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1. 发明申请

US20110125079A1 Echogenic Polymer Microcapsules and Nanocapsules and Methods for Production and Use Thereof 有权
标题翻译：超生物聚合物微胶囊和纳米胶囊及其生产和使用方法
公开(公告)号：US20110125079A1
公开(公告)日：2011-05-26
申请号：US13017345
申请日：2011-01-31
申请人： Margaret A. Wheatley , Dalia El-Sherif
发明人： Margaret A. Wheatley , Dalia El-Sherif
IPC分类号： A61M37/00 , A61K49/22 , A61K9/50 , A61K9/51 , B82Y5/00
CPC分类号： C08L67/04 , A61K47/08 , A61K47/186 , A61K49/223 , B01J13/02 , B01J13/206 , C08L29/04 , G01N29/046
摘要： Methods for producing echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive compounds as well as targeted imaging and delivery to selected tissues and cells are provided. Compositions containing these echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive agents are also provided.
摘要翻译：提供了用于生物活性化合物的诊断成像和递送以及靶向成像和递送至所选择的组织和细胞的用于产生回声聚合物微胶囊和纳米胶囊的方法。还提供了含有用于诊断成像和递送生物活性剂的这些回声聚合物微胶囊和纳米胶囊的组合物。

2. 发明申请

US20090028797A1 Novel polymeric ultrasound contrast agent and methods of making thereof 审中-公开
标题翻译：新型高分子超声造影剂及其制备方法
公开(公告)号：US20090028797A1
公开(公告)日：2009-01-29
申请号：US12157755
申请日：2008-06-13
申请人： Margaret A. Wheatley , John Lewandowski
发明人： Margaret A. Wheatley , John Lewandowski
IPC分类号： A61K49/22
CPC分类号： A61K49/226 , A61K9/1647 , A61K9/1694 , A61K9/5153 , A61K9/5192
摘要： The present invention provides a novel method of manufacturing nanosized polymeric echogenic contrast agents. The method of the present invention comprises a modified salting out process which results on nanosized polymeric capsules encapsulating an aqueous core that is subsequently evacuated. The compositions of the present invention can be used as contrast agents as well as to deliver therapeutic agents to specific targets.
摘要翻译：本发明提供一种制造纳米尺寸聚合物回声造影剂的新方法。本发明的方法包括改进的盐析过程，其导致封装随后抽空的水性核心的纳米尺寸的聚合物胶囊。本发明的组合物可用作造影剂以及将治疗剂递送至特定靶标。

3. 发明授权

US4933185A System for controlled release of biologically active compounds 失效
标题翻译：用于控制释放生物活性化合物的系统
公开(公告)号：US4933185A
公开(公告)日：1990-06-12
申请号：US223887
申请日：1988-07-11
申请人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
发明人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
IPC分类号： A61K9/16 , A61K9/50 , A61K9/62
CPC分类号： A61K9/1664 , A61K9/1652 , A61K9/5031 , Y10S514/885 , Y10S514/963 , Y10T428/2984 , Y10T428/2985
摘要： A controlled release system for delivery of a biologically-active substance. In one embodiment, there is a delayed release of a biologically-active substance. In a second embodiment, the delayed release is preceded by an initial release of biologically active substance. In other variations of the system, there are mulitple discrete releases over time or a continuous slow release combined with discrete releases. The delayed exposure is achieved through the design and construction of the system, specifically, formation of ionically-coated microcapsules around the biologically-active substance in conjunction with a microcapsule core-degrading enzyme. Release of active substance takes place in a burst at such a time as the core degrading enzyme has reduced the core to a molecular weight too low to support enough interaction with the cationic skin to maintain its integrity as a skin. In one example, microcapsules are formed of an ionically cross-linked polysaccharide, calcium alginate, which is further ionically coated with a poly-cationic skin of poly-L-lysine. The capsule coating serves a dual purpose: to control diffusion of the biologically-active substance and the core-degrading enzyme and as a substrate for the mechanism by which the biologically-active substance is released after a time delay.
摘要翻译：用于递送生物活性物质的控制释放系统。在一个实施方案中，存在生物活性物质的延迟释放。在第二个实施方案中，延迟释放之前是生物活性物质的初始释放。在系统的其他变体中，随着时间的推移有多种离散的释放，或者连续的缓慢释放与离散的释放相结合。延迟曝光是通过系统的设计和构建来实现的，具体地说，在微生物活性物质周围与微胶囊核心降解酶结合形成离子涂覆的微胶囊。活性物质的释放在核心降解酶已经将核心降低到分子量太低以至于不能支持与阳离子皮肤的足够相互作用以维持其作为皮肤的完整性的时候发生。在一个实例中，微胶囊由离子交联的多糖，藻酸钙形成，其进一步离子地涂覆有聚-L-赖氨酸的多阳离子皮肤。胶囊涂层具有双重目的：控制生物活性物质和核心降解酶的扩散，并且作为延迟后释放生物活性物质的机制的底物。

4. 发明授权

US09220709B2 Drug loaded contrast agents: combining diagnosis and therapy 有权
标题翻译：药物负荷造影剂：结合诊断和治疗
公开(公告)号：US09220709B2
公开(公告)日：2015-12-29
申请号：US12301423
申请日：2007-05-21
申请人： Margaret A. Wheatley , Odelia Mualem Burstein , John R. Eisenbrey , Dalia El-Sherif
发明人： Margaret A. Wheatley , Odelia Mualem Burstein , John R. Eisenbrey , Dalia El-Sherif
IPC分类号： A61K9/51 , A61K31/704 , A61K31/405 , A61K9/00 , A61K9/16 , A61K41/00 , A61K47/48 , A61K49/22
CPC分类号： A61K31/405 , A61K9/0009 , A61K9/1647 , A61K9/1694 , A61K9/5153 , A61K9/5192 , A61K41/0028 , A61K47/48238 , A61K47/48869 , A61K47/62 , A61K47/6925 , A61K49/225
摘要： This invention provides an improvement to methods of drug loading of ultrasound contrast agents. Echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof produced by the method of the invention wherein the echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof contain at least 10% more of a drug as compared to (1) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug prior to emulsifying or (2) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug to lyophilized polymer microcapsules, nanocapsules, or mixtures thereof.
摘要翻译：本发明提供了对超声造影剂的药物加载方法的改进。通过本发明的方法制备的具有回生性药物的聚合物微胶囊，纳米胶囊或其混合物，其中与（1）回声药物相比，含回声药物的聚合物微胶囊，纳米胶囊或其混合物含有至少10％以上的药物通过在乳化之前添加药物或（2）通过将药物加入到冻干的聚合物微胶囊，纳米胶囊或其混合物中制备的回送药物负载的聚合物微胶囊，纳米胶囊或其混合物而制备的负载聚合物微胶囊，纳米胶囊或其混合物。

5. 发明申请

US20110264117A1 TISSUE JOINING DEVICE AND INSTRUMENT FOR ENABLING USE OF A TISSUE JOINING DEVICE 审中-公开
标题翻译：组织接合装置和使用组织接合装置的仪器
公开(公告)号：US20110264117A1
公开(公告)日：2011-10-27
申请号：US12990725
申请日：2009-05-01
申请人： Bradley Edward Layton , Margaret A. Wheatley , Ari Brooks , Andrew J. Bohl , Daniel S. Frame
发明人： Bradley Edward Layton , Margaret A. Wheatley , Ari Brooks , Andrew J. Bohl , Daniel S. Frame
IPC分类号： A61B17/10 , A61B17/08
CPC分类号： A61B17/11 , A61B17/0643 , A61B17/1114 , A61B17/320016 , A61B2017/00473 , A61B2017/00893 , A61B2017/0648 , A61B2017/1135 , A61B2017/320052
摘要： A tissue joining device and a surgical instrument for employing the tissue joining device are provided. The tissue joining device may be designed such that a first member may be inserted into a second member in discrete increments so that two lumen structures can properly be combined.
摘要翻译：提供了一种用于使用组织接合装置的组织接合装置和外科器械。组织接合装置可以设计成使得第一构件可以以离散的增量插入到第二构件中，使得可以适当地组合两个内腔结构。

6. 发明申请

US20090196827A1 Drug Loaded Contrast Agents: Combining Diagnosis and Therapy 有权
标题翻译：药物加载对比剂：结合诊断和治疗
公开(公告)号：US20090196827A1
公开(公告)日：2009-08-06
申请号：US12301423
申请日：2007-05-21
申请人： Margaret A. Wheatley , Odelia Mualem Burstein , John R. Eisenbrey , Dalia El-Sherif
发明人： Margaret A. Wheatley , Odelia Mualem Burstein , John R. Eisenbrey , Dalia El-Sherif
IPC分类号： A61K49/22 , A61K9/50 , A61K9/51 , B29B9/00
CPC分类号： A61K31/405 , A61K9/0009 , A61K9/1647 , A61K9/1694 , A61K9/5153 , A61K9/5192 , A61K41/0028 , A61K47/48238 , A61K47/48869 , A61K47/62 , A61K47/6925 , A61K49/225
摘要： This invention provides an improvement to methods of drug loading of ultrasound contrast agents. Echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof produced by the method of the invention wherein the echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof contain at least 10% more of a drug as compared to (1) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug prior to emulsifying or (2) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug to lyophilized polymer microcapsules, nanocapsules, or mixtures thereof.
摘要翻译：本发明提供了对超声造影剂的药物加载方法的改进。通过本发明的方法制备的具有回生性药物的聚合物微胶囊，纳米胶囊或其混合物，其中与（1）回声药物相比，含回声药物的聚合物微胶囊，纳米胶囊或其混合物含有至少10％以上的药物通过在乳化之前添加药物或（2）通过将药物加入到冻干的聚合物微胶囊，纳米胶囊或其混合物中制备的回送药物负载的聚合物微胶囊，纳米胶囊或其混合物而制备的负载聚合物微胶囊，纳米胶囊或其混合物。

7. 发明授权

US4900556A System for delayed and pulsed release of biologically active substances 失效
标题翻译：延迟和脉冲释放生物活性物质的系统
公开(公告)号：US4900556A
公开(公告)日：1990-02-13
申请号：US161198
申请日：1988-02-23
申请人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
发明人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
IPC分类号： A61K9/127 , A61K9/16 , A61K9/50
CPC分类号： A61K9/5031 , A61K9/127 , A61K9/1652 , Y10S514/963
摘要： A system for controlled release both in vivo and in vitro of entrapped substances, either at a constant rate over a period of time or in discrete pulses, is disclosed. Biologically active substances, such as drugs, hormones, enzymes, genetic material, antigens including viruses, vaccines, or inorganic material, such as dyes and nutrients, are entrapped in liposomes which are protected from the biological environment by encapsulation within semi-permeable microcapsules. Release of the entrapped substance into the surrounding environment is governed by the permeability of both the liposome and microcapsule walls to the substance. Permeability of the liposome is engineered by modifying the composition and method for making the liposomes, thereby producing liposomes which are sensitive to a specific stimuli such as temperature, pH, or light; or by including a phospholipase within some or all of the liposomes or the microcapsule; or by destabilizing the liposomes to break down over a period of time; or by any combination of these features.
摘要翻译：公开了一种在一段时间内或以离散脉冲以恒定速率在体内和体外捕获的物质的系统。诸如药物，激素，酶，遗传物质，包括病毒的抗原，疫苗或无机材料（例如染料和营养素）的生物活性物质被包埋在通过包封在半透性微胶囊内而被保护免于生物环境的脂质体中。被截留的物质向周围环境的释放由物质的脂质体和微胶囊壁的渗透性决定。通过改变制备脂质体的组合物和方法来改进脂质体的渗透性，从而产生对特定刺激如温度，pH或光敏感的脂质体; 或者通过在一些或全部脂质体或微胶囊中包含磷脂酶; 或通过不稳定脂质体在一段时间内分解; 或通过这些特征的任意组合。

8. 发明申请

US20100114129A1 TISSUE JOINING DEVICES CAPABLE OF DELIVERY OF BIOACTIVE AGENTS AND METHODS OF USE THEREOF 审中-公开
标题翻译：能够输送生物剂的组织接合装置及其使用方法
公开(公告)号：US20100114129A1
公开(公告)日：2010-05-06
申请号：US12307976
申请日：2007-07-17
申请人： Margaret A. Wheatley , Ari D. Brooks
发明人： Margaret A. Wheatley , Ari D. Brooks
IPC分类号： A61B17/11 , A61K9/00 , A61K38/16 , A61K38/02
CPC分类号： A61B17/11 , A61B17/064 , A61B17/115 , A61B2017/00889 , A61B2017/00893 , A61B2017/0647
摘要： The instant invention concerns a device for joining tissue comprising a ring and rivet, the ring comprises a biocompatible and biodegradable polymer and contains at least one bioactive agent. The rivet has a hollow lumen. The invention also relates to methods of making such devices and the use of such devices in joining tissue.
摘要翻译：本发明涉及用于连接包括环和铆钉的组织的装置，所述环包括生物相容性和可生物降解的聚合物，并且含有至少一种生物活性剂。铆钉具有中空管腔。本发明还涉及制造这种装置的方法以及这种装置在连接组织中的用途。

9. 发明授权

US4921757A System for delayed and pulsed release of biologically active substances 失效
标题翻译：延迟和脉冲释放生物活性物质的系统
公开(公告)号：US4921757A
公开(公告)日：1990-05-01
申请号：US92554
申请日：1987-09-03
申请人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
发明人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
IPC分类号： A61K9/127 , A61K9/50 , A61K9/70
CPC分类号： A61K9/703 , A61K9/127 , A61K9/5026 , A61K9/5031 , A61K9/7084 , Y10S436/829 , Y10S514/963 , Y10S514/965 , Y10T428/2984
摘要： A system for controlled release both in vivo and in vitro of entrapped substances, either at a constant rate over a period of time or in discrete pulses, is disclosed. Biologically active substances, such as drugs, hormones, enzymes, genetic material, antigens including viruses, vaccines, or inorganic material such as dyes and nutrients, are entrapped in liposomes which are protected from the biological environment by encapsulation within semi-permeable microcapsules or a permeable polymeric matrix. Release of the entrapped substance into the surrounding environment is governed by the permeability of both the liposome and surrounding matrix to the substance. Permeability of the liposome is engineered by modifying the composition and method for making the liposomes, thereby producing liposomes which are sensitive to a specific stimuli such as temperature, pH, or light; or by including a phospholipase within some or all of the liposomes or the surrounding matrix; or by destabilizing the liposome to break down over a period of time; or by any combination of these features.
摘要翻译：公开了一种在一段时间内或以离散脉冲以恒定速率在体内和体外捕获的物质的系统。诸如药物，激素，酶，遗传物质，包括病毒的抗原，疫苗或诸如染料和营养素的无机材料的生物活性物质被包埋在通过包封在半渗透性微胶囊内的生物环境中保护的脂质体中可渗透聚合物基体。被截留的物质释放到周围环境中由脂质体和周围基质对物质的渗透性决定。通过改变制备脂质体的组合物和方法来改进脂质体的渗透性，从而产生对特定刺激如温度，pH或光敏感的脂质体; 或通过在一些或全部脂质体或周围基质中包含磷脂酶; 或通过不稳定脂质体在一段时间内分解; 或通过这些特征的任意组合。

10. 发明授权

US4863611A Extracorporeal reactors containing immobilized species 失效
标题翻译：含有固定化物种的体外反应堆
公开(公告)号：US4863611A
公开(公告)日：1989-09-05
申请号：US44245
申请日：1987-04-30
申请人： Howard Bernstein , Margaret A. Wheatley , Robert S. Langer
发明人： Howard Bernstein , Margaret A. Wheatley , Robert S. Langer
IPC分类号： A61M1/36 , B01D15/02 , B01J20/32
CPC分类号： B01D15/02 , A61M1/3675 , B01J20/321 , B01J20/3212 , B01J20/3274
摘要： An apparatus for removing material from a biological solution consisting of a reactor chamber having an inlet and an outlet, a bioactive compound immobilized on particular supports within the reactor, means for retaining the particular supports within the reactor, means for recirculating the solution and the supports at a high flow rate within the reactor, and means for agitating or dispersing the recirculating solution-support mixture throughout the reactor chamber so as to prevent packing of the supports while not subjecting the solution to excessive or damaging forces.In the given example, an apparatus for the extracorporeal removal of heparin from blood is provided. Heparinase is immobilized on cross-linked agarose beads recirculated at a high flow rate through the reactor. Agitation of the blood-bead mixture sufficient to prevent packing of the beads within the reactor chamber is provided by means of a series of openings in the recirculation tube dispersing the mixture throughout the chamber.
摘要翻译：用于从由具有入口和出口的反应器室组成的生物溶液中去除材料的装置，固定在反应器内的特定载体上的生物活性化合物，用于将特定载体保持在反应器内的装置，用于将溶液和载体反应器内的高流速，以及用于搅拌或分散循环溶液 - 载体混合物到整个反应器室的装置，以防止支撑物的包装，同时不使溶液经受过度或破坏的力。在给出的实施例中，提供了用于从血液中体外去除肝素的装置。肝素酶固定在通过反应器以高流速再循环的交联琼脂糖珠上。借助于将混合物分散在整个室中的循环管中的一系列开口提供足以防止珠在反应器室内堆积的血珠混合物的搅动。

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