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1. 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。

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

US07097832B1 Intramyocardial injection of autologous bone marrow 有权
标题翻译：心肌内注射自体骨髓
公开(公告)号：US07097832B1
公开(公告)日：2006-08-29
申请号：US09868411
申请日：2000-03-30
申请人： Ran Kornowski , Shmuel Fuchs , Stephen E. Epstein , Martin B. Leon
发明人： Ran Kornowski , Shmuel Fuchs , Stephen E. Epstein , Martin B. Leon
IPC分类号： A01N63/00 , C12N5/00 , C12N5/06
CPC分类号： A61K38/193 , A61K35/28 , A61K38/1709 , A61K2300/00
摘要： A method of treating cardiac or myocardial conditions comprises the administration of an effective amount of autologous bone marrow. The bone marrow may optionally be stimulated and/or administered in combination with a pharmaceutical drug, protein, gene or other factor or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation or migration or blood vessel formation.
摘要翻译：治疗心脏或心肌病症的方法包括施用有效量的自体骨髓。骨髓可以任选地与可以增强血管生成生长因子的骨髓产生和/或促进内皮细胞增殖或迁移或血管形成的药物，蛋白质，基因或其他因子或治疗组合而被刺激和/或施用。

5. 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。

6. 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。

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