh) | 游离形式的吡咯并喹啉醌 | |
CN102161667B (zh) | 磺苄西林钠及注射用磺苄西林钠 | |
TW201319080A (zh) | α-葡糖基橘皮苷之結晶與其用途 | |
CN102617643B (zh) | 一种核黄素磷酸钠化合物 | |
CN104129803A (zh) | 稳定的硝普钠晶体化合物、其药物组合物及制备方法 | |
JP5808429B2 (ja) | 酸性メタリン酸ナトリウムによるs−アデノシルメチオニンの安定化 | |
CN102344360B (zh) | 精氨酸右旋布洛芬的制备方法 | |
CN104086611A (zh) | 灯盏花甲素衍生物及其制备方法与用途 | |
CN104922080A (zh) | 治疗消化系统疾病的药物艾普拉唑钠冻干粉针剂组合物 | |
CN104628766A (zh) | 一种甘油磷酸胆碱的工业制造方法 | |
US3061515A (en) | Methane sulfonates of telomycins | |
JP6428527B2 (ja) | ピロロキノリンキノン結晶の製造方法 | |
CN103193661B (zh) | 门冬氨酸钾晶体及门冬氨酸钾镁药物组合物的制备方法 | |
CN101607968A (zh) | 长春氟宁盐、其制备方法及其药物组合物 | |
CN104262436A (zh) | 无定型二丁酰环磷腺苷钙无菌粉末 | |
CN104327120B (zh) | 一种核黄素磷酸钠化合物注射液及其制备方法 |
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 | ||
EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20111130 Assignee: JIANGXI PHARMACEUTICAL Co.,Ltd. Assignor: Zhou Xiaodong Contract record no.: 2013360000127 Denomination of invention: Riboflavin sodium phosphate crystalline compound and preparation method thereof Granted publication date: 20120829 License type: Common License Record date: 20130925 |
|
LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
EM01 | Change of recordation of patent licensing contract |
Change date: 20141224 Contract record no.: 2013360000127 License type after: Exclusive license License type before: General permission |
|
LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20160922 Address after: 758 No. 330006 Jiangxi province Nanchang City Xiaolan Industrial Park, West Avenue Patentee after: JIANGXI PHARMACEUTICAL Co.,Ltd. Address before: 1709 h block, Pearl Plaza, Xihu District, Jiangxi, Nanchang 330006, China Patentee before: Zhou Xiaodong |
|
TR01 | Transfer of patent right |
Effective date of registration: 20200616 Address after: 1709 h block, Pearl Plaza, Xihu District, Jiangxi, Nanchang 330006, China Patentee after: Zhou Xiaodong Address before: 758 No. 330006 Jiangxi province Nanchang City Xiaolan Industrial Park, West Avenue Patentee before: JIANGXI PHARMACEUTICAL Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20201009 Address after: No. 17, wangjiaxiang new area, Wannian County, Shangrao City, Jiangxi Province Patentee after: Wannian County deyikai Information Consulting Co.,Ltd. Patentee after: Xifeng Runyan medical science and Technology Center Address before: 1709 h block, Pearl Plaza, Xihu District, Jiangxi, Nanchang 330006, China Patentee before: Zhou Xiaodong |
|
TR01 | Transfer of patent right | ||
CI03 | Correction of invention patent |
Correction item: Patentee|Address|Patentee Correct: Wannian County Deyikai Information Consulting Co., Ltd.|335501 No. 17, Wangjiaxiang New District, Wannian County, Shangrao City, Jiangxi Province|Xifeng Runting Pharmaceutical Technology Center False: Wannian County Deyikai Information Consulting Co., Ltd.|335501 No. 17, Wangjiaxiang New District, Wannian County, Shangrao City, Jiangxi Province|Xifeng Runyan Pharmaceutical Technology Center Number: 44-01 Volume: 36 |
|
CI03 | Correction of invention patent | ||
TR01 | Transfer of patent right |
Effective date of registration: 20210210 Address after: 335501 No.17, wangjiaxiang New District, Wannian County, Shangrao City, Jiangxi Province Patentee after: Wannian County deyikai Information Consulting Co.,Ltd. Patentee after: Xifengting medical technology center Patentee after: Wannian guangmaoyuan Information Consulting Co.,Ltd. Patentee after: Zhangshu duheng Business Service Co.,Ltd. Patentee after: Zhangshu dairui Business Consulting Co.,Ltd. Address before: 335501 No.17, wangjiaxiang New District, Wannian County, Shangrao City, Jiangxi Province Patentee before: Wannian County deyikai Information Consulting Co.,Ltd. Patentee before: Xifengting medical technology center |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20220307 Address after: 330006 1709, block h, Tanzikou Pearl Plaza, Xihu District, Nanchang City, Jiangxi Province Patentee after: Zhou Xiaodong Address before: 335501 No.17, wangjiaxiang New District, Wannian County, Shangrao City, Jiangxi Province Patentee before: Wannian County deyikai Information Consulting Co.,Ltd. Patentee before: Xifengting medical technology center Patentee before: Wannian guangmaoyuan Information Consulting Co.,Ltd. Patentee before: Zhangshu duheng Business Service Co.,Ltd. Patentee before: Zhangshu dairui Business Consulting Co.,Ltd. |
|
TR01 | Transfer of patent right |