JP4320175B2 - 心不全の治療方法 - Google Patents
心不全の治療方法 Download PDFInfo
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- JP4320175B2 JP4320175B2 JP2002562349A JP2002562349A JP4320175B2 JP 4320175 B2 JP4320175 B2 JP 4320175B2 JP 2002562349 A JP2002562349 A JP 2002562349A JP 2002562349 A JP2002562349 A JP 2002562349A JP 4320175 B2 JP4320175 B2 JP 4320175B2
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- Prior art keywords
- levosimendan
- calcium
- heart failure
- pharmaceutically acceptable
- infusion
- Prior art date
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- 206010019280 Heart failures Diseases 0.000 title claims abstract description 13
- WHXMKTBCFHIYNQ-SECBINFHSA-N levosimendan Chemical compound C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1 WHXMKTBCFHIYNQ-SECBINFHSA-N 0.000 claims abstract description 51
- 229960000692 levosimendan Drugs 0.000 claims abstract description 50
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000011575 calcium Substances 0.000 claims abstract description 30
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 30
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 239000004480 active ingredient Substances 0.000 claims description 18
- 159000000007 calcium salts Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 229940127557 pharmaceutical product Drugs 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- 150000001805 chlorine compounds Chemical group 0.000 claims 1
- 239000001177 diphosphate Substances 0.000 claims 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims 1
- 235000011180 diphosphates Nutrition 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 abstract description 19
- 239000003795 chemical substances by application Substances 0.000 abstract description 17
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 abstract description 15
- 229910001424 calcium ion Inorganic materials 0.000 abstract description 15
- 206010007556 Cardiac failure acute Diseases 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 6
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- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 14
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- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 1
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- 108010044467 Isoenzymes Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 102000004016 L-Type Calcium Channels Human genes 0.000 description 1
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- DXPOSRCHIDYWHW-UHFFFAOYSA-N Xamoterol Chemical compound C=1C=C(O)C=CC=1OCC(O)CNCCNC(=O)N1CCOCC1 DXPOSRCHIDYWHW-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
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- 229960002105 amrinone Drugs 0.000 description 1
- RNLQIBCLLYYYFJ-UHFFFAOYSA-N amrinone Chemical compound N1C(=O)C(N)=CC(C=2C=CN=CC=2)=C1 RNLQIBCLLYYYFJ-UHFFFAOYSA-N 0.000 description 1
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- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
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- 229960004494 calcium gluconate Drugs 0.000 description 1
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 description 1
- 229940095618 calcium glycerophosphate Drugs 0.000 description 1
- 235000019299 calcium glycerylphosphate Nutrition 0.000 description 1
- OLOZVPHKXALCRI-UHFFFAOYSA-L calcium malate Chemical compound [Ca+2].[O-]C(=O)C(O)CC([O-])=O OLOZVPHKXALCRI-UHFFFAOYSA-L 0.000 description 1
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- 229940016114 calcium malate Drugs 0.000 description 1
- 235000011038 calcium malates Nutrition 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
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- 231100000135 cytotoxicity Toxicity 0.000 description 1
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- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
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- ZJKNESGOIKRXQY-UHFFFAOYSA-N enoximone Chemical compound C1=CC(SC)=CC=C1C(=O)C1=C(C)NC(=O)N1 ZJKNESGOIKRXQY-UHFFFAOYSA-N 0.000 description 1
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- 239000008103 glucose Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
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- 229960002725 isoflurane Drugs 0.000 description 1
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- 229940114897 levosimendan 2.5 mg/ml Drugs 0.000 description 1
- 229960003574 milrinone Drugs 0.000 description 1
- PZRHRDRVRGEVNW-UHFFFAOYSA-N milrinone Chemical compound N1C(=O)C(C#N)=CC(C=2C=CN=CC=2)=C1C PZRHRDRVRGEVNW-UHFFFAOYSA-N 0.000 description 1
- OWFJMGQSOHDIPP-UHFFFAOYSA-L monocalcium citrate Chemical compound [Ca+2].OC(=O)CC(O)(C(O)=O)CC([O-])=O.OC(=O)CC(O)(C(O)=O)CC([O-])=O OWFJMGQSOHDIPP-UHFFFAOYSA-L 0.000 description 1
- 235000012663 monocalcium citrate Nutrition 0.000 description 1
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- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
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- 229960001412 pentobarbital Drugs 0.000 description 1
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- 231100000572 poisoning Toxicity 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/42—Phosphorus; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Electrotherapy Devices (AREA)
- External Artificial Organs (AREA)
Description
実施例1 静脈内注入用濃縮溶液
(a)レボシメンダン 2.5mg/ml
(b)コリドンPF12 10mg/ml
(c)クエン酸 2mg/ml
(d)脱水エタノール 全量で1mlまで(785mg)
濃縮溶液は、殺菌製造容器において、攪拌下でクエン酸、コリドンPF12およびレボシメンダンを脱水エタノールに溶解することにより製造された。得られたバルク溶液を殺菌フィルター(0.22μm)に通してろ過した。ついで、殺菌ろ過したバルク溶液を無菌的に8mlおよび10mlの注射バイアルに(5mlおよび10ml充填容量で)注入し、ゴム栓で密封した。
120の自発呼吸をするモルモット(ダンキン ハートレイ(Dunkin Hartly)、体重470±5グラム、平均±SEM)をイソフルレンで麻酔した。左心室および鰓器官(brachial)の動脈圧を測定した。左心室に圧力変換器を導入するために頸動脈を外科的にむき出しにした。流体で満たされたポリエチレンカニューレを鰓器官動脈に挿入し、動脈圧を記録するためにもう一方の圧力変換器に接続した。圧力信号は増幅され、電子化され、サンプリングされた。安定化後、基準となる血行動態を、ベラパミルまたはジルチアゼム中毒を誘発する前に10分間記録した。
Claims (4)
- 活性成分としてレボシメンダンまたはその薬学的に許容し得る塩と、薬学的に許容し得る無機カルシウム塩とを別々に、または一緒に含有する複合製剤としての心不全の治療用医薬製品。
- 無機カルシウム塩が塩化カルシウム、リン酸カルシウム、ニリン酸カルシウムまたは炭酸カルシウムである請求項1記載の製品。
- 活性成分としてレボシメンダンまたはその薬学的に許容し得る塩と、薬学的に許容し得る無機カルシウム塩とを含む心不全の治療用医薬組成物。
- 同時、別々または連続投与のための心不全の治療用複合製剤の製造におけるレボシメンダンまたはその薬学的に許容し得る塩と、薬学的に許容し得る無機カルシウム塩との活性成分としての使用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI20010233A FI20010233A0 (fi) | 2001-02-08 | 2001-02-08 | Menetelmä sydämen vajaatoiminnan hoitoon |
PCT/FI2002/000099 WO2002062342A1 (en) | 2001-02-08 | 2002-02-08 | A method for the treatment of heart failure |
Publications (2)
Publication Number | Publication Date |
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JP2004518698A JP2004518698A (ja) | 2004-06-24 |
JP4320175B2 true JP4320175B2 (ja) | 2009-08-26 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2002562349A Expired - Fee Related JP4320175B2 (ja) | 2001-02-08 | 2002-02-08 | 心不全の治療方法 |
Country Status (9)
Country | Link |
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US (1) | US7279479B2 (ja) |
EP (1) | EP1363636B1 (ja) |
JP (1) | JP4320175B2 (ja) |
AT (1) | ATE464051T1 (ja) |
CA (1) | CA2437196C (ja) |
DE (1) | DE60235965D1 (ja) |
ES (1) | ES2343060T3 (ja) |
FI (1) | FI20010233A0 (ja) |
WO (1) | WO2002062342A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8865660B2 (en) | 2010-12-10 | 2014-10-21 | Broady Health Sciences, Llc | Method of treating neurogenic overactive bladder in a mammal or method of treating non-psychological stress-related bladder dysfunction in a female mammal by administering at least on jasmonate |
US10918778B2 (en) * | 2017-05-24 | 2021-02-16 | Sequana Medical Nv | Direct sodium removal method, solution and apparatus to reduce fluid overload in heart failure patients |
EP4076398A4 (en) | 2019-12-16 | 2024-01-03 | Tenax Therapeutics, Inc. | LEVOSIMENDAN TO TREAT PULMONARY HYPERTENSION ACCOMPANIED BY HEART FAILURE BY MEANS OF PRESERVED EJECTION FRACTION (PH-HF-PEF) |
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US4745130A (en) * | 1978-04-24 | 1988-05-17 | Massachusetts Institute Of Technology | Composition for increasing blood pressure |
EP0078152B1 (en) * | 1981-10-22 | 1986-05-07 | Tanabe Seiyaku Co., Ltd. | Salts of sulfodehydroabietic acid and treatment of gastro-intestinal diseases |
US4971982A (en) * | 1987-07-06 | 1990-11-20 | Hoffmann-La Roche Inc. | Benzopyran derivatives |
CA2020073A1 (en) | 1989-07-03 | 1991-01-04 | Eric E. Allen | Substituted quinazolinones as angiotensin ii antagonists |
US5120738A (en) * | 1989-10-06 | 1992-06-09 | Fujirebio Inc. | Pantothenic acid derivatives |
GB2251615B (en) * | 1991-01-03 | 1995-02-08 | Orion Yhtymae Oy | (-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]pro panedinitrile |
GB2266841A (en) | 1992-05-06 | 1993-11-17 | Orion Yhtymae Oy | Compounds for use as anti-ischemic medicaments |
KR20000057642A (ko) | 1996-12-18 | 2000-09-25 | 스타르크, 카르크 | 헤테로시클릭 카르복실산 유도체, 그의 제제 및 엔도텔린 수용체길항제로서의 용도 |
JP4327260B2 (ja) * | 1997-05-07 | 2009-09-09 | フアルマ・マル・エセ・ア | L型カルシウムチャンネルエンハンサーとしてのアプリジン |
US5998458A (en) * | 1997-06-25 | 1999-12-07 | University Technology Corporation | Method of treating heart failure |
US6030288A (en) * | 1997-09-02 | 2000-02-29 | Quixotic Solutions Inc. | Apparatus and process for verifying honest gaming transactions over a communications network |
FI973804A (fi) * | 1997-09-26 | 1999-03-27 | Orion Yhtymae Oy | Levosimendaanin oraalisia koostumuksia |
FI980902A (fi) * | 1998-04-23 | 1999-10-24 | Orion Yhtymae Oyj | Levosimendaanin stabiileja koostumuksia |
FI981473A (fi) | 1998-06-25 | 1999-12-26 | Orion Yhtymae Oyj | Menetelmä pulmonaalihypertension hoitamiseksi |
FI109659B (fi) * | 1999-09-10 | 2002-09-30 | Orion Yhtymae Oyj | Levosimendaanin farmaseuttisia liuoksia |
WO2001028548A1 (en) * | 1999-10-19 | 2001-04-26 | Texas Heart Institute | Treatment of heart disease with cox-2 inhibitors |
-
2001
- 2001-02-08 FI FI20010233A patent/FI20010233A0/fi unknown
-
2002
- 2002-02-08 EP EP02711903A patent/EP1363636B1/en not_active Expired - Lifetime
- 2002-02-08 DE DE60235965T patent/DE60235965D1/de not_active Expired - Lifetime
- 2002-02-08 JP JP2002562349A patent/JP4320175B2/ja not_active Expired - Fee Related
- 2002-02-08 US US10/467,459 patent/US7279479B2/en not_active Expired - Fee Related
- 2002-02-08 ES ES02711903T patent/ES2343060T3/es not_active Expired - Lifetime
- 2002-02-08 WO PCT/FI2002/000099 patent/WO2002062342A1/en active Application Filing
- 2002-02-08 CA CA2437196A patent/CA2437196C/en not_active Expired - Fee Related
- 2002-02-08 AT AT02711903T patent/ATE464051T1/de not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
DE60235965D1 (de) | 2010-05-27 |
JP2004518698A (ja) | 2004-06-24 |
EP1363636A1 (en) | 2003-11-26 |
EP1363636B1 (en) | 2010-04-14 |
CA2437196C (en) | 2010-10-19 |
ES2343060T3 (es) | 2010-07-22 |
US7279479B2 (en) | 2007-10-09 |
ATE464051T1 (de) | 2010-04-15 |
CA2437196A1 (en) | 2002-08-15 |
FI20010233A0 (fi) | 2001-02-08 |
WO2002062342A1 (en) | 2002-08-15 |
US20040092523A1 (en) | 2004-05-13 |
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