ZA200506019B - Pharmaceutical compositions for hepatitis C viral protease inhibitors - Google Patents
Pharmaceutical compositions for hepatitis C viral protease inhibitors Download PDFInfo
- Publication number
- ZA200506019B ZA200506019B ZA200506019A ZA200506019A ZA200506019B ZA 200506019 B ZA200506019 B ZA 200506019B ZA 200506019 A ZA200506019 A ZA 200506019A ZA 200506019 A ZA200506019 A ZA 200506019A ZA 200506019 B ZA200506019 B ZA 200506019B
- Authority
- ZA
- South Africa
- Prior art keywords
- pharmaceutically acceptable
- weight
- pharmaceutical composition
- alkyl
- composition according
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 47
- 208000005176 Hepatitis C Diseases 0.000 title claims description 15
- 230000003612 virological effect Effects 0.000 title claims description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 7
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title description 5
- 239000000203 mixture Substances 0.000 claims description 133
- 150000001875 compounds Chemical class 0.000 claims description 93
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 42
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 150000001412 amines Chemical class 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 239000003921 oil Substances 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 229920000642 polymer Polymers 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 15
- -1 caprylic fatty acids Chemical class 0.000 claims description 14
- 241000711549 Hepacivirus C Species 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 239000008180 pharmaceutical surfactant Substances 0.000 claims description 12
- 125000004001 thioalkyl group Chemical group 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
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- 238000011282 treatment Methods 0.000 claims description 10
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 10
- 230000009385 viral infection Effects 0.000 claims description 10
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- LDVVMCZRFWMZSG-UHFFFAOYSA-N captan Chemical compound C1C=CCC2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C21 LDVVMCZRFWMZSG-UHFFFAOYSA-N 0.000 claims description 6
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- ZAKOWWREFLAJOT-ADUHFSDSSA-N [2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate Chemical group CC(=O)OC1=C(C)C(C)=C2OC(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-ADUHFSDSSA-N 0.000 claims description 5
- 239000003963 antioxidant agent Substances 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 230000010076 replication Effects 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 4
- 229920002675 Polyoxyl Polymers 0.000 claims description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 239000007983 Tris buffer Substances 0.000 claims description 3
- 239000004359 castor oil Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 3
- 239000000347 magnesium hydroxide Substances 0.000 claims description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 claims description 2
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 claims description 2
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 claims description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
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- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
Landscapes
- Health & Medical Sciences (AREA)
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- Communicable Diseases (AREA)
- Oncology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US45976503P | 2003-04-02 | 2003-04-02 |
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| EP (1) | EP1613353A1 (zh) |
| JP (1) | JP2006522017A (zh) |
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| AR (1) | AR043795A1 (zh) |
| AU (1) | AU2004231538A1 (zh) |
| BR (1) | BRPI0409068A (zh) |
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| EC (1) | ECSP056065A (zh) |
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| PE (1) | PE20050013A1 (zh) |
| RS (1) | RS20050741A (zh) |
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| EA200600498A1 (ru) * | 2003-09-22 | 2006-10-27 | Бёрингер Ингельхайм Интернациональ Гмбх | Макроциклические пептиды, проявляющие противовирусную активность в отношении вируса гепатита с |
| US7491794B2 (en) * | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| ES2358333T3 (es) * | 2004-01-21 | 2011-05-09 | Boehringer Ingelheim International Gmbh | Péptidos macrocíclicos con acción contra el virus de la hepatitis c. |
| CA2552319C (en) | 2004-01-30 | 2012-08-21 | Medivir Ab | Hcv ns-3 serine protease inhibitors |
| US7323447B2 (en) | 2005-02-08 | 2008-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP1879607B1 (en) * | 2005-05-02 | 2014-11-12 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
| US7592336B2 (en) | 2005-05-10 | 2009-09-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7601686B2 (en) | 2005-07-11 | 2009-10-13 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TWI387603B (zh) * | 2005-07-20 | 2013-03-01 | Merck Sharp & Dohme | Ｈｃｖ ｎｓ３蛋白酶抑制劑 |
| EP2305695A3 (en) | 2005-07-25 | 2011-07-27 | Intermune, Inc. | Macrocyclic inhibitors of Hepatitis C virus replication |
| PE20070211A1 (es) | 2005-07-29 | 2007-05-12 | Medivir Ab | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
| JP4705984B2 (ja) * | 2005-08-01 | 2011-06-22 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｈｃｖｎｓ３プロテアーゼ阻害剤としての大環状ペプチド |
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| US7741281B2 (en) | 2005-11-03 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| GB0609492D0 (en) * | 2006-05-15 | 2006-06-21 | Angeletti P Ist Richerche Bio | Therapeutic agents |
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| GB0612423D0 (en) | 2006-06-23 | 2006-08-02 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| RU2008152171A (ru) | 2006-07-05 | 2010-08-10 | Интермьюн, Инк. (Us) | Новые ингибиторы вирусной репликации гепатита с |
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| AU2007335962B2 (en) * | 2006-12-20 | 2012-09-06 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Antiviral indoles |
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| US20090155209A1 (en) * | 2007-05-03 | 2009-06-18 | Blatt Lawrence M | Novel macrocyclic inhibitors of hepatitis c virus replication |
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| US9034832B2 (en) | 2011-12-29 | 2015-05-19 | Abbvie Inc. | Solid compositions |
| EP2903988A1 (en) | 2012-10-08 | 2015-08-12 | AbbVie Inc. | Compounds useful for making hcv protease inhibitors |
| LT2909205T (lt) | 2012-10-19 | 2016-12-27 | Bristol-Myers Squibb Company | 9-metilpakeistieji heksadekahidrociklopropa(e)pirolo (1,2-a)(1,4)diazaciklopentadecinilkarbamato dariniai, kaip nestruktūrinės 3 (ns3) proteazės inhibitoriai, skirti hepatito c viruso infekcijų gydymui |
| WO2014070964A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2914598B1 (en) | 2012-11-02 | 2017-10-18 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014070974A1 (en) * | 2012-11-05 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| CN105164148A (zh) | 2013-03-07 | 2015-12-16 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
| CN103965286B (zh) * | 2014-04-22 | 2017-11-03 | 南京安赛莱医药科技有限公司 | 丙型肝炎病毒（hcv）ns3蛋白酶抑制剂 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0989851T3 (da) * | 1997-07-29 | 2003-01-27 | Upjohn Co | Selvemulgerende formulering indeholdende sure lipofile forbindelser |
| US6608027B1 (en) * | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
| UA74546C2 (en) * | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
| US6458383B2 (en) * | 1999-08-17 | 2002-10-01 | Lipocine, Inc. | Pharmaceutical dosage form for oral administration of hydrophilic drugs, particularly low molecular weight heparin |
| US6828301B2 (en) * | 2002-02-07 | 2004-12-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for hepatitis C viral protease inhibitors |
| EA200600498A1 (ru) * | 2003-09-22 | 2006-10-27 | Бёрингер Ингельхайм Интернациональ Гмбх | Макроциклические пептиды, проявляющие противовирусную активность в отношении вируса гепатита с |
-
2004
- 2004-03-23 RS YUP-2005/0741A patent/RS20050741A/sr unknown
- 2004-03-23 CA CA002520886A patent/CA2520886A1/en not_active Abandoned
- 2004-03-23 US US10/807,023 patent/US7157424B2/en active Active
- 2004-03-23 AU AU2004231538A patent/AU2004231538A1/en not_active Abandoned
- 2004-03-23 EP EP04759731A patent/EP1613353A1/en not_active Withdrawn
- 2004-03-23 NZ NZ543250A patent/NZ543250A/en unknown
- 2004-03-23 KR KR1020057018703A patent/KR20050108420A/ko not_active Application Discontinuation
- 2004-03-23 CN CNB2004800087739A patent/CN100363055C/zh not_active Expired - Fee Related
- 2004-03-23 UA UAA200510334A patent/UA81028C2/uk unknown
- 2004-03-23 MX MXPA05010338A patent/MXPA05010338A/es active IP Right Grant
- 2004-03-23 EA EA200501532A patent/EA010013B1/ru not_active IP Right Cessation
- 2004-03-23 BR BRPI0409068-3A patent/BRPI0409068A/pt not_active IP Right Cessation
- 2004-03-23 WO PCT/US2004/008837 patent/WO2004093915A1/en active Application Filing
- 2004-03-23 JP JP2006501244A patent/JP2006522017A/ja active Pending
- 2004-03-31 TW TW093108968A patent/TW200505484A/zh unknown
- 2004-03-31 AR ARP040101067A patent/AR043795A1/es active Pending
- 2004-03-31 PE PE2004000340A patent/PE20050013A1/es not_active Application Discontinuation
- 2004-03-31 UY UY28250A patent/UY28250A1/es not_active Application Discontinuation
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2005
- 2005-07-27 ZA ZA200506019A patent/ZA200506019B/en unknown
- 2005-09-30 HR HR20050871A patent/HRP20050871A2/xx not_active Application Discontinuation
- 2005-09-30 EC EC2005006065A patent/ECSP056065A/es unknown
- 2005-10-28 CO CO05110321A patent/CO5640152A2/es not_active Application Discontinuation
- 2005-10-31 NO NO20055057A patent/NO20055057L/no not_active Application Discontinuation
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2006
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Also Published As
| Publication number | Publication date |
|---|---|
| HK1091130A1 (en) | 2007-01-12 |
| EP1613353A1 (en) | 2006-01-11 |
| UA81028C2 (en) | 2007-11-26 |
| EA200501532A1 (ru) | 2006-06-30 |
| CN1767856A (zh) | 2006-05-03 |
| JP2006522017A (ja) | 2006-09-28 |
| PE20050013A1 (es) | 2005-03-01 |
| BRPI0409068A (pt) | 2006-03-28 |
| CO5640152A2 (es) | 2006-05-31 |
| EA010013B1 (ru) | 2008-06-30 |
| CA2520886A1 (en) | 2004-11-04 |
| WO2004093915A1 (en) | 2004-11-04 |
| CN100363055C (zh) | 2008-01-23 |
| NO20055057L (no) | 2005-10-31 |
| NZ543250A (en) | 2008-12-24 |
| KR20050108420A (ko) | 2005-11-16 |
| MXPA05010338A (es) | 2005-11-17 |
| ECSP056065A (es) | 2006-01-27 |
| AU2004231538A1 (en) | 2004-11-04 |
| RS20050741A (en) | 2007-06-04 |
| AR043795A1 (es) | 2005-08-10 |
| TW200505484A (en) | 2005-02-16 |
| US7157424B2 (en) | 2007-01-02 |
| US20040229776A1 (en) | 2004-11-18 |
| UY28250A1 (es) | 2004-11-30 |
| HRP20050871A2 (en) | 2006-10-31 |
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