BR9815548A - Composição farmacêutica para administração em dose única diária para alteração de lipìdios num indivìduo sem causar hepatotoxicidade induzida por drogas, miopatia ou rabdomiólise, comprimido revestido para administração oral e método para administração de dita composição - Google Patents
Composição farmacêutica para administração em dose única diária para alteração de lipìdios num indivìduo sem causar hepatotoxicidade induzida por drogas, miopatia ou rabdomiólise, comprimido revestido para administração oral e método para administração de dita composiçãoInfo
- Publication number
- BR9815548A BR9815548A BR9815548-2A BR9815548A BR9815548A BR 9815548 A BR9815548 A BR 9815548A BR 9815548 A BR9815548 A BR 9815548A BR 9815548 A BR9815548 A BR 9815548A
- Authority
- BR
- Brazil
- Prior art keywords
- composition
- nicotinamide
- methyl
- administration
- rhabdomyolysis
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title abstract 3
- 206010072268 Drug-induced liver injury Diseases 0.000 title abstract 2
- 206010039020 Rhabdomyolysis Diseases 0.000 title abstract 2
- 150000002632 lipids Chemical class 0.000 title abstract 2
- 208000023137 Myotoxicity Diseases 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 abstract 6
- 239000011664 nicotinic acid Substances 0.000 abstract 4
- 229960003512 nicotinic acid Drugs 0.000 abstract 4
- 235000001968 nicotinic acid Nutrition 0.000 abstract 3
- -1 6-OH-nicotinamide Chemical compound 0.000 abstract 2
- IMRLNFKFNFLWQF-IYKITFJXSA-N sorbinicate Chemical compound O([C@H](COC(=O)C=1C=NC=CC=1)[C@@H](OC(=O)C=1C=NC=CC=1)[C@H](OC(=O)C=1C=NC=CC=1)[C@H](COC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)C(=O)C1=CC=CN=C1 IMRLNFKFNFLWQF-IYKITFJXSA-N 0.000 abstract 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 abstract 1
- 208000021642 Muscular disease Diseases 0.000 abstract 1
- 201000009623 Myopathy Diseases 0.000 abstract 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 abstract 1
- KTLRWTOPTKGYQY-UHFFFAOYSA-N N-methyl-4-pyridone-3-carboxamide Chemical compound CN1C=CC(=O)C(C(N)=O)=C1 KTLRWTOPTKGYQY-UHFFFAOYSA-N 0.000 abstract 1
- ZYVXHFWBYUDDBM-UHFFFAOYSA-N N-methylnicotinamide Chemical compound CNC(=O)C1=CC=CN=C1 ZYVXHFWBYUDDBM-UHFFFAOYSA-N 0.000 abstract 1
- KUEUWHJGRZKESU-UHFFFAOYSA-N Niceritrol Chemical compound C=1C=CN=CC=1C(=O)OCC(COC(=O)C=1C=NC=CC=1)(COC(=O)C=1C=NC=CC=1)COC(=O)C1=CC=CN=C1 KUEUWHJGRZKESU-UHFFFAOYSA-N 0.000 abstract 1
- USSFUVKEHXDAPM-UHFFFAOYSA-N Nicotinamide N-oxide Chemical compound NC(=O)C1=CC=C[N+]([O-])=C1 USSFUVKEHXDAPM-UHFFFAOYSA-N 0.000 abstract 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 229940056243 aluminium nicotinate Drugs 0.000 abstract 1
- NSFYKDVWNTWJOK-UHFFFAOYSA-K aluminum;pyridine-3-carboxylate Chemical compound [Al+3].[O-]C(=O)C1=CC=CN=C1.[O-]C(=O)C1=CC=CN=C1.[O-]C(=O)C1=CC=CN=C1 NSFYKDVWNTWJOK-UHFFFAOYSA-K 0.000 abstract 1
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 238000013265 extended release Methods 0.000 abstract 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 abstract 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 229960000827 niceritrol Drugs 0.000 abstract 1
- NPORIZAYKBQYLF-LREBCSMRSA-N nicotinyl alcohol tartrate Chemical compound OCC1=CC=CN=C1.OC(=O)[C@H](O)[C@@H](O)C(O)=O NPORIZAYKBQYLF-LREBCSMRSA-N 0.000 abstract 1
- 229960000839 nicotinyl alcohol tartrate Drugs 0.000 abstract 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 abstract 1
- 210000002966 serum Anatomy 0.000 abstract 1
- 229950007581 sorbinicate Drugs 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
<B>"COMPOSIçãO FARMACêUTICA PARA ADMINISTRAçãO EM DOSE úNICA DIáRIA PARA ALTERAçãO DE LIPìDIOS NUM INDIVìDUO SEM CAUSAR HEPATOTOXICIDADE INDUZIDA POR DROGAS, MIOPATIA OU RABDOMIóLISE, COMPRIMIDO REVESTIDO PARA ADMINISTRAçãO ORAL E MéTODO PARA ADMINISTRAçãO DE DITA COMPOSIçãO"<D> A presente invenção está relacionada com combinações farmacêuticas sólidas para administração por via oral administração por via oral compreendendo ácido nicotínico ou compostos do ácido nicotínico ou misturas dos mesmos numa forma de liberação prolongada e um inibidor de HMG-CoA redutase, que servem para alterar os níveis de lipídios em indivíduos sofrendo de, por exemplo, hiperlipidemia e arteriosclerose, sem causar hepatotoxicidade induzida por drogas, miopatia ou rabdomiólise. A presente invenção está também relacionada aos métodos de alteração de lipídios séricos em indivíduos para tratar, por exemplo, hiperlipidemia em hiperlipidêmicos, lipidemia em normolipidêmicos com diagnóstico ou predisposição a doenças cardiovasculares, e aretereoesclerose, administrando a referida composição farmacêutica sólida por via oral uma vez por dia como dose única durante o horário noturno, sem causar hepatotoxicidade induzida por drogas, miopatias ou rabdomiólise, ou sem causar, pelo menos num número apreciável de pacientes, hepatotoxicidade induzida por drogas, miopatias ou rabdomiólise de tal gravidade que imponha a suspensão do referido tratamento. Mais particularmente, a presente invenção diz respeito a composição farmacêutica sólida oral composta de, por exemplo, (1) um inibidor de HMG-CoA redutase para liberação imediata ou prolongada, (2) ácido nicotínico, um composto de ácido nicotínico ou misturas dos mesmos, e (3) um agente expansor para formar uma composição de liberação continuada para a liberação prolongada do ácido nicotínico ou composto de ácido nicotínico ou misturas dos mesmos para dosagem noturna ou vespertina para redução do percentual de lipídios séricos e aumento do colesterol HDL. De acordo com a presente invenção, e como forma de exemplo, apresenta-se uma composição para administração oral durante o horário noturno para alterar os lipídios séricos compreendendo ácido nicotínico e hidroxipropil metilcelulose na forma de um comprimido ou drágea de liberação prolongada ou continuada revestido de um revestimento composto de um inibidor de HMG-CoA redutase numa forma de liberação imediata. Também de acordo com a presente invenção, as composições farmacêuticas podem incluir um agente anti-inflamatório não-esteróidico para redução da capacidade do ácido nicotínico ou compostos de ácido nicotínico para provocar reações de rubor em indivíduos.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US90375297A | 1997-07-31 | 1997-07-31 | |
| PCT/US1998/015990 WO1999006035A2 (en) | 1997-07-31 | 1998-07-31 | COMBINATIONS OF HMG-CoA REDUCTASE INHIBITORS AND NICOTINIC ACID COMPOUNDS AND METHODS FOR TREATING HYPERLIPIDEMIA ONCE A DAY AT NIGHT |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR9815548A true BR9815548A (pt) | 2000-11-07 |
Family
ID=25418027
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR9815548-2A BR9815548A (pt) | 1997-07-31 | 1998-07-31 | Composição farmacêutica para administração em dose única diária para alteração de lipìdios num indivìduo sem causar hepatotoxicidade induzida por drogas, miopatia ou rabdomiólise, comprimido revestido para administração oral e método para administração de dita composição |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US20040053975A1 (pt) |
| EP (2) | EP1017390B1 (pt) |
| JP (2) | JP4870869B2 (pt) |
| AT (2) | ATE359785T1 (pt) |
| AU (1) | AU752673B2 (pt) |
| BR (1) | BR9815548A (pt) |
| CA (1) | CA2298549C (pt) |
| CY (1) | CY1107057T1 (pt) |
| DE (2) | DE69841395D1 (pt) |
| DK (1) | DK1017390T3 (pt) |
| ES (2) | ES2283067T3 (pt) |
| IL (2) | IL134271A0 (pt) |
| NO (1) | NO20000439L (pt) |
| NZ (1) | NZ520176A (pt) |
| PT (1) | PT1017390E (pt) |
| WO (1) | WO1999006035A2 (pt) |
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| AU2001295991A1 (en) * | 2000-10-23 | 2002-05-06 | Sankyo Company Limited | Compositions for improving lipids in blood |
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| ES2643693T3 (es) | 2011-05-20 | 2017-11-23 | Astrazeneca Uk Limited | Composición farmacéutica de rosuvastatina cálcica |
| SG10201912713YA (en) | 2014-11-14 | 2020-02-27 | Gemphire Therapeutics Inc | PROCESSES AND INTERMEDIATES FOR PREPARING α,ω-DICARBOXYLIC ACID-TERMINATED DIALKANE ETHERS |
| EP3370713A4 (en) * | 2015-11-06 | 2019-10-23 | Gemphire Therapeutics Inc. | TREATMENT OF MIXED DYSLIPIDEMIA |
| CA3059073A1 (en) | 2017-04-18 | 2018-10-25 | Gemphire Therapeutics Inc. | Gemcabene, pharmaceutically acceptable salts thereof, compositions thereof and methods of use therefor |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US3524001A (en) * | 1965-03-04 | 1970-08-11 | Upjohn Co | Compositions and method for reducing free fatty acid and cholesterol in the blood of mammals with 3,5 - disubstituted isoxazoles |
| JPS63310827A (ja) * | 1987-06-15 | 1988-12-19 | Sanwa Kagaku Kenkyusho Co Ltd | ニコチン酸誘導体を主剤とする徐放性製剤 |
| US5260305A (en) * | 1988-12-12 | 1993-11-09 | E. R. Squibb & Sons, Inc. | Combination of pravastatin and nicotinic acid or related acid and method for lowering serum cholesterol using such combination |
| US4933165A (en) * | 1989-01-18 | 1990-06-12 | Merck & Co., Inc. | Coenzyme Q10 with HMG-CoA reductase inhibitors |
| US5268181A (en) * | 1989-04-13 | 1993-12-07 | Upsher-Smith Laboratories, Inc. | Method of using niacin to control nocturnal cholesterol synthesis |
| CA2016467A1 (en) * | 1989-06-05 | 1990-12-05 | Martin Eisman | Method for treating peripheral atherosclerotic disease employing an hmg coa reductase inhibitor and/or a squalene synthetase inhibitor |
| CA2018470A1 (en) * | 1989-07-17 | 1991-01-17 | Scott Adams Biller | Phosphorus-containing squalene synthetase inhibitors and method |
| US5135935A (en) * | 1991-05-17 | 1992-08-04 | Merck & Co., Inc. | Squalene synthetase inhibitors |
| US5840339A (en) * | 1991-07-30 | 1998-11-24 | Kunin; Robert | Blood cholesterol reducing pharmaceutical composition |
| CA2124086A1 (en) * | 1991-11-22 | 1993-05-27 | Ronald H. Lane | Tocotrienols and tocotrienol-like compounds and methods for their use |
| US5292534A (en) * | 1992-03-25 | 1994-03-08 | Valentine Enterprises, Inc. | Sustained release composition and method utilizing xanthan gum and an active ingredient |
| US5609884A (en) * | 1992-08-31 | 1997-03-11 | G. D. Searle & Co. | Controlled release naproxen sodium plus naproxen combination tablet |
| US6080428A (en) * | 1993-09-20 | 2000-06-27 | Bova; David J. | Nicotinic acid compositions for treating hyperlipidemia and related methods therefor |
| US6129930A (en) * | 1993-09-20 | 2000-10-10 | Bova; David J. | Methods and sustained release nicotinic acid compositions for treating hyperlipidemia at night |
| US6369103B1 (en) * | 1994-01-18 | 2002-04-09 | Bristol-Myers Squibb Company | Method for preventing or reducing risk of onset of cardiovascular events employing an HMG CoA reductase inhibitor |
| US5582838A (en) * | 1994-12-22 | 1996-12-10 | Merck & Co., Inc. | Controlled release drug suspension delivery device |
| US5773453A (en) * | 1995-04-19 | 1998-06-30 | Vanderbilt University | Methods for administration of antilipemic drugs |
| CA2218696A1 (en) * | 1995-04-19 | 1996-10-24 | L. Jackson Ii Roberts | Compositions, kits and methods for administration of antilipemic and an ti-platelet aggregation drugs |
-
1998
- 1998-07-31 DE DE69841395T patent/DE69841395D1/de not_active Expired - Lifetime
- 1998-07-31 ES ES98938228T patent/ES2283067T3/es not_active Expired - Lifetime
- 1998-07-31 ES ES07003276T patent/ES2336492T3/es not_active Expired - Lifetime
- 1998-07-31 IL IL13427198A patent/IL134271A0/xx active IP Right Grant
- 1998-07-31 JP JP2000504849A patent/JP4870869B2/ja not_active Expired - Fee Related
- 1998-07-31 EP EP98938228A patent/EP1017390B1/en not_active Expired - Lifetime
- 1998-07-31 PT PT98938228T patent/PT1017390E/pt unknown
- 1998-07-31 DK DK98938228T patent/DK1017390T3/da active
- 1998-07-31 CA CA002298549A patent/CA2298549C/en not_active Expired - Lifetime
- 1998-07-31 WO PCT/US1998/015990 patent/WO1999006035A2/en not_active Ceased
- 1998-07-31 AT AT98938228T patent/ATE359785T1/de active
- 1998-07-31 EP EP07003276A patent/EP1792616B1/en not_active Expired - Lifetime
- 1998-07-31 DE DE69837610T patent/DE69837610T2/de not_active Expired - Lifetime
- 1998-07-31 AU AU86801/98A patent/AU752673B2/en not_active Ceased
- 1998-07-31 BR BR9815548-2A patent/BR9815548A/pt not_active Application Discontinuation
- 1998-07-31 AT AT07003276T patent/ATE451926T1/de not_active IP Right Cessation
- 1998-07-31 NZ NZ520176A patent/NZ520176A/en not_active IP Right Cessation
-
2000
- 2000-01-27 IL IL134271A patent/IL134271A/en not_active IP Right Cessation
- 2000-01-27 NO NO20000439A patent/NO20000439L/no not_active Application Discontinuation
-
2003
- 2003-09-02 US US10/260,027 patent/US20040053975A1/en not_active Abandoned
-
2007
- 2007-05-07 CY CY20071100604T patent/CY1107057T1/el unknown
-
2009
- 2009-02-27 US US12/394,441 patent/US20090226518A1/en not_active Abandoned
- 2009-07-22 JP JP2009170721A patent/JP2009235105A/ja active Pending
-
2011
- 2011-10-27 US US13/282,755 patent/US20120164221A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001511444A (ja) | 2001-08-14 |
| PT1017390E (pt) | 2007-07-24 |
| NO20000439L (no) | 2000-03-22 |
| CA2298549C (en) | 2006-01-10 |
| ES2336492T3 (es) | 2010-04-13 |
| NZ520176A (en) | 2005-02-25 |
| CA2298549A1 (en) | 1999-02-11 |
| EP1792616A1 (en) | 2007-06-06 |
| EP1017390B1 (en) | 2007-04-18 |
| HK1106153A1 (en) | 2008-03-07 |
| ATE451926T1 (de) | 2010-01-15 |
| IL134271A (en) | 2006-07-05 |
| CY1107057T1 (el) | 2012-10-24 |
| NO20000439D0 (no) | 2000-01-27 |
| AU752673B2 (en) | 2002-09-26 |
| DE69837610D1 (de) | 2007-05-31 |
| IL134271A0 (en) | 2001-04-30 |
| AU8680198A (en) | 1999-02-22 |
| WO1999006035A3 (en) | 1999-04-22 |
| ATE359785T1 (de) | 2007-05-15 |
| WO1999006035A2 (en) | 1999-02-11 |
| US20040053975A1 (en) | 2004-03-18 |
| DK1017390T3 (da) | 2007-06-11 |
| EP1792616B1 (en) | 2009-12-16 |
| US20120164221A1 (en) | 2012-06-28 |
| ES2283067T3 (es) | 2007-10-16 |
| EP1017390A2 (en) | 2000-07-12 |
| JP4870869B2 (ja) | 2012-02-08 |
| DE69837610T2 (de) | 2008-01-03 |
| US20090226518A1 (en) | 2009-09-10 |
| DE69841395D1 (de) | 2010-01-28 |
| JP2009235105A (ja) | 2009-10-15 |
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