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    • 1. 发明授权
    • Methods for treatment predicated on the presence of advanced
glycosylation endproducts in tobacco and its combustion byproducts
    • 治疗方法是基于烟草及其燃烧副产物中先进的糖基化终产物的存在
    • US6110968A
    • 2000-08-29
    • US189191
    • 1998-11-10
    • Richard J. BucalaHelen VlassaraAnthony CeramiCarla J. CeramiHenry W. Founds
    • Richard J. BucalaHelen VlassaraAnthony CeramiCarla J. CeramiHenry W. Founds
    • A24B15/36A24D3/14A61K31/27A61K31/275
    • G01N33/6842A24B15/36A24B15/365A24D3/14
    • Methods are provided for measuring the accumulation of advanced glycosylation endproducts (AGEs), and for lowering the accumulation of advanced glycosylation endproducts, which are predicated on the discovery that such AGEs and their precedent glycotoxins are present in tobacco and its byproducts. More particularly, the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs relative to non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke, and to the treatment of such individuals with agents capable of reacting with glycosylation products to either avert or diminish the accretion of AGEs in the body. Methods are also provided for the evaluation of the tobacco products to determine their storage status and organoleptic capacity and potential, for the treatment of the ambient atmosphere to lower AGE levels, and for the treatment of the tobacco products and combustion byproducts to lower AGE levels therein. For example, air or other samples may be taken and evaluated by a dosimeter or like device, to determine whether AGE levels exceed normal, after which measures could be implemented to remediate the ambient condition. Likewise, filters and similar devices for removing AGEs from tobacco smoke are provided. All such methods and corresponding materials are contemplated and included.
    • 提供了用于测量晚期糖基化终产物(AGEs)的积累以及用于降低晚期糖基化终产物的积累的方法,其基于发现这样的AGEs及其先例的糖类毒素存在于烟草及其副产物中。 更具体地说,这些方法着重于观察吸烟或以其他方式使用烟草的个体相对于非吸烟者的AGEs水平的增加。 本方法涉及测量个体和烟草及其副产物,烟雾中的AGE水平,以及能够与糖基化产物反应的试剂对这些个体的治疗,以反转或减少AGEs在体内的积累。 还提供了用于评价烟草制品以确定其储存状态和感官能力和潜力的方法,用于处理环境大气以降低AGE水平,以及用于处理烟草制品和燃烧副产物以降低其AGE水平 。 例如,空气或其他样品可以通过剂量计或类似装置进行评估,以确定AGE水平是否超过正常,之后可以实施措施来修复环境条件。 同样,提供了用于从AGE烟草烟雾中除去的过滤器和类似装置。 所有这些方法和相应的材料都被考虑并包括在内。
    • 2. 发明授权
    • Methods for measurement and treatment predicated on the presence of
advanced glycosylation endproducts in tobacco and its combustion
byproducts
    • 基于烟草及其燃烧副产物中高级糖基化终产物的存在的测量和处理方法
    • US5850840A
    • 1998-12-22
    • US772335
    • 1996-12-23
    • Carla J. CeramiRichard J. BucalaHelen VlassaraAnthony CeramiHenry W. Founds
    • Carla J. CeramiRichard J. BucalaHelen VlassaraAnthony CeramiHenry W. Founds
    • A24B15/36A24D3/14A24D3/16A24F1/10
    • G01N33/6842A24B15/36A24B15/365A24D3/14A24D3/16
    • Methods are provided for measuring the accumulation of advanced glycosylation endproducts (AGEs), and for lowering the accumulation of advanced glycosylation endproducts, which are predicated on the discovery that such AGEs and their precedent glycotoxins are present in tobacco and its byproducts. More particularly, the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs relative to non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke, and to the treatment of such individuals with agents capable of reacting with glycosylation products to either avert or diminish the accretion of AGEs in the body. Methods are also provided for the evaluation of the tobacco products to determine their storage status and organoleptic capacity and potential, for the treatment of the ambient atmosphere to lower AGE levels, and for the treatment of the tobacco products and combustion byproducts to lower AGE levels therein. For example, air or other samples may be taken and evaluated by a dosimeter or like device, to determine whether AGE levels exceed normal, after which measures could be implemented to remediate the ambient condition. Likewise, filters and similar devices for removing AGEs from tobacco smoke are provided. All such methods and corresponding materials are contemplated and included.
    • 提供了用于测量晚期糖基化终产物(AGEs)的积累以及用于降低晚期糖基化终产物的积累的方法,其基于发现这样的AGEs及其先例的糖类毒素存在于烟草及其副产物中。 更具体地说,这些方法着重于观察吸烟或以其他方式使用烟草的个体相对于非吸烟者的AGEs水平的增加。 本方法涉及测量个体和烟草及其副产物,烟雾中的AGE水平,以及能够与糖基化产物反应的试剂对这些个体的治疗,以反转或减少AGEs在体内的积累。 还提供了用于评价烟草制品以确定其储存状态和感官能力和潜力的方法,用于处理环境大气以降低AGE水平,以及用于处理烟草制品和燃烧副产物以降低其AGE水平 。 例如,空气或其他样品可以通过剂量计或类似装置进行评估,以确定AGE水平是否超过正常,之后可以实施措施来修复环境条件。 同样,提供了用于从AGE烟草烟雾中除去的过滤器和类似装置。 所有这些方法和相应的材料都被考虑并包括在内。
    • 5. 发明授权
    • Method for detecting hemoglobin advanced glycosylation endproducts
    • 检测血红蛋白进展糖基化终产物的方法
    • US5610076A
    • 1997-03-11
    • US236416
    • 1994-04-29
    • Henry W. FoundsMichael A. YaminRichard J. BucalaAnthony Cerami
    • Henry W. FoundsMichael A. YaminRichard J. BucalaAnthony Cerami
    • G01N33/53G01N33/531G01N33/72G01N33/543
    • G01N33/723Y10S435/962Y10S435/975
    • The present invention relates to methods for the diagnosis and monitoring of diseases and disorders associate with advanced glycosylation endproducts (AGE) formation, such as diabetes and the ageing process. In particular, the invention is directed to detecting AGE-modified hemoglobin (Hb-AGE) for the foregoing purposes, and in improved assay therefore. The method involves diluting the sample in a dilution buffer, which dilution buffer comprises an anionic protein denaturing detergent at a concentration sufficient to denature hemoglobin-AGE without interfering in binding of reagents with hemoglobin-AGE the dilution buffer may also include a non-ionic surfactant at a concentration sufficient to facilitate detection of hemoglobin-AGE; and a denaturing agent at a concentration sufficient to denature hemoglobin-AGE and increase assay sensitivity, without denaturing binding of reagents to hemoglobin-AGE. After diluting the sample in the dilution buffer, the sample is contacted with means for detecting the presence of hemoglobin-AGE in the sample, and the presence of hemoglobin-AGE in the sample is detected with the detection means. Dilution buffers and kits for practicing the invention are also provided. In specific examples, the level of AGE in hemoglobin in samples from human and rat normal subjects and diabetic subjects is detected. The results obtained from human samples show a high degree of correlation between the level of hemoglobin-AGE in a sample and the level of hemoglobin-A.sub.1c in a sample. Most importantly, the invention is used to detect the "aminoguanidine effect," which is the decrease in the level of hemoglobin-AGE in a sample from a subject undergoing therapy with the AGE-inhibitor aminoguanidine.
    • 本发明涉及诊断和监测与晚期糖基化终产物(AGE)形成相关的疾病和病症的方法,例如糖尿病和衰老过程。 特别地,本发明涉及为了上述目的检测AGE修饰的血红蛋白(Hb-AGE),并且因此改进了测定。 该方法包括在稀释缓冲液中稀释样品,该稀释缓冲液包含浓度足以使血红蛋白-AGE变性的阴离子蛋白质变性洗涤剂,而不干扰试剂与血红蛋白-AGE的结合,稀释缓冲液还可以包括非离子表面活性剂 浓度足以促进血红蛋白-AGE的检测; 和变性剂,其浓度足以使血红蛋白-AGE变性,并提高测定灵敏度,而不使试剂与血红蛋白-AGE结合变性。 在稀释缓冲液中稀释样品后,将样品与用于检测样品中血红蛋白-AGE的存在的装置接触,并用检测装置检测样品中血红蛋白-AGE的存在。 还提供了用于实施本发明的稀释缓冲液和试剂盒。 在具体实例中,检测来自人和大鼠正常受试者和糖尿病受试者的样品中血红蛋白的AGE水平。 从人体样品获得的结果显示样品中血红蛋白-AGE水平与样品中血红蛋白-Alc水平之间的高度相关性。 最重要的是,本发明用于检​​测来自接受AGE抑制剂氨基胍治疗的受试者的样品中血红蛋白-AGE水平的“氨​​基胍效应”。
    • 8. 发明授权
    • Methods and materials for the diagnosis and treatment of conditions such
as stroke
    • 用于诊断和治疗诸如中风的病症的方法和材料
    • US5700447A
    • 1997-12-23
    • US319747
    • 1994-10-07
    • Richard J. BucalaHelen VlassaraAnthony CeramiKevin J. Tracey
    • Richard J. BucalaHelen VlassaraAnthony CeramiKevin J. Tracey
    • A61K31/155A61K38/17G01N33/533G01N33/92G01N33/48
    • A61K31/155A61K31/00A61K31/195A61K31/415A61K31/70A61K38/1709G01N33/533G01N33/6893G01N33/92G01N2800/042G01N2800/044G01N2800/323
    • 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 and atherosclerosis. Diagnostic methods are contemplated, extending in utility from the detection of the onset and course of conditions in which variations in lipid oxidation, AGE-lipid levels, LDL levels, apolipoprotein levels, apolipoprotein receptor binding the like, may be measured, to drug discovery assays. Corresponding methods of treatment and pharmaceutical compositions are disclosed that are based on an active ingredient or ingredients that demonstrates the ability to modulate the levels of all of the foregoing markers of lipid oxidation. A further aspect of the invention relates to the treatment of stroke and related maladies, and to agents and compositions that are prepared for such purpose.
    • 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,脂褐素异常形成和各种疾病状态如糖尿病和动脉粥样硬化。 考虑到诊断方法,从检测可以测量脂质氧化,AGE-脂质水平,LDL水平,载脂蛋白水平,结合载脂蛋白受体等的药物发现测定 。 公开了相应的治疗方法和药物组合物,其基于表现出调节脂质氧化的所有前述标记物的水平的能力的活性成分或成分。 本发明的另一方面涉及治疗中风和相关疾病,以及为此目的制备的药剂和组合物。
    • 9. 发明授权
    • Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis
    • 用于高级糖基化终末产物介导的淀粉样变性调节的组合物和方法
    • US06410598B1
    • 2002-06-25
    • US08477364
    • 1995-06-07
    • Michael P. VitekAnthony CeramiRichard J. BucalaPeter C. UlrichHelen VlassaraXini Zhang
    • Michael P. VitekAnthony CeramiRichard J. BucalaPeter C. UlrichHelen VlassaraXini Zhang
    • A01N3752
    • A61K31/15A61K31/155A61K31/195A61K31/415A61K31/425A61K31/655A61K38/00C07K14/4711C07K14/575
    • The present invention relates generally to the non-enzymatic glycosylation of amyloidogenic proteins and the consequent formation of advanced glycosylation endproducts (AGEs). It has been found that formation of AGE-amyloidogenic proteins can enhance amyloidosis. The invention further relates to compositions and methods for the prevention and treatment of amyloidosis associated with amyloid diseases, particularly neurodegenerative disease and Type II diabetes, and more particularly Alzheimer's disease. In a specific example, aggregation of an amyloidogenic peptide, &bgr;AP, is enhanced by the glycosylation reaction of &bgr;AP to form AGE-&bgr;AP as defined herein. Accordingly, the invention extends to a method for modulating the in vivo aggregation of amyloid polypeptides and associated amyloidosis by controlling the formation and presence of AGE-amyloid polypeptide. A corresponding diagnostic utility comprises the measurement of the course and extent of amyloidosis by a measurement of the presence and amount of AGEs and particularly, AGE-amyloid. An assay is included that may use the AGE-amyloid polypeptide of the present invention to identify disease states characterized by the presence of AGE-amyloid. Additionally, such an assay can be utilized to monitor therapy and thus adjust a dosage regimen for a given disease state characterized by the presence of AGE-amyloid.
    • 本发明一般涉及淀粉样蛋白形成蛋白的非酶糖基化,从而形成晚期糖基化终产物(AGEs)。 已经发现AGE-淀粉样蛋白生成蛋白的形成可以增强淀粉样变性。 本发明进一步涉及用于预防和治疗与淀粉样蛋白病,特别是神经变性疾病和II型糖尿病,更特别是阿尔茨海默病有关的淀粉样变性的组合物和方法。 在具体实例中,通过βAP的糖基化反应来增强淀粉样蛋白原肽βAP的聚集,从而形成如本文所定义的AGE-βAP。 因此,本发明延伸到通过控制AGE-淀粉样蛋白多肽的形成和存在来调节淀粉样蛋白多肽的体内聚集和相关淀粉样变性的方法。 相应的诊断实用程序包括测量AGEs,特别是AGE-淀粉样蛋白的存在和量的淀粉样变性的过程和程度。 包括可以使用本发明的AGE-淀粉样蛋白多肽来鉴定以AGE-淀粉样蛋白的存在为特征的疾病状态的测定。 另外,这种测定可用于监测治疗,并因此调整特征在于AGE-淀粉样蛋白存在的给定疾病状态的剂量方案。