公开(公告)号：US20090068274A1

公开(公告)日：2009-03-12

申请号：US12253449

申请日：2008-10-17

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 ,  A61P11/00

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：US20080213373A1

公开(公告)日：2008-09-04

申请号：US11720595

申请日：2005-10-19

申请人： David A. Edwards ,  Jennifer Fiegel ,  Jean Sung

发明人： David A. Edwards ,  Jennifer Fiegel ,  Jean Sung

IPC分类号： A61K9/14

CPC分类号： A61K9/0075 ,  A61K9/1617 ,  A61K9/1694 ,  Y10S514/924

摘要： Formulations have been developed to treat or reduce the spread of respiratory infections, especially chronic or drug resistant infections, particularly tuberculosis (TB), severe acute respiratory syndrome (SARS), meningococcal meningitis, Respiratory syncytial virus (RSV), influenza, and small pox. Formulations include a drug or vaccine in the form of a microparticle, nanoparticle, or aggregate of nanoparticles, and, optionally, a carrier, which can be delivered by inhalation. Giving the drugs via an inhaler sidesteps the problems associated with oral or injectable drugs by bypassing the stomach and liver, and delivering the medication directly into the lungs. In one embodiment, the particle containing the agent is a large porous aerosol particle (LPPs). In another embodiment, the particles are nanoparticles, which can be administered as porous nanoparticle aggregates with micron diameters that disperse into nanoparticles following administration. Optionally, the nanoparticles are coated, such as with a surfactant or protein coating. The formulation may be administered as a powder or administered as a solution or via an enteral or non-pulmonary parenteral route of administration. The formulation is preferably administered as a pulmonary formulation. In the preferred embodiment for treatment of TB, the vaccine is a BCG vaccine that is stable at room temperature, or is an antibiotic effective against TB, such as capreomycin or PA-824, loaded at a very high percentage into the microparticles or nanoparticles. In one embodiment, a patient is treated with formulations delivering both antibiotic and vaccine.

摘要翻译： 已经开发了治疗或减少呼吸道感染传播的制剂，特别是慢性或耐药性感染，特别是结核病（TB），严重急性呼吸综合征（SARS），脑膜炎球菌性脑膜炎，呼吸道合胞病毒（RSV），流感和小痘 。 制剂包括纳米颗粒的微粒，纳米颗粒或骨料形式的药物或疫苗，以及任选的可以通过吸入递送的载体。 通过吸入器给药可以通过绕过胃和肝来避开与口服或可注射药物相关的问题，并将药物直接送入肺部。 在一个实施方案中，含有该试剂的颗粒是大的多孔气溶胶颗粒（LPPs）。 在另一个实施方案中，颗粒是纳米颗粒，其可以作为具有微米直径的多孔纳米颗粒聚集体施用，其在施用后分散到纳米颗粒中。 任选地，包覆纳米颗粒，例如用表面活性剂或蛋白质涂层。 制剂可以粉末形式施用或作为溶液给药或通过肠内或非肺部非肠道途径给药。 制剂优选作为肺制剂施用。 在用于治疗结核病的优选实施方案中，疫苗是在室温下稳定的BCG疫苗，或者是针对TB有效的抗生素，例如卷曲霉素或PA-824，其以非常高的百分比加载到微粒或纳米颗粒中。 在一个实施方案中，用递送抗生素和疫苗的制剂治疗患者。

公开(公告)号：US07048908B2

公开(公告)日：2006-05-23

申请号：US10202616

申请日：2002-07-23

申请人： Sujit K. Basu ,  Jeffrey Hrkach ,  Michael Lipp ,  Katharina Elbert ,  David A. Edwards

发明人： Sujit K. Basu ,  Jeffrey Hrkach ,  Michael Lipp ,  Katharina Elbert ,  David A. Edwards

IPC分类号： A61K9/12 ,  A61K9/127

CPC分类号： A61K9/0075 ,  A61K9/1617 ,  A61K38/28 ,  A61K47/544 ,  Y10S514/958

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.

公开(公告)号：US06956021B1

公开(公告)日：2005-10-18

申请号：US09383054

申请日：1999-08-25

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

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

IPC分类号： A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K38/00 ,  A61K38/27 ,  A61K47/00

CPC分类号： A61K9/0075 ,  A61K9/1617 ,  Y10S514/951 ,  Y10S514/97 ,  Y10S514/975

摘要： Spray-dried particles having improved protein stability are produced by spray-drying a mixture including a protein, a phospholipid and an organic-aqueous co-solvent. Spray-dried particles which include at least 1 weight % phospholipid, having a tap density of less than 0.4 g/cm3 can be prepared. The particles can be delivered to the pulmonary system of a patient.

摘要翻译： 具有改善的蛋白质稳定性的喷雾干燥颗粒通过喷雾干燥包括蛋白质，磷脂和有机 - 水性共溶剂的混合物而产生。 包含至少1重量％磷脂的喷雾干燥颗粒，其振实密度小于0.4g / cm 3，可以制备。 颗粒可以输送到患者的肺部系统。

公开(公告)号：US06921528B2

公开(公告)日：2005-07-26

申请号：US10681416

申请日：2003-10-08

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

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

IPC分类号： A61K9/12 ,  A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K9/72 ,  A61K31/137 ,  A61K31/198 ,  A61K31/46 ,  A61K31/56 ,  A61K38/27 ,  A61K38/28 ,  A61K39/395 ,  A61L9/04 ,  B05D7/14

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

摘要： A method for delivering a therapeutic dose of a bioactive agent to the pulmonary system, in a single, breath-activated step, 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. Another method of delivering a therapeutic dose of a bioactive agent to the pulmonary system, in a single breath, includes administering from a receptacle enclosing a mass of particles, to a subject's respiratory tract, particles which have a tap density of at least 0.4 g/cm3 and deliver at least about 10 milligrams of the bioactive agent. The receptacle can have a volume of at least 0.37 cm3.

摘要翻译： 在单一呼吸激活步骤中将治疗剂量的生物活性剂递送到肺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较小振幅密度的颗粒 超过0.4g / cm 3，并输送至少约50％的质量的颗粒。 在单次呼吸中将治疗剂量的生物活性剂递送到肺系统的另一种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至少0.4g / 并输送至少约10毫克的生物活性剂。 容器可具有至少0.37厘米3的体积。

公开(公告)号：US06858199B1

公开(公告)日：2005-02-22

申请号：US09591307

申请日：2000-06-09

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： A61K9/12 ,  A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K9/72 ,  A61K31/137 ,  A61K31/198 ,  A61K31/46 ,  A61K31/56 ,  A61K38/27 ,  A61K38/28 ,  A61K39/395 ,  A61L9/04 ,  B05D7/14

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

摘要： A method for delivering a therapeutic dose of a bioactive agent to the pulmonary system, in a single, breath-activated step, 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. Another method of delivering a therapeutic dose of a bioactive agent to the pulmonary system, in a single breath, includes administering from a receptacle enclosing a mass of particles, to a subject's respiratory tract, particles which have a tap density of at least 0.4 g/cm3 and deliver at least about 10 milligrams of the bioactive agent. The receptacle can have a volume of at least 0.37 cm3.

摘要翻译： 在单一呼吸激活步骤中将治疗剂量的生物活性剂递送到肺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较小振幅密度的颗粒 超过0.4g / cm 3并且输送至少约50％的质量的颗粒。 在单次呼吸中将治疗剂量的生物活性剂递送到肺系统的另一种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至少0.4g / 并输送至少约10毫克的生物活性剂。 容器可具有至少0.37厘米3的体积。

公开(公告)号：US06311290B1

公开(公告)日：2001-10-30

申请号：US09055032

申请日：1998-04-03

申请人： Robert N. Hasbun ,  David A. Edwards ,  Andrew H. Gafken ,  Christopher J. Spiegel

发明人： Robert N. Hasbun ,  David A. Edwards ,  Andrew H. Gafken ,  Christopher J. Spiegel

IPC分类号： H02H305

CPC分类号： G06F12/0246 ,  G06F11/0793 ,  G06F2212/7205 ,  Y10S707/99953

摘要： Methods of reliably allocating, writing, reading, de-allocating, re-allocating, and reclaiming space within a nonvolatile memory having a bifurcated storage architecture are described. Allocation, writing, reading, de-allocating, re-allocating, and reclamation are handled by a memory manager. The memory manager tracks the progress of each process during execution in order to detect whether a selected process was interrupted for purposes of recovery. The nonvolatile memory is recovered to a known state during initialization. Initialization includes the step of determining a recovery state from a recovery state lookup table. A selected recovery process is selected in accordance with the recovery state lookup table. A restart level for the selected process is determined from a corresponding restart state lookup table. The selected process is then restarted at the restart level. In one embodiment, a method of managing a nonvolatile memory includes the step of identifying an interrupted process from at least one of an allocation, a reclamation, a configuration header reclaim, and a re-allocation process initiated on the nonvolatile memory. A recovery process is selected for the interrupted process. An entry point into the recovery process is determined. The selected recovery process is then restarted at the entry point.

摘要翻译： 描述了在具有分叉存储结构的非易失性存储器内可靠地分配，写入，读取，分配，重新分配和回收空间的方法。 分配，写入，读取，取消分配，重新分配和回收由内存管理员处理。 内存管理器在执行期间跟踪每个进程的进度，以便检测所选进程是否为了恢复目的而中断。 在初始化期间，非易失性存储器恢复到已知状态。 初始化包括从恢复状态查找表确定恢复状态的步骤。 根据恢复状态查找表选择选择的恢复过程。 从相应的重新启动状态查找表确定所选进程的重新启动级别。 然后在重新启动级别重新启动所选进程。 在一个实施例中，管理非易失性存储器的方法包括从在非易失性存储器上发起的分配，回收，配置报头回收和重新分配过程中的至少一个识别中断的进程的步骤。 为中断的进程选择恢复过程。 确定恢复过程的入口点。 然后在入口点重新启动所选的恢复过程。

公开(公告)号：US06243789B1

公开(公告)日：2001-06-05

申请号：US09028159

申请日：1998-02-23

申请人： Robert N. Hasbun ,  David A. Edwards

发明人： Robert N. Hasbun ,  David A. Edwards

IPC分类号： G06F1208

CPC分类号： G06F9/3812 ,  G06F12/0292 ,  G06F12/0638 ,  G06F2212/2022

摘要： A method of executing a program includes the step of initiating execution of the program stored contiguously without code fragmentation in a nonvolatile memory. Execution of the program is halted if the program attempts to modify a page of the nonvolatile memory. The page of nonvolatile memory is then copied to a modifiable memory. The page of nonvolatile memory is then remapped to the modifiable memory. Execution of the program is then resumed. A computer system for execution of a program includes a nonvolatile memory storing a program contiguously without code fragmentation. The computer system includes a processor for executing the program. A memory management unit generates an interrupt in response to a request to modify a page of the nonvolatile memory. Execution of the program is halted and the processor copies the page of nonvolatile memory to a modifiable memory in response to the interrupt. The processor resumes execution of the program after updating an address translation table of the memory management unit to refer to the modifiable memory for subsequent program access requests to the page of nonvolatile memory.

摘要翻译： 执行程序的方法包括在非易失性存储器中开始执行连续存储的程序而没有代码碎片的步骤。 如果程序尝试修改非易失性存储器的页面，程序的执行将停止。 然后将非易失性存储器的页面复制到可修改的存储器。 然后将非易失性存储器的页面重新映射到可修改的存储器。 然后，程序的执行恢复。 用于执行程序的计算机系统包括非易失性存储器，其连续地存储程序而没有代码分段。 计算机系统包括用于执行程序的处理器。 存储器管理单元响应于修改非易失性存储器的页面的请求而产生中断。 停止执行程序，并且处理器将非易失性存储器的页面复制到可修改的存储器以响应中断。 在更新存储器管理单元的地址转换表之后，处理器恢复执行该程序，以引用可修改的存储器，以便随后的程序访问请求到非易失性存储器的页面。

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。

公开(公告)号：US5833388A

公开(公告)日：1998-11-10

申请号：US681701

申请日：1996-07-29

申请人： David A. Edwards ,  Vincent B. Dick

发明人： David A. Edwards ,  Vincent B. Dick

IPC分类号： B09C1/00 ,  B09C1/02 ,  B09C1/08 ,  B09C1/10 ,  B09B3/00 ,  E02D3/11

CPC分类号： B09C1/08 ,  B09C1/002 ,  B09C1/02 ,  B09C1/10 ,  B09C2101/00

摘要： The present invention relates to a method for treating groundwater in situ in rock or soil. An elongate permeable upgradient zone and an elongate permeable downgradient zone, each in hydraulic communication with a permeable subsurface treatment zone and having a major axis parallel to a non-zero component of the general flow direction, are provided in the subsurface by any of a number of construction methods. The upgradient zone, downgradient zone, and treatment zone are situated within the subsurface medium and have permeabilities substantially greater than the adjacent subsurface medium's permeability. Groundwater is allowed to move from the subsurface medium adjacent to the upgradient zone into the upgradient zone, where the groundwater refracts and moves to a treatment zone. After being treated in the treatment zone by an in situ treatment process, such as a process employing air sparging, sorption or reaction with zero-valent iron, the groundwater moves into, through, and out of the downgradient zone into the subsurface medium adjacent to the downgradient zone. The method does not require pumping. A method for directing groundwater around a particular location to prevent contamination of the groundwater by a contaminant located at the particular location, to prevent migration of a contaminant located at the particular location, to reduce the flow velocity of groundwater in the particular location, or to increase the residence time in an in situ treatment center located downgradient from the particular location is also disclosed.