NZ523893A - New aporphine esters and their use in therapy - Google Patents
New aporphine esters and their use in therapyInfo
- Publication number
- NZ523893A NZ523893A NZ523893A NZ52389301A NZ523893A NZ 523893 A NZ523893 A NZ 523893A NZ 523893 A NZ523893 A NZ 523893A NZ 52389301 A NZ52389301 A NZ 52389301A NZ 523893 A NZ523893 A NZ 523893A
- Authority
- NZ
- New Zealand
- Prior art keywords
- substituted
- aporphine
- group
- alkanoyl
- pct
- Prior art date
Links
- 150000008441 aporphines Chemical class 0.000 title claims abstract description 35
- 238000002560 therapeutic procedure Methods 0.000 title description 8
- 238000000034 method Methods 0.000 claims abstract description 33
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- 230000008569 process Effects 0.000 claims abstract description 17
- 208000005793 Restless legs syndrome Diseases 0.000 claims abstract description 10
- 206010019233 Headaches Diseases 0.000 claims abstract description 5
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 5
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 4
- 238000011156 evaluation Methods 0.000 claims abstract description 4
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 4
- -1 trifluoromethanesulphonyloxy Chemical group 0.000 claims description 62
- BZKUYNBAFQJRDM-UHFFFAOYSA-N aporphine Chemical compound C12=CC=CC=C2CC2N(C)CCC3=CC=CC1=C32 BZKUYNBAFQJRDM-UHFFFAOYSA-N 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 38
- 125000001589 carboacyl group Chemical group 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- 125000005843 halogen group Chemical group 0.000 claims description 36
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 34
- QCMQEZNBBPGFKQ-UHFFFAOYSA-N Thalisopynine Natural products CN1CCC2=C(OC)C(OC)=C(OC)C3=C2C1CC1=C3C=C(OC)C(O)=C1 QCMQEZNBBPGFKQ-UHFFFAOYSA-N 0.000 claims description 33
- FVRABHGHBLRNNR-UHFFFAOYSA-N liriodenine Natural products O=C1C=CC=c2c1cc3nccc4cc5OCOc5c2c34 FVRABHGHBLRNNR-UHFFFAOYSA-N 0.000 claims description 33
- 239000003921 oil Substances 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 20
- 150000005690 diesters Chemical class 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 17
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 13
- 239000002111 antiemetic agent Substances 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 238000007920 subcutaneous administration Methods 0.000 claims description 13
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 10
- 125000003435 aroyl group Chemical group 0.000 claims description 10
- 239000011541 reaction mixture Substances 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 7
- 238000001704 evaporation Methods 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
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- 238000007918 intramuscular administration Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 239000003405 delayed action preparation Substances 0.000 claims description 3
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- 238000004519 manufacturing process Methods 0.000 claims description 3
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- 239000012190 activator Substances 0.000 claims description 2
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- 125000004429 atom Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 claims 2
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- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Chemical group 0.000 claims 1
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- 229960004046 apomorphine Drugs 0.000 description 47
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 40
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 28
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 28
- 229960004502 levodopa Drugs 0.000 description 28
- 230000000694 effects Effects 0.000 description 24
- 235000019198 oils Nutrition 0.000 description 22
- 241000700159 Rattus Species 0.000 description 20
- 229940079593 drug Drugs 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 101100095563 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SEO1 gene Proteins 0.000 description 18
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- 238000012360 testing method Methods 0.000 description 13
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- 150000002367 halogens Chemical group 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
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- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 10
- 239000012346 acetyl chloride Substances 0.000 description 10
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Landscapes
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- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0002934A SE0002934D0 (sv) | 2000-08-17 | 2000-08-17 | New aporphine esters and in their use in therapy |
| PCT/SE2001/001658 WO2002014279A1 (en) | 2000-08-17 | 2001-07-20 | New aporphine esters and their use in therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ523893A true NZ523893A (en) | 2003-10-31 |
Family
ID=20280719
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ523893A NZ523893A (en) | 2000-08-17 | 2001-07-20 | New aporphine esters and their use in therapy |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US7238705B2 (enExample) |
| EP (1) | EP1309553A1 (enExample) |
| JP (1) | JP2004506041A (enExample) |
| KR (1) | KR100865503B1 (enExample) |
| CN (1) | CN1242991C (enExample) |
| AU (2) | AU2001271228B2 (enExample) |
| BR (1) | BR0113291A (enExample) |
| CA (1) | CA2419842C (enExample) |
| CZ (1) | CZ2003454A3 (enExample) |
| EA (1) | EA006388B1 (enExample) |
| HU (1) | HUP0301685A3 (enExample) |
| IL (2) | IL154096A0 (enExample) |
| MX (1) | MXPA03001465A (enExample) |
| NO (1) | NO324409B1 (enExample) |
| NZ (1) | NZ523893A (enExample) |
| PL (1) | PL360089A1 (enExample) |
| SE (1) | SE0002934D0 (enExample) |
| WO (1) | WO2002014279A1 (enExample) |
| ZA (1) | ZA200300828B (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0002934D0 (sv) | 2000-08-17 | 2000-08-17 | Axon Biochemicals Bv | New aporphine esters and in their use in therapy |
| SE0102036D0 (sv) * | 2001-06-08 | 2001-06-08 | Axon Biochemicals Bv | Pharmaceutical formulation for the efficient administration of apomorphine, 6aR- (-) -N- Propyl- norapomorphine and their derivatives and pro-drugs thereof |
| EP1634596A4 (en) * | 2003-06-19 | 2006-06-21 | Lotus Pharmaceutical Co Ltd | APORPHINE AND OXOPHORPHINE AND ITS MEDICAL USE |
| EP1644004A4 (en) | 2003-06-20 | 2010-10-06 | Ronald Aung-Din | LOCAL THERAPY FOR THE TREATMENT OF MIGRAINS, MUSCLE CLARIFICATIONS, MUSCLE SPASMS, SPASTICITY AND RELATED CONDITIONS |
| JP2007532670A (ja) | 2004-04-13 | 2007-11-15 | ザ マクレーン ホスピタル コーポレーション | Ｒ（−）−１１−ヒドロキシアポルフィン誘導体およびその使用方法 |
| GB2437488A (en) * | 2006-04-25 | 2007-10-31 | Optinose As | Pharmaceutical oily formulation for nasal or buccal administration |
| GB2463833B (en) * | 2007-06-26 | 2012-02-08 | Parkinson S Inst | Compositions that prevent or reverse alpha-synuclein fibrillation for use in the treatment of neurological disorders |
| WO2009009083A1 (en) * | 2007-07-12 | 2009-01-15 | The Mclean Hospital Corporation | R(-)-2-methoxy-11-hydroxyaporphine and derivatives thereof |
| TWI404702B (zh) * | 2007-08-31 | 2013-08-11 | Lundbeck & Co As H | 兒茶酚胺衍生物和其前藥 |
| US20090124651A1 (en) | 2007-08-31 | 2009-05-14 | H. Lundbeck A/S | Catecholamine derivatives and prodrugs thereof |
| ES2315203B1 (es) * | 2007-09-11 | 2010-01-13 | Universidade De Santiago De Compostela | Uso de oxoisoaporfinas y sus derivados como inhibidores selectivos de la monoamino oxidasa a. |
| GB0721394D0 (en) * | 2007-10-31 | 2007-12-12 | Vectura Group Plc | Compositions for trating parkinson's disease |
| CA2729346A1 (en) | 2008-06-30 | 2010-01-14 | Afgin Pharma, Llc | Topical regional neuro-affective therapy |
| CA2758948A1 (en) * | 2009-04-17 | 2010-10-21 | Somalabs, Inc. | Method for the induction of a reward response by modulation of dopaminergic systems in the central nervous system |
| PT2952191T (pt) | 2009-06-12 | 2018-11-30 | Sunovion Pharmaceuticals Inc | Apomorfina sublingual |
| EP2651357B1 (en) | 2010-12-16 | 2020-04-01 | Sunovion Pharmaceuticals Inc. | Sublingual films |
| CA2827029C (en) * | 2011-02-11 | 2019-07-02 | The Regents Of The University Of Michigan | Tripeptide compositions and methods |
| CA3127926A1 (en) | 2015-04-21 | 2016-10-27 | Sunovion Pharmaceuticals Inc. | Methods of treating parkinson's disease by administration of apomorphine to an oral mucosa |
| EP3314251A1 (en) | 2015-06-24 | 2018-05-02 | Koninklijke Philips N.V. | Sweat monitoring apparatus and monitoring method |
| PT3713933T (pt) | 2017-11-24 | 2026-05-19 | H Lundbeck As | Novos profrmacos de catecolamina para utilizao no tratamento de doena de parkinson |
| BR112020014598A2 (pt) * | 2018-01-18 | 2020-12-08 | Leukos Biotech, S. L. | Forma cristalina de partículas sólidas cocristalinas de apomorfina·ácido palmítico |
| CN112930180A (zh) * | 2018-04-20 | 2021-06-08 | 通用医疗公司 | 用于跨血脑屏障递送的乙酰化前药 |
| US11111263B2 (en) | 2019-05-20 | 2021-09-07 | H. Lundbeck A/S | Process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid |
| US11168056B2 (en) | 2019-05-20 | 2021-11-09 | H. Lundbeck A/S | Process for the manufacturing of (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4′,5′:5,6]benzo[1,2-G]quinoline and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[G]quinoline-6,7-diol |
| US11130775B2 (en) | 2019-05-20 | 2021-09-28 | H. Lundbeck A/S | Solid forms of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4A,5,10,10A-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid |
| US12391650B2 (en) | 2019-05-21 | 2025-08-19 | H. Lundbeck A/S | Catecholamine prodrugs for use in the treatment of Parkinson's disease |
| WO2020234275A1 (en) | 2019-05-21 | 2020-11-26 | H. Lundbeck A/S | New catecholamine prodrugs for use in the treatment of parkinson's diseases |
| EP3972600B1 (en) | 2019-05-21 | 2026-02-18 | H. Lundbeck A/S | Catecholamine carbamate prodrugs for use in the treatment of parkinson s disease |
| JP7641234B2 (ja) | 2019-05-21 | 2025-03-06 | ハー・ルンドベック・アクチエゼルスカベット | パーキンソン病の治療に使用するための新規なカテコールアミンプロドラッグ |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4080456A (en) | 1971-10-26 | 1978-03-21 | Schering Aktiengesellschaft | Diacylapomorphines |
| AU3140577A (en) * | 1976-12-13 | 1979-06-14 | Sterling Drug Inc | N-propylnorapormorphine diesters |
| DE2717001C2 (de) | 1977-04-18 | 1984-06-20 | Karl O. Helm Ag, 2000 Hamburg | Arzneimittel mit antithrombotischer Wirkung |
| EP0040074B1 (en) | 1980-05-08 | 1985-07-31 | Northeastern University | N-substituted aporphines, a method of inducing emesis and a method of controlling psychosis utilising the same |
| US4353912A (en) * | 1980-05-08 | 1982-10-12 | Northeastern University | N-Haloalkyl nor apomorphines and method of inactivating dopamine receptor sites and enhancing dopaminergic activity therewith |
| WO1990012574A1 (en) * | 1989-04-25 | 1990-11-01 | Northeastern University | Dopamine agonist compounds |
| GB9517062D0 (en) | 1995-08-18 | 1995-10-25 | Scherer Ltd R P | Pharmaceutical compositions |
| GB9700878D0 (en) | 1997-01-17 | 1997-03-05 | Scherer Ltd R P | Dosage forms and method for ameliorating male erectile dysfunction |
| US6403605B1 (en) | 1998-05-29 | 2002-06-11 | Queen's University At Kingston | Methods for the normalization of sexual response and amelioration of long term genital tissue degradation |
| IT1299566B1 (it) | 1998-07-17 | 2000-03-16 | Ifi Istituto Farmacoterapico I | Cerotto transdermico e composizioni farmaceutiche comprendenti r (-)- norapropilapomorfina cloridrato e/o s (+) - norapropilapomorfina |
| EP1175206A1 (en) | 1999-05-13 | 2002-01-30 | Unihart Corporation | Pharmaceutical compositions comprising apocodeine and/or its derivatives |
| KR20030036157A (ko) * | 2000-04-07 | 2003-05-09 | 탭 파마슈티칼 프로덕츠 인코포레이티드 | 아포모르핀 유도체 및 이의 사용 방법 |
| SE0102036D0 (sv) * | 2001-06-08 | 2001-06-08 | Axon Biochemicals Bv | Pharmaceutical formulation for the efficient administration of apomorphine, 6aR- (-) -N- Propyl- norapomorphine and their derivatives and pro-drugs thereof |
| SE0002934D0 (sv) | 2000-08-17 | 2000-08-17 | Axon Biochemicals Bv | New aporphine esters and in their use in therapy |
| EP1950203A1 (en) | 2007-01-24 | 2008-07-30 | Laboratorios del Dr. Esteve S.A. | Substituted pyrazoline compounds with ACAT, their preparation and use as medicaments |
-
2000
- 2000-08-17 SE SE0002934A patent/SE0002934D0/xx unknown
-
2001
- 2001-07-20 WO PCT/SE2001/001658 patent/WO2002014279A1/en not_active Ceased
- 2001-07-20 CA CA2419842A patent/CA2419842C/en not_active Expired - Fee Related
- 2001-07-20 JP JP2002519422A patent/JP2004506041A/ja active Pending
- 2001-07-20 CZ CZ2003454A patent/CZ2003454A3/cs unknown
- 2001-07-20 EP EP01950203A patent/EP1309553A1/en not_active Withdrawn
- 2001-07-20 MX MXPA03001465A patent/MXPA03001465A/es active IP Right Grant
- 2001-07-20 BR BR0113291-1A patent/BR0113291A/pt not_active Application Discontinuation
- 2001-07-20 HU HU0301685A patent/HUP0301685A3/hu unknown
- 2001-07-20 CN CNB018142222A patent/CN1242991C/zh not_active Expired - Fee Related
- 2001-07-20 US US10/344,420 patent/US7238705B2/en not_active Expired - Lifetime
- 2001-07-20 AU AU2001271228A patent/AU2001271228B2/en not_active Ceased
- 2001-07-20 IL IL15409601A patent/IL154096A0/xx unknown
- 2001-07-20 EA EA200300266A patent/EA006388B1/ru not_active IP Right Cessation
- 2001-07-20 NZ NZ523893A patent/NZ523893A/en not_active IP Right Cessation
- 2001-07-20 AU AU7122801A patent/AU7122801A/xx active Pending
- 2001-07-20 KR KR1020037002274A patent/KR100865503B1/ko not_active Expired - Fee Related
- 2001-07-20 PL PL36008901A patent/PL360089A1/xx not_active Application Discontinuation
-
2003
- 2003-01-23 IL IL154096A patent/IL154096A/en active IP Right Grant
- 2003-01-30 ZA ZA200300828A patent/ZA200300828B/en unknown
- 2003-02-11 NO NO20030677A patent/NO324409B1/no not_active IP Right Cessation
-
2005
- 2005-02-22 US US11/061,881 patent/US7332503B2/en not_active Expired - Lifetime
-
2008
- 2008-01-29 US US12/021,560 patent/US20080119504A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NO20030677L (no) | 2003-03-05 |
| HUP0301685A3 (en) | 2010-03-29 |
| NO324409B1 (no) | 2007-10-08 |
| JP2004506041A (ja) | 2004-02-26 |
| US7238705B2 (en) | 2007-07-03 |
| KR20030036703A (ko) | 2003-05-09 |
| US20080119504A1 (en) | 2008-05-22 |
| AU2001271228B2 (en) | 2006-02-02 |
| NO20030677D0 (no) | 2003-02-11 |
| MXPA03001465A (es) | 2004-12-13 |
| EA006388B1 (ru) | 2005-12-29 |
| EA200300266A1 (ru) | 2003-08-28 |
| ZA200300828B (en) | 2004-05-17 |
| IL154096A (en) | 2009-11-18 |
| SE0002934D0 (sv) | 2000-08-17 |
| EP1309553A1 (en) | 2003-05-14 |
| CA2419842C (en) | 2011-10-18 |
| BR0113291A (pt) | 2004-01-06 |
| CN1447792A (zh) | 2003-10-08 |
| PL360089A1 (en) | 2004-09-06 |
| KR100865503B1 (ko) | 2008-10-28 |
| CN1242991C (zh) | 2006-02-22 |
| US7332503B2 (en) | 2008-02-19 |
| HUP0301685A2 (hu) | 2003-08-28 |
| WO2002014279A1 (en) | 2002-02-21 |
| IL154096A0 (en) | 2003-07-31 |
| AU7122801A (en) | 2002-02-25 |
| US20050143408A1 (en) | 2005-06-30 |
| CA2419842A1 (en) | 2002-02-21 |
| US20040018956A1 (en) | 2004-01-29 |
| CZ2003454A3 (cs) | 2003-06-18 |
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| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
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Free format text: PATENT RENEWED FOR 7 YEARS UNTIL 20 JUL 2021 BY CPA GLOBAL Effective date: 20140612 |
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| EXPY | Patent expired |