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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

US09700640B2 Stabilized ultrasound contrast agent 有权
公开(公告)号：US09700640B2
公开(公告)日：2017-07-11
申请号：US13497019
申请日：2010-09-20
申请人： Margaret A. Wheatley , Boriphat Methachan , Carl D. Solis
发明人： Margaret A. Wheatley , Boriphat Methachan , Carl D. Solis
IPC分类号： A61K49/22
CPC分类号： A61K49/223
摘要： Provided is a particle-stabilized ultrasound contrast agent (UCA) and methods of preparing same. Also provided is a method for preparing a lyoprotected UCA, a freeze-dried lyoprotected UCA, and a reconstituted freeze-dried lyoprotected UCA.

5. 发明授权

US08715622B2 Echogenic polymer microcapsules and nanocapsules and methods for production and use thereof 有权
标题翻译：回生性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：US08715622B2
公开(公告)日：2014-05-06
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： A61B8/00 , A61K47/08 , A61K47/18 , A61K49/22 , G01N29/04
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。

6. 发明申请

US20120237450A1 Stabilized Ultrasound Contrast Agent 有权
标题翻译：稳定超声对比剂
公开(公告)号：US20120237450A1
公开(公告)日：2012-09-20
申请号：US13497019
申请日：2010-09-20
申请人： Margaret A. Wheatley , Boriphat Methachan , Carl D. Solis
发明人： Margaret A. Wheatley , Boriphat Methachan , Carl D. Solis
IPC分类号： A61K49/22
CPC分类号： A61K49/223
摘要： Provided is a particle-stabilized ultrasound contrast agentn (UCA) and methods of preparing same. Also provided is a method for preparing a lyoprotected UCA, a freeze-dried lyoprotected UCA, and a reconstituted freeze-dried lyoprotected UCA.
摘要翻译：提供了一种颗粒稳定的超声造影剂（UCA）及其制备方法。还提供了制备防淋淋UCA，冷冻干燥的保护性UCA和重构冷冻干燥的保乳UCA的方法。

7. 发明申请

US20080247957A1 Advanced drug delivery strategy and platform for minimally-invasive treatment of liver cancer 审中-公开
标题翻译：用于肝癌微创治疗的先进药物递送策略和平台
公开(公告)号：US20080247957A1
公开(公告)日：2008-10-09
申请号：US12070161
申请日：2008-02-15
申请人： Margaret A. Wheatley
发明人： Margaret A. Wheatley
IPC分类号： A61K49/00 , A61K9/50 , A61P43/00
CPC分类号： A61K47/08 , A61K9/0009 , A61K9/0019 , A61K9/1647 , A61K9/1694 , A61K9/19 , A61K9/5153 , A61K31/282 , A61K31/704 , A61K41/0028 , A61K47/12 , A61K47/186
摘要： The present invention comprises minimally invasive methods useful in the treatment of liver cancer. The method of the present invention comprises administering to an individual with liver cancer an injectable, echogenic nanocapsule and/or microcapsule wherein the nanocapsule and/or microcapsule comprises a therapeutic agent, a targeting moiety, or a combination thereof. The method of the present invention further comprises monitoring the distribution of the nanocapsule and/or microcapsule using ultrasound. The method of the invention delivers a therapeutic agent to a liver cancer cell either by biodegradation of a nanocapsule and/or microcapsule comprising a therapeutic agent, or by altering the biodegradation of a nanocapsule and/or microcapsule using ultrasound.
摘要翻译：本发明包括可用于治疗肝癌的微创方法。本发明的方法包括向患有肝癌的个体施用可注射的回声纳米胶囊和/或微胶囊，其中纳米胶囊和/或微胶囊包含治疗剂，靶向部分或其组合。本发明的方法还包括使用超声波监测纳米胶囊和/或微胶囊的分布。本发明的方法通过纳米胶囊和/或包含治疗剂的微胶囊的生物降解或通过使用超声波改变纳米胶囊和/或微胶囊的生物降解来向肝癌细胞递送治疗剂。

8. 发明授权

US06514209B1 Method of enhancing ultrasonic techniques via measurement of ultraharmonic signals 有权
标题翻译：通过测量超音速信号增强超声波技术的方法
公开(公告)号：US06514209B1
公开(公告)日：2003-02-04
申请号：US09589570
申请日：2000-06-07
申请人： Raghuveer Basude , Margaret A. Wheatley
发明人： Raghuveer Basude , Margaret A. Wheatley
IPC分类号： A61B814
CPC分类号： A61B8/481 , A61K49/22 , G01S7/52028 , G01S7/52038 , G01S7/52039
摘要： Methods and apparatus for enhancing the capabilities of ultrasonic techniques through use of ultraharmonics are provided.
摘要翻译：提供了通过使用超谐波增强超声波技术的能力的方法和装置。

9. 发明授权

US5352436A Surfactant-stabilized microbubble mixtures, process for preparing and methods of using the same 失效
标题翻译：表面活性剂稳定的微泡混合物，其制备方法及其使用方法
公开(公告)号：US5352436A
公开(公告)日：1994-10-04
申请号：US162421
申请日：1993-11-22
申请人： Margaret A. Wheatley , Shen Peng , Shruti Singhal , Barry B. Goldberg
发明人： Margaret A. Wheatley , Shen Peng , Shruti Singhal , Barry B. Goldberg
IPC分类号： A61K49/00 , A61B8/00 , A61K49/22
CPC分类号： A61K49/223
摘要： The present invention is a mixture including a solvent, a first surfactant and a second, dispersible surfactant different from the first surfactant, the mixture having stabilized gas microbubbles formed therein by sonication. The gas microbubbles are useful in ultrasonic diagnostics. Preferably the first surfactant is substantially soluble in the solvent and the second surfactant is substantially insoluble in the solvent. The present invention also includes a process for preparing the stabilized gas microbubbles and a method for altering the contrast of an ultrasonic image using the microbubbles as a contrast agent.
摘要翻译：本发明是包含溶剂，第一表面活性剂和不同于第一表面活性剂的第二可分散表面活性剂的混合物，该混合物通过超声处理在其中形成稳定的气体微泡。气体微泡可用于超声诊断。优选地，第一表面活性剂基本上可溶于溶剂，第二表面活性剂基本上不溶于溶剂。本发明还包括一种制备稳定气体微泡的方法以及一种使用微泡作为造影剂改变超声图像的对比度的方法。

10. 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。

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