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。

公开(公告)号：US06977087B2

公开(公告)日：2005-12-20

申请号：US10090418

申请日：2002-03-01

申请人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

发明人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

IPC分类号： A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K31/56 ,  A61K31/568 ,  A61K38/28

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/56 ,  A61K31/568 ,  A61K38/28

摘要： Improved aerodynamically light particles for delivery to the pulmonary system, and methods for their preparation and administration are provided. In a preferred embodiment, the aerodynamically light 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 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear α-hydroxy-acid polyester backbone having at least one amino acid group incorporated herein and at least on poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 μm, can be used for enhanced delivery of a therapeutic or diagnostic agent to the alveolar region of the lung. The aerodynamically light particles optionally can incorporate a therapeutic or diagnostic agent, and may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of a wide variety of incorporated agents.

摘要翻译： 提供用于递送至肺系统的改善的空气动力学轻微颗粒，以及其制备和给药方法。 在优选的实施方案中，空气动力学轻微颗粒由可生物降解的材料制成，并且振实密度小于0.4g / cm 3，质量平均直径在5μm和30μm之间。 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，颗粒可以由官能化的聚酯接枝共聚物形成，所述官能化聚酯接枝共聚物由具有至少一个引入本文的氨基酸基团和至少在从氨基酸延伸的聚（氨基酸）侧链上的直链α-羟基酸聚酯主链组成 集团在聚酯骨干。 在一个实施方案中，具有大平均直径（例如大于5μm）的空气动力学轻的颗粒可用于增强治疗或诊断剂递送至肺的肺泡区域。 空气动力学轻微颗粒任选地可以掺入治疗剂或诊断剂，并且可以有效地雾化用于给予呼吸道以允许各种并入药剂的全身或局部递送。

公开(公告)号：US06399102B1

公开(公告)日：2002-06-04

申请号：US09562988

申请日：2000-05-01

申请人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

发明人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

IPC分类号： A61K914

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/137

摘要： Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm3 and a mass mean diameter between 5 &mgr;m and 30 &mgr;m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &agr;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

公开(公告)号：US5874064A

公开(公告)日：1999-02-23

申请号：US739308

申请日：1996-10-29

申请人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

发明人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

IPC分类号： A61K9/12 ,  A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K9/72 ,  A61K31/137 ,  A61K47/32

CPC分类号： A61K9/0075 ,  A61K31/137 ,  A61K9/1647

摘要： Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light 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. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear .alpha.-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 .mu.m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

公开(公告)号：US06436443B2

公开(公告)日：2002-08-20

申请号：US09888688

申请日：2001-06-25

申请人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Robert S. Langer ,  Abdellaziz Ben-Jebria

发明人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Robert S. Langer ,  Abdellaziz Ben-Jebria

IPC分类号： A61K914

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/137 ,  Y10S514/826 ,  Y10S514/851

摘要： Improved porous particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the porous particles are made of a biodegradable material and have a mass density less than 0.4 g/cm3/. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &agr;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, porous particles having a relatively large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The porous particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

摘要翻译： 提供用于向肺系统递送药物的改进的多孔颗粒，以及用于其合成和给药的方法。 在优选的实施方案中，多孔颗粒由可生物降解的材料制成，其质量密度小于0.4g / cm 3 /。 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，颗粒可以由官能化的聚酯接枝共聚物形成，所述聚酯接枝共聚物由具有至少一个氨基酸基团的直链α-羟基酸聚酯主链和至少一个从氨基酸延伸的聚（氨基酸）侧链组成 集团在聚酯骨干。 在一个实施方案中，具有相对大的平均直径，例如大于5um的多孔颗粒可用于增强治疗剂递送至肺的肺泡区域。 掺入治疗剂的多孔颗粒可以有效地雾化，用于给予呼吸道以允许全身或局部递送多种治疗剂。

公开(公告)号：US08628754B2

公开(公告)日：2014-01-14

申请号：US13334236

申请日：2011-12-22

申请人： David A. Edwards ,  Richard P. Batycky ,  Lloyd Johnston

发明人： David A. Edwards ,  Richard P. Batycky ,  Lloyd Johnston

IPC分类号： A61K9/14

CPC分类号： A61K9/14 ,  A61K9/0075 ,  A61K9/1617 ,  A61K31/198

摘要： A method for delivering an agent to the pulmonary system, in a single, breath-activated step or a single breath, comprises administering from a receptacle enclosing a mass of particles, to a subject's respiratory tract, particles which have a tap density of less than 0.4 g/cm3 and deliver at least about 50% of the mass of particles. The particles are capable of carrying agents. The agent is (1) part of the spray-drying pre-mixture and thereby incorporated into the particles, (2) added to separately-prepared particles so that the agent is in chemical association with the particles or (3) blended so that the agent is mixed with, and co-delivered with the particles.Respirable compositions comprising carrier particles having a tap density of less than 0.4 g/cm3 and a composition comprising an agent are also disclosed. Methods of delivering these respirable compositions are also included.

摘要翻译： 用于在单个呼吸激活步骤或单次呼吸中将药物递送至肺部系统的方法包括从包围大量颗粒的容器向受试者的呼吸道施用具有小于 0.4克/厘米3，并输送至少约50％的颗粒。 颗粒能够携带。 试剂是（1）部分喷雾干燥预混合物，由此加入到颗粒中，（2）加入到单独制备的颗粒中，使得试剂与颗粒化学缔合，或（3）混合 试剂与颗粒混合并与颗粒共同传送。 还公开了包含振实密度小于0.4g / cm 3的载体颗粒和包含试剂的组合物的可吸入组合物。 还包括递送这些可呼吸组合物的方法。

公开(公告)号：US07678364B2

公开(公告)日：2010-03-16

申请号：US09822716

申请日：2001-03-30

申请人： David A. Edwards ,  Jeffrey S. Hrkach

发明人： David A. Edwards ,  Jeffrey S. Hrkach

IPC分类号： A61K9/12 ,  A61K9/14 ,  A61K38/28 ,  A61K33/30

CPC分类号： A61K9/0075 ,  A61K9/1611 ,  A61K9/1617 ,  A61K38/28

摘要： The invention generally relates to a method for pulmonary delivery of therapeutic, prophylactic and diagnostic agents to a patient wherein the agent is released in a sustained fashion, and to particles suitable for use in the method. In particular, the invention relates to a method for the pulmonary delivery of a therapeutic, prophylactic or diagnostic agent comprising administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of particles comprising a multivalent metal cation which is complexed with a therapeutic, prophylactic or diagnostic agent or any combination thereof having a charge capable of complexing with the cation upon association with the agent, a pharmaceutically acceptable carrier and optionally, a multivalent metal cation-containing component wherein the total amount of multivalent metal cation present in the particles is more than 1% weight/weight of the total weight of the agent (% w/w). Release of the agent from the administered particles occurs in a sustained fashion.

摘要翻译： 本发明一般涉及将治疗性预防和诊断试剂肺部递送给患者，其中药剂以持续方式释放，以及适用于该方法的颗粒。 特别地，本发明涉及用于肺部递送治疗性，预防性或诊断性药物的方法，其包括对需要治疗，预防或诊断的患者的呼吸道施用有效量的包含多价金属阳离子的颗粒，所述多价金属阳离子是 与治疗性，预防性或诊断剂或其任何组合复合，其具有能够与该药物结合时与阳离子络合的电荷，药学上可接受的载体和任选的多价金属阳离子组分，其中多价金属阳离子的总量 颗粒中存在的重量比重大于重量的1％（％w / w）。 药剂从给药颗粒中的释放以持续的方式发生。

公开(公告)号：US06942868B2

公开(公告)日：2005-09-13

申请号：US10441948

申请日：2003-05-20

申请人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

发明人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

IPC分类号： A61K9/12 ,  A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K9/72 ,  A61K31/137 ,  A61K47/32 ,  A61K49/00 ,  A61L15/00

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/137

摘要： Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm3 and a mass mean diameter between 5 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear α-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 μm, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

摘要翻译： 提供用于向肺系统输送药物的空气动力学轻微颗粒，以及用于其合成和给药的方法。 在优选的实施方案中，空气动力学轻微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。 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，颗粒可以由官能化的聚酯接枝共聚物形成，所述聚酯接枝共聚物由具有至少一个氨基酸基团的直链α-羟基酸聚酯主链和至少一个从氨基酸延伸的聚（氨基酸）侧链组成 集团在聚酯骨干。 在一个实施方案中，具有大平均直径（例如大于5μm）的空气动力学轻微颗粒可用于增强治疗剂递送至肺的肺泡区域。 掺入治疗剂的空气动力学轻微颗粒可以被有效地雾化，用于给予呼吸道以允许全身或局部递送多种治疗剂。

公开(公告)号：US06740310B2

公开(公告)日：2004-05-25

申请号：US10209654

申请日：2002-07-30

申请人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Robert S. Langer ,  Abdellaziz Ben-Jebria

发明人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Robert S. Langer ,  Abdellaziz Ben-Jebria

IPC分类号： A61K912

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/137 ,  Y10S514/826 ,  Y10S514/851

摘要： Improved porous particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the porous particles are made of a biodegradable material and have a mass density less than 0.4 g/cm3/. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear a-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, porous particles having a relatively large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The porous particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

公开(公告)号：US06503480B1

公开(公告)日：2003-01-07

申请号：US09194068

申请日：1999-04-08

申请人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

发明人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

IPC分类号： A61K912

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/56 ,  A61K31/568 ,  A61K38/28

摘要： Improved aerodynamically light particles for delivery to the pulmonary system, and methods for their preparation and administration are provided. In a preferred embodiment, the aerodynamically light 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. The particles may be formed of biodegradable mat as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &agr;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic or diagnostic agent to the alveolar region of the lung. The aerodynamically light particles optionally can incorporate a therapeutic or diagnostic agent, and may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of incrorporated agents.

摘要翻译： 提供用于递送至肺系统的改善的空气动力学轻微颗粒，以及其制备和给药方法。 在优选的实施方案中，空气动力学轻微颗粒由可生物降解的材料制成，并且振实密度小于0.4g / cm 3，质量平均直径在5μm和30μm之间。 颗粒可以由可生物降解的垫形成为可生物降解的聚合物。 例如，颗粒可以由官能化聚酯接枝共聚物形成，该聚酯接枝共聚物由具有至少一个氨基酸基团的直链α-羟基酸聚酯主链和至少一个从氨基酸延伸的聚（氨基酸）侧链组成 集团在聚酯骨干。 在一个实施方案中，具有大平均直径（例如大于5μm）的空气动力学轻的颗粒可用于增强治疗或诊断剂递送至肺的肺泡区域。 空气动力学轻微颗粒任选地可以掺入治疗剂或诊断剂，并且可以有效地雾化以用于向呼吸道施用以允许全身或局部递送各种各样的掺入剂。