-
公开(公告)号：US20090018033A1
公开(公告)日：2009-01-15
申请号：US12087937
申请日：2007-01-24
申请人： Jeffrey Morgan , Peter Chai , Anthony Napolitano , Edith Mathiowitz , Dylan Dean
发明人： Jeffrey Morgan , Peter Chai , Anthony Napolitano , Edith Mathiowitz , Dylan Dean
CPC分类号： C12M25/00 , B33Y80/00 , C12M21/08 , C12M23/12 , C12M25/14 , C12N5/0012 , C12N5/0062 , C12N2533/40 , C12N2533/74
摘要： The invention is a cell aggregation device comprising a hydrogel substrate having at least one, preferably a plurality, of cell-repellant compartments recessed into the uppermost surface. Each compartment is composed of an upper cell suspension seeding chamber having an open uppermost portion and a bottom portion, and one, or more than one, lower cell aggregation recess connected to the bottom portion of the upper cell suspension seeding chamber by a port. The diameter of the port may be fully contiguous with the walls of the chambers and walls of the recesses, or the diameter of the port may be more narrow than the walls of the chamber but fully contiguous with the walls of the recesses or more narrow than both the walls of the chamber and the walls of the recesses. The upper cell suspension seeding chambers are formed and positioned to funnel the cells into the lower cell aggregation recesses through gravitational force. The aggregation recesses are formed and positioned to promote cellular aggregation by coalescing cells into a finite region of minimum gravitational energy, increasing intercellular contact and minimizing or preventing cell adherence to the substrate. A device for encapsulating aggregates of live cells is provided. The device comprises (i) a biocompatible, bio-sustainable substrate having a cell-encapsulating face composed of one or more biocompatible, bio-sustainable, spaced-apart, cell-encapsulating compartments extending therefrom and (ii) a coating layer composed of a biocompatible, bio-sustainable polymer that completely surrounds the substrate and the cell-encapsulating compartments. A method for making the device is also provided.
摘要翻译： 本发明是一种细胞聚集装置，其包括具有至少一个，优选多个凹陷到最上表面的细胞排斥隔室的水凝胶基底。 每个隔室由具有开口最上部分和底部的上部细胞悬浮播种室组成，以及通过端口连接到上部细胞悬浮播种室的底部的一个或多于一个下部细胞聚集凹部。 端口的直径可以与腔室的壁和凹部的壁完全邻接，或者端口的直径可以比室的壁更窄，但是与凹部的壁完全邻接或更窄 房间的墙壁和凹槽的墙壁。 形成并定位上细胞悬浮播种室，以通过重力将细胞漏入下细胞聚集凹槽。 形成和定位聚集凹槽以通过将细胞聚结成最小引力能的有限区域，增加细胞间接触并最小化或防止细胞粘附于基底来促进细胞聚集。 提供了用于封装活细胞聚集体的装置。 所述装置包括（i）生物相容的生物可持续的底物，其具有由一个或多个生物相容性，生物可持续的间隔开的细胞包封的隔室组成的细胞封装面，所述细胞封装的区域从其延伸，和（ii）由 生物相容的，生物可持续的聚合物，其完全包围底物和细胞封装隔室。 还提供了制造该装置的方法。
-
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
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。
-
公开(公告)号：US20050181059A1
公开(公告)日：2005-08-18
申请号：US10954423
申请日：2004-09-30
申请人： Jules Jacob , Yong Jong , Danielle Abramson , Edith Mathiowitz , Camilla Santos , Michael Bassett , Stacia Furtardo
发明人： Jules Jacob , Yong Jong , Danielle Abramson , Edith Mathiowitz , Camilla Santos , Michael Bassett , Stacia Furtardo
CPC分类号： A61K38/208 , A61K9/14 , A61K9/146 , A61K9/1688 , A61K9/5026 , A61K9/5031 , A61K9/5089 , A61K31/7105 , A61K38/168 , A61K38/27 , A61K38/28
摘要： Compositions containing particles of biologically active agents with sizes in the micron and submicron range and methods for making and using such particles are described herein. In the preferred embodiment the biologically active agents are peptides, proteins, nucleic acid molecules, or hydrophilic synthetic molecules. The particles have a size ranging from an average diameter of about 100 nm to about 2000 nm, preferably about 200 nm to 600 nm. Optionally the biologically active agents contain a polymeric coating. The particles are formed by adding a biologically active agent to an aqueous solution, mixing a nonsolvent that is miscible with water with the aqueous solution, and precipitating particles of the biologically active agents out of the nonsolvent: aqueous solution combination. The nonsolvent is typically a C1 to C6 alcohol, preferably a C2 to a C5 alcohol. In the preferred embodiment, the nonsolvent is tert-butyl alcohol.
摘要翻译： 本文描述了含有尺寸在微米和亚微米范围内的生物活性剂颗粒的组合物以及制备和使用这些颗粒的方法。 在优选的实施方案中，生物活性剂是肽，蛋白质，核酸分子或亲水合成分子。 颗粒的尺寸范围为约100nm至约2000nm的平均直径，优选为约200nm至600nm。 任选地，生物活性剂含有聚合物涂层。 通过向水溶液中加入生物活性剂，将可与水混溶的非溶剂与水溶液混合并将生物活性剂的颗粒从非溶剂：水溶液组合中沉淀而形成颗粒。 非溶剂通常是C1至C6醇，优选C2至C5醇。 在优选的实施方案中，非溶剂是叔丁醇。
-
公开(公告)号：US06465002B1
公开(公告)日：2002-10-15
申请号：US09523887
申请日：2000-03-13
申请人： Edith Mathiowitz , Jules S. Jacob , Yong S. Jong , Donald E. Chickering, III , Edwin E. Edwards
发明人： Edith Mathiowitz , Jules S. Jacob , Yong S. Jong , Donald E. Chickering, III , Edwin E. Edwards
IPC分类号： A61F1300
CPC分类号： C09K19/38 , B29C55/00 , B29C55/18 , B29K2105/0079
摘要： Methods for inducing a thermoplastic polymer, which can be non-mesogenic, to exhibit liquid crystalline properties have been developed. The method includes the steps of (a) heating the polymer from an initial temperature below its glass transition temperature (Tg) to a temperature greater than its Tg and below its melting temperature (Tm); (b) exposing the polymer to a pressure greater than about 2 metric tons/in2, preferably between about 2 and 10 metric tons/in2, preferably for at least about one minute, while maintaining the temperature greater than its Tg; and (c) cooling the polymer below the Tg while maintaining the elevated pressure. Unlike many prior art transition processes which are reversible, this process provides a liquid crystal state that can be maintained for years at ambient conditions. In a preferred embodiment, the plastics are bioerodible thermoplastic polymers, such as polyanhydrides, some polyesters, polyamides, and polyaromatics. The liquid crystalline polymers can be used in the controlled release or retention of substances encapsulated in the polymers. The polymer can be in a variety of forms including films, film laminants, and microparticles. In a preferred embodiment, the LC polymers are used to encapsulate therapeutic, diagnostic, or prophylactic agents for use in medical or pharmaceutical applications.
摘要翻译： 已经开发了用于诱导可以是非介晶的热塑性聚合物以显示液晶性质的方法。 该方法包括以下步骤：（a）将聚合物从低于其玻璃化转变温度（Tg）的初始温度加热至大于其Tg并低于其熔融温度（Tm）的温度; （b）将聚合物暴露于大于约2公吨/ in2的压力下，优选约2至10公吨/ in 2，优选至少约1分钟，同时保持温度高于其Tg; 和（c）在保持升高的压力的同时将聚合物冷却至Tg以下。 与可逆的许多现有技术的过渡过程不同，该方法提供可在环境条件下保持多年的液晶状态。 在优选的实施方案中，塑料是可生物腐蚀的热塑性聚合物，例如聚酐，一些聚酯，聚酰胺和多芳族化合物。 液晶聚合物可用于控制或保留包封在聚合物中的物质。 聚合物可以是各种形式，包括膜，膜层压剂和微粒。 在优选的实施方案中，LC聚合物用于包封用于医疗或药物应用的治疗剂，诊断剂或预防剂。
-
公开(公告)号：US06262034B1
公开(公告)日：2001-07-17
申请号：US08978522
申请日：1997-11-25
IPC分类号： A61K4800
CPC分类号： A61K9/1647 , A61K9/1272 , A61K9/2027 , A61K48/00
摘要： A means for obtaining efficient introduction of exogenous genes into a patient, with long term expression of the gene, is disclosed. The gene, under control of an appropriate promoter for expression in a particular cell type, is encapsulated or dispersed with a biocompatible, preferably biodegradable polymeric matrix, where the gene is able to diffuse out of the matrix over an extended period of time, for example, a period of three to twelve months or longer. The matrix is preferably in the form of a microparticle such as a microsphere (where the gene is dispersed throughout a solid polymeric matrix) or microcapsule (gene is stored in the core of a polymeric shell), a film, an implant, or a coating on a device such as a stent. The size and composition of the polymeric device is selected to result in favorable release kinetics in tissue. The size is also selected according to the method of delivery which is to be used, typically injection or administration of a suspension by aerosol into the nasal and/or pulmonary areas. The matrix composition can be selected to not only have favorable degradation rates, but to be formed of a material which is bioadhesive, to further increase the effectiveness of transfer when administered to a mucosal surface.
摘要翻译： 公开了一种用于获得有效引入外源基因到患者中的方法，其具有该基因的长期表达。 在特定细胞类型中用于表达的适当启动子的控制下的基因用生物相容的，优选可生物降解的聚合物基质包封或分散，其中基因能够在延长的时间段内扩散出基质，例如 ，期限为三至十二个月或更长。 基质优选为微粒，例如微球（其中基因分散在整个固体聚合物基质中）或微胶囊（基因存储在聚合物壳的核心中），膜，植入物或涂层 在诸如支架的装置上。 选择聚合物装置的尺寸和组成以在组织中产生有利的释放动力学。 还根据要使用的递送方法选择大小，通常通过气雾剂将悬浮液注射或施用于鼻和/或肺部区域。 可以选择基质组合物不仅具有良好的降解速率，而且由生物粘附的材料形成，以进一步提高施用于粘膜表面时转移的有效性。
-
公开(公告)号：US06235224B1
公开(公告)日：2001-05-22
申请号：US09442723
申请日：1999-11-18
IPC分类号： B01J1304
CPC分类号： A61K9/5153 , A61K9/1641 , A61K9/1694 , A61K9/5089 , A61K9/5138 , A61K9/5146 , A61K9/5192 , A61K48/00 , B01J13/04 , B01J13/06
摘要： A process for preparing nanoparticles and microparticles is provided. The process involves forming a mixture of a polymer and a solvent, wherein the solvent is present in a continuous phase and introducing the mixture into an effective amount of a nonsolvent to cause the spontaneous formation of microparticles.
-
公开(公告)号：US5985312A
公开(公告)日：1999-11-16
申请号：US592565
申请日：1996-01-26
申请人： Jules S. Jacob , Edith Mathiowitz
发明人： Jules S. Jacob , Edith Mathiowitz
CPC分类号： A61K9/5153 , A61K47/02 , A61K9/006 , A61K9/1611 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/1658
摘要： Methods and compositions are provided for enhancing the bioadhesive properties of polymers used in drug delivery devices. The bioadhesive properties of a polymer are enhanced by incorporating a metal compound into the polymer to enhance the ability of the polymer to adhere to a tissue surface such as a mucosal membrane. Metal compounds which enhance the bioadhesive properties of a polymer include water-insoluble metal compounds such as water-insoluble metal oxides, including oxides of calcium, iron, copper and zinc. The metal compounds can be incorporated within a wide range of polymers including proteins, polysaccharides and synthetic biocompatible polymers. In one embodiment, metal oxides can be incorporated within polymers used to form or coat drug delivery devices, such as microspheres, which contain a drug or diagnostic agent. The metal oxides can be provided in the form of a fine dispersion of particles on the surface of a polymer that coats or forms the devices, which enhances the ability of the devices to bind to mucosal membranes. The polymers, for example in the form of microspheres, have improved ability to adhere to mucosal membranes, and thus can be used to deliver a drug or diagnostic agent via any of a range of mucosal membrane surfaces including those of the gastrointestinal, respiratory, excretory and reproductive tracts.
-
公开(公告)号：US4898734A
公开(公告)日：1990-02-06
申请号：US162161
申请日：1988-02-29
CPC分类号： A01N25/34 , A61K9/1641 , A61K9/1647 , A61K9/2077 , A61K9/2081 , A61K9/7023 , B01J13/025
摘要： The present invention is a method to produce novel composites based on microcapsules or microspheres embedded in contiuous polymeric matrices. Both non-bioerodible and erodible polymers can be used. Material can be incorporated into the microcapsules or microspheres for subsequent release. In one embodiment of the present invention, spheres are homogeneously dispersed in a polymer matrix and then forced to release their contents by exposure to temperature, light or ultrasound. Alternatively, polymers which degrade as a function of time or hydrolysis can be used for controlled releases. The polymer composites have completely different properties from either a continuous polymer matrix or microcapsules or microspheres and are therefore useful for a wide variety of applications. When carbon tetrachloride is the incorporated material, the film is useful as a flame retarding device. When foaming agents are used, especially UV or heat sensitive materials, gas can be evolved inside each capsulThe Government has rights in this invention pursuant to Grant Number 5-R01-GM26698 awarded by the Department of Health and Human Services.
摘要翻译： 本发明是一种基于嵌入在连续聚合物基质中的微胶囊或微球体生产新型复合材料的方法。 可以使用非生物可腐蚀和可侵蚀的聚合物。 可以将材料并入微胶囊或微球体中用于随后的释放。 在本发明的一个实施方案中，球体均匀地分散在聚合物基质中，然后通过暴露于温度，光或超声波被迫释放其内容物。 或者，作为时间或水解的函数降解的聚合物可用于受控释放。 聚合物复合材料与连续聚合物基质或微胶囊或微球具有完全不同的性质，因此可用于各种应用。 当四氯化碳是引入的材料时，该膜可用作阻燃装置。 当使用发泡剂，特别是UV或热敏材料时，可在每个胶囊内放出气体，以在聚合物中形成气泡。 当药物或其他生物活性剂掺入球体并用聚合物包封时，仅通过侵蚀或破裂的球体释放。 与从包封的微胶囊的释放相反，从聚合物复合材料的释放大约是随时间线性的。 聚合物球体的侵蚀也可用于产生多孔聚合物结构。 这种装置可用于透皮药物递送，血管移植物，伤口愈合膜或作为聚合物多孔膜。
-
公开(公告)号：US4861627A
公开(公告)日：1989-08-29
申请号：US45840
申请日：1987-05-01
申请人： Edith Mathiowitz , Robert S. Langer
发明人： Edith Mathiowitz , Robert S. Langer
IPC分类号： A01N25/28 , A61K8/00 , A61K8/18 , A61K8/87 , A61K8/88 , A61K9/16 , A61K9/50 , A61K9/56 , A61K9/58 , A61Q13/00 , B01J13/14 , C05G3/00 , C09B67/08 , C11B9/00
CPC分类号： A61K9/5089 , A61K9/1694 , Y10S514/963 , Y10T428/2987 , Y10T428/2989
摘要： A single step method for preparation of multi-layer polymeric delivery systems. Any two or three different degradable or non-degradable polymers which are not soluble in each other at a particular concentration, as dictated by their phase diagram, can be used. The multi-layer microcapsules produced by the method are distinguished by extremely uniform dimensioned layers of polymer and actual incorporation of the substance to be delivered into the polymer layers.In the preferred embodiment of the method, two polymers are dissolved in a volatile organic solvent, the substance to be encapsulated is dispersed or dissolved in the polymer solution, the mixture is suspended in an aqueous solution and stirred, and the solvent is slowly evaporated, creating microspheres with an inner core formed by one polymer and an outer layer formed by the second polymer. In another embodiment one polymer may be formed within a layer of the other polymer by increasing the rate of evaporation of the volatile solvent.
摘要翻译： 用于制备多层聚合物递送系统的单步法。 可以使用任何两种或三种不同的可降解或不可降解的聚合物，其特定浓度彼此不溶，如其相图所示。 通过该方法制备的多层微胶囊通过聚合物的非常均匀的尺寸层和实际掺入待递送到聚合物层中的物质来区分。 在该方法的优选实施方案中，将两种聚合物溶解在挥发性有机溶剂中，待包封的物质分散或溶解在聚合物溶液中，将混合物悬浮在水溶液中并搅拌，并将溶剂缓慢蒸发， 产生具有由一种聚合物形成的内芯和由第二聚合物形成的外层的微球。 在另一个实施方案中，通过增加挥发性溶剂的蒸发速率，可以在其它聚合物的层内形成一种聚合物。
-
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
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。
-
-
-
-
-
-
-
-
-
搜索结果
66 条记录 (耗时 0.036 秒)
