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1. 发明申请

WO2010030779A1 ISOLATION OF MICROBUBBLES OF SELECTED SIZE RANGE FROM POLYDISPERSE MICROBUBBLES 审中-公开
标题翻译：从多晶硅微球中分离选择尺寸范围的微生物
公开(公告)号：WO2010030779A1
公开(公告)日：2010-03-18
申请号：PCT/US2009/056513
申请日：2009-09-10
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, A. , FESHITAN, Jameel, Adebayo , CHEN, Cherry , SIRSI, Shashank, Ramesh , KWAN, James, Jing
发明人： BORDEN, Mark, A. , FESHITAN, Jameel, Adebayo , CHEN, Cherry , SIRSI, Shashank, Ramesh , KWAN, James, Jing
IPC分类号： A61B8/00
CPC分类号： A61K49/223
摘要： In one aspect of the disclosed subject matter, a method for isolating target microbubbles having a predetermined size range from polydisperse microbubbles is disclosed. The method includes applying a first centrifugal field having a first field strength to a suspension comprising the polydisperse microbubbles for a first duration of time, thereby forming a first infranatant comprising at least a portion of target microbubbles and a first supernatant cake comprising microbubbles having a greater size than the target microbubbles; removing the first supernatant cake; applying a second centrifugal field having a second field strength to the first infranatant for a second duration of time, the second field strength being greater than the first field strength, thereby forming a second supernatant cake comprising at least a portion of the target microbubbles and second infranatant comprising microbubbles having a smaller size than the target microbubbles; and isolating the second supernatant cake. In another aspect of the disclosed subject matter, a method for performing high frequency ultrasonic imaging using isolated microbubbles is provided.
摘要翻译：在所公开的主题的一个方面，公开了一种从多分散微泡分离具有预定尺寸范围的目标微泡的方法。该方法包括将第一场强度的第一离心场施加到包含多分散微泡的悬浮液的第一持续时间，由此形成包含至少一部分目标微泡的第一细胞悬液，以及包含具有更大的微泡的第一上清液滤饼尺寸比目标微泡; 去除第一上清液滤饼; 在第二持续时间内将具有第二场强的第二离心场施加到所述第一干扰素，所述第二场强大于所述第一场强，从而形成包含所述目标微泡的至少一部分的第二上清液滤饼和第二场强包含具有比目标微泡更小的微泡的微泡; 并分离第二上清液滤饼。在所公开的主题的另一方面，提供了一种使用隔离微泡进行高频超声成像的方法。

2. 发明申请

WO2011028690A1 MICROBUBBLE DEVICES, METHODS AND SYSTEMS 审中-公开
标题翻译：微型设备，方法和系统
公开(公告)号：WO2011028690A1
公开(公告)日：2011-03-10
申请号：PCT/US2010/047263
申请日：2010-08-31
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, A. , LIMA, Eric, G. , HUNG, Clark, T. , SIRSI, Shashank, Ramesh
发明人： BORDEN, Mark, A. , LIMA, Eric, G. , HUNG, Clark, T. , SIRSI, Shashank, Ramesh
IPC分类号： C12N5/00 , C12N5/02
CPC分类号： C12M41/48 , C12N5/0655 , C12N2533/76
摘要： A hydrogel tissue engineering scaffold having microbubbles dispersed therein is disclosed. Also, a system for cell culturing including a controller and actuator to apply dynamic deformational loading to a hydrogel is disclosed. Also disclosed are methods for producing hydrogels with microbubbles and for culturing cells using hydrogels with microbubbles.
摘要翻译：公开了一种其中分散有微泡的水凝胶组织工程支架。此外，公开了一种用于细胞培养的系统，包括控制器和致动器以对水凝胶施加动态变形负荷。还公开了用微泡制备水凝胶的方法以及使用具有微泡的水凝胶培养细胞的方法。

3. 发明申请

WO2010030819A1 SYSTEMS AND METHODS FOR OPENING A TISSUE 审中-公开
标题翻译：用于打开组织的系统和方法
公开(公告)号：WO2010030819A1
公开(公告)日：2010-03-18
申请号：PCT/US2009/056565
申请日：2009-09-10
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , KONOFAGOU, Elisa, E. , CHOI, James, J. , BORDEN, Mark, A.
发明人： KONOFAGOU, Elisa, E. , CHOI, James, J. , BORDEN, Mark, A.
IPC分类号： A61N7/00
CPC分类号： A61M37/0092 , A61B5/055 , A61B8/0808 , A61B8/481 , A61B2090/374 , A61M31/005 , A61N7/00 , A61N2007/0039
摘要： Systems and methods for opening a tissue to a target value are disclosed herein. In an exemplary method, a region of the tissue is targeted for opening, a size range of microbubbles corresponding to the target value is determined, microbubbles of the size range are positioned in proximity to the targeted region, and an ultrasound beam is applied to the targeted region such that the tissue is opened with the assistance of the microbubbles to the target value.
摘要翻译：本文公开了将组织打开至目标值的系统和方法。在一种示例性方法中，组织的区域被打开，确定与目标值相对应的微泡的尺寸范围，尺寸范围的微泡位于目标区域附近，并且将超声波束施加到使得组织在微泡的帮助下打开到目标值。

4. 发明申请

WO2011139927A1 METHODS DEVICES AND SYSTEMS OF PREPARING TARGETED MICROBUBBLE SHELLS 审中-公开
标题翻译：方法制备目标微泡体的装置和系统
公开(公告)号：WO2011139927A1
公开(公告)日：2011-11-10
申请号：PCT/US2011/034704
申请日：2011-04-30
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, A. , CHEN, Cherry
发明人： BORDEN, Mark, A. , CHEN, Cherry
IPC分类号： A61K9/14
CPC分类号： A61K49/223 , A61K9/0087 , A61K47/6925 , A61K49/221 , A61M37/0092 , G01N33/5432
摘要： Targeted microbubbles are generated by post-labeling buried ligand microbubbles. According to embodiments, buried ligand microbubbles are created with steric brushes protecting functionalized polymer tethers. Ligands were attached to the functionalized tethers by diffusion of ligands of a small size through the steric barrier. The steric barrier was substantially capable of hindering access to the tethers by larger molecules. The embodiments disclosed include methods for creating microbubble batches that can be loaded with selected ligands, for titrating the targeting ligands thereby to reduce waste and cost, and for using resulting buried ligand molecules for medical purposes.
摘要翻译：靶向微泡通过后置标记掩埋的配体微泡产生。根据实施方案，用保护官能化聚合物系链的空间刷产生掩埋的配体微泡。配体通过扩散小尺寸的配体通过空间屏障附着在功能化的系绳上。空间屏障基本上能够阻碍大分子进入系绳。所公开的实施方案包括用于产生可加载选定配体的微泡批料的方法，用于滴定靶向配体从而减少浪费和成本，以及将所得的掩埋配体分子用于医疗目的。

5. 发明申请

WO2011075557A1 METHODS, DEVICES, AND SYSTEMS FOR ON-DEMAND ULTRASOUND-TRIGGERED DRUG DELIVERY 审中-公开
标题翻译：超声波诱导药物递送的方法，装置和系统
公开(公告)号：WO2011075557A1
公开(公告)日：2011-06-23
申请号：PCT/US2010/060691
申请日：2010-12-16
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , KOHANE, Daniel, S. , EPSTEIN-BARASH, Hila , BORDEN, Mark, A.
发明人： KOHANE, Daniel, S. , EPSTEIN-BARASH, Hila , BORDEN, Mark, A.
IPC分类号： A61N1/30
CPC分类号： A61M37/0069 , A61K9/0009 , A61K9/06 , A61K9/107 , A61K41/0028 , A61L2300/602 , A61L2300/62 , A61L2300/626 , A61L2400/06 , A61M37/0092
摘要： Injectable or implantable drug delivery systems providing on-demand ultrasound- triggered drug release and methods for controlling the release of drug in a patient are provided herein. The on-demand drug delivery systems contain a drug depot and a drug encapsulated in an encapsulating material, where the encapsulating material is different from the depot. In the preferred embodiment, the depot also contains microbubbles that encapsulate one or more gases. The microbubbles enhance the drug release when ultrasound is applied compared to the same system in the absence of microbubbles. In a preferred embodiment, the drug delivery system, contains an encapsulating material, preferably liposomes, a drug to be delivered, microbubbles, and at least two hydrogel- forming precursor components. Following injection or implantation, the patient can control the time, location and dosage released by administering ultrasound.
摘要翻译：本文提供了提供按需超声引发的药物释放的注射或可植入药物递送系统以及用于控制患者药物释放的方法。按需药物递送系统包含药物贮库和封装在封装材料中的药物，其中封装材料不同于贮存库。在优选实施方案中，储库还包含封装一种或多种气体的微泡。当不含微泡时，微泡与超声波相比可以增强药物的释放。在优选实施方案中，药物递送系统包含封装材料，优选脂质体，待递送药物，微泡和至少两种形成水凝胶的前体组分。在注射或植入后，患者可以通过施用超声波来控制释放的时间，位置和剂量。

6. 发明申请

WO2011034892A3 SYSTEMS, METHODS, AND DEVICES FOR MICROBUBBLES 审中-公开
公开(公告)号：WO2011034892A3
公开(公告)日：2011-03-24
申请号：PCT/US2010/048887
申请日：2010-09-15
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, A. , SWANSON, Edward, J.
发明人： BORDEN, Mark, A. , SWANSON, Edward, J.
IPC分类号： A61B8/00
摘要： A suspension of gas-filled microbubbles can be synthesized by sonicating a lipid solution and a first gas in a reaction volume. The resulting microbubble suspension can be stored for later use, for example, for infusion into a patient for gas delivery thereto. Various techniques can improve the shelf life of the microbubbles. For example, the microbubble suspension can be freeze-dried to remove water and the first gas therefrom while leaving the microbubble shells intact. In an alternative, the microbubble suspension can be frozen. In still another alternative, the microbubble suspension can be formed with a first gas that has a low solubility, thereby creating microbubbles with increased stability. Prior to use, the microbubble suspension can be prepared by exchanging the gas in the microbubble cores, rehydrating, and/or raising the temperature of the stored microbubbles.

7. 发明申请

WO2011025893A1 SYSTEMS, METHODS, AND DEVICES FOR PRODUCTION OF GAS-FILLED MICROBUBBLES 审中-公开
标题翻译：用于生产气体填充的微生物的系统，方法和装置
公开(公告)号：WO2011025893A1
公开(公告)日：2011-03-03
申请号：PCT/US2010/046854
申请日：2010-08-26
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, A. , SWANSON, Edward, J.
发明人： BORDEN, Mark, A. , SWANSON, Edward, J.
IPC分类号： B01D51/08 , B01D51/00
CPC分类号： B01J13/04 , A61K49/223
摘要： Gas-filled microbubbles can be synthesized using a continuous flow chamber and a sonicator. The resulting microbubble solution can be size-sorted for a particular application, such as injection into a patient for gas delivery thereto. The microbubble solution may be concentrated to have greater than 50% volume gas while maintaining microbubble sizes below 10 μm. Control of the microbubble generation process can yield highly stable microbubbles. The microbubbles may retain over half of their original gas payload for over three weeks while exhibiting minimal change in microbubble size. The systems, methods, and devices described herein thus allow for continuous or batch- wise continuous production of gas-filled microbubbles that readily release their gas payload when introduced into an under-saturated or de- saturated solution.
摘要翻译：气体充气微泡可以使用连续流动室和超声波仪来合成。所得到的微泡溶液可以针对特定应用进行大小分类，例如向患者注射气体以输送至其中。微泡溶液可以被浓缩以具有大于50体积％的气体，同时保持低于10微米的微泡尺寸。微泡生成过程的控制可以产生高度稳定的微泡。微泡可能保留超过一半的原始气体有效载荷超过三周，同时显示微泡尺寸的最小变化。因此，本文所述的系统，方法和装置允许连续或间歇地连续生产气体填充的微泡，其在引入欠饱和或不饱和溶液时容易释放其气体有效载荷。

8. 发明公开

EP2334239A1 ISOLATION OF MICROBUBBLES OF SELECTED SIZE RANGE FROM POLYDISPERSE MICROBUBBLES 审中-公开
标题翻译：多分散微球从一定尺寸范围内分离微球
公开(公告)号：EP2334239A1
公开(公告)日：2011-06-22
申请号：EP09813604.7
申请日：2009-09-10
申请人： The Trustees of Columbia University in the City of New York
发明人： BORDEN, Mark, A. , FESHITAN, Jameel, Adebayo , CHEN, Cherry , SIRSI, Shashank, Ramesh , KWAN, James, Jing
IPC分类号： A61B8/00
CPC分类号： A61K49/223
摘要： In one aspect of the disclosed subject matter, a method for isolating target microbubbles having a predetermined size range from polydisperse microbubbles is disclosed. The method includes applying a first centrifugal field having a first field strength to a suspension comprising the polydisperse microbubbles for a first duration of time, thereby forming a first infranatant comprising at least a portion of target microbubbles and a first supernatant cake comprising microbubbles having a greater size than the target microbubbles; removing the first supernatant cake; applying a second centrifugal field having a second field strength to the first infranatant for a second duration of time, the second field strength being greater than the first field strength, thereby forming a second supernatant cake comprising at least a portion of the target microbubbles and second infranatant comprising microbubbles having a smaller size than the target microbubbles; and isolating the second supernatant cake. In another aspect of the disclosed subject matter, a method for performing high frequency ultrasonic imaging using isolated microbubbles is provided.
摘要翻译：在所公开的主题的一个方面中，公开了用于从多分散微泡分离具有预定尺寸范围的目标微泡的方法。该方法包括将具有第一场强度的第一离心场施加到包含多分散微泡的悬浮液持续第一持续时间，从而形成包含至少一部分目标微泡的第一infranatant和包含具有更大微泡的微泡的第一上清液饼尺寸比目标微泡大; 除去第一上清液滤饼; 将具有第二场强度的第二离心场施加到第一浸润液持续第二持续时间，第二场强大于第一场强度，由此形成包含至少一部分目标微泡的第二上清液块，以及第二时间段包含具有比目标微泡更小尺寸的微泡的infranatant; 并分离第二上清液滤饼。在所公开的主题的另一方面中，提供了一种使用分离的微泡进行高频超声成像的方法。

9. 发明公开

EP2470287A1 SYSTEMS, METHODS, AND DEVICES FOR PRODUCTION OF GAS-FILLED MICROBUBBLES 审中-公开
标题翻译：系统，方法和设备用于生产充气微泡
公开(公告)号：EP2470287A1
公开(公告)日：2012-07-04
申请号：EP10812628.5
申请日：2010-08-26
申请人： The Trustees of Columbia University in the City of New York
发明人： BORDEN, Mark, A. , SWANSON, Edward, J.
IPC分类号： B01D51/08 , B01D51/00
CPC分类号： B01J13/04 , A61K49/223
摘要： Gas-filled microbubbles can be synthesized using a continuous flow chamber and a sonicator. The resulting microbubble solution can be size-sorted for a particular application, such as injection into a patient for gas delivery thereto. The microbubble solution may be concentrated to have greater than 50% volume gas while maintaining microbubble sizes below 10 μm. Control of the microbubble generation process can yield highly stable microbubbles. The microbubbles may retain over half of their original gas payload for over three weeks while exhibiting minimal change in microbubble size. The systems, methods, and devices described herein thus allow for continuous or batch- wise continuous production of gas-filled microbubbles that readily release their gas payload when introduced into an under-saturated or de- saturated solution.

10. 发明公开

EP2566459A1 METHODS DEVICES AND SYSTEMS OF PREPARING TARGETED MICROBUBBLE SHELLS 审中-公开
标题翻译：方法，用于定向微观生产装置和系统BUBBLES SLEEVES
公开(公告)号：EP2566459A1
公开(公告)日：2013-03-13
申请号：EP11778080.9
申请日：2011-04-30
申请人： The Trustees of Columbia University in the City of New York
发明人： BORDEN, Mark, A. , CHEN, Cherry
IPC分类号： A61K9/14
CPC分类号： A61K49/223 , A61K9/0087 , A61K47/6925 , A61K49/221 , A61M37/0092 , G01N33/5432
摘要： Targeted microbubbles are generated by post-labeling buried ligand microbubbles. According to embodiments, buried ligand microbubbles are created with steric brushes protecting functionalized polymer tethers. Ligands were attached to the functionalized tethers by diffusion of ligands of a small size through the steric barrier. The steric barrier was substantially capable of hindering access to the tethers by larger molecules. The embodiments disclosed include methods for creating microbubble batches that can be loaded with selected ligands, for titrating the targeting ligands thereby to reduce waste and cost, and for using resulting buried ligand molecules for medical purposes.

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