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1. 发明授权

US06528035B1 Multiwall polymeric microcapsules from hydrophilic polymers 失效
标题翻译：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
申请人： Edith Mathiowitz , Jules S. Jacob , Donald E. Chickering, III , Kathleen Jo Leach
发明人： Edith Mathiowitz , Jules S. Jacob , Donald E. Chickering, III , Kathleen Jo Leach
IPC分类号： B32B516
CPC分类号： 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
摘要： 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.
摘要翻译：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。

2. 发明授权

US06465002B1 Liquid crystalline polymers 有权
标题翻译：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
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。

3. 发明授权

US06511749B1 Preparation of multiwall polymeric microcapsules from hydrophilic polymers 失效
标题翻译：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
申请人： Edith Mathiowitz , Jules S. Jacob , Donald E. Chickering, III , Kathleen Jo Pekarek
发明人： Edith Mathiowitz , Jules S. Jacob , Donald E. Chickering, III , Kathleen Jo Pekarek
IPC分类号： B32B1502
CPC分类号： 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
摘要： 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.
摘要翻译：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。

4. 发明申请

US20100172998A1 PROCESS FOR PREPARING MICROPARTICLES THROUGH PHASE INVERSION PHENOMENA 审中-公开
标题翻译：通过相变反应准备微量元素的方法
公开(公告)号：US20100172998A1
公开(公告)日：2010-07-08
申请号：US12171275
申请日：2008-07-10
申请人： Edith Mathiowitz , Donald E. Chickering, III , Yong S. Jong , Jules S. Jacob
发明人： Edith Mathiowitz , Donald E. Chickering, III , Yong S. Jong , Jules S. Jacob
IPC分类号： B01J13/02 , A61K9/50 , A61K38/28 , A61K31/7088
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.
摘要翻译：提供了制备纳米颗粒和微粒的方法。该方法包括形成聚合物和溶剂的混合物，其中溶剂以连续相存在并将混合物引入有效量的非溶剂中以引起微粒的自发形成。

5. 发明授权

US5985354A Preparation of multiwall polymeric microcapsules from hydrophilic polymers 失效
公开(公告)号：US5985354A
公开(公告)日：1999-11-16
申请号：US478103
申请日：1995-06-07
申请人： Edith Mathiowitz , Jules S. Jacob , Donald E. Chickering, III , Kathleen Jo Pekarek
发明人： Edith Mathiowitz , Jules S. Jacob , Donald E. Chickering, III , Kathleen Jo Pekarek
IPC分类号： A61K9/16 , A61K9/50 , A61K9/52 , B01J13/04 , B01J13/06 , B01J13/20
CPC分类号： 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
摘要： 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.

6. 发明授权

US06365187B2 Bioadhesive microspheres and their use as drug delivery and imaging systems 失效
标题翻译：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：US06365187B2
公开(公告)日：2002-04-02
申请号：US09773229
申请日：2001-01-31
申请人： Edith Mathiowitz , Donald E. Chickering, III , Jules Serge Jacob
发明人： Edith Mathiowitz , Donald E. Chickering, III , Jules Serge Jacob
IPC分类号： A61K914
CPC分类号： A61K9/1641 , A61K9/167 , Y10S514/962 , Y10S977/906 , Y10S977/915 , Y10S977/928
摘要： Bioadhesive polymers in the form of, or as a coating on, microcapsules containing drugs or bioactive substances which may serve for therapeutic, 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/m2) 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.
摘要翻译：描述了可以用作胃肠道疾病中的治疗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 / m 2）的生物附着力。用于制造生物粘附性微球的技术以及用于测量微球和体外胃肠道选定区段之间的生物粘附力的方法是也描述。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。

7. 发明授权

US06235224B1 Process for preparing microparticles through phase inversion phenomena 有权
公开(公告)号：US06235224B1
公开(公告)日：2001-05-22
申请号：US09442723
申请日：1999-11-18
申请人： Edith Mathiowitz , Donald Chickering, III , Yong S. Jong , Jules S. Jacob
发明人： Edith Mathiowitz , Donald Chickering, III , Yong S. Jong , Jules S. Jacob
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.

8. 发明授权

US5985312A 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
申请人： Jules S. Jacob , Edith Mathiowitz
发明人： Jules S. Jacob , Edith Mathiowitz
IPC分类号： A61K9/00 , A61K9/16 , A61K9/50 , A61K9/51 , A61K47/02 , A61K9/14 , A61K51/00 , A61K15/54
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.

9. 发明授权

US06156348A Methods and compositions for enhancing the bioadhesive properties of polymers using organic excipients 失效
标题翻译：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
申请人： Camila A. Santos , Jules S. Jacob , Benjamin A. Hertzog , Gerardo P. Carino , Edith Mathiowitz
发明人： Camila A. Santos , Jules S. Jacob , Benjamin A. Hertzog , Gerardo P. Carino , Edith Mathiowitz
IPC分类号： B82B1/00 , A61K9/16 , A61K9/51 , A61K9/50 , A61F2/02 , A61K47/30
CPC分类号： A61K9/5138 , A61K9/1641 , A61K9/1647 , A61K9/5153
摘要： 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.
摘要翻译：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。

10. 发明授权

US06696075B2 Liquid crystalline polymers 有权
标题翻译：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
申请人： Edith Mathiowitz , Jules S. Jacob , Yong S. Jong , Donald E. Chickering , Edwin E. Edwards
发明人： Edith Mathiowitz , Jules S. Jacob , Yong S. Jong , Donald E. Chickering , 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/ 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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