HRP20140138T1 - Stabilni pripravci lakvinimoda - Google Patents
Stabilni pripravci lakvinimoda Download PDFInfo
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- HRP20140138T1 HRP20140138T1 HRP20140138AT HRP20140138T HRP20140138T1 HR P20140138 T1 HRP20140138 T1 HR P20140138T1 HR P20140138A T HRP20140138A T HR P20140138AT HR P20140138 T HRP20140138 T HR P20140138T HR P20140138 T1 HRP20140138 T1 HR P20140138T1
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- Prior art keywords
- chloro
- ethyl
- methyl
- hydroxy
- phenyl
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- 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 16
- 238000002360 preparation method Methods 0.000 title claims 5
- 229960004577 laquinimod Drugs 0.000 title 1
- 238000000034 method Methods 0.000 claims 10
- LVJRRJLPMQHXBY-UHFFFAOYSA-N 5-chloro-n-ethyl-3-hydroxy-1-methyl-2,4-dioxo-n-phenylquinoline-3-carboxamide Chemical compound O=C1N(C)C2=CC=CC(Cl)=C2C(=O)C1(O)C(=O)N(CC)C1=CC=CC=C1 LVJRRJLPMQHXBY-UHFFFAOYSA-N 0.000 claims 8
- 238000006864 oxidative decomposition reaction Methods 0.000 claims 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims 7
- 229940127557 pharmaceutical product Drugs 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 6
- 150000001875 compounds Chemical class 0.000 claims 5
- SVIKJIJHAKSTTF-UHFFFAOYSA-N 2-chloro-6-[(1-ethyl-2-oxo-3h-indole-3-carbonyl)-methylamino]benzoic acid Chemical compound C12=CC=CC=C2N(CC)C(=O)C1C(=O)N(C)C1=CC=CC(Cl)=C1C(O)=O SVIKJIJHAKSTTF-UHFFFAOYSA-N 0.000 claims 4
- 238000000354 decomposition reaction Methods 0.000 claims 4
- 230000003647 oxidation Effects 0.000 claims 4
- 238000007254 oxidation reaction Methods 0.000 claims 4
- 238000013112 stability test Methods 0.000 claims 4
- 238000010521 absorption reaction Methods 0.000 claims 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 238000005259 measurement Methods 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 238000012430 stability testing Methods 0.000 claims 2
- 238000010200 validation analysis Methods 0.000 claims 2
- 238000001075 voltammogram Methods 0.000 claims 2
- 239000005711 Benzoic acid Substances 0.000 claims 1
- 235000010233 benzoic acid Nutrition 0.000 claims 1
- 238000012360 testing method Methods 0.000 claims 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B25/00—Packaging other articles presenting special problems
-
- 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- 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
- A61K31/4704—2-Quinolinones, e.g. carbostyril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D471/10—Spiro-condensed systems
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Mechanical Engineering (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Claims (12)
1. Postupak za validaciju šarže farmaceutskog produkta koji sadrži spoj N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid ili njegovu sol, te farmaceutski prihvatljiv nosilac za distribuciju, naznačen time, da obuhvaća:
a) podvrgavanje uzorka šarže ispitivanju stabilnosti;
b) određivanje ukupne količine produkta oksidacijskog raspadanja u uzorku šarže nakon ispitivanja stabilnosti: i
c) validaciju šarže za distribuciju, samo ako uzorak šarže nakon ispitivanja stabilnosti ne sadrži više od ukupno 0,5 tež.% produkata oksidacijskog raspadanja N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamida, u odnosu na N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid.
2. Postupak prema patentnom zahtjevu 1, naznačen time, da produkt oksidacijskog raspadanja jest 2-kloro-6-(1-etil-N-metil-2-oksoindolin-3-karboksamido) benzojeva kiselina, 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidro-kinolin-3-karboksamid ili 1H,3H-spiro[5-kloro-1-metilkinolin-2,4-dion-3,3'-[1]etilindolin-[2]-on], ili njihova smjesa.
3. Postupak prema patentnom zahtjevu 1, naznačen time, da se u koraku (b) količina određuje primjenom mjerenja mase, ultravioletne apsorpcije, indeksa loma, ionizacije ili voltamograma.
4. Postupak za validaciju šarže N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamida ili njegove soli za distribuciju, naznačen time, da obuhvaća:
a) podvrgavanje uzorka šarže ispitivanju stabilnosti;
b) određivanje ukupne količine produkta oksidacijskog raspadanja u uzorku šarže nakon ispitivanja stabilnosti: i
c) validaciju šarže za distribuciju, samo ako uzorak šarže nakon ispitivanja stabilnosti ne sadrži više od ukupno 0,1 tež.% produkata oksidacijskog raspadanja N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamida, u odnosu na N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid.
5. Postupak prema patentnom zahtjevu 4, naznačen time, da produkt oksidacijskog raspadanja jest 2-kloro-6-(1-etil-N-metil-2-oksoindolin-3-karboksamido) benzojeva kiselina, 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidro-kinolin-3-karboksamid ili 1H,3H-spiro[5-kloro-1-metilkinolin-2,4-dion-3,3'-[1]etilindolin-[2]-on], ili njihova smjesa.
6. Postupak prema patentnom zahtjevu 4, naznačen time, da se u koraku (b) količina određuje primjenom mjerenja mase, ultravioletne apsorpcije, indeksa loma, ionizacije ili voltamograma.
7. Postupak za pripremu farmaceutskog produkta koji sadrži N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid ili njegovu sol, i farmaceutski prihvatljiv nosilac, kod čega farmaceutski produkt nema više od ukupno 0,5 tež.% produkata oksidacijskog raspadanja 2-kloro-6-(1-etil-N-metil-2-oksoindolin-3-karboksamido) benzojeve kiseline, 1H,3H-spiro[5-kloro-1-metilkinolin-2,4-dion-3,3'-[1]etilindolin-[2]-ona], i 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidro-kinolin-3-karboksamida, u odnosu na N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid, naznačen time, da obuhvaća:
a) dobivanje šarže N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamida ili njegove soli;
b) određivanje ukupne količine produkata oksidacijskog raspadanja 2-kloro-6-(1-etil-N-metil-2-oksoindolin-3-karboksamido) benzojeve kiseline, 1H,3H-spiro[5-kloro-1-metilkinolin-2,4-dion-3,3'-[1]etilindolin-[2]-ona, i 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidro-kinolin-3-karboksamida prisutnih u šarži i
c) pripremu farmaceutskog produkta iz šarže, samo ako je određeno da šarža ne sadrži više od ukupno 0,5 tež.% produkata oksidacijskog raspadanja 2-kloro-6-(1-etil-N-metil-2-oksoindolin-3-karboksamido) benzojeve kiseline, 1H,3H-spiro[5-kloro-1-metilkinolin-2,4-dion-3,3'-[1]etilindolin-[2]-ona], i 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidro-kinolin-3-karboksamida u odnosu na N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid.
8. Postupak za ispitivanje da li uzorak sadrži nepoželjni produkt oksidacijskog raspadanja N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamida, naznačen time, da obuhvaća određivanje, da li uzorak sadrži spoj koji ima sljedeću strukturu:
[image]
9. Izolirani spoj, naznačen time, da ima sljedeću strukturu:
[image]
10. Izolirani spoj, naznačen time, da ima sljedeću strukturu:
[image]
11. Postupak prema patentnom zahtjevu 8, naznačen time, da sadrži određivanje, da li uzorak sadrži spoj koji ima sljedeću strukturu:
[image]
12. Postupak za pripremu farmaceutskog produkta koji sadrži N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid ili njegovu sol, i farmaceutski prihvatljiv nosilac, u čemu farmaceutski produkt nema više od ukupno 0,5 tež.% produkta oksidacijskog raspadanja 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidro-kinolin-3-karboksamida, u odnosu na N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid, naznačen time, da obuhvaća:
a) dobivanje šarže N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamida ili njegove soli;
b) određivanje ukupne količine 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidrokinolin-3-karboksamida prisutnog u šarži; i
c) pripremu farmaceutskog produkta iz šarže, samo ukoliko je određeno da šarža nema više od ukupno 0,5 tež.% 5-kloro-N-etil-3-hidroksi-1-metil-2,4-diokso-N-fenil-1,2,3,4-tetrahidro-kinolin-3-karboksamida, u odnosu na N-etil-N-fenil-1,2-dihidro-4-hidroksi-5-kloro-1-metil-2-oksokinolin-3-karboksamid.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US869807P | 2007-12-20 | 2007-12-20 | |
PCT/US2008/013890 WO2009082471A1 (en) | 2007-12-20 | 2008-12-19 | Stable laquinimod preparations |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20140138T1 true HRP20140138T1 (hr) | 2014-04-11 |
Family
ID=40788935
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20140138AT HRP20140138T1 (hr) | 2007-12-20 | 2014-02-13 | Stabilni pripravci lakvinimoda |
Country Status (12)
Country | Link |
---|---|
US (3) | US8178127B2 (hr) |
EP (3) | EP2234485B1 (hr) |
DK (1) | DK2234485T3 (hr) |
ES (2) | ES2445451T3 (hr) |
HK (1) | HK1220126A1 (hr) |
HR (1) | HRP20140138T1 (hr) |
IL (1) | IL205855A (hr) |
PL (2) | PL2234485T3 (hr) |
PT (2) | PT2234485E (hr) |
RS (1) | RS53199B (hr) |
SI (1) | SI2234485T1 (hr) |
WO (1) | WO2009082471A1 (hr) |
Families Citing this family (25)
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US8314124B2 (en) * | 2004-02-06 | 2012-11-20 | Active Biotech Ab | Crystalline salts of quinoline compounds and methods for preparing them |
PT1937642E (pt) | 2005-10-19 | 2014-11-25 | Teva Pharma | Cristais de sódio de laquinimod, e processos para o fabrico dos mesmos |
EP2035001B1 (en) | 2006-06-12 | 2011-11-09 | Teva Pharmaceutical Industries Limited | Stable laquinimod preparations |
US8178127B2 (en) | 2007-12-20 | 2012-05-15 | Teva Pharmaceuticals Industries, Ltd. | Stable laquinimod preparations |
KR20160079147A (ko) * | 2008-09-03 | 2016-07-05 | 테바 파마슈티컬 인더스트리즈 리미티드 | 면역 기능을 지닌 2―옥소―1,2―다이하이드로―퀴놀린 조절제 |
ME02282B (me) * | 2009-06-19 | 2016-02-20 | Teva Pharma | Tretman multiple skleroze lakvinimodom |
AU2010276748A1 (en) * | 2009-07-30 | 2012-03-15 | Teva Pharmaceutical Industries Ltd. | Treatment of Crohn's disease with laquinimod |
HUE029983T2 (en) | 2009-08-10 | 2017-04-28 | Teva Pharma | Treatment of BDNF-related diseases with laquinimod |
KR20130014523A (ko) * | 2010-03-03 | 2013-02-07 | 테바 파마슈티컬 인더스트리즈 리미티드 | 라퀴니모드 및 메토트렉세이트의 병용에 의한 류마티스 관절염의 치료 |
MX337614B (es) * | 2010-03-03 | 2016-03-10 | Teva Pharma | Tratamiento de lupus nefritis usando laquinimod. |
CA2791711A1 (en) * | 2010-03-03 | 2011-09-09 | Teva Pharmaceutical Industries Ltd. | Treatment of lupus arthritis using laquinimod |
KR20130092558A (ko) | 2010-07-09 | 2013-08-20 | 테바 파마슈티컬 인더스트리즈 리미티드 | 중수소화된 n-에틸-n-페닐-1,2-다이하이드로-4-하이드록시-5-클로로-1-메틸-2-옥소퀴놀린-3-카복스아마이드, 그의 염 및 용도 |
EP3056205A1 (en) * | 2010-07-09 | 2016-08-17 | Teva Pharmaceutical Industries, Ltd. | 5-chloro-4-hydroxy-1-methyl-2-oxo-n-phenyl-1,2-dihydroquinoline-3-carboxamide, salts and uses thereof |
AU2012322706A1 (en) | 2011-10-12 | 2014-05-22 | Teva Pharmaceutical Industries Ltd. | Treatment of multiple sclerosis with combination of laquinimod and fingolimod |
CN104093310A (zh) | 2012-02-03 | 2014-10-08 | 泰华制药工业有限公司 | 拉喹莫德用于治疗一线抗TNFα疗法失败的克罗恩氏病患者的用途 |
CN104114172A (zh) * | 2012-02-16 | 2014-10-22 | 泰华制药工业有限公司 | N-乙基-n-苯基-1,2-二氢-4,5-二-羟基-1-甲基-2-氧代-3-喹啉甲酰胺、其制备和用途 |
TW201350467A (zh) * | 2012-05-08 | 2013-12-16 | Teva Pharma | N-乙基-4-羥基-1-甲基-5-(甲基(2,3,4,5,6-五羥基己基)胺基)-2-側氧-n-苯基-1,2-二氫喹啉-3-甲醯胺 |
TW201400117A (zh) | 2012-06-05 | 2014-01-01 | Teva Pharma | 使用拉喹莫德治療眼發炎疾病 |
AR091706A1 (es) * | 2012-07-11 | 2015-02-25 | Teva Pharma | Formulaciones de laquinimod sin agentes alcalinizantes |
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2008
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EP2977049A1 (en) | 2016-01-27 |
EP2682120B1 (en) | 2016-08-03 |
PL2682120T3 (pl) | 2017-02-28 |
HK1220126A1 (zh) | 2017-04-28 |
IL205855A0 (en) | 2010-11-30 |
US8178127B2 (en) | 2012-05-15 |
EP2234485A1 (en) | 2010-10-06 |
ES2600920T3 (es) | 2017-02-13 |
ES2445451T3 (es) | 2014-03-03 |
RS53199B (en) | 2014-06-30 |
SI2234485T1 (sl) | 2014-03-31 |
PT2234485E (pt) | 2014-02-17 |
EP2682120A1 (en) | 2014-01-08 |
PL2234485T3 (pl) | 2014-06-30 |
DK2234485T3 (da) | 2014-02-10 |
US9340307B2 (en) | 2016-05-17 |
EP2234485B1 (en) | 2013-11-13 |
US8545885B2 (en) | 2013-10-01 |
US20090162432A1 (en) | 2009-06-25 |
IL205855A (en) | 2017-02-28 |
EP2234485A4 (en) | 2011-02-16 |
WO2009082471A1 (en) | 2009-07-02 |
PT2682120T (pt) | 2016-11-07 |
US20140024678A1 (en) | 2014-01-23 |
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