公开(公告)号：US09155784B2

公开(公告)日：2015-10-13

申请号：US14128411

申请日：2012-06-20

申请人： Edward H. Schuchman ,  Calogera M. Simonaro ,  Gary E. Striker ,  Helen Vlassara

发明人： Edward H. Schuchman ,  Calogera M. Simonaro ,  Gary E. Striker ,  Helen Vlassara

IPC分类号： A61K31/737 ,  A61K38/46 ,  A61K45/06

CPC分类号： A61K38/465 ,  A61K31/737 ,  A61K38/46 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention relates to methods of treating a subject with a lysosomal disorder, by administering an agent for enzyme replacement therapy and an agent for anti-TNF-α therapy; by administering a pentosan polysulfate therapy; or by administering a substrate reduction therapy and an anti-TNF-α therapy. The invention further relates to a method of reducing inflammatory cytokines in a subject with a lysosomal disorder that is being treated by enzyme replacement therapy, by administering an agent for anti-TNF-α therapy.

摘要翻译： 本发明涉及通过施用酶替代治疗剂和抗TNF-α治疗剂来治疗患有溶酶体病症的受试者的方法; 通过施用戊聚糖多硫酸盐治疗; 或通过施用底物还原疗法和抗TNF-α治疗。 本发明还涉及通过施用抗TNF-α治疗剂来减少患有通过酶替代疗法治疗的溶酶体病症的受试者的炎性细胞因子的方法。

公开(公告)号：US5733524A

公开(公告)日：1998-03-31

申请号：US479673

申请日：1995-06-07

申请人： Richard J. Bucala ,  Helen Vlassara ,  Anthony Cerami ,  Kevin J. Tracey

发明人： Richard J. Bucala ,  Helen Vlassara ,  Anthony Cerami ,  Kevin J. Tracey

IPC分类号： A61K31/155 ,  A61K38/17 ,  A61K39/00 ,  A61Q11/00 ,  C07K16/28 ,  G01N33/573 ,  G01N33/92 ,  A61K49/00 ,  G01N31/00 ,  G01N33/48

CPC分类号： A61K31/155 ,  A61K31/00 ,  A61K31/195 ,  A61K31/415 ,  A61K31/4178 ,  A61K31/70 ,  A61K38/1709 ,  A61K38/191 ,  A61K38/2006 ,  A61K38/217 ,  A61K38/38 ,  A61K39/0005 ,  A61K8/43 ,  A61Q19/08 ,  C07D405/14 ,  C07K16/28 ,  G01N33/533 ,  G01N33/573 ,  G01N33/68 ,  G01N33/6893 ,  G01N33/92 ,  A61K2039/6081 ,  G01N2333/922 ,  G01N2800/2871 ,  G01N2800/324

摘要： The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as AGE-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes, atherosclerosis, and stroke. Methods of treating stroke, and especially inhibiting the infarct size of stroke, using agents which inhibit the formation of AGE-lipids are disclosed. Additionally, a method of screening for neuroprotective agents which can be used to reduce the size and severity of the infarct size is disclosed.

摘要翻译： 已经发现脂质和含脂质分子的体内氧化是通过这种脂质物质与还原糖如葡萄糖，高级糖基化终产物例如AGE-肽或形成晚期糖基化终产物的化合物的同时反应引发的， 形成称为AGE-脂质的材料或颗粒。 AGE-脂质已经涉及老化过程，脂褐素的异常形成和各种疾病状态如糖尿病，动脉粥样硬化和中风。 公开了使用抑制AGE-脂质形成的药物治疗中风的方法，特别是抑制中风的梗死面积。 另外，公开了可用于减小梗死面积大小和严重程度的神经保护剂筛选方法。

公开(公告)号：US5585344A

公开(公告)日：1996-12-17

申请号：US749438

申请日：1991-08-23

申请人： Helen Vlassara ,  Zhi Yang ,  Anthony Cerami

发明人： Helen Vlassara ,  Zhi Yang ,  Anthony Cerami

IPC分类号： A61K8/64 ,  A61K31/155 ,  A61K31/195 ,  A61K31/415 ,  A61K31/4178 ,  A61K38/00 ,  A61K38/19 ,  A61K38/20 ,  A61K38/21 ,  A61K38/38 ,  A61K39/00 ,  A61Q11/00 ,  A61Q19/08 ,  C07D405/14 ,  C07K14/705 ,  C07K16/28 ,  G01N33/50 ,  G01N33/533 ,  G01N33/573 ,  G01N33/68 ,  A61K38/17

CPC分类号： G01N33/6893 ,  A61K31/155 ,  A61K31/195 ,  A61K31/415 ,  A61K31/4178 ,  A61K39/0005 ,  A61K8/64 ,  A61Q19/08 ,  C07D405/14 ,  C07K14/705 ,  C07K16/28 ,  C07K16/2803 ,  G01N33/5091 ,  G01N33/533 ,  G01N33/573 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6887 ,  A61K2039/6081 ,  A61K38/00 ,  C07K2317/34 ,  C07K2317/77 ,  G01N2333/922

摘要： The present invention relates to receptors for advanced glycosylation endproducts derived from rat liver membranes, and that specifically comprise proteins determined to possess molecular masses of about 90 kD and 60 kD, respectively, as assessed by migration during SDS-PAGE. Partial N-terminal sequences have been determined and diagnostic and therapeutic agents, compositions and methods are proposed.

摘要翻译： 本发明涉及来自大鼠肝膜的晚期糖基化终产物的受体，并且其特异性包括通过SDS-PAGE期间的迁移评估分别确定具有约90kD和60kD的分子量的蛋白质。 已经确定了部分N-末端序列，并提出了诊断和治疗剂，组合物和方法。

公开(公告)号：US5962245A

公开(公告)日：1999-10-05

申请号：US475055

申请日：1995-06-07

申请人： Yong Ming Li ,  Helen Vlassara ,  Anthony Cerami

发明人： Yong Ming Li ,  Helen Vlassara ,  Anthony Cerami

IPC分类号： A61K8/64 ,  A61K38/00 ,  A61K38/03 ,  A61K38/16 ,  A61K38/47 ,  A61Q11/00 ,  C07K14/79 ,  C12N9/36 ,  C12Q1/00 ,  C12Q1/34 ,  G01N33/573 ,  G01N33/66 ,  G01N33/68 ,  G01N33/566

CPC分类号： A61Q11/00 ,  A61K8/64 ,  C07K14/79 ,  G01N33/573 ,  G01N33/66 ,  G01N33/68 ,  G01N33/6842 ,  A61K38/00 ,  G01N2333/79 ,  G01N2333/924 ,  G01N2333/936

摘要： The present invention is directed to methods for detecting the presence of advanced glycosylation endproducts using the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to diagnostic methods for diseases and disorders associated with increased levels of AGEs, by using compositions having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.

摘要翻译： 本发明涉及使用意想不到的发现来检测高级糖基化终产物的存在的方法，某些抗菌蛋白，特别是溶菌酶和乳铁蛋白与高亲和力的晚期糖基化终产物（AGE）结合，并且该结合活性基本上是非竞争性的 具有细菌碳水化合物与抗菌蛋白质的结合。 因此，本发明涉及与增加水平的AGE相关的疾病和病症的诊断方法，通过使用具有与其相关联的分子的组合物，所述组分具有亲水环结构域，该结构域与AGE结合活性相关，以及包含这种结构域的组合物。 本发明还涉及用于将AGEs分离离开样品的组合物和装置。

公开(公告)号：US5811075A

公开(公告)日：1998-09-22

申请号：US487398

申请日：1995-06-07

申请人： Helen Vlassara ,  Michael Brownlee ,  Anthony Cerami

发明人： Helen Vlassara ,  Michael Brownlee ,  Anthony Cerami

IPC分类号： A61K8/43 ,  A61K8/44 ,  A61K31/155 ,  A61K39/00 ,  A61K51/12 ,  A61Q11/00 ,  A61Q19/08 ,  C07K16/28 ,  G01N33/573 ,  A61K49/00 ,  C12Q1/00

CPC分类号： A61K8/44 ,  A61K31/155 ,  A61K39/0005 ,  A61K51/1203 ,  A61K8/43 ,  A61Q19/08 ,  C07K16/28 ,  G01N33/573 ,  G01N33/6842 ,  A61K2039/6081 ,  C07K2317/77 ,  G01N2333/922 ,  G01N2800/042

摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.

公开(公告)号：US5733933A

公开(公告)日：1998-03-31

申请号：US473009

申请日：1995-06-07

申请人： Richard J. Bucala ,  Helen Vlassara ,  Anthony Cerami ,  Kevin J. Tracey

发明人： Richard J. Bucala ,  Helen Vlassara ,  Anthony Cerami ,  Kevin J. Tracey

IPC分类号： A61K31/155 ,  A61K38/17 ,  A61K39/00 ,  A61Q11/00 ,  C07K16/28 ,  G01N33/573 ,  G01N33/92

CPC分类号： G01N33/92 ,  A61K31/155 ,  A61K38/1709 ,  A61K39/0005 ,  C07K16/28 ,  G01N33/573 ,  A61K2039/6081 ,  G01N2333/922 ,  G01N2800/2871 ,  G01N2800/324

摘要： The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as AGE-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes, atherosclerosis, and stroke. Methods of treating stroke, and especially inhibiting the infarct size of stroke, using agents which inhibit the formation of AGE-lipids are disclosed. Additionally, a method of screening for neuroprotective agents which can be used to reduce the size and severity of the infarct size is disclosed.

公开(公告)号：USRE35465E

公开(公告)日：1997-02-25

申请号：US437064

申请日：1995-05-09

申请人： Helen Vlassara ,  Michael Brownlee ,  Anthony Cerami

发明人： Helen Vlassara ,  Michael Brownlee ,  Anthony Cerami

IPC分类号： A61K8/43 ,  A61K31/155 ,  A61K31/4178 ,  A61K38/19 ,  A61K38/20 ,  A61K38/21 ,  A61K38/38 ,  A61K39/00 ,  A61Q11/00 ,  A61Q19/08 ,  C07K16/28 ,  G01N33/573 ,  G01N33/68 ,  A61K31/415

CPC分类号： A61K8/43 ,  A61K31/155 ,  A61K31/4178 ,  A61K38/191 ,  A61K38/2006 ,  A61K38/217 ,  A61K39/0005 ,  A61Q19/08 ,  C07K16/28 ,  G01N33/573 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6893 ,  A61K2039/6081 ,  G01N2333/922

摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.

摘要翻译： 本发明涉及通过刺激动物的体内增加其对晚期糖基化终产物的识别和亲和力来抑制和治疗动物中蛋白质老化的方法和相关药剂。 具体地说，该方法考虑到某些药物的施用，例如晚期糖基化终产物，结合载体的终产物，刺激吞噬细胞增加其对晚期糖基化终产物的活性的单核因子，以及这些材料的混合物，单独或联合 与其他共刺激剂。 定义了许多诊断和治疗应用，并且也考虑了药物组合物。

公开(公告)号：US4900747A

公开(公告)日：1990-02-13

申请号：US91534

申请日：1987-09-03

申请人： Helen Vlassara ,  Michael Brownlee ,  Anthony Cerami

发明人： Helen Vlassara ,  Michael Brownlee ,  Anthony Cerami

IPC分类号： A61K8/43 ,  A61K8/64 ,  A61K31/155 ,  A61K31/195 ,  A61K31/415 ,  A61K31/4178 ,  A61K38/00 ,  A61K38/19 ,  A61K38/20 ,  A61K38/21 ,  A61K38/38 ,  A61K39/00 ,  A61Q11/00 ,  A61Q19/08 ,  C07D405/14 ,  C07K14/705 ,  C07K16/28 ,  G01N33/50 ,  G01N33/533 ,  G01N33/573 ,  G01N33/58 ,  G01N33/68

CPC分类号： G01N33/6893 ,  A61K31/155 ,  A61K31/195 ,  A61K31/415 ,  A61K31/4178 ,  A61K38/191 ,  A61K38/2006 ,  A61K38/217 ,  A61K38/38 ,  A61K39/0005 ,  A61K8/43 ,  A61K8/64 ,  A61Q19/08 ,  C07D405/14 ,  C07K14/705 ,  C07K16/28 ,  C07K16/2803 ,  G01N33/5091 ,  G01N33/533 ,  G01N33/573 ,  G01N33/582 ,  G01N33/68 ,  G01N33/6842 ,  A61K2039/6081 ,  C07K2317/77 ,  G01N2333/922 ,  G01N2800/042

摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.

摘要翻译： 本发明涉及通过刺激动物的体内增加其对晚期糖基化终产物的识别和亲和力来抑制和治疗动物中蛋白质老化的方法和相关药剂。 具体地说，该方法考虑到某些药物的施用，例如晚期糖基化终产物，结合载体的终产物，刺激吞噬细胞增加其对晚期糖基化终产物的活性的单核因子，以及这些材料的混合物，单独或联合 与其他共刺激剂。 定义了许多诊断和治疗应用，并且也考虑了药物组合物。

公开(公告)号：US08871741B2

公开(公告)日：2014-10-28

申请号：US13522441

申请日：2011-01-14

申请人： Gary E. Striker ,  Helen Vlassara ,  Feng Zheng

发明人： Gary E. Striker ,  Helen Vlassara ,  Feng Zheng

IPC分类号： A61K31/70 ,  A61K31/737 ,  C12Q1/02

CPC分类号： A61K31/737 ,  C12Q1/025

摘要： Oral pentosan polysulfate (PPS) compositions treat diseases such as diabetes, inflammation, atherosclerosis. The compositions are also effective in reducing matrix metalloproteinases (MMPs).

摘要翻译： 口服戊糖多糖（PPS）组合物可治疗糖尿病，炎症，动脉粥样硬化等疾病。 组合物还有效减少基质金属蛋白酶（MMPs）。

公开(公告)号：US20140205584A1

公开(公告)日：2014-07-24

申请号：US14128411

申请日：2012-06-20

申请人： Edward H. Schuchman ,  Calogera M. Simonaro ,  Gary E. Striker ,  Helen Vlassara

发明人： Edward H. Schuchman ,  Calogera M. Simonaro ,  Gary E. Striker ,  Helen Vlassara

IPC分类号： A61K38/46 ,  A61K45/06 ,  A61K31/737

CPC分类号： A61K38/465 ,  A61K31/737 ,  A61K38/46 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention relates to methods of treating a subject with a lysosomal disorder, by administering an agent for enzyme replacement therapy and an agent for anti-TNF-α therapy; by administering a pentosan polysulfate therapy; or by administering a substrate reduction therapy and an anti-TNF-α therapy. The invention further relates to a method of reducing inflammatory cytokines in a subject with a lysosomal disorder that is being treated by enzyme replacement therapy, by administering an agent for anti-TNF-α therapy.

摘要翻译： 本发明涉及通过施用酶替代治疗剂和抗TNF-α治疗剂来治疗患有溶酶体病症的受试者的方法; 通过施用戊聚糖多硫酸盐治疗; 或通过施用底物还原疗法和抗TNF-α治疗。 本发明还涉及通过施用抗TNF-α治疗剂来减少患有通过酶替代疗法治疗的溶酶体病症的受试者的炎性细胞因子的方法。