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    Liquid crystalline polymers
    1.
    发明授权
    Liquid crystalline polymers 有权
    液晶聚合物

    公开(公告)号：US06465002B1

    公开(公告)日：2002-10-15

    申请号：US09523887

    申请日：2000-03-13

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

    Inventor： Edith Mathiowitz ,  Jules S. Jacob ,  Yong S. Jong ,  Donald E. Chickering, III ,  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/ 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。

    Methods and compositions for enhancing the bioadhesive properties of polymers
    3.
    发明授权
    Methods and compositions for enhancing the bioadhesive properties of polymers 失效

    公开(公告)号：US5985312A

    公开(公告)日：1999-11-16

    申请号：US592565

    申请日：1996-01-26

    Applicant: Jules S. Jacob ,  Edith Mathiowitz

    Inventor： Jules S. Jacob ,  Edith Mathiowitz

    IPC: A61K9/00 ,  A61K9/16 ,  A61K9/50 ,  A61K9/51 ,  A61K47/02 ,  A61K9/14 ,  A61K51/00 ,  A61K15/54

    CPC classification number: A61K9/5153 ,  A61K47/02 ,  A61K9/006 ,  A61K9/1611 ,  A61K9/1635 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/1658

    Abstract: 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.

    Multiwall polymeric microcapsules from hydrophilic polymers
    4.
    发明授权
    Multiwall polymeric microcapsules from hydrophilic polymers 失效
    来自亲水聚合物的多壁聚合物微胶囊

    公开(公告)号：US06528035B1

    公开(公告)日：2003-03-04

    申请号：US09707440

    申请日：2000-11-06

    Applicant: Edith Mathiowitz ,  Jules S. Jacob ,  Donald E. Chickering, III ,  Kathleen Jo Leach

    Inventor： Edith Mathiowitz ,  Jules S. Jacob ,  Donald E. Chickering, III ,  Kathleen Jo Leach

    IPC: B32B516

    CPC classification number: B01J13/04 ,  A61K9/1641 ,  A61K9/1652 ,  A61K9/1694 ,  A61K9/5036 ,  A61K9/5052 ,  A61K9/5089 ,  B29K2003/00 ,  Y10S514/963 ,  Y10S514/965 ,  Y10T428/2984 ,  Y10T428/2985 ,  Y10T428/2989 ,  Y10T428/2991

    Abstract: Two or more hydrophilic polymers that are not soluble in each other at a particular concentration and temperature, but which have a positive spreading coefficient in solution, are used to form multi-layered polymeric microspheres. The multi-layer microspheres produced by the method are distinguished by extremely uniform dimensioned polymer layers and actual incorporation of a substance to be delivered into the polymer layers. In the preferred embodiment of the method, two polymers are dissolved in an aqueous solvent, the substance to be incorporated is dispersed or dissolved in the polymer solution, the mixture is suspended in an organic solvent or polymer/water mixture 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.

    Abstract translation: 在特定浓度和温度下彼此不溶的但在溶液中具有正扩散系数的两种或更多种亲水性聚合物用于形成多层聚合物微球体。 通过该方法制备的多层微球的特征在于非常均匀的尺寸聚合物层和实际掺入待输送到聚合物层中的物质。 在该方法的优选实施方案中，将两种聚合物溶解在水性溶剂中，将待加入的物质分散或溶解在聚合物溶液中，将混合物悬浮在有机溶剂或聚合物/水混合物中并搅拌，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。

    Preparation of multiwall polymeric microcapsules from hydrophilic polymers
    5.
    发明授权
    Preparation of multiwall polymeric microcapsules from hydrophilic polymers 失效
    从亲水聚合物制备多壁聚合物微胶囊

    公开(公告)号：US06511749B1

    公开(公告)日：2003-01-28

    申请号：US08990365

    申请日：1997-12-15

    Applicant: Edith Mathiowitz ,  Jules S. Jacob ,  Donald E. Chickering, III ,  Kathleen Jo Pekarek

    Inventor： Edith Mathiowitz ,  Jules S. Jacob ,  Donald E. Chickering, III ,  Kathleen Jo Pekarek

    IPC: B32B1502

    CPC classification number: B01J13/04 ,  A61K9/1641 ,  A61K9/1652 ,  A61K9/1694 ,  A61K9/5036 ,  A61K9/5052 ,  A61K9/5089 ,  B29K2003/00 ,  Y10S514/963 ,  Y10S514/965 ,  Y10T428/2984 ,  Y10T428/2985 ,  Y10T428/2989 ,  Y10T428/2991

    Abstract: Two or more hydrophilic polymers that are not soluble in each other at a particular concentration and temperature, but which have a positive spreading coefficient in solution, are used to form multi-layered polymeric microspheres. The multi-layer microspheres produced by the method are distinguished by extremely uniform dimensioned polymer layers and actual incorporation of a substance to be delivered into the polymer layers. In the preferred embodiment of the method, two polymers are dissolved in an aqueous solvent, the substance to be incorporated is dispersed or dissolved in the polymer solution, the mixture is suspended in an organic solvent or polymer/water mixture 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.

    Abstract translation: 在特定浓度和温度下彼此不溶的但在溶液中具有正扩散系数的两种或更多种亲水性聚合物用于形成多层聚合物微球体。 通过该方法制备的多层微球的特征在于非常均匀的尺寸聚合物层和实际掺入待输送到聚合物层中的物质。 在该方法的优选实施方案中，将两种聚合物溶解在水性溶剂中，将待加入的物质分散或溶解在聚合物溶液中，将混合物悬浮在有机溶剂或聚合物/水混合物中并搅拌，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。

    Methods and compositions for enhancing the bioadhesive properties of polymers using organic excipients
    6.
    发明授权
    Methods and compositions for enhancing the bioadhesive properties of polymers using organic excipients 失效
    使用有机赋形剂增强聚合物生物粘合性能的方法和组合物

    公开(公告)号：US06156348A

    公开(公告)日：2000-12-05

    申请号：US135248

    申请日：1998-08-17

    Applicant: Camila A. Santos ,  Jules S. Jacob ,  Benjamin A. Hertzog ,  Gerardo P. Carino ,  Edith Mathiowitz

    Inventor： Camila A. Santos ,  Jules S. Jacob ,  Benjamin A. Hertzog ,  Gerardo P. Carino ,  Edith Mathiowitz

    IPC: B82B1/00 ,  A61K9/16 ,  A61K9/51 ,  A61K9/50 ,  A61F2/02 ,  A61K47/30

    CPC classification number: A61K9/5138 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/5153

    Abstract: Methods and compositions are provided for enhancing the bioadhesive properties of polymers used in drug delivery systems. The bioadhesive properties of a polymer are enhanced by incorporating an anhydride oligomer into the polymer to enhance the ability of the polymer to adhere to a tissue surface such as a mucosal membrane. Anhydride oligomers which enhance the bioadhesive properties of a polymer include oligomers synthesized from dicarboxylic acid monomers, preferably those found in Krebs glycolysis cycle, especially fumaric acid. The oligomers can be incorporated within a wide range of polymers including proteins, polysaccharides and synthetic biocompatible polymers. In one embodiment, anhydride oligomers can be incorporated within polymers used to form or coat drug delivery systems, such as microspheres, which contain a drug or diagnostic agent. The oligomers can either be solubilized and blended with the polymer before manufacture or else used as a coating with polymers over existing systems. 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.

    Abstract translation: 提供了用于增强药物递送系统中使用的聚合物的生物粘合性质的方法和组合物。 聚合物的生物粘合性能通过将酸酐低聚物引入聚合物来增强聚合物粘附到组织表面如粘膜的能力。 增强聚合物生物粘合性能的酸酐低聚物包括由二羧酸单体合成的低聚物，优选在克雷伯糖酵解循环中发现的那些，特别是富马酸。 低聚物可以掺入宽范围的聚合物中，包括蛋白质，多糖和合成的生物相容性聚合物。 在一个实施方案中，酸酐低聚物可以掺入用于形成或涂覆药物递送系统的聚合物，例如含有药物或诊断剂的微球体。 寡聚物可以在制造之前溶解并与聚合物共混，或者在现有体系中用作具有聚合物的涂层。 聚合物，例如以微球形式，具有改善粘附于粘膜的能力，因此可用于通过任何一种粘膜膜表面（包括胃肠道，呼吸道，排泄物）的粘膜递送药物或诊断剂 和生殖道。

    Liquid crystalline polymers
    7.
    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。

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