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公开(公告)号：US08333995B2
公开(公告)日：2012-12-18
申请号：US11127704
申请日：2005-05-12
申请人： Larry Brown , Vered Bisker-Leib , Debra LaFreniere , John McGeehan , Julia Rashba-Step , Terrence Scott
发明人： Larry Brown , Vered Bisker-Leib , Debra LaFreniere , John McGeehan , Julia Rashba-Step , Terrence Scott
IPC分类号： A61K39/395
CPC分类号： C07K16/2896 , A61K9/0019 , A61K9/10 , A61K9/1688 , C07K16/2866 , C07K16/36 , C07K2317/24
摘要： The present invention relates to compositions of methods of making and compositions small compositions of particles of an active agent. In accordance with the method of production, the active agent is dissolved in an aqueous or aqueous-miscible solvent containing a dissolved phase-separation enhancing agent (PSEA) to form a solution in a single liquid phase. The solution is subjected to a liquid-solid phase separation to cause the active agent to form small spherical that are substantially amorphous or non-crystalline and are injectable through fine gauge needles at high concentrations. The invention has special application for higher molecular weight proteins.
摘要翻译： 本发明涉及制备方法的组合物和组合物活性剂颗粒的小组合物。 根据生产方法，将活性剂溶解在含有溶解的相分离增强剂（PSEA）的水溶性或水溶性溶剂中以形成单一液相中的溶液。 使溶液进行液固相分离，使活性剂形成基本上无定形或非结晶的小球形，并且可以通过高浓度的细针针进行注射。 本发明对高分子量蛋白质具有特殊应用。
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公开(公告)号：US20060024379A1
公开(公告)日：2006-02-02
申请号：US11127704
申请日：2005-05-12
申请人： Larry Brown , Vered Bisker-Leib , Debra LaFreniere , John McGeehan , Julia Rashba-Step , Terrence Scott
发明人： Larry Brown , Vered Bisker-Leib , Debra LaFreniere , John McGeehan , Julia Rashba-Step , Terrence Scott
IPC分类号： A61K39/395 , A61K9/50 , A61K9/16
CPC分类号： C07K16/2896 , A61K9/0019 , A61K9/10 , A61K9/1688 , C07K16/2866 , C07K16/36 , C07K2317/24
摘要： The present invention relates to compositions of methods of making and compositions small compositions of particles of an active agent. In accordance with the method of production, the active agent is dissolved in an aqueous or aqueous-miscible solvent containing a dissolved phase-separation enhancing agent (PSEA) to form a solution in a single liquid phase. The solution is subjected to a liquid-solid phase separation to cause the active agent to form small spherical that are substantially amorphous or non-crystalline and are injectable through fine gauge needles at high concentrations. The invention has special application for higher molecular weight proteins.
摘要翻译： 本发明涉及制备方法的组合物和组合物活性剂颗粒的小组合物。 根据生产方法，将活性剂溶解在含有溶解的相分离增强剂（PSEA）的水溶性或水溶性溶剂中以形成单一液相中的溶液。 使溶液进行液固相分离，使活性剂形成基本上无定形或非结晶的小球形，并且可以通过高浓度的细针针进行注射。 本发明对高分子量蛋白质具有特殊应用。
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3.发明申请Delivery of as-oligonucleotide microspheres to induce dendritic cell tolerance for the treatment of autoimmune type 1 diabetes 有权递送寡核苷酸微球以诱导树突状细胞耐受治疗自身免疫性1型糖尿病公开(公告)号：US20060024240A1
公开(公告)日：2006-02-02
申请号：US11127360
申请日：2005-05-12
申请人： Larry Brown , Vered Bisker-Leib , Terrence Scott , Debra Lafreniere , Jennifer Mochen , Nick Giannoukakls
发明人： Larry Brown , Vered Bisker-Leib , Terrence Scott , Debra Lafreniere , Jennifer Mochen , Nick Giannoukakls
CPC分类号： C12N15/1138 , A61K9/0019 , A61K9/1635 , A61K9/1641 , A61K9/1658 , A61K9/19 , C12N15/111 , C12N2310/11 , C12N2310/315 , C12N2320/32
摘要： AS-oligonucleotides are delivered in microsphere form in order to induce dendritic cell tolerance, particularly in the non-obese-diabetic (NOD) mouse model. The microspheres incorporate antisense (AS) oligonucleotides. A process includes using an antisense approach to prevent an autoimmune diabetes condition in NOD mice in vivo and in situ. The oligonucleotides are targeted to bind to primary transcripts CD40, CD80, CD86 and their combinations.
摘要翻译： AS寡核苷酸以微球形式递送，以诱导树突细胞耐受，特别是在非肥胖 - 糖尿病（NOD）小鼠模型中。 微球合并反义（AS）寡核苷酸。 一种方法包括使用反义方法在体内和原位抑制NOD小鼠中的自身免疫性糖尿病状况。 靶向寡核苷酸以结合初级转录物CD40，CD80，CD86及其组合。
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公开(公告)号：US09339465B2
公开(公告)日：2016-05-17
申请号：US12878783
申请日：2010-09-09
IPC分类号： A61K9/14 , A61K31/7088 , A61P37/00 , B32B5/16 , A61K9/16 , C12N15/11 , C12N15/113
CPC分类号： A61K9/1629 , C12N15/111 , C12N15/113 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2320/32 , Y10T428/2982
摘要： Nucleic acids are prepared by dissolving compounds containing them in a suitable solvent or solvent system and forming microspheres from the resulting solution. The microspheres are administered to an individual as protection from conditions where delivery of nucleic acids is useful, such as in treatment of autoimmune disease.
摘要翻译： 通过将含有它们的化合物溶解在合适的溶剂或溶剂体系中并从所得溶液中形成微球体来制备核酸。 将微球施用于个体，作为防止核酸递送有用的条件的保护，例如治疗自身免疫性疾病。
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公开(公告)号：US20060018971A1
公开(公告)日：2006-01-26
申请号：US11127362
申请日：2005-05-12
CPC分类号： A61K9/1629 , C12N15/111 , C12N15/113 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2320/32 , Y10T428/2982
摘要： Nucleic acids are prepared by dissolving compounds containg them in a suitable solvent or solvent system and forming microshperes from the resulting solution. The microspheres are administered to an individual as protection from conditions where delivery of nuceic acids is useful, such as in treatment of autoimmune disease.
摘要翻译： 通过将含有它们的化合物溶解在合适的溶剂或溶剂体系中并从所得溶液中形成微胶粒来制备核酸。 将微球体施用于个体，作为防止尿酸递送有用的条件，例如治疗自身免疫性疾病。
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6.发明申请Small spherical particles of low molecular weight organic molecules and methods of preparation and use thereof 审中-公开低分子量有机分子的小球形颗粒及其制备方法和用途公开(公告)号：US20050048127A1
公开(公告)日：2005-03-03
申请号：US10896326
申请日：2004-07-21
申请人： Larry Brown , Debra Lafreniere , John McGeehan
发明人： Larry Brown , Debra Lafreniere , John McGeehan
IPC分类号： A61K20060101 , A61K9/00 , A61K9/14
CPC分类号： A61K9/14 , A61K9/0019 , A61K9/0075
摘要： The invention provides homogeneous small spherical particles of low molecular weight organic molecules, said small spherical particles having a uniform shape, a narrow size distribution and average diameter of 0.01-200 μm. The invention further provides methods of preparation and methods of use of the small spherical particles. These small spherical particles are suitable for applications that require delivery of micron-size or nanosized particles with uniform size and good aerodynamic or flow characteristics. Pulmonary, intravenous, and other means of administration are among the delivery routes that may benefit from these small spherical particles.
摘要翻译： 本发明提供均匀的低分子量有机分子的小球形颗粒，所述小球形颗粒具有均匀的形状，窄尺寸分布和平均直径为0.01-200μm。 本发明还提供了制备方法和使用小球形颗粒的方法。 这些小球形颗粒适用于需要输送具有均匀尺寸和良好空气动力学或流动特性的微米级或纳米尺寸颗粒的应用。 可以从这些小球形颗粒中受益的输送途径之中，肺，静脉内和其它施用方式。
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7.发明申请Methods for fabrication, uses and compositions of small spherical particles of insulin prepared by controlled phase separation 审中-公开通过控制相分离制备的胰岛素小球形颗粒的制备方法，用途和组成公开(公告)号：US20050233945A1
公开(公告)日：2005-10-20
申请号：US10894432
申请日：2004-07-19
申请人： Larry Brown , John McGeehan , Yuanxi Qin , Julia Rashba-Step , Terrence Scott
发明人： Larry Brown , John McGeehan , Yuanxi Qin , Julia Rashba-Step , Terrence Scott
CPC分类号： B01J13/06 , A61K9/5026 , A61K9/5031 , A61K38/28
摘要： The present invention is related to a method for preparing small spherical particles of an active agent by providing a solution in a single liquid phase. The single liquid phase comprises an active agent, a phase separation enhancing agent, and a first solvent. A phase change is induced at a controlled rate in the solution to cause a liquid-solid phase separation of the active agent and to form a solid phase and a liquid phase. The solid phase comprises solid small spherical particles of the active agent. The liquid phase comprises the phase separation enhancing agent and the solvent. The small spherical particles are substantially spherical and having a size from about 0.01 μm to about 200 μm.
摘要翻译： 本发明涉及通过在单一液相中提供溶液来制备活性剂的小球形颗粒的方法。 单液相包含活性剂，相分离增强剂和第一溶剂。 在溶液中以受控的速率诱导相变，引起活性剂的液固相分离并形成固相和液相。 固相包含活性剂的固体小球形颗粒。 液相包含相分离增效剂和溶剂。 小球形颗粒基本上是球形的并且具有约0.01μm至约200μm的尺寸。
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8.发明申请Methods for fabrication, uses and compositions of small spherical particles prepared by controlled phase separation 有权通过控制相分离制备的小球形颗粒的制备方法，用途和组成公开(公告)号：US20050142206A1
公开(公告)日：2005-06-30
申请号：US10894430
申请日：2004-07-19
申请人： Larry Brown , John McGeehan , Julia Rashba-Step , Terrence Scott
发明人： Larry Brown , John McGeehan , Julia Rashba-Step , Terrence Scott
CPC分类号： B01J13/06 , A61K9/5026 , A61K9/5031 , A61K38/28
摘要： The present invention is related to a method for preparing small spherical particles of an active agent by providing a solution in a single liquid phase. The single liquid phase comprises an active agent, a phase separation enhancing agent, and a first solvent. A phase change is induced at a controlled rate in the solution to cause a liquid-solid phase separation of the active agent and to form a solid phase and a liquid phase. The solid phase comprises solid small spherical particles of the active agent. The liquid phase comprises the phase separation enhancing agent and the solvent. The small spherical particles are substantially spherical and having a size from about 0.01 μm to about 200 μm.
摘要翻译： 本发明涉及通过在单一液相中提供溶液来制备活性剂的小球形颗粒的方法。 单液相包含活性剂，相分离增强剂和第一溶剂。 在溶液中以受控的速率诱导相变，引起活性剂的液固相分离并形成固相和液相。 固相包含活性剂的固体小球形颗粒。 液相包含相分离增效剂和溶剂。 小球形颗粒基本上是球形的并且具有约0.01μm至约200μm的尺寸。
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9.发明申请Methods for fabrication, uses and compositions of small spherical particles of hGH prepared by controlled phase separation 审中-公开通过控制相分离制备的hGH的小球形颗粒的制备，使用和组成的方法公开(公告)号：US20050142201A1
公开(公告)日：2005-06-30
申请号：US10894408
申请日：2004-07-19
CPC分类号： B01J13/06 , A61K9/5026 , A61K9/5031 , A61K38/28
摘要： The present invention is related to a method for preparing small spherical particles of an active agent by providing a solution in a single liquid phase. The single liquid phase comprises an active agent, a phase separation enhancing agent, and a first solvent. A phase change is induced at a controlled rate in the solution to cause a liquid-solid phase separation of the active agent and to form a solid phase and a liquid phase. The solid phase comprises solid small spherical particles of the active agent. The liquid phase comprises the phase separation enhancing agent and the solvent. The small spherical particles are substantially spherical and having a size from about 0.01 μm to about 200 μm.
摘要翻译： 本发明涉及通过在单一液相中提供溶液来制备活性剂的小球形颗粒的方法。 单液相包含活性剂，相分离增强剂和第一溶剂。 在溶液中以受控的速率诱导相变，引起活性剂的液固相分离并形成固相和液相。 固相包含活性剂的固体小球形颗粒。 液相包含相分离增效剂和溶剂。 小球形颗粒基本上是球形的并且具有约0.01μm至约200μm的尺寸。
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公开(公告)号：US20080026068A1
公开(公告)日：2008-01-31
申请号：US11736372
申请日：2007-04-17
申请人： Larry Brown , John McGeehan , Qin Yuanxi , Julia Rashba-Step , Terrence Scott
发明人： Larry Brown , John McGeehan , Qin Yuanxi , Julia Rashba-Step , Terrence Scott
CPC分类号： A61K9/0075 , A61K38/28
摘要： Compositions of spherical insulin particles having improved pulmonary application potentials and methods of forming and using these compositions are disclosed in the present application. In one clinical trial with 30 healthy male human subjects, no coughing was observed upon a single pulmonary administration of the spherical insulin particles at an insulin dose of 6.5 mg, nor during the 10-hour post dosing period.
摘要翻译： 在本申请中公开了具有改善的肺部施用电位的球形胰岛素颗粒的组合物以及形成和使用这些组合物的方法。 在30名健康雄性人类受试者的一项临床试验中，在胰岛素剂量为6.5mg的单次肺部施用球素胰岛素颗粒时，也不在给药后10小时期间观察不到咳嗽。
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