CN101405738B - 用于无线监测机械式药物输送装置操作的方法和电子模块 - Google Patents

用于无线监测机械式药物输送装置操作的方法和电子模块 Download PDF

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CN101405738B
CN101405738B CN2007800098370A CN200780009837A CN101405738B CN 101405738 B CN101405738 B CN 101405738B CN 2007800098370 A CN2007800098370 A CN 2007800098370A CN 200780009837 A CN200780009837 A CN 200780009837A CN 101405738 B CN101405738 B CN 101405738B
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electronic module
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medication delivery
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CN101405738A (zh
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A·拉森
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Novo Nordisk AS
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    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • G16H20/17ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/31Details
    • A61M5/315Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/31Details
    • A61M5/315Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31565Administration mechanisms, i.e. constructional features, modes of administering a dose
    • A61M5/3159Dose expelling manners
    • A61M5/31593Multi-dose, i.e. individually set dose repeatedly administered from the same medicament reservoir
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/31Details
    • A61M2005/3125Details specific display means, e.g. to indicate dose setting
    • A61M2005/3126Specific display means related to dosing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/35Communication
    • A61M2205/3546Range
    • A61M2205/3569Range sublocal, e.g. between console and disposable
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/35Communication
    • A61M2205/3576Communication with non implanted data transmission devices, e.g. using external transmitter or receiver
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/35Communication
    • A61M2205/3576Communication with non implanted data transmission devices, e.g. using external transmitter or receiver
    • A61M2205/3584Communication with non implanted data transmission devices, e.g. using external transmitter or receiver using modem, internet or bluetooth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/58Means for facilitating use, e.g. by people with impaired vision
    • A61M2205/581Means for facilitating use, e.g. by people with impaired vision by audible feedback
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/58Means for facilitating use, e.g. by people with impaired vision
    • A61M2205/582Means for facilitating use, e.g. by people with impaired vision by tactile feedback
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178Syringes
    • A61M5/24Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic

Abstract

本发明涉及用于监测药物输送装置操作的方法。具体的,本发明涉及包括下述步骤的方法:将电子模块设置在药物输送装置附近,利用电子模块探测响应于在相关药物输送装置内发生动作而产生的可测量信号,以及利用电子模块的存储设备存储关于或代表可测量信号的信息。本发明还涉及能够执行上述方法的电子模块。

Description

用于无线监测机械式药物输送装置操作的方法和电子模块
技术领域
[0001] 本发明涉及适于定位在钢笔形药物输送装置外表面上的电子模块。具体的,本发明涉及能够测量信号的电子模块,上述信号为诸如在钢笔形药物输送装置操作期间产生的声音、光学、振动或电磁信号。
背景技术
[0002] 对于药物输送装置使用者而言,保持跟踪自药物输送装置推出剂量的量是棘手的过程。如果还要监测注射时间、注射日期等则该过程就更复杂。
[0003] US6, 482,185公开了用于钢笔形注射装置的外部显示设备。对于视力减弱的人们而言,会难于在钢笔形注射装置上设定剂量。在US6,482,185中,提供外部显示设备。该显示设备可附连到钢笔。关于剂量的经由接触和相反接触信号被传输到显示器设备并显示在较大的显示器上。在US6,482,185中提出的显示设备还可包括某种存储配置,其允许存储或记录药物的设定剂量以及与其相关的数据,像时间、日期和药物种类(例如,胰岛素制剂)等。
[0004] US6, 482, 185中提出的显示设备的缺陷是,钢笔形注射装置(预期显示设备附连到其)需要经过苛刻变型,原因在于需要特定通信配置(诸如电接触、光学端口、齿轮等) 以便将来自钢笔形注射装置的信息传送到显示设备。
[0005] W02004/1105^涉及用于检测医疗装置的设备。W02004/110528中提出的设备包括声音接收器,其能够探测由医疗装置发出的声音,以便检测医疗装置的偏差。 102004/1105¾还涉及用于检测医疗装置的方法,由此探测和分析由医疗装置发出的声音。
[0006] W02004/110528中提出的设备意旨用于探测和定位医疗装置的偏差。这样, W02004/110528中提出的设备形成用于测试医疗装置的测试设备。W02004/110528中提出的设备不适用于图示(mapping)医疗装置(诸如能够在给定时间段内输送设定剂量胰岛素的药物输送装置)的使用方式。为了获得可靠的图示结果,上述给定的时间段例如可以是几个月。根据W02004/110528的设备不适用于图示医疗装置使用方式的原因有很多。例如,W02004/110528中提出的装置不便于给医疗装置中发生的事件定时戳。该时戳的缺乏使其不可能按正确的时间顺序安排所探测到的事件。
[0007] 本发明的一个目的是提供能够监测标准并由此未变型的物输送装置的整个操作的便携式电子模块。
[0008] 本发明还有一个目的是提供便携式电子模块,其适于附连到药物输送装置而不改变或影响药物输送装置的日常使用。
[0009] 根据本发明,提出一种电子模块,其能够测量在钢笔形药物输送装置的正常操作下(诸如,在设定剂量药物的设定和推出期间)产生的外部可得到的声音和/或振动信号。
[0010] 本发明的优势是关于时间/日期和药物注射量的相应值可容易从电子模块传输到例如计算机,以便进一步处理。以该方式可避免传统的纸基记事录。此外,本发明还可用作适于常规药物输送装置的电子日志。
4[0011] 发明内容
[0012] 在第一方面,本发明通过提供用于无线监测机械式药物输送装置操作的方法而实现上述目的,该方法包括下述步骤:
[0013]-利用相互协作的耦联设备将电子模块附连到相关机械式药物输送装置,以便可释放地将电子模块耦联到相关机械式药物输送装置;
[0014]-利用电子模块探测可测量信号,并且将每一事件与时戳相关联,其中所述可测量信号响应于在相关药物输送装置内发生的事件或动作而产生;以及
[0015]-利用电子模块的存储设备存储关于所探测的可测量信号的信息,并存储相关的时戳。
[0016] 其中可测量的信号是声音和/或振动信号。
[0017] 这样,可测量信号可以是相应于药物剂量的设定产生的声音信号。药物剂量可通过激活相关机械式药物输送装置的剂量设定构件来设定。声音信号还可响应于将剂量药物从相关药物输送装置推出而产生。
[0018] 该方法还包括将与其相关或代表测量信号的信息传输到与电子模块相关的外部模块、单元或便携式设备以便进一步处理的步骤。可通过诸如蓝牙的无线设备提供到外部模块、单元或便携式设备的传输。
[0019] 至于机械式药物输送装置意味着手持式设备,设备的使用者给予所需的力以便将设定剂量的药物推出。可选的,机械式药物输送装置的使用者可通过在机械式药物输送装置的合适构件中累积能量来给设备提供能量。上述构件可包括弹性构件,诸如线性弹簧或扭簧。
[0020] 在第二方面,本发明涉及适于可释放地耦联到相关机械式药物输送装置上的便携式电子模块,该电子模块包括:
[0021]-用于无线探测可测量信号的设备,并且将每一事件或动作与时戳相关联,所述可测量信号响应于在相关机械式药物输送装置内发生的事件或动作而产生;
[0022]-用于可释放地将电子模块耦联到相关机械式药物输送装置的相互协作的耦联设备;以及
[0023]-用于存储关于所探测的可测量信号的信息并存储相关时戳的设备。
[0024] 其中可测量的信号是声音和/或振动信号。
[0025] 同样,机械式药物输送装置意旨意味着手持式设备,设备的使用者给予所需的力以便将设定剂量的药物推出。可选的,机械式药物输送装置的使用者可通过在机械式药物输送装置的合适构件中累积能量来给设备提供能量。上述构件可包括弹性构件,诸如线性弹簧或扭簧。
[0026] 电子模块还可包括用于将所探测的、所存储的或所记录的信息传输到外部模块或单元以便进一步处理的设备。此外电子模块可包括信号处理器设备,其适于在存储与其相关或代表所述一个或多个信号的信息之前处理所探测的一个或多个信号。探测设备可包括能够探测在相关机械式药物输送装置中产生的声音信号的传声器。优选的,这种传声器是微型传声器,诸如在助听器业使用类型的传声器。
[0027] 可选或另外的,探测设备可包括能够探测在相关机械式药物输送装置中产生的振动信号的机械振动仪。[0028] 传输设备可包括用于将来自电子模块的信息传输到外部模块或单元的设备。利用蓝牙可提供将来自电子模块的信息无线传输到外部模块或单元。
[0029] 电子模块还可包括适于给电子模块的使用者提供视觉信息的显示设备以及适于在激活时接通电子模块的触控板开关。可选的,可提供在药物输送装置的常规使用过程中适于接通电子模块的接触设备。这种接触设备优选隐藏在电子模块的外壳内。
附图说明
[0030] 现在将参照附图对本发明进行解释说明,其中:
[0031] 图1示出根据本发明的电子模块;以及
[0032] 图2示出根据本发明的简单版本电子模块的框图。
[0033] 由于本发明易于进行各种变型和改变到替换形式,在附图中以例子的方式示出具体实施例,并且在此进行详细描述。但是,应该理解,本发明不意旨限定到公开的特定形式。 此外,本发明意旨涵盖落入到如由所附权利要求限定的本发明精神和范围内的所有变型、 等同物和替换形式。
[0034] 具体实施方式
[0035] 在其最通常的方面,本发明涉及能够测量声音和/或振动信号的便携式电子模块,上述信号响应于构成机械式药物输送装置至少一部分的内部构件的相对移动而产生, 便携式电子模块附连到机械式药物输送装置。这种内部构件可以是机械构件,例如其在移动过程中产生诸如喀哒声的声音信号。
[0036] 根据本发明的便携式电子模块预期用于图示医疗装置(诸如能够在给定时间段内输送设定剂量胰岛素的药物输送装置)的使用方式。为了获得可靠的图示结果,上述给定的时间段通常延续超过几个月。这样,根据本发明的便携式电子模块适于附连到药物输送装置并通常延续几个月,由此可精确图示药物输送装置的使用方式。为了完成上述,在药物输送装置中发生事件的时戳是重要的,因为时戳使其可能按正确的时间顺序安排所探测的事件。
[0037] 电子模块还包括用于存储或记录从所测量信号产生的信息的设备,以及用于任选地将所存储或记录的信息传输送外部模块或设备以便进一步处理的设备。该外部模块或设备可以是计算机、便携式电话、PDA或例如能够将胰岛素的注射剂量作为时间函数显示的类似设备。这样,通过将所存储的数据传送到计算机,药物输送装置的使用者可看到显示在屏幕上的他/她的注射模式,并且他/她可选择将显示信息存储在计算机内。
[0038] 可通过插入到电子模块内的导线实现将来自电子模块的数据传输或传送到计算机、便携式电话/PDA。可选的,可通过诸如DECT或蓝牙的无线设备实现在模块和计算机、便携式电话/PDA之间的数据传输或传送。
[0039] 为了测量声音信号,电子模块包括某种压力传感器,诸如微型传声器。微型传声器能够拾取机械“喀哒声”,该“喀哒声”是当药物输送装置的塑料或金属啮合件相对彼此移动时产生的,通常是在啮合时和脱离啮合时产生的。
[0040] 连接到微型传声器的电子电路可有助于对拾取的“喀哒声”滤波。这样,如果所探测的“喀哒声”落入特定的频率范围内,比如低频率范围,将设定药物剂量。类似的,如果所探测的“喀哒声”落入高频率范围,将把剂量药物从药物输送装置推出。具体的,通过数喀
6哒数来测量发生机械喀哒的情况。一次喀哒例如相应于推出特定量的药物。在顺序推出过程中通过数喀哒数可容易计算从药物输送装置推出的药物量。
[0041] 电子模块还可存储或记录事件的完整顺序。例如,这种顺序可包括电子模块的接通、记录相应于剂量设定的低频率喀哒声以及记录响应于剂量被推出的高频率喀哒声。
[0042] 电子模块还存储喀哒声的数目和时间/日期的相应值。这样,当药物输送装置的使用者将所存储的数据从电子模块传输或传送到计算机时,机械式药物输送装置的使用者可看到时间、日期、每一设定剂量的量和每一注射剂量的量。
[0043] 应该提到的是根据本发明的电子模块还可测量除了声音信号之外的其它信号。上述其它类型信号的例子可以是振动信号。显然,如果准备测量上述非声音信号,那么可使用其它类型的传感器。例如,微型机械振动仪能够测量振动信号。
[0044] 根据本发明的电子模块还可容纳用于对所测量信号进行全部或部分处理的信号处理器。这样,传输或传送到外部单元的信息可以是原始数据或预处理数据。
[0045] 现在参照图1,示出根本发明的电子模块1。如图1中所示,模块1可安装到机械式药物输送装置2的外壳上。模块利用设置在电子模块中的磁体(诸如永磁体设备)附连到药物输送装置的上部(即,用于驱动活塞以便推出药物的配置定位的地方)。但是,也可使用模块和设备之间的其它耦联配置。活塞杆使得套筒活塞朝向药物输送装置的近端移动。
[0046] 如已经所述的,模块可配备有适于探测声音和/或振动信号的合适传感器,上述声音和/或振动信号响应于药物输送装置的常规操作而产生。例如,两个啮合齿轮(未示出)可产生喀哒声,该喀哒声可由安装在模块外壳内的诸如微型传声器的微型压力传感器记录。模块例如可适于通过数所记录的“喀哒”数来处理所记录的信号,以便可将药物设定剂量的量和药物推出量存储在模块内。如上已经所述的,存储在模块内的信息可被传送到诸如便携式计算机的外部装置以便进一步处理。
[0047] 根据本发明电子模块外壳的外表面部分可支撑电开关和/或显示构件。电开关优选作为电容性指触开关执行。激活该开关后,电子模块的电子从位于电子模块外壳中的电池激励。可选的,电开关可结合到电子模块外壳内。在机械式药物输送装置的常规使用过程中激活上述所结合的开关。这样,药物输送装置的使用者可不用特别关注开关的激活,原因在于当机械式药物输送装置由设备使用者的手握持时可自动激活开关。显示构件可以是能够将有用信息提供给电子模块使用者的平板LCD阵列。
[0048] 图2示出根据本发明的简单版本电子模块的框图。图2中所示的电子模块适于记录相应于剂量设定和剂量推出产生的喀哒声。如图所示,便携式电子模块包括传声器、低通滤波器和A/D转换器。这样,在将其提供到微处理器之前,由传声器拾取的声音信号首先低通滤波,然后转换成数字格式。至于电源,由内装式电池给电子模块供电,当例如激活电容性触控板时,电池给模块供电。例如当指尖位于触控板上时执行上述激活。
[0049] 微处理器与BootFlash (其内保存适于微处理器的控制软件)通信。为了与周围环境通信,电子模块装备有光学通信端口,IrDA,其允许将所记录的数据通信到外部设备。显然,与周围环境的上述通信可由其它设备完成,诸如将电子设备与外部设备相连的物理导线。实时时钟RTC例如确保关于剂量设定和剂量推出的数据随着与其相关的时间和日期进行存储或记录。此外,可存储随同这些参数一起的模块接通时间。

Claims (15)

1.用于无线监测机械式药物输送装置操作的方法,该方法包括下述步骤:-提供用于设定药物剂量和注射所设定的剂量的机械式药物输送装置,所述机械式药物输送装置在设定和/或推出剂量药物期间响应于构成机械式药物输送装置至少一部分的内部构件的相对移动而产生喀哒声,由此喀哒声的数目相应于所设定和/或推出的药物量;-提供便携式电子模块,所述便携式电子模块包括模块外壳和安装在模块外壳中的探测设备;-利用相互协作的耦联设备将该电子模块附连到所述机械式药物输送装置,以便可释放地将该电子模块耦联到所述机械式药物输送装置;-利用该电子模块,探测在设定和/或推出剂量药物期间响应于在相关药物输送装置内发生的事件或动作而产生的喀哒声,并且将每一事件或动作与时戳相关联;以及-利用该电子模块的存储设备存储关于包括在设定和/或推出剂量药物期间所探测的喀哒声的数目的所探测的喀哒声的信息,并存储相关的时戳。
2.根据权利要求1所述的方法,其中喀哒声响应于通过激活相关机械式药物输送装置的剂量设定构件来设定的药物剂量而产生。
3.根据权利要求1所述的方法,其中喀哒声响应于将剂量药物从相关药物输送装置推出而产生。
4.根据任一前述权利要求所述的方法,还包括将所存储的信息传输到与该电子模块相关的外部模块或单元以便进一步处理的步骤。
5.根据权利要求4所述的方法,其中通过无线设备提供到外部模块或单元的传输。
6.根据权利要求5所述的方法,其中无线设备是蓝牙。
7.用于可释放地耦联到相关机械式药物输送装置上的便携式电子模块,所述机械式药物输送装置在设定和/或推出剂量药物期间响应于构成机械式药物输送装置至少一部分的内部构件的相对移动而产生喀哒声,由此喀哒声的数目相应于所设定和/或推出的药物量,该电子模块包括:-模块外壳;-安装在模块外壳中的探测设备,用于无线探测在设定和/或推出剂量药物期间响应于在相关机械式药物输送装置内发生的事件或动作而产生的可测量信号喀哒声,并且将每一事件或动作与时戳相关联;-用于可释放地将该电子模块耦联到相关机械式药物输送装置的相互协作的耦联设备;以及-用于存储关于包括在设定和/或推出剂量药物期间所探测的喀哒声的数目的所探测的喀哒声的信息并存储相关时戳的设备。
8.根据权利要求7所述的电子模块,还包括用于将所存储的信息传输到外部模块或单元以便进一步处理的设备。
9.根据权利要求8所述的电子模块,还包括信号处理器设备,其适于在存储与其相关的信息之前处理所探测的喀哒声。
10.根据权利要求8或9所述的电子模块,其中探测设备包括能够探测在相关机械式药物输送装置中产生的喀哒声的传声器。
11.根据权利要求8或9所述的电子模块,其中传输设备包括用于将来自该电子模块的信息传输到外部模块或单元的设备。
12.根据权利要求11所述的电子模块,其中通过蓝牙提供将来自该电子模块的信息无线传输到外部模块或单元。
13.根据权利要求7、8或9所述的电子模块,还包括适于给该电子模块的使用者提供视觉信息的显示设备。
14.根据权利要求7、8或9所述的电子模块,还包括适于在激活时接通该电子模块的触控板开关。
15.根据权利要求7、8或9所述的电子模块,还包括在药物输送装置的常规使用过程中适于接通该电子模块的接触设备。
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WO2007107564A1 (en) 2007-09-27
CA2645732C (en) 2014-12-30
RU2459247C2 (ru) 2012-08-20
CN101405738A (zh) 2009-04-08
RU2008137260A (ru) 2010-04-27
US20090069742A1 (en) 2009-03-12
JP2009530002A (ja) 2009-08-27
BRPI0708856A2 (pt) 2011-06-14
CA2645732A1 (en) 2007-09-27
US9101723B2 (en) 2015-08-11
EP1999666A1 (en) 2008-12-10
AU2007228715B2 (en) 2011-11-17
AU2007228715A1 (en) 2007-09-27

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