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1. 发明申请

US20060057722A1 Conditioned medium of autologous or allogenic progenitor cells for angiogenesis treatment 审中-公开
标题翻译：用于血管生成治疗的自体或同种异体祖细胞的条件培养基
公开(公告)号：US20060057722A1
公开(公告)日：2006-03-16
申请号：US11221469
申请日：2005-09-07
申请人： Ran Kornowski , Shmuel Fuchs , Stephen Epstein , Martin Leon
发明人： Ran Kornowski , Shmuel Fuchs , Stephen Epstein , Martin Leon
IPC分类号： C12N5/08
CPC分类号： A61K35/28 , A61K35/14 , A61K35/35 , A61K38/1709 , A61K38/1825 , A61K38/193 , A61K38/195 , A61K38/44 , A61K2300/00
摘要： A therapeutic composition is provided that comprises a cell-free conditioned medium containing mixed secretion products of isolated angiogenic progenitor cells obtained from bone marrow, peripheral blood, or adipose tissue. The composition may additionally contain angiogenesis-promoting proteins obtained by transfecting the progenitors cells in culture with an angiogenesis promoting transgene. The composition is useful to promote angiogenesis when introduced into or adjacent to an ischemic site in a patient, such as in myocardium or peripheral limb. Methods are also provided for utilizing such cell-free conditioned medium to deliver angiogenesis-promoting proteins to a patient. The cell-free conditioned medium can also be injected into the blood stream for delivery to the ischemic tissue. The cells can derive from either an autologous or allogenic source and can be lyophilized or frozen for storage.
摘要翻译：提供了一种治疗组合物，其包含含有从骨髓，外周血或脂肪组织获得的分离的血管生成祖细胞的混合分泌产物的无细胞条件培养基。该组合物可另外含有通过用促血管生成促进转基因在培养物中转染祖细胞获得的促血管生成蛋白。当将该组合物引入或邻近患者（例如心肌或外周肢体）中的缺血部位时，该组合物可用于促进血管生成。还提供了使用这种无细胞条件培养基将血管生成促进蛋白递送给患者的方法。无细胞条件培养基也可以注射到血流中以输送到缺血组织。细胞可来自自体或同种异体来源，并且可以冻干或冷冻储存。

2. 发明申请

US20060094657A1 Inhibiting development of microvessels within coronary or peripheral vessel walls for restenosis/atherosclerosis prevention or therapy 审中-公开
标题翻译：抑制冠状动脉或外周血管壁内微血管的发展，用于再狭窄/动脉粥样硬化的预防或治疗
公开(公告)号：US20060094657A1
公开(公告)日：2006-05-04
申请号：US11295095
申请日：2005-12-06
申请人： Stephen Epstein , Ran Kornowski , Shmuel Fuchs , Martin Leon
发明人： Stephen Epstein , Ran Kornowski , Shmuel Fuchs , Martin Leon
IPC分类号： A61K38/17 , A61K48/00
CPC分类号： A61K45/06 , A61K38/179 , A61K38/1891
摘要： Disclosed and claimed are compositions and methods for therapy and/or prevention of restenosis and/or atherosclerosis. The compositions can include an agent for inhibiting VEGF and an agent for including vessel maturation; for instance, the soluble VEGF receptor and ang-1. Embodiments can include kits.
摘要翻译：公开并要求保护的是用于治疗和/或预防再狭窄和/或动脉粥样硬化的组合物和方法。组合物可以包括用于抑制VEGF的试剂和用于包括血管成熟的试剂; 例如，可溶性VEGF受体和ang-1。实施例可以包括套件。

3. 发明申请

US20060051334A1 Injection of bone marrow-derived conditioned medium for angiogenesis 审中-公开
标题翻译：注射用于血管生成的骨髓来源的条件培养基
公开(公告)号：US20060051334A1
公开(公告)日：2006-03-09
申请号：US11117607
申请日：2005-04-27
申请人： Ran Kornowski , Shmuel Fuchs , Stephen Epstein , Martin Leon
发明人： Ran Kornowski , Shmuel Fuchs , Stephen Epstein , Martin Leon
IPC分类号： A61K48/00
CPC分类号： C12N5/0691 , A61K35/28 , A61K38/1825 , A61K38/1866 , A61K38/44 , A61K48/00 , C12N2502/1358 , C12Y114/13039 , A61K2300/00
摘要： Methods are provided for promoting formation of collateral blood supply at an ischemic site in tissue by culturing early attaching cells derived from growth of bone marrow aspirate in vitro, collecting early attaching cells produced by the bone marrow culture and injecting conditioned medium produced by culture of the early attaching cells into an ischemic site in heart or limb. The preferred early attaching cells for use in the invention methods are marrow-derived stromal cells. Any donor's bone marrow can be used in preparation of the conditioned medium. Optionally, the early attaching cells can be transfected with an angiogenesis promoting transgene encoding hypoxia inducing factor 1 alpha, a fibroblast growth factor and/or a nitric oxide synthase. Conditioned media containing angiogenic cytokines produced such cells are also provided for injection into tissue, such as heart or peripheral limb muscle, requiring formation of collateral blood supply.
摘要翻译：提供了通过体外培养早期粘附来自骨髓吸出物生长的细胞来促进组织缺血部位形成侧支血液供应的方法，收集由骨髓培养产生的早期附着细胞并注入通过培养产生的条件培养基早期将细胞附着到心脏或肢体的缺血部位。用于本发明方法的优选早期附着细胞是骨髓来源的基质细胞。任何供体的骨髓都可用于制备条件培养基。任选地，可以用编码缺氧诱导因子1α，成纤维细胞生长因子和/或一氧化氮合酶的血管生成促进转基因转染早期附着细胞。还提供了含有产生这种细胞的血管生成细胞因子的条件培养基用于注射到组织中，例如心脏或外周肢肌，需要形成侧支血液供应。

4. 发明授权

US06835193B2 Methods for controlled depth injections into interior body cavities 失效
标题翻译：用于受控深入注入内部体腔的方法
公开(公告)号：US06835193B2
公开(公告)日：2004-12-28
申请号：US10000851
申请日：2001-10-23
申请人： Stephen Epstein , Shmuel Fuchs , Ran Kornowski
发明人： Stephen Epstein , Shmuel Fuchs , Ran Kornowski
IPC分类号： A61M3100
CPC分类号： A61M25/0084 , A61B2090/062 , A61M2025/0089 , A61M2202/0413 , A61M2205/75 , A61M2202/0021
摘要： A flexible tissue injection catheter is used to accomplish injections at a precisely controlled depth of precisely controlled volumes of a therapeutic or diagnostic agent into an interior body cavity, such as the epicardium or myocardium of the heart. In one embodiment, the invention method includes repeated injections at spaced intervals along the myocardium or epicardium of sterile fluid containing autologous bone marrow aspirate to promote angiogenesis. For myocardial injection, depth penetration is controlled by using a catheter that allows the operator to control depth penetration by means of an adjustable needle stop attached to the catheter handle. In another embodiment depth penetration during epicardial injections is controlled by use of an injection catheter having an operator-controlled adjustable needle stop that produces a sensible signal, such as a visible or audible signal, marking each increment of needle tip exposed by operation of the adjustable needle stop.
摘要翻译：使用柔性组织注射导管在精确控制的治疗或诊断剂量的精确控制的深度上将注射物完成到内部体腔（例如心脏的心外膜或心肌）中。在一个实施方案中，本发明方法包括沿着包含自体骨髓抽吸物的无菌液体的心肌或外膜以间隔间隔重复注射以促进血管发生。对于心肌注射，通过使用导管来控制深度穿透，该导管允许操作者通过附接到导管手柄的可调节针止动器来控制深度穿透。在另一个实施方案中，通过使用具有操作者控制的可调针止动器的注射导管来控制心外膜注射期间的深度穿透，其产生可见信号，例如可见或可听信号，标记通过可调节针停止。

5. 发明授权

US06595979B1 Methods for sterile aspiration/reinjection of bodily fluid 有权
标题翻译：无菌吸入/注射体液的方法
公开(公告)号：US06595979B1
公开(公告)日：2003-07-22
申请号：US09999765
申请日：2001-10-23
申请人： Stephen Epstein , Shmuel Fuchs , Ran Kornowski
发明人： Stephen Epstein , Shmuel Fuchs , Ran Kornowski
IPC分类号： A61M3100
CPC分类号： A61M5/1456 , A61B2090/062 , A61M1/0005 , A61M5/14566 , A61M25/0084 , A61M2025/0089 , A61M2202/0413 , A61M2205/75 , Y10S977/906 , A61M2202/0021
摘要： Methods for aspiration and filtering of a bodily fluid containing undesired components are provided and for treatment of the bodily fluids in a sterile environment in preparation for reinjection of treated aspirate into a donor subject. The invention methods are particularly designed to facilitate transfection of aspirated cells with angiogenesis promoting molecules without danger to the technician or the donor prior to reinjection of the treated cells, either percutaneously or via a surgical opening via a catheter or injection needle. A pressure actuator attached to the sterile container is used to express treated fluids in precisely controlled volumes. The invention methods include delivery of treated fluids using a hand-held device with audible cues that correspond to an operator-selected injection volume and/or audible cues that correspond to needle penetration depth selected by the operator.
摘要翻译：提供了含有不需要的组分的体液的抽吸和过滤的方法，并用于在无菌环境中处理体液以准备将经处理的抽吸物再注射到供体受试者中。本发明的方法特别设计用于促进血管生成促进分子的吸出细胞的转染，而不经由经皮经皮或通过经由导管或注射针的外科手术开口重新注入处理的细胞而对技术人员或供体造成危险。附接到无菌容器的压力致动器用于以精确控制的体积表示经处理的流体。本发明的方法包括使用具有对应于操作员选择的注射体积的听觉提示的手持装置递送处理的流体和/或对应于由操作者选择的穿针深度的可听见的线索。

6. 发明申请

US20190000624A1 DISTAL ANCHOR APPARATUS AND METHODS FOR MITRAL VALVE REPAIR 审中-公开
公开(公告)号：US20190000624A1
公开(公告)日：2019-01-03
申请号：US16063193
申请日：2016-11-01
申请人： Peter WILSON , Stephen EPSTEIN , Peter BOYD , University of Maryland, Baltimore
发明人： Peter Wilson , Stephen Epstein , Peter Boyd , James S. Gammie
IPC分类号： A61F2/24 , A61B17/04
摘要： In some embodiments, an apparatus includes a needle, a pusher, a distal anchor having a distal end, a proximal end, a plurality of radially expandable members between the distal end and the proximal end, and a central bore, and an artificial chordae having a proximal portion and a distal portion terminating in a stopper. The pusher is disposed within a bore of the needle for movement between a delivery position and a deployed position. The distal anchor is disposed within the bore of the needle in a delivery configuration and movable between a delivery position and a deployed position. The artificial chordae is disposed within the bore of the distal anchor with the stopper distal to a distal end of the stopper and the proximal portion proximal to the proximal end of the distal anchor. The distal anchor is reconfigurable from the delivery configuration to a deployed configuration.

7. 发明申请

US20060281083A1 Identification of genes involved in angiogenesis, and development of an angiogenesis diagnostic chip to identify patients with impaired angiogenesis 审中-公开
标题翻译：识别涉及血管生成的基因，以及血管生成诊断芯片的发展，以鉴定血管发生受损的患者
公开(公告)号：US20060281083A1
公开(公告)日：2006-12-14
申请号：US10538635
申请日：2003-12-10
申请人： Stephen Epstein , Mary Burnett
发明人： Stephen Epstein , Mary Burnett
IPC分类号： C12Q1/68 , C12P19/34 , A61K48/00
CPC分类号： C12Q1/6883 , C12Q1/6837 , C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/156 , C12Q2600/172
摘要： The invention is directed to methods for angiotyping individual patients to predict the likelihood of whether a given individual will develop good vs. poor collaterals naturally. Accordingly, this can involve obtaining and providing a list of genes involved in collateral development. In particular, angiotyping individual patients can be used to predict the likelihood of whether a given individual will develop good vs. poor collaterals in response to specific angiogenesis therapy. From an array of genes that have been determined through experimental studies as being differentially expressed in tissues in which collaterals are developing in response to arterial occlusion, single nucleotide polymorphisms (SNPs), or other epigenetic changes, such as DNA methylation patterns, can be identified. SNPs and DNA methylation patterns are detected using microchips or similar technology assaying for all, or most, of the genes determined to play a role in collateral development. In addition, abnormally low or abnormally high differential expression of any combination of the candidate genes can be detected in such tissue as peripheral blood cells. The presence of a predisposition to develop poor vs. good collaterals is indicated by the presence of SNPs, and/or alterations in DNA methylation patterns, and/or difference in expression levels involving one or more of the genes.
摘要翻译：本发明涉及用于血管紧张素化个体患者的方法来预测给定个体是否自然发展良好与差的抵押物的可能性。因此，这可以涉及获得和提供参与发展的基因的列表。特别地，血管紧张素转化个体患者可以用于预测给定个体是否会对特异性血管生成治疗响应而发展良好或差的副作用的可能性。从已经通过实验研究确定的一系列基因，其在抵抗动脉阻塞发展的组织中差异表达，可以鉴定单核苷酸多态性（SNP）或其他表观遗传学变化，例如DNA甲基化模式。使用微芯片或类似技术测定所有或大多数被确定为担保发展中的作用的基因，检测SNP和DNA甲基化模式。此外，可以在诸如外周血细胞的组织中检测候选基因的任何组合的异常低或异常高的差异表达。由DNA的存在和/或DNA甲基化模式的改变和/或涉及一个或多个基因的表达水平的差异来表明存在发展不良与良好的副作用的倾向。

8. 发明申请

US20100216704A1 NOVEL GENES AND PROTEINS THAT HOME TO DEVELOPING MICROVESSELS 有权
标题翻译：新的基因和蛋白质，家庭开发微生物
公开(公告)号：US20100216704A1
公开(公告)日：2010-08-26
申请号：US12516961
申请日：2007-11-30
申请人： Anton Wellstein , Marcel O. Schmidt , Stephan Zbinden , Stephen Epstein , Mary Susan Burnett
发明人： Anton Wellstein , Marcel O. Schmidt , Stephan Zbinden , Stephen Epstein , Mary Susan Burnett
IPC分类号： A61K38/16 , C07K14/00 , C07H21/04 , C07K16/00 , C40B30/04
CPC分类号： C07K16/00 , C07K7/08 , C07K14/001 , C07K14/47 , C07K2319/00
摘要： Described herein are polypeptides that home to developing microvasculature, (also referred to as developing microvessels), such as newly developing microvasculature in mammals, particularly in humans, and to DNA that encodes such polypeptides. These polypeptides are referred to herein as developing microvasculature homing polypeptides. In a specific embodiment, the homing peptides are collateral vessel endothelia (CVE) homing polypeptides, which have been shown to home to collateral vessel endothelia after ischemia.
摘要翻译：本文描述的是家庭发展微血管（也称为发育微血管）的多肽，例如哺乳动物，特别是人类中新发展的微血管，以及编码这些多肽的DNA。这些多肽在本文中称为显影微血管归巢多肽。在一个具体的实施方案中，归巢肽是旁侧血管内皮（CVE）归巢多肽，其已被证明在局部缺血后携带侧支血管内皮。

9. 发明申请

US20050282163A1 Polymorphisms in elastin, fibrillin and related genes as predisposing to restenosis and to a therosclerosis 审中-公开
标题翻译：弹性蛋白，纤维蛋白和相关基因的多态性倾向于再狭窄和动脉粥样硬化
公开(公告)号：US20050282163A1
公开(公告)日：2005-12-22
申请号：US10502984
申请日：2003-02-03
申请人： Stephen Epstein
发明人： Stephen Epstein
IPC分类号： A61K39/395 , A61K48/00 , C12Q1/68
CPC分类号： C12Q1/6883 , A61K48/00 , C12Q2600/156 , C12Q2600/158
摘要： Methods are provided for assessing the risk of developing restenosis in an individual, by detecting the presence of biologically important polymorphisms in genes involved in the formation of the elastin fiber network. In particular, detection of polymorphorphisms in the elastin, fibrillin, fibrillin-1, fibrillin-2, lysyl oxidase, microfibril-associated glycoprotein, biglycan, osteopontin, and/or decorin genes allows the rapid and objective prediction of the risk of developing restenosis. Methods for treating restenosis and for reducing its recurrence also are provided.
摘要翻译：提供了通过检测参与形成弹性蛋白纤维网络的基因中存在生物学上重要的多态性来评估个体发展再狭窄的风险的方法。特别地，检测弹性蛋白，原纤维蛋白，原纤维蛋白-1，原纤维蛋白-2，赖氨酰氧化酶，微纤维相关糖蛋白，双糖链球蛋白，骨桥蛋白和/或核心蛋白聚糖基因组中的多形性允许快速和客观地预测发展为再狭窄的风险。还提供了治疗再狭窄和减少其复发的方法。

10. 发明申请

US20060099608A1 Methods of diagnosing cardiovascular disease 审中-公开
标题翻译：诊断心血管疾病的方法
公开(公告)号：US20060099608A1
公开(公告)日：2006-05-11
申请号：US11078743
申请日：2005-03-11
申请人： Stephen Epstein , Mary Burnett
发明人： Stephen Epstein , Mary Burnett
IPC分类号： C12Q1/68 , A61K38/17
CPC分类号： G01N33/6893 , C12Q1/6883 , C12Q2600/158 , G01N33/74 , G01N2333/575 , G01N2800/32 , G01N2800/324
摘要： The invention relates to predicting which individuals are at risk of developing atherosclerotic vascular disease, and once having disease, which individuals are at risk of experiencing plaque rupture which, depending on the site of the plaque, could produce myocardial infarction, stroke, critical limb ischemia, or other vascular event. The invention further relates to methods of diagnosing and aiding in the diagnosis of vascular conditions such as atherosclerosis, premature coronary artery disease and coronary artery disease, by detecting a resistin gene product in an individual. The invention further relates to methods of predicting, and aiding in predicting, the likelihood that an individual will experience a vascular event, such as but not limited to, a myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack (TIA), or critical limb ischemia.
摘要翻译：本发明涉及预测哪些个体处于发展动脉粥样硬化性血管疾病的风险中，并且一旦发生疾病，哪些个体处于经历斑块破裂的风险中，根据斑块的位置，其可产生心肌梗塞，中风，关键性肢体缺血，或其他血管事件。本发明还涉及通过检测个体中抵抗素基因产物来诊断和辅助诊断血管疾病如动脉粥样硬化，冠状动脉过早冠状动脉疾病和冠状动脉疾病的方法。本发明还涉及预测和辅助预测个体将经历血管事件（例如但不限于）心肌梗塞，急性冠状动脉综合征，中风，短暂性脑缺血发作（TIA）或严重肢体缺血。

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