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WO2002072086A2 - Utilisation de l'epigallocatechin-3-gallate ou des derives de celui-ci dans la prevention et le traitement de maladies neurodegeneratives - Google Patents

Utilisation de l'epigallocatechin-3-gallate ou des derives de celui-ci dans la prevention et le traitement de maladies neurodegeneratives Download PDF

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Publication number
WO2002072086A2
WO2002072086A2 PCT/IT2002/000149 IT0200149W WO02072086A2 WO 2002072086 A2 WO2002072086 A2 WO 2002072086A2 IT 0200149 W IT0200149 W IT 0200149W WO 02072086 A2 WO02072086 A2 WO 02072086A2
Authority
WO
WIPO (PCT)
Prior art keywords
prevention
treatment
compound
use according
gallate
Prior art date
Application number
PCT/IT2002/000149
Other languages
English (en)
Other versions
WO2002072086A3 (fr
WO2002072086A8 (fr
Inventor
Hisanori Suzuki
Original Assignee
Consorzio Per Gli Studi Universitari
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
Application filed by Consorzio Per Gli Studi Universitari filed Critical Consorzio Per Gli Studi Universitari
Priority to AU2002247973A priority Critical patent/AU2002247973A1/en
Priority to EP02717053A priority patent/EP1411920A2/fr
Publication of WO2002072086A2 publication Critical patent/WO2002072086A2/fr
Publication of WO2002072086A8 publication Critical patent/WO2002072086A8/fr
Publication of WO2002072086A3 publication Critical patent/WO2002072086A3/fr

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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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to the use of a compound or its derivatives in the prevention and treatment of neurodegenerative diseases.
  • Neurodegenerative diseases are a significant problem at a socio-economic and health level. Reference may be made to Parkinson's disease and Alzheimer's disease, which are the main causes of dementia in the population of America and Europe, Creutzfeldt-Jacob syndrome caused by prion, and sleeping sickness caused by protozoa, including Trypanosoma brucei rhodensiense and Trypanosoma brucei gambiense. Sleeping sickness is one of the main causes of death in the African population.
  • Neurodegenerative disease are caused by the death of nerve cells, for example astrocytes, astroglia and neurons. These nerve cell degenerative processes are linked to the action of interferon- ⁇ (IFN- ⁇ ) (Galimberti D. et al. (1999) Biochem. Biophys . Res. Comm. 263, 251-256; Hunot S. et al. (1999) J. Neurosci. 19 3440-3447; Blasko I. et al. (1999) FAsEB J. 13 63-68; Suo Z. et al . (1998) Brain Res. 807 110-117; Delgado et al.(1998) J. Leukoc . Biol.
  • IFN- ⁇ interferon- ⁇
  • interferon- ⁇ is a cause of the onset of neurodegenerative diseases.
  • the present invention also relates to the use of compounds with the following formula (I), or its derivatives in the prevention and treatment of neurodegenerative diseases: (I)
  • the compounds according to the present invention are normally used in the in vitro experiments (see the examples) in doses of between 1 and 50 ⁇ M, preferably from 5 to 20 ⁇ M, in a DME culture, complete with 10% v/v of fetal bovine serum.
  • the inhibitory action of the compounds according to the present invention in the neurodegenerative processes described above is not attributable to the anti-oxidant , anti-inflammatory or anti-tumor activity of the compounds with formula (I).
  • Vitamin C was used as the anti-oxidant. This compound was not active even at a dose of 100 ⁇ M.
  • the anti-inflammatory compound used was hydrocortisone , a steroidal anti- inflammatory drug. This compound was also inactive, even at a dose of 100 ⁇ M.
  • the non-steroidal anti-inflammatory drug Ibuprofen was used, and was not active at a dose of 400 ⁇ M.
  • the anti-tumor compound used was cisplatin, which was not active at a dose of 17 ⁇ M.
  • the Applicant demonstrated that in order to inhibit STATl activity, the structure of the compounds with formula (I) is specific: neither gallic acid nor epigallo- catechin, which are the two polyphenolic components of EGCG, have a STATl inhibitory action.
  • Epigallocatechin-3-gallate is available on the market. It is the main ingredient of green tea extract. The methods for its isolation are indicated in Merck Index Edition 12 in the above-mentioned literature.
  • compositions containing the compounds according to the present invention contain the usual vehicles and excipients. They may be in the form of tablets, capsules or in formulations suitable for parenteral administration.
  • Effective doses of the compounds according to the present invention are those typically used in clinical medicine for epigallocatechin-3-gallate, or lower.
  • compositions containing the compounds according to the present invention can be prepared using techniques well known to experts in the field. See, for example, “Remington's Pharmaceutical Sciences 15 " ⁇ Ed.”
  • Activation of the STATl system also plays an important part in other diseases, such as asthma (Guo F.H. et al. J. Immunol. 2000, 164(11) 6970-80; Sampath e al . , J. Clin. Invest. 1999, 103(9) 1353-61), diabetes (Hill N.J. et al., Diabetes 2000 49(10) 1744-7; Sekine N. et al . J. Cell Physiol. 2000 184(1) 46-57), cardiovascular diseases (J. Biol. Chem. 2000 275 10002-8), obesity (Scarpace P.J et al., Neuropharmacology 2000, 39(10) 1872-9; Velloso L.A. et al. Cardiovasc. Res. 1998 272(26) 16216-23).
  • the products according to the present invention can also be used to treat these diseases.
  • STATl activation was measured by means of EMSA (elec- trophoretic mobility shift assay).
  • 10 tg of nuclear extract (Osborn, L., unkel, S., and Nabel, G.J. (1989) Proc . Natl . Acad. Sci . USA 86, 2336-2340) were incubated at room temperature for 20 minutes with [ 32 P]- double- stranded oligonucleotide ( 5 ' -gtegaCATTTCCCCGTAAATCg-3 ' ) (Wagner, B.J., Hayes, T.E.f Hoban, C.J., and Cochran, B.H. (1990) EMBO J. 9, 4477-4484).
  • the products were fraction- ated by means of electrophoresis on non-denaturing poly- acrylamide gel.
  • the intensity of the delayed bands was measured using the Phosphorimager system (Molecular Dynamics, Sunnyvale, CA, USA).
  • Example 1 was repeated, but with a concentration of 2 ⁇ M in the DMEM culture.
  • Example 1 was repeated, but with a concentration of 5 ⁇ M in the DMEM culture .
  • Example 1 was repeated, but with a concentration of 10 ⁇ M in the DMEM culture. The results are indicated in example 27.
  • Example 1 was repeated, but with a concentration of 20 ⁇ M in the DMEM culture.
  • Example 1 was repeated, but with a concentration of 50 ⁇ M in the DMEM culture.
  • hydrocortisone was used as a steroidal anti-inflammatory compound for comparison, in concentrations of 10 ⁇ M, 20 ⁇ M, 50 ⁇ M and 100 ⁇ M in the DMEM culture. The results are indicated in example 27.
  • ibuprofen was used as a non- steroidal anti-inflammatory compound for comparison, in concentrations of 10 ⁇ M, 50 ⁇ M, 100 ⁇ M, 200 ⁇ M and 400 ⁇ M in the DMEM culture .
  • cisplatin was used as an anti-tumor compound for comparison, in ⁇ M concentrations in the DMEM culture .
  • Examples 1 to 6 were repeated, but using epigallo- catechin as the active compound in place of EGCG.
  • Epigal- locatechin is one of the two polyphenolic components of EGCG. The results are indicated in example 27.
  • EXAMPLE 25 Comparison
  • Example 1 was repeated, but using Interleukin 6 (IL-1)
  • Interleukin 6 is a known STAT3 activator.
  • HeLa human cell lines human cervical tumor cells were also used; or HepG2 human liver tumor cell lines; or MCF7 human breast tumor cell lines.
  • the compound to be tested was EGCG (50 ⁇ M) , the com- pound with formula (I) according to the present invention.
  • IFN- ⁇ rapidly induces strong STATl activation in the U251 human glioblastoma cell line.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Selon cette invention, un composé d'épigallocatéchin-3-gallate représenté par la formule (1) ou des dérivés de celui-ci sont utilisés pour la prévention et le traitement de maladies neurodégénératives telles que par exemple la maladie de Parkinson, la maladie d'Alzheimer, le syndrome de Creutzfeldt-Jacob, la maladie du sommeil provoquée par des protozoaires, notamment le Trypanosoma brucei rhodensiense et le Trypanosoma brucei gambiense, ainsi que pour le traitement de l'asthme, du diabète, de maladies cardio-vasculaires, de l'obésité.
PCT/IT2002/000149 2001-03-12 2002-03-11 Utilisation de l'epigallocatechin-3-gallate ou des derives de celui-ci dans la prevention et le traitement de maladies neurodegeneratives WO2002072086A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2002247973A AU2002247973A1 (en) 2001-03-12 2002-03-11 Use of epigallocatechin-3-gallate or its derivatives in the prevention and treatment of neurodegenerative diseases
EP02717053A EP1411920A2 (fr) 2001-03-12 2002-03-11 Utilisation de l'epigallocatechin-3-gallate ou des derives de celui-ci dans la prevention et le traitement de maladies neurodegeneratives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT2001VR000031A ITVR20010031A1 (it) 2001-03-12 2001-03-12 Uso di epigallocatechin-3-gallato o suoi derivati nella profilassi e nel trattamento delle malattie neurodegenerative.
ITVR2001A000031 2001-03-12

Publications (3)

Publication Number Publication Date
WO2002072086A2 true WO2002072086A2 (fr) 2002-09-19
WO2002072086A8 WO2002072086A8 (fr) 2002-10-10
WO2002072086A3 WO2002072086A3 (fr) 2004-02-19

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Country Status (4)

Country Link
EP (1) EP1411920A2 (fr)
AU (1) AU2002247973A1 (fr)
IT (1) ITVR20010031A1 (fr)
WO (1) WO2002072086A2 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004047926A1 (fr) * 2002-11-28 2004-06-10 Dsm Ip Assets B.V. Nouvelles compositions nutraceutiques comprenant du gallate d'epigallocatechine et de la cetone de framboise
WO2004041257A3 (fr) * 2002-11-07 2004-08-05 Dsm Ip Assets Bv Compositions neutracetiques comprenant du gallate d'epigallocatechine
WO2005027661A1 (fr) * 2003-09-23 2005-03-31 Dsm Ip Assets B.V. Compositions permettant de traiter et de prevenir le diabete sucre
WO2005027901A1 (fr) * 2003-09-25 2005-03-31 Tel Aviv University Future Technology Development L.P. Compositions et methodes d'utilisation de ces compositions pour le traitement des maladies associees a la substance amyloide
US7491699B2 (en) 2002-12-09 2009-02-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures and methods of generating and using the same
US7504383B2 (en) 2003-01-07 2009-03-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures encapsulating a foreign material and method of manufacturing same
US7732479B2 (en) 2004-08-19 2010-06-08 Tel Aviv University Future Technology Development L.P. Compositions for treating amyloid associated diseases
EP1877422A4 (fr) * 2005-04-26 2011-08-10 Univ South Florida Activateurs d'alpha secretase de polyphenols de the vert et methodes d'utilisation associees
US20120035254A1 (en) * 2009-04-10 2012-02-09 Kao Corporation Inhibitor for elevation of gip level
US9309247B2 (en) 2013-03-20 2016-04-12 Lorus Therapeutics Inc. 2-substituted imidazo[4,5-D]phenanthroline derivatives and their use in the treatment of cancer
US10004828B2 (en) 2005-10-11 2018-06-26 Romat at Tel-Aviv University Ltd. Self-assembled Fmoc-ff hydrogels
WO2019236521A1 (fr) * 2018-06-07 2019-12-12 Avanti Biosciences, Inc. Procédés et formulations pour une administration intranasale

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005031362A2 (fr) 2003-10-02 2005-04-07 Ramot At Tel Aviv University Ltd. Nouveaux agents antibacteriens et procedes permettant de les identifier et de les utiliser
EP1781310B1 (fr) 2004-08-02 2015-10-14 Ramot at Tel Aviv University Ltd. Articles de nanostructures a base de peptides et leur procede de formation

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US5318986A (en) * 1989-10-19 1994-06-07 Mitsui Norin Co., Ltd. Method of inhibiting the activity of α-amylase
US5605929A (en) * 1992-05-27 1997-02-25 Arch Development Corp. Methods and compositions for inhibiting 5α-reductase activity
DE19627344A1 (de) * 1996-07-01 1998-01-08 Vitasyn Gmbh Entwicklung & Ver Therapeutisch wirksame bzw. gesundheitsfördernde Zubereitung aus definierten Polyphenolverbindungen
AU1289899A (en) * 1997-10-31 1999-05-24 Arch Development Corporation Methods and compositions for regulation of 5-alpha reductase activity
US5922756A (en) * 1998-02-14 1999-07-13 Chan; Marion Man-Ying Method of inhibiting nitric oxide synthase
ATE352306T1 (de) * 1998-07-31 2007-02-15 Meir S Sacks Ein präkursor der harnsäure und ein antioxidationsmittel enthaltende zusammensetzung und deren verwendung zur behandlung von neurodegenerativen erkrankungen
FI20000004A0 (fi) * 2000-01-03 2000-01-03 Slk Foundation Flavonoidilääke...

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004041257A3 (fr) * 2002-11-07 2004-08-05 Dsm Ip Assets Bv Compositions neutracetiques comprenant du gallate d'epigallocatechine
RU2340337C2 (ru) * 2002-11-28 2008-12-10 Дсм Ип Ассетс Б.В. Новые нутрицевтические композиции, включающие галлат эпигаллокатехина и кетон малины
WO2004047926A1 (fr) * 2002-11-28 2004-06-10 Dsm Ip Assets B.V. Nouvelles compositions nutraceutiques comprenant du gallate d'epigallocatechine et de la cetone de framboise
JP2006511505A (ja) * 2002-11-28 2006-04-06 ディーエスエム アイピー アセッツ ビー．ブイ． エピガロカテキンガレートおよびラズベリーケトンを含む新規なニュートラシューティカル組成物
US7491699B2 (en) 2002-12-09 2009-02-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures and methods of generating and using the same
US7504383B2 (en) 2003-01-07 2009-03-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures encapsulating a foreign material and method of manufacturing same
WO2005027661A1 (fr) * 2003-09-23 2005-03-31 Dsm Ip Assets B.V. Compositions permettant de traiter et de prevenir le diabete sucre
US7691420B2 (en) 2003-09-23 2010-04-06 Dsm Ip Assets B.V. Compositions for the treatment and prevention of diabetes mellitus
JP2007506732A (ja) * 2003-09-25 2007-03-22 テル アヴィヴ ユニヴァーシティ フューチャー テクノロジー ディヴェロップメント エル．ピー． アミロイド関連疾患を処置するための組成物及びその使用方法
WO2005027901A1 (fr) * 2003-09-25 2005-03-31 Tel Aviv University Future Technology Development L.P. Compositions et methodes d'utilisation de ces compositions pour le traitement des maladies associees a la substance amyloide
US7732479B2 (en) 2004-08-19 2010-06-08 Tel Aviv University Future Technology Development L.P. Compositions for treating amyloid associated diseases
EP1877422A4 (fr) * 2005-04-26 2011-08-10 Univ South Florida Activateurs d'alpha secretase de polyphenols de the vert et methodes d'utilisation associees
US20130261045A1 (en) * 2005-04-26 2013-10-03 University Of South Florida Green tea polyphenol alpha secretase enhancers and methods of use
US10004828B2 (en) 2005-10-11 2018-06-26 Romat at Tel-Aviv University Ltd. Self-assembled Fmoc-ff hydrogels
US20120035254A1 (en) * 2009-04-10 2012-02-09 Kao Corporation Inhibitor for elevation of gip level
US9309247B2 (en) 2013-03-20 2016-04-12 Lorus Therapeutics Inc. 2-substituted imidazo[4,5-D]phenanthroline derivatives and their use in the treatment of cancer
WO2019236521A1 (fr) * 2018-06-07 2019-12-12 Avanti Biosciences, Inc. Procédés et formulations pour une administration intranasale

Also Published As

Publication number Publication date
ITVR20010031A1 (it) 2002-09-12
WO2002072086A3 (fr) 2004-02-19
ITVR20010031A0 (it) 2001-03-12
AU2002247973A1 (en) 2002-09-24
EP1411920A2 (fr) 2004-04-28
WO2002072086A8 (fr) 2002-10-10

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