ITVR20010031A1 - USE OF EPIGALLOCATECHIN-3-GALLATO OR ITS DERIVATIVES IN THE PROPHYLAXIS AND TREATMENT OF NEURODEGENERATIVE DISEASES. - Google Patents
USE OF EPIGALLOCATECHIN-3-GALLATO OR ITS DERIVATIVES IN THE PROPHYLAXIS AND TREATMENT OF NEURODEGENERATIVE DISEASES. Download PDFInfo
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- ITVR20010031A1 ITVR20010031A1 IT2001VR000031A ITVR20010031A ITVR20010031A1 IT VR20010031 A1 ITVR20010031 A1 IT VR20010031A1 IT 2001VR000031 A IT2001VR000031 A IT 2001VR000031A IT VR20010031 A ITVR20010031 A IT VR20010031A IT VR20010031 A1 ITVR20010031 A1 IT VR20010031A1
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Classifications
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- 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
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- 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
Description
Descrizione del trovato avente per titolo: Description of the invention having as title:
"USO DI EPIGALLOCATECHIN-3-GALLATO O SUOI DERIVATI NELLA PROFILASSI E NEL TRATTAMENTO DELLE MALATTIE NEURODEGENERATIVE" "USE OF EPIGALLOCATECHIN-3-GALLATE OR ITS DERIVATIVES IN THE PROPHYLAXIS AND TREATMENT OF NEURODEGENERATIVE DISEASES"
CAMPO DI APPLICAZIONE FIELD OF APPLICATION
La presente invenzione riguarda l'uso di un composto o suoi derivati nella profilassi e nel trattamento delle malattie neurodegenerative. The present invention relates to the use of a compound or its derivatives in the prophylaxis and treatment of neurodegenerative diseases.
Le malattie neurodegenerative costituiscono un problema rilevante a livello socio-economico e sanitario. Si possono citare il morbo di Parkinson e il morbo di Alzheimer, che sono le principali cause di demenza nella popolazione americana ed europea, la sindrome di Creutzfeldt-Jacob causata dal prione, e la malattia del sonno causata da protozoi, tra cui il Tripanosoma brucei rhodensiense e il Trypanosoma brucei gambiense. La malattia del sonno rappresenta una delle cause principali della mortalità nella popolazione africana. Neurodegenerative diseases are a significant socio-economic and health problem. Parkinson's disease and Alzheimer's disease, which are the main causes of dementia in the American and European population, Creutzfeldt-Jacob syndrome caused by the prion, and sleeping sickness caused by protozoa, including Trypanosoma brucei, can be cited. rhodensiense and Trypanosoma brucei gambiense. Sleeping sickness is a major cause of mortality in the African population.
I farmaci attualmente disponibili per il trattamento delle malattie neurodegenerative non consentono di realizzare terapie efficaci e pertanto il trattamento farmacologico di queste malattie è insoddisfacente. The drugs currently available for the treatment of neurodegenerative diseases do not allow for effective therapies and therefore the pharmacological treatment of these diseases is unsatisfactory.
Le malattie neurodegenerative sono causate dalla morte delle cellule nervose, come ad es. astrociti, astroglia e neuroni. Questi processi degenerativi delle cellule nervose sono correlati all'azione dell 'interferone-γ (IFN-γ) (Galimberti D. et al. (1999) Biochem. Biophys. Res. Comm. Neurodegenerative diseases are caused by the death of nerve cells, such as eg. astrocytes, astroglia and neurons. These degenerative processes of nerve cells are related to the action of interferon-γ (IFN-γ) (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 ai.(1998) J. Leukoc . Biol. 63 740-745; Rossi F, Bianchini E. (1996) Biochem. Biophys. Res. Co~un. 225 474-478; MedaL . et al (1995) Nature 374, 647-650) che mediante l'attivazione di un fattore nucleare STATI (Signal transducers and activators of transcr iption 1), svolge le varie azioni pleiotropiche (Boehm, U. et al.(1997) Annu . Rev . Immunol. 15, 749-795; Kordula T. et al. (1998) J. Biol. Chem. 273 4112-4118; Kitamura Y. et al Neurosci. Lett. 237 17-20). Tra le diverse azioni dell'interferone γ nella cellula è particolarmente importante la sua capacità di modulare l'espressione di un enzima, l'ossido nitrico sintasi inducibile (iNOS), che producendo grandi quantità di NO può indurre la morte delle cellule nervose. Questo spiega perché l'interferone γ sia una causa dell'insorgenza di patologie neuro degenerative. 263, 251-256; Hunot S. et al. (1999) J. Neurosci. 19 3440-3447; Blasko I. et al. (1999) FAsEB J. 13 63-68; His Z. et al. (1998) Brain Res. 807 110-117; Delgado et al. (1998) J. Leukoc. Biol. 63 740-745; Rossi F, Bianchini E. (1996) Biochem. Biophys. Res. Co ~ a. 225 474-478; MedaL. et al (1995) Nature 374, 647-650) which, through the activation of a nuclear factor STATES (Signal transducers and activators of transcr iption 1), carries out the various pleiotropic actions (Boehm, U. et al. (1997) Annu . Rev. Immunol. 15, 749-795; Kordula T. et al. (1998) J. Biol. Chem. 273 4112-4118; Kitamura Y. et al Neurosci. Lett. 237 17-20). Among the various actions of interferon γ in the cell, its ability to modulate the expression of an enzyme, inducible nitric oxide synthase (iNOS), which produces large quantities of NO can induce the death of nerve cells, is particularly important. This explains why interferon γ is a cause of the onset of neuro degenerative diseases.
Era sentita l'esigenza di avere a disposizione farmaci per la profilassi ed il trattamento delle malattie neuro degenerative, particolarmente efficaci nell'inibizione dell'attivazione dello STATI. The need was felt to have available drugs for the prophylaxis and treatment of neuro degenerative diseases, particularly effective in inhibiting the activation of the STATE.
Questo problema tecnico è stato risolto mediante l'impiego del composto epigallocatechin-3-gallato , o suoi derivati . This technical problem has been solved by using the compound epigallocatechin-3-gallate, or its derivatives.
Costituisce pertanto un oggetto della presente invenzione l'uso nella profilassi e nel trattamento delle malattie neuro degenerative di composti della seguente formula (I), o suoi derivati: Therefore, an object of the present invention is the use in the prophylaxis and treatment of neurodegenerative diseases of compounds of the following formula (I), or its derivatives:
L'attività dei composti di formula (I) nelle patologie neurodegenerative è stata dimostrata nella presente invenzione mediante un modello sperimentale in vitro, utilizzando cellule di glioblastoma umano U251. In questo esperimento è stato dimostrato che, ad esempio utilizzando come composto dell'invenzione epigallocatechin-3 -gallato (EGCG), in concentrazione 5 μΜ, i composti dell'invenzione sono efficaci nel trattamento delle patologie neurodegenerative, infatti inibiscono il 50 % dell ' attivazione massimale di STATI indotta dall ' interferone Y-I composti dell'invenzione vengono utilizzati negli esperimenti in vitro (si vedano gli esempi) in genere in dosi comprese tra 1 e 50 μΜ, preferibilmente da 5 a 20 μΜ, in mezzo di coltura DME, completato con 10% v/v di siero di feto bovino. The activity of the compounds of formula (I) in neurodegenerative pathologies has been demonstrated in the present invention by means of an in vitro experimental model, using human glioblastoma U251 cells. In this experiment it has been shown that, for example by using epigallocatechin-3 -gallate (EGCG) as the compound of the invention, in a concentration of 5 μΜ, the compounds of the invention are effective in the treatment of neurodegenerative diseases, in fact they inhibit 50% of the maximal activation of STATES induced by interferon Y-The compounds of the invention are used in in vitro experiments (see examples) generally in doses ranging from 1 to 50 μΜ, preferably from 5 to 20 μΜ, in DME culture medium, completed with 10% v / v of bovine fetus serum.
E' stato trovato dal Richiedente che in generale l'inibizione di STATI avviene in modo dose dipendente. It has been found by the Applicant that in general the inhibition of STATES occurs in a dose dependent manner.
L'azione inibitoria dei composti dell'invenzione nei processi neurodegenerativi sopra descritti non è attribuibile all'attività antiossidante, antiinfiammatoria o antitumorale dei composti di formula (I). Infatti utilizzando cellule di glioblastoma umano U251 è stato dimostrato che utilizzando farmaci antiossidanti, antiinfiammatori o antitumorali, non sono in grado di inibire l'attivazione di STATI indotta dall'interferone γ (si vedano gli esempi). Come farmaci ad attività antiossidante è stata utilizzata la vitamina C. Questo composto non è risultato attivo neanche alla dose 100 μΜ. Come composti antiinf iammatori è stato utilizzato un antiinfiammatorio steroideo, Idrocortisone . Anche questo composto non è risultato attivo neanche alla dose 100 μΜ. Ε' stato utilizzato anche un antiinf iammatorio non steroideo, Ibuprofen, che non è risultato attivo alla dose 400 μM. Come composto antitumorale è stato utilizzato il cisplatino, che non è risultato attivo àlla dose 17 μΜ. The inhibitory action of the compounds of the invention in the neurodegenerative processes described above is not attributable to the antioxidant, anti-inflammatory or antitumor activity of the compounds of formula (I). In fact, using human glioblastoma U251 cells it has been shown that using antioxidant, anti-inflammatory or anticancer drugs, they are not able to inhibit the activation of STATES induced by interferon γ (see examples). Vitamin C was used as drugs with antioxidant activity. This compound was not active even at the 100 μΜ dose. An anti-inflammatory steroid, Hydrocortisone, was used as anti-inflammatory compounds. Even this compound was not active even at the 100 μΜ dose. A non-steroidal anti-inflammatory drug, Ibuprofen, was also used, which was not active at the 400 μM dose. Cisplatin was used as an anticancer compound, which was not active at the 17 μΜ dose.
Ε' stato dimostrato dal Richiedente che per inibire l'attività di STATI la struttura dei composti di formula <(>I<) >è specifica: infatti né l'acido gallico né 1 'epigallocatechina, che sono i due componenti polifenolici di EGCG, posseggono attività inibente su STATI. It has been demonstrated by the Applicant that in order to inhibit the activity of STATES, the structure of the compounds of formula <(> I <)> is specific: in fact, neither gallic acid nor epigallocatechin, which are the two polyphenolic components of EGCG, they possess inhibitory activity on STATES.
L 'epigallocatechin-3-gallato è disponibile sul mercato. Esso è il componente principale dell'estratto di tè verde, i metodi per 1'isolamento sono indicati nel Merck Index 12a Ed. nella letteratura ivi citata. Epigallocatechin-3-gallate is available on the market. It is the main component of green tea extract, the methods for isolation are indicated in the Merck Index 12th Ed. In the literature cited therein.
Le formulazioni farmaceutiche contenenti i composti dell'invenzione contengono gli usuali veicoli ed eccipienti. Possono essere nella forma compresse, capsule o in formulazioni adatte per la somministrazione parenterale. The pharmaceutical formulations containing the compounds of the invention contain the usual carriers and excipients. They can be in tablet, capsule form or in formulations suitable for parenteral administration.
Le dosi efficaci dei composti dell'invenzione sono quelle tipiche, o inferiori, utilizzate in clinica per epigallocatechin-3-gallato . The effective doses of the compounds of the invention are those typical, or lower, used in the clinic for epigallocatechin-3-gallate.
Le formulazioni farmaceutiche contenenti i composti dell 'invenzione si possono preparare con tecniche ben note all'esperto del ramo. Si veda ad es. il volume "Remington's Pharmaceutical Sciences 15<th >Ed." The pharmaceutical formulations containing the compounds of the invention can be prepared with techniques well known to those skilled in the art. See e.g. the volume "Remington's Pharmaceutical Sciences 15 <th> Ed."
L'attivazione del sistema STATI svolge un ruolo rilevante anche in altre patologie quali ad esempio asma (Guo F.H. et al. J. Immunol. 2000, 164(11) 6970-80; Sampath e al., J. Clin. Invest. 1999, 103(9) 1353-61), diabete (Hill N.J.et al., Diabetes 200049(10) 1744-7; Sekine N. et al. J. Celi Physiol. 2000 184(1) 46-57), malattie cardiovascolari (J. Biol. Chem. 2000275 10002-8), obesità (Scarpace P.J et al., Neuropharmacology 2000, 39(10) 1872-9; Velloso L.A. et al. Cardiovasc. Res . 1998 272(26) 16216-23). I prodotti dell'invenzione possono essere usati anche nella terapia di queste patologie. The activation of the STATE system also plays an important role in other pathologies such as for example asthma (Guo F.H. et al. J. Immunol. 2000, 164 (11) 6970-80; Sampath et al., J. Clin. Invest. 1999 , 103 (9) 1353-61), diabetes (Hill N.J.et al., Diabetes 200049 (10) 1744-7; Sekine N. et al. J. Celi Physiol. 2000 184 (1) 46-57), cardiovascular disease (J. Biol. Chem. 2000275 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 of the invention can also be used in the therapy of these pathologies.
I seguenti esempi illustrano l'invenzione ma non ne limitano lo scopo. The following examples illustrate the invention but do not limit its scope.
ESEMPIO 1 EXAMPLE 1
La linea cellulare di glioblastoma umano U251 è stata coltivata, a 37°C, in mezzo di coltura DMEM 12-614(Dulbecco's midified eagle medium BioWhittaker Co.) completato con 10% di siero del feto bovino. Il siero è stato eliminato 4 ore prima del trattamento con 1'interferone-γ (250 U/ml). La concentrazione dell ' epigallo catechin gallato (R = H, indicato con EGCG) utilizzato era di 1 μΜ in mezzo dì coltura DMEM. The human glioblastoma cell line U251 was cultured, at 37 ° C, in DMEM 12-614 culture medium (Dulbecco's midified eagle medium BioWhittaker Co.) supplemented with 10% bovine fetal serum. The serum was eliminated 4 hours before treatment with interferon-γ (250 U / ml). The concentration of the epigallium catechin gallate (R = H, indicated with EGCG) used was 1 μΜ in DMEM culture medium.
L'attivazione dello STATI è stata misurata mediante 1 'EMSA (electrophoretic mobility shift assay). 10 tg di estratto nucleare (Osborn, L., Kunkel, S., and Nabel, G.J. (1989) Proc. Nati . Acad. Sci . USA 86, 2336-2340) sono stati incubati a temperatura ambiente per 20 min con [ <32>]-oligonucleotide a doppio filamento (5'-gtegaCATTTCCCCGTAAATCg- 3 ' ) (Wagner, B.J., Hayes, T.E.f Hoban, C.J., and Cochran, B.H. (1990) EMBO J. 9, 4477-4484). I prodotti sono stati frazionati mediante l'elettroforesi sul gel di polìacrilamide in condizioni non-denaturanti . L'intensità delle bande ritardate è stata misurata con Phosphorimager (Molecular Dynamics, Sunnyvale, CA, USA). STA activation was measured by the electrophoretic mobility shift assay (EMSA). 10 tg of nuclear extract (Osborn, L., Kunkel, S., and Nabel, G.J. (1989) Proc. Nati. Acad. Sci. USA 86, 2336-2340) were incubated at room temperature for 20 min with [< 32>] - 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 fractionated by electrophoresis on the polyacrylamide gel under non-denaturing conditions. The intensity of the delayed bands was measured with Phosphorimager (Molecular Dynamics, Sunnyvale, CA, USA).
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPIO 2 EXAMPLE 2
E' stato ripetuto l'esempio 1 ma concentrazione di 2 μM in mezzo di coltura DMEM. Example 1 was repeated but concentration of 2 μM in DMEM culture medium.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPIO 3 EXAMPLE 3
E' stato ripetuto l'esempio 1 ma utilizzando la concentrazione di 5 μΜ in mezzo di coltura DMEM. Example 1 was repeated but using the 5 μΜ concentration in DMEM culture medium.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPIO 4 EXAMPLE 4
E' stato ripetuto l'esempio 1 ma utilizzando la concentrazione di 10 μΜ in mezzo di coltura DMEM. Example 1 was repeated but using the concentration of 10 μΜ in DMEM culture medium.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPIO 5 EXAMPLE 5
E' stato ripetuto l'esempio 1 ma utilizzando la concentrazione di 20 μΜ in mezzo di coltura DMEM. Example 1 was repeated but using the concentration of 20 μΜ in DMEM culture medium.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPIO 6 EXAMPLE 6
E' stato ripetuto l'esempio 1 ma utilizzando la concentrazione di 50 μM in mezzo di coltura DMEM. Example 1 was repeated but using the 50 μM concentration in DMEM culture medium.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPI 7-10 confronto con un composto antiossidante EXAMPLES 7-10 comparison with an antioxidant compound
In questi esempi è stata utilizzata come composto antiossidante di confronto la vitamina C in concentrazioni di 10 μΜ 20 μΜ, 50 μΜ e 100 μΜ in mezzo di coltura DME. In these examples, vitamin C in concentrations of 10 μΜ 20 μΜ, 50 μΜ and 100 μΜ in DME culture medium was used as the comparator antioxidant compound.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPI 11-14 EXAMPLES 11-14
Confronto con un antiinfiammatorio steroideo Comparison with a steroid anti-inflammatory
In questi esempi è stata utilizzata come composto di confronto un antiinfiammatorio steroideo Idrocortisone in concentrazioni di 10 μΜ 20 μΜ, 50 μΜ e 100 aM in mezzo di coltura DMEM. In these examples, a steroidal anti-inflammatory hydrocortisone in concentrations of 10 μΜ 20 μΜ, 50 μΜ and 100 aM in DMEM culture medium was used as the comparison compound.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPI 15-19 EXAMPLES 15-19
confronto con un &ntiinfiammatorio non steroideo comparison with a non-steroidal anti-inflammatory & nti-inflammatory
In questi esempi è stata utilizzata come composto di confronto un antiinfiammatorio non-steroideo ibuprofene in concentrazioni di 10 μΜ, 50 μΜ, 100 μΜ, 200 μΜ e 400 μΜ in mezzo di coltura DMEM. In these examples, a non-steroidal anti-inflammatory ibuprofen in concentrations of 10 μΜ, 50 μΜ, 100 μΜ, 200 μΜ and 400 μΜ in DMEM culture medium was used as the comparison compound.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPI 20-23 EXAMPLES 20-23
confronto con un antitumorale comparison with an antitumor
In questi esempi è stata utilizzato come composto di confronto il composto anti tumorale ci splatino in concentrazioni di μΜ in mezzo di coltura DMEM. In these examples, the anti-tumor compound ci splatin in concentrations of μΜ in DMEM culture medium was used as the comparison compound.
I risultati sono riportati nell'esempio 27. The results are reported in Example 27.
ESEMPIO 24 Confronto EXAMPLE 24 Comparison
Sono stati ripetuti gli esempi da 1 a 6 ma utilizzando come composto attivo al posto di EGCG, 1 ' epigallocatechina, che è uno dei due componenti polifenolici di EGCG . I risultati sono riportati nell ' esempio 27 . Examples 1 to 6 were repeated but using epigallocatechin, which is one of the two polyphenolic components of EGCG, as the active compound in place of EGCG. The results are reported in example 27.
ESEMPIO 25 Confronto EXAMPLE 25 Comparison
Sono stati ripetuti gli esempi da 1 a 6 ma utilizzando come composto attivo al posto di EGCG, acido gallico, che è il secondo componente polifenolico di EGCG. I risultati sono riportati nell'esempio 27. Examples 1 to 6 were repeated but using gallic acid, which is the second polyphenolic component of EGCG, as the active compound in place of EGCG. The results are reported in Example 27.
ESEMPIO 26 Confronto EXAMPLE 26 Comparison
E' stato ripetuto l'esempio 1 ma utilizzando invece di IFN-1 come attivatore dello STATi, Interleukina 6 (IL-6) che è un attivatore noto dello STAT3 e utilizzando linee cellulari umane HeLa (cellule di carcinoma cervicale umano); oppure linee cellulari di epatocarcinomaumano HepG2; oppure linee cellulari di carcinoma mammario umano MCF7. Example 1 was repeated but using instead of IFN-1 as STATi activator, Interleukin 6 (IL-6) which is a known activator of STAT3 and using human HeLa cell lines (human cervical cancer cells); or HepG2 human hepatocellular carcinoma cell lines; or MCF7 human breast cancer cell lines.
Come composto da testare è stato utilizzato EGCG (50 μΜ) composto di formula (I) dell'invenzione. EGCG (50 μΜ) compound of formula (I) of the invention was used as the compound to be tested.
ESEMPIO 27 Risultati EXAMPLE 27 Results
IFN-γ induce rapidamente una forte attivazione di STATI nella linea cellulare umana di glioblastoma U251. IFN-γ rapidly induces strong STA activation in the human glioblastoma U251 cell line.
TUtti i composti dell'invenzione e quelli di confronto vengono somministrati alla coltura delle cellule U251 mezz'ora prima del trattamento con IFN-γ. All the compounds of the invention and the comparative ones are administered to the culture of the U251 cells half an hour before the treatment with IFN-γ.
Claims (6)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001VR000031A ITVR20010031A1 (en) | 2001-03-12 | 2001-03-12 | USE OF EPIGALLOCATECHIN-3-GALLATO OR ITS DERIVATIVES IN THE PROPHYLAXIS AND TREATMENT OF NEURODEGENERATIVE DISEASES. |
| PCT/IT2002/000149 WO2002072086A2 (en) | 2001-03-12 | 2002-03-11 | Use of epigallocatechin-3-gallate or its derivatives in the prevention and treatment of neurodegenerative diseases |
| 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 (en) | 2001-03-12 | 2002-03-11 | Use of epigallocatechin-3-gallate or derivatives thereof in the prophylaxis and treatment of neurodegenerative diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001VR000031A ITVR20010031A1 (en) | 2001-03-12 | 2001-03-12 | USE OF EPIGALLOCATECHIN-3-GALLATO OR ITS DERIVATIVES IN THE PROPHYLAXIS AND TREATMENT OF NEURODEGENERATIVE DISEASES. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ITVR20010031A0 ITVR20010031A0 (en) | 2001-03-12 |
| ITVR20010031A1 true ITVR20010031A1 (en) | 2002-09-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| IT2001VR000031A ITVR20010031A1 (en) | 2001-03-12 | 2001-03-12 | USE OF EPIGALLOCATECHIN-3-GALLATO OR ITS DERIVATIVES IN THE PROPHYLAXIS AND TREATMENT OF NEURODEGENERATIVE DISEASES. |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1411920A2 (en) |
| AU (1) | AU2002247973A1 (en) |
| IT (1) | ITVR20010031A1 (en) |
| WO (1) | WO2002072086A2 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2006508096A (en) * | 2002-11-07 | 2006-03-09 | ディーエスエム アイピー アセッツ ビー．ブイ． | A novel nutritional supplement composition containing epigallocatechin gallate |
| KR20050071709A (en) * | 2002-11-28 | 2005-07-07 | 디에스엠 아이피 어셋츠 비.브이. | Nutraceutical compositions comprising epigallocatechin gallate and raspberry ketone |
| US7491699B2 (en) | 2002-12-09 | 2009-02-17 | Ramot At Tel Aviv University Ltd. | Peptide nanostructures and methods of generating and using the same |
| WO2004060791A1 (en) | 2003-01-07 | 2004-07-22 | Ramot At Tel Aviv University Ltd. | Peptide nanostructures encapsulating a foreign material and method of manufacturing same |
| CN100518733C (en) * | 2003-09-23 | 2009-07-29 | 帝斯曼知识产权资产管理有限公司 | Compositions for the treatment and prevention of diabetes mellitus |
| CA2540407A1 (en) * | 2003-09-25 | 2005-03-31 | Tel Aviv University Future Technology Development L.P. | Compositions and methods using same for treating amyloid-associated diseases |
| WO2006013552A2 (en) | 2004-08-02 | 2006-02-09 | Ramot At Tel Aviv University Ltd. | Articles of peptide nanostructures and method of forming the same |
| US7732479B2 (en) | 2004-08-19 | 2010-06-08 | Tel Aviv University Future Technology Development L.P. | Compositions for treating amyloid associated diseases |
| US20100040558A1 (en) * | 2005-04-26 | 2010-02-18 | 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 |
| JP5576694B2 (en) * | 2009-04-10 | 2014-08-20 | 花王株式会社 | GIP elevation inhibitor |
| JP2016516082A (en) | 2013-03-20 | 2016-06-02 | アプトース バイオサイエンシーズ， インコーポレイテッド | 2-Substituted imidazo [4,5-D] phenanthroline derivatives and their use in the treatment of cancer |
| WO2019236521A1 (en) * | 2018-06-07 | 2019-12-12 | Avanti Biosciences, Inc. | Methods and formulations for intranasal administration |
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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 (en) * | 1996-07-01 | 1998-01-08 | Vitasyn Gmbh Entwicklung & Ver | Therapeutic composition containing epicatechin and/or theaflavin |
| JP4738592B2 (en) * | 1997-10-31 | 2011-08-03 | アーチ・デヴェロップメント・コーポレイション | Methods and compositions for modulating 5α-reductase activity |
| US5922756A (en) * | 1998-02-14 | 1999-07-13 | Chan; Marion Man-Ying | Method of inhibiting nitric oxide synthase |
| WO2000006171A1 (en) * | 1998-07-31 | 2000-02-10 | Hme Enterprises, Llc | Antioxidant composition and method of treating diseases using same |
| FI20000004A0 (en) * | 2000-01-03 | 2000-01-03 | Slk Foundation | Flavonoidilääke ... |
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2001
- 2001-03-12 IT IT2001VR000031A patent/ITVR20010031A1/en unknown
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2002
- 2002-03-11 EP EP02717053A patent/EP1411920A2/en not_active Withdrawn
- 2002-03-11 AU AU2002247973A patent/AU2002247973A1/en not_active Abandoned
- 2002-03-11 WO PCT/IT2002/000149 patent/WO2002072086A2/en not_active Application Discontinuation
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| Publication number | Publication date |
|---|---|
| WO2002072086A3 (en) | 2004-02-19 |
| EP1411920A2 (en) | 2004-04-28 |
| AU2002247973A1 (en) | 2002-09-24 |
| ITVR20010031A0 (en) | 2001-03-12 |
| WO2002072086A2 (en) | 2002-09-19 |
| WO2002072086A8 (en) | 2002-10-10 |
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