CA2487167A1 - Combination of a dpp iv inhibitor and a cardiovascular compound - Google Patents
Combination of a dpp iv inhibitor and a cardiovascular compound Download PDFInfo
- Publication number
- CA2487167A1 CA2487167A1 CA002487167A CA2487167A CA2487167A1 CA 2487167 A1 CA2487167 A1 CA 2487167A1 CA 002487167 A CA002487167 A CA 002487167A CA 2487167 A CA2487167 A CA 2487167A CA 2487167 A1 CA2487167 A1 CA 2487167A1
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- inhibitor
- hypertension
- dpp
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB0212412.1A GB0212412D0 (en) | 2002-05-29 | 2002-05-29 | Combination of organic compounds |
| GB0212412.1 | 2002-05-29 | ||
| PCT/EP2003/005639 WO2003099279A1 (en) | 2002-05-29 | 2003-05-28 | Combination of a dpp iv inhibitor and a cardiovascular compound |
Publications (1)
| Publication Number | Publication Date |
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| CA2487167A1 true CA2487167A1 (en) | 2003-12-04 |
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| CA002487167A Abandoned CA2487167A1 (en) | 2002-05-29 | 2003-05-28 | Combination of a dpp iv inhibitor and a cardiovascular compound |
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| Country | Link |
|---|---|
| US (2) | US20060074058A1 (https=) |
| EP (1) | EP1511484A1 (https=) |
| JP (2) | JP2005532330A (https=) |
| CN (2) | CN101518650A (https=) |
| AU (1) | AU2003242593A1 (https=) |
| BR (1) | BR0311397A (https=) |
| CA (1) | CA2487167A1 (https=) |
| CO (1) | CO5621286A2 (https=) |
| GB (1) | GB0212412D0 (https=) |
| IL (1) | IL165101A0 (https=) |
| MX (1) | MXPA04011785A (https=) |
| NO (1) | NO20045557L (https=) |
| NZ (2) | NZ548971A (https=) |
| PL (1) | PL372571A1 (https=) |
| RU (2) | RU2336876C2 (https=) |
| WO (1) | WO2003099279A1 (https=) |
| ZA (1) | ZA200408990B (https=) |
Families Citing this family (84)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ATE422884T1 (de) * | 2002-06-03 | 2009-03-15 | Novartis Pharma Gmbh | Verwendung von substituierten cyanopyrrolidinen zur behandlung von hyperlipidämie |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| CA2518465A1 (en) | 2003-03-25 | 2004-10-14 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| US20040214804A1 (en) * | 2003-04-25 | 2004-10-28 | Pharmacia Corporation | Combination of an aldosterone receptor antagonist and an anti-obesity agent |
| JP2007511467A (ja) | 2003-05-14 | 2007-05-10 | タケダ サン ディエゴ インコーポレイテッド | ジペプチジルペプチダーゼインヒビター |
| US7678909B1 (en) | 2003-08-13 | 2010-03-16 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| KR20060041309A (ko) | 2003-08-13 | 2006-05-11 | 다케다 야쿠힌 고교 가부시키가이샤 | ４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도 |
| US7169926B1 (en) | 2003-08-13 | 2007-01-30 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP1699777B1 (en) | 2003-09-08 | 2012-12-12 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| RU2385723C2 (ru) * | 2003-11-17 | 2010-04-10 | Новартис Аг | Применение ингибиторов дипептидилпептидазы iv |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| US7732446B1 (en) | 2004-03-11 | 2010-06-08 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| UA85871C2 (uk) | 2004-03-15 | 2009-03-10 | Такеда Фармасьютікал Компані Лімітед | Інгібітори дипептидилпептидази |
| NZ549535A (en) * | 2004-03-17 | 2010-11-26 | Novartis Ag | Use of aliskiren for treating renal and other disorders |
| WO2005099695A1 (en) * | 2004-04-19 | 2005-10-27 | Novartis Ag | Drug delivery systems for the prevention and treatment of vascular diseases |
| US7687638B2 (en) | 2004-06-04 | 2010-03-30 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| CN1972679B (zh) * | 2004-06-23 | 2010-07-28 | 索尔瓦药物有限公司 | 包括nep-抑制剂、内源性内皮缩血管肽产生系统抑制剂和at1受体拮抗剂的药物组合物 |
| WO2006019965A2 (en) | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| ES2384637T3 (es) * | 2004-10-08 | 2012-07-10 | Novartis Ag | Uso de inhibidores de la renina para la prevención o el tratamiento de disfunción diastólica o insuficiencia cardiaca diastólica |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| JP2008524331A (ja) | 2004-12-21 | 2008-07-10 | 武田薬品工業株式会社 | ジペプチジルペプチダーゼ阻害剤 |
| WO2006066361A1 (en) | 2004-12-24 | 2006-06-29 | The University Of Queensland | Method of treatment or prophylaxis |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| MY146830A (en) * | 2005-02-11 | 2012-09-28 | Novartis Ag | Combination of organic compounds |
| GB0503062D0 (en) * | 2005-02-14 | 2005-03-23 | Novartis Ag | Combination of organic compounds |
| KR20080000665A (ko) | 2005-04-22 | 2008-01-02 | 알란토스 파마슈티컬즈 홀딩, 인코포레이티드 | 디펩티딜 펩티다아제-ⅳ 억제제 |
| JP4967136B2 (ja) * | 2005-06-24 | 2012-07-04 | 国立大学法人 東京医科歯科大学 | 薬剤溶出性ステント |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| US20130131007A1 (en) | 2005-09-07 | 2013-05-23 | Bebaas, Inc. | Vitamin b12 compositions |
| MY147393A (en) | 2005-09-14 | 2012-11-30 | Takeda Pharmaceutical | Administration of dipeptidyl peptidase inhibitors |
| CA2622642C (en) | 2005-09-16 | 2013-12-31 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US20070196510A1 (en) * | 2006-02-17 | 2007-08-23 | Gerber Michael J | Method for treating resistant hypertension |
| CA2866540A1 (en) | 2006-03-20 | 2007-09-27 | Spinifex Pharmaceuticals Pty Ltd. | Method of treatment or prophylaxis of inflammatory pain |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| EP2540725A1 (de) | 2006-05-04 | 2013-01-02 | Boehringer Ingelheim International GmbH | Polymorphe von 1-((4-Methyl-chinazolin-2-yl)methyl)-3-methyl-7-(2-butin-1-yl)-8-(3-(R)-amino-piperidin-1-yl)xanthin |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| AU2008210988B2 (en) * | 2007-02-01 | 2012-09-06 | Allocure, Inc. | Potentiation of stem cell homing and treatment of organ dysfunction or organ failure |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| EP2545920A1 (en) | 2007-08-22 | 2013-01-16 | Abbott GmbH & Co. KG | Therapy for complications of diabetes |
| EP2062874B1 (en) | 2007-11-20 | 2014-12-17 | KRKA, tovarna zdravil, d.d., Novo mesto | Process and intermediates for the preparation of aliskiren |
| PE20091730A1 (es) | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| EP2108960A1 (en) | 2008-04-07 | 2009-10-14 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditons modulated by PYY |
| BRPI0916997A2 (pt) | 2008-08-06 | 2020-12-15 | Boehringer Ingelheim International Gmbh | Inibidor de dpp-4 e seu uso |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| UA102502C2 (uk) * | 2008-08-08 | 2013-07-25 | Віктор Павлович Кутняк | Антигіпертензивна органічна сіль |
| CN102149407A (zh) | 2008-09-10 | 2011-08-10 | 贝林格尔.英格海姆国际有限公司 | 治疗糖尿病和相关病症的组合疗法 |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| EP2189442B1 (en) | 2008-11-20 | 2014-10-01 | Krka Tovarna Zdravil, D.D., Novo Mesto | Process and intermediates for the preparation of aliskiren |
| CN102256976A (zh) | 2008-12-23 | 2011-11-23 | 贝林格尔.英格海姆国际有限公司 | 有机化合物的盐形式 |
| AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| KR20240090632A (ko) | 2009-11-27 | 2024-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료 |
| JP5602250B2 (ja) | 2010-01-14 | 2014-10-08 | ノバルティス アーゲー | 副腎ホルモン修飾剤の使用 |
| CA2795513A1 (en) | 2010-04-06 | 2011-10-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| CN102946875A (zh) | 2010-05-05 | 2013-02-27 | 贝林格尔.英格海姆国际有限公司 | 组合疗法 |
| WO2011161161A1 (en) | 2010-06-24 | 2011-12-29 | Boehringer Ingelheim International Gmbh | Diabetes therapy |
| EP3323818A1 (en) | 2010-09-22 | 2018-05-23 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| AR083878A1 (es) | 2010-11-15 | 2013-03-27 | Boehringer Ingelheim Int | Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento |
| PT2640371T (pt) * | 2010-11-15 | 2020-04-17 | Boehringer Ingelheim Int | Terapia antidiabética vasoprotetora e cardioprotetora |
| US20140018371A1 (en) | 2011-04-01 | 2014-01-16 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012145361A1 (en) | 2011-04-19 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US20140051714A1 (en) | 2011-04-22 | 2014-02-20 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| US20140038889A1 (en) | 2011-04-22 | 2014-02-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| CN102247345A (zh) * | 2011-05-30 | 2011-11-23 | 北京阜康仁生物制药科技有限公司 | 一种新型降血脂组合物 |
| WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US8883800B2 (en) | 2011-07-15 | 2014-11-11 | Boehringer Ingelheim International Gmbh | Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions |
| WO2013030725A1 (en) * | 2011-08-26 | 2013-03-07 | Wockhardt Limited | Methods for treating cardiovascular disorders |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| JP6218811B2 (ja) | 2012-05-14 | 2017-10-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｓｉｒｓ及び／又は敗血症の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| JP6224084B2 (ja) | 2012-05-14 | 2017-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
| CN105555275B (zh) | 2013-06-26 | 2021-04-20 | 东亚St株式会社 | 含有dpp-iv抑制剂的用于预防和治疗肾脏疾病的组合物 |
| EP3110449B1 (en) | 2014-02-28 | 2023-06-28 | Boehringer Ingelheim International GmbH | Medical use of a dpp-4 inhibitor |
| EA201791982A1 (ru) | 2015-03-09 | 2020-02-17 | Интекрин Терапьютикс, Инк. | Способы лечения неалкогольной жировой болезни печени и/или липодистрофии |
| CN109310697A (zh) | 2016-06-10 | 2019-02-05 | 勃林格殷格翰国际有限公司 | 利格列汀和二甲双胍的组合 |
| JP2020515639A (ja) | 2017-04-03 | 2020-05-28 | コヒラス・バイオサイエンシズ・インコーポレイテッド | 進行性核上性麻痺の処置のためのＰＰＡＲγアゴニスト |
| CN107029208A (zh) * | 2017-06-13 | 2017-08-11 | 江苏黄河药业股份有限公司 | 一种治疗心血管疾病的赖诺普利复方制剂及其制备方法 |
| EA034975B1 (ru) * | 2018-03-13 | 2020-04-13 | Владимир Александрович Горшков-Кантакузен | Способ лечения лабильной и пароксизмальной гипертензии |
| CN116688135B (zh) * | 2023-07-28 | 2024-10-29 | 四川大学华西医院 | 一种骨关节炎药物治疗组合物及其制备方法和应用 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5175187A (en) * | 1989-03-06 | 1992-12-29 | Soorianarain Baligadoo | Synergistic compositions for the treatment of coronary insufficiency and methods of use thereof |
| US5350771A (en) * | 1989-03-22 | 1994-09-27 | Peter K. T. Pang | Method and treatment for hypertension using combination therapy involving exogenous calcium and calcium channel blockers |
| WO1994003055A1 (en) * | 1992-07-31 | 1994-02-17 | The Government Of The United States Of America, Asrepresented By The Secretary Of The Department Of Health And Human Services | Producing increased numbers of hematopoietic cells by administering inhibitors of dipeptidyl peptidase iv |
| US5780473A (en) * | 1995-02-06 | 1998-07-14 | Bristol-Myers Squibb Company | Substituted biphenyl sulfonamide endothelin antagonists |
| AU725689B2 (en) * | 1995-06-07 | 2000-10-19 | G.D. Searle & Co. | Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for treatment of congestive heart failure |
| US5645839A (en) * | 1995-06-07 | 1997-07-08 | Trustees Of Boston University | Combined use of angiotensin inhibitors and nitric oxide stimulators to treat fibrosis |
| US6008221A (en) * | 1996-11-06 | 1999-12-28 | Bristol-Myers Squibb Company | Method for treating Alzheimer's disease with folic acid |
| EP1047450B1 (en) * | 1997-12-23 | 2002-10-02 | Warner-Lambert Company | Ace inhibitor-mmp inhibitor combinations |
| US6204281B1 (en) * | 1998-07-10 | 2001-03-20 | Novartis Ag | Method of treatment and pharmaceutical composition |
| WO2000010549A1 (en) * | 1998-08-21 | 2000-03-02 | Point Therapeutics, Inc. | Regulation of substrate activity |
| EP1743655B1 (en) * | 2000-01-21 | 2014-06-25 | Novartis AG | Combinations comprising dipeptidylpeptidase-iv inhibitors and antidiabetic agents |
| GB0014969D0 (en) * | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
| US20020037829A1 (en) * | 2000-08-23 | 2002-03-28 | Aronson Peter S. | Use of DPPIV inhibitors as diuretic and anti-hypertensive agents |
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2002
- 2002-05-29 GB GBGB0212412.1A patent/GB0212412D0/en not_active Ceased
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2003
- 2003-05-28 CA CA002487167A patent/CA2487167A1/en not_active Abandoned
- 2003-05-28 US US10/515,864 patent/US20060074058A1/en not_active Abandoned
- 2003-05-28 BR BR0311397-3A patent/BR0311397A/pt not_active IP Right Cessation
- 2003-05-28 WO PCT/EP2003/005639 patent/WO2003099279A1/en not_active Ceased
- 2003-05-28 NZ NZ548971A patent/NZ548971A/en not_active IP Right Cessation
- 2003-05-28 JP JP2004506803A patent/JP2005532330A/ja not_active Withdrawn
- 2003-05-28 RU RU2004139025/15A patent/RU2336876C2/ru not_active IP Right Cessation
- 2003-05-28 MX MXPA04011785A patent/MXPA04011785A/es active IP Right Grant
- 2003-05-28 PL PL03372571A patent/PL372571A1/xx not_active Application Discontinuation
- 2003-05-28 CN CNA2009100075473A patent/CN101518650A/zh active Pending
- 2003-05-28 NZ NZ536758A patent/NZ536758A/en not_active IP Right Cessation
- 2003-05-28 AU AU2003242593A patent/AU2003242593A1/en not_active Abandoned
- 2003-05-28 EP EP03755149A patent/EP1511484A1/en not_active Withdrawn
- 2003-05-28 CN CNA038121840A patent/CN1655786A/zh active Pending
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2004
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2010
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|---|---|
| US20070293474A1 (en) | 2007-12-20 |
| EP1511484A1 (en) | 2005-03-09 |
| AU2003242593A1 (en) | 2003-12-12 |
| CN1655786A (zh) | 2005-08-17 |
| PL372571A1 (en) | 2005-07-25 |
| NZ536758A (en) | 2007-02-23 |
| NZ548971A (en) | 2008-04-30 |
| RU2004139025A (ru) | 2005-09-10 |
| ZA200408990B (en) | 2006-07-26 |
| NO20045557L (no) | 2005-02-28 |
| JP2005532330A (ja) | 2005-10-27 |
| WO2003099279A1 (en) | 2003-12-04 |
| CO5621286A2 (es) | 2006-03-31 |
| JP2010090173A (ja) | 2010-04-22 |
| RU2336876C2 (ru) | 2008-10-27 |
| IL165101A0 (en) | 2005-12-18 |
| GB0212412D0 (en) | 2002-07-10 |
| US20060074058A1 (en) | 2006-04-06 |
| RU2008119956A (ru) | 2009-11-27 |
| BR0311397A (pt) | 2005-03-15 |
| MXPA04011785A (es) | 2005-03-31 |
| CN101518650A (zh) | 2009-09-02 |
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