WO2000023057A2 - Therapie visant a ameliorer la cognition - Google Patents

Therapie visant a ameliorer la cognition Download PDF

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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
Application number
PCT/EP1999/007804
Other languages
English (en)
Other versions
WO2000023057A3 (fr
Inventor
Paul Leonce Irma De Nijs
Wim Louis Julien Parys
Original Assignee
Janssen Pharmaceutica N.V.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to IL14258899A priority Critical patent/IL142588A0/xx
Priority to AU64727/99A priority patent/AU6472799A/en
Priority to HU0103781A priority patent/HUP0103781A3/hu
Priority to EP99952580A priority patent/EP1121131A2/fr
Priority to BR9914419-0A priority patent/BR9914419A/pt
Priority to EEP200100136A priority patent/EE200100136A/xx
Priority to KR1020017002286A priority patent/KR20010072878A/ko
Priority to SK459-2001A priority patent/SK4592001A3/sk
Application filed by Janssen Pharmaceutica N.V. filed Critical Janssen Pharmaceutica N.V.
Priority to JP2000576832A priority patent/JP2002527469A/ja
Priority to CA002345767A priority patent/CA2345767A1/fr
Priority to PL99348107A priority patent/PL348107A1/xx
Publication of WO2000023057A2 publication Critical patent/WO2000023057A2/fr
Publication of WO2000023057A3 publication Critical patent/WO2000023057A3/fr
Priority to BG105302A priority patent/BG105302A/xx
Priority to NO20011403A priority patent/NO20011403L/no
Priority to HR20010262A priority patent/HRP20010262A2/hr
Priority to HK02100158.6A priority patent/HK1039745A1/zh

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.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

Cette invention a trait à des compositions pharmaceutiques renfermant un excipient et, comme premier ingrédient actif, un agent antipsychotique atypique (I), ainsi que, comme second ingrédient actif, un inhibiteur de l'acétylcholinestérase (II), chacun sous des quantités produisant un effet thérapeutique bénéfique chez des patients atteints de psychose, de la maladie d'Alzheimer ou de démences connexes. Cet effet thérapeutique bénéfique peut être un effet de synergie sur le fonctionnement cognitif de patients atteints de la maladie d'Alzheimer ou de démences connexes, être prophylactique, évitant une dégradation ultérieure de la cognition chez ces patients, ou encore atténuant les réactions indésirables dues à l'action sur l'un des ingrédients actifs des autres ingrédients actifs.
PCT/EP1999/007804 1998-10-16 1999-10-12 Therapie visant a ameliorer la cognition WO2000023057A2 (fr)

Priority Applications (15)

Application Number Priority Date Filing Date Title
JP2000576832A JP2002527469A (ja) 1998-10-16 1999-10-12 認識を改良するための療法
AU64727/99A AU6472799A (en) 1998-10-16 1999-10-12 Therapy for improving cognition
CA002345767A CA2345767A1 (fr) 1998-10-16 1999-10-12 Therapie visant a ameliorer la 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
KR1020017002286A KR20010072878A (ko) 1998-10-16 1999-10-12 인식을 개선하기 위한 아세틸콜린에스테라제 억제제와배합된 비정형 항정신병제
SK459-2001A SK4592001A3 (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
HU0103781A HUP0103781A3 (en) 1998-10-16 1999-10-12 Pharmaceutical compositions comprising atypical antiphsychotic agent in combination with acetylcholinesterase inhibitor for improving cognition
EP99952580A EP1121131A2 (fr) 1998-10-16 1999-10-12 Therapie visant a ameliorer la cognition
PL99348107A PL348107A1 (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 NO20011403L (no) 1998-10-16 2001-03-20 Terapi for å 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 1998-10-16
EP98203454.8 1998-10-16

Publications (2)

Publication Number Publication Date
WO2000023057A2 true WO2000023057A2 (fr) 2000-04-27
WO2000023057A3 WO2000023057A3 (fr) 2000-07-27

Family

ID=8234219

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/007804 WO2000023057A2 (fr) 1998-10-16 1999-10-12 Therapie visant a ameliorer la cognition

Country Status (20)

Country Link
EP (1) EP1121131A2 (fr)
JP (1) JP2002527469A (fr)
KR (1) KR20010072878A (fr)
CN (1) CN1367697A (fr)
AU (1) AU6472799A (fr)
BG (1) BG105302A (fr)
BR (1) BR9914419A (fr)
CA (1) CA2345767A1 (fr)
EE (1) EE200100136A (fr)
HK (1) HK1039745A1 (fr)
HR (1) HRP20010262A2 (fr)
HU (1) HUP0103781A3 (fr)
ID (1) ID28441A (fr)
IL (1) IL142588A0 (fr)
NO (1) NO20011403L (fr)
PL (1) PL348107A1 (fr)
SK (1) SK4592001A3 (fr)
TR (1) TR200101082T2 (fr)
WO (1) WO2000023057A2 (fr)
ZA (1) ZA200103081B (fr)

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004084905A2 (fr) * 2003-03-24 2004-10-07 University Of Florida Methodes de traitement de l'hyperhidrose idiopathique et de pathologies associees
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 (fr) * 2003-12-31 2005-07-21 Actavis Group Hf Formulations de donepezil
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 (fr) 2006-11-09 2008-05-15 Probiodrug Ag Dérivés 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one utiles en tant qu' inhibiteurs de la glutaminyl-cyclase dans le traitement des ulcères, du cancer et d'autres maladies
WO2008065141A1 (fr) 2006-11-30 2008-06-05 Probiodrug Ag Nouveaux inhibiteurs de glutaminylcyclase
WO2008104580A1 (fr) 2007-03-01 2008-09-04 Probiodrug Ag Nouvelle utilisation d'inhibiteurs de la glutaminyl cyclase
WO2009011560A1 (fr) * 2007-07-16 2009-01-22 Espinosa Abdala Leopoldo De Je Composition pharmaceutique combinant de la rispéridone et du donepezile, et utilisation de celle-ci dans le traitement de troubles psychotiques tels que la schizophrénie et la démence du type alzheimer
WO2011100373A1 (fr) 2010-02-09 2011-08-18 The Johns Hopkins University Procédés et compositions pour améliorer la fonction cognitive
WO2011107530A2 (fr) 2010-03-03 2011-09-09 Probiodrug Ag Nouveaux inhibiteurs
WO2011110613A1 (fr) 2010-03-10 2011-09-15 Probiodrug Ag Inhibiteurs hétérocycliques de la glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (fr) 2010-04-21 2011-10-27 Probiodrug Ag Nouveaux inhibiteurs
US8227488B2 (en) 2002-07-15 2012-07-24 Novartis Ag Injectable depot formulation comprising crystals of iloperidone
WO2012123563A1 (fr) 2011-03-16 2012-09-20 Probiodrug Ag Dérivés de benzimidazole en tant qu'inhibiteurs de la glutaminyl cyclase
WO2014144801A1 (fr) 2013-03-15 2014-09-18 Agenebio Inc. Procédés et compositions pour améliorer la fonction cognitive
EP2865670A1 (fr) 2007-04-18 2015-04-29 Probiodrug AG Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase
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 (fr) 2017-09-29 2019-04-03 Probiodrug AG Inhibiteurs de la 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)

* Cited by examiner, † Cited by third party
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
EP1824848A1 (fr) * 2004-12-10 2007-08-29 Abbott Laboratories Derives polycycliques de quinuclidine substitues par un bicycloheterocycle condense

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Cited By (31)

* Cited by examiner, † Cited by third party
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 (fr) * 2003-03-24 2005-04-28 Univ Florida Methodes de traitement de l'hyperhidrose idiopathique et de pathologies associees
WO2004084905A2 (fr) * 2003-03-24 2004-10-07 University Of Florida Methodes de traitement de l'hyperhidrose idiopathique et de pathologies associees
WO2005065645A2 (fr) * 2003-12-31 2005-07-21 Actavis Group Hf Formulations de donepezil
WO2005065645A3 (fr) * 2003-12-31 2005-10-27 Alpharma Inc Formulations de donepezil
WO2008055945A1 (fr) 2006-11-09 2008-05-15 Probiodrug Ag Dérivés 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one utiles en tant qu' inhibiteurs de la glutaminyl-cyclase dans le traitement des ulcères, du cancer et d'autres maladies
WO2008065141A1 (fr) 2006-11-30 2008-06-05 Probiodrug Ag Nouveaux inhibiteurs de glutaminylcyclase
EP2481408A2 (fr) 2007-03-01 2012-08-01 Probiodrug AG Nouvelle utilisation d'inhibiteurs glutaminyle cyclase
WO2008104580A1 (fr) 2007-03-01 2008-09-04 Probiodrug Ag Nouvelle utilisation d'inhibiteurs de la glutaminyl cyclase
EP2865670A1 (fr) 2007-04-18 2015-04-29 Probiodrug AG Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase
WO2009011560A1 (fr) * 2007-07-16 2009-01-22 Espinosa Abdala Leopoldo De Je Composition pharmaceutique combinant de la rispéridone et du donepezile, et utilisation de celle-ci dans le traitement de troubles psychotiques tels que la schizophrénie et la démence du type alzheimer
WO2011100373A1 (fr) 2010-02-09 2011-08-18 The Johns Hopkins University Procédés et compositions pour améliorer la fonction cognitive
WO2011107530A2 (fr) 2010-03-03 2011-09-09 Probiodrug Ag Nouveaux inhibiteurs
WO2011110613A1 (fr) 2010-03-10 2011-09-15 Probiodrug Ag Inhibiteurs hétérocycliques de la glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (fr) 2010-04-21 2011-10-27 Probiodrug Ag Nouveaux inhibiteurs
WO2012123563A1 (fr) 2011-03-16 2012-09-20 Probiodrug Ag Dérivés de benzimidazole en tant qu'inhibiteurs de la 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 (fr) 2013-03-15 2014-09-18 Agenebio Inc. Procédés et compositions pour améliorer la fonction cognitive
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 (fr) 2017-09-29 2019-04-03 Probiodrug AG Inhibiteurs de la glutaminyl-cyclase

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Publication number Publication date
ID28441A (id) 2001-05-24
AU6472799A (en) 2000-05-08
ZA200103081B (en) 2002-07-12
HRP20010262A2 (en) 2002-06-30
CA2345767A1 (fr) 2000-04-27
NO20011403D0 (no) 2001-03-20
SK4592001A3 (en) 2001-12-03
CN1367697A (zh) 2002-09-04
KR20010072878A (ko) 2001-07-31
HUP0103781A3 (en) 2003-09-29
BG105302A (en) 2001-11-30
EE200100136A (et) 2002-06-17
HUP0103781A2 (hu) 2002-03-28
NO20011403L (no) 2001-03-20
JP2002527469A (ja) 2002-08-27
EP1121131A2 (fr) 2001-08-08
HK1039745A1 (zh) 2002-05-10
TR200101082T2 (tr) 2001-09-21
WO2000023057A3 (fr) 2000-07-27
IL142588A0 (en) 2002-03-10
PL348107A1 (en) 2002-05-06
BR9914419A (pt) 2001-06-26

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