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1. 发明申请

WO2012019146A1 SYSTEMS, METHODS, AND DEVICES FOR ULTRASONIC ASSESSMENT OF CANCER AND RESPONSE TO THERAPY 审中-公开
标题翻译：用于癌症超声评估和治疗反应的系统，方法和装置
公开(公告)号：WO2012019146A1
公开(公告)日：2012-02-09
申请号：PCT/US2011/046830
申请日：2011-08-05
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, Andrew , KANDEL, Jessica , SIRSI, Shashank, Ramesh , YAMASHIRO, Darrell
发明人： BORDEN, Mark, Andrew , KANDEL, Jessica , SIRSI, Shashank, Ramesh , YAMASHIRO, Darrell
IPC分类号： A61B17/20
CPC分类号： A61K49/223 , A61B8/085 , A61B8/481 , A61K49/221 , A61N7/02 , A61N2007/0039
摘要： Microbubbles can be injected into the bloodstream of a patient, for example, a cancer patient undergoing a treatment specifically targeting a biological process in a tumor. The injected microbubbles can act as vascular contrast agents, which can be detected in vivo using high-frequency ultrasound imaging. The microbubbles can have a surface chemistry that allows them to bind to molecular targets in the tumor vasculature. After injection, the microbubbles can selectively adhere to endothelia expressing a target receptor. The selective adhesion can be used to quantify the tumor vasculature in vivo. By imaging the adhered microbubbles with ultrasound, an indication of how tumor vasculature is affected by a specific cancer treatment can be obtained. Such techniques can be used in a clinical setting for rapid determination of anti- cancer treatment efficacy for individual patients.
摘要翻译：微泡可以注射到患者的血液中，例如，经历特异性靶向肿瘤中生物过程的治疗的癌症患者。注射的微泡可以作为血管造影剂，其可以使用高频超声成像在体内检测。微泡可以具有允许它们结合肿瘤脉管系统中的分子靶标的表面化学物质。注射后，微泡可以选择性地粘附到表达目标受体的内皮。选择性粘附可用于体内肿瘤脉管系统的定量。通过用超声波对粘附的微泡进行成像，可以获得肿瘤脉管系统如何受特定癌症治疗影响的指示。这样的技术可以用于临床环境中，用于快速测定个体患者的抗癌治疗功效。

2. 发明申请

WO2012030675A1 SYSTEMS, METHODS, AND DEVICES FOR PLASMID GENE TRANSFECTION USING POLYMER-MODIFIED MICROBUBBLES 审中-公开
标题翻译：使用聚合物改性的微生物进行PLASMID基因转移的系统，方法和设备
公开(公告)号：WO2012030675A1
公开(公告)日：2012-03-08
申请号：PCT/US2011/049455
申请日：2011-08-26
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, Andrew , SIRSI, Shashank, Ramesh
发明人： BORDEN, Mark, Andrew , SIRSI, Shashank, Ramesh
IPC分类号： A61B8/00 , A61K49/00
CPC分类号： A61K9/1075 , A61K31/7088 , A61K41/0028 , A61K47/59 , A61K47/60 , A61K47/62 , A61K47/6845 , A61K47/6925 , A61K48/0041 , A61K49/223
摘要： Thiolated polyethylenimine (PEI) polymers can be covalently attached to lipid shell microbubbles. The PEI polymer can be modified with polyethylene glycol (PEG) chains to improve biocompatibility. The covalent attachment of the PEI polymer to the microbubble shell can result from a bond between a free sulfhydryl group (SH) of the thiolated PEI and a free maleimide group on the microbubble shell. DNA can be electrostatically bound to the PEI polymers to form polyplexes. A plurality of the polyplex -microbubble hybrids can be injected into a patient and can be imaged via ultrasound. While circulating in the bloodstream, and in particular, within a region of interest, high-pressure, low-frequency acoustic energy can be applied, thereby causing destruction by cavitation. Such cavitation can transiently increase the permeability of the endothelial vasculature thereby allowing plasmid DNA of the polyplexes carried by the microbubbles to be delivered to targeted cells.
摘要翻译：硫醇化聚乙烯亚胺（PEI）聚合物可以共价连接到脂壳微泡。 PEI聚合物可以用聚乙二醇（PEG）链改性以提高生物相容性。 PEI聚合物与微泡壳的共价连接可以由硫醇化PEI的游离巯基（SH）与微泡壳上的游离的马来酰亚胺基团之间的键形成。 DNA可以静电结合到PEI聚合物上以形成复合物。多个复合微泡混合物可以注射到患者体内并且可以通过超声波成像。虽然在血流中，特别是在感兴趣的区域内循环，但是可以施加高压，低频声能，从而引起空化破坏。这种气蚀可以瞬时地增加内皮脉管系统的通透性，从而允许由微泡承载的复合物的质粒DNA被递送到靶细胞。

3. 发明申请

WO2009043031A2 MICROBUBBLES AND METHODS FOR OXYGEN DELIVERY 审中-公开
标题翻译：微管和氧气输送方法
公开(公告)号：WO2009043031A2
公开(公告)日：2009-04-02
申请号：PCT/US2008/078167
申请日：2008-09-29
申请人： CHILDREN'S MEDICAL CENTER CORPORATION , THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , KHEIR, John , BORDEN, Mark, Andrew , MCGOWAN, Francis, X.
发明人： KHEIR, John , BORDEN, Mark, Andrew , MCGOWAN, Francis, X.
IPC分类号： A61K47/48 , A61P9/10
CPC分类号： A61K47/6925
摘要： Compositions containing a carrier and microbubbles encapsulating one or more gases, preferably oxygen, and methods for making and using the compositions are described herein. The microbubbles contain a lipid envelope formed of at least one base lipid and at least one emulsifying agent. The compositions may be administered to a patient to quickly deliver large amounts of oxygen to the patient's blood supply or directly to a tissue in need of oxygen. The compositions may be administered via injection or as a continuous infusion. The compositions contain a concentrated microbubble suspension, where the suspension contains at least 40 ml oxygen/dl suspension. The microbubbles are preferably less than 20 microns in diameter, more preferably less than 15 microns in diameter. The microbubbles described herein may be administered to a patient in an effective amount to increase in oxygen concentration in the patient's blood, and/or one or more tissues or organs. The microbubbles may be administered alone or in combination with other treatments as an adjunctive therapy.
摘要翻译：本文描述了含有包封一种或多种气体（优选氧气）的载体和微泡的组合物以及制备和使用该组合物的方法。微泡包含由至少一种基础脂质和至少一种乳化剂形成的脂质包膜。可将组合物给予患者以快速将大量氧气递送至患者的血液供应或直接输送至需要氧气的组织。该组合物可以通过注射或作为连续输注来施用。该组合物含有浓缩的微泡悬浮液，其中该悬浮液含有至少40ml氧/ dl悬浮液。微泡直径优选小于20微米，更优选直径小于15微米。本文所述的微泡可以以有效量施用给患者以增加患者血液和/或一种或多种组织或器官中的氧浓度。微泡可以单独使用或与其他治疗组合使用作为辅助治疗。

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