CN102740911B - 用于雾化的无防腐剂胰岛素制剂和系统以及方法 - Google Patents

用于雾化的无防腐剂胰岛素制剂和系统以及方法 Download PDF

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CN102740911B
CN102740911B CN201180005836.5A CN201180005836A CN102740911B CN 102740911 B CN102740911 B CN 102740911B CN 201180005836 A CN201180005836 A CN 201180005836A CN 102740911 B CN102740911 B CN 102740911B
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约翰·S·巴顿
赖安·S·巴顿
郭美常
耶胡达·伊夫里
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Abstract

一个实施例描述了一种具体地用于雾化的胰岛素制剂。所述制剂包括大量的水和少量的胰岛素。而且，所述制剂不含防腐剂，不含间甲酚、甲酚或者苯酚，以允许使用振动孔板雾化所述制剂，而所述胰岛素制剂没有大量发泡。

Description

用于雾化的无防腐剂胰岛素制剂和系统以及方法
相关申请的交叉参考
本申请要求2011年1月11日提交的美国申请U.S.13/004,546的优先权，该申请要求2010年1月12日提交的美国临时申请61/335,769的权益，并且为部分继续申请，其全部内容通过引用并入本文。
本申请还和与本申请为同一申请日，名称为“无防腐剂单一剂量吸入器系统”的美国申请13/004,662相关，其全部内容通过引用并入本文。
技术领域
本申请总体涉及胰岛素制剂领域，并且具体涉及可以使用高频振动网格的雾化器雾化的胰岛素制剂。
背景技术
多种胰岛素制剂已经广泛使用多年。这些制剂主要设计有一个长的保质期并典型地通过注射给药。本申请涉及特定地适用于以雾化喷雾形式通过吸入输送的一种胰岛素制剂。
发明内容
在一个实施例中，提供一种具体地用于雾化的胰岛素制剂。该制剂包括大量的水和少量的胰岛素。进一步，制剂不含防腐剂以允许使用振动孔板雾化制剂，而胰岛素制剂没有大量发泡。例如，该制剂不包括间甲酚、甲酚或者苯酚等。在一个方面，胰岛素具有大约100IU/ml到大约1200IU/ml的人胰岛素浓度，更优选地，具有大约200IU/ml到大约800IU/ml的人胰岛素浓度。而且，水的体积量可为大约99.8%到大约97.0%，以及人胰岛素的体积量可为大约0.2%到大约3.0%。
在另一个实施例中，提供一种具体地用于雾化的胰岛素制剂。该制剂主要包括大量的水和少量的胰岛素、HCl、NaOH。该制剂不含防腐剂，从而使该制剂可以由振动孔板雾化，而所述胰岛素制剂没有大量发泡。
在一个方面，胰岛素具有大约100IU/ml到大约1200IU/ml的人胰岛素浓度，更优选地，具有大约200IU/ml到大约800IU/ml的人胰岛素浓度。同时，水的体积量可为大约99.8%到大约97.0%，以及人胰岛素的体积量占大约0.2%到大约3.0%。
在另一个实施例中，本发明提供一种具体地用于雾化的胰岛素制剂，该制剂包括大量的水和少量的胰岛素。该制剂能够使用振动孔板被雾化为喷雾，该具有多个孔的振动孔板的振动频率在大约50kHz到150kHz。并且，胰岛素制剂的量最大到大约200μL，并且其中雾化97%的制剂的时间小于大约22秒。
在特定的方面，该胰岛素制剂不含防腐剂，从而使该制剂可以由振动孔板雾化，而该制剂没有大量发泡。进一步，胰岛素可具有大约100IU/ml到大约1200IU/ml的人胰岛素浓度，更优选地，可具有大约200IU/ml到大约800IU/ml的人胰岛素浓度。
本发明的一个实施例还提供一种用于雾化胰岛素制剂的示例性的方法，该方法包括使用胰岛素制剂，该胰岛素制剂包括大量的水，以及少量的胰岛素、HCl和NaOH。将一定量的胰岛素制剂供给到具有多个孔的振动孔板的后侧。当胰岛素制剂在后侧时使孔板振动。振动使供给的胰岛素作为雾化的喷雾从孔板的前侧喷出，而不用大量发泡该胰岛素制剂。
在一个步骤，至少大约97%的制剂被喷出。同时，胰岛素制剂的量最大到大约200μL，并且其中雾化97%的制剂的时间小于大约11秒。在另一方面，振动孔板的振幅小于大约4μm，有些情况下小于大约3μm，并且在另外的情况下小于大约2μm。进一步，雾化的喷雾可以包括平均尺寸在大约3μm到大约8μm、优选地在大约3μm到大约6μm的范围内的雾化液滴。当孔板振动时，有少于3%的制剂，在一些情况下少于大约1%，并且更优选地少于约0.1%的制剂转化为泡沫。
在一个特定的方面，胰岛素具有大约200IU/ml到大约800IU/ml的人胰岛素浓度。同时，孔板的直径范围可以从大约5mm到大约8mm，孔的尺寸范围从大约3μm到大约8μm，厚度范围从大约50微米到大约70微米，以及在大约50kHz到大约150kHz的频率范围内振动。
在另一实施例中，本发明提供一种雾化系统，包括：吸入器，其包括限定喷口的外壳和设置在所述外壳中的气雾发生器。该气雾发生器包括具有前表面和后表面的可振动膜和用于使该膜振动的可振动元件。该系统还包括容纳一定量的胰岛素制剂的容器，该制剂主要包括大量的水和少量的胰岛素。制剂不含防腐剂，使得所述制剂可以使用振动孔板进行雾化，而所述制剂没有大量发泡。
在一个方面，胰岛素具有大约200IU/ml到大约800IU/ml的人胰岛素浓度。在另一方面，孔板具有的孔的尺寸范围从大约3μm到大约8μm。进一步，可振动膜可被构造成以小于大约2μm的频率振动。
附图说明
图1是根据本发明的分配设备的一个实施例的部分剖开的透视图。
图2是图1的分配设备的更多细节的视图。
图3是显示雾化不同的胰岛素制剂所需要的时间的图表。
图4是显示雾化不同的胰岛素制剂以及水和盐水所需要的时间的图表。
图5是显示当添加乙二醇时雾化不同的胰岛素制剂所需要的时间的图表，包括示例1-3的制剂。
具体实施方式
本发明的一个特定实施例提供一种无防腐剂的胰岛素制剂，该制剂可以用于雾化设备来提供胰岛素雾化喷雾。更具体地，该胰岛素制剂不含任何防腐剂，包括苯酚、间甲酚、氯甲酚、百里香酚和其混合物，等。由于没有防腐剂，该制剂可以使用以高频率工作的振动网格或者振动孔板将其作为液体喷雾来雾化。由于没有防腐剂，允许一定剂量的制剂与振动网格接触，而该制剂没有大量发泡。反过来，制剂可以更快的雾化。进一步，基本上所有的液体都可以被雾化。
该制剂包括大量的水和少量的人胰岛素。该制剂还可以包括不同浓度的人胰岛素。例如，制剂的胰岛素浓度范围可以从大约100IU/ml到大约1200IU/ml，更优选地，具有从大约200IU/ml到大约800IU/ml的范围。
除了水和人胰岛素，制剂还可以包括锌，醋酸盐，氯化物和钠。锌离子和醋酸根离子来自药物物质，例如胰岛素。氯离子和钠离子在胰岛素溶解并调整pH值期间被添加。只是作为举例，对于800IU/ml的胰岛素制剂，NaCl浓度可以为大约20mM，对于400IU/ml的胰岛素制剂，NaCl浓度可以为大约10mM，对于200IU/ml的胰岛素制剂，NaCl浓度可以为大约5mM。
以下为根据本发明使用的非限定性的不同的无防腐剂制剂的实例。
例1800IU/ml的胰岛素制剂
在该例子中，通过将1400mg的人胰岛素（每个胰岛素六聚体具有2到4个Zn2+）悬浮在44ml水中制得50ml的800IU的胰岛素溶液，然后通过加入1.0ml的1N HCl使pH值约为3.0来溶解胰岛素。在胰岛素全部溶解后，慢慢加入1.6ml的1N NaOH来用滴定法测量胰岛素溶液，使pH值为7.4。最后，加水至50ml。
例2400IU/ml的胰岛素制剂
在该第二例子中，通过将700mg的人胰岛素（每个胰岛素六聚体具有2到4个Zn2+）悬浮在44ml的水中制得50ml的400IU的胰岛素溶液，然后通过加入0.5ml的1N HCl使pH值为约3.0来溶解胰岛素。在胰岛素全部溶解后，慢慢加入约0.8ml的1N NaOH来用滴定法测量胰岛素溶液，使pH值为7.4。最后，加水至50ml。
例3200IU/ml的胰岛素制剂
在该第三例子中，通过将350mg的人胰岛素（每个胰岛素六聚体具有2到4个Zn2+）悬浮在44ml的水中制得50ml的200IU的胰岛素溶液，然后通过加入0.25ml的1N HCl使pH值为约3.0来溶解胰岛素。在胰岛素全部溶解后，慢慢加入约0.4ml的1N NaOH来用滴定法测量胰岛素溶液，使pH值为7.4。最后，加水至50ml。
多种吸入器或雾化器可以用于雾化无防腐剂溶液。例如，一种雾化设备，可包括：外壳，该外壳限定分配出口；可振动膜，该可振动膜的前表面在出口处露出，后表面用于接收待分配的液体；以及振动机构，该振动机构连接至外壳并且可操作成使该振动膜振动，以分配通过该膜的液体的喷雾。在一些情况下，液体输送系统可以用于从膜的后表面输送测定量的液体。以这种方式，通过使振动机构运行足以完全雾化后表面的测定量的液体的操作时段，使该测定量的液体在出口处是可分配的。
可以使用的雾化器的几种类型的例子在与本申请同日提交的、名称为“无防腐剂的单一剂量吸入器系统”的共同待审的美国申请13/004,622,中描述，在前通过引用并入本文。
参照图1，描述了吸入器的一个实施例。图1是吸入器100的局部剖开的视图。吸入器100可以用于连接到供给液体胰岛素的各种容器。例如，吸入器100可以与单位剂量的泡罩封装件一起使用来供给测定量的胰岛素到吸入器。吸入器100包括两个组件102和112。第一组件102限定用于电子电路和电池的隔室，以及第二组件112限定具有分配出口105的外壳，并包括可振动膜气雾发生器108和可以沿着所示的箭头115闭合的盖子104。气雾发生器108具有暴露于出口管111处露出的前表面和与待分配的液体接触的后表面109。气雾发生器108连接到组件112的外壳并且可以操作成经由喷口105来分配喷雾形式的活性药物制剂。美国专利5164740、6629646、6926208、7108197、5938117、6540153、6540154、7040549、6921020、7083112、7628339、5586550、5758637、6085740、6467476、6640804、7174888、6014970、6205999、6755189、6427682、6814071、7066398、6978941、7100600、7032590、7195011中描述的示例性的气雾发生器可以在此使用，通过引用并入本文。这些参考文献描述了示例性的气雾发生器，制造这种气雾发生器的方式以及供应液体到气雾发生器的方式，至少这些特征通过引用并入本文。气雾发生器可包括可振动膜，该可振动膜具有锥形孔，其尺寸在大约3μm到大约8μm的范围，优选的，为大约3μm到大约6μm的范围，在有些情况下为大约4μm。可振动膜可以是圆顶形的并且由环绕孔的环形压电元件振动。可振动膜的直径在大约5mm到大约8mm的范围内。可振动膜的厚度范围为大约50微米到大约70微米。典型地，可振动膜将在以大约50kHz到150kHz的范围内的频率振动。
进一步，为了最小化胰岛素制剂的发泡，可振动膜可以小于大约4μm、优选地小于3μm并且更优选地小于2μm的振幅振动。
每次测定量的液体供给到吸入器100，其被输送到气雾发生器的后表面109。因此，对于每次使用，通过气雾发生器的操作，测定量的雾化药品制剂可以在喷口出口105处分配。
吸入器100还包括接收容器的内容物的槽107，从而该内容物可以供给到气雾发生器108。槽107具有凹形并限定通向振动的气雾发生器108的流体通道。
图2显示了气雾发生器108的振动膜109的更多细节。当一定量的液体被分配时，指示灯120开始闪烁以告诉病人吸入器100准备运行。此后不久的任何时间，患者可以通过喷口105吸入。患者吸入量通过流量传感器探测，其反过来激活雾化发生器108产生雾化颗粒进入管道111。气雾沿着箭头121显示的方向夹带在吸入气流中，并通过呼吸系统流入病人的肺部。当所有剂量被雾化，这可能需要一次或几次呼吸，“剂量结束”指示灯121第二次亮，来示意病人所有剂量已经被输送。全部剂量的输送是当至少95%的剂量被输送，更优选98%的剂量被输送，更优选当超过99%的剂量被输送时实现的。在一个实施例中，到雾化发生器的开口漏斗足够大，使得输送到雾化发生器的液体全部输送。为了接受这些剂量，病人可能需要做几次吸入或者一次吸入，这取决于输送到网格的量和病人的肺活量。每次吸入需要做深呼吸来保证气雾到达肺的深处。
不含防腐剂的胰岛素制剂是特别有用的，因为它们接触到振动膜时不会大量的发泡。反过来，这允许制剂被迅速雾化。关键的特征在于，一定剂量的制剂需要被迅速雾化，使用户可以在很短的时间内吸入胰岛素。在大多数情况下，希望限制服用制剂所需的吸入次数。根据用户的吸入能力，希望以约1至3次呼吸服用整个剂量。典型的剂量的范围从约40μL至200μL左右。
足够快地雾化这些量，以允许它们在几次呼吸中被吸入，是本发明的关键特征。希望在少于约22秒、更优选地少于约15秒，雾化这些量，从而允许他们将在1至3次呼吸中被吸入。
图3和图4的图表显示了本发明的胰岛素制剂如何提供了这个关键的特征，同时市场上的胰岛素制剂无法在可接受的时间范围内进行雾化。如图所示，优泌林（Humalin）、来得时（Lantus）和优泌乐（Humalog）制剂雾化100μL的胰岛素制剂花了超过30秒的时间。这是因为这些制剂存在大量的发泡，阻止了制剂从振动膜的前端面作为液滴喷射出。进一步，对于Lantus的制剂，在测试结束时剩余6.9μL。优选地，基本上所有的液体都被雾化，并且典型地剩余少于大约3μL，其对应的雾化效率最少为97%。
与包含防腐剂的胰岛素制剂对比，本发明的胰岛素制剂（浓度为200IU、400IU和800IU，分别对应于示例3、示例2、示例1）在约10秒钟内均被雾化。剩余的制剂不到3μL，超过97%的制剂都被雾化。由于在10秒左右雾化这个剂量，大多数人，包括儿童，都能够在约1到3次呼吸中吸入全部剂量。本发明的胰岛素制剂能够以与水和盐溶液基本上以相同的速率雾化。
发泡的一个重要的原因是由于在制剂中使用的防腐剂。例如，许多制剂中含有2.5-3.15毫克/毫升的防腐剂间甲酚。然而，图4发现这种添加剂对发泡没有影响。因此，去除这种防腐剂会大幅消除发泡和显著增加雾化倍率。
作为一个具体的例子，每毫升HUMALOG含有100IU赖脯，16毫克甘油，1.88毫克磷酸氢二钠，3.15毫克元间甲酚，氧化锌含量调节到提供0.0197毫克锌离子，微量苯酚和注射用水。赖脯胰岛素的pH值为7.0-7.8，并且盐酸（10%）和/或氢氧化钠（10%）可以被添加来调节pH值。
作为另一个例子，LANTUS包括溶解在透明的含水流体中的甘精胰岛素。每毫升LANTUS（甘精胰岛素注射液）含有100IU（3.6378毫克）甘精胰岛素。对于10ml小玻璃容器，非活性成分为30微克锌、2.7毫克间甲苯酚、20毫克85%甘油、20微克聚山梨醇酯20和注射用水。对于3毫升容器，非活性成分为30微克锌、2.7毫克间甲苯酚、20毫克85%甘油和注射用水。通过添加盐酸和氢氧化钠的水溶液来调节pH值。LANTUS的pH值约为4。
此外，每毫升Humulin含有500IU的人胰岛素、16毫克甘油，2.5毫克间甲苯酚作为防腐剂，以及计算补充内源性锌的氧化锌，以获得总锌含量为0.017毫克/100单位。可在制造过程中添加氢氧化钠和/或盐酸，来调节pH值。
作为另一个例子，Humalin R制剂是100IU重组人胰岛素，16毫克（174mM）甘油、2.5毫克间甲酚（22.7mM，0.25%），HCl和氢氧化钠。
最后，Novolin R制剂是100IU重组人胰岛素、甘油、间甲酚、HCl和氢氧化钠。
其他含有防腐剂的制剂，在美国专利NO.6,489,292和6,211,144中描述，通过引用并入本文。这些防腐剂可以包括苯酚、间甲酚、氯甲酚、麝香草酚及其混合物。一些类似的非苯酚的防腐剂，包括双环或三环脂肪醇和嘌呤，如双环脂肪醇，包括单醇类，例如异松蒎醇、2,3-蒎烷二醇（pinandiol）、桃金娘醇（myrtanol），冰片、降冰片（norborneol）或葑醇、三环脂肪醇、1-金刚烷醇和嘌呤，如腺嘌呤、鸟嘌呤或次黄嘌呤等。如这些专利中所述，这些防腐剂确保胰岛素的稳定。然而，在这些专利中所描述的包含在制剂中的防腐剂会导致制剂在面临振动的孔板时发泡，显著增加雾化时间。
本发明的制剂不含有防腐剂或稳定剂。这样，很少或根本没有泡沫出现，使几乎所有的气雾发生器迅速雾化制剂。
一些胰岛素制剂还包括表面活性剂或洗涤剂。这些也可以导致在存在振动的孔板或网格时产生泡沫。本发明的制剂也避免使用这种表面活性剂或洗涤剂。
尽管本发明的制剂没有使用防腐剂，制剂的完整性仍然可以通过适当的包装和保质期的管理来保证。这样，制剂可以不含防腐剂，但商业上是可行的。
图5示出当以每100IU（1毫升）加入20μL 乙二醇添加到示例1-3的制剂时发生了什么。然后将这些与图4的Humalin、Lantus和Humalog，盐水和水的例子对比。如图所示，乙二醇的加入基本上对示例1-3的雾化时间没有影响，从而确定乙二醇没有促进发泡，如前所述发泡主要是防腐剂造成的。
为了清楚和理解，现在已经详细描述了本发明。但可以理解，在附属的权利要求的范围内可以进行某些修改和变化。

Claims (17)

1.一种具体地用于雾化的胰岛素制剂，所述制剂包括：
大量的水；
少量的胰岛素；
少量的HCL；以及
少量的NaOH；
其特征在于，
对于每个胰岛素六聚体具有2到4个Zn2+，并且所述制剂不含防腐剂，以允许使用具有多个孔的圆顶形振动孔板使所述制剂雾化，而所述胰岛素制剂没有大量发泡，并且，当所述制剂保持在所述孔板的后表面上时，产生喷雾而所述制剂没有产生大量发泡，仅通过所述孔板的振动，所述喷雾从所述孔板的前表面喷出，使用环绕所述孔的环形可振动元件使得所述孔板振动。
2.如权利要求1所述的胰岛素制剂，其中所述胰岛素具有100IU/ml到1200IU/ml的人胰岛素浓度。
3.如权利要求2所述的胰岛素制剂，其中所述水的体积量为99.8％到97.0％，以及所述人胰岛素的体积量为0.2％到3.0％。
4.如权利要求1所述的胰岛素制剂，其中所述制剂不包括间甲酚、甲酚或者苯酚。
5.如权利要求1至4中任一项所述的胰岛素制剂，其中，
所述孔板以从50kHz到150kHz的范围内的频率振动，以在小于22秒的时间内雾化达到200μL范围内的97％的胰岛素制剂。
6.一种雾化胰岛素制剂的方法，所述方法包括：
提供胰岛素制剂，所述胰岛素制剂包括大量的水，以及少量的胰岛素、HCl和NaOH，其特征在于，
供给从40μL到200μL的范围内的量的胰岛素制剂到具有多个孔的孔板的后侧，在位于所述后侧上时所述量的胰岛素制剂被储存，其中所述孔板的几何形状是圆顶形的，并且，所述孔板通过环绕所述孔的环形压电元件而振动；
当所述量的胰岛素制剂在所述后侧时利用所述环形压电元件振动所述孔板，其中振动使供给的胰岛素作为雾化的喷雾从所述孔板的前侧喷出，而所述胰岛素制剂没有大量发泡。
7.如权利要求6所述的方法，其中至少97％的制剂被喷出。
8.如权利要求7所述的方法，其中所述胰岛素制剂的体积量最大达到100μL，并且其中雾化97％的制剂的时间小于11秒。
9.如权利要求6所述的方法，还包括以小于2μm的振幅振动所述孔板。
10.如权利要求6所述的方法，其中所述雾化的喷雾包括平均尺寸在3μm到8μm的范围内的雾化液滴。
11.如权利要求6所述的方法，其中在振动所述孔板时，小于3％的所述制剂转化为泡沫。
12.如权利要求6所述的方法，其中所述胰岛素具有100IU/ml到1200IU/ml的人胰岛素浓度。
13.如权利要求6所述的方法，其中所述孔板具有尺寸范围从3μm至8μm的孔，并且以从50kHz至150kHz的范围内的频率振动。
14.一种雾化系统，包括：
吸入器(100)，所述吸入器包括限定喷口(105)的外壳和设置在所述外壳中的气雾发生器(108)，其特征在于，所述气雾发生器(108)包括具有前表面、后表面和多个孔的可振动膜(109)和用于使所述可振动膜(109)振动的可振动元件；其中，所述前表面暴露于大气中，所述膜的几何形状是圆顶形的，并且所述可振动元件的几何形状是环形的并且环绕所述孔；
容器，所述容器容纳一定量的胰岛素制剂，所述制剂包括大量的水、少量的胰岛素、少量的HCL；以及少量的NaOH，
其中所述制剂不含防腐剂，使得所述制剂可以使用振动孔板进行雾化，而所述制剂没有大量发泡，并且所述一定量的胰岛素被供给至所述后表面，所述胰岛素保持在所述后表面上，直到仅通过所述孔板的振动而雾化，其中，所述容器配置成分配测定量的胰岛素制剂，并且所述测定量的胰岛素制剂在40μL到200μL的范围内，其中所述膜的直径为5mm至8mm，使得所述测定量的胰岛素制剂保持在所述后表面上直到雾化。
15.如权利要求14所述的系统，其中所述胰岛素具有100IU/ml到1200IU/ml的人胰岛素浓度。
16.如权利要求15所述的系统，其中所述孔板具有孔，所述孔板的孔的尺寸范围从3μm到8μm。
17.如权利要求15所述的系统，其中所述可振动膜被构造成以小于2μm的振幅振动。
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Families Citing this family (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8109266B2 (en) 2004-02-20 2012-02-07 Pneumoflex Systems, Llc Nebulizer having flow meter function
US9022027B2 (en) 2004-02-20 2015-05-05 Pneumoflex Systems, Llc Nebulizer with intra-oral vibrating mesh
US10842951B2 (en) 2010-01-12 2020-11-24 Aerami Therapeutics, Inc. Liquid insulin formulations and methods relating thereto
US20130269684A1 (en) 2012-04-16 2013-10-17 Dance Pharmaceuticals, Inc. Methods and systems for supplying aerosolization devices with liquid medicaments
US8950394B2 (en) 2010-01-12 2015-02-10 Dance Biopharm Inc. Preservative-free single dose inhaler systems
US9545488B2 (en) 2010-01-12 2017-01-17 Dance Biopharm Inc. Preservative-free single dose inhaler systems
US10154923B2 (en) 2010-07-15 2018-12-18 Eyenovia, Inc. Drop generating device
EP2665557B1 (en) 2011-01-21 2020-01-01 Biodot, Inc. Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube
US9532597B2 (en) 2012-02-22 2017-01-03 Altria Client Services Llc Electronic smoking article
US8984650B2 (en) 2012-10-19 2015-03-17 Pearson Education, Inc. Privacy server for protecting personally identifiable information
EP2735328A1 (en) * 2012-11-27 2014-05-28 PARI Pharma GmbH Fluid reservoir for an aerosol generation device, combination of fluid reservoir and primary fluid package, and aerosol generation device for use with the fluid reservoir
US10130288B2 (en) 2013-03-14 2018-11-20 Cell and Molecular Tissue Engineering, LLC Coated sensors, and corresponding systems and methods
US10405961B2 (en) 2013-03-14 2019-09-10 Cell and Molecular Tissue Engineering, LLC Coated surgical mesh, and corresponding systems and methods
AU2014253997B2 (en) * 2013-04-16 2019-01-03 Aerami Therapeutics, Inc. Liquid dispensing and methods for dispensing liquids
EP2986268B1 (en) * 2013-04-16 2019-05-22 Dance Biopharm Inc. Liquid dispensing
WO2014179083A1 (en) * 2013-05-02 2014-11-06 Pneumoflex Systems, Llc Nebulizer with intra-oral vibrating mesh
US11471618B2 (en) 2014-11-09 2022-10-18 Sipnose Ltd. Adjustable dosing delivery and multi sectioned drug compartment
US11278682B2 (en) 2014-11-09 2022-03-22 Sipnose Ltd. Device and method for aerosolized delivery of substance to a natural orifice of the body
US11116914B2 (en) 2014-11-09 2021-09-14 Sipnose Ltd. Device and method for aerosolized delivering of substance to a natural orifice of the body
DE202013105715U1 (de) * 2013-08-22 2014-02-19 Sipnose Ltd. Vorrichtung zur Abgabe einer vorbestimmten Menge einer Substanz an eine natürliche Öffnung des Körpers
US11992604B2 (en) 2014-11-09 2024-05-28 Sipnose Ltd. Devices and methods for delivering a substance to a body cavity
EP2910268A1 (en) * 2014-02-25 2015-08-26 PARI Pharma GmbH Inhalator and inhalator set
US10307550B2 (en) 2014-06-09 2019-06-04 Dance Biopharm Inc. Liquid drug cartridges and associated dispenser
USD765831S1 (en) * 2014-06-17 2016-09-06 Koninklijke Philips N.V. Mouthpiece for handheld respiratory device
US10471222B2 (en) * 2014-07-01 2019-11-12 Dance Biopharm Inc. Aerosolization system with flow restrictor and feedback device
US11273271B2 (en) 2014-07-01 2022-03-15 Aerami Therapeutics, Inc. Aerosolization system with flow restrictor and feedback device
US10857313B2 (en) * 2014-07-01 2020-12-08 Aerami Therapeutics, Inc. Liquid nebulization systems and methods
CN106999681B (zh) * 2014-08-28 2021-02-02 诺顿（沃特福特）有限公司 吸入器的依从性辅助模块
WO2016137569A1 (en) * 2015-02-25 2016-09-01 Dance Biopharm, Inc. Liquid insulin formulations and methods relating thereto
EP3253433A4 (en) * 2015-04-10 2018-08-22 Kedalion Therapeutics, Inc. Piezoelectric dispenser with replaceable ampoule
US10455863B2 (en) 2016-03-03 2019-10-29 Altria Client Services Llc Cartridge for electronic vaping device
US10433580B2 (en) 2016-03-03 2019-10-08 Altria Client Services Llc Methods to add menthol, botanic materials, and/or non-botanic materials to a cartridge, and/or an electronic vaping device including the cartridge
US10368580B2 (en) 2016-03-08 2019-08-06 Altria Client Services Llc Combined cartridge for electronic vaping device
US10368581B2 (en) 2016-03-11 2019-08-06 Altria Client Services Llc Multiple dispersion generator e-vaping device
US10357060B2 (en) 2016-03-11 2019-07-23 Altria Client Services Llc E-vaping device cartridge holder
EP3448466A1 (en) 2016-04-25 2019-03-06 Koska Family Ltd. Medical delivery system
KR20190092517A (ko) * 2016-12-09 2019-08-07 마이크로도스 테라퓨특스, 인코포레이티드 흡입기
WO2018172293A1 (en) * 2017-03-20 2018-09-27 Vectura Delivery Devices Limited Container for cleaning the membrane of a nebulizer
JP7227163B2 (ja) 2017-06-10 2023-02-21 アイノビア，インコーポレイティド 流体を取扱い、目に流体を送出するための方法および装置
JP7219757B2 (ja) 2017-08-30 2023-02-08 ノボ・ノルデイスク・エー／エス 保存剤を有する流れ連通ユニット
WO2019042801A1 (en) 2017-08-30 2019-03-07 Novo Nordisk A/S MULTI-PURPOSE DRUG DELIVERY DEVICE FOR MEDICAMENTS WITH LESS PRESERVATIVES
DE102017124742A1 (de) * 2017-10-23 2019-04-25 Nebu-Tec Med. Produkte Eike Kern Gmbh Automatische Medikamentendosierung bei Verneblern
EP3710086A4 (en) 2017-11-17 2021-11-17 Koska Family Limited SYSTEMS AND PROCESSES FOR FLUID DISPENSERS
CN108080203B (zh) * 2018-02-01 2023-10-27 佛山市顺德区雅洛特电器有限公司 一种超声雾化精油器
JP7434361B2 (ja) * 2019-05-07 2024-02-20 キンデーバ ドラッグ デリバリー リミティド パートナーシップ 警告システム、吸入器及び警告生成方法
EP3993774A1 (en) 2019-07-03 2022-05-11 Aerami Therapeutics, Inc. Exenatide compositions for pulmonary administration and use thereof
US20220265940A1 (en) 2019-08-02 2022-08-25 Stamford Devices Limited Buccal administration of aerosol
EP4265287A4 (en) * 2020-12-18 2024-08-28 Shenzhen Smoore Technology Ltd ELECTRONIC NEBULIZATION DEVICE
USD992110S1 (en) 2021-08-10 2023-07-11 Koska Family Limited Sealed fluid container

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5915378A (en) * 1993-01-29 1999-06-29 Aradigm Corporation Creating an aerosolized formulation of insulin
US6312665B1 (en) * 1998-12-21 2001-11-06 Generex Pharmaceuticals Incorporated Aerosol formulations for buccal and pulmonary application
CN2461580Y (zh) * 2001-02-09 2001-11-28 鲁崇恭 超声波雾化胰岛素吸入装置

Family Cites Families (175)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1947310A (en) 1933-04-07 1934-02-13 Warren M Sample Liquid dispenser
US2463922A (en) 1946-02-15 1949-03-08 William E Turner Liquid dispenser with receptacle operated outlet valve
GB1383761A (en) 1971-02-25 1974-02-12 Woodcraft Dc Inhalation device for use with an aerosol container
US3874380A (en) 1974-05-28 1975-04-01 Smithkline Corp Dual nozzle intranasal delivery device
US4771769A (en) 1982-12-20 1988-09-20 Schering Corporation Hand held metered spray dispenser
US4564129A (en) 1983-01-27 1986-01-14 Hoechst-Roussel Pharmaceuticals Inc. Dosage dispensing unit
DE3339180C2 (de) 1983-10-28 1993-10-14 Pfeiffer Erich Gmbh & Co Kg Austragvorrichtung für Medien
DE3734306A1 (de) 1987-10-10 1989-04-27 Pfeiffer Erich Gmbh & Co Kg Austragvorrichtung fuer fliessfaehige medien
US5152456A (en) * 1989-12-12 1992-10-06 Bespak, Plc Dispensing apparatus having a perforate outlet member and a vibrating device
US5060642A (en) 1990-01-05 1991-10-29 Gilman Thomas H Wound dressing with air permeable bacteria impermeable reservoir
GB9015077D0 (en) 1990-07-09 1990-08-29 Riker Laboratories Inc Inhaler
GB9026191D0 (en) 1990-12-01 1991-01-16 Harris Pharma Ltd Breath actuated dispensing device
WO1992011050A1 (en) 1990-12-17 1992-07-09 Minnesota Mining And Manufacturing Company Inhaler
US6540154B1 (en) 1991-04-24 2003-04-01 Aerogen, Inc. Systems and methods for controlling fluid feed to an aerosol generator
US6629646B1 (en) 1991-04-24 2003-10-07 Aerogen, Inc. Droplet ejector with oscillating tapered aperture
US5938117A (en) 1991-04-24 1999-08-17 Aerogen, Inc. Methods and apparatus for dispensing liquids as an atomized spray
US5164740A (en) 1991-04-24 1992-11-17 Yehuda Ivri High frequency printing mechanism
US7628339B2 (en) 1991-04-24 2009-12-08 Novartis Pharma Ag Systems and methods for controlling fluid feed to an aerosol generator
US5363842A (en) 1991-12-20 1994-11-15 Circadian, Inc. Intelligent inhaler providing feedback to both patient and medical professional
US5333106A (en) 1992-10-09 1994-07-26 Circadian, Inc. Apparatus and visual display method for training in the power use of aerosol pharmaceutical inhalers
GB2272389B (en) 1992-11-04 1996-07-24 Bespak Plc Dispensing apparatus
US5888477A (en) 1993-01-29 1999-03-30 Aradigm Corporation Use of monomeric insulin as a means for improving the bioavailability of inhaled insulin
US6131567A (en) 1993-01-29 2000-10-17 Aradigm Corporation Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US5672581A (en) 1993-01-29 1997-09-30 Aradigm Corporation Method of administration of insulin
US6024090A (en) 1993-01-29 2000-02-15 Aradigm Corporation Method of treating a diabetic patient by aerosolized administration of insulin lispro
US5743250A (en) 1993-01-29 1998-04-28 Aradigm Corporation Insulin delivery enhanced by coached breathing
US5364838A (en) 1993-01-29 1994-11-15 Miris Medical Corporation Method of administration of insulin
US5694919A (en) 1993-01-29 1997-12-09 Aradigm Corporation Lockout device for controlled release of drug from patient-activated dispenser
US7448375B2 (en) 1993-01-29 2008-11-11 Aradigm Corporation Method of treating diabetes mellitus in a patient
CH686872A5 (de) * 1993-08-09 1996-07-31 Disetronic Ag Medizinisches Inhalationsgeraet.
US5479920A (en) 1994-03-01 1996-01-02 Vortran Medical Technology, Inc. Breath actuated medicinal aerosol delivery apparatus
RU2175556C2 (ru) * 1994-03-07 2001-11-10 Инхейл Терапьютик Системз Способы и композиции для легочной доставки инсулина
KR100419037B1 (ko) 1994-03-07 2004-06-12 넥타르 테라퓨틱스 폐를통한인슐린의전달방법및그조성물
US5385180A (en) 1994-06-09 1995-01-31 Empak, Inc. Liquid saver funnel system
US6014970A (en) 1998-06-11 2000-01-18 Aerogen, Inc. Methods and apparatus for storing chemical compounds in a portable inhaler
US5758637A (en) 1995-08-31 1998-06-02 Aerogen, Inc. Liquid dispensing apparatus and methods
US6427682B1 (en) 1995-04-05 2002-08-06 Aerogen, Inc. Methods and apparatus for aerosolizing a substance
US5586550A (en) 1995-08-31 1996-12-24 Fluid Propulsion Technologies, Inc. Apparatus and methods for the delivery of therapeutic liquids to the respiratory system
US6085740A (en) 1996-02-21 2000-07-11 Aerogen, Inc. Liquid dispensing apparatus and methods
US6782886B2 (en) * 1995-04-05 2004-08-31 Aerogen, Inc. Metering pumps for an aerosolizer
US6205999B1 (en) 1995-04-05 2001-03-27 Aerogen, Inc. Methods and apparatus for storing chemical compounds in a portable inhaler
US5809997A (en) 1995-05-18 1998-09-22 Medtrac Technologies, Inc. Electronic medication chronolog device
US5823179A (en) * 1996-02-13 1998-10-20 1263152 Ontario Inc. Nebulizer apparatus and method
US5915376A (en) * 1996-02-20 1999-06-29 Mclean; Vincent C. Evacuated solar collector
AU4959897A (en) 1996-11-18 1998-06-10 Pbt International Limited An inkjet cartridge refill device
US6712762B1 (en) 1997-02-28 2004-03-30 Ors Diagnostic, Llc Personal computer card for collection of real-time biological data
US20060239930A1 (en) 1997-08-04 2006-10-26 Herbert Lamche Process for nebulizing aqueous compositions containing highly concentrated insulin
DE19819748A1 (de) 1998-05-02 1999-11-04 Pfeiffer Erich Gmbh & Co Kg Spender für Medien
US6440929B1 (en) * 1998-07-27 2002-08-27 Emisphere Technologies, Inc. Pulmonary delivery of active agents
GB9820937D0 (en) 1998-09-26 1998-11-18 Glaxo Group Ltd Inhalation device
US6234167B1 (en) 1998-10-14 2001-05-22 Chrysalis Technologies, Incorporated Aerosol generator and methods of making and using an aerosol generator
US6635617B1 (en) 1998-10-16 2003-10-21 Novo Nordisk A/S Insulin preparations for pulmonary delivery containing menthol
US6211144B1 (en) 1998-10-16 2001-04-03 Novo Nordisk A/S Stable concentrated insulin preparations for pulmonary delivery
US6489292B1 (en) 1998-11-18 2002-12-03 Novo Nordisk A/S Stable aqueous insulin preparations without phenol and cresol
DE69914934T2 (de) 1998-11-18 2005-01-05 Novo Nordisk A/S Stabile, wässrige insulin-präparate ohne phenol und cresol
US6164498A (en) 1999-09-01 2000-12-26 Mcneil-Ppc. Inc. Pump dispenser
US6235177B1 (en) 1999-09-09 2001-05-22 Aerogen, Inc. Method for the construction of an aperture plate for dispensing liquid droplets
EP1217942A1 (en) 1999-09-24 2002-07-03 Healthetech, Inc. Physiological monitor and associated computation, display and communication unit
JP2003511760A (ja) 1999-10-01 2003-03-25 グラクソ グループ リミテッド 患者データ監視システム
CN2406684Y (zh) * 1999-11-26 2000-11-22 北京亚都科技股份有限公司 医用雾化器
GB0003197D0 (en) 2000-02-11 2000-04-05 Aid Medic Ltd Improvements in and relating to controlling drug delivery
GB2360219A (en) 2000-03-18 2001-09-19 Astrazeneca Uk Ltd Inhaler
US7100600B2 (en) 2001-03-20 2006-09-05 Aerogen, Inc. Fluid filled ampoules and methods for their use in aerosolizers
US7600511B2 (en) 2001-11-01 2009-10-13 Novartis Pharma Ag Apparatus and methods for delivery of medicament to a respiratory system
US6948491B2 (en) 2001-03-20 2005-09-27 Aerogen, Inc. Convertible fluid feed system with comformable reservoir and methods
US6626171B2 (en) * 2000-05-12 2003-09-30 Iep Pharmaceutical Devices Inc. Powder/liquid metering valve
JP4147234B2 (ja) 2004-09-27 2008-09-10 キヤノン株式会社 吐出用液体、吐出方法、カートリッジ及び吐出装置
GB2368061B (en) 2000-10-20 2005-05-11 Gw Pharmaceuticals Ltd Dose dispensing apparatus
US6546927B2 (en) * 2001-03-13 2003-04-15 Aerogen, Inc. Methods and apparatus for controlling piezoelectric vibration
AU2002336246B8 (en) 2001-03-15 2006-02-02 Creare Incorporated Nebulizer having cooling chamber
US6732944B2 (en) 2001-05-02 2004-05-11 Aerogen, Inc. Base isolated nebulizing device and methods
JP4812190B2 (ja) * 2001-06-20 2011-11-09 オリンパス株式会社 画像ファイル装置
CA2456203A1 (en) 2001-08-13 2003-02-27 Novo Nordisk A/S Portable device and method of communicating medical data information
US20080177154A1 (en) 2001-08-13 2008-07-24 Novo Nordisk A/S Portable Device and Method Of Communicating Medical Data Information
PT1446172E (pt) 2001-09-06 2010-05-06 Microdose Therapeutx Inc Inalador do tipo dpi
US20080148193A1 (en) 2001-09-13 2008-06-19 John Moetteli System and method of efficient web browsing
US20030068361A1 (en) 2001-10-09 2003-04-10 Rimona Margalit Liposome-encapsulated insulin formulations
US6684880B2 (en) 2001-12-04 2004-02-03 Hewlett-Packard Development Company, L.P. Applicator for dispensing bioactive compositions and methods for using the same
WO2003051424A2 (en) 2001-12-17 2003-06-26 Mcfarland Joseph L Jr Portable, handheld, pneumatic driven medicinal nebulizer
AU2003202925B2 (en) 2002-01-07 2008-12-18 Aerogen, Inc. Devices and methods for nebulizing fluids for inhalation
ES2603067T3 (es) * 2002-01-15 2017-02-23 Novartis Ag Métodos y sistemas para hacer funcionar un generador de aerosol
FR2835435B1 (fr) * 2002-02-01 2004-04-23 Diffusion Tech Francaise Sarl Dispositif de protection du circuit sonique d'un generateur d'aerosol therapeutique
AU2003236201A1 (en) 2002-05-07 2003-11-11 Novo Nordisk A/S Soluble formulations comprising monomeric insulin and acylated insulin
US20040045546A1 (en) * 2002-09-05 2004-03-11 Peirce Management, Llc Pharmaceutical delivery system for oral inhalation through nebulization consisting of inert substrate impregnated with substance (S) to be solubilized or suspended prior to use
GB0222295D0 (en) 2002-09-25 2002-10-30 3M Innovative Properties Co Breath actuated medicament dispensing devices
US7204248B2 (en) 2002-09-27 2007-04-17 Cook Critical Care Incorporated Fiberoptic nebulizer
US20040100509A1 (en) 2002-11-27 2004-05-27 Microsoft Corporation Web page partitioning, reformatting and navigation
US7683029B2 (en) * 2003-05-07 2010-03-23 Philip Morris Usa Inc. Liquid aerosol formulations containing insulin and aerosol generating devices and methods for generating aerosolized insulin
US7600512B2 (en) 2003-07-14 2009-10-13 Vortran Medical Technology 1, Inc. Inhaler with breath actuated dose counter
US8616195B2 (en) 2003-07-18 2013-12-31 Novartis Ag Nebuliser for the production of aerosolized medication
US20050030953A1 (en) 2003-08-04 2005-02-10 Subramanian Vasudevan Method of controlling reverse link transmission
US20050172958A1 (en) 2003-08-20 2005-08-11 The Brigham And Women's Hospital, Inc. Inhalation device and system for the remote monitoring of drug administration
US20050133024A1 (en) 2003-11-25 2005-06-23 Coifman Robert E. Devices for measuring inspiratory airflow
WO2005065756A2 (en) 2003-12-30 2005-07-21 Oriel Therapeutics, Inc. Dry powder nebulizers and associated methods of dispensing dry powders
US7380550B2 (en) 2004-01-30 2008-06-03 Hewlett-Packard Development Company, L.P. Systems and methods for particle detection
US7819115B2 (en) 2004-01-30 2010-10-26 Hewlett-Packard Development Company, L.P. Inhalers and methods of controlling airflow in inhalers
US7712466B2 (en) 2004-02-20 2010-05-11 Pneumoflex Systems, Llc Intra-oral nebulizer
US7063112B2 (en) * 2004-03-17 2006-06-20 Husky Corporation Fuel dispensing nozzle having a dripless spout
EP1737517B1 (en) 2004-04-02 2010-10-06 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services Aerosol delivery systems
GB0408836D0 (en) 2004-04-21 2004-05-26 Univ Hull A system
EP1824541A4 (en) 2004-10-22 2009-11-04 Multi Vet Ltd MOBILE ELECTRONIC DEVICE WITH LIQUID DISPENSING SYSTEM
WO2006062449A1 (en) 2004-12-10 2006-06-15 Ernst Hörlins Ingenjörsbyra AB Breath actuated dose inhaler
FR2879574B1 (fr) 2004-12-17 2011-01-21 Valois Sas Dispositif de distribution de produit fluide.
EP1848541A4 (en) * 2005-02-07 2013-01-16 Pharmalight Inc METHOD AND DEVICE FOR OPHTHALMIC DELIVERY OF PHARMACEUTICALLY ACTIVE INGREDIENTS
US7219664B2 (en) 2005-04-28 2007-05-22 Kos Life Sciences, Inc. Breath actuated inhaler
WO2007035913A2 (en) 2005-09-21 2007-03-29 Kurve Technology, Inc. Medicament delivery control, monitoring, and reporting system and method
FR2892158B1 (fr) 2005-10-17 2011-10-21 Valois Sas Pompe de distribution de produit fluide
JP2009512709A (ja) 2005-10-20 2009-03-26 エムディーアールエヌエー，インコーポレイテッド 速効型インスリンの経鼻投与
DE102005052898A1 (de) 2005-11-03 2007-05-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren und Vorrichtung zum Dosieren von Arzneimitteln
DE102005056488A1 (de) * 2005-11-21 2007-05-24 Ing. Erich Pfeiffer Gmbh Spender und Dosierbaugruppe für die Mediumdosierung
SG166814A1 (en) 2005-11-21 2010-12-29 Mannkind Corp Powder dispensing and sensing apparatus and methods
CN101389650B (zh) 2005-12-28 2012-10-10 诺沃-诺迪斯克有限公司 包含酰化胰岛素和锌的组合物以及制备所述组合物的方法
JP2009530243A (ja) * 2006-03-13 2009-08-27 ノボ・ノルデイスク・エー／エス アシル化単鎖インスリン
JP5004483B2 (ja) * 2006-03-15 2012-08-22 株式会社Ａｄｅｋａ プリプレグ用エポキシ樹脂硬化性組成物
WO2007116953A1 (en) 2006-04-10 2007-10-18 Canon Kabushiki Kaisha Ingesta administration device
GB0610666D0 (en) * 2006-05-30 2006-07-05 Glaxo Group Ltd Fluid dispenser
DE102006026786A1 (de) 2006-06-07 2007-12-13 Joachim Kern Dosierinhalator
US9208500B2 (en) 2006-07-21 2015-12-08 Microsoft Technology Licensing, Llc Fixed position multi-state interactive advertisement
CN101495168A (zh) 2006-08-01 2009-07-29 佳能株式会社 药物喷射设备
JP5207679B2 (ja) 2006-08-01 2013-06-12 キヤノン株式会社 薬剤吐出装置
US20100180890A1 (en) * 2006-09-29 2010-07-22 Canon Kabushiki Kaisha Inhaler
US20080306794A1 (en) 2006-11-27 2008-12-11 Ooggieya Ltd. Measurement of content placement effectiveness over web pages and like media
US8342172B2 (en) 2007-02-05 2013-01-01 The Brigham And Women's Hospital, Inc. Instrumented metered-dose inhaler and methods for predicting disease exacerbations
US20090301472A1 (en) * 2007-02-08 2009-12-10 Kim Matthew H J Aerosol delivery systems and methods
WO2008103649A2 (en) 2007-02-20 2008-08-28 Conagra Foods Rdm, Inc. Food dispensing apparatus
US7904062B2 (en) 2007-03-08 2011-03-08 Yahoo! Inc. Scrolling mobile advertisements
US20090241948A1 (en) * 2007-03-28 2009-10-01 Dermot Joseph Clancy Humidification in breathing circuits
CN103418062B (zh) 2007-03-30 2017-04-12 菲利普莫里斯生产公司 用于输送药剂的装置和方法
EP2514412A1 (en) 2007-04-30 2012-10-24 Novo Nordisk A/S Highly Concentrated Insulin Solutions and Compositions
US8261738B2 (en) * 2007-07-24 2012-09-11 Respironics Respiratory Drug Delivery (Uk) Ltd. Apparatus and method for maintaining consistency for aerosol drug delivery treatments
US20090151716A1 (en) 2007-09-18 2009-06-18 Robert Abrams Semi-automatic emergency medication dose nebulizer
CA2702261A1 (en) 2007-10-12 2009-04-16 Map Pharmaceuticals, Inc. Inhalation drug delivery
US20090156952A1 (en) 2007-12-13 2009-06-18 Hunter C Eric Apparatuses and Methods for Diagnosing and Treating Respiratory Conditions
US20090151718A1 (en) 2007-12-13 2009-06-18 Next Safety, Inc. Apparatuses and Methods for Diagnosing and Treating Respiratory Conditions
US9550031B2 (en) 2008-02-01 2017-01-24 Reciprocal Labs Corporation Device and method to monitor, track, map, and analyze usage of metered-dose inhalers in real-time
WO2009111612A1 (en) 2008-03-07 2009-09-11 Novartis Ag Aerosolization device
TWI394580B (zh) 2008-04-28 2013-05-01 Halozyme Inc 超快起作用胰島素組成物
JP2009268665A (ja) * 2008-05-07 2009-11-19 Canon Inc 吸入装置
CN102131540B (zh) 2008-07-10 2015-04-22 邦及奥卢夫森美迪康股份公司 吸入器及操作其的方法
DE102008054431B3 (de) * 2008-12-09 2010-06-17 Pari Pharma Gmbh Aerosoltherapievorrichtung
US8356247B2 (en) 2008-12-16 2013-01-15 Rich Media Worldwide, Llc Content rendering control system and method
JP5180109B2 (ja) 2009-01-26 2013-04-10 株式会社エヌ・ティ・ティ・ドコモ 移動通信方法及び無線基地局
US8736227B2 (en) 2009-02-27 2014-05-27 Fairchild Semiconductor Corporation Peripheral device host charging
US9163883B2 (en) 2009-03-06 2015-10-20 Kevlin Thermal Technologies, Inc. Flexible thermal ground plane and manufacturing the same
NZ575836A (en) 2009-03-27 2009-08-28 Nexus6 Ltd Improvements in or Relating to Medicament Delivery Systems
US7886783B2 (en) 2009-05-22 2011-02-15 The General Electric Company Anesthetic vaporizer filling system
CN102459564B (zh) 2009-06-04 2018-10-02 通用医疗公司 生物人工肺
US8495998B2 (en) 2009-06-17 2013-07-30 British American Tobacco (Investments) Limited Inhaler
US9395827B2 (en) 2009-07-21 2016-07-19 Qualcomm Incorporated System for detecting orientation of magnetically coupled devices
US20130269684A1 (en) 2012-04-16 2013-10-17 Dance Pharmaceuticals, Inc. Methods and systems for supplying aerosolization devices with liquid medicaments
US8950394B2 (en) 2010-01-12 2015-02-10 Dance Biopharm Inc. Preservative-free single dose inhaler systems
US9545488B2 (en) 2010-01-12 2017-01-17 Dance Biopharm Inc. Preservative-free single dose inhaler systems
CN102802710B (zh) 2010-01-14 2015-11-25 皇家飞利浦电子股份有限公司 利用负压支持的伺服通气
US20120285236A1 (en) 2010-01-20 2012-11-15 Koninklijke Philips Electronics, N.V. Method of using a temperature-based aerosol detector
US20110225008A1 (en) 2010-03-09 2011-09-15 Respira Dv, Llc Self-Similar Medical Communications System
WO2011112982A2 (en) 2010-03-12 2011-09-15 Kocks Peter F Systems and methods for organizing and displaying electronic media content
US20130172690A1 (en) 2010-04-11 2013-07-04 Proteus Digital Health, Inc. Apparatus, system and method for detection and delivery of a medicinal dose
WO2011130583A2 (en) 2010-04-15 2011-10-20 Spectrum Health Innovations, LLC Inhaler module and related system
KR20120013727A (ko) 2010-08-06 2012-02-15 삼성전자주식회사 디스플레이장치 및 그 제어방법
EP2608613A1 (en) 2010-08-17 2013-06-26 Fujitsu Limited Method, system and transmitter for allocating resources
WO2012048320A2 (en) 2010-10-08 2012-04-12 Myspace, Inc. Hd website skin
TW201219010A (en) 2010-11-05 2012-05-16 Univ Nat Cheng Kung Portable asthma detection device and stand-alone portable asthma detection device
JP5487093B2 (ja) 2010-12-17 2014-05-07 三菱航空機株式会社 耐雷ファスナ、耐雷ファスナの取付構造、航空機
US9451386B2 (en) 2011-07-12 2016-09-20 Intel Corporation Resource scheduling for machine-to-machine devices
US8326964B1 (en) 2011-11-14 2012-12-04 Limelight Networks, Inc. Website data content access progression
GB2498569A (en) 2012-01-20 2013-07-24 Intellectual Ventures Holding 81 Llc Terminal device communicating on a narrow subset frequency contained within a main frequency band
US20130269694A1 (en) 2012-04-16 2013-10-17 Dance Pharmaceuticals, Inc. Inhaler controlled by mobile device
US8671361B2 (en) 2012-05-24 2014-03-11 Blackberry Limited Presentation of image on display screen with combination crop and rotation and with auto-resizing of crop field
AR094821A1 (es) 2012-07-25 2015-09-02 Hanmi Pharm Ind Co Ltd Formulación líquida de un conjugado de péptido insulinotrópico de acción prolongada
AR091902A1 (es) 2012-07-25 2015-03-11 Hanmi Pharm Ind Co Ltd Formulacion liquida de un conjugado de insulina de accion prolongada
US9248246B2 (en) 2013-09-27 2016-02-02 Cellco Partnership Category 1 M2M device data transmission via a long term evolution network
US10307550B2 (en) 2014-06-09 2019-06-04 Dance Biopharm Inc. Liquid drug cartridges and associated dispenser
US10857313B2 (en) 2014-07-01 2020-12-08 Aerami Therapeutics, Inc. Liquid nebulization systems and methods
US10471222B2 (en) 2014-07-01 2019-11-12 Dance Biopharm Inc. Aerosolization system with flow restrictor and feedback device
WO2016137569A1 (en) 2015-02-25 2016-09-01 Dance Biopharm, Inc. Liquid insulin formulations and methods relating thereto

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5915378A (en) * 1993-01-29 1999-06-29 Aradigm Corporation Creating an aerosolized formulation of insulin
US6312665B1 (en) * 1998-12-21 2001-11-06 Generex Pharmaceuticals Incorporated Aerosol formulations for buccal and pulmonary application
CN2461580Y (zh) * 2001-02-09 2001-11-28 鲁崇恭 超声波雾化胰岛素吸入装置

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