WO2000023057A2 - Atypical antiphsychotic in combination with acetylcholinesterase inhibitor for improving cognition - Google Patents
Atypical antiphsychotic in combination with acetylcholinesterase inhibitor for improving cognition Download PDFInfo
- Publication number
- WO2000023057A2 WO2000023057A2 PCT/EP1999/007804 EP9907804W WO0023057A2 WO 2000023057 A2 WO2000023057 A2 WO 2000023057A2 EP 9907804 W EP9907804 W EP 9907804W WO 0023057 A2 WO0023057 A2 WO 0023057A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- atypical antipsychotic
- acetylcholinesterase inhibitor
- patients suffering
- alzheimer
- disease
- Prior art date
Links
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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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 concerned with pharmaceutical compositions comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (H), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, or Alzheimer's disease or related dementias.
- Said therapeutically beneficial effect can be a synergistic effect on the cognitive functioning of patients suffering from Alzheimer's disease or related dementias, or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
- an atypical antipsychotic agent (I) for the preparation of a medicament for reducing adverse effects associated with acetylcholinesterase inhibitors (LI) in patients suffering from Alzheimer's disease or related dementias, such as nausea, vomiting, sweating, restlessness and insomnia.
- an atypical antipsychotic agent (I) for the preparation of a medicament for improving sleep in patients suffering from Alzheimer's disease or related dementias while being treated with acetylcholinesterase inhibitors (II).
- the present invention is concerned with a pharmaceutical composition
- a pharmaceutical composition comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, or Alzheimer's disease or related dementias.
- Said therapeutically beneficial effect can be a synergistic effect on the cognitive functioning of patients suffering from Alzheimer's disease or related dementias, or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
- the atypical antipsychotic (I) is selected from risperidone, 9-hydroxyrisperidone or a o- 20 alkanoic acid ester thereof, olanzapine, quetiapine, iloperidone or ziprasidone, and the acetylcholinesterase inhibitor (II) is selected from galantamine, rivastigmine or donepezil, or therapeutically active acid addition salt form of any of the foregoing.
- Said salts comprise salt forms which the active ingredients (I) and (H) are able to form with appropriate acids, such as, for example, inorganic acids such as hydrohalic acids, e.g.
- hydrochloric or hydrobromic acid sulfuric; nitric; phosphoric and the like acids; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic, maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, -toluenesulfonic, cyclamic, salicylic, p-amino- salicylic, pamoic and the like acids.
- galantamine may conveniently be used as the ( 1 : 1 ) hydrobromide salt.
- a lkanoic acids are selected from the group consisting of decanoic (capric), undecanoic, dodecanoic (lauric), tridecanoic, tetradecanoic (myristic), pentadecanoic, hexadecanoic (palmitic), heptadecanoic, octadecanoic (stearic), nonadecanoic and eicosanoic acid. Due to their limited aqueous solubility, it was generally believed that the esters had to be suspended into oils.
- the ester having a C15 (pentadecyl) chain and the active ingredient corresponding thereto being the 9-hydroxyrisperidone palmitate ester was found to be the superior ester from a pharmacokinetic, as well as from a tolerance point of view.
- the amount of each of the active ingredients is equal to or less than that which is approved in monotherapy with said active ingredient.
- compositions wherein the atypical antipsychotic (I) is risperidone and the acetylcholinesterase inhibitor (II) is galantamine, in particular as galantamine hydrobromide are particularly preferred.
- the amount of risperidone is 0.5, 1, 2, 4, or 6 mg and that of galantamine (as base) is 8, 16, 24 or 32 mg per dosage form.
- the present invention also relates to products containing as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), as combined preparations for simultaneous, separate or sequential use in the treatment of patients suffering from psychosis, Alzheimer's disease or related dementias.
- an atypical antipsychotic agent I
- an acetylcholinesterase inhibitor II
- the present invention also concerns the use of an acetylcholinesterase inhibitor (II) for the preparation of a medicament for enhancing the effect of an atypical antipsychotic agent (I) on cognition in patients suffering from psychosis.
- II acetylcholinesterase inhibitor
- the present invention also concerns the use of an atypical antipsychotic agent (I) for the preparation of a medicament for enhancing the effect of an acetylcholinesterase inhibitor (II) on cognition in patients suffering from Alzheimer's disease or related dementias. Additionally, the present invention concerns the use of an atypical antipsychotic agent
- acetylcholinesterase inhibitors H
- Said adverse effect can be nausea, vomiting, sweating, restlessness or insomnia.
- an atypical antipsychotic agent (I) for the preparation of a medicament for improving sleep in patients suffering from Alzheimer's disease or related dementias while being treated with acetylcholinesterase inhibitors (II).
- the present invention also concerns the use of an acetylcholinesterase inhibitor
- the atypical antipsychotic (I) is preferably risperidone and the acetylcholinesterase inhibitor (II) is preferably galantamine, in particular the (1:1) hydrobromide.
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL99348107A PL348107A1 (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
KR1020017002286A KR20010072878A (ko) | 1998-10-16 | 1999-10-12 | 인식을 개선하기 위한 아세틸콜린에스테라제 억제제와배합된 비정형 항정신병제 |
HU0103781A HUP0103781A3 (en) | 1998-10-16 | 1999-10-12 | Pharmaceutical compositions comprising atypical antiphsychotic agent in combination with acetylcholinesterase inhibitor for improving cognition |
BR9914419-0A BR9914419A (pt) | 1998-10-16 | 1999-10-12 | Terapia para melhoria da percepção |
EEP200100136A EE200100136A (et) | 1998-10-16 | 1999-10-12 | Atsetüülkoliini esteraasi inhibiitori ja psühhoosivastase toimeaine kasutamine ravimi valmistamiseks, mis on ette nähtud kognitsiooni- ja psühhoosihäirete raviks, ning neid aineid sisaldav farmatseutiline kompositsioon |
SK459-2001A SK4592001A3 (en) | 1998-10-16 | 1999-10-12 | Atypical antipsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
JP2000576832A JP2002527469A (ja) | 1998-10-16 | 1999-10-12 | 認識を改良するための療法 |
EP99952580A EP1121131A2 (en) | 1998-10-16 | 1999-10-12 | Atypical antipsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
IL14258899A IL142588A0 (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
AU64727/99A AU6472799A (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
CA002345767A CA2345767A1 (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
BG105302A BG105302A (en) | 1998-10-16 | 2001-03-01 | Means for improving cognition |
NO20011403A NO20011403D0 (no) | 1998-10-16 | 2001-03-20 | Terapi for Õ forbedre kongestion |
HR20010262A HRP20010262A2 (en) | 1998-10-16 | 2001-04-10 | Therapy for improving cognition |
HK02100158.6A HK1039745A1 (zh) | 1998-10-16 | 2002-01-10 | 用於改善識別的非典型抗精神病藥和乙酰膽碱酯酶 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98203454.8 | 1998-10-16 | ||
EP98203454 | 1998-10-16 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000023057A2 true WO2000023057A2 (en) | 2000-04-27 |
WO2000023057A3 WO2000023057A3 (en) | 2000-07-27 |
Family
ID=8234219
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1999/007804 WO2000023057A2 (en) | 1998-10-16 | 1999-10-12 | Atypical antiphsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
Country Status (20)
Country | Link |
---|---|
EP (1) | EP1121131A2 (pt) |
JP (1) | JP2002527469A (pt) |
KR (1) | KR20010072878A (pt) |
CN (1) | CN1367697A (pt) |
AU (1) | AU6472799A (pt) |
BG (1) | BG105302A (pt) |
BR (1) | BR9914419A (pt) |
CA (1) | CA2345767A1 (pt) |
EE (1) | EE200100136A (pt) |
HK (1) | HK1039745A1 (pt) |
HR (1) | HRP20010262A2 (pt) |
HU (1) | HUP0103781A3 (pt) |
ID (1) | ID28441A (pt) |
IL (1) | IL142588A0 (pt) |
NO (1) | NO20011403D0 (pt) |
PL (1) | PL348107A1 (pt) |
SK (1) | SK4592001A3 (pt) |
TR (1) | TR200101082T2 (pt) |
WO (1) | WO2000023057A2 (pt) |
ZA (1) | ZA200103081B (pt) |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004084905A2 (en) * | 2003-03-24 | 2004-10-07 | University Of Florida | Use of 5-ht2c receptor activity affecting compounds for treating idiopathic hyperhidrosis and associated conditions |
JP2005508975A (ja) * | 2001-10-30 | 2005-04-07 | ノバルティス アクチエンゲゼルシャフト | イロペリドンおよび星形ポリマーのデポー製剤 |
WO2005065645A2 (en) * | 2003-12-31 | 2005-07-21 | Actavis Group Hf | Donepezil formulations |
AU2002231766B2 (en) * | 2001-02-05 | 2005-12-22 | Novartis Ag | New use of iloperidone |
AU2006201188B2 (en) * | 2001-02-05 | 2007-11-15 | Novartis Ag | New use of iloperidone |
WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
WO2008065141A1 (en) | 2006-11-30 | 2008-06-05 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
WO2008104580A1 (en) | 2007-03-01 | 2008-09-04 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
WO2009011560A1 (es) * | 2007-07-16 | 2009-01-22 | Espinosa Abdala Leopoldo De Je | Composición farmacéutica que comprende la combinación de risperidone y donepezilo, y su uso en el tratamiento de trastornos psicóticos, como la esquizofrenia y demencias de tipo alzheimer |
WO2011100373A1 (en) | 2010-02-09 | 2011-08-18 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
WO2011110613A1 (en) | 2010-03-10 | 2011-09-15 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
US8227488B2 (en) | 2002-07-15 | 2012-07-24 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
WO2012123563A1 (en) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Benz imidazole derivatives as inhibitors of glutaminyl cyclase |
WO2014144801A1 (en) | 2013-03-15 | 2014-09-18 | Agenebio Inc. | Methods and compositions for improving cognitive function |
EP2865670A1 (en) | 2007-04-18 | 2015-04-29 | Probiodrug AG | Thiourea derivatives as glutaminyl cyclase inhibitors |
US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
US10159648B2 (en) | 2015-05-22 | 2018-12-25 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
EP3461819A1 (en) | 2017-09-29 | 2019-04-03 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200501962A (en) * | 2003-04-01 | 2005-01-16 | Novartis Ag | Use of carbamazepine derivatives for the treatment of agitation in dementia patients |
JP2008523058A (ja) * | 2004-12-10 | 2008-07-03 | アボット・ラボラトリーズ | 縮合ビシクロ複素環置換キヌクリジン誘導体 |
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EP0515301A2 (en) * | 1991-05-14 | 1992-11-25 | Ernir Snorrason | Improvements in benzodiazepine treatment by cholinesterterase inhibitors |
EP0879596A2 (en) * | 1991-05-14 | 1998-11-25 | Ernir Snorasson | Use of cholinesterase inhibitors to reduce benzodiazepine side effects |
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1999
- 1999-10-12 SK SK459-2001A patent/SK4592001A3/sk unknown
- 1999-10-12 HU HU0103781A patent/HUP0103781A3/hu unknown
- 1999-10-12 WO PCT/EP1999/007804 patent/WO2000023057A2/en not_active Application Discontinuation
- 1999-10-12 PL PL99348107A patent/PL348107A1/xx unknown
- 1999-10-12 CA CA002345767A patent/CA2345767A1/en not_active Abandoned
- 1999-10-12 CN CN99812184A patent/CN1367697A/zh active Pending
- 1999-10-12 IL IL14258899A patent/IL142588A0/xx unknown
- 1999-10-12 TR TR2001/01082T patent/TR200101082T2/xx unknown
- 1999-10-12 EP EP99952580A patent/EP1121131A2/en not_active Withdrawn
- 1999-10-12 ID IDW20010828A patent/ID28441A/id unknown
- 1999-10-12 BR BR9914419-0A patent/BR9914419A/pt not_active IP Right Cessation
- 1999-10-12 JP JP2000576832A patent/JP2002527469A/ja not_active Withdrawn
- 1999-10-12 EE EEP200100136A patent/EE200100136A/xx unknown
- 1999-10-12 AU AU64727/99A patent/AU6472799A/en not_active Abandoned
- 1999-10-12 KR KR1020017002286A patent/KR20010072878A/ko not_active Application Discontinuation
-
2001
- 2001-03-01 BG BG105302A patent/BG105302A/xx unknown
- 2001-03-20 NO NO20011403A patent/NO20011403D0/no not_active Application Discontinuation
- 2001-04-10 HR HR20010262A patent/HRP20010262A2/hr not_active Application Discontinuation
- 2001-04-12 ZA ZA200103081A patent/ZA200103081B/en unknown
-
2002
- 2002-01-10 HK HK02100158.6A patent/HK1039745A1/zh unknown
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EP0879596A2 (en) * | 1991-05-14 | 1998-11-25 | Ernir Snorasson | Use of cholinesterase inhibitors to reduce benzodiazepine side effects |
WO1999007378A1 (en) * | 1997-08-11 | 1999-02-18 | THE UNIVERSITY OF SOUTH FLORIDA A Corporation of the State of Florida | Nicotine antagonists for nicotine-responsive neuropsychiatric disorders |
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Cited By (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002231766B2 (en) * | 2001-02-05 | 2005-12-22 | Novartis Ag | New use of iloperidone |
AU2006201188B2 (en) * | 2001-02-05 | 2007-11-15 | Novartis Ag | New use of iloperidone |
JP2005508975A (ja) * | 2001-10-30 | 2005-04-07 | ノバルティス アクチエンゲゼルシャフト | イロペリドンおよび星形ポリマーのデポー製剤 |
US8815293B2 (en) | 2001-10-30 | 2014-08-26 | Novartis Ag | Organic compounds |
US7767230B2 (en) | 2001-10-30 | 2010-08-03 | Novartis Ag | Organic compounds |
US8227488B2 (en) | 2002-07-15 | 2012-07-24 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
US8614232B2 (en) | 2002-07-15 | 2013-12-24 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
US8293765B2 (en) | 2002-07-15 | 2012-10-23 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
WO2004084905A3 (en) * | 2003-03-24 | 2005-04-28 | Univ Florida | Use of 5-ht2c receptor activity affecting compounds for treating idiopathic hyperhidrosis and associated conditions |
WO2004084905A2 (en) * | 2003-03-24 | 2004-10-07 | University Of Florida | Use of 5-ht2c receptor activity affecting compounds for treating idiopathic hyperhidrosis and associated conditions |
WO2005065645A2 (en) * | 2003-12-31 | 2005-07-21 | Actavis Group Hf | Donepezil formulations |
WO2005065645A3 (en) * | 2003-12-31 | 2005-10-27 | Alpharma Inc | Donepezil formulations |
WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
WO2008065141A1 (en) | 2006-11-30 | 2008-06-05 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
EP2481408A2 (en) | 2007-03-01 | 2012-08-01 | Probiodrug AG | New use of glutaminyl cyclase inhibitors |
WO2008104580A1 (en) | 2007-03-01 | 2008-09-04 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
EP2865670A1 (en) | 2007-04-18 | 2015-04-29 | Probiodrug AG | Thiourea derivatives as glutaminyl cyclase inhibitors |
WO2009011560A1 (es) * | 2007-07-16 | 2009-01-22 | Espinosa Abdala Leopoldo De Je | Composición farmacéutica que comprende la combinación de risperidone y donepezilo, y su uso en el tratamiento de trastornos psicóticos, como la esquizofrenia y demencias de tipo alzheimer |
WO2011100373A1 (en) | 2010-02-09 | 2011-08-18 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
WO2011110613A1 (en) | 2010-03-10 | 2011-09-15 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
WO2012123563A1 (en) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Benz imidazole derivatives as inhibitors of glutaminyl cyclase |
US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
US10624875B2 (en) | 2012-11-14 | 2020-04-21 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
WO2014144801A1 (en) | 2013-03-15 | 2014-09-18 | Agenebio Inc. | Methods and compositions for improving cognitive function |
US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
US11160785B2 (en) | 2013-03-15 | 2021-11-02 | Agenebio Inc. | Methods and compositions for improving cognitive function |
US10159648B2 (en) | 2015-05-22 | 2018-12-25 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
US10925834B2 (en) | 2015-05-22 | 2021-02-23 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
EP3461819A1 (en) | 2017-09-29 | 2019-04-03 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
Also Published As
Publication number | Publication date |
---|---|
NO20011403L (no) | 2001-03-20 |
WO2000023057A3 (en) | 2000-07-27 |
HRP20010262A2 (en) | 2002-06-30 |
NO20011403D0 (no) | 2001-03-20 |
CN1367697A (zh) | 2002-09-04 |
IL142588A0 (en) | 2002-03-10 |
EP1121131A2 (en) | 2001-08-08 |
SK4592001A3 (en) | 2001-12-03 |
TR200101082T2 (tr) | 2001-09-21 |
PL348107A1 (en) | 2002-05-06 |
KR20010072878A (ko) | 2001-07-31 |
HK1039745A1 (zh) | 2002-05-10 |
ZA200103081B (en) | 2002-07-12 |
ID28441A (id) | 2001-05-24 |
EE200100136A (et) | 2002-06-17 |
BG105302A (en) | 2001-11-30 |
CA2345767A1 (en) | 2000-04-27 |
AU6472799A (en) | 2000-05-08 |
HUP0103781A3 (en) | 2003-09-29 |
HUP0103781A2 (hu) | 2002-03-28 |
BR9914419A (pt) | 2001-06-26 |
JP2002527469A (ja) | 2002-08-27 |
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