公开(公告)号：US06368586B1

公开(公告)日：2002-04-09

申请号：US09535421

申请日：2000-03-27

Applicant: Jules S. Jacob ,  Edith Mathiowitz

Inventor： Jules S. Jacob ,  Edith Mathiowitz

IPC: A61K3174

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

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 anhydrideoligome into the polymer to enhance the ability of the polymer to adhere to a tissue surface such as a mucosal membrane. Anhydrideoligomes which enhance the bioadhesive properties of a polymer include water-insoluble anhydrideoligomes such as water-insoluble metal oxides, including oxides of calcium, iron, copper and zinc. The anhydrideoligomes 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.

Abstract translation: 提供了用于增强药物递送装置中使用的聚合物的生物粘合性能的方法和组合物。 聚合物的生物粘合性能通过将酸酐加入到聚合物中来增强聚合物粘附到组织表面如粘膜上的能力。 增强聚合物生物粘合性能的寡聚寡糖包括水不溶性的酸酐，如水不溶性金属氧化物，包括钙，铁，铜和锌的氧化物。 酸酐偶联物可以掺入到宽范围的聚合物中，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，金属氧化物可以掺入用于形成或涂覆药物递送装置的聚合物，例如含有药物或诊断剂的微球体。 金属氧化物可以以涂覆或形成器件的聚合物表面上的细颗粒分散体的形式提供，这增强了器件结合粘膜的能力。 聚合物例如以微球的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递送药物或诊断剂，包括胃肠道，呼吸道， 排泄和生殖道。

公开(公告)号：US06235313B1

公开(公告)日：2001-05-22

申请号：US08824172

申请日：1997-03-26

Applicant: Edith Mathiowitz ,  Donald Chickering, III ,  Jules S. Jacob

Inventor： Edith Mathiowitz ,  Donald Chickering, III ,  Jules S. Jacob

IPC: A61K914

CPC classification number: A61K9/1641 ,  A61K9/167 ,  Y10S514/962 ,  Y10S977/906 ,  Y10S977/915 ,  Y10S977/928

Abstract: 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.

公开(公告)号：US06217908B1

公开(公告)日：2001-04-17

申请号：US08052473

申请日：1993-04-23

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, 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.

Abstract translation: 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。 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。

公开(公告)号：US6123965A

公开(公告)日：2000-09-26

申请号：US135705

申请日：1998-08-18

Applicant: Jules S. Jacob ,  Edith Mathiowitz

Inventor： Jules S. Jacob ,  Edith Mathiowitz

IPC: A61K9/00 ,  A61K9/16 ,  A61K9/50 ,  A61K9/51 ,  A61K47/02 ,  A61K9/52

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.

Abstract translation: 提供了用于增强药物递送装置中使用的聚合物的生物粘合性能的方法和组合物。 聚合物的生物粘合性能通过将金属化合物引入聚合物来增强聚合物粘附到组织表面如粘膜上的能力。 提高聚合物生物粘合性能的金属化合物包括水不溶性金属化合物，如水不溶性金属氧化物，包括钙，铁，铜和锌的氧化物。 金属化合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，金属氧化物可以掺入用于形成或涂覆药物递送装置的聚合物，例如含有药物或诊断剂的微球体。 金属氧化物可以以涂覆或形成器件的聚合物表面上的细颗粒分散体的形式提供，这增强了器件结合粘膜的能力。 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。

公开(公告)号：US5853698A

公开(公告)日：1998-12-29

申请号：US745676

申请日：1996-11-08

Applicant: Julie Ann Straub ,  Edith Mathiowitz ,  Howard Bernstein ,  Henry T. Brush ,  Richard E. Wing

Inventor： Julie Ann Straub ,  Edith Mathiowitz ,  Howard Bernstein ,  Henry T. Brush ,  Richard E. Wing

IPC: A61B8/00 ,  A61K49/22 ,  A61B8/13

CPC classification number: A61B8/481 ,  A61K49/223

Abstract: It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.

Abstract translation: 已经发现，与合并有空气的微粒相比，将氟化气体，特别是全氟化碳如八氟丙烷掺入到合成的聚合物微粒中显着增强回波反应性。 制造微胶囊化全氟化碳，其直径适用于待成像的目标组织，例如用于静脉内或口服给药。 在一个实施方案中，形成生物粘附微粒用于增强粘膜表面的成像。

公开(公告)号：US5100668A

公开(公告)日：1992-03-31

申请号：US206520

申请日：1988-06-14

Applicant: Elazer R. Edelman ,  Robert S. Langer ,  Michael Klagsburn ,  Edith Mathiowitz

Inventor： Elazer R. Edelman ,  Robert S. Langer ,  Michael Klagsburn ,  Edith Mathiowitz

IPC: A61K9/16 ,  A61K9/50 ,  A61K38/18 ,  A61K47/48

CPC classification number: A61K47/4823 ,  A61K38/1825 ,  A61K9/167 ,  A61K9/5036 ,  Y10S530/813 ,  Y10S530/815 ,  Y10S530/816

Abstract: A system for stabilizing fibroblast-derived growth factors, maintaining their bioactivity over a prolonged period of time and controllably releasing them for use is disclosed. The system uses growth factors bound to biocompatible substrates via heparin or heparin derived compounds to maintain the bioactivity of the growth factors. A growth factor bound to a heparin coated substrate can be used independently as a controlled release device, or can be incorporated into a reservoir or matrix type controlled release devices to further enhance the controlled release properties. The stabilized growth factors can be implanted into a patient, thereby providing a means for producing an in vivo controlled release of a growth factor to the patient.

Abstract translation: 公开了一种用于稳定成纤维细胞衍生生长因子的系统，其在长时间内保持其生物活性并且可控地释放它们以供使用。 该系统使用通过肝素或肝素衍生的化合物结合生物相容性底物的生长因子，以维持生长因子的生物活性。 与肝素包被的底物结合的生长因子可以独立地用作控释装置，或者可以并入储存器或基质型受控释放装置中以进一步增强控制释放性质。 可以将稳定的生长因子植入患者体内，从而提供生产体内受控制的生长因子释放给患者的手段。