CA2441099A1 - Proanthocyanidins for the treatment of amyloid and alpha-synuclein diseases - Google Patents
Proanthocyanidins for the treatment of amyloid and alpha-synuclein diseases Download PDFInfo
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- CA2441099A1 CA2441099A1 CA002441099A CA2441099A CA2441099A1 CA 2441099 A1 CA2441099 A1 CA 2441099A1 CA 002441099 A CA002441099 A CA 002441099A CA 2441099 A CA2441099 A CA 2441099A CA 2441099 A1 CA2441099 A1 CA 2441099A1
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- epicatechin
- proanthocyanidin
- composition
- disease
- procyanidin
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Abstract
A method of treating an amyloid disease, or a disease characterized by .alpha.-synuclein or NAC fibrillogenesis, in a mammalian subject. The method includes administering to the mammal a therapeutically effective amount of a various disclosed proanthocyanidins or a proanthocyanidin characterized by disclosed general formulae. A pharmaceutical composition comprising a therapeutically effective amount of a proanthocyanidin and a pharmaceutically acceptable excipient. The therapeutic amount of the proanthocyanidin is selected for efficacy in treating amyloid, .alpha.-synuclein or NAC fibrillogenesis in a mammalian subject.
Claims (56)
1. A method of treating an amyloid disease, or a disease characterized by .alpha.-synuclein or NAC
fibrillogenesis, in a mammalian subject, the method comprising administering to the mammal a therapeutically effective amount of a proanthocyanidin, selected from the group of the proanthocyanidins characterized by Formula I or Formula II, and proanthocyanidins characterized by oligomeric combinations of Formula I and Formula II, and pharmaceutically acceptable salts of the foregoing proanthocyanidins:
where:
n is an interger of 2 to 20;
R1 and R2 are independently selected from hydrogen and hydroxy;
R3 is selected from the group consisting of hydrogen, optionally substituted O-glycosyl, -C(O)-(optionally substituted aryl), and -C(O)-(optionally substituted heteroaryl);
R4 is selected from the group consisting of hydrogen, catechin, epicatechin, epiafzelechin, and gallates of catechin and epicatechin;
the lines at the 2-, 3- and 4-position denote optional R and S configurations;
the lines at the 4- and 8-positions in Formula I and at the 4- and 6-positions in Formula II
denote possible oligomer bonds between individual units, and the substitutions at R1, R2, R3, and R4, and the configurations at the 2-, 3-, and 4-positions, and the oligomer bond configurations of 4-8 and 4-6 are independently selected for each individual unit.
fibrillogenesis, in a mammalian subject, the method comprising administering to the mammal a therapeutically effective amount of a proanthocyanidin, selected from the group of the proanthocyanidins characterized by Formula I or Formula II, and proanthocyanidins characterized by oligomeric combinations of Formula I and Formula II, and pharmaceutically acceptable salts of the foregoing proanthocyanidins:
where:
n is an interger of 2 to 20;
R1 and R2 are independently selected from hydrogen and hydroxy;
R3 is selected from the group consisting of hydrogen, optionally substituted O-glycosyl, -C(O)-(optionally substituted aryl), and -C(O)-(optionally substituted heteroaryl);
R4 is selected from the group consisting of hydrogen, catechin, epicatechin, epiafzelechin, and gallates of catechin and epicatechin;
the lines at the 2-, 3- and 4-position denote optional R and S configurations;
the lines at the 4- and 8-positions in Formula I and at the 4- and 6-positions in Formula II
denote possible oligomer bonds between individual units, and the substitutions at R1, R2, R3, and R4, and the configurations at the 2-, 3-, and 4-positions, and the oligomer bond configurations of 4-8 and 4-6 are independently selected for each individual unit.
2. The method of claim 1 where the proanthocyanidin is characterized by Formula I.
3. The method of claim 1 where the proanthocyanidin is characterized by Formula II.
4. The method of claim 1 where n is an interger of 2 through 5.
5. The method of claim 1 where the chiral configuration at each 2-position is R.
6. The method of claim 1 where each R3 is selected from hydrogen, 2,3-dihydroxybenzoyl, 3,4-dihydroxybenzoyl; 2,3,4-trihydroxybenzoyl, and 3,4,5-trihydroxybenzoyl.
7. The method of claim 2 where n is 2 or 3.
8. The method of claim 7 where each R3 is hydrogen.
9. The method of claim 8 where each R1 is hydroxy and each R2 is hydrogen.
10. The method of claim 1 where each R3 is optionally substituted O-glycosyl.
11. A method of treatment of an amyloid disease, or a disease characterized by .alpha.-synuclein or NAC fibrillogenesis, in a mammalian subject, the method comprising the step of administering to the subject a therapeutically effective amount of a proanthocyanidin.
12. The method of claim 11, wherein the therapeutically effective amount of proanthocyanidin is a procyanidin oligomer having from 2 to 20 units.
13. The method of claim 12 in which the oligomer units are in the general form of flavanoid units and the procyanidin oligomer contains 2 to 5 units.
14. The method of claim 13 in which each flavanoid unit is selected from the group consisting of catechins, including catechin, epicatechin, epiafzelechin, gallocatechin, galloepicatechin, epigallocatechin and the gallates of the catechins, and flavanols, flavonols, flavandiols, leucocyanidins, and anthocyanidins.
15. The method of claim 1 where the amyloid disease is selected from the group of diseases consisting of Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, incusion body myositosis, the amyloidosis of chronic inflammation, the amyloidosis of malignancy and Familial Mediterranean Fever, the amyloidosis of multiple myeloma and B-cell dyscraisa, the amyloidosis of type 2 diabetes, the amyloidosis of prion diseases, Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome, kuru, scrapie, mad cow disease, the amyloidosis associated with long-term hemodialysis, the amyloidosis with carpal tunnel syndrome, senile cardiac amyloidosis, Familial Amyloidotic Polyneuropathy, the amyloidosis associated with endocrine tumors, systemic AA
amyloidosis, AL amyloidosis, A.beta. amyloidoisis and PrP amyloidosis.
amyloidosis, AL amyloidosis, A.beta. amyloidoisis and PrP amyloidosis.
16. The method of claim 15 where the amyloid disease is Alzheimer's disease.
17. The method of claim 1 where the .alpha.-synuclein or NAC fibrillogenesis is a fibrillogenesis selected from the group consisting of Lewy body disease, Parkinson's disease and multiple system atrophy.
18. A method of treatment of amyloid, .alpha.-synuclein or NAC
fibrillogenesis, in an in vitro environment, the method comprising the step of administering into the in vitro environment a therapeutically effective amount of a proanthocyanidin.
fibrillogenesis, in an in vitro environment, the method comprising the step of administering into the in vitro environment a therapeutically effective amount of a proanthocyanidin.
19. The method of claim 14 wherein the procyanidin comprises an oligomer of epicatechin and/or catechin units, epiafzelechin and/or epicatechin units, and/or epicatechin gallates and/or catechin gallates.
20. The method of claim 19 wherein the procyanidin is a procyanidin selected from the group consisting of A, B and C type procyanidins.
21. The method of claim 20 wherein the procyanidin is a dimer or trimer of epicatechin and/or catechin units.
22. The method of claim 21 wherein the procyanidin is a dimer and is selected from the group consisting of type B1, B2, B3, B4, B5, B6, B7, and B8 type procyanidins.
23. The method of claim 22 wherein the procyanidin dimer is epicatechin-4B.fwdarw.8-epicatechin.
24. The method of claim 22 wherein the procyanidin dimer is catechin-4.alpha..fwdarw.8-epicatechin.
25. The method of claim 22 wherein the procyanidin dimer is epiafzelechin-4.beta..fwdarw.8-epicatechin.
26. The method of claim 21 wherein the procyanidin is an epicatechin trimer, epicatechin-4.beta..fwdarw.8-epicatechin-4.beta..fwdarw.8-epicatechin.
27. The method of claim 11 further comprising an administration step whereby, the therapeutic amount of proanthocyanidin is administered to the subject, selected from the group of administration steps consisting of oral administration, parenteral injection, intraperitoneal injection, intravenous injection, subcutaneous injection, intramuscular injection, topical administration, and aerosal spray administration.
28. A pharmaceutical composition comprising a therapeutically effective amount of a proanthocyanidin and a pharmaceutically acceptable carrier, diluent, or excipient, the therapeutic amount of the proanthocyanidin selected for efficacy in treating amyloid, .alpha.-synuclein or NAC fibrillogenesis in a mammalian subject.
29. The composition of claim 27 wherein the therapeutically effective amount of the proanthocyanidin comprises a dosage in the range of about 10 to 1,000 mg/kg of body weight of the subject.
30. The composition of claim 29 wherein the therapeutically effective amount of the proanthocyanidin comprises a dosage in the range of about 10 to 100 mg/kg of body weight of the subject.
31. The composition of claim 28 wherein the proanthocyanidin is selected from the group consisting of chlorogenic acid, epicatechin, epiafzelechin, and the dimers and trimers of epicatechin, epiafzelechin and catechin, and the pharmaceutically acceptable analogs and derivatives thereof.
32. The composition of claim 31 wherein the proanthocyanidin is the procyanidin dimer epicatechin-4.beta..fwdarw.8-epicatechin.
33. The composition of claim 31 wherein the proanthocyanidin is the procyanidin dimer catechin-4.alpha..fwdarw.8-epicatechin.
34. The composition of claim 31 wherein the proanthocyanidin is the procyanidin dimer epiafzelechin-4.beta..fwdarw.-epicatechin.
35. The composition of claim 31 wherein the proanthocyanidin is the procyanidin trimer epicatechin-4.beta..fwdarw.8-epicatechin-4.beta..fwdarw.8-epicatechin.
36. The composition of claim 31 comprising a mixture of two or more of the proanthocyanidins selected from the group consisting of chlorogenic acid, epicatechin and the dimers and trimers of epicatechin, epiafzelechin and catechin, and the pharmaceutically acceptable analogs and derivatives thereof.
37. The composition of claim 36 comprising a mixture of two or more of the procyanidins selected from the group consisting of the dimers and trimers of epicatechin, and the pharmaceutically acceptable analogs and derivatives thereof.
38. The composition of claim 36 comprising a mixture of two or more of the proanthocyanidins selected from the group consisting of epicatechin-4.beta..fwdarw.8-epicatechin, catechin-4.alpha..fwdarw.-epicatechin, epiafzelechin-4.beta..fwdarw.8-epicatechin, and epicatechin-4.beta..fwdarw.8-epicatechin-4.beta..fwdarw.8-epicatechin.
39. The composition of claim 31 wherein each proanthocyanidin selected is present in a percentage purity that significantly exceeds a proportion percentage of the proanthocyanidin presence in a plant, or extract from a plant.
40. The composition of claim 39 wherein the proanthocyanidin selected is at least a substantially pure proanthocyanidin.
41. The composition of claim 40 wherein the proanthocyanidin selected is in substantially pure isolated or synthetic form.
42. A method of isolation of a proanthocyanidin from a plant material containing proanthocyanidins, the method comprising the steps of:
a) dissolving the plant material with methanol or the like, b) then loading the methanol-extracted plant material onto a silica gel column, c) eluting the column with a series of increasing proportions of methanol in chloroform to elute the proanthocyanidins, d) separating the proanthocyanidins in the extract by reverse phase HPLC, and e) collecting and freeze drying the pure proanthocyanidin.
a) dissolving the plant material with methanol or the like, b) then loading the methanol-extracted plant material onto a silica gel column, c) eluting the column with a series of increasing proportions of methanol in chloroform to elute the proanthocyanidins, d) separating the proanthocyanidins in the extract by reverse phase HPLC, and e) collecting and freeze drying the pure proanthocyanidin.
43. The method of claim 42 where the series of methanol in chlorofom comprises at least 10%
methanol in chloroform, 20% methanol in chloroform, 40% methanol in chloroform, 50%
methanol in chloroform, and 100% methanol in chloroform.
methanol in chloroform, 20% methanol in chloroform, 40% methanol in chloroform, 50%
methanol in chloroform, and 100% methanol in chloroform.
44. A proanthocyanidin composition made from the process of claim 43.
45. The composition of claim 44 wherein the proanthocyanidin composition comprises primarily procyanidin dimers and trimers eluted from the silica gel column with the 20%
methanol chloroform step of the series.
methanol chloroform step of the series.
46. The composition of claim 44 wherein the proanthocyanidin composition primarily procyanidin trimers and tetramers eluted from the silica gel column with the 40% methanol in chloroform step of the series.
47. The composition of claim 44 wherein the proanthocyanidin composition comprises primarily procyanidin trimers, tetramers, pentamers, and hexamers eluted from the silica gel column with the 50% methanol in chloroform step of the series.
48. The composition of claim 44 wherein the proanthocyanidin composition comprises primarily procyanidin tetramers, pentamers, hexamers, and oligomers of greater than six units eluted from the silica gel column with the 100% methanol in chloroform step of the series.
49. A method of isolation of a proanthocyanidin from a plant material containing proanthocyanidins, the method comprising the steps of:
a) dissolving the plant material with ethanol or the like, b) then loading the ethanol-extracted plant material onto a LH20 column, c) eluting the column with a series of increasing proportions of ethanol, followed by acetone in ethanol and/or methanol to elute the proanthocyanidins, d) separating the proanthocyanidins in the extract by reverse phase HPLC, and e) collecting and freeze drying the pure proanthocyanidin.
a) dissolving the plant material with ethanol or the like, b) then loading the ethanol-extracted plant material onto a LH20 column, c) eluting the column with a series of increasing proportions of ethanol, followed by acetone in ethanol and/or methanol to elute the proanthocyanidins, d) separating the proanthocyanidins in the extract by reverse phase HPLC, and e) collecting and freeze drying the pure proanthocyanidin.
50. A method of treatment of an amyloid disease, or a disease characterized by .alpha.-synuclein or NAC fibrillogenesis, in a mammalian subject, the method comprising the step of administering to the subject a therapeutic amount of the proanthocyanidin of claim 44.
51. The method of Claim 1 wherein the proanthocyanidin is present in a percentage purity that significantly exceeds a proportion percentage of the proanthocyanidin presence in a plant or extract from the plant.
52. The method of claim 11 wherein said amyloid disease for treatment is selected from the group of amyloid diseases associated with Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositosis, the amyloidosis associated with type 2 diabetes, the amyloidosis associated with chronic inflammation, various forms of malignancy, and Familial Mediterranean Fever, the amyloidosis associated with multiple myeloma and other B-cell dyscrasias, the amyloidosis associated with the prion diseases including Creutzfeldt-Jakob disease, Gerstmann-Strausller syndrome, kuru, animal scrapie, and mad cow disease, the amyloidosis associated with long-term hemodialysis and carpal tunnel syndrome, the amyloidosis associated with endocrine tumors such as medullary carcinoma of the thyroid, and the .alpha.-synuclein/NAC disease is selected from the group consisting of Parkinson's disease, Lewy body disease and multiple system atrophy.
53. The method of claim 42 where the plant material is derived from Uncaria tomentosa.
54. A composition comprising: a pharmaceutically acceptable carrier, diluent or excipient, or the like, and a proanthocyanidin having a structure selected selected from the group of proanthocyanidin oligomers characterized by Formula I or Formula II, and proanthocyanidins characterized by oligomeric combinations of Formula I and Formula II, and pharmaceutically acceptable salts of the foregoing proanthocyanidins, in an amount effective to treat an amyloid disease, or a disease characterized by .alpha.-synuclein or NAC
fibrillogenesis, in a mammalian subject;
wherein n is an interger in the range of 2 to 20;
R1 and R2 are independently selected from hydrogen and hydroxy;
R3 is selected from the group consisting of hydrogen, optionally substituted O-glycosyl, -C(O)-(optionally substituted aryl), and -C(O)-(optionally substituted heteroaryl);
R4 is selected from the group consisting of hydrogen, catechin, epicatechin, and gallates of catechin and epicatechin;
the lines at the 2-, 3- and 4-position denote optional R and S configurations;
the lines at the 4- and 8-positions in Formula I and at the 4- and 6-positions in Formula II
denote possible oligomer bonds between individual units, and the substitutions at R1, R2, R3, and R4, and the configurations at the 2-, 3-, and 4-positions, and the oligomer bond configurations of 4-8 and 4-6 are independently selected for each individual unit.
fibrillogenesis, in a mammalian subject;
wherein n is an interger in the range of 2 to 20;
R1 and R2 are independently selected from hydrogen and hydroxy;
R3 is selected from the group consisting of hydrogen, optionally substituted O-glycosyl, -C(O)-(optionally substituted aryl), and -C(O)-(optionally substituted heteroaryl);
R4 is selected from the group consisting of hydrogen, catechin, epicatechin, and gallates of catechin and epicatechin;
the lines at the 2-, 3- and 4-position denote optional R and S configurations;
the lines at the 4- and 8-positions in Formula I and at the 4- and 6-positions in Formula II
denote possible oligomer bonds between individual units, and the substitutions at R1, R2, R3, and R4, and the configurations at the 2-, 3-, and 4-positions, and the oligomer bond configurations of 4-8 and 4-6 are independently selected for each individual unit.
55. A pharmaceutical composition comprising a therapeutically effective amount of a mixture of substantially pure proanthocyanidins.
56. The composition of claim 55 wherein one or more of the proanthocyanidins are selected from the group consisting of the dimers and trimers of epicatechin, epiafzelechin, and catechin, and the pharmaceutically acceptable analogs and derivatives thereof.
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27686601P | 2001-03-15 | 2001-03-15 | |
| US60/276,866 | 2001-03-15 | ||
| US09/938,987 US6607758B2 (en) | 1997-05-15 | 2001-08-24 | Methods for inhibiting and reducing amyloid fibril formation associated with Alzheimer's Disease and other amyloidoses |
| US09/938,987 | 2001-08-24 | ||
| PCT/US2001/051131 WO2002042429A2 (en) | 2000-11-03 | 2001-11-02 | Methods of isolating amyloid-inhibiting compounds and use of compounds isolated from uncaria tomentosa and related plants |
| US10/053,625 US6929808B2 (en) | 2000-11-03 | 2001-11-02 | Methods of isolating amyloid-inhibiting compounds and use of compounds isolated from Uncaria tomentosa and related plants |
| WOPCT/US01/51131 | 2001-11-02 | ||
| US10/053,625 | 2001-11-02 | ||
| US33872101P | 2001-12-04 | 2001-12-04 | |
| US60/338,721 | 2001-12-04 | ||
| US33903301P | 2001-12-10 | 2001-12-10 | |
| US33896901P | 2001-12-10 | 2001-12-10 | |
| US60/338,969 | 2001-12-10 | ||
| US60/339,033 | 2001-12-10 | ||
| PCT/US2002/004764 WO2002076381A2 (en) | 2001-03-15 | 2002-02-15 | Proanthocyanidins for the treatment of amyloid and alpha-synuclein diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2441099A1 true CA2441099A1 (en) | 2002-10-03 |
| CA2441099C CA2441099C (en) | 2011-04-19 |
Family
ID=56290250
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2441099A Expired - Fee Related CA2441099C (en) | 2001-03-15 | 2002-02-15 | Proanthocyanidins for the treatment of amyloid and alpha-synuclein diseases |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1377287A4 (en) |
| JP (1) | JP4380991B2 (en) |
| AU (1) | AU2002250117B2 (en) |
| CA (1) | CA2441099C (en) |
| NZ (1) | NZ528322A (en) |
| WO (1) | WO2002076381A2 (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070208087A1 (en) | 2001-11-02 | 2007-09-06 | Sanders Virginia J | Compounds, compositions and methods for the treatment of inflammatory diseases |
| US7514107B2 (en) * | 2002-03-21 | 2009-04-07 | Mars, Incorporated | Treatment of diseases involving defective gap junctional communication |
| SI2527315T1 (en) * | 2002-05-31 | 2014-06-30 | Proteotech Inc., | Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as Alzheimer's disease, type 2 diabetes and Parkinson's disease |
| WO2004033448A2 (en) * | 2002-10-11 | 2004-04-22 | Proteotech, Inc. | Isolation, purification and synthesis of procyanidin b2 and uses thereof |
| JP2006232670A (en) * | 2003-05-20 | 2006-09-07 | Ajinomoto Co Inc | Medicine for nervous disorder |
| JP4505555B2 (en) * | 2004-03-02 | 2010-07-21 | 康 大泉 | Neurodegenerative disease therapeutic agent |
| US8263589B2 (en) * | 2006-03-29 | 2012-09-11 | Wista Laboratories Ltd. | Inhibitors of protein aggregation |
| WO2009104556A1 (en) * | 2008-02-19 | 2009-08-27 | 株式会社岐阜セラツク製造所 | Composition |
| JP5738755B2 (en) * | 2008-05-09 | 2015-06-24 | アイカーン スクール オブ メディシン アット マウント シナイ | Methods for preventing and treating neurodegenerative diseases |
| US20140179774A1 (en) * | 2012-12-26 | 2014-06-26 | Industrial Technology Research Institute | Methods for inhibition of shc-1/p66 to combat aging-related diseases |
| EP3272351A4 (en) | 2015-05-11 | 2018-12-05 | Meiji Co., Ltd. | Composition for facilitating production of brain-derived neurotrophic factor |
| KR102441381B1 (en) * | 2016-07-18 | 2022-09-07 | (주)아모레퍼시픽 | Composition for enhancing cognitive function comprising trans-3-O-galloyl-3,3',5,5',7- pentahydroxyflavan |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4698360B1 (en) * | 1985-04-09 | 1997-11-04 | D Investigations Pharmacologiq | Plant extract with a proanthocyanidins content as therapeutic agent having radical scavenger effect and use thereof |
| US6346280B1 (en) * | 1997-05-15 | 2002-02-12 | University Of Washington | Composition and methods for inhibiting the formation of brain amyloid deposits |
| ES2285772T3 (en) * | 1997-05-15 | 2007-11-16 | University Of Washington | COMPOSITION AND METHODS TO TREAT ALZHEIMER'S DISEASE AND OTHER AMYLOIDOSIS. |
| US5922756A (en) * | 1998-02-14 | 1999-07-13 | Chan; Marion Man-Ying | Method of inhibiting nitric oxide synthase |
| WO1999045797A1 (en) * | 1998-03-12 | 1999-09-16 | Mars, Incorporated | Products containing polyphenol(s) and l-arginine to stimulate nitric oxide production |
| WO2000057707A1 (en) * | 1999-03-15 | 2000-10-05 | Proteotech, Inc. | Methods of treating alzheimer's disease and other amyloidoses using hypericum perforatum and derivatives thereof |
| CA2395695A1 (en) * | 1999-12-30 | 2001-07-12 | Proteotech, Inc. | Catechins and green tea extract for the treatment of amyloidosis in alzheimer's disease and other amyloidoses |
-
2002
- 2002-02-15 JP JP2002574897A patent/JP4380991B2/en not_active Expired - Fee Related
- 2002-02-15 EP EP02719009A patent/EP1377287A4/en not_active Withdrawn
- 2002-02-15 NZ NZ528322A patent/NZ528322A/en not_active IP Right Cessation
- 2002-02-15 AU AU2002250117A patent/AU2002250117B2/en not_active Ceased
- 2002-02-15 WO PCT/US2002/004764 patent/WO2002076381A2/en active IP Right Grant
- 2002-02-15 CA CA2441099A patent/CA2441099C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2005505497A (en) | 2005-02-24 |
| WO2002076381A2 (en) | 2002-10-03 |
| EP1377287A4 (en) | 2007-11-14 |
| EP1377287A2 (en) | 2004-01-07 |
| AU2002250117B8 (en) | 2002-10-08 |
| JP4380991B2 (en) | 2009-12-09 |
| NZ528322A (en) | 2005-03-24 |
| AU2002250117B2 (en) | 2007-11-29 |
| CA2441099C (en) | 2011-04-19 |
| WO2002076381A3 (en) | 2002-11-21 |
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