公开(公告)号：US6149864A

公开(公告)日：2000-11-21

申请号：US104775

申请日：1998-06-25

申请人： Angela K. Dillow ,  Robert S. Langer ,  Neil Foster ,  Jeffrey S. Hrkach

发明人： Angela K. Dillow ,  Robert S. Langer ,  Neil Foster ,  Jeffrey S. Hrkach

IPC分类号： A61L2/18 ,  A61L2/00

CPC分类号： A61L2/18 ,  A61L2/16

摘要： A method is provided for sterilizing materials, particularly polymers, for drug delivery and implantation, wherein the material is treated with supercritical fluid carbon dioxide at pressures in the range of 2000 to 3000 psi (140 to 210 bar) and temperatures preferably between 30 and 45.degree. C. for periods between 20 minutes and six hours, more preferably between 0.5 and 2 hours. Agitation, pressure cycling, and the presence of water were found to enhance the sterilization method, which promotes diffusion of the supercritical fluid carbon dioxide into the cells of the microorganism to thereby alter the pH within the cells, killing them. The magnitude and frequency of the pressure cycling, as well as the process time and temperature, may vary according to the type and form of the material to be sterilized and the type of organisms to be killed.

摘要翻译： 提供了一种用于消毒材料，特别是用于药物递送和植入的聚合物的方法，其中用超临界流体二氧化碳在2000-3000psi（140-210巴）范围内的压力下处理材料，温度优选在30和45之间 时间为20分钟至6小时，更优选为0.5小时至2小时。 发现搅拌，压力循环和水的存在增强灭菌方法，促进超临界流体二氧化碳向微生物细胞的扩散，从而改变细胞内的pH，从而杀死它们。 压力循环的大小和频率以及工艺时间和温度可以根据要灭菌的材料的类型和形式以及要杀死的生物体的类型而变化。

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：US07435408B2

公开(公告)日：2008-10-14

申请号：US10818902

申请日：2004-04-06

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： A61K9/00 ,  A61K9/12 ,  A61K9/14 ,  A61K38/00 ,  A61K33/00 ,  A61K31/00 ,  A61K31/70 ,  A61K31/7052

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 μm, 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，并具有小于0.4g / cm 3的质量密度。 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，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至少一个（氨基酸）侧链 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：US06635283B2

公开(公告)日：2003-10-21

申请号：US10027212

申请日：2001-12-20

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： 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.

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：US06447753B2

公开(公告)日：2002-09-10

申请号：US09891131

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： 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 &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：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.