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1. 发明授权

US09133176B2 Isolation, purification and synthesis of procyanidin B2 and uses thereof 有权
标题翻译：原花青素B2的分离，纯化和合成及其用途
公开(公告)号：US09133176B2
公开(公告)日：2015-09-15
申请号：US12119212
申请日：2008-05-12
申请人： Gerardo Castillo , Beth Nguyen , Paula Choi , Lesley Larsen , Stephen Lorimer , Alan Snow
发明人： Gerardo Castillo , Beth Nguyen , Paula Choi , Lesley Larsen , Stephen Lorimer , Alan Snow
IPC分类号： C07D323/00 , C07D321/00 , C07D311/00 , C07D407/04 , C07D321/10 , C07D311/62
CPC分类号： C07D407/04 , C07D311/62 , C07D321/10 , C07D323/00
摘要： Methods for the synthesis, isolation, and purification of procyanidin B2 are disclosed. The synthetic methods utilize epicatechin as a starting material and produce procyanidin B2 in high yields. The isolation methods extract procyanidin B2 from a sample of bark powder from plant matter of the genus Uncaria. The isolated and/or synthesized procyanidin B2 is used to treat amyloid disease, such as Alzheimer's disease and Parkinson's disease as well as improve cognitive performance and increase learning and memory in Alzheimer's patients. Pharmaceutical compositions containing the synthesized and/or isolated procyanidin B2 are also disclosed.
摘要翻译：公开了原花青素B2的合成，分离和纯化方法。合成方法利用表儿茶素作为原料，以高产率生产原花青素B2。分离方法从Uncaria属植物物质的树皮粉样品中提取原花青素B2。分离和/或合成的原花青素B2用于治疗淀粉样变性疾病，如阿尔茨海默病和帕金森病，以及提高阿尔茨海默病患者的认知能力和增加学习和记忆能力。还公开了含有合成和/或分离的原花青素B2的药物组合物。

2. 发明申请

US20080306286A1 Isolation, Purification and Synthesis of Procyanidin B2 and Uses Thereof 审中-公开
标题翻译：原花青素B2的分离，纯化和合成及其用途
公开(公告)号：US20080306286A1
公开(公告)日：2008-12-11
申请号：US12124929
申请日：2008-05-21
申请人： Alan Snow , Gerardo Castillo , Paula Choi , Beth Nguyen , Stephen Lorimer , Lesley Larsen
发明人： Alan Snow , Gerardo Castillo , Paula Choi , Beth Nguyen , Stephen Lorimer , Lesley Larsen
IPC分类号： C07D407/02
CPC分类号： C07D407/04 , C07D311/62 , C07D321/10 , C07D323/00
摘要： Methods for the synthesis, isolation, and purification of procyanidin B2 are disclosed. The synthetic methods utilize epicatechin as a starting material and produce procyanidin B2 in high yields. The isolation methods extract procyanidin B2 from a sample of bark powder from plant matter of the genus Uncaria. The isolated and/or synthesized procyanidin B2 is used to treat amyloid disease, such as Alzheimer's disease and Parkinson's disease as well as improve cognitive performance and increase learning and memory in Alzheimer's patients. Pharmaceutical compositions containing the synthesized and/or isolated procyanidin B2 are also disclosed.
摘要翻译：公开了原花青素B2的合成，分离和纯化方法。合成方法利用表儿茶素作为原料，以高产率生产原花青素B2。分离方法从Uncaria属植物物质的树皮粉样品中提取原花青素B2。分离和/或合成的原花青素B2用于治疗淀粉样变性疾病，如阿尔茨海默病和帕金森病，以及提高阿尔茨海默病患者的认知能力和增加学习和记忆能力。还公开了含有合成和/或分离的原花青素B2的药物组合物。

3. 发明申请

US20080306142A1 Isolation, purification and synthesis of procyanidin B2 and uses thereof 有权
标题翻译：原花青素B2的分离，纯化和合成及其用途
公开(公告)号：US20080306142A1
公开(公告)日：2008-12-11
申请号：US12119212
申请日：2008-05-12
申请人： Gerardo Castillo , Beth Nguyen , Paula Choi , Lesley Larsen , Stephen Lorimer , Alan Snow
发明人： Gerardo Castillo , Beth Nguyen , Paula Choi , Lesley Larsen , Stephen Lorimer , Alan Snow
IPC分类号： A61K31/353 , A61P25/28
CPC分类号： C07D407/04 , C07D311/62 , C07D321/10 , C07D323/00
摘要： Methods for the synthesis, isolation, and purification of procyanidin B2 are disclosed. The synthetic methods utilize epicatechin as a starting material and produce procyanidin B2 in high yields. The isolation methods extract procyanidin B2 from a sample of bark powder from plant matter of the genus Uncaria. The isolated and/or synthesized procyanidin B2 is used to treat amyloid disease, such as Alzheimer's disease and Parkinson's disease as well as improve cognitive performance and increase learning and memory in Alzheimer's patients. Pharmaceutical compositions containing the synthesized and/or isolated procyanidin B2 are also disclosed.
摘要翻译：公开了原花青素B2的合成，分离和纯化方法。合成方法利用表儿茶素作为原料，以高产率生产原花青素B2。分离方法从Uncaria属植物物质的树皮粉样品中提取原花青素B2。分离和/或合成的原花青素B2用于治疗淀粉样变性疾病，如阿尔茨海默病和帕金森病，以及提高阿尔茨海默病患者的认知能力和增加学习和记忆能力。还公开了含有合成和/或分离的原花青素B2的药物组合物。

4. 发明申请

US20070225362A1 Compounds, compositions and methods for the treatment of amyloid diseases such as systemic AA amyloidosis 有权
标题翻译：用于治疗淀粉样变性疾病如全身性AA淀粉样变性的化合物，组合物和方法
公开(公告)号：US20070225362A1
公开(公告)日：2007-09-27
申请号：US11714894
申请日：2007-03-05
申请人： Alan Snow , Beth Nguyen , Gerardo Castillo , Virginia Sanders , Thomas Lake , Lesley Larsen , Rex Weavers , Stephen Lorimer , David Larsen , David Coffen , Charlotte Coffen
发明人： Alan Snow , Beth Nguyen , Gerardo Castillo , Virginia Sanders , Thomas Lake , Lesley Larsen , Rex Weavers , Stephen Lorimer , David Larsen , David Coffen , Charlotte Coffen
IPC分类号： A61K31/165 , A61K31/135 , A61K31/167 , A61K31/357
CPC分类号： C07C39/15 , C07C39/16 , C07C39/17 , C07C69/017 , C07D207/16 , C07D211/74 , C07D213/30 , C07D213/69 , C07D213/85 , C07D221/08 , C07D221/18 , C07D231/06 , C07D241/08 , C07D263/38 , C07D265/38 , C07D295/096 , C07D295/192 , C07D311/60 , C07D317/50 , C07D317/54 , C07D317/58 , C07D317/60 , C07D317/66 , C07D317/68 , C07D333/16 , C07D405/14 , C07D407/14 , C07D409/14 , C07D413/14 , C07D451/06 , C07D471/04 , C07D487/08 , C07D491/08
摘要： Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, AA/SAA amyloidosis, such as observed in systemic AA amyloidosis and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.
摘要翻译：双 - 和三 - 二羟基芳基化合物及其亚甲二氧基类似物和药学上可接受的酯，其合成，含有它们的药物组合物及其在治疗淀粉样蛋白病，尤其是Aβ淀粉样变性中的用途，例如在阿尔茨海默病，IAPP淀粉样变性在2型糖尿病中观察到，AA / SAA淀粉样变性，例如在全身性AA淀粉样变性和突触核蛋白病中观察到的，例如在帕金森病中观察到的，以及制备用于这种治疗的药物。

5. 发明申请

US20110104055A1 SUBSTITUTED N-ARYL BENZAMIDES AND RELATED COMPOUNDS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES 审中-公开
标题翻译：取代的N-亚苄基苯甲酸和相关化合物用于治疗淀粉样变性疾病和综合征
公开(公告)号：US20110104055A1
公开(公告)日：2011-05-05
申请号：US12940330
申请日：2010-11-05
申请人： Alan Snow , Manfred Weigele , Lesley Larsen , Beth Nguyen , Thomas Lake , Gerardo Castillo , Virginia Sanders , Rex T. Weavers , Stephen Lorimer , David Larsen , David L. Coffen , Charlotte Coffen
发明人： Alan Snow , Manfred Weigele , Lesley Larsen , Beth Nguyen , Thomas Lake , Gerardo Castillo , Virginia Sanders , Rex T. Weavers , Stephen Lorimer , David Larsen , David L. Coffen , Charlotte Coffen
IPC分类号： A61K31/167 , C07C233/75 , A61K51/00 , A61P43/00
CPC分类号： C07C235/56
摘要： Compounds and their pharmaceutically acceptable salts, their synthesis and labeling, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided. Also provided is the use of the disclosed compounds as imaging agents and methods for in vivo imaging and detection of amyloid and synuclein.
摘要翻译：化合物及其药学上可接受的盐，它们的合成和标记，含有它们的药物组合物及其在治疗淀粉样疾病中的用途，包括A＆bgr; 提供淀粉样变性，例如在阿尔茨海默病中观察到的，IAPP淀粉样变性，例如在2型糖尿病中观察到的，以及突触核蛋白病，例如在帕金森病中观察到的，并且制备用于这种治疗的药物。还提供了所公开的化合物作为淀粉样蛋白和突触核蛋白的体内成像和检测的成像剂和方法的用途。

6. 发明申请

US20090060838A1 SUBSTITUTED N-ARYL BENZAMIDES AND RELATED COMPOUNDS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES 审中-公开
标题翻译：取代的N-亚苄基苯甲酸和相关化合物用于治疗淀粉样变性疾病和综合征
公开(公告)号：US20090060838A1
公开(公告)日：2009-03-05
申请号：US12201183
申请日：2008-08-29
申请人： Alan Snow , Manfred Weigele , Lesley Larsen , Beth Nguyen , Thomas Lake , Gerardo Castillo
发明人： Alan Snow , Manfred Weigele , Lesley Larsen , Beth Nguyen , Thomas Lake , Gerardo Castillo
IPC分类号： A61K51/04 , C07C233/88 , A61K101/02 , A61K31/167
CPC分类号： C07C311/08
摘要： Substituted n-aryl benzamides, related compounds and their pharmaceutically acceptable salts, their synthesis and labeling, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided. Also provided is the use of the disclosed compounds as imaging agents and methods for in vivo imaging and diagnosis of amyloid and synuclein diseases.
摘要翻译：取代的正芳基苯甲酰胺，相关化合物及其药学上可接受的盐，它们的合成和标记，含有它们的药物组合物及其在治疗淀粉样蛋白疾病中的用途，包括Aβ淀粉样变性，例如在阿尔茨海默病，IAPP淀粉样变性在2型糖尿病中观察到，并且提供突触核蛋白病，例如在帕金森病中观察到的，并且提供了用于这种治疗的药物的制造。还提供了所公开的化合物作为淀粉样蛋白和突触核蛋白疾病的体内成像和诊断的显像剂和方法的用途。

7. 发明申请

US20080306143A1 Cathechins for the Treatment of Fibrillogenesis in Alzheimer's Disease, Parkinson's Disease, Systemic AA Amyloidosis, and Other Amyloid Disorders 审中-公开
标题翻译：用于治疗阿尔茨海默病，帕金森病，系统性AA淀粉样变性和其他淀粉样变性的纤维发生的Cathechins
公开(公告)号：US20080306143A1
公开(公告)日：2008-12-11
申请号：US12119416
申请日：2008-05-12
申请人： Paula Choi , Gerardo Castillo , Beth Nguyen , Alan Snow , Joel Cummings
发明人： Paula Choi , Gerardo Castillo , Beth Nguyen , Alan Snow , Joel Cummings
IPC分类号： A61K31/353 , A61P25/16 , C12N5/00
CPC分类号： A61K31/215 , A61K31/352 , A61K31/353 , A61K31/7048 , A61K36/16 , A61K36/258 , A61K36/53 , A61K36/74 , A61K36/80 , A61K36/82 , A61K45/06 , A61K2300/00
摘要： 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 catechins or green tea extract. A pharmaceutical composition comprising a therapeutically effective amount of a catechin and a pharmaceutically acceptable excipient. The therapeutic amount of the catechin or green tea extract is selected for efficacy in treating amyloid, alpha-synuclein or NAC fibrillogenesis in a mammalian subject.
摘要翻译：在哺乳动物受试者中治疗淀粉样蛋白病或以α-突触核蛋白或NAC原纤维发生为特征的疾病的方法。该方法包括向哺乳动物施用治疗有效量的各种公开的儿茶素或绿茶提取物。一种药物组合物，其包含治疗有效量的儿茶素和药学上可接受的赋形剂。选择儿茶素或绿茶提取物的治疗量用于在哺乳动物受试者中治疗淀粉样蛋白，α-突触核蛋白或NAC原纤维发生的功效。

8. 发明申请

US20080044917A1 Rapid induction of Alzheimer's amyloid plaque formation by sulfated glycosaminoglycans 审中-公开
标题翻译：通过硫酸化糖胺聚糖快速诱导阿尔茨海默氏淀粉样斑块形成
公开(公告)号：US20080044917A1
公开(公告)日：2008-02-21
申请号：US11487149
申请日：2006-07-14
申请人： Beth Nguyen , Paula Choi , Virginia Sanders , Gerardo Castillo , Alan Snow
发明人： Beth Nguyen , Paula Choi , Virginia Sanders , Gerardo Castillo , Alan Snow
IPC分类号： G01N33/00
CPC分类号： G01N33/6896 , G01N2400/40 , G01N2500/00 , Y10T436/143333
摘要： A method of induction of amyloid plaques includes immobilizing a quantity of a selected sulfated glycosaminoglycan (SGAG) on a selected medium and adding to the immobilized SGAG on the medium a quantity of dissolved low fibrillar Aβ 1-40 (LFAβ). The LFAβ is added preferably in a Aβ:SGAG w/w ratio of about 1:1. SGAGs are preferably selected from heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate and chondroitin-6-sulfate. Screening methods and kits for screening either immobilize a quantity of a selected sulfated glycosaminoglycan (SGAG) on a selected medium, followed by adding to a quantity of dissolved low fibrillar Aβ 1-40 (LFAβ) a selected quantity of the selected amyloid therapeutic candidate to create a test solution, and then adding to the immobilized SGAG on the medium a selected quantity of the test solution to test for inhibition, or preform amyloid plaques on the medium by immobilizing a quantity of a selected sulfated glycosaminoglycan (SGAG) or a GAG-related macromolecule on a selected medium and then adding a selected quantity of dissolved low fibrillar Aβ 1-40 (LFAβ), followed by adding to the amyloid plaques on the medium a selected quantity of a test solution of a selected amyloid therapeutic candidate to test for disruption.
摘要翻译：诱导淀粉样蛋白斑块的方法包括将一定数量的选择的硫酸葡糖胺聚糖（SGAG）固定在选定的培养基上，并向培养基上的固定化SGAG加入一定量的溶解的低纤维Aβ1-40（LFAbeta）。 LFAbeta优选以约1:1的Abeta：SGAG w / w比添加。 SGAG优选选自肝素，硫酸乙酰肝素，硫酸角质素，硫酸皮肤素，硫酸软骨素-4-硫酸盐和硫酸软骨素-6-硫酸盐。用于筛选的筛选方法和试剂盒在选定的培养基上固定一定量的选择的硫酸葡糖胺聚糖（SGAG），然后将一定量的所选择的淀粉样蛋白治疗候选物加入到一定量的溶解的低纤维Aβ1-40（LFAbeta）中产生一个测试溶液，然后在培养基上加入一定量的测试溶液中的固定化SGAG以测试抑制，或者通过将一定量的选择的硫酸糖胺聚糖（SGAG）或GAG- 然后加入选定量的溶解的低纤维Abeta 1-40（LFAbeta），然后向培养基上的淀粉样蛋白斑添加选定量的所选淀粉样蛋白治疗候选物的测试溶液，以测试中断

9. 发明申请

US20050244334A1 Small peptides for the treatment of Alzheimer's disease and other beta-amyloid protein fibrillogenesis disorders 有权
标题翻译：用于治疗阿尔茨海默病和其他β-淀粉样蛋白原纤维发生障碍的小肽
公开(公告)号：US20050244334A1
公开(公告)日：2005-11-03
申请号：US11016706
申请日：2004-12-16
申请人： Gerardo Castillo , Thomas Lake , Beth Nguyen , Virginia Sanders , Alan Snow
发明人： Gerardo Castillo , Thomas Lake , Beth Nguyen , Virginia Sanders , Alan Snow
IPC分类号： A61K38/08 , A61K38/10 , A61K51/00
CPC分类号： A61K38/08 , A61K38/10 , C07K7/08 , G01N33/6896 , G01N2800/2821
摘要： A pharmaceutical composition that includes a peptide of formula Y-(X-aa)-Z. (X-aa) is generally an amino acid sequence selected from -Arg-Val-Ser-Val-Arg-Trp-, -Arg-Val-Ala-Val-Ile-, -His-Gly-Arg-Leu-Val-Phe-, -Leu-Ala-Phe-Val-Leu-Arg-, and -Thr-Leu-Phe-Leu-Ala-Arg-. And Y is generally an amino terminal modifying group selected from an amino acid, a N-acylated amino acid, a peptide, a N-acylated peptide, and hydrogen. And Z- is carboxyl-terminal modifying group selected from hydrogen, an amino acid, a C-amidated amino acid, a peptide, a C-amidated peptide, or an amide or hydroxyl group such as an alkyl amide, an aryl amide, or an alcohol. A composition of matter that includes at least one of the peptide sequences -Arg-Val-Ala-Val-Ile-, -Leu-Ala-Phe-Val-Leu-Arg-, -Thr-Leu-Phe-Leu-Ala-Arg-, -Arg-Val-Ser-Val-Arg-Trp-, -His-Gly-Arg-Leu-Val-Phe-. Preferably at least one amino acid of the peptide sequence is a D-amino acid.
摘要翻译：一种药物组合物，其包含式Y-（X-aa）-Z的肽。（X-aa）通常是选自-Arg-Val-Ser-Val-Arg-Trp-，-Arg-Val-Ala-Val-Ile-，-His-Gly-Arg-Leu-Val- Phe-，-Leu-Ala-Phe-Val-Leu-Arg-和-Thr-Leu-Phe-Leu-Ala-Arg-。 Y通常是选自氨基酸，N-酰化氨基酸，肽，N-酰化肽和氢的氨基末端修饰基团。 Z-是选自氢，氨基酸，C-酰胺化氨基酸，肽，C-酰胺化肽或酰胺或羟基的羧基末端修饰基团，例如烷基酰胺，芳基酰胺或一个酒精。包含至少一个肽序列-Arg-Val-Ala-Val-Ile-，-Leu-Ala-Phe-Val-Leu-Arg-，-Thr-Leu-Phe-Leu-Ala- Arg-，-Arg-Val-Ser-Val-Arg-Trp-，-His-Gly-Arg-Leu-Val-Phe-。优选地，肽序列的至少一个氨基酸是D-氨基酸。

10. 发明申请

US20060199838A1 Substituted N-aryl benzamides and related compounds for treatment of amyloid diseases and synucleinopathies 有权
标题翻译：取代的N-芳基苯甲酰胺和相关化合物用于治疗淀粉样蛋白病和突触核蛋白病
公开(公告)号：US20060199838A1
公开(公告)日：2006-09-07
申请号：US11328748
申请日：2006-01-09
申请人： Alan Snow , Beth Nguyen , Thomas Lake , Gerardo Castillo , Manfred Weigele
发明人： Alan Snow , Beth Nguyen , Thomas Lake , Gerardo Castillo , Manfred Weigele
IPC分类号： A61K31/46 , C07D457/02 , A61K31/165
CPC分类号： C07C311/08
摘要： Substituted n-aryl benzamides, related compounds and their pharmaceutically acceptable derivatives, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided.
摘要翻译：取代的正芳基苯甲酰胺，相关化合物及其药学上可接受的衍生物，其合成，含有它们的药物组合物及其在治疗淀粉样蛋白疾病中的用途，包括Aβ淀粉样变性，例如在阿尔茨海默病，IAPP淀粉样变性中观察到的提供2型糖尿病和突触核蛋白病，例如在帕金森病中观察到的，并且提供了用于这种治疗的药物的制造。

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