公开(公告)号：US6004958A

公开(公告)日：1999-12-21

申请号：US794433

申请日：1997-02-05

申请人： Truman R. Brown ,  Francis Kappler ,  Benjamin Szwergold ,  Sundeep Lal ,  Bangying Su

发明人： Truman R. Brown ,  Francis Kappler ,  Benjamin Szwergold ,  Sundeep Lal ,  Bangying Su

IPC分类号： G01N33/50 ,  A61K31/13 ,  A61K31/197 ,  A61K31/198 ,  A61K31/275 ,  A61K31/5375 ,  A61K31/7028 ,  A61P3/10 ,  A61P25/02 ,  A61P27/02 ,  C07C215/14 ,  C07C229/26 ,  C07C255/26 ,  C07H15/04 ,  C07H19/20 ,  A61K31/535 ,  A61K31/045 ,  A61K31/19

CPC分类号： A61K31/13 ,  A61K31/197 ,  A61K31/198 ,  A61K31/275 ,  A61K31/5375 ,  C07H19/20

摘要： The present invention is based on the discovery of a metabolic pathway in which a specific kinase converts fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction. Fructose-lysine-3-phosphate (FL3P) is then broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins), which are believed to be a cause of diabetic complications. Disclosed is a class of compounds which inhibit the action of FL3P kinase in the above-mentioned pathway. Also disclosed are therapeutic methods of using such inhibitors to reduce formation of AGE-proteins and thereby lessen, reduce and delay diabetic complications, as well as methods for assessing a diabetic's risk of developing complications and for determining the efficacy of the disclosed inhibitor therapy by measuring the ratio of 3DG to 3DF in a biological sample following an oral dose of a fructose-lysine-containing food product.

摘要翻译： 本发明基于在ATP依赖性反应中特异性激酶将果糖 - 赖氨酸转化为果糖 - 赖氨酸-3-磷酸的代谢途径的发现。 然后将果糖 - 赖氨酸-3-磷酸（FL3P）分解形成游离赖氨酸，无机磷酸酯和3-脱氧葡萄糖醛（3DG），后者是反应性蛋白质改性剂。 3DG可以通过还原成3-脱氧果糖（3DF）来解毒，或者可以与内源蛋白反应形成晚期糖基化终产物修饰蛋白（AGE-蛋白），这被认为是糖尿病并发症的原因。 公开了一类抑制FL3P激酶在上述途径中的作用的化合物。 还公开了使用这种抑制剂减少AGE-蛋白质形成并由此降低，减少和延迟糖尿病并发症的治疗方法，以及用于评估糖尿病发展并发症的风险的方法以及通过测定测定所公开的抑制剂治疗的功效 口服剂量的含果糖赖氨酸的食品后的生物样品中3DG与3DF的比例。

公开(公告)号：US20100310482A1

公开(公告)日：2010-12-09

申请号：US12793520

申请日：2010-06-03

申请人： Annette Tobia ,  Francis Kappler

发明人： Annette Tobia ,  Francis Kappler

IPC分类号： A61K8/00 ,  A61K31/133 ,  A61K31/195 ,  A61P17/00 ,  A61P17/06 ,  A61P35/00 ,  A61Q17/04 ,  A61Q19/08

CPC分类号： A61Q19/08 ,  A61K8/44 ,  A61K31/00

摘要： The invention relates to a method of removing 3-deoxyglucosone and other alpha-dicarbonyl sugars from skin. The invention further relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin. The invention also relates to methods of treating 3-deoxyglucosone and other alpha-dicarbonyl sugars associated diseases and disorders of skin.

摘要翻译： 本发明涉及从皮肤中除去3-脱氧葡萄糖醛和其它α-二羰基糖的方法。 本发明还涉及抑制皮肤中3-脱氧葡萄糖醛和其他α-二羰基糖的产生和功能的方法。 本发明还涉及治疗3-脱氧葡萄糖醛和其它α-二羰基糖相关疾病和皮肤疾病的方法。

公开(公告)号：US07749503B2

公开(公告)日：2010-07-06

申请号：US11818997

申请日：2007-06-15

申请人： Annette Tobia ,  Francis Kappler

发明人： Annette Tobia ,  Francis Kappler

IPC分类号： A01N37/32

CPC分类号： A61Q19/08 ,  A61K8/44 ,  A61K31/00

摘要： The invention relates to a method of removing 3-deoxyglucosone and other alpha-dicarbonyl sugars from skin. The invention further relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin. The invention also relates to methods of treating 3-deoxyglucosone and other alpha-dicarbonyl sugars associated diseases and disorders of skin.

摘要翻译： 本发明涉及从皮肤中除去3-脱氧葡萄糖醛和其它α-二羰基糖的方法。 本发明还涉及抑制皮肤中3-脱氧葡萄糖醛和其他α-二羰基糖的产生和功能的方法。 本发明还涉及治疗3-脱氧葡萄糖醛和其它α-二羰基糖相关疾病和皮肤疾病的方法。

公开(公告)号：US20060110439A1

公开(公告)日：2006-05-25

申请号：US11256291

申请日：2005-10-21

申请人： Annette Tobia ,  Francis Kappler

发明人： Annette Tobia ,  Francis Kappler

IPC分类号： A61K9/127

CPC分类号： A61K9/0014 ,  A61K8/14 ,  A61K8/368 ,  A61K8/41 ,  A61K8/44 ,  A61K9/127 ,  A61K2800/782 ,  A61Q19/08

摘要： The present invention relates to methods and compositions for the treatment of skin-related conditions and disorders. In one aspect, the invention features methods and compositions for the transdermal delivery of compounds for the treatment of skin-related conditions and disorders, wherein the compositions include meglumine and a liposome component.

摘要翻译： 本发明涉及用于治疗皮肤相关病症和病症的方法和组合物。 一方面，本发明的特征在于用于透皮递送化合物用于治疗皮肤相关病症和病症的方法和组合物，其中所述组合物包括葡甲胺和脂质体组分。

公开(公告)号：US20110034522A1

公开(公告)日：2011-02-10

申请号：US12911195

申请日：2010-10-25

申请人： Truman R. Brown ,  Francis Kappler

发明人： Truman R. Brown ,  Francis Kappler

IPC分类号： A61K31/44 ,  A61K31/133 ,  A61K31/198 ,  A61K31/155 ,  A61K31/415 ,  A61K31/4196 ,  A61P3/10

CPC分类号： A61K31/7008 ,  A61K31/00 ,  A61K31/13 ,  A61K31/197 ,  A61K31/198 ,  A61K31/275 ,  A61K31/5375 ,  C07H1/00 ,  C07H19/20 ,  G01N33/66

摘要： Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins) Also disclosed are therapeutic methods of using such inhibitors to alleviate deleterious effects of 3DG.

摘要翻译： 公开了一类在新发现的代谢途径中ATP依赖性反应中抑制果糖 - 赖氨酸转化为果糖 - 赖氨酸-3-磷酸的化合物。 根据该途径的正常功能，果糖 - 赖氨酸-3-磷酸（FL3P）被分解形成游离赖氨酸，无机磷酸酯和3-脱氧葡萄糖醛（3DG），后者是反应性蛋白质改性剂。 3DG可以通过还原为3-脱氧果糖（3DF）进行解毒，或者可以与内源蛋白反应形成晚期糖基化终产物修饰蛋白（AGE-蛋白）。还公开了使用这种抑制剂减轻3DG有害作用的治疗方法 。

公开(公告)号：US07622117B2

公开(公告)日：2009-11-24

申请号：US10198706

申请日：2002-07-18

申请人： Annette Tobia ,  Francis Kappler

发明人： Annette Tobia ,  Francis Kappler

IPC分类号： A01N37/32

CPC分类号： A61Q19/08 ,  A61K8/44 ,  A61K31/00

摘要： The invention relates to a method of removing 3-deoxyglucosone and other alpha-dicarbonyl sugars from skin. The invention further relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin. The invention also relates to methods of treating 3-deoxyglucosone and other alpha-dicarbonyl sugars associated diseases and disorders of skin.

摘要翻译： 本发明涉及从皮肤中除去3-脱氧葡萄糖醛和其它α-二羰基糖的方法。 本发明还涉及抑制皮肤中3-脱氧葡萄糖醛和其他α-二羰基糖的产生和功能的方法。 本发明还涉及治疗3-脱氧葡萄糖醛和其它α-二羰基糖相关疾病和皮肤疾病的方法。

公开(公告)号：US20070021357A1

公开(公告)日：2007-01-25

申请号：US11454353

申请日：2006-06-16

申请人： Annette Tobia ,  Francis Kappler

发明人： Annette Tobia ,  Francis Kappler

IPC分类号： A61K31/7008 ,  A61K31/5415 ,  A61K31/4152 ,  A61K31/405 ,  A61K31/60

CPC分类号： A61K31/00 ,  A61K31/047 ,  A61K31/133 ,  A61K31/192 ,  A61K31/198 ,  A61K31/30 ,  A61K31/405 ,  A61K31/4152 ,  A61K31/5415 ,  A61K31/60 ,  A61K31/7008 ,  A61K33/34 ,  A61K45/06 ,  A61K2300/00

摘要： The invention relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin thereby treating or prevention various diseases, disorders or conditions. Additionally, the invention relates to treatment of various diseases, disorders or conditions associated with or mediated by oxidative stress since 3DG induces ROS and AGEs, which are associated with the inflammatory response caused by oxidative stress.

摘要翻译： 本发明涉及抑制皮肤中3-脱氧葡萄糖醛和其他α-二羰基糖的产生和功能的方法，从而治疗或预防各种疾病，病症或病症。 此外，本发明涉及治疗与氧化应激相关或介导的各种疾病，病症或病症，因为3DG诱导与由氧化应激引起的炎症反应相关的ROS和AGE。

公开(公告)号：US07071298B2

公开(公告)日：2006-07-04

申请号：US09974323

申请日：2001-10-10

申请人： Truman R. Brown ,  Francis Kappler

发明人： Truman R. Brown ,  Francis Kappler

IPC分类号： C07K2/00

CPC分类号： A61K31/7008 ,  A61K31/00 ,  A61K31/13 ,  A61K31/197 ,  A61K31/198 ,  A61K31/275 ,  A61K31/5375 ,  C07H1/00 ,  C07H19/20 ,  G01N33/66

摘要： Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins). Also disclosed are therapeutic methods of using such inhibitors to treat glycogen storage diseases, including Fanconi's syndrome, as well as other pathological conditions resulting from the formation of AGE-proteins.

摘要翻译： 公开了一类在新发现的代谢途径中ATP依赖性反应中抑制果糖 - 赖氨酸转化为果糖 - 赖氨酸-3-磷酸的化合物。 根据该途径的正常功能，果糖 - 赖氨酸-3-磷酸（FL3P）被分解形成游离赖氨酸，无机磷酸酯和3-脱氧葡萄糖醛（3DG），后者是反应性蛋白质改性剂。 3DG可以通过还原成3-脱氧果糖（3DF）进行解毒，或者可以与内源蛋白反应形成晚期糖基化终产物修饰蛋白（AGE-蛋白）。 还公开了使用这种抑制剂治疗糖原储存疾病（包括范科尼综合征）以及由AGE-蛋白质形成引起的其它病理状况的治疗方法。

公开(公告)号：US20060089316A1

公开(公告)日：2006-04-27

申请号：US10972971

申请日：2004-10-25

申请人： Truman Brown ,  Francis Kappler ,  Steven Seeholzer

发明人： Truman Brown ,  Francis Kappler ,  Steven Seeholzer

IPC分类号： A61K31/70 ,  A61K31/60 ,  A61K31/5377 ,  A61K31/53 ,  A61K31/44 ,  A61K31/415

CPC分类号： A61K31/415 ,  A61K31/44 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/60 ,  A61K31/70

摘要： Disclosed are methods of using various compounds, which are known to bind to 3-deoxyglucosone (3DG) or precursors thereof, in order to reduce a susceptibility to tumor formation and/or to prevent or delay onset of tumor formation induced by 3DG and its precursors. Also disclosed is the reduction of 3DG levels in high fructose corn syrop so that the high fructose corn syrup is less likely to induce tumor formation.

摘要翻译： 公开了使用已知结合3-脱氧葡萄糖醛酮（3DG）或其前体的各种化合物的方法，以减少对肿瘤形成的敏感性和/或预防或延缓由3DG及其前体引起的肿瘤形成的发生 。 还公开了降低高果糖玉米sy of中的3DG水平，使得高果糖玉米糖浆不太可能诱导肿瘤形成。