CN104736110A - 用于利用负压来处理和封闭伤口的装置和方法 - Google Patents
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Abstract
本发明涉及负压伤口封闭系统和用于使用这种系统的方法。本发明的优选实施例通过优先地收缩以提供用于组织的移动来促进伤口的封闭。
Description
相关申请的交叉引用
本申请要求2012年5月24日提交的,名称为DEVICES AND METHODS FOR TREATING AND CLOSING
WOUNDS WITH NEGATIVE PRESSURE的美国临时申请No. 61/651,483,以及2013年3月14日提交的,名称为DEVICES AND METHODS FOR TREATING AND CLOSING
WOUNDS WITH NEGATIVE PRESSURE的61/782,270的优先权,上述文献的内容通过引用整体并入本文中,如同其在本文中完整陈述。前述申请的优先权的权益根据适当的法律基础要求保护,包括但不限于根据35U.S.C.§119(e)。
技术领域
本文中描述的实施例涉及可用于利用负压来处理伤口的装置和方法。特定实施例还可用于辅助伤口例如,在腹部的伤口的封闭。
背景技术
在现有技术中,由于大气压力朝下且朝外抵靠伤口的边缘压缩伤口填充器,则负压的应用可有时在伤口边缘上施加朝外的力。伤口填充物的该朝下的压缩减缓了康复过程且减缓或者防止了伤口封闭。因此,存在对提供改进的用于处理和封闭伤口的器械、方法和系统的需要。
发明内容
总体上,本文中描述的实施例可用于辅助利用负压来处理伤口。实施例可在处理大的伤口,诸如腹部伤口中尤其有用,其中,伤口边缘的封闭和接近是富有挑战的。通过限制对伤口填充物施加的竖直压力的量,通过增强伤口填充物的水平塌陷,以及通过增强伤口填充物到伤口边缘的附连,连同本文中描述的附加细节,可获得改进的伤口封闭。
在一些实施例中,用于在利用负压来处理伤口中使用的伤口填充物包括:
多孔填充材料;
多个竖直延伸的部件,其构造成在伤口填充物定位在伤口床(wound bed)内时竖直延伸,竖直延伸的部件由比多孔伤口填充材料更坚硬的材料制成;以及
其中,在对伤口填充物施加负压时,伤口填充物构造成水平地收缩,其中,竖直延伸的部件减小伤口填充物的竖直移动。
在特定实施例中,竖直延伸的部件可为撑材、板层、圆柱或瓦片。在一些实施例中,上述伤口填充物实施例中的任一个的竖直延伸的部件是伸长部件,其构造成横过伤口床纵长地延伸且彼此平行对准。在特定实施例中,上述伤口填充物实施例中的任一个的多孔伤口填充材料可环绕竖直延伸的部件。在一些实施例中,上述伤口填充物实施例中的任一个的多孔伤口填充材料可在竖直延伸的部件之间延伸。在特定实施例中,上述伤口填充物实施例中的任一个的多孔伤口填充材料可包括多个裂缝或区域,更致密或更坚硬的撑材或板层插入该多个裂缝或区域中。
在特定实施例中,上述实施例中的任一个的伤口填充物可包括定位在竖直延伸的部件之间的柔韧的材料,以允许在伤口填充物定位在伤口床内以及在负压下放置时竖直延伸的部件朝彼此在水平平面中压缩。在一些实施例中,上述伤口填充物实施例中的任一个的竖直延伸的部件可粘附到多孔伤口填充材料。
在一些实施例中,一个或多个拉线或绳可延伸通过伤口填充物,使得拉线的拉动导致伤口填充物在水平平面中的收缩。
在特定实施例中,负压伤口治疗系统包括诸如本文中描述的那些的伤口填充物以及构造成放置在伤口填充物的上方的伤口覆盖件。在特定实施例中,上文中描述的负压伤口治疗系统还包括用于将伤口覆盖件连接到负压源的连接。在一些实施例中,上述负压伤口治疗系统还包括负压源,其构造成连接到伤口覆盖件,以在放置在伤口床内时对伤口填充物提供负压。
在一些实施例中,处理伤口的方法包括:
将之前描述的实施例中的任一个的伤口填充物定位到伤口床内;
利用伤口覆盖件覆盖伤口填充物;以及
对伤口覆盖件施加负压,其中,负压的施加导致伤口填充物水平地收缩,其中,竖直延伸的部件减小伤口填充物的竖直移动。
在下文中描述伤口封闭装置的其他实施例、稳定结构和关联器械。
附图说明
本发明的其他特征和优势将从结合附图的本发明的以下详细描述中显而易见,在附图中:
图1示出负压伤口治疗系统的一个实施例。
图2A是通过水平平面截取的伤口填充物的一个实施例的截面视图。
图2B是带有定位在其中的伤口填充物的伤口的截面视图。
图2C是带有定位在其中的伤口填充物的另一类型的伤口的截面视图。
图2D是带有定位在其中的伤口填充物的另一类型的伤口的截面视图。
图2E是带有定位在其中的伤口填充物的另一实施例的伤口的截面视图。
图3A-C图示了包括一个或多个拉线的伤口填充物的实施例。
图4A-B图示了包含坚硬的圆柱或瓦片的伤口填充物的实施例。
图Al-A11以及A13-A19图示了本申请的更多实施例。
具体实施方式
可与在下文中的描述的实施例一起利用的伤口填充物以及其他伤口处理器械和方法的实施例和/或可提供关于在下文中描述的实施例的更多细节的实施例在2012年5月24日提交的、美国临时申请No. 61/651,483中找到,该文献的全部通过引用并入本文中,且其一部分在下文中包括在名称为“其他负压治疗器械、敷料、伤口填充物以及方法”的章节中。
现在将参考以下附图和随后的描述来描述用于处理伤口的各种实施例。当然将理解,在不脱离本公开的精神的情况下,可在所示实施例的形式和细节中做出各种省略、替换和改变。另外,本文中描述的各种特征和过程可彼此独立地使用,或者可以以各种方式组合。所有可能的组合和子组合预期落在本公开的范围内。本文中描述的许多实施例包括类似的构件,且因此,这些类似的构件可在不同的实施例中互换。
本文中公开的实施例涉及利用减少的压力处理伤口的器械和方法,包括泵和伤口敷料构件以及器械。大体上,包括本文中描述的伤口填充物的实施例可与负压系统组合使用,负压系统包括放置在填充物的上方的盖层(drape)或伤口覆盖件。诸如泵的真空源可连接到盖,例如,通过连接到在盖中或盖的下面做出的孔口或端口的一个或多个管。包括伤口覆盖和包扎材料(如果有的话)的器械和构件在本文中有时统称为敷料。现在参考以下申请,其通过参考全部并入本文中:美国申请序列No. 12/886,088,名称为“SYSTEMS AND METHODS FOR
USING NEGATIVE PRESSURE WOUND THERAPY TO MANAGE OPEN ABDOMINAL WOUNDS”,2011年9月1日以US 2011/0213287公开;以及美国申请序列No. 13/092,042,名称为“WOUND DRESSING AND
METHOD OF USE”,2011年11月17日以US 2011/0282309公开。
将理解贯穿本说明书参考伤口或多个伤口。将理解术语伤口应当宽泛地理解且包含开放的以及封闭的伤口,其中皮肤撕裂、切割或刺破,或者其中,外伤导致创伤,或者在病人的皮肤上的任何其他表面的或其他的状况或缺陷,或者以其他方式受益于减少的压力处理。伤口因此宽泛地限定为其中可或可不产生流体的任一被损坏的组织区域。这种伤口的示例包括但不限于,急性的伤口、慢性的伤口、外科的切口和其他切口;亚急性和裂开的伤口、创伤伤口、瓣(flaps)和皮肤移植、裂伤、擦伤、挫伤、烧伤、糖尿病性溃疡、压力溃疡、人造口(stoma)、外科伤口、外伤和静脉溃疡等。在一些实施例中,本文中描述的负压处理系统的构件可尤其适用于流出小量的伤口流出物的切口伤口。
如在本文中使用地,减少的压力或负压水平,诸如-X mmHg,代表低于标准大气压力的压力水平,标准大气压力对应于760mmHg(或者1 atm,29.93 inHg,101.325 kPa,14.696 psi等)。因此,-X mmHg的负压值反映比760mmHg低X mmHg的绝对压力,或者换言之,(760-X)mmHg的绝对压力。此外,比X mmHg“更少的”或者“更小的”负压对应于更接近大气压力(例如,- 40mmHg小于 -60mmHg)的压力。比-X mmHg“更多”或者“更大”的负压对应于更远离大气压力的压力(例如,-80mmHg比-60mmHg更多)。
用于本公开的一些实施例的负压范围可大约为-80mmHg或在大约-20mmHg和-200mmHg之间。注意这些压力是相对于正常的环境大气压力。因此,-200mmHg以实际术语可为大约560mmHg。在一些实施例中,压力范围可在大约-40mmHg和-150mmHg之间。备选地,可使用多达-75mmHg,多达-80mmHg或超过-80mmHg的压力范围。在其他实施例还可使用低于-75mmHg的压力范围。备选地,可通过负压器械供应超过大约- 100mmHg或甚至150mmHg的压力范围。
如本文中所用地,在参考伤口时,术语“水平”指示大体平行于环绕伤口的皮肤的方向或平面。在参考伤口时,术语“竖直”大体指的是垂直于水平平面延伸的方向。在参考伤口时,术语“纵向”大体指的是沿着水平平面中伤口沿着其最长的方向截取的方向。在参考伤口时,术语“侧向”大体指的是在水平平面中垂直于纵向方向的方向。术语“水平”、“竖直”、“纵向”和“侧向”还可用于描述贯穿本说明书中描述的伤口填充物或其他装置。在描述这些伤口填充物或装置时,这些术语不应当理解为要求结构或装置必须沿特定定向放置到伤口内,虽然在特定实施例中,如此做可以是优选的。
如本文中所用地,在非限制方式中,术语“填充材料”包括多孔伤口填充物材料和柔韧的材料。如本文中所用地,可压缩的材料包括在柔韧的材料的范围内。
转向图1,在特定实施例中利用负压的伤口处理使用如此处示意地所示的负压处理系统101。在该实施例中,伤口位置110,此处示出为腹部的伤口位置,可受益于利用负压来处理。这种腹部的伤口位置可为例如事故的结果或由于外科介入。在一些情形中,诸如腹腔间隔室综合征、腹内高压、败血病或水肿的医学状况可要求利用通过腹部壁的外科切口以暴露腹膜空间的腹部解压,其后开口可需要维持在开放易接近的状态,直到状况解决为止。其他状况也可需要开口-尤其是腹腔中的—保持开放,例如如果要求多个外科过程(对于外伤而言可能是偶然的),或者如果存在诸如腹膜炎或引起坏死的筋膜炎的临床状况。
在其中存在伤口,尤其是在腹部中的情况下,期望涉及器官和腹膜空间的暴露的可能的并发症的管理,不管伤口是否保持开放或者如果其将封闭。优选地使用负压施加的治疗目标可为最小化传染的风险,同时促进组织生存能力以及从伤口位置移除有毒的物质。已经发现到伤口位置的减少的压力或者负压的施加大体促进更快的康复、增加的血液流动、减小的细菌负担、粒状组织形成的增加速率、刺激纤维原细胞的增殖,刺激内皮细胞的增殖、封闭长期开放的伤口、抑制烧伤渗透和/或提高瓣和移植物附连等。还已经报道表现出对通过负压施加的处理的积极响应的伤口包括被感染的开放伤口、褥疮溃疡、裂开的切口、部分厚度烧伤和瓣或移植物已经附连到其上的各种损伤。因此,对病人来说,到伤口位置110的负压施加可以是有益的。
因此,特定实施例提供用于待放置在伤口位置110上方的伤口接触层105。优选地,伤口接触层105可为薄的柔韧的材料,其将不粘附到伤口位置或紧密接近暴露的内脏。可使用诸如聚氨酯、聚乙烯、聚四氟乙烯的聚合物或其掺合物。在一个实施例中,伤口接触层是可渗透的。例如,伤口接触层105可设有开口,诸如孔、裂缝或通道,以允许从伤口位置110移除流体或者将负压传递到伤口位置110。
负压处理系统101的特定实施例还可使用多孔伤口填充物103,其可布置在伤口接触层105的上方。该衬垫103可从多孔材料构造,例如泡沫,其柔软、弹性柔韧,且对伤口位置110大体可适应。这种泡沫可包括例如由聚合体制成的开放的单元状(celled)以及网状泡沫。合适的泡沫包括由例如聚氨酯、硅酮和聚乙烯醇组成的泡沫。优选地,在对伤口施加负压时,该衬垫103可通过其本身引导伤口流出物和其他流体。一些衬垫103可包括用于这种目的的预成型通道或开口。在特定实施例中,衬垫103可具有在大约一英寸和大约两英寸之间的厚度。衬垫还可具有在大约16和17英寸之间的长度,以及在大约11和12英寸之间的宽度。在其他实施例中,厚度、宽度和/或长度可具有其他合适的值。下文中更详细讨论了可代替或者添附到衬垫103使用的伤口填充物的其他实施例。
优选地,盖层107用于密封伤口位置110。盖层107可为至少部分液体不能渗透的,使得在伤口位置可维持至少一个部分负压。用于盖层107的合适的材料包括但不限于不显著地吸收含水流体的合成的聚合物材料,包括诸如聚乙烯和聚丙烯的聚烯烃、聚氨酯、聚硅氧烷、聚酰胺、聚酯以及其他共聚物及其混合物。在盖层中使用的材料可为疏水性的或亲水性的。合适的材料的示例包括从Smith & Nephew可得的DeRoyal and OpSite®的Transeal®。为了辅助病人舒适且避免皮肤浸渍作用,在特定实施例中的盖层至少部分地可呼吸,使得水蒸气能够通过而没有保持困在敷料下方。粘性层可设在盖层107的底侧的至少一部分上,以将盖层紧固到病人的皮肤,虽然特定实施例可替代地使用分离的粘性或粘性条。可选地,释放层可布置在粘性层上方,以在使用之前保护它且促进盖层107的处理;在一些实施例中,释放层可由多个区段组成。
负压系统101可连接到负压源,例如,泵114。合适的泵的一个示例是从Smith & Nephew可得的Renasys EZ泵。盖层107可经由导管112连接到负压源114。导管112可连接到在盖层107中位于孔口109上方的端口113,或者另外导管112可通过孔口109直接连接而不使用端口。在更多的备选项中,导管可在盖层下方经过且从盖层的侧部延伸。美国专利No. 7,524,315公开了负压系统的其他类似的方面,且因此通过参考全部并入本文中,且应当被认为是该说明书的一部分。
在许多申请中,容器或其他存储单元115可在负压源114和导管112之间插入,以便允许伤口流出物和其他流体从伤口位置移除以存储而不进入负压源。特定类型的负压源-例如,蠕动泵-还可允许容器115放置在泵114后。一些实施例还可使用过滤器以防止流体、气溶胶和其他微生物污染物离开容器115和/或进入负压源114。更多实施例还可包括在容器中的截流阀或咬合的疏水性的和/或疏油性的过滤器以防止溢出;其他实施例可包括感测元件,诸如电容性传感器或其他流体水平探测器,其在容器中的流体水平接近容量时起作用以停止或关闭负压源。在泵出口处,还可优选地提供气味过滤器,诸如活性炭罐。
图2A-2E图示了可在上文中所述的系统中使用的伤口填充物200的实施例,其包括填充材料202和延伸部件204。在一些优选实施例中,填充材料是诸如上文中描述的多孔伤口填充物材料。在特定优选实施例中,填充材料202是柔韧的。如在图2A中的水平截面中所示,伤口填充物200可包括包含在椭圆形填充材料202内的多个延伸部件204。将理解,填充材料202可具有其他形状,诸如矩形或正方形,且在图2A中示出的形状可简单地由于填充物通过保健医生切割成适当大小而得到。如在图2A中所示的伤口填充物示出为当从上方观察伤口时带有外侧尺寸,其定尺寸成配合在椭圆形伤口内。
在一些实施例中,延伸部件204比填充材料202更致密。在一些实施例中,延伸部件204为填充材料的密度的1到2倍之间、2到4倍之间、4到6倍之间、6到8倍之间或8倍或密度更大。在特定实施例中,延伸部件204比填充材料202更坚硬。在一些实施例中,延伸部件为多孔伤口填充材料的硬度的1到2倍之间、2到4倍之间、4到6倍之间、6到8倍之间或8倍或硬度更大。
在特定优选实施例中,以及如在图2B-2E中所示,延伸部件204是伸长部件,其当伤口填充物200定位在伤口床内时竖直延伸。在特定实施例中,如在图2A中所示,延伸部件204是伸长部件,其还在伤口填充物200定位在伤口床内时横过伤口填充物的一部分或整个纵向长度水平延伸。在一些实施例中,延伸部件204是片材,其可具有平行面,而在其他实施例中,延伸部件204可包括撑材、板层、圆柱或瓦片。在其他实施例中,延伸部件204从伤口的水平或竖直平面以一定角度延伸。
延伸部件204可彼此平行或大致平行,且可或者相等地或不相等地间隔开204。在如在图2A中所示的水平截面中,延伸部件中的每一个可具有相同厚度,或者备选地,其可具有不同的厚度。在如在图2B-2E是示出的竖直截面中,延伸部件可具有相同的竖直高度或长度,或者可具有不同的竖直高度或长度。伤口填充物的尺寸,以及尤其延伸部件的水平长度和竖直高度,以及延伸部件的数量可取决于填充物材料通过保健医生所切割成的大小。在所示实施例中,延伸部件可在水平和竖直截面中都具有矩形截面,其中,水平长度大于厚度,且竖直高度大于厚度。在一些实施例中,延伸部件可包括片材。在一个实施例中,伤口填充物构造成放置在伤口中,使得延伸部件的水平长度平行或大体平行于伤口的纵向长度,且延伸部件的厚度尺寸沿侧向方向延伸。
在一些实施例中,如在图2A中所示,填充材料202包含用于插入延伸部件204的裂缝或区域。在一些实施例中,延伸部件204可在伤口填充物200已经放置在伤口中之后插入。在其他实施例中,延伸部件204在插入到伤口内之前放置在伤口填充物内。在一些实施例中,用于插入的裂缝或区域可在伤口填充物200已经放置在伤口中之后制成。在特定实施例中,用于插入的裂缝或区域在伤口填充物放置在伤口中以前制成。在其中填充材料202包含裂缝或区域用于插入延伸部件的实施例中,裂缝可对填充材料的顶部表面和/或底部表面开放,以允许延伸部件竖直插入。如在图2A中所示,延伸部件的水平长度可比填充材料202的水平尺寸更短,使得延伸部件204通过填充材料202在水平平面中完全地环绕。在一些实施例中,延伸部件可附连到填充材料,诸如利用粘合剂、倒钩、Velcro®或者其他附连机构。在其他实施例中,延伸部件可简单地插入到用于插入填充材料的裂缝或区域内且通过摩擦、过盈配合、延伸部件的轻微膨胀或其他机械力连接。
如在图2B-2D中所示,在定位在伤口内时延伸部件可竖直。图2B示出定位在伤口206内的伤口填充物200的实施例的侧部或竖直截面视图,其带有竖直延伸的部件204和填充材料202。延伸部件可类似于图2A中示出的那些,或者其可由可彼此平行或大致平行的备选的板层的材料构成。因此,在一些实施例中,代替具有通过填充材料插入或环绕的延伸部件,延伸部件和填充材料可包括多个层、片材或板层,其交替地堆叠和粘附在一起以形成合成层压件。例如,更柔韧的或可压缩的伤口填充物(例如,泡沫)的层可与更坚硬的伤口填充物的层交替地堆叠。将理解甚至在这种构型中,诸如泡沫的多孔材料的更多的层可放置在伤口填充物200上方以及下方,或者整个伤口填充物可通过诸如泡沫的多孔材料环绕。
在一些实施例中,在例如使用之前关于图1描述的系统对伤口填充物200施加负压之后,伤口填充物200构造成水平地收缩208,其中,竖直延伸的部件204减小伤口填充物200的竖直移动。填充材料202在多个竖直延伸的部件204之间延伸,且填充材料和竖直延伸的部件可粘附在一起。如在图2B中所示,当施加负压以封闭伤口206时,在竖直延伸的部件204之间的填充材料202可以可期望地压缩,以便伤口封闭时竖直延伸的部件变得更靠近在一起。
图2C示出在浅的伤口206中的伤口填充物200的实施例的截面视图,其包括带有定位在其中的多个延伸部件204的间隔区域的填充材料202。以关于在图2A-2B中描述的实施例类似的方式,伤口填充物构造成水平压缩208,但是竖直压缩是有限的。
图2D示出用于在伤口206中使用的伤口填充物200的实施例的另一截面视图,其类似于在图2A-2C中描述的实施例,包括与更低密度材料202交替的更致密材料204,这类似于上文中所述的实施例。在图2D的实施例中,伤口填充物200可具有如下形状或切割成如下形状,即,伤口填充物的上部和下部表面平行或大致平行。如所示,更致密材料204的延伸部件可具有相同的竖直高度。
图2E示出类似于在图2A-2D中描述的那些的伤口填充物的实施例,其中,伤口填充物可放置在通过腹部组织212环绕的腹部伤口210中。在一些实施例中,类似于上文中所述的实施例,伤口填充物200包括填充材料202和延伸部件204。在特定实施例中,当施加负压时,伤口填充物200构造成在水平平面中收缩,同时在竖直平面中保持坚硬。
在本文中描述的实施例的任一个中,伤口填充物可切割成适当的形状和大小以配合在伤口内。伤口填充物可以以任意方式修整成形,例如,通过围绕椭圆形伤口填充物的圆周修整,或者通过修整正方形或矩形伤口填充物的水平边缘。
在一些实施例中,在伤口填充物恰当地定尺寸后,延伸部件可对准,使得在放置在伤口腔中时,其与伤口床垂直且沿竖直方向延伸。在特定实施例中,真空的施加可然后导致填充材料大致仅在水平平面中收缩,因为延伸部件减小沿竖直方向的移动(以及还可抵抗水平移动)。在一些实施例中,填充物的压缩可辅助在水平平面中封闭伤口腔。
在一些实施例中,优选地可适用于在图2A-2E中描述的实施例,延伸部件的厚度可在从1到10mm(或者大约1到大约10mm)的范围内变化,例如,大约1mm到大约2mm,大约2mm到大约3mm,大约3mm到大约4mm,大约4mm到大约5mm,大约5mm到大约6mm,大约6mm到大约7mm,大约7mm到大约8mm,大约8mm到大约9mm,大约9mm到大约10mm,以及大于10mm(或者大于大约10mm)。在特定实施例中,填充材料的宽度可在从1到20mm的范围内变化(或者大约1到大约20mm),例如大约1mm到大约5mm,大约5mm到大约10mm,大约10mm到大约15mm,大约15mm到大约20mm,以及大于20mm(或者大于大约20mm)。在本文中描述的实施例中的任一个中,填充材料可粘附到延伸部件。在特定实施例中,填充材料通过粘结剂粘附到延伸部件。在特定优选实施例中,填充材料经由Velcro®带粘附到延伸部件。
在本文中描述的实施例中的任一个中,延伸部件可从诸如聚苯乙烯、聚碳酸脂、聚甲基丙烯酸酯的坚硬的塑料以及诸如硅酮的半硬式材料或者从坚硬的泡沫或黏结的柔韧泡沫制成。在一些实施例中,黏结的柔韧泡沫可通过使例如那些用作多孔可压缩填充物的柔韧泡沫经受热和压力以生产致密的、仍然多孔的半硬式泡沫而制成。这种构型还可提高水平移动,以便允许更大的伤口封闭。
在一些实施例中(未示出但是在临时申请No. 61/651,483中描述),提供伤口填充物,其包括通过可压缩的外侧层环绕的最小可压缩的中央核芯。这种构型可减小竖直移动,且允许伤口边缘沿朝中央核芯的方向朝内移动,因此辅助封闭伤口。而且,封闭的量可通过改变中央核芯的大小而受控制。在一些实施例中,中央核芯包括一个或多个坚硬泡沫、封闭的单元泡沫以及硅酮弹性体或者坚硬的柔韧泡沫。更多的实施例还可包括更坚硬(或者更致密)材料以及硬度更低(或密度更低)材料的交替的同心环。
在特定实施例中(未示出,但是在临时申请No. 61/651,483中在图3中描述),实施例可以与在以上段落中描述的实施例相反的方式构造,其中,最小可压缩的外侧层环绕可压缩的核芯。最小可压缩的外侧层可构造成抵抗竖直压缩,而中央核芯的压缩可辅助伤口封闭。与之前段落中的实施例类似,该实施例可以以同心圆周或椭圆形构型或者线性构型配置。
图3A示出包括填充材料302和一个或多个拉线或绳304的伤口填充物300的实施例。一个或多个拉线或绳可延伸通过填充材料,优选地带有从伤口填充物的顶侧延伸的自由端(即,在伤口填充物插入到伤口内时填充物的将面朝外的侧部)。在使用诸如上文中所述的系统施加负压时,拉线(其从伤口覆盖件延伸出来或在伤口覆盖件下方延伸)可被变紧,例如,通过沿竖直方向306拉动,由此导致伤口填充物大致仅在水平平面中收缩。
图3B示出伤口填充物310的实施例,其包括诸如在上述实施例中的任一个中描述的填充材料302和延伸部件308,以及一个或多个拉线或绳304。一个或多个拉线或绳延伸通过伤口填充物310,优选地带有从伤口填充物顶侧延伸的自由端。在优选实施例中,填充材料302和延伸部件308可交替。以与图2A-2E中描述的实施例类似的方式,延伸部件308可致密、更坚硬,或者比填充材料更致密以及坚硬。一个或多个拉线可延伸通过伤口填充物,优选地带有从伤口填充物的顶侧延伸的自由端(即,在伤口填充物插入到伤口内时填充物的将面朝外的侧部)。
在图3B的实施例中,因为拉线或绳304在邻近的或间隔开的延伸部件308之间形成环,所以拉动拉线可导致延伸部件在其间压缩填充材料且将延伸部件拉得更靠近在一起。在一些实施例中,拉线可附连或紧固在对于延伸部件308而言的期望位置,以促进将延伸部件拉得更靠近一起的能力。在一些实施例中,在使用诸如上文中所述的系统施加负压时,拉线或绳可例如通过沿竖直方向306拉动而变紧,因此导致伤口填充物大致仅在水平平面中收缩。
图3C示出类似于在图3B中描述的实施例的伤口填充物320的实施例,其包括填充材料302、延伸部件308和多个拉线324,其构造成导致伤口填充物320沿水平方向收缩。如图所示,拉线324可紧固到外侧延伸部件308,且可通过邻近的延伸部件从伤口填充物竖直延伸出来。在特定实施例中,在使用诸如上文中所述的系统施加负压时,拉线或绳324可例如通过沿竖直方向306拉动而变紧,因此导致伤口填充物大致仅在水平平面中收缩。在特定实施例中,伤口填充物包含多于2个、多于4个、多于6个或多于8个的拉线或绳。图4A-B图示类似于在图1A-G中所述的实施例的伤口填充物400的实施例的不同的视图。图4A描述了伤口填充物400的水平截面视图,其包括填充材料402和沿竖直平面或方向延伸的延伸部件404。优选地,延伸部件可为坚硬的圆柱或瓦片。在优选实施例中,在施加负压时,伤口填充物将优选地水平塌陷,而坚硬的圆柱或瓦片404大致防止伤口填充物竖直地塌陷,从而辅助伤口封闭。在一些优选实施例中,当圆柱或瓦片404优选地贯穿伤口填充物散布时,伤口填充物400可切割成伤口的大小。在优选实施例中,填充材料402包括泡沫。图4B示出在图4A中描述的伤口填充物的实施例的竖直截面。
在一些实施例中,坚硬的圆柱可包括诸如聚苯乙烯、聚碳酸脂的坚硬的塑料或诸如硅酮的半硬式材料。在特定实施例中,坚硬的圆柱可包括坚硬或黏结的泡沫。在一些实施例中,圆柱可具有圆形的截面,且可具有例如从5mm到10mm(或者大约5mm到大约10mm)的直径,且带有围绕其的5mm到10mm(或者大约5mm到大约10mm)的间隙。例如,圆柱的直径可为大约1mm、大约2mm、大约3mm、大约4mm、大约5mm、大约6mm、大约7mm、大约8mm、大约9mm、大约10mm或大于10mm(或大于大约10mm)。在特定实施例中,在圆柱之间的空隙可在从大约1mm到5mm、大约5mm到10mm、大约10mm到15mm、大约15mm到20mm或大于20mm(或者大于大约20mm)的范围内变化。
在一些实施例中(未示出,但是在临时申请No. 61/651,483中在图14中描述),伤口填充物可包括一个或多个管路,其延伸到面朝伤口的周界且构造成传达负压。此处,一旦伤口密封在盖层之下,则一个或多个管路可对伤口施加负压,因此接触在伤口的内部周界上的一个或多个区域。伤口填充物可包括如上文中描述的填充材料和延伸部件。伤口填充物优选地构造成包含一个或多个带子或者细丝,其带有沿竖直方向远离伤口延伸的自由端。在负压施加后,以及一旦伤口的边缘已经与伤口填充物变得接触,则可拉动一个或多个带子或者细丝,以便使伤口填充物朝内塌陷,因此辅助封闭伤口。在一些实施例中,带子或者细丝附连到延伸部件,且可包括本文中先前描述的拉线实施例中的任一项。
在一些实施例中,上述伤口填充物中的任一个可包括可分解的泡沫。在特定实施例中,伤口填充物可包括可分解泡沫的区域,其环绕在普通的生理状况下不溶解的一个或多个泡沫区域或者通过其环绕。在特定实施例中,可分解的泡沫区域可在中央,且通过一个或多个非可分解的泡沫带环绕。在一些实施例中,可分解的泡沫还处于环构型中,且可至少在水平平面上通过非可分解的泡沫环绕(或者反之亦然)。在特定实施例中,在植入伤口内时,泡沫的可分解的部分可至少部分地溶解,例如在与伤口流出物接触之后,由此提供用于非可分解的泡沫朝其塌陷的附加的空间。在优选实施例中,该塌陷可用于促进伤口的水平封闭。在一些实施例中,可分解的泡沫可包括聚乙烯醇泡沫(PVA)。
在特定实施例中,可分解的泡沫可通过可吸收的填充物(例如,可吸收组织填充物支架)替换。在一些实施例中,该组织填充物可从诸如聚乳酸、聚乙醇酸或两种聚合物的任意组合的生物可降解聚合物构造。在特定实施例中,可吸收支架可构造成释放有益的分子。在一些实施例中,支架构造成释放生长因子。在特定实施例中,支架构造成释放抗菌分子。在特定实施例中,这种支架可播种有益的细胞,诸如纤维原细胞或干细胞。在一些实施例中,这种支架可播种角化细胞。
在一些实施例中,上述伤口填充物中的任一个可从三维材料构造,三维材料包括更硬的竖直构件和沿侧向方向延伸的可压缩的构件,诸如3D织物以及纤维。在一些实施例中,材料可呈现为三维的非编织材料。在特定实施例中,这种伤口填充物材料可沿水平方向优选地塌陷或更容易塌陷,同时抵抗沿竖直方向的塌陷。
在一些实施例中,上述伤口填充物材料中的任一项可包括带有不同大小的气泡的泡沫材料。在一些实施例中,由于更小的气泡比更大的气泡更抵抗塌陷,所以泡沫大小可定制以控制伤口填充物的收缩。在特定实施例中,气泡可以以梯度配置,诸如纵长的或者圆形的梯度,以控制伤口填充物的可塌陷性。在特定实施例中,有气泡的该配置可使用双分配注入过程(dual dispense injection process)制造,其中,具有第一密度的第一材料(例如,第一小孔/气泡/空隙大小)以及具有第二密度的第二材料(例如,第二小孔/气泡/空隙大小)注入一个模具或者多个模具内。在一些实施例中,第二材料可为与第一材料相同的材料,但是具有在其中的不同的小孔大小或不同大小的空隙或气泡。在特定实施例中,不同的小孔、气泡的泡沫或空隙大小或密度可联接在一起。
一些实施例可包括带有各种压缩性的泡沫,其通过在生产泡沫时改变用于制造泡沫的材料的化学性质或组成而获得。例如,在没有限制的情况下,更长的柔软的(更可压缩的)聚合体嵌段或塑化剂可用于制造更可压缩的泡沫的全部或一部分。在一些实施例中,填充物的柔软(更可压缩的)嵌段或柔软(更可压缩的)部分可从聚丙二醇或聚丁二醇或其他类似的材料制成。在一些实施例中,填充物可具有从任一合适的充分高分子量的材料制成的柔软(更可压缩的)嵌段或柔软(更可压缩的)部分。
在一些实施例中,在泡沫材料的制造期间,传递通过用于注入或分配泡沫材料的注入器或分配器的材料的组成可变化,使得泡沫的密度或硬度沿着泡沫的长度改变。例如,在没有限制的情况下,泡沫可制造成使得,更柔软的、更可压缩的部分夹置或定位在泡沫的相同长度的更坚硬的、更少压缩的部分之间。因此,具有变化的压缩性的泡沫可一体地产生。在特定实施例中,包括本文中的实施例的任一个,其中,泡沫或填充物可在多个级中产生,更柔软更可压缩的泡沫部分可注入到或者以其他方式插入到更少可压缩的泡沫材料的空隙或气泡内,或者反之亦然,或者可形成(即,注入)或者定位在更少可压缩的泡沫材料的部分之间。在一些实施例中,如果形成在分离的泡沫嵌段或层中,则附加的材料可层压或以其他方式与其将与其一起使用的其他一种或多种材料联接。
在一些实施例中,处理伤口的方法可包括将上述伤口填充物中的任一项定位到伤口床内且利用伤口覆盖件覆盖伤口填充物。施加负压到这种实施例可导致伤口填充物水平地收缩,其中,竖直延伸的部件减小伤口填充物的竖直移动。
其他负压治疗器械、敷料、伤口填充物以及方法
可单独或者与本文中描述的实施例组合地使用的负压治疗器械、敷料、伤口填充物以及使用其的方法的更多的实施例以及上文中发现的实施例的更多描述在2012年5月24日提交的美国临时申请No. 61/651,483中发现,其全部通过参考并入本文中。作为附录包括在美国临时申请No. 61/782,270中的美国临时申请No. 61/651,483的部分在下文中复制。
图A1A-C图示了带有更致密的多孔伤口填充材料已经插入其中的裂缝或区域的多孔伤口填充材料的实施例,类似于在图2A-E中公开的实施例。实施例构造成插入到伤口内。在一些实施例中,多孔伤口填充材料是泡沫,例如开放的单元泡沫。上述实施例还可提高水平移动,以便允许更大的伤口封闭。
以类似于图2B中公开的实施例的方式,图A1B示出伤口填充物材料的实施例,其可切割成形且可由柔韧的或可压缩的伤口填充物(例如,泡沫)的备选板层连同更坚硬的伤口填充物构成。图A2示出伤口填充物,其包括由可压缩的外侧层环绕的最小可压缩的中央核芯。这种构型可减小竖直移动,且允许伤口边缘沿朝中央核芯的方向朝内移动,因此辅助封闭伤口。而且,封闭的量可通过改变中央核芯的大小而受控制。在一些实施例中,中央核芯包括一个或多个坚硬泡沫、封闭的单元泡沫以及硅酮弹性体。
图A3示出实施例,其以与上文中图A2相反的方式构造,带有环绕可压缩的核芯的最小可压缩的外侧层。最小可压缩的外侧层可构造成抵抗竖直压缩,而中央核芯的压缩可辅助伤口封闭。与图A2类似,图A3可配置成同心圆或椭圆形构型或线性构型。
在该实施例中,处理装置包括带有可收缩管的伤口填充物(例如,泡沫)。伤口填充物可放置到伤口腔内,其中可收缩管定位横过伤口的主轴且在填充物和伤口周边区域的顶部上定位。在其他实施例中,管可通过伤口填充物集成。盖层可然后放置在处理装置上方,且整个组件流体附连到负压源。
负压施加将导致填充物在水平平面中塌陷,但是管将减小填充物的竖直移动(其可另外施加使得伤口封闭更困难的水平力)。随着伤口边缘收缩,可收缩管将沿着其长度塌陷,因此与伤口一起封闭。
参考图A5,在该实施例中,诸如泡沫的伤口填充材料放置到伤口腔内。一个或多个加固件可然后放置在伤口、伤口填充物和伤口周边区域上方。一个或多个加固件可从抵抗压缩的坚硬或半硬式材料(诸如封闭单元泡沫)构造。真空的施加导致泡沫在水平平面中塌陷,然而一个或多个加固件减小泡沫的竖直压缩。
图A6示出伤口填充物的实施例,其带有在其基底上的最小粘附的伤口接触层且构造成与伤口床接触地放置。在一些实施例中,伤口接触层可包括硅酮,或者带有在其一个侧部上的更厚的皮肤的泡沫。在施加真空时,最小粘附的伤口接触层可促进泡沫水平地收缩,以便允许更大的伤口封闭。本文中的公开的实施例中的任一个,包括但不限于具有泡沫的那些或其他填充物或伤口包扎、具有圆柱或撑材的那些或其他支承元件,可具有在其一个或多个伤口接触表面的硅酮或其他光滑的材料或薄膜,以减小关于伤口的粘附或粘性。
图A7示出实施例,其中可从泡沫构造的伤口填充物包括插入其中的一个或多个穿线或者丝线。丝线优选地在水平平面中延伸,且可从形状记忆体聚合体或金属构造。丝线优选地以延伸形状插入或铸型(cast)到伤口填充物内,且在施加刺激之后,伤口填充物优选地在水平平面中收缩。在一些实施例中,导致穿线或丝线的收缩的刺激可为湿气、热或减少的压力的施加。
在一些实施例中,伤口填充物可包括完全地或部分地弹性形状记忆体泡沫。形状记忆体泡沫可施加预应力到延伸构型内,且在暴露于湿气后将收缩。合适的形状记忆体泡沫的示例是Elast-Eon®。
在该实施例中,伤口填充物具有延伸通过其的一个或多个拉线或绳,优选地带有从伤口填充物的顶侧延伸的自由端(即,在伤口填充物插入到伤口内时,填充物的侧部将面朝外)。在施加负压时,拉线可拉紧,例如通过沿竖直方向拉动,因此导致泡沫大致仅在水平平面中收缩。
图A8示出类似于在图3A-C中描述的实施例的实施例。拉线或绳可延伸通过结构。拉线在负压下拉紧且导致结构在仅一个平面中收缩。
图A9示出带有伤口填充物材料的实施例,其中,坚硬的圆柱或瓦片在竖直平面或方向中延伸,其为类似于在图4A-B中描述的实施例的实施例。在施加负压时,可包括泡沫的伤口填充物将优选地水平塌陷。坚硬圆柱或瓦片将大致防止伤口填充物竖直塌陷,因此辅助伤口封闭。有利地,当圆柱或瓦片优选地贯穿伤口填充物散布时,伤口填充物可切割成伤口的大小。
图A10示出伤口封闭装置的实施例,其包括坚硬的绿洲(oasis)或核芯,其由诸如网状泡沫的柔软、可适应伤口填充物环绕。核芯包括一个或多个在填充物材料和负压源之间连通的通路。在负压施加后,伤口填充物将朝核芯塌陷,因此优选地在水平平面中塌陷且便于伤口封闭。在一个实施例中,核芯包括构造成连接到负压源的中央导管(例如,经由导管或微型泵),其中,中央导管以与填充物的流体性连通联结到一个或多个周边管路。
图A11示出伤口封闭系统的实施例,其包括放置在伤口内部且利用盖层和框架覆盖的伤口填充物。框架可放置或组装在泡沫上方以及到盖层外部的伤口周边区域中,以及附连至盖层,以便约束盖层和伤口填充物的竖直移动。因此,填充物的水平塌陷将最大化。
参考图A13A,该实施例可具有可充气的囊,其至少部分通过诸如泡沫的多孔伤口填充物材料环绕。可充气的囊可填充有液体,且优选地包括一个或多个端口(例如,注射器端口),其可用于调整在其中的流体的量。在使用中,装置放置到伤口内且利用盖层覆盖,以及在负压施加后,流体可从可充气的囊抽出,以控制伤口边缘的收缩的量。优选地,流体经由通过盖层或在盖层下方连接的管抽出,该管将端口连接到不同的负压源,诸如注射器。
以类似于图A13A中示出的实施例的方式,图A13B示出带有通过诸如泡沫的伤口填充物至少部分环绕的可充气的包的实施例。此处,可充气的包填充有空气或气体,且可施加抽吸(与用于处理伤口的负压源分离)以控制泡沫的收缩的量。
图A14示出半硬式伤口填充物,其包括构造成传达负压的延伸到填充物的面朝伤口的周界的一个或多个管路。此处,一旦伤口在盖层之下密封,则一个或多个管路对伤口施加负压,因此接触在伤口的内部周界上的一个或多个区域。半硬式伤口填充物优选地构造成包含一个或多个带子或者细丝,其带有沿竖直方向远离伤口延伸的自由端。在负压施加后,以及一旦伤口的边缘已经与伤口填充物变得接触,则可拉动带子,以便使伤口填充物塌陷,因此辅助封闭伤口。
在图A15中,诸如泡沫的伤口填充物的实施例可具有使得其外部(面朝伤口)边缘切割,以提供附加的表面区域和突出以辅助固定到伤口表面。这些边缘可因此通过在负压施加后辅助一起拉动伤口边缘而提高伤口封闭。例如,锯齿剪切或者其他锯齿状切割实施可用于对伤口填充物增加锯齿、波浪形、皱褶、不规则的或粗糙不平的外侧周界。其他实施例可提供用于喷砂处理、磨光或增加微粒到伤口填充物的表面。
图A16示出用于在伤口中使用的压力响应泡沫的实施例。在负压施加后,常规泡沫倾向于在施加到其的治疗负压范围上方塌陷到大约相同尺寸。然而,通过修整其中体积跨治疗负压范围改变的压力响应泡沫,可实现在伤口封闭上方的更大控制。例如,这种泡沫可具有在给定的压力P1处的给定体积V1。如果负压增加到新的压力P2,则泡沫的体积可减少到小于V1的体积V2。因此,伤口封闭可通过对伤口施加负压而受控制。
图A17示出包括可分解的泡沫的伤口填充物的实施例。此处,伤口填充物可包括可分解泡沫的区域,其环绕在普通的生理状况下不溶解的一个或多个泡沫区域或者通过其环绕。在一些配置中,可分解的泡沫区域可在中央,且通过一个或多个非可分解的泡沫带环绕。可分解的泡沫还处于环构型中,且可至少在水平平面上通过非可分解的泡沫环绕(或者反之亦然)。在植入伤口内时,泡沫的可分解的部分可至少部分地溶解,例如在与伤口流出物接触之后,由此提供用于非可分解的泡沫朝其塌陷的附加的空间。其可用于促进伤口的水平封闭。在一些实施例中,可分解的泡沫可包括聚乙烯醇泡沫(PVA)。在一些实施例中,可分解的泡沫可通过可吸收的填充物(例如,可吸收组织填充物支架)替换。在一些实施例中,这种支架可播种有益的细胞,诸如纤维原细胞或干细胞。
图A18示出伤口封闭装置的实施例,其包括照相机快门或多件伤口填充物材料的虹膜状构型。优选地,伤口填充物材料至少在竖直的平面中大致坚硬。在负压施加后,多件伤口填充物材料优选地构造成从上文中示出的开放构型朝内移动到封闭构型,因此在水平平面中收缩伤口边缘。多件伤口填充物材料的朝内移动可类似照相机快门的朝内移动。
图A19示出伤口填充物装置的实施例,其包括布置在其外侧周界上,且优选地沿着水平外侧周界的一个或多个钩。一个或多个钩构造成接合伤口的边缘,以便辅助填充物的附连,因此辅助在负压施加后的伤口封闭。一个或多个钩可通过使用突然的局部热量“爆破(blast)”制成,该“爆破”可部分地熔化泡沫边缘以便生产带尖、钩或其他突出。静电能量到伤口填充物的施加还可用于制成一个或多个钩。
结合特定方面、实施例或示例描述的特征、材料、特性或组应当理解成可适用于本文中描述的任一其他方面、实施例或示例,除非与其不相容。在该说明书公开的全部特征(包括任一附随权利要求、摘要和附图),和/或如此公开的任一方法或过程的全部步骤可在任一组合中组合,除非在其中这种特征和/或步骤中的至少一些相互排斥的组合。保护不受限于任一前述实施例的细节。在该说明书中公开的特征的保护延伸到任一新颖的一个,或者任一新颖的组合(包括任一附随的权利要求、摘要和附图),或者到如此公开的任一方法或过程的步骤的任一新颖的一个、或任一新颖组合。
虽然已经描述了特定实施例,但是这些实施例仅通过示例的方式示出,且不预期限制保护范围。实际上,本文中描述的新颖的方法和系统可以以多种其他形式具体化。此外,可做出对本文中描述的方法和系统的形式的各种省略、替换和改变。本领域技术人员将理解,在一些实施例中,在所示出和/或公开的过程中采取的实际步骤可与在附图中示出的那些不同。取决于实施例,上文中所述的特定步骤可移除,其他的可增加。此外,上文中公开的具体实施例的特征和属性可以以不同的方式组合以形成附加的实施例,其全部落入本公开的范围内。
虽然本公开包括特定的实施例、示例和申请,但是本领域技术人员将理解,本公开延伸超出特定公开实施例到其他备选实施例和/或用途以及其明显的修改和等价物,包括不提供本文中陈述的全部特征和优势的实施例。因此,本公开的范围不预期通过本文中的优选实施例的具体公开限制,而是可通过本文中示出或如在未来示出的权利要求限定。
Claims (13)
1. 一种用于在利用负压来处理伤口中使用的伤口填充物,包括:
多孔伤口填充材料;以及
多个竖直延伸的部件,其构造成当所述伤口填充物定位在伤口床内时竖直延伸,所述竖直延伸的部件由比所述多孔伤口填充材料更坚硬的材料制成;
其中,在对所述伤口填充物施加负压时,所述伤口填充物构造成水平地收缩,其中,所述竖直延伸的部件减小所述伤口填充物的竖直移动。
2. 根据权利要求1所述的伤口填充物,其特征在于,所述竖直延伸的部件包括撑材、板层、圆柱、或瓦片中的一种。
3. 根据在先权利要求中的任一项所述的伤口填充物,其特征在于,所述竖直延伸的部件是伸长部件,其构造成横过伤口床纵长地延伸且彼此平行对准。
4. 根据在先权利要求中的任一项所述的伤口填充物,其特征在于,所述多孔伤口填充材料环绕所述多个竖直延伸的部件。
5. 根据在先权利要求中的任一项所述的伤口填充物,其特征在于,所述多孔伤口填充材料在所述多个竖直延伸的部件之间延伸。
6. 根据在先权利要求中的任一项所述的伤口填充物,其特征在于,所述多孔伤口填充材料包括多个裂缝或区域,更致密或更坚硬的撑材或板层插入所述多个裂缝或区域中。
7. 根据在先权利要求中的任一项所述的伤口填充物,其特征在于,柔韧的材料定位在所述竖直延伸的部件之间,以在所述伤口填充物定位在伤口床内且在负压下放置时,允许所述竖直延伸的部件朝彼此在水平平面中压缩。
8. 根据在先权利要求中的任一项所述的伤口填充物,其特征在于,所述多个竖直延伸的部件粘附到所述多孔伤口填充材料。
9. 根据在先权利要求中的任一项所述的伤口填充物,其特征在于,还包括延伸通过所述伤口填充物的一个或多个拉线或绳,其构造成使得拉动所述拉线将导致所述伤口填充物在水平平面中的收缩。
10. 一种负压伤口治疗系统,包括:
根据在先权利要求中的任一项所述的伤口填充物;以及
伤口覆盖件,其构造成放置在所述伤口填充物的上方。
11. 根据权利要求10所述的系统,其特征在于,还包括:用于将所述伤口覆盖件连接到负压源的连接。
12. 根据权利要求10或11所述的系统,其特征在于,还包括负压源,其构造成连接到所述伤口覆盖件,以当放置在所述伤口床内时对所述伤口填充物提供负压。
13. 一种处理伤口的方法,包括:
将根据权利要求1-9中的任一项所述的伤口填充物定位到伤口床内;
利用伤口覆盖件覆盖所述伤口填充物;以及
对所述伤口覆盖件施加负压,其中,负压的施加导致所述伤口填充物水平地收缩,其中,所述竖直延伸的部件减小伤口填充物的竖直移动。
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CN110167495B (zh) * | 2016-11-02 | 2022-06-14 | 史密夫和内修有限公司 | 伤口闭合设备 |
CN110167495A (zh) * | 2016-11-02 | 2019-08-23 | 史密夫和内修有限公司 | 伤口闭合设备 |
CN110612076A (zh) * | 2016-12-22 | 2019-12-24 | 应用纸巾技术有限公司 | 用于伤口处理的装置和方法 |
CN110740715A (zh) * | 2017-06-14 | 2020-01-31 | 史密夫及内修公开有限公司 | 用于伤口闭合的可塌缩片材及使用方法 |
CN110740715B (zh) * | 2017-06-14 | 2022-04-12 | 史密夫及内修公开有限公司 | 用于伤口闭合的可塌缩片材及使用方法 |
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US10117782B2 (en) | 2018-11-06 |
US20150150729A1 (en) | 2015-06-04 |
US11241337B2 (en) | 2022-02-08 |
ZA201408546B (en) | 2020-03-25 |
AU2013264937A1 (en) | 2015-01-15 |
US20220117791A1 (en) | 2022-04-21 |
EP3954347A1 (en) | 2022-02-16 |
EP2854734B1 (en) | 2018-08-22 |
JP6285421B2 (ja) | 2018-02-28 |
US20190231599A1 (en) | 2019-08-01 |
CN104736110B (zh) | 2019-05-31 |
JP2015517371A (ja) | 2015-06-22 |
AU2013264937B2 (en) | 2018-04-19 |
EP2854734A1 (en) | 2015-04-08 |
WO2013175309A1 (en) | 2013-11-28 |
MX2014014325A (es) | 2015-08-06 |
EP3470029A1 (en) | 2019-04-17 |
CA2874581A1 (en) | 2013-11-28 |
CA2874581C (en) | 2022-06-07 |
AU2013264937A2 (en) | 2018-04-12 |
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