CN1738782A - 氘化的儿茶酚胺衍生物以及含有该化合物的药物 - Google Patents
氘化的儿茶酚胺衍生物以及含有该化合物的药物 Download PDFInfo
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- CN1738782A CN1738782A CNA2003801089900A CN200380108990A CN1738782A CN 1738782 A CN1738782 A CN 1738782A CN A2003801089900 A CNA2003801089900 A CN A2003801089900A CN 200380108990 A CN200380108990 A CN 200380108990A CN 1738782 A CN1738782 A CN 1738782A
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- deuteriums
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- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 229960001335 benserazide hydrochloride Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000011545 carbonate/bicarbonate buffer Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940087613 comtan Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- AYYNUGSDPRDVCH-UHFFFAOYSA-N ethyl 3,4-dimethoxybenzoate Chemical compound CCOC(=O)C1=CC=C(OC)C(OC)=C1 AYYNUGSDPRDVCH-UHFFFAOYSA-N 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940064918 levodopa and decarboxylase inhibitor Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012731 long-acting form Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 1
- IYETZZCWLLUHIJ-UHFFFAOYSA-N methyl-(1-phenylpropan-2-yl)-prop-2-ynylazanium;chloride Chemical compound Cl.C#CCN(C)C(C)CC1=CC=CC=C1 IYETZZCWLLUHIJ-UHFFFAOYSA-N 0.000 description 1
- 229940032007 methylethyl ketone Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 229960003678 selegiline hydrochloride Drugs 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (63)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10261807.0 | 2002-12-19 | ||
DE10261807A DE10261807A1 (de) | 2002-12-19 | 2002-12-19 | Deuterierte Catecholaminderivate sowie diese Verbindungen enthaltende Arzneimittel |
Publications (2)
Publication Number | Publication Date |
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CN1738782A true CN1738782A (zh) | 2006-02-22 |
CN100584807C CN100584807C (zh) | 2010-01-27 |
Family
ID=32404400
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200380108990A Expired - Fee Related CN100584807C (zh) | 2002-12-19 | 2003-12-18 | 氘化的儿茶酚胺衍生物以及含有该化合物的药物 |
Country Status (18)
Country | Link |
---|---|
US (2) | US8168820B2 (zh) |
EP (1) | EP1613571B1 (zh) |
JP (5) | JP2006510686A (zh) |
CN (1) | CN100584807C (zh) |
AT (1) | ATE451340T1 (zh) |
AU (1) | AU2003289841B2 (zh) |
CA (1) | CA2513088C (zh) |
DE (2) | DE10261807A1 (zh) |
DK (1) | DK1613571T3 (zh) |
EA (1) | EA009258B1 (zh) |
ES (1) | ES2337046T3 (zh) |
HK (1) | HK1086548A1 (zh) |
IL (1) | IL169203A (zh) |
MX (1) | MXPA05006408A (zh) |
NZ (1) | NZ541047A (zh) |
PL (1) | PL219269B1 (zh) |
PT (1) | PT1613571E (zh) |
WO (1) | WO2004056724A1 (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100360109B1 (ko) * | 2000-12-19 | 2002-11-07 | 주식회사 포스코 | 미분을 재활용하는 분철광석의 유동층식 용융환원장치 및이를 이용한 용융환원방법 |
DE10261807A1 (de) | 2002-12-19 | 2004-07-01 | Turicum Drug Development Ag | Deuterierte Catecholaminderivate sowie diese Verbindungen enthaltende Arzneimittel |
CN101384545B (zh) | 2006-02-17 | 2014-09-03 | 比罗利纳创新研究与发展服务药物有限公司 | 氘化的儿茶酚胺衍生物及包含所述化合物的药物 |
CN101855218A (zh) * | 2007-09-13 | 2010-10-06 | 康塞特医药品有限公司 | 氘化的儿茶酚和苯并[d][1,3]间二氧杂环戊烯及其衍生物的合成 |
US9763904B2 (en) | 2013-02-05 | 2017-09-19 | Teva Pharmaceuticals International Gmbh | Position-specific asymmetric deuterium enriched catecholamine derivatives and medicaments comprising said compounds |
AU2014214055A1 (en) * | 2013-02-05 | 2015-07-16 | Teva Pharmaceuticals International Gmbh | Position-specific asymmetric deuterium enriched catecholamine derivatives and medicaments comprising said compounds |
PE20160556A1 (es) * | 2013-07-08 | 2016-06-11 | Auspex Pharmaceuticals Inc | Compuestos neurotransmisores de dihidroxifenilo, composiciones y metodos |
EP2918266A1 (en) | 2014-03-11 | 2015-09-16 | CDRD Berolina AB | Composition comprising a dopamine agonist and an L-DOPA derivative for treating Parkinson's disease |
JP2018530612A (ja) | 2015-10-09 | 2018-10-18 | テバ、ファーマスーティカルズ、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Teva Pharmaceuticals International Gmbh | パーキンソン病の治療のための重水素化レボドパとカルビドパおよびオピカポンとの組合せ |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3699158A (en) * | 1969-08-25 | 1972-10-17 | Merck & Co Inc | Selective deuteration of tyrosine, aspartic and glutamic acids |
US3769424A (en) | 1970-10-01 | 1973-10-30 | Merck & Co Inc | Composition and method of treating dopamine deficiency in brain tissue |
DE2049115C3 (de) | 1970-10-06 | 1981-07-30 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai, Tokyo | Verwendung von Calcium-5-butylpicolinat und/oder Calcium-5-pentylpicolinat bei der Bekämpfung des Parkinsonismus mit 3-(3,4-Dihydroxyphenyl)-L-alanin (L-Dopa) |
US4663349A (en) | 1985-12-30 | 1987-05-05 | Merck & Co., Inc. | Rectally absorbable form of L-dopa |
EP0252290B1 (en) | 1986-06-10 | 1992-06-03 | CHIESI FARMACEUTICI S.p.A. | Pharmaceutical compositions containing levodopa methyl ester, preparation and therapeutic applications thereof |
JP2718504B2 (ja) * | 1988-02-22 | 1998-02-25 | アローンサクル シャオバニー | 中枢神経系疾患治療法及びアルツハイマー病診断法 |
IT1226902B (it) | 1988-07-12 | 1991-02-21 | Mini Ricerca Scient Tecnolog | Processo per la sintesi del levodopa |
US5354885A (en) | 1992-12-24 | 1994-10-11 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Process for preparing ethyl ester of L-DOPA |
US6221335B1 (en) * | 1994-03-25 | 2001-04-24 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
IL119417A (en) * | 1996-10-13 | 2003-02-12 | Moshe Kushnir | Pharmaceutical composition for transdermal administration of levodopa for parkinson's disease |
DE69832984T2 (de) | 1997-10-08 | 2006-09-21 | Isotechnika, Inc., Edmonton | DEUTERIERtE und undeuterierte CYCLOSPORIN-ANALOGA UND IHRE VERWENDUNG ALS IMMUNMODULIERENDE AGENtIEN |
US6440710B1 (en) * | 1998-12-10 | 2002-08-27 | The Scripps Research Institute | Antibody-catalyzed deuteration, tritiation, dedeuteration or detritiation of carbonyl compounds |
NO309305B1 (no) | 1999-02-19 | 2001-01-15 | Norsk Hydro As | Anvendelse av benzaldehydderivater ved fremstilling av farmasöytiske preparater for forebygging og/eller behandling av kreft, samt visse nye benzaldehydderivater |
DE60001623T2 (de) * | 1999-12-03 | 2003-12-18 | Pfizer Products Inc., Groton | Sulfamoylheteroarylpyrazolverbindungen zur Verwendung als analgetisches/entzündungshemmendes Mittel |
JP2001203263A (ja) | 2000-01-20 | 2001-07-27 | Hitachi Ltd | 半導体集積回路装置の製造方法および半導体集積回路装置 |
JP2002097137A (ja) | 2000-07-19 | 2002-04-02 | Junichi Sudo | パーキンソン病の予防および/または治療剤 |
DE10123129A1 (de) | 2001-05-02 | 2002-11-14 | Berolina Drug Dev Ab Svedala | Deuterierte 3-Piperidinopropiophenone sowie diese Verbindungen enthaltende Arzneimittel |
DE10261807A1 (de) | 2002-12-19 | 2004-07-01 | Turicum Drug Development Ag | Deuterierte Catecholaminderivate sowie diese Verbindungen enthaltende Arzneimittel |
-
2002
- 2002-12-19 DE DE10261807A patent/DE10261807A1/de not_active Withdrawn
-
2003
- 2003-12-18 EP EP03782168A patent/EP1613571B1/de not_active Expired - Lifetime
- 2003-12-18 MX MXPA05006408A patent/MXPA05006408A/es active IP Right Grant
- 2003-12-18 US US10/539,845 patent/US8168820B2/en not_active Ceased
- 2003-12-18 CN CN200380108990A patent/CN100584807C/zh not_active Expired - Fee Related
- 2003-12-18 PT PT03782168T patent/PT1613571E/pt unknown
- 2003-12-18 AT AT03782168T patent/ATE451340T1/de active
- 2003-12-18 EA EA200500958A patent/EA009258B1/ru not_active IP Right Cessation
- 2003-12-18 AU AU2003289841A patent/AU2003289841B2/en not_active Ceased
- 2003-12-18 CA CA2513088A patent/CA2513088C/en not_active Expired - Fee Related
- 2003-12-18 US US14/464,444 patent/USRE46629E1/en not_active Expired - Fee Related
- 2003-12-18 DK DK03782168.3T patent/DK1613571T3/da active
- 2003-12-18 PL PL377584A patent/PL219269B1/pl unknown
- 2003-12-18 NZ NZ541047A patent/NZ541047A/en not_active IP Right Cessation
- 2003-12-18 ES ES03782168T patent/ES2337046T3/es not_active Expired - Lifetime
- 2003-12-18 JP JP2004561054A patent/JP2006510686A/ja active Pending
- 2003-12-18 DE DE50312224T patent/DE50312224D1/de not_active Expired - Lifetime
- 2003-12-18 WO PCT/DE2003/004203 patent/WO2004056724A1/de active Application Filing
-
2005
- 2005-06-16 IL IL169203A patent/IL169203A/en active IP Right Grant
-
2006
- 2006-06-07 HK HK06106498.8A patent/HK1086548A1/xx not_active IP Right Cessation
-
2011
- 2011-11-07 JP JP2011243559A patent/JP2012087124A/ja active Pending
-
2015
- 2015-07-03 JP JP2015134444A patent/JP2015178537A/ja active Pending
- 2015-07-03 JP JP2015134445A patent/JP2015212287A/ja not_active Withdrawn
-
2017
- 2017-07-06 JP JP2017132662A patent/JP2018193356A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
JP2018193356A (ja) | 2018-12-06 |
JP2015178537A (ja) | 2015-10-08 |
EA009258B1 (ru) | 2007-12-28 |
PT1613571E (pt) | 2010-02-10 |
ATE451340T1 (de) | 2009-12-15 |
MXPA05006408A (es) | 2006-03-08 |
CN100584807C (zh) | 2010-01-27 |
USRE46629E1 (en) | 2017-12-12 |
HK1086548A1 (en) | 2006-09-22 |
JP2012087124A (ja) | 2012-05-10 |
EP1613571A1 (de) | 2006-01-11 |
CA2513088A1 (en) | 2004-07-08 |
DE10261807A1 (de) | 2004-07-01 |
DK1613571T3 (da) | 2010-04-12 |
AU2003289841A1 (en) | 2004-07-14 |
CA2513088C (en) | 2012-03-06 |
JP2015212287A (ja) | 2015-11-26 |
EP1613571B1 (de) | 2009-12-09 |
US20060135615A1 (en) | 2006-06-22 |
PL377584A1 (pl) | 2006-02-06 |
PL219269B1 (pl) | 2015-04-30 |
WO2004056724A1 (de) | 2004-07-08 |
US8168820B2 (en) | 2012-05-01 |
AU2003289841B2 (en) | 2010-01-28 |
IL169203A (en) | 2012-05-31 |
EA200500958A1 (ru) | 2006-02-24 |
JP2006510686A (ja) | 2006-03-30 |
DE50312224D1 (de) | 2010-01-21 |
ES2337046T3 (es) | 2010-04-20 |
NZ541047A (en) | 2008-09-26 |
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