CN106176046A - 用于滴注疗法使用的流体的刺激和激活的系统和方法 - Google Patents
用于滴注疗法使用的流体的刺激和激活的系统和方法 Download PDFInfo
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- CN106176046A CN106176046A CN201610847233.4A CN201610847233A CN106176046A CN 106176046 A CN106176046 A CN 106176046A CN 201610847233 A CN201610847233 A CN 201610847233A CN 106176046 A CN106176046 A CN 106176046A
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Abstract
本申请涉及用于滴注疗法使用的流体的刺激和激活的系统和方法。在此披露了刺激或激活在伤口处理系统中使用的流体的系统和方法。
Description
本申请是申请日为2012年5月22日,申请号为201280022323.X,发明名称为“用于滴注疗法使用的流体的刺激和激活的系统和方法”的申请的分案申请。
相关申请的交叉引用
本申请要求2011年5月26日提交的美国临时专利申请序列号61/490,150的优先权,该申请的全部内容通过引用结合在此。
背景技术
1.发明领域
本发明总体上涉及伤口的治愈和伤口处理疗法。更具体地但非限制性地,本发明涉及流体滴注和负压伤口疗法。
2.背景技术
临床研究和实践已显示,在一个组织部位附近提供治疗流体、特别是连同减压,增进并且加速在该组织部位处的新组织的生长。这种现象的应用很多,但减压的应用在治疗伤口方面一直特别成功。这种治疗(在医学界时常称为“负压伤口疗法”、“减压疗法”、或“真空疗法”)提供了许多益处,包括加快治愈和增强肉芽组织形成。典型地,通过一个伤口插入物(例如,一个多孔垫或其他歧管器件)向组织施加减压。该伤口插入物典型地含有多个洞或孔,这些洞或孔能够使减压分布于组织并且引导从该组织吸取的流体。该伤口插入物能够被结合到一个伤口敷件上,该伤口敷件具有有助于处理的其他部件如(例如)盖布(例如,粘性手术盖布)。滴注流体可以被递送到该伤口插入物并保持在该伤口部位处的适当位置,从而进一步改进治疗效果。
伤口处理系统包括例如多个滴注治疗单元(如可从美国德克萨斯州圣安东尼奥市铠唏尔公司(Kinetic Concepts,Inc.,San Antonio,Texas U.S.A.)购得的V.A.C.Ulta治疗系统),该伤口处理系统可以用于递送流体显现出比盐水更明显的治疗效果,并且实际上可以在复杂性上和能力上扩展,以便能够根据伤口条件出于不同目的递送多种流体。据信,流体将能够用来减少感染、帮助清创、改善敷件可移除性、以及处理积聚在伤口中的生物膜。
某些系统提供具有多个分子的流体,这些分子是特制的并有效地提供以上所述的这些效果,但经常不是设计用于随着时间给予该流体并使该流体暴露于管道和其他塑料部件的系统。例如,伤口处理流体可以含有一种活性分子,该活性分子与不同类型的塑料和光(包括,例如,紫外光)进行反应,从而减弱分子效力并使它到伤口部位的实际递送更加困难。
因此,在具有可以对某些材料或光接触的负面影响敏感的多个分子的系统中所希望的是保护它们或使它们对这些范围的有害影响免疫直到该系统确定它们应该是活性的为止。
如在此所描述的,可能的是提供对伤口处理系统中所使用的流体的刺激或激活的控制。
概述
在此提供了刺激或激活伤口处理系统中所使用的流体的系统和方法。
某些实施例包括一种伤口处理系统,该系统包括:一个伤口敷件;一个流体存储装置,该装置包括一种流体,其中该流体存储装置与该伤口敷件处于流体连通;以及一个能量源,该能量源被配置成将能量引导到该流体并激活该流体的一种治疗特性。多个具体实施例进一步包括联接到该伤口敷件上的一个负压源。在某些实施例中,该流体在暴露于该能量源之前包含具有一个涂层的多个分子。在多个具体实施例中,该能量源被配置成降解该保护性涂层。在多个特定实施例中,该能量源被配置成激活使该保护性涂层降解的该流体的一个组分。
在某些实施例中,该保护性涂层包括一个聚合物外壳。在多个具体实施例中,该保护性涂层包括一种生物可吸收玻璃。在多个特定实施例中,该保护性涂层包括一种陶瓷制品。
在多个具体实施例中,该能量源发射超声能。在某些实施例中,该能量源发射磁能。在多个特定实施例中,该能量源发射射频能。在多个具体实施例中,该能量源发射电离辐射能。在某些实施例中,该能量源发射微波能。在某些实施例中,该能量源发射光能。在多个具体实施例中,该能量源被配置成将能量引导到该伤口敷件附近的流体。
多个特定实施例包括与该流体存储装置和该伤口敷件处于流体连通的一个导管。在某些实施例中,该能量源被配置成将能量引导到该导管中的流体。多个具体实施例包括一个联接构件,该联接构件将该导管联接到该伤口敷件上。在某些实施例中,该能量源被配置成将能量引导到该联接构件。在多个特定实施例中,该治疗特性包括一种抗生特性。在某些实施例中,该治疗特性包括一种止痛特性。在多个具体实施例中,该治疗特性帮助组织的清创。在某些实施例中,该治疗特性改进了将该伤口敷件从一个伤口移除的能力。在多个特定实施例中,该治疗特性减少了积聚在一个伤口的生物膜。
多个具体实施例包括一种处理伤口的方法,其中该方法包括:将一个伤口敷件施加到一个伤口上;将流体输送到该伤口敷件;并且将能量引导到该流体并激活该流体的一种治疗特性。在某些实施例中,该能量被引导到该伤口敷件附近的流体。多个特定实施例还包括将一种负压施加到该伤口敷件上。多个具体实施例还包括提供一个流体存储装置和一个导管与该伤口敷件处于流体连通。在某些实施例中,当该流体在该导管中时,将该能量引导到该流体。多个具体实施例还包括一个联接构件,该联接构件将该导管联接到该伤口敷件上。在多个特定实施例中,该能量被引导到该联接构件处的流体。在某些实施例中,该流体包含多个分子,这些分子具有一个涂层和一种活性剂,并且将能量引导到该流体使该保护性涂层分解。
多个具体实施例包括一种伤口处理系统,该系统包括:一个伤口敷件;一个负压源,该负压源被联接到该伤口敷件上;一种流体存储装置,该装置包括一种流体,该流体含有具有一个涂层的多个分子,其中该流体存储装置被配置成用于与该伤口敷件处于流体连通;以及一个能量源,该能量源被配置成将能量引导到该流体并使该涂层降解。
在多个特定实施例中,该能量源将光能引导到该流体。在某些实施例中,该能量源将超声能引导到该流体。在某些实施例中,该能量源将磁能引导到该流体。在多个具体实施例中,该能量源将射频能引导到该流体。在某些实施例中,该能量源将电离辐射能引导到该流体。在多个具体实施例中,当该涂层被降解时,该流体的一种治疗特性被激活。
某些实施例包括一种处理伤口的方法,其中该方法包括:将一个伤口敷件施加到一个伤口上;将流体输送到该伤口敷件上,其中该流体包含具有一个涂层的多个分子;并且将能量引导到该流体并使该涂层降解。在多个特定实施例中,使该涂层降解激活了该流体的一种治疗特性。在多个具体实施例中,该治疗特性包括一种抗生特性。在某些实施例中,该治疗特性包括一种止痛特性。在多个具体实施例中,该治疗特性帮助组织的清创。在某些实施例中,该治疗特性改进了将该伤口敷件从一个伤口移除的能力。在多个具体实施例中,该治疗特性减少了积聚在一个伤口的生物膜。
以下附图通过举例方式而不是限制性方式进行说明。为了简明和清楚起见,在显现给定结构的每幅图中没有总是标记该给定结构的每个特征。相同参考数字未必指示相同结构。而是,相同参考数字可以用于指示类似特征或具有类似功能的特征,不相同参考数字同样可以如此。
附图简要说明
图1示出了一种伤口处理系统的一个实施例的示意图。
图2示出了图1的实施例的示意视图。
说明性实施例的说明
术语“联接”被定义为连接,虽然未必是直接地并且未必是机械地;被“联接”的两个项可以彼此整合。术语“一个(种)”被定义作为一个(种)或多个(种),除非本披露明确另有所指。术语“大致上”、“大约”、以及“约”被定义为所指明的大部分但未必是全部的,正如本领域中的普通技术人员所理解的那样。
术语“包括(comprise)”(以及包括的任何形式,如“包括了(comprises)”和“包括有(comprising)”)、“具有”(以及具有的任何形式,如“具有(has)”和“具有了(having)”)、“包含(including)”(以及包含的任何形式,如“包含了(includes)”和“包含有(including)”)、以及“含有(contain)”(以及含有的任何形式,如“含有了(contains)”和“含有着(containing)”)是开放式连系动词。因此,“包括”、“具有”、“包含”、或“含有”一个或多个步骤的一种伤口处理方法拥有那些一个或多个步骤,但不限于仅拥有那些一个或多个步骤。类似地,“包括、”、“具有”、“包含”、或“含有”一个或多个元件的一个伤口敷件拥有那些一个或多个元件,但不限于仅拥有那些元件。例如,在包括本伤口插入物和一个盖布中的一个的一个伤口敷件中,该伤口敷件包括这些特定元件但不限于仅具有那些元件。例如,这样一个伤口敷件还可以包括一个连接垫,该连接垫被配置成联接到一个负压伤口治疗(NPWT)设备(例如,包括一个真空源和/或一个流体源)上。
另外,以某种方式配置的一个装置或结构至少是以那种方式进行配置,但它也可以按除了确切描述的那些之外的其他方式进行配置。
现转向这些附图,图1描述了一个伤口处理系统100的示意图,该系统包括一个伤口敷件110、一个流体存储装置120、一个能量源130、以及一个负压源140。首先将提供操作伤口处理系统100的概述,接着提供对一个示例性实施例的更详细的讨论。
在图1所示的示例性实施例中,流体存储装置120与伤口敷件110经由一个导管150处于流体连通。此外,能量源130联接到一个联接构件160上,该联接构件转而联接到伤口敷件110上。
在这个示例性实施例中,流体存储装置120包括一种流体170,该流体具有分子175,这些分子具有包围一种活性剂177的一个保护性涂层176。在操作过程中,将流体170从流体存储装置120穿过导管150和联接构件160输送到伤口敷件110上。在所示的实施例中,可以激活能量源130以便将能量引导到联接构件160处的流体170。流体170暴露于从能量源130发射的能量可以使保护性涂层176降解或分解并允许活性剂177是暴露的,从而激活流体170的一种治疗特性。然后,负压源140可以将流体170从伤口敷件110吸取到一个适合的存储容器(未示出)中。
现参照图2,在此提供了对伤口处理系统100的一个更详细的视图和讨论。在这个实施例中,流体存储装置120和能量源130与一个供给泵126和一个控制系统127一起容纳在伤口处理设备180中。如先前所解释的,流体存储装置包括流体170,该流体具有分子175,这些分子具有包围活性剂177的保护性涂层176。在这个实施例中,控制系统127用来控制供给泵126,该泵将流体170泵送到伤口敷件110上。应理解,在其他示例性实施例中,在不用供给泵126的情况下,负压源140可以用于将流体从流体存储装置120吸出。
在这个实施例中,伤口敷件110包括一个伤口插入物112,该伤口插入物被示出放置在一位患者(未示出)的伤口116中。一个盖布114被放置在伤口116和伤口插入物112之上,这样使得伤口插入物112处于盖布114与伤口116之间。在所说明的实施例中,盖布114被联接到该患者的皮肤118上。在这个示例性实施例中,伤口插入物112通过导管150联接到一个流体存储装置120上。伤口处理设备180还可以包括负压源140,该负压源被配置成通过一个导管145或导管150(如果该导管是如下面进一步解释的一个多腔导管)将负压施加到伤口插入物112上。
伤口插入物112可以是一个泡沫构件,该泡沫构件可以是开孔的和/或网状的。在多个特定实施例中,该伤口插入物包括一种开孔网状泡沫。开孔网状泡沫具有一种网状微结构,其中即使有闭合的孔也是极少数的。在某些实施例中,孔隙率的范围可以是从95%-98%,但可以使用孔更少的泡沫或孔更多的泡沫。
在某些实施例中,伤口插入物112可以包括一种聚氨酯,如聚氨酯-聚酯或聚氨酯-聚醚;聚烯烃类,如聚丙烯(PP)或聚乙烯(PE);硅氧烷聚合物;聚氯乙烯;聚酰胺类;聚酯类;丙烯酸类;热塑性弹性体,如苯乙烯-丁烯-苯乙烯(SBS)或苯乙烯-乙烯-丁烯-苯乙烯(SEBS);聚醚-酰胺嵌段共聚物(PEBAX);弹性体,如丁苯橡胶(SBR);乙丙橡胶(EPR);三元乙丙改良橡胶(EPDM);天然橡胶(NR);乙烯乙酸乙烯酯(EVA);聚乙烯醇(PVOH);聚乙烯醇缩乙醛;或聚乙烯醇缩丁醛(PVB)。此外,伤口插入物20可以包括一种生物可吸收聚合物,该聚合物的实例包括聚乳酸、聚交酯(PLA)、聚乙醇酸、聚乙交酯(PGA)、以及聚己酸内酯(PCL)。制造开孔网状泡沫的方法是众所周知的。开孔网状泡沫可从各种来源商购,包括美国德克萨斯州圣安东尼奥市铠唏尔公司(www.kcil.com)。
伤口插入物112可以是具有深度尺寸的任何适合的形状,包括一种薄片、一种矩形棱柱、一种圆锥体、一种圆柱体、一种球体、或任何其他合适的形状。
在所示的示例性实施例中,伤口处理设备180包括一个流体存储装置120,该流体存储装置被配置成将流体170穿过导管150输送到伤口敷件110上。在某些示例性实施例中,流体170可以包括医学流体、抗菌流体、或冲洗流体。
在多个特定的示例性实施例中,导管150可以包括一个单腔导管(例如,在一个真空源和/或一个流体源之间切换)、或可以包括多个单腔导管、或一个多腔导管,这样使得(例如)可以单独地或同时地递送流体到伤口敷件110和/或可以将负压施加到该伤口敷件上。在其他示例性实施例中,导管150可以(例如)如在一个单个导管中包括多个腔,其中一个中央腔用于施加负压和/或递送流体;以及一个或多个外围腔,这个或这些外围腔邻近或包围该中央腔布置,这样使得可以将这些外围腔联接到一个压力传感器上,以感测和/或检测盖布114与伤口表面之间的一个压力或负压。在所示的实施例中,系统100进一步包括一个联接构件160,该构件被配置成联接到导管150上。适合的联接构件160的一个实例是“V.A.C.T.R.A.C.(R)垫”,它可从美国德克萨斯州圣安东尼奥市美国铠唏尔公司(KCI USA,San Antonio,Texas U.S.A.)商购获得。适合的盖布114的一个实例是“V.A.C.(R)盖布”,它可从美国德克萨斯州圣安东尼奥市铠唏尔公司(www.kcil.com)商购获得。不同的伤口治疗系统和部件可通过铠唏尔公司及其附属公司商购获得。
在图2所示的实施例中,伤口处理设备180可以被配置成将滴注流体递送到伤口116上、将流体从伤口116去除、并且将负压穿过盖布114和伤口插入物112施加到伤口116上。
伤口处理设备180可以被激活以便将流体170从流体存储装置120穿过通过联接构件160联接到伤口插入物112的导管150递送到伤口116上。负压源140还可以被致动以便将负压穿过盖布114和伤口插入物112提供到伤口116上。
可以被递送到伤口116上的流体170的实例包括次氯酸(HOCl)和次氯酸离子(ClO-,通常也被称为OCl-、一般被理解为与其同义并且在本披露中可以与其可互换地提及),它们都是用于杀生作用的有效的抗微生物剂的实例。例如,HOCl典型地能够杀死大范围的微生物(例如,真菌、细菌、病毒、真菌、酵母等);经常在相对短的时间段内(例如,能够在小于10秒的一段时间内杀死大于99%的微生物)。
此类抗微生物剂可以通过本发明的反应剂与流体(例如,水和/或水溶液,例如像,盐水溶液)的组合产生或形成,并且可以比在过去的伤口处理中所使用的抗生素和其他通常使用的抗微生物剂更有效和/或更通用。例如,抗生素可以是细菌-特异性的,以使得可能需要测试来确定用于一种特定伤口或感染的一种适合的抗生素;和/或以使得抗生素可能仅具有针对单独伤口和/或感染的有限的有效性(例如,在不执行测试的情况下和/或在一个伤口被多种不同的细菌感染的情况下)。
这种测试可能花费长达数天的时间以便确定一种适当的抗生素,从而延迟了处理或一种有效的抗生素的选择。此外,细菌可能发展出对抗生素的耐受性,这样使得抗生素可能在一定量的时间之后具有减少的效力。此外,抗生素典型地以静脉的方式(系统性地)给予,这样使得抗生素可能杀死有益的细菌(例如,在患者的消化系统中)和/或可能引起器官损伤(例如,对患者的肝脏)。
此外,伤口处理设备180可以被配置成从伤口116去除余下的滴注流体、分泌物、和/或被感染的组织。不希望的流出液可以通过启动负压源140来去除;流出液可以流入伤口插入物中,穿过导管145,并且流入联接到伤口处理设备180上的一个废物室中。
如前所述,在这个示例性实施例中,流体170包含分子175,这些分子具有包围一种活性剂177的一个保护性涂层176。在某些实施例中,保护性涂层176可以使用一种叠层技术(LbL)组成,其中聚丙烯胺盐酸盐(PAH)/聚4-苯乙烯磺酸钠(PSS)可以是用于形成涂层的层。
在操作过程中,随着将流体170最初从流体存储装置120输送并穿过导管150,保护性涂层176包围分子175的活性剂177。在到达联接构件160时,能量源130将能量引导到流体170并使保护性涂层176降解或分解。应理解,在其他实施例中,能量源130可以将能量引导到伤口处理系统100内的其他位置处的流体150。例如,能量源130可以将能量引导到伤口处理设备180内的一个位置处的流体170,沿着导管150或直接到伤口敷件110中。
在某些实施例中,可能有利的是使能量源130将能量引导到伤口敷件110附近的一个位置处的流体170。这样的配置可以允许保护性涂层176在流体170被输送到伤口敷件110时仍然留在适当的位置。这可以最小化流体170暴露于可能影响流体170的活性剂177的材料或环境条件(例如,光、温度等)的影响。
在某些实施例中,能量源130可以将超声能、磁能、射电能、电离辐射能、微波能、或光能引导到流体170。在多个特定实施例中,能量源130可以将紫外光波、红外光波、或可见光波引导到流体170。在某些实施例中,能量源130可以发射具有范围为约400nm-450nm的波长的光。在多个具体实施例中,能量源130可以发射γ射线、x射线、或电子束形式的电离辐射。
在多个具体实施例中,能量源130可以激活流体170的一个组分,该组分进而使保护性涂层176降解或分解。例如,流体170可以包含一个组分,该组分在具体温度或光条件下不使保护性涂层降解。然而,当能量源130将能量引导到流体170时,这些环境条件充分地改变使得该组分使保护性涂层176降解。在其他实施例中,能量源130可以被配置成直接使保护性涂层176降解而不使用流体170中的额外组分。
在保护性涂层176降解后,活性剂177可以对患者提供一种治疗效果。可能对患者提供的治疗效果的非限制性实例包括抗生特性和止痛特性。治疗特性还可以帮助清创、改进移除该伤口敷件的能力、以及减少积聚在该伤口中的生物膜。
通过保护保护性涂层176中的活性剂177直到流体170接近伤口敷件110,相信可以实现更精确的活性剂177的给药。例如,在某些现有技术的对活性成分不提供保护的伤口处理系统中,考虑到递送过程中的降解可能必须要在一个流体容器中增加活性成分的剂量或浓度水平。伤口处理系统100可以减少整个流体170输送过程中活性剂177降解的量。
在此所描述的装置、系统、以及方法的不同说明性实施例不旨在被限制于所披露的这些具体形式。而是,它们包括处于权利要求的范围内的所有修改和替代。例如,在某些示例性实施例中,该保护性涂层可以包括一种紫外线激活保护罩,该保护罩是部分激活的以便在行进通过该导管到达该伤口敷件时(或在存储在流体存储装置中期间)被环境光分解。然后,可以通过该伤口敷件附近的一个能量源完成该保护性涂层的分解。
在某些示例性实施例中,该流体而不是一种保护性涂层可以包含多个构造的分子,以便通过一种光敏分支(light sensitive branch)来抑制该活性剂。在这类实施例中,例如,暴露于紫外光可以用来打破该分支并激活这种化合物。这类配置在使用多种活性剂下会是有用的,这些活性剂因为一种自发反应或与周围环境的相互作用而具有一个较短的使用寿命。在多个具体实施例中,光抑制还可以用于控制这些活性剂的状态。
某些示例性实施例还可以包括一种凝血剂,例如纤维蛋白、壳聚糖、以及三价盐(如Fe+++和Al+++)。在多个具体实施例中,一个Fe+++化合物(如氯化铁)可以封装在一个葡萄糖敏感微胶囊(例如戊二醛交联的血红蛋白和葡萄糖氧化酶)中。在遇到葡萄糖(该葡萄糖可以存在于伤口流体中,或由用户灌输)时,微胶囊的可渗透性增加,从而允许Fe+++剂的释放。该伤口流体还可以进入该微胶囊并开始凝血反应。在多个特定实施例中,该凝血剂可施加到该伤口敷件上。该凝血剂可以通过一个活性层来保护,该活性层能够被血红蛋白激活并局部地释放该凝血剂。在某些实施例中,该凝血剂是在具有一个保护性涂层的一个分子中的活性剂,并且可以如在先前的示例性实施例中所描述的那样被激活。
在多个具体实施例中,凝血酶可以(例如)与纤维蛋白原结合在凝血机制中使用。在多个特定实施例中,可以由对脒基苯基-(E)-4-二乙基氨基-2-羟基-α-肉桂酸甲酯盐酸盐通过共价键键合而抑制或‘阻断’凝血酶。通过使阻断的凝血酶暴露于光(例如,在约366nm处),该凝血酶可以疏通,并可能发生凝血。
在其他示例性实施例中,该流体可以在该流体中包含多种分子、颗粒或试剂,这些分子、颗粒或试剂通过不同波长的光或不同频率的能量激活,它们在即将进入该伤口或一在该伤口中时被递送,以便激活它们。例如,在某些实施例中,一种光激活的基团(例如,如上所述的凝血酶纤维蛋白原基团)可以在一个位置处移植到一个分子上。在该分子上的另一个位置处,可以移植一个基团,该基团在暴露于于不同于366nm的波长的光时释出多个阳离子。可以用来释出阳离子的这类化学基团的非限制性实例包括(光产酸源[PAG]),处于150nm至350nm的UV光范围的是碳硼烷以及二苯基碘硝酸盐(在约226nm处激活)。避免移植的一种简单的替代方案将是将这两种敏感材料(凝血剂和阳离子剂)混合。阳离子剂将是酸性的并可以帮助清创。
在具体的示例性实施例中,通过一种靶标组织(如坏死组织)局部的伤口插入物上的一个涂层,或通过局部化的外部刺激,该能量源的局部激活可以被用于该伤口。在某些示例性实施例中,可以利用该伤口流体中的多个分子,这些分子基于与该伤口中的生物标志物(例如,炎症应答标记物)反应而激活。
权利要求不旨在包括、并且不应被解释为包括装置加功能或步骤加功能式限制,除非在给定权利要求中相应地使用一个或多个术语“装置用于”或“步骤用于”明确地详述了这样的限制。
Claims (10)
1.一种伤口处理系统,包括:
一个伤口敷件;
一个流体存储装置,所述流体存储装置被配置成将流体递送到所述伤口敷件;以及
一个能量源,所述能量源被配置成将能量引导到所述流体并且激活所述流体的一种治疗特性。
2.根据权利要求1所述的伤口处理系统,其中所述流体在暴露于所述能量源之前包含具有一个涂层的多个分子。
3.根据权利要求2所述的伤口处理系统,其中所述能量源被配置成使所述涂层降解。
4.根据权利要求2所述的伤口处理系统,其中所述能量源被配置成激活使所述涂层降解的所述流体的一个组分。
5.根据权利要求2所述的伤口处理系统,其中所述涂层包括一种生物可吸收玻璃。
6.根据权利要求2所述的伤口处理系统,其中所述涂层包括一种陶瓷制品。
7.根据权利要求1所述的伤口处理系统,其中所述能量源发射超声能。
8.根据权利要求1所述的伤口处理系统,其中所述能量源发射磁能。
9.根据权利要求1所述的伤口处理系统,其中所述能量源发射射频能。
10.根据权利要求1所述的伤口处理系统,其中所述能量源发射电离辐射能。
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- 2012-05-22 WO PCT/US2012/038932 patent/WO2012162287A1/en not_active Ceased
- 2012-05-22 EP EP12724062.0A patent/EP2714117B2/en active Active
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2014
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2016
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2017
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| US20140200526A1 (en) | 2014-07-17 |
| AU2016228240A1 (en) | 2016-10-06 |
| EP2714117A1 (en) | 2014-04-09 |
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| US9623224B2 (en) | 2017-04-18 |
| AU2012258916B2 (en) | 2016-06-16 |
| US20170239096A1 (en) | 2017-08-24 |
| EP2714117B1 (en) | 2016-01-06 |
| CA2834702A1 (en) | 2012-11-29 |
| JP6449015B2 (ja) | 2019-01-09 |
| US8708981B2 (en) | 2014-04-29 |
| JP2014519380A (ja) | 2014-08-14 |
| CN103517722B (zh) | 2016-10-19 |
| US20190336739A1 (en) | 2019-11-07 |
| WO2012162287A1 (en) | 2012-11-29 |
| CN103517722A (zh) | 2014-01-15 |
| CA2834702C (en) | 2019-03-26 |
| US10406337B2 (en) | 2019-09-10 |
| US20120302973A1 (en) | 2012-11-29 |
| AU2012258916A1 (en) | 2013-10-31 |
| AU2016228240B2 (en) | 2018-07-19 |
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