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11. 发明授权

US6024090A Method of treating a diabetic patient by aerosolized administration of insulin lispro 失效
标题翻译：通过雾化给予赖脯胰岛素治疗糖尿病患者的方法
公开(公告)号：US6024090A
公开(公告)日：2000-02-15
申请号：US88534
申请日：1998-06-01
申请人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61J7/04 , A61K9/00 , A61K9/12 , A61K38/28 , A61M15/00 , A61M16/00 , A61M16/14 , A61M11/00
CPC分类号： A61K9/007 , A61K38/28 , A61K9/0073 , A61K9/0075 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0045 , A61M15/0065 , A61M15/008 , A61M16/142 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61M15/0051 , A61M15/0066 , A61M15/0085 , A61M15/009 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206
摘要： The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a handheld, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be used to control the point of drug release.
摘要翻译：可以通过递送雾化的单体胰岛素制剂来减少或消除通过注射递送胰岛素的需要。相对于常规胰岛素，给药的重复性更特别是血液浓度对时间曲线的重复性得到改善。血液浓度与时间分布基本上不受患者在分娩时呼吸机动的特定方面的影响。此外，通过使用单体胰岛素来增加血糖降低的速度。胰岛素的颗粒，特别是递送到肺组织表面的单体胰岛素将被吸收到循环系统中。单体胰岛素可以是干粉，但是优选地是从手持式独立装置递送到患者的液体制剂中，其自动释放雾化的制剂爆发。该装置包括传感器，其优选是电子的，其测量吸气流量和体积，该测量可用于控制药物释放点。

12. 发明授权

US5888477A Use of monomeric insulin as a means for improving the bioavailability of inhaled insulin 失效
标题翻译：使用单体胰岛素作为改善吸入胰岛素生物利用度的手段
公开(公告)号：US5888477A
公开(公告)日：1999-03-30
申请号：US792616
申请日：1997-01-31
申请人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61M11/02 , A61J7/04 , A61K9/00 , A61K38/28 , A61M15/00 , A61M16/00 , A61M16/14 , A61K9/12
CPC分类号： A61K9/007 , A61K38/28 , A61K9/0073 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0043 , A61M15/0045 , A61M15/0051 , A61M15/0066 , A61M15/008 , A61M16/142 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61M15/0085 , A61M15/009 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206 , Y10S514/866
摘要： The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of monomeric insulin and/or an inhale-exhale breathing maneuver. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by the monomeric form of insulin and by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulin or insulin analog may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be used to control the point of drug release. The sensor can also assist the patient in the inhale-exhale maneuver.
摘要翻译：可以通过以下方法减少或消除对通过注射递送胰岛素的需要：将雾化的胰岛素制剂输送到患者的肺中，并且通过使用单体胰岛素和/或胰岛素来增加胰岛素被吸收到血液中的速率，或吸气呼气机动。胰岛素的颗粒，特别是递送到肺组织表面的单体胰岛素将被吸收到循环系统中。通过胰岛素的单体形式和通过指导患者最大限度吸入，然后最大程度地呼出，吸收速率增强。这种操作导致胰岛素进入循环系统的速率的峰值，从而增加从循环系统中除去葡萄糖的速率。胰岛素或胰岛素类似物可以是干粉，但是优选地是从手持式独立装置输送到患者的液体制剂，其自动释放雾化的制剂爆发。该装置包括传感器，其优选是电子的，其测量吸气流量和体积，该测量可用于控制药物释放点。传感器还可以帮助患者进行吸气呼气操作。

13. 发明申请

US20080264416A1 Method of Treating Diabetes Mellitus in a Patient 审中-公开
标题翻译：治疗患者糖尿病的方法
公开(公告)号：US20080264416A1
公开(公告)日：2008-10-30
申请号：US12166711
申请日：2008-07-02
申请人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61M15/00 , A61B19/00
CPC分类号： A61K9/007 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61K9/0073 , A61K9/0075 , A61K38/28 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0045 , A61M15/0051 , A61M15/0065 , A61M15/0066 , A61M15/008 , A61M15/0085 , A61M15/009 , A61M16/142 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206
摘要： Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.
摘要翻译：通过控制患者吸入的空气的总体积，将吸入胰岛素的剂量控制在狭窄的范围内。通过以相同的总吸入体积的空气重复递送雾化胰岛素，每次输送给患者的胰岛素量是一致的。公开了一种用于通过吸入递送胰岛素的装置，该装置包括用于测量吸入体积并在预定点停止吸入的装置。该装置还包括可调节装置，用于根据施加的力将不同量的力施加到制剂容器以从容器中排出不同量的药物。

14. 发明授权

US07028686B2 Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume 失效
公开(公告)号：US07028686B2
公开(公告)日：2006-04-18
申请号：US10701967
申请日：2003-11-04
申请人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61M11/00
CPC分类号： A61K9/007 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61K9/0073 , A61K38/28 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0043 , A61M15/0045 , A61M15/0051 , A61M15/0066 , A61M15/008 , A61M15/0085 , A61M15/009 , A61M16/142 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206 , Y10S514/866
摘要： Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.

15. 发明授权

US06688304B2 Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume 失效
公开(公告)号：US06688304B2
公开(公告)日：2004-02-10
申请号：US09950562
申请日：2001-09-10
申请人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61M1100
CPC分类号： A61K9/007 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61K9/0073 , A61K38/28 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0043 , A61M15/0045 , A61M15/0051 , A61M15/0066 , A61M15/008 , A61M15/0085 , A61M15/009 , A61M16/142 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206 , Y10S514/866
摘要： Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.

16. 发明授权

US06250298B1 Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin 失效
标题翻译：使用单体胰岛素作为改善吸入胰岛素再现性的手段的方法
公开(公告)号：US06250298B1
公开(公告)日：2001-06-26
申请号：US09656535
申请日：2000-09-07
申请人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61M1100
CPC分类号： A61K9/007 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61K9/0073 , A61K9/0075 , A61K38/28 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0045 , A61M15/0051 , A61M15/0065 , A61M15/0066 , A61M15/008 , A61M15/0085 , A61M15/009 , A61M16/142 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206
摘要： The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be used to control the point of drug release.
摘要翻译：可以通过递送雾化的单体胰岛素制剂来减少或消除通过注射递送胰岛素的需要。相对于常规胰岛素，给药的重复性更特别是血液浓度对时间曲线的重复性得到改善。血液浓度与时间分布基本上不受患者在分娩时呼吸机动的特定方面的影响。此外，通过使用单体胰岛素来增加血糖降低的速度。胰岛素的颗粒，特别是递送到肺组织表面的单体胰岛素将被吸收到循环系统中。单体胰岛素可以是干粉，但是优选地是从手持式独立装置输送到患者的液体制剂，其自动释放雾化的制剂爆发。该装置包括传感器，其优选是电子的，其测量吸气流量和体积，该测量可用于控制药物释放点。

17. 发明授权

US06167880A Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume 失效
标题翻译：通过控制总吸入量增加吸入胰岛素剂量控制
公开(公告)号：US06167880A
公开(公告)日：2001-01-02
申请号：US09378638
申请日：1999-08-20
申请人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61M1100
CPC分类号： A61K9/007 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61K9/0073 , A61K38/28 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0043 , A61M15/0045 , A61M15/0051 , A61M15/0066 , A61M15/008 , A61M15/0085 , A61M15/009 , A61M16/142 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206 , Y10S514/866
摘要： Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.
摘要翻译：通过控制患者吸入的空气的总体积，将吸入胰岛素的剂量控制在狭窄的范围内。通过以相同的总吸入体积的空气重复递送雾化胰岛素，每次输送给患者的胰岛素量是一致的。公开了一种用于通过吸入递送胰岛素的装置，该装置包括用于测量吸入体积并在预定点停止吸入的装置。该装置还包括可调节装置，用于根据施加的力将不同量的力施加到制剂容器以从容器中排出不同量的药物。

18. 发明授权

US5829436A Ventilation imaging using a fine particle aerosol generator 失效
标题翻译：通气成像使用细粒子气溶胶发生器
公开(公告)号：US5829436A
公开(公告)日：1998-11-03
申请号：US789551
申请日：1997-01-27
申请人： Reid M. Rubsamen , Stephen J. Farr , Fred Silverstein
发明人： Reid M. Rubsamen , Stephen J. Farr , Fred Silverstein
IPC分类号： A61B5/08 , A61K51/12 , A61M11/00
CPC分类号： A61K51/1206 , A61B5/0813 , A61B6/4258 , A61K2123/00
摘要： A method of diagnosing a patient is carried out by delivering an aerosolized dose of a radioactive formulation to a patient and making a ventilation image of radioactive material deposited in the lung. This image is compared with a separately generated image (perfusion image) taken after injecting radiolabled particles into the pulmonary arterial circulation. Devices, packaging and methodology for creating aerosols are provided which allow for efficient and repeatable delivery of radioaerosols to the lungs of a patient. Devices may be plug-in units or hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The device is loaded with a container of a radioactive formulation such as .sup.99m Tc-labelled diethylene-triamine pentaacetic acid (DTPA). Actuation of the device forces the radioactive formulation through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 6.0 microns. The container includes radioactive shielding in the form of a lead coating and/or a lead surrounding packet. The porous membrane is positioned in alignment with a surface of a channel through which a patient inhales air.
摘要翻译：通过将放射性制剂的雾化剂量递送到患者并且放置在肺中的放射性物质的通风图像来进行诊断患者的方法。将该图像与在肺动脉循环中注射放射性粒子后分离产生的图像（灌注图像）进行比较。提供了用于产生气溶胶的装置，包装和方法，其允许放射性天然气对患者的肺的有效和可重复的递送。设备可以是插入式单元或手持的独立单元，其在患者的吸气流循环中在相同的释放点自动启动。该装置装载有放射性制剂的容器，例如99mTc标记的二亚乙基三胺五乙酸（DTPA）。该装置的致动迫使放射性制剂通过容器的多孔膜，该膜具有直径在约0.25至6.0微米范围内的孔。容器包括铅涂层和/或铅包围形式的放射性屏蔽。多孔膜定位成与患者吸入空气的通道的表面对准。

19. 发明授权

US5792057A Ventilation imaging using a fine particle aerosol generator 失效
标题翻译：通气成像使用细粒子气溶胶发生器
公开(公告)号：US5792057A
公开(公告)日：1998-08-11
申请号：US979394
申请日：1997-11-26
申请人： Reid M. Rubsamen , Stephen J. Farr
发明人： Reid M. Rubsamen , Stephen J. Farr
IPC分类号： A61J1/03 , A61K51/12 , A61M15/00 , A61B6/00
CPC分类号： A61K51/1206 , A61M15/0043 , A61B6/4258 , A61J1/035
摘要： A method of diagnosing a patient is carried out by delivering an aerosolized dose of a radioactive formulation to a patient and making a ventilation image of radioactive material deposited in the lung. This image is compared with a separately generated image (perfusion image) taken after injecting radiolabled particles into the pulmonary arterial circulation. A diagnosis of a pulmonary embolism can be made when areas of the lung which are shown in the ventilation image are not shown within the perfusion image, indicating that air flow to that area exists, whereas a blood flow to that area has been blocked. Devices, packaging and methodology for creating aerosols are provided which allow for efficient and repeatable delivery of radioaerosols to the lungs of a patient. Devices may be plug-in units or hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The release point is automatically determined either mechanically or, more preferably calculated by a microprocessor which receives data from a sensor making it possible to determine inspiratory flow rate and inspiratory volume. The device is loaded with a container of a radioactive formulation such as .sup.99m Tc-labelled diethylene-triamine pentaacetic acid (DTPA). Actuation of the device forces the radioactive formulation through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 6.0 microns. The container includes radioactive shielding in the form of a lead coating and/or a lead surrounding packet.
摘要翻译：通过将放射性制剂的雾化剂量递送到患者并且放置在肺中的放射性物质的通风图像来进行诊断患者的方法。将该图像与在肺动脉循环中注射放射性粒子后分离产生的图像（灌注图像）进行比较。当通气图像中显示的肺部区域没有显示在灌注图像中时，可以进行肺栓塞的诊断，指示存在到该区域的空气流，而到该区域的血流已被阻塞。提供了用于产生气溶胶的装置，包装和方法，其允许放射性天然气对患者的肺的有效和可重复的递送。设备可以是插入式单元或手持的独立单元，其在患者的吸气流循环中在相同的释放点自动启动。释放点自动地被机械地确定，或者更优选地由接收来自传感器的数据的微处理器来计算，从而可以确定吸气流速和吸气体积。该装置装载有放射性制剂的容器，例如99mTc标记的二亚乙基三胺五乙酸（DTPA）。该装置的致动迫使放射性制剂通过容器的多孔膜，该膜具有直径在约0.25至6.0微米范围内的孔。容器包括铅涂层和/或铅包围形式的放射性屏蔽。

20. 发明申请

US20090241950A1 METHOD OF TREATING DIABETES MELLITUS IN A PATIENT 审中-公开
标题翻译：在患者中治疗糖尿病的方法
公开(公告)号：US20090241950A1
公开(公告)日：2009-10-01
申请号：US12464627
申请日：2009-05-12
申请人： Igor Gonda , Reid M. Rubasamen , Stephen J. Farr
发明人： Igor Gonda , Reid M. Rubasamen , Stephen J. Farr
IPC分类号： A61M15/00 , A61M16/10
CPC分类号： A61K9/007 , A61J7/0418 , A61J7/0427 , A61J7/0445 , A61K9/0073 , A61K9/0075 , A61K38/28 , A61M11/001 , A61M15/00 , A61M15/0031 , A61M15/0045 , A61M15/0051 , A61M15/0065 , A61M15/0066 , A61M15/008 , A61M15/0085 , A61M15/009 , A61M16/142 , A61M2016/0021 , A61M2016/0036 , A61M2202/062 , A61M2202/064 , A61M2205/50 , A61M2205/8206
摘要： The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient=s breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be used to control the point of drug release.
摘要翻译：可以通过递送雾化的单体胰岛素制剂来减少或消除通过注射递送胰岛素的需要。相对于常规胰岛素，给药的重复性更特别是血液浓度对时间曲线的重复性得到改善。血液浓度对时间曲线基本上不受患者在分娩时呼吸机动的特定方面的影响。此外，通过使用单体胰岛素来增加血糖降低的速度。胰岛素的颗粒，特别是递送到肺组织表面的单体胰岛素将被吸收到循环系统中。单体胰岛素可以是干粉，但是优选地是从手持式独立装置输送到患者的液体制剂，其自动释放雾化的制剂爆发。该装置包括传感器，其优选是电子的，其测量吸气流量和体积，该测量可用于控制药物释放点。

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