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1. 发明申请

US20050239807A1 Reactive oxygen generating enzyme inhibitor with nitric oxide bioactivity and uses thereof 失效
标题翻译：具有一氧化氮生物活性的活性氧发生酶抑制剂及其应用
公开(公告)号：US20050239807A1
公开(公告)日：2005-10-27
申请号：US10829940
申请日：2004-04-23
申请人： Jonathan Stamler , Eric Toone , Joshua Hare
发明人： Jonathan Stamler , Eric Toone , Joshua Hare
IPC分类号： A61K31/519 , C07D487/02 , C07D487/04
CPC分类号： C07D487/04 , A61K31/519
摘要： A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, e.g., 1,5-bis(3-nitrooxypropyyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle. Where the disorder is heart failure, administration of the enzyme inhibitor mediates amelioration of acute coronary symptoms and/or myocardial infarction.
摘要翻译：具有NO供体生物活性的活性氧产生酶抑制剂，例如硝化别嘌呤醇，例如1,5-双（3-硝基氧基丙基）-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮可用于治疗心力衰竭，稳定型心绞痛，缺血障碍，缺血再灌注损伤，动脉粥样硬化，镰状细胞病，糖尿病，阿尔茨海默氏病，帕金森病，ALS和哮喘，并获得心脏，骨骼和平滑肌的适当收缩。在疾病是心力衰竭的地方，酶抑制剂的施用介导急性冠状动脉症状和/或心肌梗死的改善。

2. 发明申请

US20060194820A1 Reactive oxygen generating enzyme inhibitor with nitric oxide bioactivity and uses thereof 有权
公开(公告)号：US20060194820A1
公开(公告)日：2006-08-31
申请号：US11430986
申请日：2006-05-10
申请人： Jonathan Stamler , Eric Toone , Joshua Hare
发明人： Jonathan Stamler , Eric Toone , Joshua Hare
IPC分类号： A61K31/519 , C07D487/02
CPC分类号： C07D487/04 , A61K31/519
摘要： A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle.

3. 发明申请

US20100260727A1 METHOD TO AMPLIFY CARDIAC STEM CELLS IN VITRO AND IN VIVO 有权
标题翻译：在体外和体内放大心脏干细胞的方法
公开(公告)号：US20100260727A1
公开(公告)日：2010-10-14
申请号：US12751445
申请日：2010-03-31
申请人： Joshua Hare , Konstantinos Chatzistergos
发明人： Joshua Hare , Konstantinos Chatzistergos
IPC分类号： A61K35/28 , A61K35/12 , C07K14/52 , C07K16/24 , A61P9/00 , C12N5/0775
CPC分类号： A61K35/34 , A61K35/28 , A61K2035/124 , C12N5/0663
摘要： Compositions comprising stem cells delivered into infarcted myocardium by endocardial injection, engraft and differentiate into myocytes, endothelial cells, and vascular smooth muscle, and do so without the requirement for survival enhancing modification. These cells engraft whether injected acutely (days) or late (months) after myocardial infarction, and the efficiency of engraftment correlates with the functional recovery of the heart. The stem cells also recruit endogenous cardiac precursor cells, reconstitute myocardial stem cell niches, and enhance endogenous cell differentiation into myocytes.
摘要翻译：包含通过心内膜注射输入梗塞心肌的干细胞的组合物，移植并分化成肌细胞，内皮细胞和血管平滑肌，并且不需要增强生存改变。这些细胞是否在心肌梗死后急性（天）或晚（月）注入，并且移植效率与心脏的功能恢复相关。干细胞还招募内源性心脏前体细胞，重建心肌干细胞龛，并增强内源细胞分化成肌细胞。

4. 发明授权

US09962409B2 Therapy using cardiac stem cells and mesenchymal stem cells 有权
公开(公告)号：US09962409B2
公开(公告)日：2018-05-08
申请号：US12751445
申请日：2010-03-31
申请人： Joshua Hare , Konstantinos Chatzistergos
发明人： Joshua Hare , Konstantinos Chatzistergos
IPC分类号： A61K35/34 , A61K35/28 , C12N5/0775 , A61K35/12
CPC分类号： A61K35/34 , A61K35/28 , A61K2035/124 , C12N5/0663
摘要： Compositions comprising stem cells delivered into infarcted myocardium by endocardial injection, engraft and differentiate into myocytes, endothelial cells, and vascular smooth muscle, and do so without the requirement for survival enhancing modification. These cells engraft whether injected acutely (days) or late (months) after myocardial infarction, and the efficiency of engraftment correlates with the functional recovery of the heart. The stem cells also recruit endogenous cardiac precursor cells, reconstitute myocardial stem cell niches, and enhance endogenous cell differentiation into myocytes.

5. 发明申请

US20060246484A1 Identification of gene expression by heart failure etiology 审中-公开
标题翻译：通过心力衰竭病因鉴定基因表达
公开(公告)号：US20060246484A1
公开(公告)日：2006-11-02
申请号：US11373812
申请日：2006-03-10
申请人： Joshua Hare , Michelle Kittleson
发明人： Joshua Hare , Michelle Kittleson
IPC分类号： C12Q1/68 , G06F19/00
CPC分类号： C12Q1/6883 , C12Q2600/112 , C12Q2600/158 , G16B25/00 , G16B40/00
摘要： Differential gene expression profiles identifying heart failure etiology and the use thereof are disclosed.
摘要翻译：公开了鉴定心力衰竭病因的差异基因表达谱及其用途。

6. 发明授权

US08507433B1 Cardioprotective effects of GHRH agonists 有权
标题翻译： GHRH激动剂的心脏保护作用
公开(公告)号：US08507433B1
公开(公告)日：2013-08-13
申请号：US12914023
申请日：2010-10-28
申请人： Andrew V. Schally , Norman L Block , Joshua Hare , Rosemeire Miyuki Kanashiro Takeuchi
发明人： Andrew V. Schally , Norman L Block , Joshua Hare , Rosemeire Miyuki Kanashiro Takeuchi
IPC分类号： A61K38/25 , C07K14/60 , A61P9/10
CPC分类号： A61K38/25 , C07K14/60
摘要： Whether the growth hormone (GH)/Insulin-like growth factor 1(IGF-I) axis exerts cardioprotective effects remains controversial; and the underlying mechanism(s) for such actions are unclear. Here we tested the hypothesis that growth-hormone releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-I independent fashion. Following experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4 week period, either placebo (n=14), rat recombinant GH (rrGH, n=8) or JI-38 (n=8; 50 μg/Kg/day), a potent GHRH-agonist. JI-38 did not elevate serum levels of GH or IGF-I, but markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, circulating GH and IGF-I, but did not offset the decline in cardiac structure and function. Whereas, both JI-38 and GH augmented levels of cardiac precursor cell proliferation, only JI-38 increased anti-apoptotic gene expression. The receptor for GHRH was detectable on myocytes supporting direct activation of cardiac signal transduction. Collectively, these findings demonstrate that within the heart GHRH-agonists can activate cardiac repair following MI, suggesting the existence of a potential signaling pathway based on GHRH in the heart. The phenotypic profile of the response to a potent GHRH agonist has therapeutic implications.
摘要翻译：生长激素（GH）/胰岛素样生长因子1（IGF-I）轴是否发挥心脏保护作用仍然是有争议的; 而这些行动的基本机制尚不清楚。在这里，我们测试了生长激素释放激素（GHRH）以GH / IGF-I独立的方式直接激活受伤心脏内的细胞修复机制的假说。在实验心肌梗死（MI）后，随机分配大鼠，在4周期间接受安慰剂（n = 14），大鼠重组GH（rrGH，n = 8）或JI-38（n = 8; 50杯） / Kg /天），一种有效的GHRH激动剂。 JI-38没有升高GH或IGF-I的血清水平，但显着减弱了心脏功能下降和损伤后重塑的程度。相比之下，GH治疗体重显着升高，心脏重量，循环GH和IGF-I，但并没有抵消心脏结构和功能的下降。而JI-38和GH两者均增加心脏前体细胞增殖水平，仅JI-38增加抗凋亡基因表达。在支持心脏信号转导的直接激活的心肌细胞上检测到GHRH受体。总而言之，这些研究结果表明，在心脏内GHRH激动剂可以激活MI后的心脏修复，这表明存在基于心脏GHRH的潜在信号通路。对有效GHRH激动剂的反应的表型谱具有治疗意义。

7. 发明申请

US20050158756A1 Identification of a gene expression profile that differentiates ischemic and nonischemic cardiomyopathy 失效
标题翻译：鉴定区分缺血性和非缺血性心肌病的基因表达谱
公开(公告)号：US20050158756A1
公开(公告)日：2005-07-21
申请号：US11012778
申请日：2004-12-15
申请人： Joshua Hare , Michelle Kittleson
发明人： Joshua Hare , Michelle Kittleson
IPC分类号： C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： C12Q1/6883 , C12Q2600/158 , G01N2800/325
摘要： A method of preparing a gene expression prediction profile for distinguishing ischemic and nonischemic cardiomyopathy comprises the steps of obtaining clinical specimens from patients suffering from ischemic or nonischemic cardiomyopathy, isolating nucleic acid sequences from at least a plurality of said specimens, obtaining a gene expression level corresponding to each individual of said nucleic acid sequence by a gene expression profiling method, identifying genes having differences in gene expression by comparing the gene expression level of an ischemic specimen with the gene expression level of a nonischemic specimen, and identifying a gene expression prediction profile comprises genes identified as having differences in gene expression so that said prediction profile distinguishes ischemic and nonischemic cardiomyopathy.
摘要翻译：制备用于区分缺血性和非缺血性心肌病的基因表达预测曲线的方法包括以下步骤：从患有缺血性或非缺血性心肌病的患者获得临床标本，从至少多个所述标本分离核酸序列，获得相应的基因表达水平通过基因表达谱分析方法对所述核酸序列的每个个体进行鉴定，通过比较缺血标本的基因表达水平与非缺血标本的基因表达水平来鉴定基因表达差异的基因，以及鉴定基因表达预测谱包括鉴定为具有基因表达差异的基因，使得所述预测特征区分缺血性和非缺血性心肌病。

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