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    METHODS AND SYSTEMS FOR PROLONGED LOCALIZATION OF DRUG DELIVERY
    22.
    发明申请
    METHODS AND SYSTEMS FOR PROLONGED LOCALIZATION OF DRUG DELIVERY 有权
    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

    Applicant: Bryan Laulicht ,  Edith Mathiowitz

    Inventor： Bryan Laulicht ,  Edith Mathiowitz

    IPC: A61M37/00 ,  A61B18/00 ,  A61B6/00 ,  A61N5/00 ,  H01F7/00 ,  B29B9/00

    CPC classification number: H01F1/0054 ,  A61B5/062 ,  A61B6/12 ,  A61J3/071 ,  A61J3/10 ,  A61K9/501 ,  A61K9/5031 ,  A61K9/5036 ,  A61K9/5057 ,  A61K9/5094

    Abstract: 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.

    Abstract translation: 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。

    METHODS AND SYSTEMS FOR PROLONGED LOCALIZATION OF DRUG DELIVERY
    23.
    发明申请
    METHODS AND SYSTEMS FOR PROLONGED LOCALIZATION OF DRUG DELIVERY 有权
    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

    Applicant: Bryan Laulicht ,  Edith Mathiowitz

    Inventor： Bryan Laulicht ,  Edith Mathiowitz

    IPC: 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 classification number: A61K9/0009 ,  A61K9/0004 ,  A61K9/1658 ,  A61K9/4808 ,  H01F1/0054

    Abstract: 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.

    Abstract translation: 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。

    Cell Aggregation and Encapsulation Device and Method
    25.
    发明申请
    Cell Aggregation and Encapsulation Device and Method 有权
    细胞聚集和包封装置及方法

    公开(公告)号：US20090018033A1

    公开(公告)日：2009-01-15

    申请号：US12087937

    申请日：2007-01-24

    Applicant: Jeffrey Morgan ,  Peter Chai ,  Anthony Napolitano ,  Edith Mathiowitz ,  Dylan Dean

    Inventor： Jeffrey Morgan ,  Peter Chai ,  Anthony Napolitano ,  Edith Mathiowitz ,  Dylan Dean

    IPC: C40B50/06 ,  C12M1/00 ,  C12N5/00 ,  B29C33/40 ,  C40B60/00

    CPC classification number: C12M25/00 ,  B33Y80/00 ,  C12M21/08 ,  C12M23/12 ,  C12M25/14 ,  C12N5/0012 ,  C12N5/0062 ,  C12N2533/40 ,  C12N2533/74

    Abstract: 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.

    Abstract translation: 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。

    Controlled regional oral delivery
    26.
    发明申请
    Controlled regional oral delivery 审中-公开
    受控区域口服

    公开(公告)号：US20060045865A1

    公开(公告)日：2006-03-02

    申请号：US11214206

    申请日：2005-08-28

    Applicant: Jules Jacob ,  Edith Mathiowitz ,  Avinash Nangia ,  Ze'ev Shaked ,  Peyman Moslemy

    Inventor： Jules Jacob ,  Edith Mathiowitz ,  Avinash Nangia ,  Ze'ev Shaked ,  Peyman Moslemy

    IPC: A61K31/74

    CPC classification number: A61K9/5031 ,  A61K9/006 ,  A61K9/0092 ,  A61K9/1641 ,  A61K9/1652 ,  A61K9/1676 ,  A61K9/2018 ,  A61K9/2031 ,  A61K9/204 ,  A61K9/2054 ,  A61K9/2077 ,  A61K9/2086 ,  A61K9/209 ,  A61K9/4808 ,  A61K9/4891 ,  A61K9/5026 ,  A61K9/5084 ,  A61K31/74

    Abstract: A composite formulation has been developed for selective, high efficacy delivery to specific regions of the mouth and gastrointestinal tract. The formulation is typically in the form of a tablet or capsule, which may include microparticles or beads. The formulation uses bioadhesive and controlled release elements to direct release to specific regions, where the drug is absorbed in enhanced amounts relative to the formulation in the absence of the bioadhesive and/or controlled release elements. This is demonstrated by an example showing delivery of gabapentin with a greater area under the curve (“AUC”) relative to the FDA reference immediate release drug, i.e., the AUC of the composite bioadhesive formulation is greater than 100% of the AUC of the immediate release drug. In the preferred embodiments, the formulation includes drug to be delivered, controlled release elements, and one or more bioadhesive elements. The bioadhesive polymer may be either dispersed in the matrix of the tablet or applied as a direct compressed coating to the solid oral dosage form. The controlled release elements are selected to determine the site of release. The bioadhesive components are selected to provide retention of the formulation at the desired site of uptake and administration. By selecting for both release and retention at a specific site, typically based on time of transit through the gastrointestinal tract, one obtains enhanced efficacy of uptake of the drug. This is particularly useful for drugs with narrow windows of absorption, and drugs with poor solubility such as the BCE class III and class IV drugs.

    Abstract translation: 已经开发了复合制剂用于选择性，高效率地递送到口腔和胃肠道的特定区域。 制剂通常为片剂或胶囊形式，其可包括微粒或珠粒。 制剂使用生物粘附和控制释放元件将释放引导到特定区域，其中药物在没有生物粘附和/或控制释放元件的情况下相对于制剂以增强的量被吸收。 这通过示例显示，相对于FDA参考即时释放药物，在曲线下具有更大面积（“AUC”）的加巴喷丁的递送，即复合生物粘附制剂的AUC大于AUC的100％ 立即释放药物。 在优选的实施方案中，制剂包括待递送的药物，控制释放元件和一种或多种生物粘附元件。 生物粘附聚合物可以分散在片剂的基质中或作为直接压片包被施用于固体口服剂型。 选择受控释放元件以确定释放位点。 选择生物粘附组分以使制剂保留在所需的摄取和给药部位。 通过选择在特定部位的释放和保留，通常基于通过胃肠道的转运时间，获得药物摄取的增强的功效。 这对于具有窄吸收窗口的药物和溶解性差的药物如BCE III类和IV类药物特别有用。

    Liquid crystalline polymers
    27.
    发明授权
    Liquid crystalline polymers 有权
    液晶聚合物

    公开(公告)号：US06696075B2

    公开(公告)日：2004-02-24

    申请号：US10231723

    申请日：2002-08-30

    Applicant: Edith Mathiowitz ,  Jules S. Jacob ,  Yong S. Jong ,  Donald E. Chickering ,  Edwin E. Edwards

    Inventor： Edith Mathiowitz ,  Jules S. Jacob ,  Yong S. Jong ,  Donald E. Chickering ,  Edwin E. Edwards

    IPC: A61F1300

    CPC classification number: C09K19/38 ,  B29C55/00 ,  B29C55/18 ,  B29K2105/0079

    Abstract: 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.

    Abstract translation: 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/ in 2的压力下，优选在约2至10公吨/ in 2之间，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。

    Bioadhesive microspheres and their use as drug delivery and imaging systems
    30.
    发明授权
    Bioadhesive microspheres and their use as drug delivery and imaging systems 失效
    生物粘附微球及其作为药物递送和成像系统的用途

    公开(公告)号：US06197346B1

    公开(公告)日：2001-03-06

    申请号：US07873480

    申请日：1992-04-24

    Applicant: Edith Mathiowitz ,  Donald Chickering ,  Jules Serge Jacob

    Inventor： Edith Mathiowitz ,  Donald Chickering ,  Jules Serge Jacob

    IPC: A61K916

    CPC classification number: A61K9/1641 ,  A61K9/167 ,  Y10S977/795 ,  Y10S977/906 ,  Y10S977/929

    Abstract: Bioadhesive polymers in the form of, or as a coating on, microcapsules containing drugs or bioactive substances which may serve for therapeutic, diagnostic, or diagnostic purposes in diseases of the gastrointestinal tract, are described. The polymeric microspheres all have a bioadhesive force of at least 11 mN/cm2 (110 N/CM2). Techniques for the fabrication of bioadhesive microspheres, as well as a method for measuring bioadhesive forces between microspheres and selected segments of the gastrointestinal tract in vitro are also described. This quantitative method provides a means to establish a correlation between the chemical nature, the surface morphology and the dimensions of drug-loaded microspheres on one hand and bioadhesive forces on the other, allowing the screening of the most promising materials from a relatively large group of natural and synthetic polymers which, from theoretical consideration, should be used for making bioadhesive microspheres.

    Abstract translation: 描述了可能在胃肠道疾病中用于治疗，诊断或诊断目的的药物或生物活性物质的形式或作为包衣形式的生物粘附聚合物。 聚合物微球全部具有至少11mN / cm 2（110N / CM 2）的生物粘附力。 还描述了用于制造生物粘附微球的技术，以及用于测量体外微球和胃肠道的选定区段之间的生物粘附力的方法。 这种定量方法提供了一种手段来建立化学性质，表面形态和药物负载微球的尺寸与生物粘附力之间的相关性，另一方面可以从相对较大的组中筛选出最有希望的材料 天然和合成的聚合物，从理论上考虑，应用于制造生物粘附微球。

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