ZA200110468B - Dinucleotide crystals. - Google Patents
Dinucleotide crystals. Download PDFInfo
- Publication number
- ZA200110468B ZA200110468B ZA200110468A ZA200110468A ZA200110468B ZA 200110468 B ZA200110468 B ZA 200110468B ZA 200110468 A ZA200110468 A ZA 200110468A ZA 200110468 A ZA200110468 A ZA 200110468A ZA 200110468 B ZA200110468 B ZA 200110468B
- Authority
- ZA
- South Africa
- Prior art keywords
- crystals
- dcp4u
- uridine
- ump
- deoxycytidine
- Prior art date
Links
- 239000013078 crystal Substances 0.000 title claims description 58
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 31
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 claims description 22
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 claims description 22
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 18
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 16
- 229940023032 activated charcoal Drugs 0.000 claims description 15
- 238000004587 chromatography analysis Methods 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 11
- NCMVOABPESMRCP-SHYZEUOFSA-N 2'-deoxycytosine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 NCMVOABPESMRCP-SHYZEUOFSA-N 0.000 claims description 10
- 239000011541 reaction mixture Substances 0.000 claims description 10
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 claims description 8
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 8
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 8
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 8
- 229940045145 uridine Drugs 0.000 claims description 8
- 238000005571 anion exchange chromatography Methods 0.000 claims description 7
- DJJCXFVJDGTHFX-UHFFFAOYSA-N Uridinemonophosphate Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- DJJCXFVJDGTHFX-ZAKLUEHWSA-N uridine-5'-monophosphate Chemical compound O[C@@H]1[C@@H](O)[C@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-ZAKLUEHWSA-N 0.000 claims description 6
- YDHWWBZFRZWVHO-UHFFFAOYSA-H [oxido-[oxido(phosphonatooxy)phosphoryl]oxyphosphoryl] phosphate Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O YDHWWBZFRZWVHO-UHFFFAOYSA-H 0.000 claims description 5
- 235000011180 diphosphates Nutrition 0.000 claims description 4
- ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims 1
- 239000000047 product Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical class CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 11
- 238000002441 X-ray diffraction Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 150000004691 decahydrates Chemical class 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 238000001160 cross-polarisation magic angle spinning nuclear magnetic resonance spectrum Methods 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- -1 alkali metal salts Chemical class 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 150000001447 alkali salts Chemical class 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229920001429 chelating resin Polymers 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000011369 resultant mixture Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- WGODGFXCRIJNLS-UHFFFAOYSA-N 2-amino-6-methyl-5-pyridin-4-ylpyridine-3-carbonitrile Chemical compound CC1=NC(N)=C(C#N)C=C1C1=CC=NC=C1 WGODGFXCRIJNLS-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
- JYYNAJVZFGKDEQ-UHFFFAOYSA-N 2,4-Dimethylpyridine Chemical compound CC1=CC=NC(C)=C1 JYYNAJVZFGKDEQ-UHFFFAOYSA-N 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- 206010009137 Chronic sinusitis Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000000033 Purinergic Receptors Human genes 0.000 description 2
- 108010080192 Purinergic Receptors Proteins 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 208000027157 chronic rhinosinusitis Diseases 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000004292 cyclic ethers Chemical class 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000005270 trialkylamine group Chemical group 0.000 description 2
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical class CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- 238000004482 13C cross polarization magic angle spinning Methods 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- ZJIJYZSGABIPDP-UHFFFAOYSA-N 2-n,4-n-dimethylpyridine-2,4-diamine Chemical compound CNC1=CC=NC(NC)=C1 ZJIJYZSGABIPDP-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229920001890 Novodur Polymers 0.000 description 1
- 102100028045 P2Y purinoceptor 2 Human genes 0.000 description 1
- 101710096700 P2Y purinoceptor 2 Proteins 0.000 description 1
- 102100028070 P2Y purinoceptor 4 Human genes 0.000 description 1
- 108050009478 P2Y purinoceptor 4 Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005384 cross polarization magic-angle spinning Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical class CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- YUWFEBAXEOLKSG-UHFFFAOYSA-N hexamethylbenzene Chemical compound CC1=C(C)C(C)=C(C)C(C)=C1C YUWFEBAXEOLKSG-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18495099 | 1999-06-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200110468B true ZA200110468B (en) | 2003-04-04 |
Family
ID=16162200
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200110468A ZA200110468B (en) | 1999-06-30 | 2001-12-20 | Dinucleotide crystals. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6617444B1 (pl) |
| EP (2) | EP1191032B1 (pl) |
| JP (1) | JP3421666B2 (pl) |
| KR (1) | KR100593723B1 (pl) |
| CN (1) | CN1144811C (pl) |
| AT (2) | ATE300551T1 (pl) |
| AU (1) | AU767136B2 (pl) |
| BR (1) | BR0012205A (pl) |
| CA (1) | CA2376860C (pl) |
| CZ (1) | CZ303172B6 (pl) |
| DE (2) | DE60006814T2 (pl) |
| EA (1) | EA004707B1 (pl) |
| ES (2) | ES2211566T3 (pl) |
| HU (1) | HU229225B1 (pl) |
| IL (1) | IL147163A (pl) |
| MX (1) | MXPA02000035A (pl) |
| NO (1) | NO321169B1 (pl) |
| NZ (1) | NZ516301A (pl) |
| PL (2) | PL202200B1 (pl) |
| SK (1) | SK284178B6 (pl) |
| WO (1) | WO2001002416A1 (pl) |
| ZA (1) | ZA200110468B (pl) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7223744B2 (en) | 1997-02-10 | 2007-05-29 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof |
| US7078391B2 (en) | 1997-02-10 | 2006-07-18 | Inspire Pharmaceuticals, Inc. | Method of treating edematous retinal disorders |
| US6818629B2 (en) | 1997-02-10 | 2004-11-16 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising P1-(2'-deoxycytidine 5'-)P4-(uridine 5'-) tetraphosphate |
| US6548658B2 (en) * | 1997-07-25 | 2003-04-15 | Inspire Pharmaceuticals, Inc. | Di-(uridine 5′)-tetraphosphate and salts thereof |
| US6872710B2 (en) | 1997-07-25 | 2005-03-29 | Inspire Pharmaceuticals, Inc. | Di(uridine 5′)-tetraphosphate and salts thereof |
| SK284178B6 (sk) * | 1999-06-30 | 2004-10-05 | Yamasa Corporation | Kryštalická forma P1-(2'-deoxycytidín-5'-)P4-(uridín-5'- )tetrafosfátu a spôsob ich prípravy |
| US6867199B2 (en) | 2000-08-21 | 2005-03-15 | Inspire Pharmaceuticals, Inc. | Dinucleoside polyphosphate compositions and their therapeutic use |
| US7161029B2 (en) * | 2003-12-17 | 2007-01-09 | Ajinomoto Co., Inc. | DiL-lysine monosulfate trihydrate crystal and method of making |
| CN100363376C (zh) * | 2006-06-12 | 2008-01-23 | 南京工业大学 | 一种5’-核苷三磷酸钠盐的结晶方法 |
| JPWO2017002827A1 (ja) * | 2015-06-29 | 2018-04-26 | ヤマサ醤油株式会社 | Ｐ１，ｐ４−ビス（５’−ウリジル）テトラホスフェート結晶の保管方法 |
| CN109843901B (zh) * | 2016-10-25 | 2022-04-26 | Yamasa 酱油株式会社 | P1,p4-二(尿苷5’-)四磷酸的纯化方法 |
| CN111253456B (zh) * | 2020-03-13 | 2021-05-11 | 广东先强药业有限公司 | 一种地纽福索钠的制备方法 |
| CN111704637A (zh) * | 2020-06-28 | 2020-09-25 | 南京工业大学 | 一种采用膜蒸馏结晶精制核苷酸的方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07242685A (ja) * | 1994-01-12 | 1995-09-19 | Unitika Ltd | ジアデノシン四リン酸水和物の製造方法 |
| US5837861A (en) * | 1997-02-10 | 1998-11-17 | Inspire Pharmaceuticals, Inc. | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
| US5900407A (en) * | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
| CN1262556C (zh) * | 1997-02-06 | 2006-07-05 | 印斯拜尔药品股份有限公司 | 特定的二核苷酸和它们作为粘膜纤毛清除和纤毛颤动频率调节剂的应用 |
| US6596725B2 (en) * | 1997-02-10 | 2003-07-22 | Inspire Pharmaceuticals, Inc. | Use of certain dinucleotides to stimulate removal of fluid in retinal detachment and retinal edema |
| TW593331B (en) * | 1997-07-25 | 2004-06-21 | Inspire Pharmaceuticals Inc | Method for large-scale production of di(uridine 5')-tetraphosphate and salts thereof |
| DK1012154T3 (da) * | 1997-07-25 | 2004-07-26 | Inspire Pharmaceuticals Inc | Salte af di(uridin-5'-tetraphosphat), fremgangsmåde til fremstilling og anvendelser deraf |
| WO1999061012A2 (en) * | 1998-05-22 | 1999-12-02 | Inspire Pharmaceuticals, Inc. | Therapeutic dinucleotide and derivatives |
| SK283729B6 (sk) * | 1998-10-02 | 2003-12-02 | Yamasa Corporation | Kryštály P1, P4-di(uridín-5')-tetrafosfátu alebo kryštály jeho soli, spôsob ich výroby, kryštály tetrasodnej soli P1, P4-di(uridín-5')-tetrafosfátu a kryštály jej hydrátov |
| WO2000039145A1 (en) * | 1998-12-23 | 2000-07-06 | The University Of North Carolina At Chapel Hill | Targeted gene transfer using g protein coupled receptors |
| SK284178B6 (sk) * | 1999-06-30 | 2004-10-05 | Yamasa Corporation | Kryštalická forma P1-(2'-deoxycytidín-5'-)P4-(uridín-5'- )tetrafosfátu a spôsob ich prípravy |
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2000
- 2000-06-30 SK SK1870-2001A patent/SK284178B6/sk not_active IP Right Cessation
- 2000-06-30 MX MXPA02000035A patent/MXPA02000035A/es active IP Right Grant
- 2000-06-30 WO PCT/JP2000/004336 patent/WO2001002416A1/ja not_active Application Discontinuation
- 2000-06-30 AT AT03018399T patent/ATE300551T1/de not_active IP Right Cessation
- 2000-06-30 US US09/700,728 patent/US6617444B1/en not_active Expired - Lifetime
- 2000-06-30 PL PL352363A patent/PL202200B1/pl unknown
- 2000-06-30 ES ES00942412T patent/ES2211566T3/es not_active Expired - Lifetime
- 2000-06-30 NZ NZ516301A patent/NZ516301A/en not_active IP Right Cessation
- 2000-06-30 DE DE60006814T patent/DE60006814T2/de not_active Expired - Lifetime
- 2000-06-30 JP JP2001507852A patent/JP3421666B2/ja not_active Expired - Fee Related
- 2000-06-30 EP EP00942412A patent/EP1191032B1/en not_active Expired - Lifetime
- 2000-06-30 BR BR0012205-0A patent/BR0012205A/pt not_active Application Discontinuation
- 2000-06-30 CZ CZ20014502A patent/CZ303172B6/cs not_active IP Right Cessation
- 2000-06-30 CA CA002376860A patent/CA2376860C/en not_active Expired - Fee Related
- 2000-06-30 IL IL14716300A patent/IL147163A/xx not_active IP Right Cessation
- 2000-06-30 PL PL384307A patent/PL202176B1/pl unknown
- 2000-06-30 CN CNB008097356A patent/CN1144811C/zh not_active Expired - Fee Related
- 2000-06-30 EP EP03018399A patent/EP1362862B1/en not_active Expired - Lifetime
- 2000-06-30 AT AT00942412T patent/ATE255123T1/de not_active IP Right Cessation
- 2000-06-30 DE DE60021629T patent/DE60021629T2/de not_active Expired - Lifetime
- 2000-06-30 ES ES03018399T patent/ES2245431T3/es not_active Expired - Lifetime
- 2000-06-30 EA EA200200109A patent/EA004707B1/ru not_active IP Right Cessation
- 2000-06-30 KR KR1020017016184A patent/KR100593723B1/ko not_active IP Right Cessation
- 2000-06-30 AU AU57067/00A patent/AU767136B2/en not_active Ceased
- 2000-06-30 HU HU0201531A patent/HU229225B1/hu not_active IP Right Cessation
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2001
- 2001-12-20 ZA ZA200110468A patent/ZA200110468B/en unknown
- 2001-12-27 NO NO20016381A patent/NO321169B1/no not_active IP Right Cessation
Also Published As
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| Publication | Publication Date | Title |
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| EP1191032B1 (en) | Dinucleotide crystals | |
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| ZA200102683B (en) | Crystal of diuridine tetraphosphate or salt thereof and method for preparing the same, and method for producing said compound. | |
| JP3964809B2 (ja) | ジヌクレオチドの製造法 | |
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