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1. 发明申请

US20080193543A1 Drug Delivery Formulations For Targeted Delivery 审中-公开
标题翻译：用于定向输送的药物配制
公开(公告)号：US20080193543A1
公开(公告)日：2008-08-14
申请号：US11914394
申请日：2006-05-17
申请人： Arthur Peter Morello, III , Joshua Reineke , Peter Matthew Cheifetz , Bryan Laulicht , Edith Mathiowitz
发明人： Arthur Peter Morello, III , Joshua Reineke , Peter Matthew Cheifetz , Bryan Laulicht , Edith Mathiowitz
IPC分类号： A61K9/16 , A61N2/00
CPC分类号： A61K9/0004 , A61K9/0009
摘要： The size and location of microsphere uptake/delivery are important determinants of the final biodistribution of oral microsphere systems. Formulations, kits, methods of administering the formulations, and using the kits are described herein. The formulations are oral dosage formulations. In one embodiment, the formulations contain microparticles and/or nanoparticles having a homogenous size range selected to optimize uptake in a specific region of the GI tract and target drug delivery to specific organs. In some embodiments, the dosage formulation contains an enteric coating and/or a magnetic material. In a preferred embodiment, the formulation contains a magnetic material and an active agent to be delivered, optionally the active agent is in the form of micro- or nano-particles. In some embodiments metallomucoadhesive materials and/or magnetic materials are employed as magnetic and/or mucoadhesive sources. Formulations containing magnetic materials can be localized using the kits and methods disclosed herein. In one embodiment, the method includes orally administering the formulation and applying an extracorporeal magnet to a site on the outside surface of the patient's body in an area that closely apposes the location in the gastrointestinal tract to which delivery of the formulation is desired. The extracorporeal magnet is applied for a suitable time period to allow for the drug to be released from the formulation and/or to allow for the formulation to adhere to the site. Both magnetic and mucoadhesive forces may be utilized to site-direct and retain the dosage form in the region of the gastrointestinal (GI) tract most suitable for the desired delivery.
摘要翻译：微球吸收/释放的大小和位置是口腔微球系统最终生物分布的重要决定因素。本文描述了制剂，试剂盒，施用制剂的方法和使用试剂盒。制剂是口服剂型。在一个实施方案中，制剂含有选择的均匀尺寸范围的微粒和/或纳米颗粒，以优化GI道的特定区域中的摄取并将靶向药物递送至特定器官。在一些实施方案中，剂量制剂含有肠溶衣和/或磁性材料。在优选的实施方案中，制剂含有磁性材料和待递送的活性剂，任选的活性剂是微粒或纳米颗粒的形式。在一些实施方案中，金属粘着粘附材料和/或磁性材料用作磁性和/或粘膜粘附源。可以使用本文公开的试剂盒和方法将含有磁性材料的制剂定位。在一个实施方案中，该方法包括口服施用该制剂并将一个体外磁体施加到患者身体的外表面上的一个位置，该区域紧密地形成需要递送制剂的胃肠道中的位置。将体外磁体施加合适的时间段以允许药物从制剂中释放和/或允许制剂粘附到部位。可以利用磁性和粘膜粘附力来定位直接并将剂型保留在最适合于所需递送的胃肠道（GI）区域中。

2. 发明申请

US20120179031A1 METHODS AND SYSTEMS FOR PROLONGED LOCALIZATION OF DRUG DELIVERY 有权
标题翻译：用于药物递送的局部化的方法和系统
公开(公告)号：US20120179031A1
公开(公告)日：2012-07-12
申请号：US13333014
申请日：2011-12-21
申请人： Bryan Laulicht , Edith Mathiowitz
发明人： Bryan Laulicht , Edith Mathiowitz
IPC分类号： A61M37/00 , A61B18/00 , A61B6/00 , A61N5/00 , H01F7/00 , B29B9/00
CPC分类号： H01F1/0054 , A61B5/062 , A61B6/12 , A61J3/071 , A61J3/10 , A61K9/501 , A61K9/5031 , A61K9/5036 , A61K9/5057 , A61K9/5094
摘要： An effective method for prolonging localization of therapeutics within the rat gastrointestinal tract of at least about 12 hours is provided. The method includes localization of therapeutic agents that are nanoparticulated or nanoencapsulated. Attractive forces between an orally administered magnetic dose and an external magnet were monitored and internal dose motion in real time using biplanar videofluoroscopy was visualized. Tissue elasticity was quantified as a measure of tissue health by combining data streams. The methods address safety, efficacy, and monitoring capacity of magnetically localized doses and show a platform for testing the benefits of localized drug delivery.
摘要翻译：提供了延长大鼠胃肠道内治疗剂定位至少约12小时的有效方法。该方法包括纳米颗粒或纳米包封的治疗剂的定位。监测口服给药的磁剂和外部磁体之间的吸引力，并且使用双平面视频荧光检查实时内部剂量运动。通过组合数据流将组织弹性量化为组织健康的量度。这些方法解决了磁性局部剂量的安全性，有效性和监测能力，并展示了一种用于测试局部药物递送的益处的平台。

3. 发明申请

US20120053451A1 METHODS AND SYSTEMS FOR PROLONGED LOCALIZATION OF DRUG DELIVERY 有权
标题翻译：用于药物递送的局部化的方法和系统
公开(公告)号：US20120053451A1
公开(公告)日：2012-03-01
申请号：US13217883
申请日：2011-08-25
申请人： Bryan Laulicht , Edith Mathiowitz
发明人： Bryan Laulicht , Edith Mathiowitz
IPC分类号： A61B5/05 , A61K9/19 , A61P23/00 , A61P1/04 , A61P11/00 , A61P11/08 , A61P39/00 , A61P3/10 , A61P7/10 , A61P37/06 , H01F1/00 , A61P31/00
CPC分类号： A61K9/0009 , A61K9/0004 , A61K9/1658 , A61K9/4808 , H01F1/0054
摘要： An effective method for prolonging localization of therapeutics within the rat gastrointestinal tract of at least about 12 hours is provided. Attractive forces between an orally administered magnetic dose and an external magnet were monitored and internal dose motion in real time using biplanar videofluoroscopy was visualized. Tissue elasticity was quantified as a measure of tissue health by combining data streams. The methods address safety, efficacy, and monitoring capacity of magnetically localized doses and show a platform for testing the benefits of localized drug delivery.
摘要翻译：提供了延长大鼠胃肠道内治疗剂定位至少约12小时的有效方法。监测口服给药的磁剂和外部磁体之间的吸引力，并且使用双平面视频荧光检查实时内部剂量运动。通过组合数据流将组织弹性量化为组织健康的量度。这些方法解决了磁性局部剂量的安全性，有效性和监测能力，并展示了一种用于测试局部药物递送的益处的平台。

4. 发明申请

US20120053156A1 COMPOSITIONS AND METHODS FOR LOOP DIURETICS WITH CONSISTENT BIOAVAILABILITY 有权
标题翻译：具有一致性生物利用度的环路滤膜的组合物和方法
公开(公告)号：US20120053156A1
公开(公告)日：2012-03-01
申请号：US13217764
申请日：2011-08-25
申请人： Edith Mathiowitz , Bryan Laulicht
发明人： Edith Mathiowitz , Bryan Laulicht
IPC分类号： A61K31/635 , A61K47/32 , A61P3/00 , A61P5/00 , A61P13/12 , A61P9/00 , C07D307/54 , A61P1/16
CPC分类号： A61K31/635 , A61K9/146 , A61K9/19 , C07D213/74 , C07D277/42 , C07D295/155 , C07D307/14 , C07D409/12
摘要： Diuretic bioactivity profiles of phase inversion micronized furosemide and furosemide co-precipitated with Eudragit L100, and mixtures of those formulations with stock furosemide, reduced or eliminated the rapid spike in diuresis associated with immediate release formulations and maintained cumulative urine output. Of the formulations tested, each of a mixture of micronized furosemide with stock furosemide, and Eudragit L100 polymer with stock furosemide demonstrated optimal diuretic bioactivity profiles in subjects.
摘要翻译：与Eudragit L100共沉淀的相转化微粉碎呋塞米和呋塞米的利尿生物活性曲线，以及那些制剂与储备呋塞米的混合物，减少或消除了与立即释放制剂相关的利尿的快速穗状态，并维持累积的尿量。在所测试的制剂中，微粉化呋塞米与储备呋塞米的混合物以及具有储备呋塞米的Eudragit L100聚合物在受试者中表现出最佳的利尿生物活性曲线。

5. 发明申请

US20120009267A1 NANOPARTICLE COMPOSITIONS AND METHODS FOR IMPROVED ORAL DELIVERY OF ACTIVE AGENTS 有权
标题翻译：纳米材料组合物和改进的活性剂的口服递送方法
公开(公告)号：US20120009267A1
公开(公告)日：2012-01-12
申请号：US13179205
申请日：2011-07-08
申请人： Daniel Cho , Joshua Reineke , Edith Mathiowitz , Bryan Laulicht
发明人： Daniel Cho , Joshua Reineke , Edith Mathiowitz , Bryan Laulicht
IPC分类号： A61K9/50 , A61K38/02 , A61K48/00 , B29B9/12 , A61K47/34 , A61K47/32 , A61K47/36 , A61K38/22 , A61K31/713
CPC分类号： A61K31/713 , A61K9/5026 , A61K9/5031 , A61K9/5073 , A61K9/5089 , A61K9/5138 , A61K9/5146 , A61K9/5192 , A61K38/00
摘要： Nanoparticles, compositions, and methods for the improved uptake of active agents are disclosed herein. The compositions contain a monodisperse population of nanoparticles, preferably including an active agent, where the nanoparticles are formed from a polymeric material possessing specified bioadhesion characteristics. Following enteral administration, preferably oral administration, the nanoparticles exhibit total intestinal uptakes of greater than 20%, preferably greater than 45%, more preferably greater than 65%. When compared to uptake of the same composition in the absence of the bioadhesive polymeric material, the nanoparticles have significantly increased uptake with intestinal uptake of the increased by more than 100%, preferably even greater than 500%. Further disclosed herein is a method of producing multi-walled nanoparticles, as well as methods of using thereof. Multi-walled particles prepared using the method disclosed herein are useful for controlling the release of active agents.
摘要翻译：本文公开了用于改善摄取活性剂的纳米颗粒，组合物和方法。组合物含有单分散的纳米颗粒群体，优选包括活性剂，其中纳米颗粒由具有特定生物粘附特性的聚合物形成。在肠内施用之后，优选口服给药，纳米颗粒显示出大于20％，优选大于45％，更优选大于65％的总肠吸收。当与没有生物粘附性聚合物材料的相同组合物的吸收相比时，纳米颗粒具有显着增加的摄取，肠吸收增加超过100％，优选甚至大于500％。本文进一步公开的是制备多壁纳米颗粒的方法及其使用方法。使用本文公开的方法制备的多壁颗粒可用于控制活性剂的释放。

6. 发明申请

US20070275080A1 Polymer-Based Microstructures 审中-公开
标题翻译：基于聚合物的微结构
公开(公告)号：US20070275080A1
公开(公告)日：2007-11-29
申请号：US10577785
申请日：2004-10-29
申请人： Bryan Laulicht , Sasha Bakhru
发明人： Bryan Laulicht , Sasha Bakhru
IPC分类号： A61K9/14 , B41J2/01
CPC分类号： B01J13/14 , B01J13/08
摘要： The present invention relates to the fields of controlled release of drugs, proteins, nucleic acids, and other pharmaceuticals. It also relates to delivery systems for these agents and other compounds. The invention also relates to stable encapsulation of cells and molecules. The invention provides a population of microstructures comprising a permeable polymer shell, wherein the standard variance in the volume of the microstructures is usually less than or equal to 20%, preferably 10%, of the mean, and wherein the diffusion characteristics of the polymer shell vary within the population of microstructures. It also provides for an apparatus and a method of forming a population of microstructures, which method for making microstructures by introducing drops of a polymer solution into a receiving solution under conditions that permit cross-linking of the polymer in the receiving solution. Microstructures of calcium-cross-linked alginate with a chitosin capsule are disclosed.
摘要翻译：本发明涉及药物，蛋白质，核酸和其他药物的控制释放领域。它还涉及这些试剂和其它化合物的递送系统。本发明还涉及细胞和分子的稳定包封。本发明提供了包含可渗透聚合物壳的微观组织群，其中微结构体积的标准差异通常小于或等于平均值的20％，优选10％，并且其中聚合物壳的扩散特性在微观结构的群体内变化。它还提供了一种形成微观结构群的装置和方法，该方法通过在允许聚合物在接收溶液中交联的条件下将聚合物溶液的液滴引入接收溶液来制备微结构。公开了钙交联藻酸盐与壳聚糖胶囊的微结构。

7. 发明授权

US09165703B2 Methods and systems for prolonged localization of drug delivery 有权
标题翻译：药物递送延长定位的方法和系统
公开(公告)号：US09165703B2
公开(公告)日：2015-10-20
申请号：US13333014
申请日：2011-12-21
申请人： Bryan Laulicht , Edith Mathiowitz
发明人： Bryan Laulicht , Edith Mathiowitz
IPC分类号： A61M37/00 , A61B18/00 , A61B6/00 , A61N5/00 , H01F7/00 , B29B9/00 , H01F1/00 , A61K9/50 , A61B5/06 , A61B6/12 , A61J3/10 , A61J3/07
CPC分类号： H01F1/0054 , A61B5/062 , A61B6/12 , A61J3/071 , A61J3/10 , A61K9/501 , A61K9/5031 , A61K9/5036 , A61K9/5057 , A61K9/5094
摘要： An effective method for prolonging localization of therapeutics within the rat gastrointestinal tract of at least about 12 hours is provided. The method includes localization of therapeutic agents that are nanoparticulated or nanoencapsulated. Attractive forces between an orally administered magnetic dose and an external magnet were monitored and internal dose motion in real time using biplanar videofluoroscopy was visualized. Tissue elasticity was quantified as a measure of tissue health by combining data streams. The methods address safety, efficacy, and monitoring capacity of magnetically localized doses and show a platform for testing the benefits of localized drug delivery.
摘要翻译：提供了延长大鼠胃肠道内治疗剂定位至少约12小时的有效方法。该方法包括纳米颗粒或纳米包封的治疗剂的定位。监测口服给药的磁剂和外部磁体之间的吸引力，并且使用双平面视频荧光检查实时内部剂量运动。通过组合数据流将组织弹性量化为组织健康的量度。这些方法解决了磁性局部剂量的安全性，有效性和监测能力，并展示了一种用于测试局部药物递送的益处的平台。

8. 发明授权

US08673359B2 Nanoparticle compositions and methods for improved oral delivery of active agents 有权
标题翻译：纳米颗粒组合物和用于改善活性剂口服递送的方法
公开(公告)号：US08673359B2
公开(公告)日：2014-03-18
申请号：US13179205
申请日：2011-07-08
申请人： Daniel Cho , Joshua Reineke , Edith Mathiowitz , Bryan Laulicht
发明人： Daniel Cho , Joshua Reineke , Edith Mathiowitz , Bryan Laulicht
IPC分类号： A61K9/50 , A61K38/02 , A61K48/00 , A61K47/34
CPC分类号： A61K31/713 , A61K9/5026 , A61K9/5031 , A61K9/5073 , A61K9/5089 , A61K9/5138 , A61K9/5146 , A61K9/5192 , A61K38/00
摘要： Nanoparticles, compositions, and methods for the improved uptake of active agents are disclosed herein. The compositions contain a monodisperse population of nanoparticles, preferably including an active agent, where the nanoparticles are formed from a polymeric material possessing specified bioadhesion characteristics. Following enteral administration, preferably oral administration, the nanoparticles exhibit total intestinal uptakes of greater than 20%, preferably greater than 45%, more preferably greater than 65%. When compared to uptake of the same compositon in the absence of the bioadhesive polymeric material, the nanoparticles have significantly increased uptake with intestinal uptake of the increased by more than 100%, preferably even greater than 500%. Further disclosed herein is a method of producing multi-walled nanoparticles, as well as methods of using thereof. Multi-walled particles prepared using the method disclosed herein are useful for controlling the release of active agents.
摘要翻译：本文公开了用于改善摄取活性剂的纳米颗粒，组合物和方法。组合物含有单分散的纳米颗粒群体，优选包括活性剂，其中纳米颗粒由具有特定生物粘附特性的聚合物形成。在肠内施用之后，优选口服给药，纳米颗粒显示出大于20％，优选大于45％，更优选大于65％的总肠吸收。当与没有生物粘附性聚合物材料的相同组合物的摄取相比时，纳米颗粒具有显着增加的摄取，肠吸收增加超过100％，优选甚至大于500％。本文进一步公开的是制备多壁纳米颗粒的方法及其使用方法。使用本文公开的方法制备的多壁颗粒可用于控制活性剂的释放。

9. 发明申请

US20160020436A1 Safely Ingestible Batteries 有权
标题翻译：安全摄入电池
公开(公告)号：US20160020436A1
公开(公告)日：2016-01-21
申请号：US14774984
申请日：2014-03-05
申请人： Bryan LAULICHT , Janet FREILICH , Jeffrey M. KARP , Robert LANGER
发明人： Bryan Laulicht , Janet Freilich , Jeffrey M. Karp , Robert Langer
IPC分类号： H01M2/02 , H01M10/42 , H01M2/34 , H01M2/18 , H01M2/08
CPC分类号： H01M2/0222 , H01M2/025 , H01M2/0267 , H01M2/08 , H01M2/18 , H01M2/30 , H01M2/34 , H01M10/4235 , H01M2200/00 , H01M2220/00 , H01M2220/30
摘要： A battery for use in electronic devices and which is safely ingested into a body and a related method of making the battery. The battery includes an anode, a cathode and a quantum tunneling composite coating. The quantum tunneling composite coating covers at least a portion of at least one of the anode or the cathode and provides pressure sensitive conductive properties to the battery including a compressive stress threshold for conduction. The compressive stress threshold may be greater than a pre-determined applied stress in a digestive tract of the body in order to prevent harm if the battery is ingested. The battery may include a waterproof seal that extends between the quantum tunneling composite coating and a gasket separating the anode and cathode to inhibit the battery from short circuiting in a conductive fluid below the compressive stress threshold.
摘要翻译：一种用于电子设备并被安全地摄入身体的电池和相关的制造电池的方法。电池包括阳极，阴极和量子隧道复合涂层。量子隧道复合涂层覆盖阳极或阴极中的至少一个的至少一部分，并且为电池提供压敏导电性能，包括用于传导的压应力阈值。压缩应力阈值可能大于身体消化道中预先确定的施加应力，以防止电池摄入时的危害。电池可以包括在量子隧道复合涂层和分隔阳极和阴极的垫圈之间延伸的防水密封件，以阻止电池在低于压缩应力阈值的导电流体中短路。

10. 发明授权

US08776802B2 Methods and systems for prolonged localization of drug delivery 有权
标题翻译：药物递送延长定位的方法和系统
公开(公告)号：US08776802B2
公开(公告)日：2014-07-15
申请号：US13217883
申请日：2011-08-25
申请人： Edith Mathiowitz , Bryan Laulicht
发明人： Edith Mathiowitz , Bryan Laulicht
IPC分类号： A61B5/05 , A61K9/48
CPC分类号： A61K9/0009 , A61K9/0004 , A61K9/1658 , A61K9/4808 , H01F1/0054
摘要： An effective method for prolonging localization of therapeutics within the rat gastrointestinal tract of at least about 12 hours is provided. Attractive forces between an orally administered magnetic dose and an external magnet were monitored and internal dose motion in real time using biplanar videofluoroscopy was visualized. Tissue elasticity was quantified as a measure of tissue health by combining data streams. The methods address safety, efficacy, and monitoring capacity of magnetically localized doses and show a platform for testing the benefits of localized drug delivery.
摘要翻译：提供了延长大鼠胃肠道内治疗剂定位至少约12小时的有效方法。监测口服给药的磁剂和外部磁体之间的吸引力，并且使用双平面视频荧光检查实时内部剂量运动。通过组合数据流将组织弹性量化为组织健康的量度。这些方法解决了磁性局部剂量的安全性，有效性和监测能力，并展示了一种用于测试局部药物递送的益处的平台。

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