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    PARTICLES FOR INHALATION HAVING RAPID RELEASE PROPERTIES
    1.
    发明申请
    PARTICLES FOR INHALATION HAVING RAPID RELEASE PROPERTIES 审中-公开
    具有快速释放特性的吸入颗粒

    公开(公告)号：US20080226730A1

    公开(公告)日：2008-09-18

    申请号：US11860302

    申请日：2007-09-24

    申请人： Jennifer L. Schmitke ,  Donghao Chen ,  Richard P. Batycky ,  David A. Edwards ,  Jeffrey S. Hrkach

    发明人： Jennifer L. Schmitke ,  Donghao Chen ,  Richard P. Batycky ,  David A. Edwards ,  Jeffrey S. Hrkach

    IPC分类号： A61K9/14 ,  A61K38/28

    CPC分类号： A61K9/1617 ,  A61K9/0075 ,  A61K38/28 ,  A61K47/544

    摘要： The invention generally relates to formulations having particles comprising phospholipids, bioactive agent and excipients and the pulmonary delivery thereof. Dry powder inhaled insulin formulations are disclosed. Improved formulations comprising DPPC, insulin and sodium citrate which are useful in the treatment of diabetes are disclosed. Also, the invention relates to a method of for the pulmonary delivery of a bioactive agent comprising administering to the respiratory tract of a patient in need of treatment, or diagnosis an effective amount of particles comprising a bioactive agent or any combination thereof in association, wherein release of the agent from the administered particles occurs in a rapid fashion.

    摘要翻译： 本发明一般涉及具有包含磷脂，生物活性剂和赋形剂以及其肺部递送的颗粒的制剂。 公开了干粉吸入胰岛素制剂。 公开了包含可用于治疗糖尿病的DPPC，胰岛素和柠檬酸钠的改进制剂。 此外，本发明涉及一种用于肺部递送生物活性剂的方法，包括向需要治疗的患者的呼吸道施用或相关地诊断包含生物活性剂或其任何组合的有效量的颗粒，其中 药剂从施用的颗粒的释放以快速方式发生。

    Control of process humidity to produce large, porous particles
    3.
    发明授权
    Control of process humidity to produce large, porous particles 有权
    控制工艺湿度以产生大的多孔颗粒

    公开(公告)号：US07469488B2

    公开(公告)日：2008-12-30

    申请号：US10977088

    申请日：2004-10-29

    申请人： Donghao Chen ,  Richard P. Batycky ,  Lloyd Johnston ,  Jeffrey Mintzes

    发明人： Donghao Chen ,  Richard P. Batycky ,  Lloyd Johnston ,  Jeffrey Mintzes

    IPC分类号： E02F5/10 ,  A01N25/02 ,  A61K9/14 ,  A05D7/00

    CPC分类号： A61K9/0075 ,  A61K9/1694 ,  Y10S514/951

    摘要： Spray dried particles having specified aerodynamic characteristics are produced by atomizing a liquid feed and contacting the liquid feed with a drying gas, such as, for example, air or nitrogen. The humidity of the drying gas is controlled to a value, expressed, for instance, as dew point, which is known to produce particles having a specified tap density or aerodynamic diameter. Particles having a volume median geometric diameter greater than about 5 microns and a tap density less than about 0.4 g/cm3 are preferred.

    摘要翻译： 通过雾化液体进料并使液体进料与例如空气或氮气的干燥气体接触来产生具有特定空气动力特性的喷雾干燥颗粒。 干燥气体的湿度被控制为例如表示为露点，其已知产生具有特定振实密度或空气动力学直径的颗粒。 体积中值几何直径大于约5微米且振实密度小于约0.4g / cm 3的颗粒是优选的。

    Preparation of novel particles for inhalation
    5.
    发明授权
    Preparation of novel particles for inhalation 有权
    用于吸入的新型颗粒的制备

    公开(公告)号：US06652837B1

    公开(公告)日：2003-11-25

    申请号：US09394233

    申请日：1999-09-13

    申请人： David A. Edwards ,  Robert S. Langer ,  Rita Vanbever ,  Jeffrey Mintzes ,  Jue Wang ,  Donghao Chen

    发明人： David A. Edwards ,  Robert S. Langer ,  Rita Vanbever ,  Jeffrey Mintzes ,  Jue Wang ,  Donghao Chen

    IPC分类号： A61K912

    CPC分类号： A61K9/0075 ,  A61K9/1617 ,  A61K9/1623 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/1658 ,  A61K31/135 ,  A61K31/137 ,  A61K38/28 ,  A61K38/38 ,  A61K47/6927 ,  Y10S514/958

    摘要： Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 &mgr;m and 30 &mgr;m, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration.

    摘要翻译： 提供了将具有正或负电荷的治疗剂的表面活性剂和/或亲水或疏水配合物和用于药物递送至肺系统的带电分子的相反电荷的颗粒，以及用于其合成和给药的方法。 在一个优选的实施方案中，颗粒由可生物降解的材料制成，并且具有小于0.4g / cm 3的振实密度和5μm和30μm之间的质量平均直径，这两个颗粒之间的颗粒的空气动力学直径在 大约一到三微米。 颗粒可以由可生物降解的材料如可生物降解的聚合物形成。 例如，颗粒可以由聚（乳酸）或聚（乙醇酸）或其共聚物形成。 或者，颗粒可以仅由治疗剂或诊断剂和表面活性剂形成。 表面活性剂可以结合在颗粒表面上，例如通过在颗粒形成之后涂覆颗粒，或者通过在形成颗粒之前将表面活性剂并入形成颗粒的材料中。 示例性表面活性剂包括磷酸甘油酯，例如二棕榈酰磷脂酰胆碱（DPPC）。 这些颗粒可以有效地雾化，用于给呼吸道施用以允许全身或局部递送各种各样的治疗剂。 正电荷或带负电荷的治疗剂与相反电荷分子的复合物的形成可以允许在给药后将药剂释放到血流中的释放速率。

    Preparation of particles for inhalation
    8.
    发明授权
    Preparation of particles for inhalation 失效
    吸入颗粒的制备

    公开(公告)号：US5985309A

    公开(公告)日：1999-11-16

    申请号：US971791

    申请日：1997-11-17

    申请人： David A. Edwards ,  Robert S. Langer ,  Rita Vanbever ,  Jeffrey Mintzes ,  Jue Wang ,  Donghao Chen

    发明人： David A. Edwards ,  Robert S. Langer ,  Rita Vanbever ,  Jeffrey Mintzes ,  Jue Wang ,  Donghao Chen

    IPC分类号： A61K9/16 ,  A61K31/135 ,  A61K31/137 ,  A61K38/28 ,  A61K38/38 ,  A61K13/00

    CPC分类号： A61K9/1647 ,  A61K31/135 ,  A61K31/137 ,  A61K38/28 ,  A61K38/38

    摘要： Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm.sup.3 and a mass mean diameter between 5 .mu.m and 30 .mu.m, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration.

    摘要翻译： 提供了将具有正或负电荷的治疗剂的表面活性剂和/或亲水或疏水配合物和用于药物递送至肺系统的带电分子的相反电荷的颗粒，以及用于其合成和给药的方法。 在优选的实施方案中，颗粒由可生物降解的材料制成，并且具有小于0.4g / cm 3的振实密度和5μm至30μm之间的质量平均直径，其一起产生颗粒的空气动力学直径在约 一和三微米。 颗粒可以由可生物降解的材料如可生物降解的聚合物形成。 例如，颗粒可以由聚（乳酸）或聚（乙醇酸）或其共聚物形成。 或者，颗粒可以仅由治疗剂或诊断剂和表面活性剂形成。 表面活性剂可以结合在颗粒表面上，例如通过在颗粒形成之后涂覆颗粒，或者通过在形成颗粒之前将表面活性剂并入形成颗粒的材料中。 示例性表面活性剂包括磷酸甘油酯，例如二棕榈酰磷脂酰胆碱（DPPC）。 这些颗粒可以有效地雾化，用于给呼吸道施用以允许全身或局部递送各种各样的治疗剂。 正电荷或带负电荷的治疗剂与相反电荷分子的复合物的形成可以允许在给药后将药剂释放到血流中的释放速率。

    Method of producing an air-hardenable bainite-martensite steel
    10.
    发明授权
    Method of producing an air-hardenable bainite-martensite steel 失效
    制造空气可硬化的贝氏体 - 马氏体钢的方法

    公开(公告)号：US5123970A

    公开(公告)日：1992-06-23

    申请号：US519048

    申请日：1990-05-04

    申请人： Hongsheng Fang ,  Yankang Zheng ,  Xiuyun Chen ,  Donghao Chen ,  Rufa Zhao

    发明人： Hongsheng Fang ,  Yankang Zheng ,  Xiuyun Chen ,  Donghao Chen ,  Rufa Zhao

    IPC分类号： C22C38/38

    CPC分类号： C22C38/38

    摘要： Air-hardenable steels of duplex bainite/martensite microstructure consisting essentially of 0.10 to 0.7% C, 0.1 to 2% Si, 2.1 to 3.5% Mn, 0.0005 to 0.005% B, up to 3.5% Cr and preferably containing Cr in amount of at least 0.1%, balance Fe except for incidental impurities. Optional elements are up to 1.5% W, 1.0% Mo, 0.15% V, 0.2% S, 0.1% Ca, 0.1% Pb, 0.1% Ti and 0.2% total rare earths. At least 1.0% Cr is especially preferred and if below such amount, total Mn and Si is at least 3% and in such case, if C is under 0.47%, at least 0.6% Si is present. The steels are hardenable to R.sub.c 2o to R.sub.c 58 and have a hardenable diameter in the range between 35 mm and 80 to 100 mm by air-cooling only, together with good strength, toughness and fatigue- and wear-resistance.

    摘要翻译： 双相贝氏体/马氏体组织的空气硬化钢基本上由C：0.10〜0.7％，Si：0.1〜2％，Mn：2.1〜3.5％，B：0.005〜0.005％，Cr：3.5％以下，优选含有Cr量 至少0.1％，平衡Fe，除了杂质。 可选元素可达1.5％W，1.0％Mo，0.15％V，0.2％S，0.1％Ca，0.1％Pb，0.1％Ti和0.2％总稀土。 至少1.0％的Cr是特别优选的，如果低于该量，则总Mn和Si至少为3％，在这种情况下，如果C在0.47％以下，则存在至少0.6％的Si。 钢可以硬化到Rc 2o到Rc 58，并且通过仅通过空气冷却，并且具有良好的强度，韧性和耐疲劳性和耐磨性，其可固化直径在35mm至80-100mm的范围内。