CN1323664C - 雷诺嗪缓释制剂 - Google Patents
雷诺嗪缓释制剂 Download PDFInfo
- Publication number
- CN1323664C CN1323664C CNB018061850A CN01806185A CN1323664C CN 1323664 C CN1323664 C CN 1323664C CN B018061850 A CNB018061850 A CN B018061850A CN 01806185 A CN01806185 A CN 01806185A CN 1323664 C CN1323664 C CN 1323664C
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- Prior art keywords
- ranolazine
- concentration
- dosage form
- patient
- sustained release
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Images
Classifications
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
溶液pH | 溶解度(mg/ml) | USP溶解度分类 |
4.81 | 161 | 自由溶解 |
4.89 | 73.8 | 溶解 |
4.90 | 76.4 | 溶解 |
5.04 | 49.4 | 溶解 |
5.35 | 16.7 | 略溶 |
5.82 | 5.48 | 微溶 |
6.46 | 1.63 | 微溶 |
6.73 | 0.83 | 极微溶 |
7.08 | 0.39 | 极微溶 |
7.59(未缓冲水) | 0.24 | 极微溶 |
7.73 | 0.17 | 极微溶 |
12.66 | 0.18 | 极微溶 |
成分 | 重量范围(%) | 优选范围(%) | 最佳范围(%) |
雷诺嗪 | 50-95 | 70-90 | 75 |
微晶纤维素(填充剂) | 1-35 | 5-15 | 10.6 |
甲基丙烯酸共聚物 | 1-35 | 5-12.5 | 10.0 |
氢氧化钠 | 0.1-1.0 | 0.2-0.6 | 0.4 |
羟丙基甲基纤维素 | 0.5-5.0 | 1-3 | 2.0 |
硬脂酸镁 | 0.5-5.0 | 1-3 | 2.0 |
治疗 | |||||
运动变量平均值(全体患者,分钟) | 双盲安慰剂 | 雷诺嗪400mg bid | 雷诺嗪267mg tid | 雷诺嗪400mg tid | |
心绞痛发生时间 | 峰 | 9.01 | 9.33 | 9.40 | 9.33 |
谷 | 8.58 | 8.77 | 8.78 | 8.65 | |
运动持续时间 | 峰 | 10.67 | 10.83 | 10.87 | 10.84 |
谷 | 10.50 | 10.55 | 10.56 | 10.60 | |
到1mmST段压低时间 | 峰 | 9.58 | 9.86 | 9.99 | 9.94 |
谷 | 9.04 | 9.22 | 9.22 | 9.31 |
雷诺嗪400mg bid | 雷诺嗪267mg tid | 雷诺嗪400mg tid | |
峰(ng/ml) | |||
全体患者 | 1882(1094) | 1346(823) | 2128(1198) |
男性 | 1762(1762) | 1261(774) | 1917(1046) |
女性 | 2171(1253) | 1594(904) | 2654(1385) |
谷(ng/ml) | |||
全体患者 | 235(288) | 316(336) | 514(500) |
男性 | 235(264) | 316(336) | 518(494) |
女性 | 235(342) | 316(340) | 505(517) |
时间(小时) | 制剂溶出百分率 | |||
制剂 | ||||
IR | A | B | C | |
0.25 | 88.1 | |||
0.5 | 100.5 | 13.9 | 17.6 | 17.5 |
1 | 101.7 | 19.9 | 26.0 | 25.7 |
2 | 27.8 | 47.5 | 35.9 | |
4 | 39.0 | 69.2 | 48.4 | |
8 | 52.4 | 90.1 | 64.7 | |
12 | 61.6 | 99.6 | 74.2 | |
24 | 80.8 | 105.6 | 95.4 |
制剂 | ||||
IR | A | B | C | |
Cmax(ISD)(ng/ml) | 1940(807) | 753(264) | 657(316) | 925(747) |
C谷(ISD)(ng/ml) | 165(111) | 158(114) | 182(110) | 290(163) |
Tmax(ISD)(小时) | 1.27(0.5) | 4.09(1.14) | 4.05(1.31) | 6.55(2.93) |
AUC0-24(ISD)(ng.hr/ml) | 6530 | 5640 | 5280 | 5820 |
平均值±SD药物动力学参数(n=8除*n=7外) | |||||
剂量缓释(mg) | 组 | Cmax(ng/ml) | C谷(ng/ml) | Tmax(hr) | AUC0-30rh(ng.hr/ml) |
50075010001250150017502000 | 111*2323 | 883±3531300±10601610±9592210±7161980±10503670±15702440±1120 | 382±251455±353695±438943±5411070±7542400±12601640±937 | 4.63±1.194.25±0.8865.71±2.146.21±3.524.75±0.8865.25±2.315.21±2.30 | 9380±425012500±900018100±963025000±809025400±1600049200±1820035400±19100 |
第5天的雷诺嗪药物动力学参数(平均值±SD) | |||
参数 | 雷诺嗪 缓释500mg bid(n=7) | 雷诺嗪 缓释750mg bid(n=7) | 雷诺嗪 缓释1000mg bid(n=7) |
Cmax(ng/ml)Tmax(hr)Cmin(ng/ml) | 1760±7152.00±1.15585±340 | 2710±6574.33±1.621260±501 | 3660±10904.17±2.481960±812 |
参数 | 1500mg缓释bid | 2000mg缓释bid | ||
RS雷诺嗪 | (+)R雷诺嗪 | (-)S雷诺嗪 | RS雷诺嗪 | |
Cmax(ng/ml)Cmin(ng/ml)Median tmax(h)C96h(ng/ml)C108h(ng/ml)AUC96-108h(ng/ml)Cave(ng/ml)波动程度 | 5284±24342932±19184.003656±19182942±193749516±239454126±19950.664±0.336 | 2909±13081436±10464.002009±11371447±107125731±133852144±11150.833±0.402 | 2944±14261514±12014.002399±12051541±126026407±148492201±12370.824±0.443 | 7281±27004149±22284.005042±17974398±239668459±258425705±21530.591±0.240 |
安慰剂 | 500mg bid | 1000mg bid | 1500mg bid | |||||
谷 | 峰 | 谷 | 峰 | 谷 | 峰 | 谷 | 峰 | |
运动持续时间(秒) | 511 | 504 | 533 | 532 | 545 | 555 | 559 | 561 |
与安慰剂相对比的p值 | - | - | 0.003 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
到心绞痛时间(秒) | 412 | 418 | 437 | 452 | 457 | 474 | 472 | 487 |
与安慰剂相对比的p值 | - | - | 0.005 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
到1mm ST段压低时间(秒) | 448 | 442 | 470 | 479 | 491 | 502 | 514 | 508 |
与安慰剂相对比的p值 | - | - | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
剂量 | 500mg BID | 1000mg BID | 1500mg BID |
峰(ng/ml) | 1122(727) | 2461(1525) | 3935(2084) |
谷(ng/ml) | 846(651) | 1949(1425) | 3266(1973) |
Claims (4)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/520,932 US6479496B1 (en) | 1998-09-10 | 2000-03-08 | Methods for treating angina with ranolazine |
US09/520,932 | 2000-03-08 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1443069A CN1443069A (zh) | 2003-09-17 |
CN1323664C true CN1323664C (zh) | 2007-07-04 |
Family
ID=24074628
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB018061850A Expired - Lifetime CN1323664C (zh) | 2000-03-08 | 2001-03-07 | 雷诺嗪缓释制剂 |
Country Status (17)
Country | Link |
---|---|
US (1) | US6479496B1 (zh) |
EP (1) | EP1263439A2 (zh) |
JP (2) | JP4108980B2 (zh) |
CN (1) | CN1323664C (zh) |
AU (3) | AU2001240092B8 (zh) |
BR (1) | BR0109091A (zh) |
CA (1) | CA2402222C (zh) |
CZ (1) | CZ20022996A3 (zh) |
HK (1) | HK1058003A1 (zh) |
HU (1) | HUP0204409A3 (zh) |
IL (1) | IL151575A0 (zh) |
MX (1) | MXPA02008654A (zh) |
NO (1) | NO20024270L (zh) |
NZ (1) | NZ521292A (zh) |
PL (1) | PL357273A1 (zh) |
RU (1) | RU2002126615A (zh) |
WO (1) | WO2001066093A2 (zh) |
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US6479496B1 (en) * | 1998-09-10 | 2002-11-12 | Cv Therapeutics, Inc. | Methods for treating angina with ranolazine |
US6544555B2 (en) | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
US20020068078A1 (en) | 2000-10-13 | 2002-06-06 | Rudnic Edward M. | Antifungal product, use and formulation thereof |
EP1505977B1 (en) | 2002-05-21 | 2014-09-10 | Gilead Sciences, Inc. | Administration of a partial fatty acid oxidation inhibitor such as ranolazine for the treatment of diabetes |
US8822473B2 (en) * | 2002-05-21 | 2014-09-02 | Gilead Sciences, Inc. | Method of treating diabetes |
US8313776B2 (en) | 2003-07-21 | 2012-11-20 | Shionogi Inc. | Antibiotic product, use and formulation thereof |
AU2004258953B2 (en) | 2003-07-21 | 2011-02-10 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
EP1648418A4 (en) | 2003-07-21 | 2011-11-16 | Middlebrook Pharmaceuticals Inc | ANTIBIOTIC PRODUCT, ITS USE AND FORMULATION |
EP1653925A1 (en) | 2003-08-11 | 2006-05-10 | Advancis Pharmaceutical Corporation | Robust pellet |
AU2004264356B2 (en) | 2003-08-12 | 2011-01-27 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
JP5686494B2 (ja) | 2003-08-29 | 2015-03-18 | シオノギ インコーポレイテッド | 抗生物質製剤、その使用法及び作成方法 |
WO2005027877A1 (en) | 2003-09-15 | 2005-03-31 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
JP2008505124A (ja) | 2004-07-02 | 2008-02-21 | アドバンシス ファーマスーティカル コーポレイション | パルス送達用錠剤 |
EP1841411A2 (en) * | 2005-01-06 | 2007-10-10 | Cv Therapeutics, Inc. | Sustained release pharmaceutical formulations comprising ranolazine |
US8357394B2 (en) | 2005-12-08 | 2013-01-22 | Shionogi Inc. | Compositions and methods for improved efficacy of penicillin-type antibiotics |
US8778924B2 (en) | 2006-12-04 | 2014-07-15 | Shionogi Inc. | Modified release amoxicillin products |
US8299052B2 (en) | 2006-05-05 | 2012-10-30 | Shionogi Inc. | Pharmaceutical compositions and methods for improved bacterial eradication |
CN100455288C (zh) * | 2006-06-26 | 2009-01-28 | 哈药集团制药总厂 | 一种盐酸雷诺嗪制剂配方 |
US20080031949A1 (en) * | 2006-07-24 | 2008-02-07 | Cima Labs Inc. | High dose orally dissolvable/disintegrable lyophilized dosage form |
JP2010518169A (ja) * | 2007-02-13 | 2010-05-27 | ギリアード・パロ・アルト・インコーポレイテッド | 心血管疾患の処置のためのラノラジンの使用 |
US20080248112A1 (en) * | 2007-02-13 | 2008-10-09 | Brent Blackburn | Use of ranolazine for the treatment of coronary microvascular diseases |
JP2010518171A (ja) * | 2007-02-13 | 2010-05-27 | ギリアード・パロ・アルト・インコーポレイテッド | 非冠微小血管疾患の処置のためのラノラジンの使用 |
US20090111826A1 (en) * | 2007-02-13 | 2009-04-30 | Louis Lange | Use of ranolazine for the treatment of cardiovascular diseases |
EP2139877B1 (en) * | 2007-03-07 | 2011-05-11 | Concert Pharmaceuticals Inc. | Deuterated piperazine derivatives as anti-anginal compounds |
US20080233191A1 (en) * | 2007-03-22 | 2008-09-25 | Brent Blackburn | Use of ranolazine for elevated brain-type natriuretic peptide |
KR20100038322A (ko) * | 2007-05-31 | 2010-04-14 | 씨브이 쎄러퓨틱스, 인코포레이티드 | 당뇨병 치료 방법 |
KR20100033490A (ko) * | 2007-05-31 | 2010-03-30 | 질레드 팔로 알토 인코포레이티드 | 상승된 뇌-형 나트륨이뇨 펩티드에 대한 라놀라진 |
AU2008266124A1 (en) * | 2007-06-13 | 2008-12-24 | Auspex Pharmaceuticals, Inc. | Substituted piperazines |
US20090012103A1 (en) * | 2007-07-05 | 2009-01-08 | Matthew Abelman | Substituted heterocyclic compounds |
KR20110013348A (ko) * | 2008-02-06 | 2011-02-09 | 길리애드 사이언시즈, 인코포레이티드 | 통증 치료를 위한 라놀라진의 용도 |
US20100292217A1 (en) * | 2009-05-14 | 2010-11-18 | Gilead Palo Alto, Inc. | Ranolazine for the treatment of cns disorders |
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CA2849505A1 (en) | 2011-09-21 | 2013-03-28 | Gilead Sciences, Inc. | Sodium channel blockers reduce glucagon secretion |
TW201717919A (zh) | 2015-07-02 | 2017-06-01 | 國際藥品股份公司 | 雷諾多重壓縮錠劑 |
WO2018001582A1 (en) | 2016-06-30 | 2018-01-04 | Interquim, S.A. | Ranolazine multiple compressed tablets |
AU2020408323A1 (en) | 2019-12-16 | 2022-08-11 | Tenax Therapeutics, Inc. | Levosimendan for treating pulmonary hypertension with heart failure with preserved ejection fraction (PH-HF-pEF) |
JP7500379B2 (ja) | 2020-09-30 | 2024-06-17 | 文化シヤッター株式会社 | 開閉装置 |
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EP0407780A2 (en) * | 1989-06-23 | 1991-01-16 | Syntex Pharmaceuticals Ltd. | Ranolazine and related piperazines used in the treatment of tissues experiencing a physical or chemical insult |
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IL81419A0 (en) * | 1986-01-30 | 1987-08-31 | Syntex Inc | Long acting sustained release pharmaceutical compositions containing dihydropyridines and their preparation |
US5209933A (en) | 1990-01-10 | 1993-05-11 | Syntex (U.S.A.) Inc. | Long acting calcium channel blocker composition |
JPH06199657A (ja) * | 1992-12-10 | 1994-07-19 | Sumitomo Pharmaceut Co Ltd | 徐放性製剤 |
US5455045A (en) * | 1993-05-13 | 1995-10-03 | Syntex (U.S.A.) Inc. | High dose formulations |
JPH09188617A (ja) * | 1996-01-08 | 1997-07-22 | Pola Chem Ind Inc | 徐放性医薬組成物 |
US6479496B1 (en) * | 1998-09-10 | 2002-11-12 | Cv Therapeutics, Inc. | Methods for treating angina with ranolazine |
US6303607B1 (en) * | 1998-09-10 | 2001-10-16 | Cv Therapeutics, Inc. | Method for administering a sustained release ranolanolazine formulation |
JP2000336032A (ja) * | 1999-05-26 | 2000-12-05 | Kissei Pharmaceut Co Ltd | ピペラジンアセトアミド誘導体を含有する徐放性経口医薬品組成物 |
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2000
- 2000-03-08 US US09/520,932 patent/US6479496B1/en not_active Expired - Lifetime
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2001
- 2001-03-07 CA CA002402222A patent/CA2402222C/en not_active Expired - Lifetime
- 2001-03-07 CN CNB018061850A patent/CN1323664C/zh not_active Expired - Lifetime
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- 2001-03-07 PL PL01357273A patent/PL357273A1/xx not_active Application Discontinuation
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- 2001-03-07 IL IL15157501A patent/IL151575A0/xx unknown
- 2001-03-07 MX MXPA02008654A patent/MXPA02008654A/es active IP Right Grant
- 2001-03-07 JP JP2001564746A patent/JP4108980B2/ja not_active Expired - Lifetime
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- 2001-03-07 HU HU0204409A patent/HUP0204409A3/hu unknown
- 2001-03-07 BR BR0109091-7A patent/BR0109091A/pt not_active Application Discontinuation
- 2001-03-07 WO PCT/US2001/007287 patent/WO2001066093A2/en active IP Right Grant
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2002
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2004
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2007
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0407780A2 (en) * | 1989-06-23 | 1991-01-16 | Syntex Pharmaceuticals Ltd. | Ranolazine and related piperazines used in the treatment of tissues experiencing a physical or chemical insult |
Also Published As
Publication number | Publication date |
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RU2002126615A (ru) | 2004-03-20 |
CA2402222C (en) | 2009-11-03 |
CA2402222A1 (en) | 2001-09-13 |
HUP0204409A3 (en) | 2005-04-28 |
NO20024270L (no) | 2002-11-06 |
WO2001066093A2 (en) | 2001-09-13 |
JP2008069159A (ja) | 2008-03-27 |
IL151575A0 (en) | 2003-04-10 |
WO2001066093A3 (en) | 2002-03-14 |
AU2008212005A1 (en) | 2008-09-25 |
PL357273A1 (en) | 2004-07-26 |
HUP0204409A2 (en) | 2003-05-28 |
JP2003525896A (ja) | 2003-09-02 |
HK1058003A1 (en) | 2004-04-30 |
NO20024270D0 (no) | 2002-09-06 |
NZ521292A (en) | 2008-07-31 |
AU2001240092B2 (en) | 2004-10-14 |
CN1443069A (zh) | 2003-09-17 |
MXPA02008654A (es) | 2004-09-06 |
AU2001240092B8 (en) | 2004-12-02 |
CZ20022996A3 (cs) | 2003-09-17 |
BR0109091A (pt) | 2005-02-15 |
AU4009201A (en) | 2001-09-17 |
US6479496B1 (en) | 2002-11-12 |
JP4108980B2 (ja) | 2008-06-25 |
EP1263439A2 (en) | 2002-12-11 |
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