CN1950120A - 一氧化氮气体的间歇计量 - Google Patents

一氧化氮气体的间歇计量 Download PDF

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CN1950120A
CN1950120A CNA200580014839XA CN200580014839A CN1950120A CN 1950120 A CN1950120 A CN 1950120A CN A200580014839X A CNA200580014839X A CN A200580014839XA CN 200580014839 A CN200580014839 A CN 200580014839A CN 1950120 A CN1950120 A CN 1950120A
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A·斯滕茨勒
C·米勒
B·麦穆林
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Abstract

描述了一种用于抵抗微生物和感染的方法和相应的装置，其间歇性地将高剂量一氧化氮输送到哺乳动物一段时间，并在高和低浓度一氧化氮气体之间循环。高浓度的一氧化氮优选间歇性地输送一段短时间，其交替有输送无一氧化氮或者低浓度一氧化氮的时间段。该方法是有利的，因为高浓度的一氧化氮气体克服了病原体的防御机制，该病原体使用哺乳动物的身体补充它们的硫醇防御系统。在高浓度一氧化氮的突发之间输送的低剂量或浓度的一氧化氮气体保持了对病原体的亚硝基化应力压力，还降低了一氧化氮中毒的风险。

Description

一氧化氮气体的间歇计量
                    技术领域
本发明的领域涉及用于将外源或气态一氧化氮气体输送到哺乳动物的方法和装置。
                    背景技术
NO是作为燃烧的副产品产生的环境污染物。在极高浓度下(一般在或者高于1000ppm)，NO是有毒的。NO还是一种自然存在的气体，由呼吸系统的内皮组织产生。在20世纪80年代，研究人员发现，人体的内皮组织产生NO，并且NO是内源性血管扩张剂，也就是说，是一种使血管的内径扩大的试剂。
随着该发现，大量的研究人员研究了用低浓度外源吸入的NO来治疗人类患者中的各种肺病。例如，参见Higenbottam等人，Am.Rev.Resp.Dis.Suppl.137：107，1988。确定，例如，原发性肺动脉高血压(PPH)可通过吸入低浓度的NO进行治疗。对于肺动脉高血压，已经发现吸入的NO降低了肺动脉压(PAP)以及肺血管阻力(PVR)。将吸入的NO用于PPH患者接着就是将吸入的NO用于其它呼吸道疾病。例如，NO被研究用于治疗患有由于肺气肿、慢性支气管炎、哮喘、成人呼吸窘迫综合症(ARDS)和慢性阻塞性肺病(COPD)导致气道阻力增加的患者。在1999年，FDA批准将一氧化氮气体市售用于新生儿期或者近新生儿期持续性肺动脉高血压。由于已知从患有肺动脉高血压的患者吸入的气体中停止使用一氧化氮会引起严重而危险的PVR增加，称为“反弹效应”，一氧化氮必须在连续的基础上被输送给这些患者。
除了其对肺脉管的作用外，NO还可作为针对病原体的抗微生物试剂经吸入或者通过局部施用引入。例如，参见WO00/30659，美国专利US6432077，它们的全部内容都在此引用作为参考。如果产生大量耐抗生素的细菌，则将气态一氧化氮用于抑制或者杀死病原体被认为是有益的。例如，如果与其情况相关的耐抗生菌的菌株增加，则患有肺炎或痨病的患者可能不对抗生素产生响应。
由于潜在毒性，临床使用吸入的一氧化氮通常被限制于低浓度一氧化氮。毒性源于一氧化氮与血红蛋白结合引发高铁血红蛋白或者源于一氧化氮转化成二氧化氮(NO2)。但是，为了克服对一氧化氮的病源防御机制，需要以比通常用于吸入的临床使用更高的浓度输送一氧化氮(例如，为150ppm到250ppm，甚至到400ppm)。因此需要有效地对抗好战的病原体并将中毒的风险降到最低的输送方法。
                    发明内容
预想输送间歇性高剂量的一氧化氮一段时间并在高与低浓度的一氧化氮之间循环的方法和装置是理想的，有用的，并克服了毒性的问题。高浓度的一氧化氮优选在短暂的时间段被间歇性地输送，该短暂时间段与没有一氧化氮输入或者低浓度的一氧化氮输入的时间段交替。这保持了暴露于克服病原体对一氧化氮防御机制所需要的高浓度一氧化氮到一平均水平，该平均水平对人类吸入而言是安全的。
在优选实施方式中，高浓度一氧化氮可以以80ppm到300ppm的浓度被输送，优选在150ppm到250ppm，更优选在160ppm到200ppm。低浓度的一氧化氮优选以零(0)ppm到80ppm的浓度被输送，优选在20ppm到40ppm之间的浓度。
时间段是可以变化的，并且在较宽的范围中，优选每天输送x倍的600到1000ppmhr的剂量。例如，该方法可每4小时以160ppm输送30分钟，在更高的浓度输送之间以20ppm输送3.5小时。高浓度还可在10分钟到45分钟的时间段输送，输送低浓度的时间段比输送高浓度的时间段更长。但是，还可输送与高浓度的一氧化氮相同的时间段，而循环数较少，以实现基本相同的每天一氧化氮的ppmhr量。因此，高和低浓度被交替输送，输送循环可以是一天，两天，三天或者医生规定的任何其它时间。
用于输送一氧化氮的装置可从市场上购买得到，并可包括连续流动装置，流动匹配装置或者脉冲计量装置。例如，FDA已经批准在美国市售三种不同的一氧化氮输送系统：AeroNOxDelivery System和ViaNOx DS System(Pulmonox，Canada)以及INOventDeliverySystem(Datex-Ohmeda，Wisconsin)。其它装置已经在文献中和各种出版物和专利中描述(例如，美国专利US6,581,599，其全文在此引用作为参考)。
在本发明的另一方面，用于输送间歇性高剂量一氧化氮的装置可包括一氧化氮气体源(例如，压缩气瓶中的一氧化氮气体)，控制器(例如电子控制器或者微处理器)，一氧化氮分析仪和定时器，其中输送的一氧化氮浓度在定时基础上自动变化到由操作人员设定的浓度和持续由操作人员定义的设定时间段。装置可包括逻辑(例如，软件或者固体)，允许设定两个不同的一氧化氮浓度并且每种浓度的输送具有单独的时间设定。装置还可包括气体混合器(例如气体搅拌器或者流量控制阀与T或Y形管连接件的组合)，管件，稀释气体源(例如室内空气，氧气或者惰性气体)和用于控制一氧化氮气体或者其它稀释气体的释放或者对两者的释放都控制的电子调控的针阀或者其它的阀机构。
作为替代，装置还可包括两个一氧化氮气体源，其中一个源提供高浓度的一氧化氮，另一个源提供低浓度的一氧化氮。然后提供转换阀(优选为电子控制的)，基于预定的时间转换一氧化氮气体从高浓度到低浓度的流动，或者相反。还可提供稀释气体第三源，用于稀释一氧化氮气体。
                    附图说明
图1-3示出了根据本发明的一个方面的一氧化氮输送装置的各种实施方式的示意性表示。
图4示出了设定用于高和低浓度一氧化氮气体的交替输送模式的逻辑。
图5示出了用于输送交替的高和低浓度一氧化氮气体的逻辑。
图6显示了当以160ppm一氧化氮气体30分钟和20ppm 3.5小时，总暴露时间为24小时，交替暴露于NO气体(gNO)时对S.aureus(ATCC#25923)存活的影响。
图7显示了当以160ppm一氧化氮气体30分钟和20ppm 3.5小时，总暴露时间为24小时，交替暴露于NO气体(gNO)时对P.aeruginosa(ATCC#27853)存活的影响。
图8显示了当以160ppm一氧化氮气体30分钟和20ppm 3.5小时，总暴露时间为24小时，交替暴露于NO气体(gNO)时对P.aeruginosa(来自Cystic Fibrosis的临床菌株)存活的影响。
图9显示了当以160ppm一氧化氮气体30分钟和20ppm 3.5小时，总暴露时间为24小时，交替暴露于NO气体(gNO)时对E.coli(ATCC#27853)存活的影响。
图10显示了当暴露于200ppmNO气体(gNO)时对MshA分支硫醇(mycothiol)缺陷型突变株Mycobacterium smegmatis和其野生型对应物的存活的影响。
图11显示了暴露于400ppm NO气体(gNO)空气暴露于相比，野生型Mycobacterium smegmatis中的分支硫醇的水平。
                    具体实施方式
目前认为更高浓度的一氧化氮气体克服了，使用哺乳动物身体来补充它们的硫醇防御系统的病原体的防御机制。该硫醇防御系统例如可包括用于分支杆菌的分支硫醇或者用于其它细菌的谷胱甘肽。一旦防御系统被耗尽，病原体就对一氧化氮的杀死效果没有抵抗。在高浓度一氧化氮突发之间输送的更低剂量或者浓度的一氧化氮气体保持对病原体的亚硝基化应力压力，防止它们将它们的防御系统重建到足够的水平。因此，抗抵病原体的优选治疗或者输送方案可包括在多个时间段内输送第一浓度的一氧化氮，各时间段之间散布着间隔，在该间隔内施用第二浓度的一氧化氮。第一浓度优选是足够杀死或者抑制微生物生长的高浓度。例如，第一浓度可为大约80ppm到大约400ppm，更优选150到250ppm，特别优选160ppm到200ppm。
第二浓度优选是低浓度的一氧化氮气体，例如从20到80ppm。作为替代，还应理解，第二浓度也可以是零ppm或者接近痕量的一氧化氮气体。
现在转向附图，图1-3示出了用于本发明的一氧化氮输送装置的各种实施方式。图1显示，在其最通常的意义中，包括一氧化氮源8的NO输送装置2适于将NO气体经输送界面6输送给哺乳动物。图1示出了本发明的一种优选实施方式。
在图1中，NO气体源8是含有NO气体的加压气瓶。虽然使用加压气瓶是储存含NO气体源8的优选方法，但其它储存和输送装置，例如专用的供料管线(壁给料)也可采用。典型地，NO气体源8是N2和NO的混合物。虽然典型地使用N2稀释加压气瓶中的NO浓度，但任何惰性气体都可采用。当NO气体源8存储在加压气瓶中时，优选加压气瓶中的NO浓度落入大约800ppm到10000ppm的范围内。商业一氧化氮生产商通常生产大约1000ppm的范围的医用一氧化氮混合物。含有低浓度NO(例如，少于100ppm NO)的加压气瓶还可根据这里公开的装置和方式使用。当然，使用的NO的浓度越低，加压气瓶将需要更换得越频繁。
图1还显示了稀释气体14源作为NO输送装置2的一部分，其用于稀释NO的浓度。稀释气体14源可含有N2，O2，空气，惰性气体或这些气体的混合物。优选以较低浓度使用气体例如N2或惰性气体来稀释NO的浓度，因为这些气体不能象O2或者空气那样将NO氧化成N2。然而，对于输送高浓度的NO的吸入应用而言，其中已经存在更高浓度的氮，那么NO流可使用氧气补充或者稀释，防止可导致窒息的氧被氮取代。优选地，特别是当输送更高浓度的NO气体时，注射部位或者气体搅拌器下游的输送管线被最小化以降低NO2形成的风险。
稀释气体14源显示为被储存在加压气瓶中。虽然在图1中显示加压气瓶作为存储稀释气体14源的部件，但其它存储和输送装置，例如专用的供料管线(壁给料)也可采用。稀释气体源还可以是通风装置，气泵，鼓风机或者使可吸入空气运动的其它机械装置。
来自NO气体源8的NO气体和来自稀释气体源14的稀释气体优选通过压力调节器16，以减小进入NO输送装置2的气体的压力。各气流经管件18到达气体搅拌器20。气体搅拌器20将NO气体与稀释气体混合产生含NO的气体，与源8中含有的NO气体相比，其具有降低的NO浓度。优选地，控制器36经电连接线42控制气体搅拌器，使气体搅拌器可被设定为将气体混合成理想的NO浓度(例如，对于高浓度阶段而言为160ppm-200ppm，对于低浓度阶段而言为20ppm-40ppm)并经管件24输出。
任选的流量控制阀22可设置在气体搅拌器20的下游，以控制NO气体向输送界面6的流动。流量控制阀22可包括，例如，以逐渐增加(或者如果关闭则减少)的方式打开(或关闭)的按比例控制阀。作为另一种例子，流量控制阀22可包括质量流控制器。流量控制阀22控制输入到输送装置6的含NO的气体的流速。
输送界面6可以是适于将气体输送到哺乳动物的任何类型的界面。例如，如果NO气体将被输送到哺乳动物的气管或者肺，则输送界面6可包括面罩，鼻插入物或者与哺乳动物的呼吸系统连接的气管内导管。应理解，输送界面6的类型不受到限制，其取决于特定的应用和气体输送的部位。在另一例子中，如果NO气体被局部输送到身体表面，诸如皮肤或者眼睛，器官如心脏、胃的表面等，则可使用如在由发明人之一提出的美国专利US6432077中描述的浴装置。美国专利US6432077在此引用作为参考，如同在此全文阐述一样。输送界面6的又一个例子可以是透析循环或者体外循环界面，其中NO气体被直接输送到血液或者体液以将血液或者体液暴露于NO气体。这样的输送界面例如在2003年9月9日提交的美国专利申请NO.10/658665中描述，其在此全文引用作为参考。
仍然参见图1，输送装置2优选包括能够控制流量控制阀22和气体搅拌器20的控制器36。控制器36优选是与输入装置(未显示)连接的以微处理器为基础的控制器36。输入装置可由操作人员使用，以调节输送装置的各种参数，例如NO浓度和治疗/暴露时间段。任选的显示器也可与控制器36连接以显示测得的参数和设定，例如设定点NO浓度，流到输送界面6的NO浓度，NO2浓度，气体流进输送界面6中的速率，治疗/暴露的总时间，和/或在高浓度和低浓度NO气体之间交替的循环数。
控制器优选包括用于倒记时输送不同浓度NO气体的时间段的定时器。此外，控制器优选包括逻辑，诸如用于在预定或者用户可编程时间段执行交替输送高浓度和低浓度NO气体的固件或者软件程序。用于由所述逻辑执行的程序在图4和5中示出。
如果所述分析仪40存在于输送装置2中，控制器36还优选通过信号线48从分析仪40接收与气体浓度有关的信号。信号线42和44分别与气体搅拌器20和流量控制阀22连接，用于传送和接收控制信号。
在一氧化氮输送装置的另一种实施方式中，控制器36可完全被省略，气体搅拌器20可以以需要的一氧化氮气体高或低浓度人工设定。时间段还可人工示踪，并且在合适的设定时间段下，气体搅拌器被调节到增加到高浓度NO气体或者降低到低浓度NO气体。气体进入输送界面6中的流动速率可人工预先设定或者调节。
图2显示了一氧化氮输送装置52的替代实施方式，其中希望浓度的NO气体基于流自NO气体源8的NO气体和流自稀释气体源74的稀释气体的流速，通过用T或者Y形连接件70混合来获得。各流速经流量控制阀72和75控制。气体混合在T或Y形连接点70开始并连续经过输送线78。NO分析仪80在靠近输送界面的接合点对气体混合物取样，以测定流到输送界面76的气体混合物的NO浓度。测得的NO浓度然后经过信号线88反馈到控制器86，其进而通过将测得的NO浓度与设定的需要的NO气体浓度相比较来处理该信息。如果合适的话，则控制器86通过线82和84发送控制信号调节流量控制阀72和75，使流速可被调节以获得流到输送界面76的所需的NO气体浓度。应理解，控制器86同样可包括上述在图1中与控制器36有关的全部特征。同样地，输送界面76可与输送界面6相似地使用，如图1中的有关描述。
图3示出了根据本发明的一个方面的一氧化氮输送装置的又一种实施方式。在该输送装置102中没有气体混合器(例如，气体搅拌器或者T或Y形连接件)，输送装置102利用转换阀104在高浓度NO气体源106和低浓度NO气体源108之间转换。根据本发明，转换阀104由控制器116控制，在适当时间在高和低浓度NO气体之间转换。应理解，如果所需的低NO浓度是0ppm的NO气体的话，低浓度NO气体源108还可被非NO气体源取代，例如空气。
现在参见图4和5，举例说明可由编程到控制器36、86和116中的逻辑(固体或者软件)来执行的程序。图4示出了用于设定用于NO气体输送所需的浓度和时间段的程序，始自步骤400“开始”。在步骤405，逻辑进入开始子程序，用于设定所需的NO浓度和时间段。在步骤410，逻辑验证是否有设定为NO输送方案的浓度值。如果值已经被设定，则程序继续步骤415以验证设定为用于输送时间段的值。如果用于NO浓度的值还没有被设定，则逻辑调用子程序，包括步骤412和414，其被调用以设定用于待输送的治疗方案的第一和第二NO浓度。例如，第一NO浓度可被设定为大约160ppm到300ppm的待输送NO气体，第二NO浓度可被设定为0ppm到80ppm的待输送NO气体。在图5中示出的程序中通过控制器使用所设定的NO浓度，以设定气体搅拌器或者流速控制阀。
在已经设定NO浓度值之后，然后进行逻辑，以在步骤415中设定输送NO气体的时间段。如果时间段还没有被设定，则包括步骤417和149的子程序被调用，其中与第一NO浓度对应的第一时间段和与NO浓度对应的第二时间段被设定。
在已经设定NO浓度值和时间段之后，然后进行逻辑，以设定待输送的第一和第二NO气体浓度的交替循环数。作为选择，可设定总治疗时间，其中NO气体的输送将在总治疗时间结束时停止。如果总治疗时间或者循环数没有被设定，则包括步骤422的子程序被调用并且这些值被设定。然后，设置程序结束并且装置转被输送用于治疗的NO气体。
图5示出了由控制器36、56和116中的逻辑执行的程序，用于交替输送高和低浓度的NO气体。一旦输入图4中的NO气体输送值，步骤500中的“开始治疗”就可开始。在步骤505，控制器36(图1)然后可通过线42将控制信号发送到气体搅拌器来设定合适的气体混合器设置，达到第一NO气体浓度，其值在图4的设置步骤中设定。该程序还可包括从NO分析仪40(图1)向控制器36的反馈控制，使气体搅拌器的控制可被精细调节，从而被输送到输送到界面6的实际NO气体浓度与设定NO气体浓度匹配。
作为备选，步骤505中，控制器可将控制信号发送到流量控制阀72和75(图2)，为气体的混合设定合适的流速，达到图4的设置步骤中设定的第一浓度。该程序同样可包括从NO分析仪80(图2)向控制器56的反馈控制。在又一种实施方式中，步骤505中，控制器可设定转换阀104(图3)，从与在图4的设置步骤中设定的第一NO气体浓度对应的源选择NO气体的输送。
根据在步骤505中的设置进行NO气体的输送。在步骤510，包含在控制器36、56或者116中的定时器及时地将在图4中设定的第一时间段的值与实际的倒记时相比较。如果时间段没有结束，则气体搅拌器、流量控制阀或者转换阀设置保持与步骤512中相同。如果第一时间段已经结束，则步骤515将气体搅拌器、流速或者转换阀设置设定成与第二NO气体浓度对应，其值在图4的设置步骤中设定。然后，以第二浓度进行NO气体的输送，直到第二时间段结束。
在第二时间段完成时，逻辑进行到步骤525，询问总治疗时间的设定循环数是否已经结束。如果总治疗时间的设定循环数已经达到，治疗在步骤530中结束。反之，该程序重复步骤505、510、515和525。
输送方法的进一步的例子
高剂量NO气体的间歇性输送的执行可以采用很多方式。例如，通过吸入的输送或者向呼吸气管的输送可送到自发呼吸的哺乳动物或者用机械通气维持的哺乳动物中。就自发呼吸的哺乳动物而言，输送可经许多先前描述的气体输送系统来实现，例如面罩或者鼻插管。用于这些哺乳动物的装置可包括流量计或者流量传感器，用于测定呼吸(例如，吸入对呼出)的开始，使一氧化氮气体仅仅在哺乳动物吸入时被输送。机械通气的哺乳动物可使一氧化氮被输送到通风设备回路的吸入通路中，并同样仅仅可在通气设备将呼吸循环入哺乳动物时被触发。
在这些执行中，一氧化氮输送模式可取决于哺乳动物肺部感染的目标部位和残留在输送回路中的一氧化氮的最低希望浓度而变化。例如，如果感染在肺部的肺泡中，那么当气体即将仅仅被输送到气管中时，一氧化氮可向着呼吸的末端关闭。作为替代，如果感染仅仅在气管中，则开始气体可能具有更低的一氧化氮浓度。
此外，当使用更高浓度的NO气体时，优选NO气体输送的注入部位靠近患者的气管，以缩短转化成NO2的时间。这将吸入前NO气体在输送管中的停留时间降到最短。作为备选，输送系统可在呼吸的时间点利用高浓度推注，并允许NO的稀释可在肺部发生。
虽然已经显示并描述了本发明的实施方式，但仍可进行各种修改而不背离本发明的精神。因此，除下面的权利要求书及其等同物外，本发明不应受到限制。
实验结果
检验并证实了间歇性高剂量输送一氧化氮气体在防止微生物中的有效性。简言之，实验方法如下。变化的细菌接种体被制备成2.5×108cfu/ml的悬液，并在无菌生理盐水中按1∶1000稀释。在无菌培养位置中每孔使用3毫升的接种体。接种体的暴露在暴露室中进行，该暴露室例如在Ghafarri，A.等人的“用于细菌和哺乳动物细胞培养的直接一氧化氮气体输送系统”，Nitric Oxide.12(3)：129-40(2005年5月)中描述，其内容如同在此全部被阐述那样引入本申请作为参考。将接种体暴露于流速为2.5升每分钟的160ppm NO气体30分钟，接着暴露于20ppm的NO气体3.5小时。暴露于高和低浓度的NO气体在24小时中每4小时重复循环。在各个时间(例如，0，4，8和12小时)，取出样品并置于盘中，通过cfu/ml计数测定来测定细菌的存活能力。
图6-9显示在采用NO的试验中使用的各种细菌的存活，其与暴露于空气中作为对照来进行比较。从这些附图中看出，循环暴露于高和低浓度的一氧化氮是杀死细菌的有效方法。虽然观察到在更长的时间段循环暴露于高和低浓度的一氧化氮的效果与连续暴露于高浓度下的效果相同，但循环暴露提供了更好的安全模式，将高铁血红蛋白的形成危险降到最低。
进行了另外的研究来检验NO气体在杀死微生物方面的效果与硫醇基团有关的假设。基于使用各种微生物的研究，观察到Mycobacteria对NO气体损害的敏感性较低。这可能是由于Mycobacteria具有例外的硫醇，分支硫醇，这保持了细胞中的氧化还原平衡，并保护细胞不受到亚硝基化(nitrosative)和氧化应力。为了检验这种假设，通过将两种菌株都暴露于200ppm的NO气体，在分支硫醇缺陷型Mycobacteria smegmant突变体MshA与其野生型对应物mc2155之间比较它们对NO气体的敏感性。MshA是在分支硫醇生物合成中所需的酶。
图10显示了分支硫醇缺陷型MshA突变体比其野生型对应物对NO气体更敏感，并比其野生型对应物在更短的时间内被杀死。
在野生型M.smegmant中，在暴露于400ppm NO气体之后使用HPLC进行了进一步的实验来检测和测定分支硫醇水平，并与暴露于空气中之后的分支硫醇水平进行比较。图11显示当暴露于400ppm NO气体时，与暴露于空气中相比分支杆菌中的分支硫醇水平降低。
因此，三种结果显示，NO气体可能起到消耗分支硫醇的作用，这是分支杆菌保护自身不受氧化应力的机制。
在其它细菌中，据信与在分支杆菌中的分支硫醇类似的分子是谷胱甘肽。谷胱甘肽库通常用于保护细菌不受内源NO和H2O2影响，这些气体由巨噬细胞抵抗病原体而释放。外源NO的输送可由此用于控制谷胱甘肽库，消除免受H2O2影响的细菌保护，并结合引起O2消耗停止和电子传递中心分裂的基于铁的酶，并将金属离子释放到细菌细胞液中。游离的氧，金属离子，NO，和过氧化氢还产生通过脱氨基作用损害细菌DNA的反应性的氮和氧种质以及金属离子。因此，据信循环或者交替输送的NO气体浓度足以破坏谷胱甘肽防御机制一段时间，更低浓度的NO气体可有效地抵抗微生物诸如细菌，分支杆菌和真菌，同时表现出更好的安全性。
微生物还可包括病毒。虽然病毒自身不具有基于硫的解毒途径，但是它们仍可固有地对亚硝基化应力更敏感。NO可抑制病毒的核糖核酸还原酶，这是一种病毒DNA合成必须的组成酶，从而抑制病毒复制。一氧化氮还可在复制循环的早期抑制病毒的复制，涉及vRNA和mRNA编码的病毒蛋白质的合成。由于病毒还取决于宿主细胞来解毒身体防御途径，NO进入宿主细胞的直接细胞毒性机制和其产生的细胞内变化还可说明通过病毒DNA的脱氨基作用杀病毒效果。因此据信，以高和低浓度循环或者交替输送NO气体针对病毒可能也是有效的。

Claims (24)

1.一种将一氧化氮气体输送给哺乳动物的方法，该方法包括下列步骤：
提供一氧化氮气体源；
稀释一氧化氮气体；
以范围为80ppm到400ppm一氧化氮气体的第一浓度将一氧化氮气体施用给哺乳动物第一时间段，以比第一浓度低的第二浓度施用第二时间段，交替施用多个循环。
2.权利要求1的方法，其中第二时间段比第一时间段长。
3.权利要求1的方法，其中一氧化氮气体的第一浓度为大约160ppm到大约300ppm。
4.权利要求1的方法，其中一氧化氮气体的第二浓度为大约20ppm到大约40ppm。
5.权利要求1的方法，其中第一时间段为大约30分钟，第二时间段为大约3.5小时。
6.权利要求1的方法，其中施用步骤是通过吸入一氧化氮气体。
7.权利要求1的方法，其中施用步骤是局部应用一氧化氮气体。
8.一种将一氧化氮输送给哺乳动物的方法，所述方法包括将第一浓度的一氧化氮气体施用给哺乳动物多个时间段，在这些时间段之间散布着间隔，其中在间隔期间施用第二浓度的一氧化氮气体。
9.权利要求8的方法，其中一氧化氮气体的第二浓度比一氧化氮的第一浓度低。
10.权利要求9的方法，其中一氧化氮气体的第二浓度小于大约80ppm。
11.权利要求8的方法，其中一氧化氮气体的第一浓度是足以杀死或者抑制微生物生长的浓度。
12.权利要求11的方法，其中微生物选自细菌，分支杆菌，病毒和真菌。
13.权利要求8的方法，其中施用步骤是通过吸入一氧化氮气体。
14.权利要求8的方法，其中施用步骤是局部应用一氧化氮气体。
15.一种用于输送一氧化氮气体的装置，包括：
一氧化氮气体源；
稀释气体源；
适于从源将一氧化氮气体输送到哺乳动物的输送界面；
用于混合一氧化氮气体和稀释气体的气体混合器；
与气体混合器连通的控制器，其中控制器包括用于设定包括至少两种不同浓度的一氧化氮气体的一氧化氮输送方案和用于以时间为基础在至少两种不同浓度的一氧化氮气体之间自动转换的逻辑。
16.权利要求15的装置，其中输送方案还包括至少第一和第二时间段，其分别对应于所述至少两种不同的一氧化氮气体浓度中的每一个。
17.权利要求16的装置，其中第一时间段比第二时间段短。
18.权利要求15的装置，其中气体混合器包括T或Y形管连接件和流量控制阀。
19.权利要求15的装置，其中气体混合器包括气体搅拌器。
20.权利要求15的装置，其中输送界面包括浴装置，用于将一氧化氮气体局部输送到身体表面。
21.权利要求15的装置，其中输送界面包括选自面罩、鼻插入物和气管内管一个界面。
22.权利要求15的装置，还包括一氧化氮气体分析仪，用于测定流到输送界面的一氧化氮气体的浓度，其中一氧化氮气体分析仪将信号发送到控制器。
23.一种用于输送一氧化氮气体的装置，包括：
具有第一浓度的一氧化氮气体源；
可吸入气体源；
适于从源将一氧化氮气体输送给哺乳动物的输送界面；
在一氧化氮气体源的下游和输送界面的上游的转换阀，所述转换阀用于引导一氧化氮从源到输送界面的流动。
用于控制转换阀的控制器，其命令转换阀以时间为基础在一氧化氮气体源和可呼吸气体源之间转换。
24.权利要求23的输送装置，其中可吸入气体源包括浓度比一氧化氮气体的第一浓度低的一氧化氮气体。
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102818115A (zh) * 2011-06-09 2012-12-12 乔治洛德方法研究和开发液化空气有限公司 用于封装no/n2混合物的方法
CN102933250A (zh) * 2010-04-29 2013-02-13 迈柯唯销售服务德国有限公司 用于给借助呼吸装置人工呼吸的病人施加至少一种医疗气体的方法和装置
CN103379935A (zh) * 2011-02-21 2013-10-30 皇家飞利浦有限公司 用于生成含一氧化氮的气体气流的方法和装置
CN107106079A (zh) * 2014-10-20 2017-08-29 卡普尼亚公司 用于筛查感染性疾病的呼吸分析系统及方法
CN108355215A (zh) * 2012-12-04 2018-08-03 马林克罗特医疗产品知识产权公司 用于在氧化氮递送期间对给药的稀释最小化的套管
US11058324B2 (en) 2011-12-21 2021-07-13 Capnia, Inc. Collection and analysis of a volume of exhaled gas with compensation for the frequency of a breathing parameter
US11191449B2 (en) 2013-08-30 2021-12-07 Capnia, Inc. Neonatal carbon dioxide measurement system
US11331004B2 (en) 2013-02-12 2022-05-17 Capnia, Inc. Sampling and storage registry device for breath gas analysis

Families Citing this family (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070086954A1 (en) * 1998-11-23 2007-04-19 Miller Christopher C Method and apparatus for treatment of respiratory infections by nitric oxide inhalation
CA2254645A1 (en) * 1998-11-23 2000-05-23 Pulmonox Medical Corporation Method and apparatus for treatment of respiratory infections by nitric oxide inhalation
US20080167603A1 (en) * 2000-12-26 2008-07-10 Alex Stenzler Method and device to prevent ventilator acquired pneumonia using nitric oxide
US6432077B1 (en) 2000-12-26 2002-08-13 Sensormedics Corporation Device and method for treatment of surface infections with nitric oxide
US7122018B2 (en) 2000-12-26 2006-10-17 Sensormedics Corporation Device and method for treatment of wounds with nitric oxide
US9675637B2 (en) 2003-07-09 2017-06-13 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Use of nitrite salts for the treatment of cardiovascular conditions
US8017074B2 (en) 2004-01-07 2011-09-13 Noxilizer, Inc. Sterilization system and device
EP1701747B1 (en) * 2004-01-07 2014-03-12 Noxilizer, Inc. Sterilisation method
JP2007537267A (ja) * 2004-05-11 2007-12-20 センサーメディックス・コーポレイション 一酸化窒素ガスの間欠的投与
US8518457B2 (en) 2004-05-11 2013-08-27 Pulmonox Technologies Corporation Use of inhaled gaseous nitric oxide as a mucolytic agent or expectorant
US7362274B1 (en) * 2004-07-09 2008-04-22 Huan-Cheng Lien Coupled feed-in butterfly shaped left/right hand circularly polarized microstrip antenna
US9358150B2 (en) * 2005-05-13 2016-06-07 Benechill, Inc. Methods and devices for non-invasive cerebral and systemic cooling alternating liquid mist/gas for induction and gas for maintenance
US8557300B2 (en) * 2005-05-19 2013-10-15 University Of Cincinnati Methods for treating bacterial respiratory tract infections in an individual using acidified nitrite
US7523752B2 (en) 2005-09-21 2009-04-28 Ino Therapeutics, Llc System and method of administering a pharmaceutical gas to a patient
US8893717B2 (en) 2005-09-21 2014-11-25 Ino Therapeutics Llc Systems and methods of administering a pharmaceutical gas to a patient
US20070181126A1 (en) * 2006-02-08 2007-08-09 Tolmie Craig R Method and apparatus for ventilating a patient with a breathing gas mixture formed from nitric oxide, air, and oxygen
US8079998B2 (en) 2006-10-20 2011-12-20 Pulmonox Technologies Corporation Methods and devices for the delivery of therapeutic gases including nitric oxide
US20090196930A1 (en) * 2007-12-27 2009-08-06 Aires Pharmaceuticals, Inc. Aerosolized nitrite and nitric oxide -donating compounds and uses thereof
WO2010014818A1 (en) * 2008-07-30 2010-02-04 Nitric Biotherapeutics, Inc. Methods of treating an infection with nitric oxide
US20100040703A1 (en) * 2008-08-13 2010-02-18 Chris Miller Use of nitric oxide
US10960168B2 (en) * 2008-08-21 2021-03-30 Vero Biotech LLC Delivery of high concentration nitric oxide
US8701657B2 (en) * 2008-08-21 2014-04-22 Geno Llc Systems for generating nitric oxide
EP2361099B1 (en) 2009-02-23 2012-09-12 Noxilizer, Inc. Method for gas sterilization
JP5692561B2 (ja) * 2009-03-23 2015-04-01 エア・ウォーター株式会社 医薬性ガス投与装置
US20120093948A1 (en) * 2009-11-20 2012-04-19 Fine David H Nitric Oxide Treatments
US20110240019A1 (en) * 2010-02-01 2011-10-06 Geno Llc Nitric Oxide Delivery System
DE102010054361B4 (de) * 2010-12-13 2013-02-21 Nli Gmbh Therapiegerät
CA2860158A1 (en) * 2011-01-07 2012-07-12 Somerset Group Enterprises, Inc. Modular extracorporeal systems and methods for treating blood-borne diseases
WO2013039713A2 (en) 2011-09-14 2013-03-21 3M Innovative Properties Company Positive pressure medical dressings with valve and kits containing same
US10426913B2 (en) 2011-11-07 2019-10-01 Mallinckrodt Hospital Products IP Limited Apparatus and method for monitoring nitric oxide delivery
CA2854776C (en) * 2011-11-07 2020-08-18 Ino Therapeutics Llc Apparatus and method for monitoring nitric oxide delivery
CA2897426A1 (en) * 2012-01-09 2013-07-18 Somerset Group Enterprises, Inc. Modular extracorporeal systems and methods for treating blood-borne diseases
ES2690398T3 (es) * 2012-03-07 2018-11-20 Advanced Inhalation Therapies (Ait) Ltd. Inhalación de óxido nítrico para el tratamiento de enfermedades respiratorias
JP6104513B2 (ja) * 2012-03-09 2017-03-29 エア・ウォーター株式会社 人工呼吸器
AU2013231976B9 (en) * 2012-03-15 2017-12-14 Mallinckrodt Hospital Products IP Limited Methods of administering high concentrations of nitric oxide
US9265922B2 (en) 2012-04-16 2016-02-23 Astuce, Inc. System and method for improving outcome of cerebral ischemia
FR2991026B1 (fr) * 2012-05-24 2014-07-04 Air Liquide Sante Int Conditionnement a haute pression d'un melange gazeux no/azote
FR2991025B1 (fr) * 2012-05-24 2014-07-04 Air Liquide Sante Int Conditionnement d'un melange gazeux no/azote a haute concentration en no
US20140000596A1 (en) * 2012-06-29 2014-01-02 Ino Therapeutics Llc Methods And Apparatus To Zero A Patient Trigger Sensor
US9364388B2 (en) 2012-09-27 2016-06-14 Barry university Methods of treatment with nitric oxide at pressures greater than one atmosphere
CA2890203A1 (en) * 2012-11-05 2014-05-08 Geno Llc Dual platform system for the delivery of nitric oxide
US20160022731A1 (en) 2013-03-07 2016-01-28 Advanced Inhalation Therapies (Ait) Ltd. Inhalation of nitric oxide for treating respiratory diseases
PL2968824T3 (pl) * 2013-03-13 2018-05-30 Ino Therapeutics Llc Aparat do monitorowania dostarczania tlenku azotu
CA3112015A1 (en) 2013-03-15 2014-09-18 The General Hospital Corporation Inspiratory synthesis of nitric oxide
BR112015022468B1 (pt) 2013-03-15 2022-11-01 The General Hospital Corporation Aparelho e método para síntese do gás óxido nítrico para inalação
CN103982771A (zh) * 2013-05-12 2014-08-13 摩尔动力(北京)技术股份有限公司 液压蓄能罐
US10335567B2 (en) * 2013-08-27 2019-07-02 12th Man Technologies, Inc. Nitric oxide upper airway delivery system and method
US20150072023A1 (en) * 2013-09-11 2015-03-12 Advanced Inhalation Therapies (Ait) Ltd. Inhalation of nitric oxide for treating respiratory diseases
US10226592B2 (en) 2014-04-01 2019-03-12 Mallinckrodt Hospital Product Ip Limited Systems and method for delivery of therapeutic gas to patients in need thereof using enhanced breathing circuit gas (BCG) flow measurement
US9833643B2 (en) * 2014-04-03 2017-12-05 Mark Squibb Apparatus for providing controlled flow of inhalation-air
US20150290417A1 (en) * 2014-04-09 2015-10-15 12th Man Technologies. Inc. System and Method for High Concentration Nitric Oxide Delivery
US10525226B2 (en) * 2014-05-14 2020-01-07 Mallinckrodt Hospital Products IP Limited Systems and methods for indicating lifetime of an NO2-to-NO reactor cartridge used to deliver NO for inhalation therapy to a patient
JP6947633B2 (ja) 2014-10-20 2021-10-13 ザ ジェネラル ホスピタル コーポレイション 一酸化窒素の合成のためのシステム及び方法
US20160121071A1 (en) * 2014-10-30 2016-05-05 Nu-Med Plus Controlled delivery of medical gases using diffusion membranes
AU2015346202A1 (en) 2014-11-13 2017-06-08 Hansen Pharmaceutical, Llc. Nitric oxide delivery system and methods of use
US11633551B2 (en) 2014-11-13 2023-04-25 Hansen Pharmaceutical, Llc Gaseous nitric oxide delivery system and methods of use
EP3020438A1 (en) * 2014-11-13 2016-05-18 Linde AG Device for ventilating a patient and method for operating a device for ventilating a patient
JP6719467B2 (ja) * 2014-12-19 2020-07-08 マケット・クリティカル・ケア・アーベー バックアップを備えた添加ガス送達装置
US10039781B2 (en) * 2015-03-24 2018-08-07 Ait Therapeutics, Inc. Pulse inhalation of nitric oxide for treating respiratory diseases
WO2017042636A1 (en) 2015-09-09 2017-03-16 Advanced Inhalation Therapies (Ait) Ltd. Nitric oxide inhalation therapy for infants with bronchiolitis
MX2018004020A (es) 2015-10-01 2018-09-11 Mallinckrodt Hospital Products Ip Ltd Dispositivo y método para la dispersión de no de concentración alta con gas de terapia de inhalación.
JP6666701B2 (ja) * 2015-12-01 2020-03-18 日本光電工業株式会社 水素ガス供給装置
KR20190005839A (ko) 2016-03-25 2019-01-16 더 제너럴 하스피탈 코포레이션 산화질소의 전기 플라즈마 합성을 위한 전달 시스템 및 방법
MX2020010523A (es) 2017-02-27 2021-02-09 Third Pole Inc Sistemas y metodos para generar oxido nitrico.
WO2018157172A1 (en) 2017-02-27 2018-08-30 Third Pole, Inc. Systems and methods for generating nitric oxide
CA3054660C (en) 2017-02-27 2022-05-03 Third Pole, Inc. Systems and methods for ambulatory generation of nitric oxide
BR112019020317A2 (pt) 2017-03-31 2020-04-28 Massachusetts Gen Hospital sistemas e métodos para um gerador de óxido nítrico resfriado
EP3424550A1 (en) * 2017-07-06 2019-01-09 Monatomics Technology Gas mixtures containing low concentrations of xenon and argon provide neuroprotection without inhibiting the catalytic activity of thrombolytic agents
CA3081341A1 (en) * 2017-11-02 2019-05-09 Beyond Air, Inc. Inhalation of nitric oxide
US11717634B2 (en) 2018-10-02 2023-08-08 MaxxO2, LLC Therapeutic oxygen breathing apparatus and exercise system
WO2020084993A1 (ja) * 2018-10-25 2020-04-30 帝人ファーマ株式会社 一酸化窒素投与装置
US10682486B1 (en) * 2019-01-31 2020-06-16 Nu-Med Plus Inc. Single treatment disposable nitric oxide delivery
JP6667817B1 (ja) * 2019-03-13 2020-03-18 住友精化株式会社 ガス組成物及びその製造方法、並びにガス製品
FR3093926B1 (fr) * 2019-03-22 2022-10-28 Air Liquide Appareil et installation de fourniture d’un mélange gazeux à un patient
EP3969416A4 (en) 2019-05-15 2023-11-01 Third Pole, Inc. SYSTEMS AND METHODS FOR GENERATING NITRIC OXIDE
EP3969415A4 (en) 2019-05-15 2023-08-16 Third Pole, Inc. ELECTRODES FOR NITRIC OXIDE GENERATION
JP7457795B2 (ja) * 2019-08-23 2024-03-28 ノータ ラボラトリーズ，リミティド ライアビリティ カンパニー 一酸化窒素発生システム
US20230338416A1 (en) 2019-11-25 2023-10-26 Beyond Air, Inc. Methods employing gaseous nitric oxide for inhibiting tumor growth
EP4069069A1 (en) 2020-01-11 2022-10-12 Third Pole, Inc. Systems and methods for nitric oxide generation with humidity control
WO2021224894A1 (en) * 2020-05-08 2021-11-11 Kersten Erich Ventilator and method of ventilation
US20210395905A1 (en) 2020-06-18 2021-12-23 Third Pole, Inc. Systems and methods for preventing and treating infections with nitric oxide
WO2023049873A1 (en) 2021-09-23 2023-03-30 Third Pole, Inc. Systems and methods for delivering nitric oxide
US20240131292A1 (en) * 2022-10-21 2024-04-25 Vero Biotech Inc. Dual sensor feedback control system for nitric oxide dosing

Family Cites Families (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3036584A (en) 1961-07-18 1962-05-29 Invengineering Inc Non-rebreathing valve for gas administration
BE660318A (zh) 1961-08-15
US4127121A (en) 1976-09-17 1978-11-28 University Of Utah Oxygen and anesthesia delivery and monitoring device
US4191952A (en) 1978-08-25 1980-03-04 N.A.D., Inc. Low oxygen flow alarm for anesthesia systems
US4224941A (en) * 1978-11-15 1980-09-30 Stivala Oscar G Hyperbaric treatment apparatus
JPS55166163A (en) 1979-06-13 1980-12-25 Citizen Watch Co Ltd Controller for anesthetic gas
US4328823A (en) 1980-05-14 1982-05-11 N.A.D. Inc. Oxygen flow ratio controller for anesthesia apparatus
US4336798A (en) 1980-10-06 1982-06-29 Anthony V. Beran Medical corrugated respiratory tube
SE430213B (sv) 1981-03-10 1983-10-31 Siemens Elema Ab Respirator, avsedd att anslutas till andningsvegarna pa menniska eller djur
US4442856A (en) 1981-08-18 1984-04-17 Puritan-Bennett Oxygen regulator and alarm system for an anesthesia machine
SE429197B (sv) 1981-10-14 1983-08-22 Frese Nielsen Anordning for behandling av sar
DE3401923A1 (de) 1984-01-20 1985-08-01 Drägerwerk AG, 2400 Lübeck Vorrichtung zur beimischung fluessiger narkosemittel in das dem patienten zuzufuehrende atemgas
US4770168A (en) 1985-12-16 1988-09-13 Tibor Rusz Electrically controllable anesthesia vaporizer
DE3712598A1 (de) * 1987-04-14 1988-10-27 Siemens Ag Inhalations-anaesthesiegeraet
US4954526A (en) 1989-02-28 1990-09-04 The United States Of America As Represented By The Department Of Health And Human Services Stabilized nitric oxide - primary amine complexes useful as cardiovascular agents
FR2656218A1 (fr) 1989-12-21 1991-06-28 France Prod Oxygenes Co Dispositif de traitement local a gaz du corps humain ou animal.
US5155137A (en) 1990-09-20 1992-10-13 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Complexes of nitric oxide with polyamines
US5159924A (en) 1990-10-03 1992-11-03 Cegielski Michael J Method and apparatus for selectively mixing gases
US5570683A (en) 1990-12-05 1996-11-05 The General Hospital Corporation Methods and devices for treating pulmonary vasoconstriction and asthma
AU657726B2 (en) 1990-12-05 1995-03-23 General Hospital Corporation, The Devices for treating pulmonary vasoconstriction and asthma
US5396882A (en) 1992-03-11 1995-03-14 The General Hospital Corporation Generation of nitric oxide from air for medical uses
US5536241A (en) 1990-12-05 1996-07-16 The General Hospital Corporation Methods and devices for relaxing smooth muscle contractions
DE4105148A1 (de) 1991-02-20 1992-08-27 Draegerwerk Ag Narkosemitteldosiervorrichtung
US5154697A (en) 1991-04-02 1992-10-13 Topox, Inc. Collapsible topical hyperbaric apparatus
ES2179828T3 (es) 1992-02-07 2003-02-01 Vasogen Ireland Ltd Procedimiento para incrementar la concentracion de oxido nitrico en la sangre.
US5814666A (en) 1992-04-13 1998-09-29 The United States As Represented By The Department Of Health And Human Services Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents
US5954680A (en) 1992-06-19 1999-09-21 Augustine Medical, Inc. Near hyperthermic heater wound covering
US5632981A (en) 1992-08-24 1997-05-27 The United States Of America As Represented By The Department Of Health And Human Services Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same
US5405919A (en) 1992-08-24 1995-04-11 The United States Of America As Represented By The Secretary Of Health And Human Services Polymer-bound nitric oxide/nucleophile adduct compositions, pharmaceutical compositions and methods of treating biological disorders
US6200558B1 (en) 1993-09-14 2001-03-13 The United States Of America As Represented By The Department Of Health And Human Services Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same
FR2695831B1 (fr) 1992-09-24 1994-11-10 Air Liquide Installation et procédé de fourniture d'un mélange gazeux aux voies respiratoires d'un utilisateur.
US5427797A (en) 1993-04-06 1995-06-27 Brigham And Women's Hospital Systemic effects of nitric oxide inhalation
EP0621051B1 (de) 1993-04-17 2001-08-22 MESSER GRIESHEIM AUSTRIA Ges.m.b.H. Gerät zur kontrollierten Zudosierung von NO zur Atemluft von Patienten
GB2279014B (en) 1993-06-02 1997-07-16 Niall Keaney Device for controlling delivery of respiratory drugs
SE9302478L (sv) 1993-07-22 1994-11-07 Siemens Elema Ab Gasblandning och apparat för att tillföra gasblandningen till lungorna hos ett levande väsen
SE9302477L (sv) 1993-07-22 1995-01-23 Siemens Elema Ab Apparat för tillförsel av andningsgas
WO1995009612A1 (en) * 1993-10-07 1995-04-13 Entremed, Inc. Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents
CA2173738A1 (en) 1993-10-08 1995-04-20 James B. Mitchell Use of nitric oxide-releasing compounds as hypoxic cell radiation sensitizers
US5840759A (en) 1993-10-08 1998-11-24 The United States Of America As Represented By The Department Of Health And Human Services Use of nitric oxide releasing compounds to protect noncancerous cells from chemotherapeutic agents
GB9320978D0 (en) * 1993-10-12 1993-12-01 Higenbottam Timohy W Nitric oxide treatment
SE9303369L (sv) * 1993-10-12 1995-04-13 Lars Erik Gustafsson Respiratorisk anordning
ATE192922T1 (de) 1993-11-02 2000-06-15 Us Health Verwendung von stickstoffoxid freisetzenden verbindungen zur herstellung eines arzneimittels zum schutz gegen die ischämischen reperfusionsschäden
US5558083A (en) * 1993-11-22 1996-09-24 Ohmeda Inc. Nitric oxide delivery system
US5514204A (en) 1994-07-07 1996-05-07 The Boc Group, Inc. Process for the purification of nitric oxide
US5615669A (en) 1994-07-22 1997-04-01 Siemens Elema Ab Gas mixture and device for delivering the gas mixture to the lungs of a respiratory subject
US6190704B1 (en) 1994-09-23 2001-02-20 New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery Regulation of wound healing by nitric oxide
US6747062B2 (en) 1994-09-26 2004-06-08 New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery Regulation of wound healing by nitric oxide
US5519020A (en) 1994-10-28 1996-05-21 The University Of Akron Polymeric wound healing accelerators
US5648101A (en) 1994-11-14 1997-07-15 Tawashi; Rashad Drug delivery of nitric oxide
US5700830A (en) 1994-11-22 1997-12-23 The United States Of America As Represented By The Department Of Health And Human Services Use of nitric oxide-releasing agents for reducing metastasis risk
IT1272861B (it) * 1995-01-04 1997-07-01 Ausimont Spa Copolimeri dell'etilene con tetrafluoroetilene e/o clorotrifluoroetilene,aventi migliorate proprieta' meccaniche alle alte temperature
US6063407A (en) 1995-02-16 2000-05-16 The General Hospital Corporation Treatment of vascular thrombosis and restenosis with inhaled nitric oxide
US5823180A (en) 1995-04-03 1998-10-20 The General Hospital Corporation Methods for treating pulmonary vasoconstriction and asthma
US5722392A (en) 1995-05-19 1998-03-03 University Of Florida Breathable gas mixing devices, breathing systems and methods
SE506208C2 (sv) * 1995-07-05 1997-11-24 Aerocrine Systems Kb Anordning för uppsamling av gas från de övre luftvägarna och leverans av denna gas till inandningsluften i en respirator
GB9515807D0 (en) 1995-08-02 1995-10-04 Cantwell Evelyna D Topical hyperbaric bandage
JP3139364B2 (ja) 1995-11-29 2001-02-26 松下電器産業株式会社 キャビネット
SE9504310D0 (sv) 1995-12-01 1995-12-01 Siemens Elema Ab Doseringsanordning
ES2190467T3 (es) 1996-02-27 2003-08-01 Koster Henk W Sistema de respiracion con un modulo de administracion de gas adicional.
US5725492A (en) * 1996-03-04 1998-03-10 Cormedics Corp Extracorporeal circulation apparatus and method
PT914103E (pt) 1996-04-05 2006-09-29 Gen Hospital Corp Tratamento de uma hemoglobinopatia
US5765548A (en) 1996-05-07 1998-06-16 Perry; Bryan J. Use of nitric oxide in the treatment of exercised induced pulmonary hemorrhaging in equine
US5810795A (en) 1996-05-13 1998-09-22 Westwood; Joseph R. Hyperbaric device with secondary pressure zone
US5692497A (en) 1996-05-16 1997-12-02 Children's Medical Center Corporation Microprocessor-controlled ventilator system and methods
US5688236A (en) 1996-05-17 1997-11-18 Stephen's Medical, Inc. Topical hyperbaric device for treating skin disorders
US5848998A (en) 1996-07-11 1998-12-15 Marasco, Jr.; Patrick V. Tissue debriding apparatus
SE9602959L (sv) * 1996-08-12 1998-02-09 Siemens Elema Ab Förfarande vid blandning av gaser och en anordning för blandning av gaser
US5732693A (en) 1996-10-02 1998-03-31 Ohmeda Inc. Pause control of nitric oxide therapy
JP3207365B2 (ja) 1996-11-28 2001-09-10 株式会社タイコーデバイス 電磁継電器の製法
US6110895A (en) 1996-12-16 2000-08-29 University Of Southern California Method of promoting healing in skin grafts
DE59813457D1 (de) 1997-01-17 2006-05-11 Ino Therapeutics Gmbh Brunn Am Gesteuertes gasversorgungssystem
DE19701617A1 (de) * 1997-01-17 1998-07-23 Messer Griesheim Gmbh Gesteuertes Gasetherapiegerät
EP1001677A4 (en) 1997-02-04 2003-01-08 Gen Hospital Corp METHOD FOR TREATING EPIDERMAL OR DERMAL SKIN CONDITIONS
CA2225013C (en) * 1997-04-04 2006-06-06 Institut Du N.O. Inc. Injection system for delivery of a gaseous substance
JP4570696B2 (ja) 1997-04-10 2010-10-27 ジョンズ・ホプキンズ・ユニバーシティ ガスシリンジ装置
US5918596A (en) * 1997-04-22 1999-07-06 Instrumentarium Corp. Special gas dose delivery apparatus for respiration equipment
US6571790B1 (en) 1997-05-12 2003-06-03 Robert E. Weinstein Method and device for organizing and coordinating the combined use of liquid medications for continuous nebulization for the treatment of respiratory disorders
US6125846A (en) 1997-05-16 2000-10-03 Datex-Ohmeda, Inc. Purge system for nitric oxide administration apparatus
US6164276A (en) 1997-05-16 2000-12-26 Datex-Ohmeda, Inc. Accurate dose nitric oxide pulse delivery device with monitoring and alarms
ATE499343T1 (de) 1997-07-03 2011-03-15 Us Gov Health & Human Serv Stickoxid freistetzende amidin- und enaminverwandte diazeniumdiolate, zubereitungen und verwendungen davon und verfahren zu ihrer herstellung
US6067983A (en) 1997-09-19 2000-05-30 Sensormedics Corporation Method and apparatus for controlled flow sampling from the airway
US6796966B2 (en) 1997-10-15 2004-09-28 Jeffrey E. Thomas Apparatus, and kits for preventing of alleviating vasoconstriction or vasospasm in a mammal
AU9596698A (en) 1997-10-15 1999-05-03 Thomas Jefferson University Nitric oxide donor compositions, methods, apparatus, and kits for preventing or alleviating vasoconstriction or vasospasm in a mammal
US6109260A (en) 1998-02-18 2000-08-29 Datex-Ohmeda, Inc. Nitric oxide administration device with timed pulse
US6142147A (en) * 1998-03-31 2000-11-07 The General Hospital Corporation Nasal delivery system for inhaled nitric oxide
US6060020A (en) 1998-04-09 2000-05-09 S.P.M. Recovery Technologies Ltd Method and apparatus for treating objects with ozone
US6131572A (en) 1998-05-20 2000-10-17 Instrumentarium Oy Medical dosing device having dosing chamber with a pressure sensor
US6089229A (en) 1998-05-26 2000-07-18 Datex-Ohmeda, Inc. High concentration no pulse delivery device
US6103275A (en) 1998-06-10 2000-08-15 Nitric Oxide Solutions Systems and methods for topical treatment with nitric oxide
US6073627A (en) 1998-07-30 2000-06-13 Medizone International, Inc. Apparatus for the application of ozone/oxygen for the treatment of external pathogenic conditions
US20070086954A1 (en) 1998-11-23 2007-04-19 Miller Christopher C Method and apparatus for treatment of respiratory infections by nitric oxide inhalation
CA2254645A1 (en) * 1998-11-23 2000-05-23 Pulmonox Medical Corporation Method and apparatus for treatment of respiratory infections by nitric oxide inhalation
CA2350883A1 (en) 1998-11-23 2000-06-02 Pulmonox Medical Corporation Method and apparatus for treatment of respiratory infections by nitric oxide inhalation
KR100692422B1 (ko) 1999-03-03 2007-03-09 옵티노즈 에이에스 코 내부로 물질을 전달하는 장치
US6581599B1 (en) * 1999-11-24 2003-06-24 Sensormedics Corporation Method and apparatus for delivery of inhaled nitric oxide to spontaneous-breathing and mechanically-ventilated patients
US7516742B2 (en) * 1999-11-24 2009-04-14 Cardinal Health 207, Inc. Method and apparatus for delivery of inhaled nitric oxide to spontaneous-breathing and mechanically-ventilated patients with intermittent dosing
DE19961206A1 (de) * 1999-12-18 2001-07-05 Messer Austria Gmbh Gumpoldski Atemzugsvolumenabhängige Gasdosierung
JP2001178817A (ja) 1999-12-24 2001-07-03 Terumo Corp 人工腎臓用装置およびこれを用いた品質評価装置ならびに流体回路
US6758214B2 (en) 2000-01-28 2004-07-06 Cyterra Corporation Simple nitric oxide generator for ambulatory and/or bedside inhaled no treatment
AU2001241908A1 (en) 2000-03-08 2001-09-17 Frederick A. Gage Kidney perfusion solution containing nitric oxide donor
US20050142217A1 (en) 2000-04-26 2005-06-30 Adams Michael A. Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype
US7678391B2 (en) 2000-04-26 2010-03-16 Queen's University At Kingston Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype
US6270779B1 (en) 2000-05-10 2001-08-07 United States Of America Nitric oxide-releasing metallic medical devices
US6601580B1 (en) 2000-06-28 2003-08-05 The General Hospital Corporation Enhancing therapeutic effectiveness of nitric oxide inhalation
US6668828B1 (en) * 2000-10-16 2003-12-30 Pulmonox Technologies Corporations System and elements for managing therapeutic gas administration to a spontaneously breathing non-ventilated patient
US20020069877A1 (en) 2000-12-13 2002-06-13 Villareal Daniel C. Ventilation transport device
US6780849B2 (en) 2000-12-21 2004-08-24 Scimed Life Systems, Inc. Lipid-based nitric oxide donors
US7122018B2 (en) 2000-12-26 2006-10-17 Sensormedics Corporation Device and method for treatment of wounds with nitric oxide
US6432077B1 (en) 2000-12-26 2002-08-13 Sensormedics Corporation Device and method for treatment of surface infections with nitric oxide
US7335181B2 (en) 2000-12-26 2008-02-26 Pulmonox Technologies Corporation Nitric oxide decontamination of the upper respiratory tract
US20040009238A1 (en) * 2002-07-09 2004-01-15 Chris Miller Exogenenous nitric oxide gas (gNO) therapy in wound healing
US6706274B2 (en) 2001-01-18 2004-03-16 Scimed Life Systems, Inc. Differential delivery of nitric oxide
JP4681132B2 (ja) 2001-01-29 2011-05-11 味の素株式会社 一酸化窒素合成酵素産生促進剤および化粧料若しくは医薬組成物
ZA200306564B (en) 2001-02-26 2004-10-15 Optinose As Nasal devices.
US20020138051A1 (en) * 2001-03-26 2002-09-26 Hole Douglas R. System and method for the prevention and treatment of animal wound infections using nitric oxide
US20020155164A1 (en) 2001-04-18 2002-10-24 Curtis Figley System and method for the prevention of infections in human patients using nitric oxide
US20030228564A1 (en) 2001-05-30 2003-12-11 Edrich Richard Alan Nitric oxide in a pathogen inactivation process
KR100382183B1 (ko) 2001-07-26 2003-05-09 주식회사 자광 산화질소 및 인터페론-γ 생성 증가용 의약 조성물 및 그제조방법
US6867194B2 (en) 2001-08-09 2005-03-15 Wayne State University Enzyme activated nitric oxide donors
WO2003020211A2 (en) * 2001-09-05 2003-03-13 Cyterra Corporation Nitric oxide generation
US6673338B1 (en) 2001-09-10 2004-01-06 The United States Of America As Represented By The Department Of Health And Human Services Nitric oxide-releasing imidate and thioimidate diazeniumdiolates, compositions, uses thereof and method of making same
US6703046B2 (en) 2001-10-04 2004-03-09 Medtronic Ave Inc. Highly cross-linked, extremely hydrophobic nitric oxide-releasing polymers and methods for their manufacture and use
US6472390B1 (en) 2001-11-13 2002-10-29 Duke University Use of therapeutic dosages for nitric oxide donors which do not significantly lower blood pressure or pulmonary artery pressure
US6920876B2 (en) 2001-12-10 2005-07-26 Pulmonox Technologies Corporation Device for administration of nitric oxide to horses spontaneously breathing
AU2003210952A1 (en) 2002-02-08 2003-09-02 Gambro, Inc. Nitric oxide in a pathogen inactivation process
CA2480033C (en) 2002-03-21 2011-05-10 The University Of Utah Research Foundation In vivo use of glutathionone s-transferase activated nitric oxide donors
AU2003223491A1 (en) 2002-04-05 2003-10-27 Nitromed, Inc. Nitric oxide donors, compositions and methods of use
EP1507526A2 (en) 2002-05-07 2005-02-23 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES Polydiazeniumdiolated cyclic polyamines with polyphasic nitric oxide release and related compounds, compositions comprising same and methods of using same
EP1509236A4 (en) 2002-05-13 2008-07-30 Children S Hospital Los Angele TREATMENT AND PREVENTION OF ABNORMAL SCALING IN KELOIDS AND OTHER SKIN OR INTERNAL WOUNDS OR LESIONS
AU2003279236B8 (en) 2002-06-21 2009-02-19 Beth Israel Deaconess Medical Center, Inc. Pharmaceutical use of nitric oxide, heme oxygenase-1 and products of heme degradation
US20070065473A1 (en) 2002-07-09 2007-03-22 Miller Christopher C Nitric oxide gas (gO) as a cosmetic and wound healing agent
US6949530B2 (en) 2002-07-18 2005-09-27 The United States Of America As Represented By The Department Of Health And Human Services Nitric oxide-releasing amidine diazeniumdiolates, compositions and uses thereof and method of making same
CA2493082A1 (en) 2002-07-26 2004-02-05 Merck Frosst Canada & Co. Nitric oxide releasing prodrugs of diaryl-2-(5h)-furanones as cyclooxygenase-2 inhibitors
US20040081580A1 (en) 2002-09-10 2004-04-29 Doug Hole Use of nitric oxide and a device in the therapeutic management of pathogens in mammals
US20030039697A1 (en) 2002-09-12 2003-02-27 Yi-Ju Zhao Matrices containing nitric oxide donors and reducing agents and their use
US6854405B2 (en) 2002-10-15 2005-02-15 Cnh America Llc Internal tank augers for air seeder hoppers
US6938357B2 (en) 2003-09-09 2005-09-06 Carter Day International, Inc. Forced air circulation for centrifugal pellet dryer
US7485324B2 (en) 2003-09-29 2009-02-03 Pulmonox Technologies Corporation Use of exogenous gaseous nitric oxide in the treatment and disinfection of biofilms
US20050217668A1 (en) 2003-10-24 2005-10-06 Pulmonox Technologies Corporation System and elements for managing therapeutic gas administration to a spontaneously breathing non-ventilated patient
AU2004305016A1 (en) 2003-12-10 2005-07-07 Nitromed, Inc. Nitric oxide releasing pyruvate compounds, compositions and methods of use
US20050251117A1 (en) 2004-05-07 2005-11-10 Anderson Robert S Apparatus and method for treating biological external tissue
US8518457B2 (en) 2004-05-11 2013-08-27 Pulmonox Technologies Corporation Use of inhaled gaseous nitric oxide as a mucolytic agent or expectorant
AU2005244079A1 (en) 2004-05-11 2005-11-24 Pulmonox Technologies Corporation The use of inhaled gaseous nitric oxide as a mucolytic agent or expectorant
JP2007537267A (ja) * 2004-05-11 2007-12-20 センサーメディックス・コーポレイション 一酸化窒素ガスの間欠的投与
WO2005112954A1 (en) 2004-05-14 2005-12-01 William Marsh Rice University Nitric oxide releasing compositions and associated methods
US20060008529A1 (en) 2004-07-12 2006-01-12 Meyerhoff Mark E Use of additive sites to control nitric oxide release from nitric oxide donors contained within polymers

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102933250A (zh) * 2010-04-29 2013-02-13 迈柯唯销售服务德国有限公司 用于给借助呼吸装置人工呼吸的病人施加至少一种医疗气体的方法和装置
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US11058324B2 (en) 2011-12-21 2021-07-13 Capnia, Inc. Collection and analysis of a volume of exhaled gas with compensation for the frequency of a breathing parameter
CN108355215A (zh) * 2012-12-04 2018-08-03 马林克罗特医疗产品知识产权公司 用于在氧化氮递送期间对给药的稀释最小化的套管
US11331004B2 (en) 2013-02-12 2022-05-17 Capnia, Inc. Sampling and storage registry device for breath gas analysis
US11191449B2 (en) 2013-08-30 2021-12-07 Capnia, Inc. Neonatal carbon dioxide measurement system
CN107106079A (zh) * 2014-10-20 2017-08-29 卡普尼亚公司 用于筛查感染性疾病的呼吸分析系统及方法

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