TWI501969B - 丁基原啡因衍生物及其用途 - Google Patents
丁基原啡因衍生物及其用途 Download PDFInfo
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- TWI501969B TWI501969B TW096110534A TW96110534A TWI501969B TW I501969 B TWI501969 B TW I501969B TW 096110534 A TW096110534 A TW 096110534A TW 96110534 A TW96110534 A TW 96110534A TW I501969 B TWI501969 B TW I501969B
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- Prior art keywords
- butyl
- compound
- acid
- dose
- morphine
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- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical class C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 61
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- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 208000002193 Pain Diseases 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 208000004224 Opium Dependence Diseases 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 98
- JSRRLKCQVUJIDE-OBRACTJBSA-N (4R,4aR,7S,7aR,12bS)-9-butoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol Chemical compound C(CCC)OC=1C=CC=2C[C@@H]3[C@@H]4C=C[C@@H]([C@H]5[C@@]4(C=2C=1O5)CCN3C)O JSRRLKCQVUJIDE-OBRACTJBSA-N 0.000 description 84
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- 238000000034 method Methods 0.000 description 27
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 25
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
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- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
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- 239000012071 phase Substances 0.000 description 1
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
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- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
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- 238000011084 recovery Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 229910001925 ruthenium oxide Inorganic materials 0.000 description 1
- WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- CIJQGPVMMRXSQW-UHFFFAOYSA-M sodium;2-aminoacetic acid;hydroxide Chemical compound O.[Na+].NCC([O-])=O CIJQGPVMMRXSQW-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
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- 229910001220 stainless steel Inorganic materials 0.000 description 1
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- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical compound O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- UVZICZIVKIMRNE-UHFFFAOYSA-N thiodiacetic acid Chemical compound OC(=O)CSCC(O)=O UVZICZIVKIMRNE-UHFFFAOYSA-N 0.000 description 1
- YCGAZNXXGKTASZ-UHFFFAOYSA-N thiophene-2,5-dicarboxylic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)S1 YCGAZNXXGKTASZ-UHFFFAOYSA-N 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- RUDFQVOCFDJEEF-UHFFFAOYSA-N yttrium(III) oxide Inorganic materials [O-2].[O-2].[O-2].[Y+3].[Y+3] RUDFQVOCFDJEEF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/09—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems
- C07D489/10—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems with a bridge between positions 6 and 14
- C07D489/12—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems with a bridge between positions 6 and 14 the bridge containing only two carbon atoms
-
- 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
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
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| GBGB0606124.6A GB0606124D0 (en) | 2006-03-28 | 2006-03-28 | Buprenorphine derivatives and uses thereof |
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| TW200806672A TW200806672A (en) | 2008-02-01 |
| TWI501969B true TWI501969B (zh) | 2015-10-01 |
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| TW096110534A TWI501969B (zh) | 2006-03-28 | 2007-03-27 | 丁基原啡因衍生物及其用途 |
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| EP (1) | EP2001891B1 (enExample) |
| JP (1) | JP5167446B2 (enExample) |
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| DK (1) | DK2001891T3 (enExample) |
| ES (1) | ES2432169T3 (enExample) |
| GB (1) | GB0606124D0 (enExample) |
| IL (1) | IL193917A (enExample) |
| MX (1) | MX2008011984A (enExample) |
| MY (1) | MY151025A (enExample) |
| NZ (1) | NZ570997A (enExample) |
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| RU (1) | RU2435773C2 (enExample) |
| TW (1) | TWI501969B (enExample) |
| WO (1) | WO2007110636A1 (enExample) |
| ZA (1) | ZA200807614B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7511054B2 (en) | 2006-09-22 | 2009-03-31 | Alltranz Inc. | Transdermally deliverable opioid prodrugs, abuse-resistant compositions and methods of using opioid prodrugs |
| PT2307420E (pt) * | 2008-04-24 | 2012-02-14 | Janssen Pharmaceutica Nv | Pró-fármacos de di-éster de nalmefeno |
| FR2975912B1 (fr) | 2011-05-30 | 2013-06-14 | Flamel Tech Sa | Composition a liberation controlee de buprenorphine |
| MX2018004835A (es) * | 2015-10-26 | 2018-08-01 | Orphomed Inc | Etilenglicol eter de buprenorfina. |
| CA3016510A1 (en) | 2016-03-09 | 2017-09-14 | Indivior Uk Limited | Abuse-resistant pharmaceutical formulations |
| CN109789137B (zh) | 2016-09-13 | 2023-01-13 | 昱展新药生技股份有限公司 | 丁丙诺啡缓释制剂 |
| WO2019064026A1 (en) | 2017-09-29 | 2019-04-04 | Orexo Ab | NEW PHARMACEUTICAL COMPOSITIONS |
| KR102839314B1 (ko) * | 2018-05-11 | 2025-07-29 | 에일러 파마슈티컬스 아이엔씨. | 오래 지속되는 주사용 제제와 부프레노핀 유도체 |
| GB201904767D0 (en) | 2019-04-04 | 2019-05-22 | Orexo Ab | New pharmaceutical compositions |
| WO2023102489A1 (en) * | 2021-12-03 | 2023-06-08 | Board Of Regents Of The University Of Nebraska | Compounds, nanoparticles, and pharmaceutical compositions for the treatment of drug addiction |
| CN116283893B (zh) * | 2023-03-22 | 2024-04-26 | 阜阳欣奕华制药科技有限公司 | 硫代羟基乙酸酐的制备方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2004039317A2 (en) * | 2002-10-25 | 2004-05-13 | Euro-Celtique S.A. | Analogs and prodrugs of buprenorphine |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4668685A (en) | 1984-07-05 | 1987-05-26 | E.I. Du Pont De Nemours And Company | Substituted benzoate ester prodrug derivatives of 3-hydroxymorphinans, which are analgesics or narcotic antagonists |
| GB8728294D0 (en) | 1987-12-03 | 1988-01-06 | Reckitt & Colmann Prod Ltd | Treatment compositions |
| US5985880A (en) | 1996-06-05 | 1999-11-16 | Delta Pharmaceuticals | Compositions and methods for reducing respiratory depression and attendant side effects of mu opioid compounds |
| US5512593A (en) | 1993-03-02 | 1996-04-30 | John S. Nagle | Composition and method of treating depression using natoxone or naltrexone in combination with a serotonin reuptake inhibitor |
| US5750534A (en) | 1994-03-16 | 1998-05-12 | National Science Council | Nalbuphine esters having long acting analgesic action and method of use |
| US6004969A (en) | 1996-04-15 | 1999-12-21 | National Science Council | Transdermal delivery of buprenorphine preparations |
| KR100204659B1 (ko) | 1996-05-28 | 1999-06-15 | 강재헌 | 신규한 부프레노핀계 진통제용 화합물 |
| US6225321B1 (en) | 1997-06-05 | 2001-05-01 | Oliver Yoa-Pu Hu | Long analgesic acting nalbuphine polyester derivative and method of use |
| ES2298323T3 (es) | 1998-11-13 | 2008-05-16 | Jagotec Ag | Inhalador de polvo seco multidosis con reserva de polvo. |
| US6716449B2 (en) | 2000-02-08 | 2004-04-06 | Euro-Celtique S.A. | Controlled-release compositions containing opioid agonist and antagonist |
| EP2517710B1 (en) | 2000-02-08 | 2015-03-25 | Euro-Celtique S.A. | Tamper-resistant oral opioid agonist formulations |
| JP2005523876A (ja) | 2001-09-26 | 2005-08-11 | ペンウェスト ファーマシューティカルズ カンパニー | 乱用の可能性が低減したオピオイド製剤 |
| US20040033253A1 (en) | 2002-02-19 | 2004-02-19 | Ihor Shevchuk | Acyl opioid antagonists |
| US7666876B2 (en) | 2002-03-19 | 2010-02-23 | Vernalis (R&D) Limited | Buprenorphine formulations for intranasal delivery |
| US7776314B2 (en) | 2002-06-17 | 2010-08-17 | Grunenthal Gmbh | Abuse-proofed dosage system |
| DE10250084A1 (de) | 2002-10-25 | 2004-05-06 | Grünenthal GmbH | Gegen Missbrauch gesicherte Darreichungsform |
| DE10250087A1 (de) | 2002-10-25 | 2004-05-06 | Grünenthal GmbH | Gegen Missbrauch gesicherte Darreichungsform |
| US20050186139A1 (en) | 2002-10-25 | 2005-08-25 | Gruenenthal Gmbh | Abuse-proofed dosage form |
| US20050191244A1 (en) | 2002-10-25 | 2005-09-01 | Gruenenthal Gmbh | Abuse-resistant pharmaceutical dosage form |
| RU2215741C1 (ru) * | 2002-11-05 | 2003-11-10 | Открытое Акционерное Общество "Международная Научно-Технологическая Корпорация" | Сложные эфиры n-замещенных 14-гидроксиморфинанов и способ их получения |
| CN1263760C (zh) * | 2002-11-12 | 2006-07-12 | 财团法人奇美医院 | 新颖的丁丙诺啡酯衍生物及其制备方法，以及长效作用镇痛药学组合物 |
| ATE382050T1 (de) * | 2002-11-25 | 2008-01-15 | Chi Mei Foundation Medical Ct | Buprenorphinesterderivate, verfahren zu ihrer herstellung, und langwirksame analgetische arzneimittel |
| JP2004175706A (ja) * | 2002-11-26 | 2004-06-24 | Chi Mei Foundation Medical Center | 新規なブプレノルフィンのエステル誘導体及びそれらの調製方法、及び長時間効力持続性鎮痛薬剤組成物 |
| TW200500067A (en) * | 2003-01-21 | 2005-01-01 | Control Delivery Sys Inc | Salts of codrugs and uses related thereto |
| US7501113B2 (en) | 2003-02-04 | 2009-03-10 | Philip Morris Usa Inc. | Aerosol formulations and aerosol delivery of buprenorphine |
| US7195882B2 (en) | 2003-06-03 | 2007-03-27 | Roche Diagnostics Operations, Inc. | Monoclonal antibodies specific for buprenorphine and metabolites thereof |
| US7759358B2 (en) | 2003-07-23 | 2010-07-20 | Crooks Peter A | Oral bioavailable prodrugs |
| US7589233B2 (en) | 2003-07-29 | 2009-09-15 | Signature R&D Holdings, Llc | L-Threonine derivatives of high therapeutic index |
| US7220842B2 (en) | 2004-04-05 | 2007-05-22 | Dade Behring Inc. | Immunoassays for buprenorphine and norbuprenorphine |
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Also Published As
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|---|---|
| JP5167446B2 (ja) | 2013-03-21 |
| RU2435773C2 (ru) | 2011-12-10 |
| CA2647417C (en) | 2014-09-23 |
| RU2008142527A (ru) | 2010-05-10 |
| MX2008011984A (es) | 2008-10-03 |
| EP2001891A1 (en) | 2008-12-17 |
| NZ570997A (en) | 2011-08-26 |
| CA2647417A1 (en) | 2007-10-04 |
| US20100234412A1 (en) | 2010-09-16 |
| PT2001891E (pt) | 2013-10-30 |
| WO2007110636A1 (en) | 2007-10-04 |
| BRPI0709157A2 (pt) | 2011-06-28 |
| EP2001891B1 (en) | 2013-07-24 |
| AU2007231133A8 (en) | 2011-08-25 |
| AU2007231133A1 (en) | 2007-10-04 |
| CN104151320A (zh) | 2014-11-19 |
| AU2007231133B2 (en) | 2011-09-01 |
| JP2009531406A (ja) | 2009-09-03 |
| AU2007231133A2 (en) | 2008-10-16 |
| PL2001891T3 (pl) | 2014-03-31 |
| GB0606124D0 (en) | 2006-05-03 |
| KR101430626B1 (ko) | 2014-08-18 |
| IL193917A (en) | 2014-12-31 |
| BRPI0709157A8 (pt) | 2018-04-24 |
| DK2001891T3 (da) | 2013-11-04 |
| CN101410402A (zh) | 2009-04-15 |
| ES2432169T3 (es) | 2013-12-02 |
| TW200806672A (en) | 2008-02-01 |
| KR20080105124A (ko) | 2008-12-03 |
| US7964610B2 (en) | 2011-06-21 |
| MY151025A (en) | 2014-03-31 |
| ZA200807614B (en) | 2009-10-28 |
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