WO2015000370A1 - 吡咯喹啉醌锂盐晶体及其制备方法和应用 - Google Patents
吡咯喹啉醌锂盐晶体及其制备方法和应用 Download PDFInfo
- Publication number
- WO2015000370A1 WO2015000370A1 PCT/CN2014/080542 CN2014080542W WO2015000370A1 WO 2015000370 A1 WO2015000370 A1 WO 2015000370A1 CN 2014080542 W CN2014080542 W CN 2014080542W WO 2015000370 A1 WO2015000370 A1 WO 2015000370A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pyrroloquinoline quinone
- lithium salt
- quinone lithium
- salt crystal
- pharmaceutical composition
- Prior art date
Links
- NKASWPXBKCCMFT-UHFFFAOYSA-N [Li].OC(=O)c1cc2c([nH]1)-c1c(cc(nc1C(=O)C2=O)C(O)=O)C(O)=O Chemical compound [Li].OC(=O)c1cc2c([nH]1)-c1c(cc(nc1C(=O)C2=O)C(O)=O)C(O)=O NKASWPXBKCCMFT-UHFFFAOYSA-N 0.000 title claims abstract description 70
- 239000013078 crystal Substances 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 16
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 13
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 238000010521 absorption reaction Methods 0.000 claims abstract description 10
- 238000000113 differential scanning calorimetry Methods 0.000 claims abstract description 5
- MMXZSJMASHPLLR-UHFFFAOYSA-N pyrroloquinoline quinone Chemical compound C12=C(C(O)=O)C=C(C(O)=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 MMXZSJMASHPLLR-UHFFFAOYSA-N 0.000 claims description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 9
- 238000002329 infrared spectrum Methods 0.000 claims description 9
- -1 nitromethyl Chemical group 0.000 claims description 9
- 239000013067 intermediate product Substances 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- 238000004458 analytical method Methods 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000007884 disintegrant Substances 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 3
- 238000001514 detection method Methods 0.000 claims description 3
- 150000004683 dihydrates Chemical class 0.000 claims description 3
- 206010027175 memory impairment Diseases 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 150000004682 monohydrates Chemical class 0.000 claims description 3
- 150000004690 nonahydrates Chemical class 0.000 claims description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- 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 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 102000004316 Oxidoreductases Human genes 0.000 claims description 2
- 108090000854 Oxidoreductases Proteins 0.000 claims description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 229960005168 croscarmellose Drugs 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 239000002002 slurry Substances 0.000 claims description 2
- 239000001341 hydroxy propyl starch Substances 0.000 claims 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 claims 1
- HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 claims 1
- 230000009225 memory damage Effects 0.000 abstract description 2
- 238000004566 IR spectroscopy Methods 0.000 abstract 1
- 239000002689 soil Substances 0.000 description 25
- 238000001228 spectrum Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 229910003002 lithium salt Inorganic materials 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 238000012347 Morris Water Maze Methods 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 239000012154 double-distilled water Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 238000010175 APPswe/PSEN1dE9 Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000001267 GSK3 Human genes 0.000 description 2
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 208000018937 joint inflammation Diseases 0.000 description 2
- 159000000002 lithium salts Chemical class 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000035806 respiratory chain Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XMDBJQOQTPRRJM-UHFFFAOYSA-N 1-nitro-n-oxido-n-oxomethanimidamide Chemical compound NC(=N)[N+]([O-])=O XMDBJQOQTPRRJM-UHFFFAOYSA-N 0.000 description 1
- ZIUYHTQZEPDUCZ-UHFFFAOYSA-N 7h-pyrrolo[2,3-h]quinoline Chemical compound C1=CN=C2C(C=CN3)=C3C=CC2=C1 ZIUYHTQZEPDUCZ-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 229920003084 Avicel® PH-102 Polymers 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 241000031708 Saprospiraceae Species 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- QFLZIQOIERJRJV-UHFFFAOYSA-N [Li+].c1ccc2ncccc2c1 Chemical compound [Li+].c1ccc2ncccc2c1 QFLZIQOIERJRJV-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Natural products C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000012362 drug development process Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 241001233061 earthworms Species 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N para-benzoquinone Natural products O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 231100001055 skeletal defect Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 230000006886 spatial memory Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 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
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the invention relates to a pyrroloquinoline quinone lithium salt crystal and a preparation method and application thereof. Background technique
- the powder X-ray diffraction pattern of the pyrroloquinoline quinone lithium salt crystal has an absorption peak at 24.044 ⁇ 0.2, 25.497 soil 0.2, 27.541 soil 0.2, 30.736 soil 0.2 and 32.306 soil 0.2 degree, and the infrared spectrum is 1500.35. There are also peaks at 1243.86, 1147.44, 808.03, 761.74 and 570.83 cm- 1 .
- the organic solvent is any one of methanol, ethanol, isopropanol, pentanol, acetone, methyl ethyl ketone, tetrahydrofuran, nitroformamidine, acetonitrile, chloroform, dichloromethane, and methyl tert-butyl ether.
- the ratio of pyrroloquinoline quinone to the organic solvent is 20 mg: 1 mL.
- the present invention also provides a pharmaceutical composition
- a pharmaceutical composition comprising the above-mentioned pyrroloquinoline quinone lithium salt crystal and a pharmaceutically acceptable excipient thereof.
- the excipient is one or more of a filler, a disintegrant, a binder, and a lubricant.
- the crystal of the present invention is a B-type pyrroloquinoline quinone lithium salt, and the X-ray powder diffraction pattern of the B-type pyrroloquinoline quinone lithium salt is substantially the same as that of the graph A, the DSC spectrum, the DVS spectrum and the infrared spectrum.
- the beneficial effects of the present invention are:
- Figure a is an X-ray powder diffraction pattern of a crystal of pyrroloquinoline quinone lithium salt
- Figure b is a DSC spectrum of a pyrroloquinoline quinone lithium salt crystal
- Figure c is a DVS diagram of a crystal of pyrroloquinoline quinone lithium salt
- XRPD spectrum Detected at room temperature using an XRD6500 X-ray diffractometer from Shimadzu Corporation, 2° angle scan from 5° to 40°, Cu-Ka, scanning speed: 2°/min.
- DSC spectrum It was detected by a DSC8500 differential scanning calorimeter from Elmer, USA, with an atmosphere of nitrogen and a heating rate of 10 ° C / min.
- IR spectrum It was detected at room temperature by Nicolot-Magna FT-IR750 infrared spectrometer from Nico, USA. The detection range was: 4000-350 cm -1 wave number.
- Table 1 X-ray powder diffraction data of pyrroloquinoline quinone lithium salt B crystal form
- the compound is stably present in the presence of nonahydrate, forming a monohydrate in a range of relative humidity of 20 to 50%; in the range of relative humidity of 70% to 100%, a dihydrate is formed, and the humidity may further increase.
- a polyhydrate is formed.
- the Anritsu group 1 tablet (5 mg) was ground and dissolved in 0.5% CMC to obtain a 0.15 mg/ml Ammon solution.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES14819418T ES2794078T3 (es) | 2013-07-01 | 2014-06-23 | Cristal de sal de trilitio de pirroloquinolin quinona, método de preparación y aplicación del mismo |
BR112015031797-9A BR112015031797B1 (pt) | 2013-07-01 | 2014-06-23 | Cristal de sal de lítio de pirroloquinolina quinina, método de preparação do cristal de sal de lítio de pirroloquinolina quinina e composição farmacêutica |
EP14819418.6A EP2998305B1 (en) | 2013-07-01 | 2014-06-23 | Pyrroloquinoline quinone lithium salt crystal and preparation method and application thereof |
JP2016520268A JP6130595B2 (ja) | 2013-07-01 | 2014-06-23 | ピロロキノリンキノンリチウム塩の結晶体及び調製方法と応用 |
US14/897,926 US9738639B2 (en) | 2013-07-01 | 2014-06-23 | Pyrroloquinoline quinone lithium salt crystal and preparation method and application thereof |
PL14819418T PL2998305T3 (pl) | 2013-07-01 | 2014-06-23 | Kryształ soli trilitowej chinonu pirolochinoliny, sposób jego otrzymywania i zastosowanie |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310270885.2A CN103351387B (zh) | 2013-07-01 | 2013-07-01 | 吡咯喹啉醌锂盐晶体及其制备方法和应用 |
CN201310270885.2 | 2013-07-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2015000370A1 true WO2015000370A1 (zh) | 2015-01-08 |
Family
ID=49307822
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2014/080542 WO2015000370A1 (zh) | 2013-07-01 | 2014-06-23 | 吡咯喹啉醌锂盐晶体及其制备方法和应用 |
Country Status (8)
Country | Link |
---|---|
US (1) | US9738639B2 (zh) |
EP (1) | EP2998305B1 (zh) |
JP (1) | JP6130595B2 (zh) |
CN (1) | CN103351387B (zh) |
ES (1) | ES2794078T3 (zh) |
PL (1) | PL2998305T3 (zh) |
PT (1) | PT2998305T (zh) |
WO (1) | WO2015000370A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017114844A (ja) * | 2015-12-22 | 2017-06-29 | 三菱瓦斯化学株式会社 | 認識能力向上食品 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112274513B (zh) | 2020-12-28 | 2021-03-26 | 上海日馨生物科技有限公司 | 含有吡咯喹啉醌三锂盐九水化合物的药物组合物、胶囊剂及其制备方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008029907A1 (fr) * | 2006-09-08 | 2008-03-13 | Kyowa Hakko Bio Co., Ltd. | Agent améliorant l'hypertension |
CN101193888A (zh) * | 2005-03-24 | 2008-06-04 | Clf医疗技术加速程序有限公司 | 吡咯喹啉醌(pqq)的合成方法 |
CN101851234A (zh) * | 2009-04-03 | 2010-10-06 | 上海日馨生物科技有限公司 | 吡咯喹啉醌锂盐衍生物及其制备方法 |
CN101885725A (zh) * | 2009-05-12 | 2010-11-17 | 江苏道琪生物科技有限公司 | 吡咯喹啉醌钠盐衍生物及其制备方法 |
JP2011126812A (ja) * | 2009-12-17 | 2011-06-30 | Mitsubishi Gas Chemical Co Inc | ピロロキノリンキノンLi塩の製造方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011026812A (ja) | 2009-07-23 | 2011-02-10 | Mano Kogyo Kk | 引込管の施工方法 |
-
2013
- 2013-07-01 CN CN201310270885.2A patent/CN103351387B/zh active Active
-
2014
- 2014-06-23 JP JP2016520268A patent/JP6130595B2/ja active Active
- 2014-06-23 PL PL14819418T patent/PL2998305T3/pl unknown
- 2014-06-23 EP EP14819418.6A patent/EP2998305B1/en active Active
- 2014-06-23 PT PT148194186T patent/PT2998305T/pt unknown
- 2014-06-23 US US14/897,926 patent/US9738639B2/en active Active
- 2014-06-23 ES ES14819418T patent/ES2794078T3/es active Active
- 2014-06-23 WO PCT/CN2014/080542 patent/WO2015000370A1/zh active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101193888A (zh) * | 2005-03-24 | 2008-06-04 | Clf医疗技术加速程序有限公司 | 吡咯喹啉醌(pqq)的合成方法 |
WO2008029907A1 (fr) * | 2006-09-08 | 2008-03-13 | Kyowa Hakko Bio Co., Ltd. | Agent améliorant l'hypertension |
CN101851234A (zh) * | 2009-04-03 | 2010-10-06 | 上海日馨生物科技有限公司 | 吡咯喹啉醌锂盐衍生物及其制备方法 |
CN101885725A (zh) * | 2009-05-12 | 2010-11-17 | 江苏道琪生物科技有限公司 | 吡咯喹啉醌钠盐衍生物及其制备方法 |
JP2011126812A (ja) * | 2009-12-17 | 2011-06-30 | Mitsubishi Gas Chemical Co Inc | ピロロキノリンキノンLi塩の製造方法 |
Non-Patent Citations (2)
Title |
---|
KOBAYASHI, M. ET AL.: "Pyrroloquinoline Quinone (PQQ) Prevents Fibril Formation of A-synuclein", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 349, no. 3, 31 December 2006 (2006-12-31), pages 1139 - 1144, XP024924550 * |
NUNOME, K. ET AL.: "Pyrroloquinoline Quinone Prevents Oxidative Stress-induced Neuronal Death Probably through Changes in Oxidative Status of DJ-1", BIOL. PHARM. BULL, vol. 31, no. 7, 31 December 2008 (2008-12-31), XP055299256 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017114844A (ja) * | 2015-12-22 | 2017-06-29 | 三菱瓦斯化学株式会社 | 認識能力向上食品 |
Also Published As
Publication number | Publication date |
---|---|
PT2998305T (pt) | 2020-07-09 |
US20160137641A1 (en) | 2016-05-19 |
PL2998305T3 (pl) | 2020-11-02 |
BR112015031797A2 (pt) | 2017-07-25 |
US9738639B2 (en) | 2017-08-22 |
CN103351387A (zh) | 2013-10-16 |
JP2016522224A (ja) | 2016-07-28 |
EP2998305A1 (en) | 2016-03-23 |
ES2794078T3 (es) | 2020-11-17 |
JP6130595B2 (ja) | 2017-05-17 |
CN103351387B (zh) | 2016-03-02 |
EP2998305B1 (en) | 2020-04-08 |
EP2998305A4 (en) | 2017-01-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5017115B2 (ja) | 4−(4−(3−(4−クロロ−3−トリフルオロメチルフェニル)ウレイド)−3−フルオロフェノキシ)ピリジン−2−カルボン酸を含んでなる過剰増殖性疾患の治療のための新規薬剤組成物 | |
US8227463B2 (en) | Amorphous body composed of heterocyclic compound, solid dispersion and pharmaceutical preparation each comprising the same, and process for production of the same | |
BR112020014487A2 (pt) | composições farmacêuticas para tratamento de fi-brose cística | |
BR112018011154B1 (pt) | Dispersões sólidas compreendendo um estimulador de sgc | |
JP7241807B2 (ja) | 15β-ヒドロキシ-酢酸オサテロンの結晶多形 | |
KR102522895B1 (ko) | Jak 키나아제 억제제 바이설페이트의 결정형 및 이의 제조방법 | |
US20160159745A1 (en) | Preparation of (-)-huperzine a | |
EP3135666B1 (en) | (s)-oxiracetam crystal form iii, preparation method therefor, and application thereof | |
WO2014117700A1 (zh) | 一种原人参二醇衍生物、其制备方法及其应用 | |
CN106397298A (zh) | 含吲哚布芬的药物组合物和用途 | |
WO2015000370A1 (zh) | 吡咯喹啉醌锂盐晶体及其制备方法和应用 | |
CN104910147B (zh) | 阿哌沙班晶体及其制备方法 | |
CN113197865A (zh) | 醋酸阿比特龙与反式乌头酸的共晶、其制备方法、药物组合物及其应用 | |
WO2015149638A1 (zh) | 达比加群酯甲磺酸盐晶型、其制备方法以及药物组合物 | |
US9643993B2 (en) | Crystalline polymorphic form of ulipristal acetate | |
CA3159265C (en) | Crystalline form of acetylcholinesterase inhibitor and preparation method therefor and application thereof | |
WO2023143427A1 (zh) | Arv-110的晶型及其制备方法和用途 | |
CN106554357B (zh) | 吗啡衍生物晶型i及其制备方法和用途 | |
WO2014050105A1 (en) | Amorphous ulipristal acetate | |
CN106554376B (zh) | 吗啡衍生物晶型ii及其制备方法和用途 | |
CN111918869A (zh) | 甘草酸衍生物的结晶、其结晶组合物、药物组合物及用途 | |
BR112015031797B1 (pt) | Cristal de sal de lítio de pirroloquinolina quinina, método de preparação do cristal de sal de lítio de pirroloquinolina quinina e composição farmacêutica | |
CN101607960A (zh) | 醋茶溴索及其组合物 | |
TW201011018A (en) | 5-lipoxygenase-activating protein inhibitor |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 14819418 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 14897926 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2014819418 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2016520268 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112015031797 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112015031797 Country of ref document: BR Kind code of ref document: A2 Effective date: 20151217 |