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51. 发明授权

US06824791B2 Methods for micronization of hydrophobic drugs 失效
公开(公告)号：US06824791B2
公开(公告)日：2004-11-30
申请号：US10758990
申请日：2004-01-16
申请人： Edith Mathiowitz , Christopher Thanos , Zhi Liu
发明人： Edith Mathiowitz , Christopher Thanos , Zhi Liu
IPC分类号： A61K952
CPC分类号： A61K9/5138 , A61K9/14 , A61K9/146 , A61K9/1688 , A61K9/1694 , A61K9/5146 , A61K9/5192 , B01D9/00 , B01J13/06 , Y10T428/2982 , Y10T428/2985 , Y10T428/2989 , Y10T428/31685 , Y10T428/31696
摘要： The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.

52. 发明授权

US06217908B1 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：US06217908B1
公开(公告)日：2001-04-17
申请号：US08052473
申请日：1993-04-23
申请人： Edith Mathiowitz , Donald Chickering , Jules Serge Jacob
发明人： Edith Mathiowitz , Donald Chickering , Jules Serge Jacob
IPC分类号： A61K916
CPC分类号： A61K9/1641 , A61K9/167 , Y10S977/795 , Y10S977/906 , Y10S977/929
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。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。

53. 发明授权

US5853698A Method for making porous microparticles by spray drying 失效
标题翻译：通过喷雾干燥制备多孔微粒的方法
公开(公告)号：US5853698A
公开(公告)日：1998-12-29
申请号：US745676
申请日：1996-11-08
申请人： Julie Ann Straub , Edith Mathiowitz , Howard Bernstein , Henry T. Brush , Richard E. Wing
发明人： Julie Ann Straub , Edith Mathiowitz , Howard Bernstein , Henry T. Brush , Richard E. Wing
IPC分类号： A61B8/00 , A61K49/22 , A61B8/13
CPC分类号： A61B8/481 , A61K49/223
摘要： 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.
摘要翻译：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。

54. 发明授权

US5100668A Controlled release systems containing heparin and growth factors 失效
标题翻译：含有HEPARIN和生长因子的控制释放系统
公开(公告)号：US5100668A
公开(公告)日：1992-03-31
申请号：US206520
申请日：1988-06-14
申请人： Elazer R. Edelman , Robert S. Langer , Michael Klagsburn , Edith Mathiowitz
发明人： Elazer R. Edelman , Robert S. Langer , Michael Klagsburn , Edith Mathiowitz
IPC分类号： A61K9/16 , A61K9/50 , A61K38/18 , A61K47/48
CPC分类号： A61K47/4823 , A61K38/1825 , A61K9/167 , A61K9/5036 , Y10S530/813 , Y10S530/815 , Y10S530/816
摘要： 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.
摘要翻译：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。

55. 发明申请

US20120053156A1 COMPOSITIONS AND METHODS FOR LOOP DIURETICS WITH CONSISTENT BIOAVAILABILITY 有权
标题翻译：具有一致性生物利用度的环路滤膜的组合物和方法
公开(公告)号：US20120053156A1
公开(公告)日：2012-03-01
申请号：US13217764
申请日：2011-08-25
申请人： Edith Mathiowitz , Bryan Laulicht
发明人： Edith Mathiowitz , Bryan Laulicht
IPC分类号： A61K31/635 , A61K47/32 , A61P3/00 , A61P5/00 , A61P13/12 , A61P9/00 , C07D307/54 , A61P1/16
CPC分类号： A61K31/635 , A61K9/146 , A61K9/19 , C07D213/74 , C07D277/42 , C07D295/155 , C07D307/14 , C07D409/12
摘要： Diuretic bioactivity profiles of phase inversion micronized furosemide and furosemide co-precipitated with Eudragit L100, and mixtures of those formulations with stock furosemide, reduced or eliminated the rapid spike in diuresis associated with immediate release formulations and maintained cumulative urine output. Of the formulations tested, each of a mixture of micronized furosemide with stock furosemide, and Eudragit L100 polymer with stock furosemide demonstrated optimal diuretic bioactivity profiles in subjects.
摘要翻译：与Eudragit L100共沉淀的相转化微粉碎呋塞米和呋塞米的利尿生物活性曲线，以及那些制剂与储备呋塞米的混合物，减少或消除了与立即释放制剂相关的利尿的快速穗状态，并维持累积的尿量。在所测试的制剂中，微粉化呋塞米与储备呋塞米的混合物以及具有储备呋塞米的Eudragit L100聚合物在受试者中表现出最佳的利尿生物活性曲线。

56. 发明申请

US20120009267A1 NANOPARTICLE COMPOSITIONS AND METHODS FOR IMPROVED ORAL DELIVERY OF ACTIVE AGENTS 有权
标题翻译：纳米材料组合物和改进的活性剂的口服递送方法
公开(公告)号：US20120009267A1
公开(公告)日：2012-01-12
申请号：US13179205
申请日：2011-07-08
申请人： Daniel Cho , Joshua Reineke , Edith Mathiowitz , Bryan Laulicht
发明人： Daniel Cho , Joshua Reineke , Edith Mathiowitz , Bryan Laulicht
IPC分类号： A61K9/50 , A61K38/02 , A61K48/00 , B29B9/12 , A61K47/34 , A61K47/32 , A61K47/36 , A61K38/22 , A61K31/713
CPC分类号： A61K31/713 , A61K9/5026 , A61K9/5031 , A61K9/5073 , A61K9/5089 , A61K9/5138 , A61K9/5146 , A61K9/5192 , A61K38/00
摘要： Nanoparticles, compositions, and methods for the improved uptake of active agents are disclosed herein. The compositions contain a monodisperse population of nanoparticles, preferably including an active agent, where the nanoparticles are formed from a polymeric material possessing specified bioadhesion characteristics. Following enteral administration, preferably oral administration, the nanoparticles exhibit total intestinal uptakes of greater than 20%, preferably greater than 45%, more preferably greater than 65%. When compared to uptake of the same composition in the absence of the bioadhesive polymeric material, the nanoparticles have significantly increased uptake with intestinal uptake of the increased by more than 100%, preferably even greater than 500%. Further disclosed herein is a method of producing multi-walled nanoparticles, as well as methods of using thereof. Multi-walled particles prepared using the method disclosed herein are useful for controlling the release of active agents.
摘要翻译：本文公开了用于改善摄取活性剂的纳米颗粒，组合物和方法。组合物含有单分散的纳米颗粒群体，优选包括活性剂，其中纳米颗粒由具有特定生物粘附特性的聚合物形成。在肠内施用之后，优选口服给药，纳米颗粒显示出大于20％，优选大于45％，更优选大于65％的总肠吸收。当与没有生物粘附性聚合物材料的相同组合物的吸收相比时，纳米颗粒具有显着增加的摄取，肠吸收增加超过100％，优选甚至大于500％。本文进一步公开的是制备多壁纳米颗粒的方法及其使用方法。使用本文公开的方法制备的多壁颗粒可用于控制活性剂的释放。

57. 发明申请

US20110166218A1 METHODS FOR MICRONIZATION OF HYDROPHOBIC DRUGS 有权
标题翻译：疏水药物微量化方法
公开(公告)号：US20110166218A1
公开(公告)日：2011-07-07
申请号：US12140701
申请日：2008-06-17
申请人： Edith Mathiowitz , Christopher Thanos , Zhi Liu
发明人： Edith Mathiowitz , Christopher Thanos , Zhi Liu
IPC分类号： A61K31/352 , B29B9/12 , A61K31/337 , A61P3/10 , A61P31/10 , A61P9/12 , A61P31/00 , A61P35/00 , A61P25/08 , A61P25/18 , A61P19/02 , A61P31/12 , A61P37/02
CPC分类号： A61K9/5138 , A61K9/14 , A61K9/146 , A61K9/1688 , A61K9/1694 , A61K9/5146 , A61K9/5192 , B01D9/00 , B01J13/06 , Y10T428/2982 , Y10T428/2985 , Y10T428/2989 , Y10T428/31685 , Y10T428/31696
摘要： The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.
摘要翻译：本发明涉及与疏水性药物的微粉化相关的方法和产品。提供了使用一组包括水溶液的溶液来微粉化疏水性药物的方法。本发明还涉及微粉化疏水药物的产品和相关使用方法。

58. 发明申请

US20090311295A1 PARTICLES WITH HIGH UNIFORM LOADING OF NANOPARTICLES AND METHODS OF PREPARATION THEREOF 审中-公开
标题翻译：具有高均匀加载纳米颗粒的颗粒及其制备方法
公开(公告)号：US20090311295A1
公开(公告)日：2009-12-17
申请号：US12300304
申请日：2007-05-14
申请人： Edith Mathiowitz , Ljiljana Kundakovic , A. Peter Morello , Michael W. Harrison , Joshua James Reineke
发明人： Edith Mathiowitz , Ljiljana Kundakovic , A. Peter Morello , Michael W. Harrison , Joshua James Reineke
IPC分类号： A61K8/11 , C08L33/12 , A61K9/14 , A61K47/32 , A61P43/00 , A61Q90/00 , B01J13/04 , B01J13/00
CPC分类号： A61K9/1694 , A61K8/11 , A61K49/0021 , A61K49/0034 , A61K49/0036 , A61K49/0091 , A61K49/0093 , A61K2800/412 , A61Q1/02 , A61Q19/00 , C09C1/00
摘要： Methods to produce polymeric microparticles containing nanoparticles such, as pigments, dyes and other chromophores for cosmetic use, plastic surgery therapeutic use, and tattoos have been developed. The microparticles contain within the polymer a very uniform dispersion of dye particles. The methods by which the particles are made ensure a homogeneous mixture and high loading. The microparticles are made using air, one of a number of known methods such as phase inversion, solvent evaporation, and melt processing. The improvement is in the use of a method that makes, a stable dispersion of the nanoparticles in the liquid polymer before formation of the microparticles. This is achieved through selection of appropriate solvent, optionally including surfactant, and then subjecting the dispersion to mechanical processing that stabilizes the dispersion within the polymer solvent, so that the nanoparticles remain suspended for at least thirty minutes, in some cases two hours to 48 hours, sometimes up to three months. The mechanical processing can be sonication and/or production of shear forces, for examples, resulting from use of an open blade or rotor stator mixer or milling with a concentric shaft, at a speed such as between 5000 and 25,000 RPM.
摘要翻译：已经开发了制备含有纳米颗粒的聚合物微粒，例如颜料，染料和用于化妆品用途的其它发色团，整容手术治疗用途和纹身的方法。微粒在聚合物内含有非常均匀的染料颗粒分散体。制备颗粒的方法可确保均匀的混合物和高负载量。微粒使用空气制成，已知的方法之一是相转化，溶剂蒸发和熔融加工。改进之处在于使用在形成微粒之前使纳米颗粒稳定地分散在液体聚合物中的方法。这通过选择合适的溶剂，任选地包括表面活性剂，然后使分散体经受使聚合物溶剂中的分散体稳定的机械加工来实现，使得纳米颗粒保持悬浮至少30分钟，在一些情况下为2小时至48小时有时长达三个月。例如，通过使用开式叶片或转子定子混合器或以同心轴铣削，以5000至25,000RPM之间的速度，机械加工可以是超声处理和/或产生剪切力。

59. 发明申请

US20090022777A1 Methods for progenitor cell recruitment and isolation 有权
标题翻译：祖细胞募集和分离方法
公开(公告)号：US20090022777A1
公开(公告)日：2009-01-22
申请号：US10587884
申请日：2004-05-17
申请人： Edith Mathiowitz , Diana M. James
发明人： Edith Mathiowitz , Diana M. James
IPC分类号： A61F2/00 , A61K38/00 , A61P43/00
CPC分类号： A61K9/0024 , A61K9/1647 , A61K35/28 , A61K35/30 , A61K35/36 , A61K35/44 , A61K38/1866 , A61K38/193 , A61L27/38 , A61L27/3878 , A61L27/507
摘要： The invention relates to the use of one or more growth factors in a drug delivery system, optionally with an external mesh housing, to recruit and optionally harvest progenitor cells. These cells include those that normally reside in the bone marrow.
摘要翻译：本发明涉及一种或多种生长因子在药物递送系统中的应用，任选地具有外部网状物外壳，以募集和任选地收获祖细胞。这些细胞包括通常存在于骨髓中的细胞。

60. 发明申请

US20080311191A1 Multi-Layer Tablets and Bioadhesive Dosage Forms 审中-公开
标题翻译：多层片剂和生物粘附剂用量
公开(公告)号：US20080311191A1
公开(公告)日：2008-12-18
申请号：US11661541
申请日：2005-08-29
申请人： Avinash Nangia , Jules Jacob , Edith Mathiowitz , Thomas Ricketts , Mark R. Kreitz
发明人： Avinash Nangia , Jules Jacob , Edith Mathiowitz , Thomas Ricketts , Mark R. Kreitz
IPC分类号： A61K9/52 , A61K9/32 , A61K9/48 , A61K9/24
CPC分类号： A61K9/0065 , A61K9/209 , A61K9/2886 , A61K31/19 , A61K31/198 , A61K31/496 , A61K31/522
摘要： Bioadhesives coatings increase the gastrointestinal retention time of orally-ingested medicaments. Certain bioadhesive coatings producing a fracture strength of at least 100 N/m2, as measured on rat intestine, when applied to at least one surface of a pharmaceutical dosage form for oral delivery of a drug, result in a gastrointestinal retention time of at least 4 hours in a fed beagle dog model, during which the drug is released from the dosage form.Multi-layer tablets, particularly those including hydrophobic excipients, are useful in administering hygroscopic and/or deliquescent drugs. In addition, varying the amount of drug in multi-layer tablets allows the release rate of the drug to be controlled.
摘要翻译：生物粘合剂涂层增加了口服药物的胃肠停留时间。当在大鼠肠道上测量时产生至少100N / m 2的断裂强度的某些生物粘合剂涂层当应用于用于口服递送药物的药物剂型的至少一个表面时，导致胃肠停留时间至少为4 在喂养的比格犬模型中，药物从剂型中释放出来。多层片剂，特别是包括疏水性赋形剂的片剂，可用于施用吸湿和/或潮解性药物。此外，改变多层片剂中的药物的量允许控制药物的释放速率。

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