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公开(公告)号：US20120121718A1
公开(公告)日：2012-05-17
申请号：US13289196
申请日：2011-11-04
申请人： Samuel K. Lai , Ming Yang , Ying-Ying Wang , Olcay Mert , Laura Ensign , Justin Hanes
发明人： Samuel K. Lai , Ming Yang , Ying-Ying Wang , Olcay Mert , Laura Ensign , Justin Hanes
CPC分类号： A61K9/1641 , A61K9/0034 , A61K9/5146 , A61K31/355 , A61K45/06 , A61K47/60 , A61K47/6935 , A61K49/0002 , Y10T428/2998
摘要： The present invention generally relates to reducing the mucoadhesive properties of a particle. In some embodiments, the particle is coated with and/or associated with a (poly(ethylene glycol))-(poly(propylene oxide))-(poly(ethylene glycol)) triblock copolymer. Methods for preparing inventive particles using a poly(ethylene glycol)-vitamin E conjugate as a surfactant are also provided. In some embodiments, methods are provided comprising administering to a subject a composition of particles of the present invention. Such particles with reduced mucoadhesive properties are useful in delivering agents to mucosal tissues such as oral, ophthalmic, gastrointestinal, nasal, respiratory, and genital mucosal tissues.
摘要翻译： 本发明一般涉及降低颗粒的粘膜粘附性质。 在一些实施方案中，颗粒用（聚（乙二醇）） - （聚（环氧丙烷）） - （聚（乙二醇））三嵌段共聚物涂覆和/或与其相关联。 还提供了使用聚（乙二醇） - 维生素E缀合物作为表面活性剂制备本发明颗粒的方法。 在一些实施方案中，提供了包括向受试者施用本发明颗粒组合物的方法。 具有降低的粘膜粘附性质的这种颗粒可用于将药物递送到粘膜组织如口服，眼科，胃肠道，鼻腔，呼吸道和生殖器粘膜组织。
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公开(公告)号：US20100215580A1
公开(公告)日：2010-08-26
申请号：US12310751
申请日：2007-09-07
申请人： Justin Hanes , Samuel K. Lai
发明人： Justin Hanes , Samuel K. Lai
CPC分类号： A61K47/6929 , A61K9/0014 , A61K9/0034 , A61K9/0048 , A61K9/5146 , A61K31/70 , A61K47/549 , A61K47/60 , A61K47/6927 , A61K47/6933 , B82Y5/00
摘要： The invention generally relates to compositions and methods for transporting substances across mucosal barriers. The invention also relates to methods of making and using such substances.
摘要翻译： 本发明一般涉及通过粘膜屏障输送物质的组合物和方法。 本发明还涉及制备和使用这些物质的方法。
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公开(公告)号：US20050158249A1
公开(公告)日：2005-07-21
申请号：US11064065
申请日：2005-02-23
申请人： David Edwards , Giovanni Caponetti , Jeffrey Hrkach , Noah Lotan , Justin Hanes , Abdellaziz Ben-Jebria , Robert Langer
发明人： David Edwards , Giovanni Caponetti , Jeffrey Hrkach , Noah Lotan , Justin Hanes , Abdellaziz Ben-Jebria , Robert Langer
IPC分类号： A61K9/12 , A61K9/00 , A61K9/14 , A61K9/16 , A61K9/72 , A61K31/137 , A61K47/32 , A61K48/00 , A61K31/353 , A61K31/4439 , A61K31/56 , A61K31/573 , A61K38/09
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.
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公开(公告)号：US06447752B2
公开(公告)日：2002-09-10
申请号：US09888781
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。
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公开(公告)号：US6136295A
公开(公告)日：2000-10-24
申请号：US211940
申请日：1998-12-15
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 , A61L9/04 , A61F2/00
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.
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-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，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。
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公开(公告)号：US5855913A
公开(公告)日：1999-01-05
申请号：US784421
申请日：1997-01-16
申请人： Justin Hanes , David A. Edwards , Carmen Evora , Robert Langer
发明人： Justin Hanes , David A. Edwards , Carmen Evora , Robert Langer
IPC分类号： A61K9/00 , A61K9/12 , A61K9/14 , A61K9/16 , A61K31/135 , A61K31/137 , A61K38/28 , A61K38/38 , A61K47/48
CPC分类号： A61K9/0075 , A61K31/135 , A61K31/137 , A61K38/28 , A61K38/38 , A61K9/1617 , A61K9/1623 , A61K9/1641 , A61K9/1647 , A61K9/1658
摘要： Aerodynamically light particles incorporating a surfactant on the surface thereof 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 poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of the drug 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 L-.alpha.-phosphatidylcholine dipalmitoyl. The aerodynamically light particles incorporating a therapeutic or diagnostic agent and a surfactant may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents.
摘要翻译： 提供了在其表面上并入表面活性剂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-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，颗粒可以由聚（乳酸）或聚（乙醇酸）或其共聚物形成。 或者，颗粒可以仅由药物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。 示例性的表面活性剂包括磷酸甘油酯如L-α-磷脂酰胆碱二棕榈酰基。 包含治疗剂或诊断剂和表面活性剂的空气动力学轻微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各种各样的治疗剂。
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7.发明授权公开(公告)号：US08957034B2
公开(公告)日：2015-02-17
申请号：US10587512
申请日：2005-01-28
申请人： Justin Hanes , Michelle Rose Dawson , Denis Wirtz , Jie Fu , Eric Mark Krauland
发明人： Justin Hanes , Michelle Rose Dawson , Denis Wirtz , Jie Fu , Eric Mark Krauland
CPC分类号： A61K9/5153 , A61K9/0073 , A61K9/167 , A61K9/5031 , A61K9/5123 , A61K9/5146 , A61K47/543 , A61K47/6935 , A61K47/6937 , A61K48/0033 , A61K48/0041 , B82Y5/00
摘要： The invention generally relates to polymeric particles suitable for transporting bioactive agents across mucosal barriers. The invention also relates to methods of making and using those polymeric particles.
摘要翻译： 本发明一般涉及适合于通过粘膜屏障传递生物活性剂的聚合物颗粒。 本发明还涉及制备和使用这些聚合物颗粒的方法。
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公开(公告)号：US08354476B2
公开(公告)日：2013-01-15
申请号：US11721123
申请日：2005-12-09
申请人： Justin Hanes , Jie Fu
发明人： Justin Hanes , Jie Fu
CPC分类号： B82Y5/00 , A61K47/59 , A61K47/60 , A61K47/6907 , A61K47/6929 , C08G2261/126
摘要： The present application is directed to biodegradable polymers, compositions, including microspheres and nanospheres, formed of such polymers, and methods of using such polymers and compositions. In certain embodiments, the subject polymer compositions include therapeutic agents, optionally providing sustained release of the encapsulated agent after administration to a patient.
摘要翻译： 本申请涉及由这样的聚合物形成的可生物降解的聚合物，包括微球和纳米球的组合物，以及使用这种聚合物和组合物的方法。 在某些实施方案中，本发明聚合物组合物包括治疗剂，任选地在给予患者后提供包封的药剂的持续释放。
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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。
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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。
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