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1. 发明授权

US07052678B2 Particles for inhalation having sustained release properties 有权
公开(公告)号：US07052678B2
公开(公告)日：2006-05-30
申请号：US10094955
申请日：2002-03-07
申请人： Rita Vanbever , Robert S. Langer , David A. Edwards , Jeffrey Mintzes , Jue Wang , Donghao Chen
发明人： Rita Vanbever , Robert S. Langer , David A. Edwards , Jeffrey Mintzes , Jue Wang , Donghao Chen
IPC分类号： A61K9/12 , A61K9/14
CPC分类号： A61K9/0075 , A61K9/1617 , A61K9/1623 , A61K9/1641 , A61K9/1647 , A61K9/1658 , A61K31/135 , A61K31/137 , A61K38/28 , A61K38/38 , A61K47/6921
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 polycationic complexing agent which is complexed with a therapeutic, prophylactic or diagnostic agent or any combination thereof having a charge capable of complexing with the polycationic complexing agent upon association with the bioactive agent. The particles can further comprise a pharmaceutically acceptable carrier. The amount of polycationic complexing agent present in the particles is an amount sufficient to sustain the release of diagnostic, therapeutic or prophylactic agent from the particles. For example, the amount of complexing agent present can be at about 5% weight/weight (w/w) or more of the total weight of the complexing agent and therapeutic, diagnostic or prophylactic agent. Release of the agent from the administered particles occurs in a sustained fashion.

2. 发明授权

US06652837B1 Preparation of novel particles for inhalation 有权
标题翻译：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。

3. 发明申请

US20120107241A1 Particles for Inhalation Having Sustained Release Properties 审中-公开
标题翻译：具有持续释放性质的吸入颗粒
公开(公告)号：US20120107241A1
公开(公告)日：2012-05-03
申请号：US13220334
申请日：2011-08-29
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： A61K49/00 , A61K9/00
CPC分类号： A61K9/0073 , A61K9/0075 , A61K9/16 , A61K9/1617 , A61K9/1623 , A61K9/1641 , A61K9/1647 , A61K9/1658 , A61K9/1694 , A61K31/135 , A61K31/137 , A61K31/566 , A61K38/28 , A61K38/38 , A61K47/12 , A61K47/183 , A61K47/24 , A61K47/6927
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 therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. 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治疗性，预防性或诊断性的颗粒药剂或其任何组合与带电脂质相结合，其中带电脂质具有与药剂相关的与药剂相反的总净电荷。药剂从给药颗粒中的释放以持续的方式发生。

4. 发明授权

US07628977B2 Particles for inhalation having sustained release properties 失效
公开(公告)号：US07628977B2
公开(公告)日：2009-12-08
申请号：US10420071
申请日：2003-04-18
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： A61K9/14 , A61K31/66 , A61K31/661 , A61K31/6615
CPC分类号： A61K9/0073 , A61K9/0075 , A61K9/16 , A61K9/1617 , A61K9/1623 , A61K9/1641 , A61K9/1647 , A61K9/1658 , A61K9/1694 , A61K31/135 , A61K31/137 , A61K31/566 , A61K38/28 , A61K38/38 , A61K47/12 , A61K47/183 , A61K47/24 , A61K47/6927
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 therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. Release of the agent from the administered particles occurs in a sustained fashion.

5. 发明授权

US5985309A Preparation of particles for inhalation 失效
标题翻译：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。

6. 发明申请

US20080253971A9 Particles for inhalation having sustained release properties 失效
公开(公告)号：US20080253971A9
公开(公告)日：2008-10-16
申请号：US10420071
申请日：2003-04-18
申请人： David Edwards , Robert Langer , Rita Vanbever , Jeffrey Mintzes , Jue Wang , Donghao Chen
发明人： David Edwards , Robert Langer , Rita Vanbever , Jeffrey Mintzes , Jue Wang , Donghao Chen
IPC分类号： A61K9/14 , A61L9/04 , A61K38/00
CPC分类号： A61K9/0073 , A61K9/0075 , A61K9/16 , A61K9/1617 , A61K9/1623 , A61K9/1641 , A61K9/1647 , A61K9/1658 , A61K9/1694 , A61K31/135 , A61K31/137 , A61K31/566 , A61K38/28 , A61K38/38 , A61K47/12 , A61K47/183 , A61K47/24 , A61K47/6927
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 therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. Release of the agent from the administered particles occurs in a sustained fashion.

7. 发明申请

US20070014738A1 Particles for inhalation having sustained release properties 审中-公开
标题翻译：具有持续释放性质的吸入颗粒
公开(公告)号：US20070014738A1
公开(公告)日：2007-01-18
申请号：US11523914
申请日：2006-09-20
申请人： David Edwards , Robert Langer , Rita Vanbever , Jeffrey Mintzes , Jue Wang , Donghao Chen
发明人： David Edwards , Robert Langer , Rita Vanbever , Jeffrey Mintzes , Jue Wang , Donghao Chen
IPC分类号： A61K38/17 , A61K9/14 , A61L9/04
CPC分类号： A61K9/0073 , A61K9/0075 , A61K9/16 , A61K9/1617 , A61K9/1623 , A61K9/1641 , A61K9/1647 , A61K9/1658 , A61K9/1694 , A61K31/135 , A61K31/137 , A61K31/566 , A61K38/28 , A61K38/38 , A61K47/12 , A61K47/183 , A61K47/24 , A61K47/6927
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 therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. 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治疗性，预防性或诊断性的颗粒药剂或其任何组合与带电脂质相结合，其中带电脂质具有与药剂相关的与药剂相反的总净电荷。药剂从给药颗粒中的释放以持续的方式发生。

8. 发明授权

US5911223A Introduction of modifying agents into skin by electroporation 失效
标题翻译：通过电穿孔将改性剂引入皮肤
公开(公告)号：US5911223A
公开(公告)日：1999-06-15
申请号：US695367
申请日：1996-08-09
申请人： James C. Weaver , Tani Chen , Christopher Cullander , Richard Guy , Robert S. Langer , Thomas E. Zewert , Uwe Pliquett , Rita Vanbever , Mark R. Prausnitz
发明人： James C. Weaver , Tani Chen , Christopher Cullander , Richard Guy , Robert S. Langer , Thomas E. Zewert , Uwe Pliquett , Rita Vanbever , Mark R. Prausnitz
IPC分类号： A61B17/00 , A61N1/32 , A61B19/00
CPC分类号： A61N1/0424 , A61N1/325 , A61B2017/00765 , A61N1/0428 , Y10S607/901
摘要： A method of modifying epidermis for transport of a material by electroporation includes applying to epidermis an agent that, upon entry into the epidermis, will modify the epidermis to thereby cause and altered rate of transport of a material across the epidermis. Typically, the altered rate will be an increased rate of transport. The epidermis is electroporated, whereby at least a portion of the modifying agent enters the electroporated epidermis, thereby modifying the epidermis to cause an altered rate of transport of a material across the epidermis. In another embodiment, the modifying agent can modify the epidermis to enable measurement and/or monitoring of physiological conditions or change within or beneath the epidermis. The modifying agents can also be employed to facilitate discharge of fluids from within an organism, such as by providing pathways for discharge of fluids from a tumor. Examples of modifying agents include: oxidizing agents; reducing agents; particles, such as optical indicator beads or beads that include drugs to be released into tissue; electrically-charged particles or molecules; etc. Materials that can be transported by the method of the invention include, for example, proteins, nucleic acids, electrically charged molecules or particles, microorganisms suitable for immunization, etc. Also, tissues other than skin can be employed in the method of the invention.
摘要翻译：通过电穿孔来改变用于运输材料的表皮的方法包括向表皮施加一种在进入表皮时将改变表皮从而引起和改变材料穿过表皮的运输速率的试剂。通常，改变率将是增加的运输速度。表皮被电穿孔，由此至少一部分改性剂进入电穿孔表皮，从而改变表皮，导致材料穿过表皮的转运速率。在另一个实施方案中，修饰剂可以修饰表皮以使得能够测量和/或监测生理条件或在表皮内或下表面的变化。还可以使用改性剂来促进从生物体内排出流体，例如通过提供从肿瘤排出流体的途径。改性剂的实例包括：氧化剂; 还原剂; 颗粒，例如包括要释放到组织中的药物的光学指示剂珠粒或珠粒; 带电粒子或分子; 可以通过本发明的方法传输的材料包括例如蛋白质，核酸，带电分子或颗粒，适合免疫的微生物等。另外，皮肤以外的组织可以用于发明。

9. 发明申请

US20050008633A1 Chemical and physical modulators of bioavailability of inhaled compositions 审中-公开
标题翻译：吸入组合物的生物利用度的化学和物理调节剂
公开(公告)号：US20050008633A1
公开(公告)日：2005-01-13
申请号：US10843693
申请日：2004-05-11
申请人： Rita Vanbever , David Edwards
发明人： Rita Vanbever , David Edwards
IPC分类号： A61K31/66 , A61K38/00 , A61K38/22 , A61K38/28 , A61K39/395 , A61K45/06
CPC分类号： A61K45/06 , A61K31/66 , A61K38/24 , A61K38/27 , A61K38/28 , A61K39/395 , A61K2300/00
摘要： The present invention is drawn to methods of enhancing bioavailability, pulmonary absorption and/or optimal dosing of a biologically active agent. The methods of the invention enhance the pulmonary absorption and bioavailability of a biologically active agent by administering to the pulmonary system of a subject, a biologically active agent and a macrophage inhibiting agent that is suitable for administration to a subject's pulmonary system.
摘要翻译：本发明涉及提高生物活性剂的生物利用度，肺吸收和/或最佳给药的方法。本发明的方法通过向受试者的肺系统施用适于给予受试者的肺部系统的生物活性剂和巨噬细胞抑制剂来增强生物活性剂的肺吸收和生物利用度。

10. 发明授权

US6085115A Biopotential measurement including electroporation of tissue surface 失效
标题翻译：生物电位测量，包括组织表面的电穿孔
公开(公告)号：US6085115A
公开(公告)日：2000-07-04
申请号：US83497
申请日：1998-05-22
申请人： James C. Weaver , Uwe Pliquett , Rita Vanbever , Thiruvallur R. Gowrishankar , Thomas E. Zewert
发明人： James C. Weaver , Uwe Pliquett , Rita Vanbever , Thiruvallur R. Gowrishankar , Thomas E. Zewert
IPC分类号： A61B5/0402 , A61B5/04
CPC分类号： A61B5/04025
摘要： A method for measuring biopotential of an organism includes electroporating a portion of a tissue surface of the organism. The biopotential of the organism is then measured with electrodes at the electroporated portion of the organism. The portion of the organism that is electroporated can be, for example, a skin surface of the organism. A resistance-decreasing agent, such as heparin, sodium thiosulfate, thioglycolic acid solution and dithioglycolic acid can be applied to the tissue surface to facilitate reduction in electrical resistance. Another example of a resistance-decreasing agent is a keratin-disrupting agent, such as sulforhodamine. Examples of suitable biopotential measurements include electrocardiographic, electroencephalographic, electromyographic, electrohysterographic and elctrokymographic measurements. The method decreases skin resistance to diminish unwanted electrical voltages that compete with biopotential measurements, thereby significantly improving the biopotential measurement.
摘要翻译：用于测量生物体的生物潜力的方法包括电穿孔生物体的组织表面的一部分。然后用生物体的电穿孔部分的电极测量生物体的生物潜力。电穿孔的生物体的部分可以是例如生物体的皮肤表面。电阻降低剂如肝素，硫代硫酸钠，巯基乙酸溶液和二硫代乙醇酸可以施加到组织表面以便于降低电阻。抗性降低剂的另一个实例是角蛋白破坏剂，例如磺酰罗丹明。合适的生物电位测量的实例包括心电图，脑电图，肌电描记术，电积电图和电压测量。该方法降低皮肤抵抗力，减少与生物电位测量竞争的不需要的电压，从而显着改善生物电位测量。

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