EP1263424A2 - Traitement de troubles lies au systeme serotonergique - Google Patents
Traitement de troubles lies au systeme serotonergiqueInfo
- Publication number
- EP1263424A2 EP1263424A2 EP01921387A EP01921387A EP1263424A2 EP 1263424 A2 EP1263424 A2 EP 1263424A2 EP 01921387 A EP01921387 A EP 01921387A EP 01921387 A EP01921387 A EP 01921387A EP 1263424 A2 EP1263424 A2 EP 1263424A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- deramciclane
- treatment
- anxiety
- use according
- daily dosage
- 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.)
- Withdrawn
Links
- 229950011405 deramciclane Drugs 0.000 title claims abstract description 58
- QOBGWWQAMAPULA-RLLQIKCJSA-N n,n-dimethyl-2-[[(1r,3s,4r)-4,7,7-trimethyl-3-phenyl-3-bicyclo[2.2.1]heptanyl]oxy]ethanamine Chemical compound C1([C@@]2([C@]3(C)CC[C@@H](C3(C)C)C2)OCCN(C)C)=CC=CC=C1 QOBGWWQAMAPULA-RLLQIKCJSA-N 0.000 title claims abstract description 58
- 238000011282 treatment Methods 0.000 title claims abstract description 34
- 208000019901 Anxiety disease Diseases 0.000 title claims abstract description 29
- 230000036506 anxiety Effects 0.000 title claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 208000035475 disorder Diseases 0.000 claims abstract description 14
- 230000000862 serotonergic effect Effects 0.000 claims abstract description 8
- 241000282412 Homo Species 0.000 claims description 11
- 241000282414 Homo sapiens Species 0.000 claims description 10
- 208000011688 Generalised anxiety disease Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 2
- 239000012735 once-a-day formulation Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 5
- 241000700159 Rattus Species 0.000 description 20
- 230000000694 effects Effects 0.000 description 13
- 239000000902 placebo Substances 0.000 description 11
- 229940068196 placebo Drugs 0.000 description 11
- 238000012360 testing method Methods 0.000 description 9
- 230000036470 plasma concentration Effects 0.000 description 7
- 238000010171 animal model Methods 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 206010054089 Depressive symptom Diseases 0.000 description 4
- 239000002249 anxiolytic agent Substances 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 230000003997 social interaction Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 229960005333 tetrabenazine Drugs 0.000 description 2
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- 206010061623 Adverse drug reaction Diseases 0.000 description 1
- 206010002869 Anxiety symptoms Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 206010049816 Muscle tightness Diseases 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- -1 acetic acid Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 102000015007 alpha-adrenergic receptor activity proteins Human genes 0.000 description 1
- 108040006816 alpha-adrenergic receptor activity proteins Proteins 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 229960002495 buspirone Drugs 0.000 description 1
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
Definitions
- the present invention is directed to deramciclane, (lR,2S,4R)-(-)-2-[N,N- (d ⁇ methylam ⁇ noethoxy)]-2-phenyl-l,7,7-t ⁇ methyl-b ⁇ cyclo[2 2 l]heptane, and its use in the treatment of disorders relating to the serotonergic system Specifically, the present invention is directed to the use of deramciclane in the treatment of depression
- the present invention is directed to the use of deramciclane m the treatment of anxiety, specifically chronic anxiety including GAD, m an oral daily dosage of about 30 mg in humans.
- the daily dosage may be given as a once-a-day formulation or it may be divided
- a once-a-day fomiulation may be used, and may lead to greater patient compliance than a multiple-dose daily formulation
- deramciclane as a free base and as a fumarate salt has been desc ⁇ bed m Hunga ⁇ an Patent No 212,547
- Other pharmaceutically acceptable acid addition salts of deramciclane may be formed with inorganic (e g , hydrochlo ⁇ c acid, sulfu ⁇ c acid) or organic acids (e g , acetic acid, tarta ⁇ c acid)
- the fumarate salt is an example of such a pharmaceutically acceptable acid addition salt
- Deramciclane has shown anxiolytic-hke effects m some conventional animal models with various routes of administration, and in receptor binding studies in vitro deramciclane has shown to bind with high affinity to serotonin 5HT A - and 5-HT 2 - receptor subtypes, being a potent antagonist of these receptors (Gacsalyi, I et al , Drug Dv Res (1997) 40 333-348) In punished drinking test in rats (Vogel, J R et al , Psychopharmacologia (1971) 21 : 1-7) deramciclane was active, after single oral administration at doses of 1 mg/kg and 10 mg/kg. In social interaction test in rats (File, S.E. J. Neurosci Methods (1980) 2:219-238) deramciclane enhanced the social interaction time in some extend, the minimum effective dose after single intraperitoneal administration was 0.7 mg/kg. In two compartment test in mice
- Mithani 1984, Effects of Alpha- Adrenoceptor Agonists and Antagonists in a Maze- Exploration Model of "Fear"-Motivated Behaviour, Naunyn-Schmiedeberg's Archives of Pharmacology. 327, 1-5) after single intraperitoneal doses at range of 0.1 mg/kg - 5 mg/kg.
- deramciclane was able to attenuate the caerulein- induced decrease in exploratory behavior at an intraperitoneal dose of 0.5 mg/kg in the elevated plus maze test.
- deramciclane was clearly ineffective at oral doses of 25 and 100 mg/kg.
- deramcilane has been effective in some animal models of anxiety after oral doses at range from 1 mg kg to 30 mg/kg in mice and rats.
- deramciclane has showed negligible effects in animal models of depression even after high peroral doses in mice and rats, which is in line with the results reporting that 5-HT 2 c - receptor agonists are effective in animal models of depression (Moreau J-L. et al. European Neuropsychopharmacology 6:169-175, 1996).
- Anxiety is a normal emotional feeling related to different situations of threat or fear. External threat is experienced as a fear whereas obscure and unidentified feeling of threat may be experienced as anxiety. When anxiety persists it can develop into a pathological disorder.
- Anxiety disorders are divided more specifically in diagnostic disorders e.g., panic disorder, phobias, and generalised anxiety disorder (GAD).
- GAD is a chronic illness associated with excessive anxiety and worry lasting for at least six months.
- the anxiety and worry are associated with restlessness, fatigue, difficulties in concentrating or mind going blank, irritability, muscle tension, and sleeping disturbances. The symptoms may be triggered by different events of life, and the control of anxiety is very difficult to the patient.
- Anxiety is currently treated with benzodiazepines, SSRI's and buspirone, which are not optimal treatments regarding the adverse drug reaction and efficacy profiles.
- benzodiazepines SSRI's and buspirone
- SSRI's SSRI's
- buspirone buspirone
- relapse of the disease different kinds of withdrawal effects, development of tolerance as well as relapse and recurrence often happen, when traditional anxiolytics are used.
- the doctors usually gradually taper the dosage of the medicine (i.e. gradually diminish its daily dosage) before the treatment may be stopped.
- Patients tend to develop tolerance to those traditional compounds as well. Development of tolerance occurs when, for example, a patient requires greater quantities of a compound over time to achieve the same therapeutic effect.
- the improved condition can be maintained, and relapses can thus be prevented by continuing the treatment in those who have responded to the treatment or who have reached remission during it.
- the disease can be prevented by continuing the treatment further by the so called maintenance treatment, during which the daily dosage may be decreased, for example to a half from the original.
- Figure 1 shows the number of responders (at least 50 % reduction in HAM-A scale).
- An object of the present invention is to provide an oral daily dosage of about 20 to about 30 mg of deramciclane for the treatment of disorders of serotonergic systems in humans.
- One disorder of the serotonergic system treatable according to the present invention is anxiety, for example chronic anxiety.
- the present invention also includes the treatment of GAD.
- Another object of the present invention is directed to the treatment of chronic anxiety where the patient does not experience relapse of the anxiety.
- Another object of the present invention is directed to the method of treating depression in a human.
- the patient may continue receiving the full treatment dosage up to the point of termination of the treatment, and will not suffer withdrawal effects that would have otherwise followed using other conventional treatments.
- a standard daily dosage of deramciclane is given to the patient for a period long enough, e.g. for from three weeks to ten years, e.g. for from two months to five years, e.g. for from eight months to two years, to cause relief of the symptoms, whereafter the treatment is abruptly terminated.
- a dosage of about 30 mg of deramciclane may be used, for example in a conventional relatively fast release formulation.
- the dosage may be also lower, for example about 20 mg.
- deramciclane is effective in treating depressive disorders in humans.
- the same oral daily deramciclane dosage of 30 mg, which was effective in the treatment of anxiety was found to be effective on the depressive symptoms in the Montgomery Asberg Depression Rating Scale (MADRS).
- MADRS Montgomery Asberg Depression Rating Scale
- HAM-A efficacy variable Hamilton Anxiety Scale
- the HAM-A score decreased 14.5 points from baseline in groups receiving either
- Number of responders (at least 50 % reduction in HAM-A scale) is presented in Figure 1.
- deramciclane did not cause any withdrawal symptoms after abrupt discontinuation of the treatment. Therefore, it may be used as a treatment for serotonergic diseases without any withdrawal effects.
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
L"invention concerne le deramciclane, (1R,2S,4R)-(-)-2-[N,N-(diméthylaminoéthoxy)]-2-phényl-1,7,7-triméthyl-bicyclo[2.2.1]heptane, et son utilisation dans le traitement de troubles liés au système sérotonergique chez des êtres humains, en particulier dans le traitement de la dépression et de l"anxiété.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01921387A EP1263424A2 (fr) | 2000-03-17 | 2001-03-16 | Traitement de troubles lies au systeme serotonergique |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00302207 | 2000-03-17 | ||
| EP00302207A EP1133986A1 (fr) | 2000-03-17 | 2000-03-17 | Utilisation de la deramciclane pour le traitement de la dépression et de l'anxiété |
| PCT/FI2001/000266 WO2001068067A2 (fr) | 2000-03-17 | 2001-03-16 | Traitement de troubles lies au systeme serotonergique |
| EP01921387A EP1263424A2 (fr) | 2000-03-17 | 2001-03-16 | Traitement de troubles lies au systeme serotonergique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1263424A2 true EP1263424A2 (fr) | 2002-12-11 |
Family
ID=8172804
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00302207A Withdrawn EP1133986A1 (fr) | 2000-03-17 | 2000-03-17 | Utilisation de la deramciclane pour le traitement de la dépression et de l'anxiété |
| EP01921387A Withdrawn EP1263424A2 (fr) | 2000-03-17 | 2001-03-16 | Traitement de troubles lies au systeme serotonergique |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00302207A Withdrawn EP1133986A1 (fr) | 2000-03-17 | 2000-03-17 | Utilisation de la deramciclane pour le traitement de la dépression et de l'anxiété |
Country Status (19)
| Country | Link |
|---|---|
| EP (2) | EP1133986A1 (fr) |
| JP (1) | JP2004500394A (fr) |
| KR (1) | KR20020089399A (fr) |
| CN (1) | CN1418094A (fr) |
| AR (1) | AR028260A1 (fr) |
| AU (2) | AU2001248383A1 (fr) |
| BG (1) | BG107196A (fr) |
| BR (1) | BR0109172A (fr) |
| CA (1) | CA2403350A1 (fr) |
| CZ (1) | CZ20023025A3 (fr) |
| EA (1) | EA200200987A1 (fr) |
| HU (1) | HUP0204528A3 (fr) |
| IL (1) | IL151493A0 (fr) |
| MX (1) | MXPA02008998A (fr) |
| NO (1) | NO20024331D0 (fr) |
| PL (1) | PL359288A1 (fr) |
| SK (1) | SK12982002A3 (fr) |
| WO (1) | WO2001068067A2 (fr) |
| ZA (1) | ZA200207111B (fr) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI20002612A0 (fi) * | 2000-11-28 | 2000-11-28 | Orion Yhtymae Oyj | Yhdistelmäterapia serotoniinivälityksen häiriöiden hoitamiseksi |
| CN105497021A (zh) * | 2014-09-25 | 2016-04-20 | 中国人民解放军军事医学科学院毒物药物研究所 | 胺类化合物治疗焦虑障碍的医药用途 |
| CN105497020A (zh) * | 2014-09-25 | 2016-04-20 | 中国人民解放军军事医学科学院毒物药物研究所 | 胺类化合物的光学异构体治疗疼痛的医药用途 |
| CN109758452A (zh) * | 2014-09-25 | 2019-05-17 | 石药集团中奇制药技术（石家庄）有限公司 | 胺类化合物治疗疼痛的医药用途 |
| CN109758454A (zh) * | 2014-09-25 | 2019-05-17 | 石药集团中奇制药技术（石家庄）有限公司 | 胺类化合物的光学异构体治疗焦虑障碍的医药用途 |
-
2000
- 2000-03-17 EP EP00302207A patent/EP1133986A1/fr not_active Withdrawn
-
2001
- 2001-03-16 PL PL01359288A patent/PL359288A1/xx unknown
- 2001-03-16 IL IL15149301A patent/IL151493A0/xx unknown
- 2001-03-16 AU AU2001248383A patent/AU2001248383A1/en not_active Abandoned
- 2001-03-16 CZ CZ20023025A patent/CZ20023025A3/cs unknown
- 2001-03-16 CN CN01806697A patent/CN1418094A/zh active Pending
- 2001-03-16 SK SK1298-2002A patent/SK12982002A3/sk unknown
- 2001-03-16 KR KR1020027012243A patent/KR20020089399A/ko not_active Withdrawn
- 2001-03-16 CA CA002403350A patent/CA2403350A1/fr not_active Abandoned
- 2001-03-16 EP EP01921387A patent/EP1263424A2/fr not_active Withdrawn
- 2001-03-16 WO PCT/FI2001/000266 patent/WO2001068067A2/fr not_active Ceased
- 2001-03-16 AR ARP010101239A patent/AR028260A1/es unknown
- 2001-03-16 AU AU4838301A patent/AU4838301A/xx active Pending
- 2001-03-16 EA EA200200987A patent/EA200200987A1/ru unknown
- 2001-03-16 HU HU0204528A patent/HUP0204528A3/hu unknown
- 2001-03-16 BR BR0109172-7A patent/BR0109172A/pt not_active Application Discontinuation
- 2001-03-16 JP JP2001566631A patent/JP2004500394A/ja active Pending
- 2001-03-16 MX MXPA02008998A patent/MXPA02008998A/es unknown
-
2002
- 2002-09-04 ZA ZA200207111A patent/ZA200207111B/en unknown
- 2002-09-10 NO NO20024331A patent/NO20024331D0/no not_active Application Discontinuation
- 2002-10-15 BG BG107196A patent/BG107196A/bg unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0168067A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA02008998A (es) | 2003-04-25 |
| NO20024331L (no) | 2002-09-10 |
| ZA200207111B (en) | 2003-12-04 |
| AU4838301A (en) | 2001-09-24 |
| KR20020089399A (ko) | 2002-11-29 |
| HUP0204528A3 (en) | 2004-08-30 |
| AU2001248383A1 (en) | 2002-07-16 |
| CA2403350A1 (fr) | 2001-09-20 |
| EP1133986A1 (fr) | 2001-09-19 |
| JP2004500394A (ja) | 2004-01-08 |
| EA200200987A1 (ru) | 2003-04-24 |
| CN1418094A (zh) | 2003-05-14 |
| PL359288A1 (en) | 2004-08-23 |
| BR0109172A (pt) | 2002-11-26 |
| NO20024331D0 (no) | 2002-09-10 |
| HUP0204528A2 (en) | 2003-05-28 |
| IL151493A0 (en) | 2003-04-10 |
| BG107196A (bg) | 2003-02-28 |
| WO2001068067A2 (fr) | 2001-09-20 |
| CZ20023025A3 (cs) | 2003-05-14 |
| AR028260A1 (es) | 2003-04-30 |
| SK12982002A3 (sk) | 2003-05-02 |
| WO2001068067A3 (fr) | 2002-07-11 |
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