AU2014236232A1 - Crystals of laquinimod sodium and improved process for the manufacture thereof - Google Patents
Crystals of laquinimod sodium and improved process for the manufacture thereof Download PDFInfo
- Publication number
- AU2014236232A1 AU2014236232A1 AU2014236232A AU2014236232A AU2014236232A1 AU 2014236232 A1 AU2014236232 A1 AU 2014236232A1 AU 2014236232 A AU2014236232 A AU 2014236232A AU 2014236232 A AU2014236232 A AU 2014236232A AU 2014236232 A1 AU2014236232 A1 AU 2014236232A1
- Authority
- AU
- Australia
- Prior art keywords
- amount
- laquinimod
- relative
- methyl
- pharmaceutical composition
- 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.)
- Abandoned
Links
- 229960004577 laquinimod Drugs 0.000 title claims abstract description 966
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 title claims abstract description 791
- 238000000034 method Methods 0.000 title claims abstract description 370
- 230000008569 process Effects 0.000 title claims abstract description 120
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 50
- 239000013078 crystal Substances 0.000 title claims description 35
- 230000001976 improved effect Effects 0.000 title description 18
- 239000000203 mixture Substances 0.000 claims abstract description 485
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 445
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 359
- 239000012535 impurity Substances 0.000 claims abstract description 225
- 239000002245 particle Substances 0.000 claims abstract description 166
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 238000009826 distribution Methods 0.000 claims abstract description 38
- 239000003937 drug carrier Substances 0.000 claims abstract description 34
- 238000012360 testing method Methods 0.000 claims abstract description 31
- 229910001385 heavy metal Inorganic materials 0.000 claims abstract description 24
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 20
- 229940127557 pharmaceutical product Drugs 0.000 claims abstract description 4
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 claims description 364
- JWHPPWBIIQMBQC-UHFFFAOYSA-M sodium;5-chloro-3-[ethyl(phenyl)carbamoyl]-1-methyl-2-oxoquinolin-4-olate Chemical compound [Na+].[O-]C=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 JWHPPWBIIQMBQC-UHFFFAOYSA-M 0.000 claims description 178
- 239000000243 solution Substances 0.000 claims description 161
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 117
- FTBWKSJUFWRKGL-UHFFFAOYSA-N 5-chloro-4-hydroxy-1-methyl-2-oxoquinoline-3-carboxylic acid Chemical compound C1=CC(Cl)=C2C(O)=C(C(O)=O)C(=O)N(C)C2=C1 FTBWKSJUFWRKGL-UHFFFAOYSA-N 0.000 claims description 101
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 91
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 83
- 239000000523 sample Substances 0.000 claims description 77
- 239000011734 sodium Substances 0.000 claims description 77
- PAIDZDPOJWEZLX-UHFFFAOYSA-N methyl 5-chloro-4-hydroxy-1-methyl-2-oxoquinoline-3-carboxylate Chemical compound C1=CC=C2N(C)C(=O)C(C(=O)OC)=C(O)C2=C1Cl PAIDZDPOJWEZLX-UHFFFAOYSA-N 0.000 claims description 73
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 68
- ZFPGGAUWFSIDEL-UHFFFAOYSA-N 5-chloro-4-hydroxy-1-methylquinolin-2-one Chemical compound C1=CC(Cl)=C2C(O)=CC(=O)N(C)C2=C1 ZFPGGAUWFSIDEL-UHFFFAOYSA-N 0.000 claims description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 59
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 58
- 239000012086 standard solution Substances 0.000 claims description 54
- 229910052708 sodium Inorganic materials 0.000 claims description 52
- 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 claims description 51
- 239000002775 capsule Substances 0.000 claims description 50
- 239000012488 sample solution Substances 0.000 claims description 50
- POQZLXDTXDVHMY-UHFFFAOYSA-N ethyl 5-chloro-4-hydroxy-1-methyl-2-oxoquinoline-3-carboxylate Chemical compound C1=CC=C2N(C)C(=O)C(C(=O)OCC)=C(O)C2=C1Cl POQZLXDTXDVHMY-UHFFFAOYSA-N 0.000 claims description 48
- 238000002425 crystallisation Methods 0.000 claims description 45
- 230000008025 crystallization Effects 0.000 claims description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 41
- 201000006417 multiple sclerosis Diseases 0.000 claims description 37
- 239000007853 buffer solution Substances 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 36
- 239000007787 solid Substances 0.000 claims description 36
- 239000003085 diluting agent Substances 0.000 claims description 35
- 239000012490 blank solution Substances 0.000 claims description 33
- 238000012430 stability testing Methods 0.000 claims description 32
- ZIPTZCNNYJFVOF-UHFFFAOYSA-N 2-chloro-6-[[3-(n-ethylanilino)-2-hydroxy-3-oxopropanoyl]-methylamino]benzoic acid Chemical compound C=1C=CC=CC=1N(CC)C(=O)C(O)C(=O)N(C)C1=CC=CC(Cl)=C1C(O)=O ZIPTZCNNYJFVOF-UHFFFAOYSA-N 0.000 claims description 31
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 30
- 230000014759 maintenance of location Effects 0.000 claims description 30
- 238000001953 recrystallisation Methods 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 239000007864 aqueous solution Substances 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 238000001816 cooling Methods 0.000 claims description 22
- 238000001914 filtration Methods 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000003756 stirring Methods 0.000 claims description 21
- 239000000725 suspension Substances 0.000 claims description 21
- 239000012071 phase Substances 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 239000002552 dosage form Substances 0.000 claims description 19
- 229960000583 acetic acid Drugs 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 18
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
- 238000010521 absorption reaction Methods 0.000 claims description 17
- 238000010438 heat treatment Methods 0.000 claims description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 239000011541 reaction mixture Substances 0.000 claims description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 15
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 14
- 239000005695 Ammonium acetate Substances 0.000 claims description 14
- 235000019257 ammonium acetate Nutrition 0.000 claims description 14
- 229940043376 ammonium acetate Drugs 0.000 claims description 14
- 239000011575 calcium Substances 0.000 claims description 14
- 238000001704 evaporation Methods 0.000 claims description 14
- -1 oxo- Chemical class 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 13
- 239000012362 glacial acetic acid Substances 0.000 claims description 13
- 238000005406 washing Methods 0.000 claims description 13
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 229910052782 aluminium Inorganic materials 0.000 claims description 12
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 12
- 229910052791 calcium Inorganic materials 0.000 claims description 12
- 239000010949 copper Substances 0.000 claims description 12
- 238000005443 coulometric titration Methods 0.000 claims description 12
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 11
- 229910052802 copper Inorganic materials 0.000 claims description 11
- 208000024891 symptom Diseases 0.000 claims description 11
- RDXOTRDYNZHUNL-UHFFFAOYSA-N 4-hydroxy-1-methyl-2-oxoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(O)=C(C(O)=O)C(=O)N(C)C2=C1 RDXOTRDYNZHUNL-UHFFFAOYSA-N 0.000 claims description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 10
- 159000000000 sodium salts Chemical class 0.000 claims description 10
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims description 9
- 206010003246 arthritis Diseases 0.000 claims description 9
- 150000007942 carboxylates Chemical class 0.000 claims description 9
- 206010025135 lupus erythematosus Diseases 0.000 claims description 9
- YFDWFVLGERLACT-UHFFFAOYSA-N n-ethyl-4,5-dihydroxy-1-methyl-2-oxo-n-phenylquinoline-3-carboxamide Chemical compound OC=1C2=C(O)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 YFDWFVLGERLACT-UHFFFAOYSA-N 0.000 claims description 9
- 239000011701 zinc Substances 0.000 claims description 9
- 102000012234 Cannabinoid receptor type 1 Human genes 0.000 claims description 8
- 108050002726 Cannabinoid receptor type 1 Proteins 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
- 239000004411 aluminium Substances 0.000 claims description 8
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 229910052725 zinc Inorganic materials 0.000 claims description 8
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 claims description 7
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 claims description 7
- 208000011231 Crohn disease Diseases 0.000 claims description 7
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 7
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 7
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 7
- 239000012074 organic phase Substances 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- YPNVJUPWZCUTOD-UHFFFAOYSA-L disodium;2,2-dimethylpropanedioate Chemical compound [Na+].[Na+].[O-]C(=O)C(C)(C)C([O-])=O YPNVJUPWZCUTOD-UHFFFAOYSA-L 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- JJPRBJSNMKCUQV-UHFFFAOYSA-N methyl 2-oxo-1h-quinoline-3-carboxylate Chemical compound C1=CC=C2NC(=O)C(C(=O)OC)=CC2=C1 JJPRBJSNMKCUQV-UHFFFAOYSA-N 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 239000012267 brine Substances 0.000 claims description 4
- 238000010583 slow cooling Methods 0.000 claims description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 4
- 235000011152 sodium sulphate Nutrition 0.000 claims description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 4
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 claims description 3
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 claims description 3
- 238000007865 diluting Methods 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 235000019837 monoammonium phosphate Nutrition 0.000 claims description 3
- 238000004806 packaging method and process Methods 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- 230000000171 quenching effect Effects 0.000 claims description 3
- YTZGGKRLAQFFTL-UHFFFAOYSA-N 3-chloro-4-hydroxy-1-methylquinolin-2-one Chemical compound C1=CC=C2C(O)=C(Cl)C(=O)N(C)C2=C1 YTZGGKRLAQFFTL-UHFFFAOYSA-N 0.000 claims description 2
- BZKCTVZVKAXVFH-UHFFFAOYSA-N 5-chloro-4-hydroxy-1-methyl-2-oxo-n-phenylquinoline-3-carboxamide Chemical compound O=C1N(C)C2=CC=CC(Cl)=C2C(O)=C1C(=O)NC1=CC=CC=C1 BZKCTVZVKAXVFH-UHFFFAOYSA-N 0.000 claims description 2
- 102000018208 Cannabinoid Receptor Human genes 0.000 claims description 2
- 108050007331 Cannabinoid receptor Proteins 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
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- 239000006194 liquid suspension Substances 0.000 claims description 2
- CFHGSFGKHACWIX-UHFFFAOYSA-N n-ethyl-4-hydroxy-1-methyl-2-oxo-5-(2,3,4,5,6-pentahydroxyhexylamino)-n-phenylquinoline-3-carboxamide Chemical compound OC=1C2=C(NCC(O)C(O)C(O)C(O)CO)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 CFHGSFGKHACWIX-UHFFFAOYSA-N 0.000 claims description 2
- RSJNDADBGUDAQN-UHFFFAOYSA-N n-ethyl-4-hydroxy-1-methyl-5-[methyl(2,3,4,5,6-pentahydroxyhexyl)amino]-2-oxo-n-phenylquinoline-3-carboxamide Chemical compound OC=1C2=C(N(C)CC(O)C(O)C(O)C(O)CO)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 RSJNDADBGUDAQN-UHFFFAOYSA-N 0.000 claims description 2
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- 238000004448 titration Methods 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 43
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- 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
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- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/16—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Food Science & Technology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361785575P | 2013-03-14 | 2013-03-14 | |
| US61/785,575 | 2013-03-14 | ||
| PCT/US2014/029292 WO2014153145A2 (en) | 2013-03-14 | 2014-03-14 | Crystals of laquinimod sodium and improved process for the manufacture thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2014236232A1 true AU2014236232A1 (en) | 2015-11-05 |
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|---|---|---|---|
| AU2014236232A Abandoned AU2014236232A1 (en) | 2013-03-14 | 2014-03-14 | Crystals of laquinimod sodium and improved process for the manufacture thereof |
Country Status (19)
| Country | Link |
|---|---|
| US (4) | US9233927B2 (OSRAM) |
| EP (1) | EP2970129A2 (OSRAM) |
| JP (1) | JP2016514162A (OSRAM) |
| KR (1) | KR20150143499A (OSRAM) |
| CN (1) | CN105051013A (OSRAM) |
| AR (1) | AR095562A1 (OSRAM) |
| AU (1) | AU2014236232A1 (OSRAM) |
| BR (1) | BR112015021602A2 (OSRAM) |
| CA (1) | CA2901849A1 (OSRAM) |
| CL (1) | CL2015002712A1 (OSRAM) |
| EA (1) | EA201591699A1 (OSRAM) |
| HK (2) | HK1220444A1 (OSRAM) |
| IL (1) | IL240356A0 (OSRAM) |
| MX (1) | MX2015011627A (OSRAM) |
| NZ (1) | NZ630427A (OSRAM) |
| PE (1) | PE20151935A1 (OSRAM) |
| SG (1) | SG11201506409RA (OSRAM) |
| TW (1) | TW201519892A (OSRAM) |
| WO (1) | WO2014153145A2 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2011223702B2 (en) * | 2010-03-03 | 2016-07-14 | Teva Pharmaceutical Industries Ltd. | Treatment of lupus arthritis using laquinimod |
| JP2015505564A (ja) | 2012-02-03 | 2015-02-23 | テバ ファーマシューティカル インダストリーズ リミティド | 第一選択の抗ＴＮＥα療法に失敗したクローン病患者を治療するためのラキニモドの使用 |
| TW201410244A (zh) | 2012-08-13 | 2014-03-16 | Teva Pharma | 用於治療ｇａｂａ媒介之疾病之拉喹莫德（ｌａｑｕｉｎｉｍｏｄ） |
| US9233927B2 (en) * | 2013-03-14 | 2016-01-12 | Teva Pharmaceutical Industries, Ltd. | Crystals of laquinimod sodium and improved process for the manufacture thereof |
| AU2015253330A1 (en) | 2014-04-29 | 2016-12-01 | Teva Pharmaceutical Industries Ltd. | Laquinimod for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with a high disability status |
| CN107966506B (zh) * | 2017-11-20 | 2019-09-13 | 福州大学 | 一种橡胶及橡胶制品中n-乙基苯胺含量的检测方法 |
| KR102069868B1 (ko) * | 2018-02-28 | 2020-01-23 | 고려대학교 산학협력단 | 합성가스 발효 균의 합성가스 발효 시의 대사체 분석을 위한 대사체 샘플링 및 분석 방법 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US607785A (en) | 1898-07-19 | Ore-car | ||
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| FR2340735A1 (fr) | 1976-02-11 | 1977-09-09 | Roussel Uclaf | Nouveaux derives de l'acide 3-quinoleine carboxylique, leur procede de preparation et leur application comme medicament |
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-
2014
- 2014-03-14 US US14/214,191 patent/US9233927B2/en not_active Expired - Fee Related
- 2014-03-14 HK HK16107245.0A patent/HK1220444A1/zh unknown
- 2014-03-14 CN CN201480014512.1A patent/CN105051013A/zh active Pending
- 2014-03-14 EP EP14721137.9A patent/EP2970129A2/en not_active Withdrawn
- 2014-03-14 EA EA201591699A patent/EA201591699A1/ru unknown
- 2014-03-14 BR BR112015021602A patent/BR112015021602A2/pt not_active IP Right Cessation
- 2014-03-14 NZ NZ630427A patent/NZ630427A/en not_active IP Right Cessation
- 2014-03-14 HK HK16104113.6A patent/HK1216311A1/zh unknown
- 2014-03-14 WO PCT/US2014/029292 patent/WO2014153145A2/en not_active Ceased
- 2014-03-14 SG SG11201506409RA patent/SG11201506409RA/en unknown
- 2014-03-14 JP JP2016503050A patent/JP2016514162A/ja not_active Withdrawn
- 2014-03-14 MX MX2015011627A patent/MX2015011627A/es unknown
- 2014-03-14 KR KR1020157029570A patent/KR20150143499A/ko not_active Withdrawn
- 2014-03-14 PE PE2015001974A patent/PE20151935A1/es not_active Application Discontinuation
- 2014-03-14 TW TW103109454A patent/TW201519892A/zh unknown
- 2014-03-14 AU AU2014236232A patent/AU2014236232A1/en not_active Abandoned
- 2014-03-14 US US14/773,683 patent/US20160046582A1/en not_active Abandoned
- 2014-03-14 CA CA2901849A patent/CA2901849A1/en not_active Abandoned
- 2014-03-17 AR ARP140101184A patent/AR095562A1/es unknown
-
2015
- 2015-08-04 IL IL240356A patent/IL240356A0/en unknown
- 2015-09-14 CL CL2015002712A patent/CL2015002712A1/es unknown
- 2015-12-03 US US14/958,396 patent/US20160158216A1/en not_active Abandoned
-
2017
- 2017-08-01 US US15/666,259 patent/US20170327464A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NZ630427A (en) | 2017-06-30 |
| US9233927B2 (en) | 2016-01-12 |
| SG11201506409RA (en) | 2015-09-29 |
| HK1216311A1 (zh) | 2016-11-04 |
| TW201519892A (zh) | 2015-06-01 |
| EA201591699A1 (ru) | 2016-02-29 |
| CL2015002712A1 (es) | 2016-04-15 |
| PE20151935A1 (es) | 2016-01-15 |
| CA2901849A1 (en) | 2014-09-25 |
| CN105051013A (zh) | 2015-11-11 |
| WO2014153145A2 (en) | 2014-09-25 |
| KR20150143499A (ko) | 2015-12-23 |
| US20160158216A1 (en) | 2016-06-09 |
| HK1220444A1 (zh) | 2017-05-05 |
| US20170327464A1 (en) | 2017-11-16 |
| BR112015021602A2 (pt) | 2017-07-18 |
| EP2970129A2 (en) | 2016-01-20 |
| IL240356A0 (en) | 2015-09-24 |
| MX2015011627A (es) | 2016-05-16 |
| US20160046582A1 (en) | 2016-02-18 |
| US20140271878A1 (en) | 2014-09-18 |
| AR095562A1 (es) | 2015-10-28 |
| WO2014153145A3 (en) | 2015-04-23 |
| JP2016514162A (ja) | 2016-05-19 |
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