HRP990182A2 - Crystalline efavirenz - Google Patents
Crystalline efavirenz Download PDFInfo
- Publication number
- HRP990182A2 HRP990182A2 HR60/088,981A HRP990182A HRP990182A2 HR P990182 A2 HRP990182 A2 HR P990182A2 HR P990182 A HRP990182 A HR P990182A HR P990182 A2 HRP990182 A2 HR P990182A2
- Authority
- HR
- Croatia
- Prior art keywords
- efavirenz
- crystalline
- compound
- solution
- crystalline efavirenz
- Prior art date
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- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 title claims description 192
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 title claims description 190
- 229960003804 efavirenz Drugs 0.000 title claims description 175
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 50
- 150000001875 compounds Chemical class 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 31
- 238000001757 thermogravimetry curve Methods 0.000 claims description 29
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- 102100034343 Integrase Human genes 0.000 claims description 18
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- 239000003814 drug Substances 0.000 claims description 15
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 9
- 230000029812 viral genome replication Effects 0.000 claims description 9
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical group CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 117
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- RXBWRFDZXRAEJT-SZNOJMITSA-N palinavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)C(C)C)[C@H](O)CN1[C@@H](C[C@@H](CC1)OCC=1C=CN=CC=1)C(=O)NC(C)(C)C)C1=CC=CC=C1 RXBWRFDZXRAEJT-SZNOJMITSA-N 0.000 description 1
- 229950006460 palinavir Drugs 0.000 description 1
- 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 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- AFDMODCXODAXLC-UHFFFAOYSA-N phenylmethanimine Chemical compound N=CC1=CC=CC=C1 AFDMODCXODAXLC-UHFFFAOYSA-N 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 235000019204 saccharin Nutrition 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
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- STOSPPMGXZPHKP-UHFFFAOYSA-N tetrachlorohydroquinone Chemical compound OC1=C(Cl)C(Cl)=C(O)C(Cl)=C1Cl STOSPPMGXZPHKP-UHFFFAOYSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- AAAQKTZKLRYKHR-UHFFFAOYSA-N triphenylmethane Chemical compound C1=CC=CC=C1C(C=1C=CC=CC=1)C1=CC=CC=C1 AAAQKTZKLRYKHR-UHFFFAOYSA-N 0.000 description 1
- 229950000977 trovirdine Drugs 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 239000008170 walnut oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/18—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8898198P | 1998-06-11 | 1998-06-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP990182A2 true HRP990182A2 (en) | 2000-02-29 |
Family
ID=22214647
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR60/088,981A HRP990182A2 (en) | 1998-06-11 | 1999-06-08 | Crystalline efavirenz |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1086087A1 (pl) |
| JP (1) | JP2002517487A (pl) |
| CN (1) | CN1307568A (pl) |
| AR (3) | AR018670A1 (pl) |
| AU (1) | AU758114C (pl) |
| BR (1) | BR9911523A (pl) |
| CA (1) | CA2333550A1 (pl) |
| EE (1) | EE05547B1 (pl) |
| HR (1) | HRP990182A2 (pl) |
| HU (1) | HUP0103819A3 (pl) |
| IL (1) | IL139793A (pl) |
| MY (1) | MY126450A (pl) |
| NO (1) | NO20006255L (pl) |
| NZ (1) | NZ507713A (pl) |
| PL (1) | PL198504B1 (pl) |
| SG (3) | SG111980A1 (pl) |
| SK (1) | SK18182000A3 (pl) |
| TW (1) | TWI235152B (pl) |
| UA (1) | UA74324C2 (pl) |
| WO (1) | WO1999064405A1 (pl) |
| ZA (1) | ZA200006173B (pl) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5965729A (en) | 1997-02-05 | 1999-10-12 | Merck & Co., Inc. | Process for the crystallization of a reverse transcriptase inhibitor using an anti-solvent |
| WO2006018853A2 (en) | 2004-08-19 | 2006-02-23 | Hetero Drugs Limited | Novel polymorphs of efavirenz |
| PE20060587A1 (es) * | 2004-09-02 | 2006-07-09 | Bristol Myers Squibb Co | Sintesis de (s)-6-cloro-4-ciclopropiletinil-4-trifluorometil-1,4-dihidro-2h-3,1-benzoxazin-2-ona |
| WO2008108630A1 (en) * | 2007-03-02 | 2008-09-12 | Ultimorphix Technologies B.V. | Polymorphic forms of efavirenz |
| WO2009011567A1 (en) * | 2007-07-16 | 2009-01-22 | Ultimorphix Technologies B.V. | Crystalline forms of efavirenz |
| PL2303267T3 (pl) * | 2008-02-04 | 2013-11-29 | Pfizer Ltd | Polimorficzna postać pochodnej [1,2,4]triazolo[4,3-a]pirydyny do leczenia chorób zapalnych |
| WO2010073254A2 (en) | 2008-12-22 | 2010-07-01 | Hetero Research Foundation | Process for preparing efavirenz polymorph |
| DE102009041443A1 (de) | 2009-09-16 | 2011-03-31 | Archimica Gmbh | Salze des 6-Chlor-4-(cyclopropylethinyl)-1,4-dihydro-4-(trifluormethyl)-2H-3,1-benzoxazin-2-ons und deren Synthese, Aufreinigung und Anwendung als Vorstufen für Efavirenz |
| EP2471783A1 (en) | 2010-12-23 | 2012-07-04 | Esteve Química, S.A. | Novel polymorphic form of efavirenz |
| CN103508973B (zh) * | 2012-06-25 | 2016-04-27 | 上海迪赛诺药业有限公司 | 制备依非韦伦i型结晶的方法 |
| CN102924398B (zh) * | 2012-11-22 | 2015-11-18 | 安徽贝克生物制药有限公司 | 用于除去依非韦伦对应异构体的方法 |
| WO2014114971A1 (en) * | 2013-01-23 | 2014-07-31 | Alienor Farma | Increased dosage of efavirenz for the treatment of cancer |
| CN105037175B (zh) * | 2014-07-18 | 2017-02-22 | 盐城迪赛诺制药有限公司 | 一种用于提高依非韦伦中间体光学纯度的方法 |
| CN105001101B (zh) * | 2015-05-28 | 2017-11-28 | 乐平市瑞盛制药有限公司 | 一种4‑氯‑2‑三氟乙酰基苯胺水合物盐酸盐的合成方法 |
| CN108947855B (zh) * | 2018-08-10 | 2021-10-22 | 江苏沙星化工有限公司 | 一种依非韦伦关键中间体的合成方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL106507A (en) * | 1992-08-07 | 1997-11-20 | Merck & Co Inc | Pharmaceutical compositions containing benzoxazinones and some novel compounds of this type |
| WO1995020389A1 (en) * | 1994-01-28 | 1995-08-03 | Merck & Co., Inc. | Benzoxazinones as inhibitors of hiv reverse transcriptase |
| US5633405A (en) * | 1995-05-25 | 1997-05-27 | Merck & Co., Inc. | Asymmetric synthesis of (-)-6-chloro-4-cyclopropyl-ethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxanzin-2-one |
| AU3736197A (en) * | 1996-07-26 | 1998-02-20 | Du Pont Pharmaceuticals Company | A practical synthesis of benzoxazinones useful as hiv reverse transcripta se inhibitors |
| DE69724630T2 (de) * | 1996-10-02 | 2004-07-29 | Bristol-Myers Squibb Pharma Co. | 4,4-disubstituierte 1,4-dihydro-2h-3,1-benzoxazin-2-one die anwendbar sind als hiv-reverstranskriptase-inhibitoren, zwischenprodukte und verfahren zu ihrer herstellung |
| DE69841972D1 (de) * | 1997-02-05 | 2010-12-09 | Merck Sharp & Dohme | Verfahren zur kristallisation eines reverstranskriptase-inhibitors, bei welchem ein anti-lösungsmittel benutzt wird |
-
1999
- 1999-06-08 HR HR60/088,981A patent/HRP990182A2/hr not_active Application Discontinuation
- 1999-06-10 SG SG200207220A patent/SG111980A1/en unknown
- 1999-06-10 PL PL345221A patent/PL198504B1/pl unknown
- 1999-06-10 CN CN99807219A patent/CN1307568A/zh active Pending
- 1999-06-10 BR BR9911523-9A patent/BR9911523A/pt not_active Application Discontinuation
- 1999-06-10 WO PCT/US1999/013199 patent/WO1999064405A1/en not_active Ceased
- 1999-06-10 NZ NZ507713A patent/NZ507713A/en not_active IP Right Cessation
- 1999-06-10 CA CA002333550A patent/CA2333550A1/en not_active Abandoned
- 1999-06-10 AU AU44364/99A patent/AU758114C/en not_active Expired
- 1999-06-10 UA UA2000127048A patent/UA74324C2/uk unknown
- 1999-06-10 SG SG200207221A patent/SG111981A1/en unknown
- 1999-06-10 IL IL139793A patent/IL139793A/en not_active IP Right Cessation
- 1999-06-10 EE EEP200000743A patent/EE05547B1/xx unknown
- 1999-06-10 JP JP2000553414A patent/JP2002517487A/ja active Pending
- 1999-06-10 MY MYPI99002384A patent/MY126450A/en unknown
- 1999-06-10 SG SG200207226-2A patent/SG134977A1/en unknown
- 1999-06-10 EP EP99927468A patent/EP1086087A1/en not_active Withdrawn
- 1999-06-10 HU HU0103819A patent/HUP0103819A3/hu unknown
- 1999-06-10 SK SK1818-2000A patent/SK18182000A3/sk unknown
- 1999-06-11 AR ARP990102809A patent/AR018670A1/es not_active Application Discontinuation
- 1999-07-03 TW TW088109817A patent/TWI235152B/zh not_active IP Right Cessation
-
2000
- 2000-10-31 ZA ZA200006173A patent/ZA200006173B/xx unknown
- 2000-12-08 NO NO20006255A patent/NO20006255L/no not_active Application Discontinuation
-
2010
- 2010-07-08 AR ARP100102491A patent/AR077469A2/es not_active Application Discontinuation
- 2010-07-08 AR ARP100102490A patent/AR077407A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0103819A2 (hu) | 2002-02-28 |
| PL198504B1 (pl) | 2008-06-30 |
| SG134977A1 (en) | 2007-09-28 |
| EE05547B1 (et) | 2012-06-15 |
| NO20006255L (no) | 2001-02-12 |
| SG111981A1 (en) | 2005-06-29 |
| EE200000743A (et) | 2002-10-15 |
| PL345221A1 (en) | 2001-12-03 |
| WO1999064405A1 (en) | 1999-12-16 |
| MY126450A (en) | 2006-10-31 |
| AR077407A2 (es) | 2011-08-24 |
| IL139793A (en) | 2006-10-31 |
| CA2333550A1 (en) | 1999-12-16 |
| ZA200006173B (en) | 2001-10-31 |
| JP2002517487A (ja) | 2002-06-18 |
| AR018670A1 (es) | 2001-11-28 |
| UA74324C2 (uk) | 2005-12-15 |
| AU4436499A (en) | 1999-12-30 |
| CN1307568A (zh) | 2001-08-08 |
| NO20006255D0 (no) | 2000-12-08 |
| SK18182000A3 (sk) | 2001-08-06 |
| EP1086087A1 (en) | 2001-03-28 |
| NZ507713A (en) | 2003-08-29 |
| IL139793A0 (en) | 2002-02-10 |
| TWI235152B (en) | 2005-07-01 |
| AU758114B2 (en) | 2003-03-13 |
| BR9911523A (pt) | 2001-09-18 |
| AU758114C (en) | 2003-10-30 |
| AR077469A2 (es) | 2011-08-31 |
| HUP0103819A3 (en) | 2003-05-28 |
| SG111980A1 (en) | 2005-06-29 |
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