CN101815551B - 具有射流元件的毛细管系统 - Google Patents
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Abstract
一种浮质产生系统,具有浮质发生器,其中液体组分至少部分地在毛细通道中汽化,并且从毛细通道中排出,以形成浮质。浮质产生系统包括:泵送单元(50),适于将液体组分供给到浮质发生器(90);以及射流元件(100),布置在泵送单元与浮质发生器的毛细通道之间,其中,当液体组分进入浮质发生器的毛细通道时,射流元件增大液体组分的压力。
Description
背景技术
毛细管浮质技术和毛细管浮质发生器已经在US 5743251中描述,该专利的内容由此通过参考全部包括。
发明内容
按照一个实施例,一种浮质产生系统,包括:浮质发生器,其中液体组分至少部分地在毛细通道中汽化,并且从毛细通道中排出,以形成浮质;泵送单元,适于将液体组分供给到浮质发生器的毛细通道;及射流元件,布置在泵送单元与浮质发生器的毛细通道之间,其中,当液体组分进入毛细通道时,射流元件增大液体组分的压力。
按照另一个实施例,一种生产浮质的方法包括:将液体材料按20μl/s(微升每秒)的流量供给到被加热的毛细通道,从而在通向毛细通道的进口处的液体的压力至少为7MPa(1000psi(磅每平方英寸));和用被加热的毛细管产生浮质。
附图说明
图1是按照一个实施例的浮质产生系统的立体图,该浮质产生系统具有在敞开位置的加热器块。
图2是图1的浮质产生系统的立体图,该浮质产生系统的加热器块在关闭位置。
图3是图1的浮质产生系统的易处置组件的立体图。
图4是图3的易处置组件的侧视图。
图5是按照一个实施例的阀调节组件和射流元件的示意性原理图。
图6A是按照一个实施例的射流元件的立体图,该射流元件供图1的浮质产生系统使用。
图6B是按照一个实施例的射流元件的剖视图。
图7A是按照一个实施例的直线射流元件的曲线图,表示相对于时间在系统内的背压。
图7B是一个曲线图,表示在没有射流元件的情况下相对于时间在系统内的背压。
图8是一个表格,用于比较在有射流元件和没有射流元件的情况下组分的颗粒尺寸。
图9是按照供浮质产生系统使用的一个实施例的射流元件的立体图。
图10是按照供浮质产生系统使用的另一个实施例的射流元件的分解视图。
图11是按照供浮质产生系统使用的另一个实施例的射流元件的分解视图。
图12是按照供浮质产生系统使用的另一个实施例的射流元件的分解视图。
图13是按照一个实施例的浮质产生系统的原理图。
具体实施方式
浮质的用途非常广泛。例如,常常希望的是,采用液体和/或固体的细分颗粒(例如,粉末、药物,等等)的浮质来喷射治疗呼吸疾病,或者借助于这些浮质喷射输送药品,这些药品吸入到病人的肺脏中。可采用下列方法由被加热的毛细管浮质发生器产生浮质:通过将在液体状态下的溶液或悬浮液(即,液体组分或液体材料)供给到毛细管,同时充分地加热毛细管使溶液(或悬浮液的载体部分)挥发,从而在从被加热的毛细管中排出时,溶液(或悬浮液)呈浮质的形式。除其它因素外,毛细管的长度可取决于由要产生的浮质的成分规定的加热要求。直接与被加热的毛细管浮质发生器相关联的潜在问题是:在毛细管内的宽广的温度变化可能导致过加热和形成低标准浮质,引起毛细管的堵塞和/或毛细管浮质发生器的失效。
可认识到的是,浮质产生系统可用来从容器封闭系统吸出液体材料或组分,并且将它通过浮质发生器或毛细管子组件分配,以实现连续的浮质化传输。希望的是,通过提供一种系统和方法来提高毛细管浮质产生系统的可靠性和坚固性,该系统和方法通过增大用于浮质化的阈值背压(即,保持流动一致性和毛细管湿润所需要的最小压力)可稳定在浮质产生单元的毛细通道内的名义操作压力,并且由于液体材料或组分转化成蒸汽和在液体材料或组分内的大颗粒,使得在系统内的压力振荡减小。
按照一个实施例,射流元件布置在泵送单元与浮质发生器的毛细管之间,其中,射流元件增大液体组分的背压,从而导热加热器块使热量传递最大化,该热量传递大体均匀和一致地从导热加热器块到毛细管。
在操作中,电气引线将电力从电源传输到各加热器筒,所述加热器筒插入在导热加热器块中,由此加热导热加热器块。当加热时,导热加热器块将热量传递到浮质产生单元或毛细管,并因而大体均匀和一致地将毛细管加热到足以至少部分地使引入到被加热的毛细管中的液体材料或液体组分挥发的温度。例如,至少部分地挥发的液体材料或液体组分可被驱动穿过限流器,以雾化液体材料或组分。挥发的材料与由被加热的铠装空气源供给的空气相混合,并且形成浮质,该铠装空气源在浮质约束部件内在加热器块的远端处。
参照图1,按照一个实施例,表示浮质产生系统10的立体图。液体组分或液体材料优选地通过连接到液体材料源上的毛细管的进口引入到毛细管中。挥发的材料通过毛细管的输出口,即来自液体材料源的液体的压力,被驱动到毛细管外,该压力使液体从输出口喷射。
按照一个实施例,如图1中所示,浮质产生系统(或药品输送系统)10具有浮质发生器和加热器块,加热器块和导热材料的温度被加热到操作温度(即,在该温度下,毛细管中的液体材料被挥发)并且维持在该操作温度下,该操作温度可在约250℃至400℃的范围中。然而,当用这个浮质产生系统10产生浮质时,由于液体组分的汽化以及泵送蒸汽/液体穿过在浮质发生器的出口处的减小孔口,系统10可能产生在4MPa至6MPa(600psi至900psi)量级下的显著背压(即,在系统内从在浮质产生单元的毛细管或毛细管道的出口处的输出口或减小孔口到注射泵的压力)。另外,系统10可能经历在毛细管中的不一致流动、组分中的大颗粒以及次最优汽化,这可在系统10中引起在15MPa至20MPa(2000psi至3000psi)量级下的突然压力尖峰。
系统10也可能经历在不同批次中(在一个单元内)在毛细管或毛细通道内的名义压力变化、压力分布的振荡、在名义压力低于7MPa(1000psi)的情况下出口孔口的堵塞以及具有比在毛细管系统10中的出口孔口的直径大的尺寸的颗粒。例如,当名义压力在7MPa(1000psi)以下时,系统10可能经历浮质脉动,这引起毛细管操作压力尖峰。另外,当这些压力尖峰发生时,浮质产生系统10可能不能够承受这样高的压力,并且引起毛细管的堵塞。当失效发生时,易处置输送包构件和在输送包中的配件失效,这引起单元的不工作。相应地,希望提供一种用来提高毛细管浮质发生器的可靠性和坚固性的系统和方法,其中液体组分被部分地汽化,以形成用于吸入的浮质。
如图1中所示,浮质产生(或药品输送)系统10包括基础单元20,该基础单元20适于接纳呈消毒的易处置流体系统形式的易处置组件40。基础单元20包括壳体22、适于接纳易处置组件40的易处置组件壳体30以及紧凑的、可重新构造的输入/输出(I/O)控制器组件(未示出)和用户界面24。用户界面24可以是如图1中所示的触摸屏幕面板或用于信息输入和从系统10接收操作数据的其它适当界面系统。易处置组件壳体30优选地包括蛤壳状壳体,它适于接纳易处置组件40,该易处置组件40具有浮质产生单元(或浮质发生器)90和射流元件100。如图1中所示,在基础单元20中的易处置组件壳体30包括上部或第一半部和下部或第二半部,该易处置组件壳体适于按蛤壳式构造成围绕易处置组件40,该蛤壳式构造包括便于使壳体30打开和关闭的手柄。易处置组件40配合在壳体30的下部或第二半部内,并且保证易处置组件40的构件与它们在基础单元20内的相应连接部相匹配。
在使用中,浮质产生单元90可包括间接加热块组件(未示出),该间接加热块组件包围被加热的毛细管,以加热液体材料或液体组分26,该液体材料或液体组分26按恒定和连续速率由泵送单元50泵送穿过浮质产生单元。泵送单元50优选地包括两个注射泵52、54和阀调节装置或组件60(图3),该阀调节装置或组件60是可操作的,以在由一个注射泵52、54将液体组分输送到浮质产生单元期间,将液体组分供给到另一个注射泵52、54的进口中。按照一个实施例,泵送单元50和阀调节装置60按约15μl/s至25μl/s、并且更优选地约18μl/s至22μl/s以及最优选地约20μl/s,将液体组分26连续地输送到毛细管。
图2是图1的浮质产生系统10的立体图,该浮质产生系统10具有在关闭位置中的易处置组件壳体30。易处置组件40可附接到液体材料或液体组分26的源上,该液体材料或液体组分26被部分发汽化以形成浮质。毛细管浮质产生系统10适于将液体材料或液体组分作为浮质连续地输送,其中液体材料或液体组分26在浮质产生单元90中被加热,以部分地汽化至少一些液体材料或液体组分26。浮质产生系统10可包括基础单元20和润湿的构件,这些润湿的构件包括消毒的易处置流体系统或易处置组件40。
参照图3和5,易处置组件40优选地包括阀组件(或阀调节装置)60、输入流体管组件80、浮质产生单元90以及射流元件100。阀组件60优选地包括多个阀62、64、66、68。射流元件100布置在阀64、68与浮质产生单元90的被加热的毛细通道70之间。被加热的毛细通道70和加热器或加热单元72优选地布置在浮质产生单元90内。第一和第二注射泵52、54在它们的相应输送行程期间与毛细通道70和射流元件100交替地连通,并且在它们的相应抽吸(吸入)行程期间与流体(组分)源交替地连通,全部这样的动作与阀62、64、66、68相配合地执行。例如,如图5中所示,当第一注射泵52正在排出时,其输出沿流动路径“X1”从第一注射泵52指向毛细通道70。流动路径x1通过阀62的关闭和阀64的打开而形成。同时,第二注射泵54正在执行其吸入行程,以从源通过流动110沿标记为“X2”的路径抽吸流体。为了形成这个流动路径“X2”,阀66打开并且阀68关闭。
图4是如图3中所示的易处置组件40的侧视图。如图4中所示,易处置组件40包括4阀组件60、输入流体管组件80、浮质产生单元90以及射流元件100。注射泵52、54优选地包括驱动系和控制电子装置,以允许双注射泵52、54的同时操作,以便连续地分配液体材料或液体组分。注射泵52、54也将优选地产生用来使阀62、64、66、68打开和关闭的信号,并且将信号发送到可编程自动控制器。
按照一个实施例,泵送单元50应该能够支承高达至少2000psi,并且更优选地高达20MPa至30MPa(3000psi至4000psi)的背压。另外,注射泵52、54优选地安装在耐流体外罩中,并且可包括在每个注射-安装支架上的力传感器,以在流体输送期间监视柱塞力。注射泵52、54的泵送能力便于高粘性组分(如肺脏表面活性剂)的处理。
浮质产生单元90可包括:呈加热器块组件形式的加热器或加热单元72,该加热器或加热单元72包括上部或顶部组件和下部或底部组件;热电偶;及呈毛细通道或管70形式的浮质发生器。浮质产生单元90包括:毛细通道70,在该毛细通道70中,液体组分26(图3)被至少部分地汽化;加热器本体或块,可操作以将毛细通道70加热到对至少部分地挥发在毛细通道或管70中的液体组分有效的温度范围。毛细管70可包括进给管端部或近端部以及圆顶形的毛细管端部或远端部。毛细管70优选具有的内径在约0.05mm至0.53mm的范围中,并且更优选地在约0.1mm至0.2mm的范围中。毛细管70的特别优选内径是约0.1905mm(或0.0075英寸)。按照一个实施例,毛细管70具有的长度约为90mm至120mm,并且更优选地为100mm至110mm。然而,可认识到,毛细管70的长度基于在毛细管70内液体材料或液体组分26的流量。按照一个实施例,毛细管70是如在美国专利申请No.20050235991中所描述的尖头毛细管,该专利申请的内容由此通过参考全部包括。
按照一个实施例,诱导射流元件100的背压可在泵送单元50的阀组件60与浮质产生单元90的毛细管系统的进口之间引入。射流元件100将额外背压引入到系统10,从而名义压力或背压增大到希望阈值压力以上(例如,大于8MPa(1200psi))。可认识到,通过将系统10的背压增大到希望阈值压力以上,射流元件100为系统10提供一种缓冲在系统10内的压力振荡的方法。另外,在系统10内的增大的压力提供一种在进入被加热的毛细管70之前剪切液体组分26(或液体材料)的手段,这防止出口孔口被液体组分26的颗粒(这些颗粒具有比尖头的毛细管端部大的直径)堵塞。
如图6A和6B中所示,射流元件100优选地是管状部件102,该管状部件102具有的内径(ID)120在约0.05mm至0.25mm(0.002英寸至0.010英寸)之间,并且更优选地为0.13mm(0.005英寸),具有的长度122在约4英寸至12英寸长之间,并且更优选地约为6英寸。按照一个实施例,射流元件100优选地具有的长度122约为100mm至300mm(4英寸至12英寸)并且具有的内径为0.05mm至0.25mm(0.002英寸至0.010英寸)。射流元件100优选地将额外背压引入到浮质产生系统10中,该额外背压从约1MPa至7MPa(150psi至1000psi),并且更优选地从约2MPa至约2.4MPa(约300psi至约350psi),并且这在加热期间将在系统10内的整体操作压力或背压增大到约7.9MPa至约10MPa(约1150psi至约1450psi),如图7A中所示。
例如,按照一个实施例,射流元件100在泵送单元50与浮质产生单元90之间实施,该射流元件100包括管状部件102,该管状部件102具有的内径120为0.13mm和0.25mm(0.005英寸和0.010英寸)。如图7A中所示,借助于射流元件100的添加而得到在系统10中增大至7.9MPa(1150psi)的背压。关于90分钟或更长的浮质化运行时间,如图7A中所示,数据表明,由于在系统内增大的名义压力,以及压力振荡的最小化,在系统10中的背压提高了系统10的整体成功性得以提高。
相反,如图7B中所示,在没有额外背压添加到系统10的情况下,系统10表现出增加的失效,并且在系统中较低且变化较大的背压或名义操作压力(即,基于特定毛细管尺寸的系统的操作压力,该毛细管尺寸包括尖头毛细管的尺寸或直径)的振荡显著较高。
按照另一个实施例,如图8中所示,射流元件100也可通过剪切在液体组分26中的颗粒,来控制液体组分或液体材料26的颗粒尺寸。例如,其中具有颗粒的液体组分26(如肺脏表面活性剂组分)可包括药物颗粒,这些颗粒可超过毛细管输出口或毛细管的尖头端部的尺寸。相应地,通过引入射流元件100,在液体组分或液体材料26内的颗粒,在液体组分26进入毛细通道之前,可被剪切到优选地小于输出口的直径的颗粒尺寸。
可认识到,射流元件100可以是如图6A中所示的直线管状部件102,或者在可选择实施例中,射流元件100是盘绕式管状部件102,该盘绕式管状部件102适于配合在自包含壳体130内。如图9中所示,射流元件100可以是盘绕式管状部件102,该盘绕式管状部件102设计成配合在完整输送包内。管状部件102的盘绕也增大在操作流量下的背压,从而呈盘绕样式的管状部件102的长度120与直线管状部件102相比,可产生不同的背压。按照另一个实施例,盘绕式管状部件102的长度110与直线管状部件102相比将是变化的,以在系统10内得到希望的或最佳的背压。
图10是射流元件100的分解立体图,该射流元件100具有包含在壳体130内的盘绕式管状部件102。如图10中所示,射流元件100包括壳体130,该壳体130包括:基础单元132,该基础单元132中具有适于接纳管状部件102的空腔133;可除去帽134;及紧固件136,用来将可除去帽134附接到基础单元132上。管状部件102优选地包括进口部分104、盘绕部分106以及输出口部分108。进口部分104和输出口部分108优选地是直线的,然而,可认识到,进口部分104和输出口部分108可以是带有角度的,或者在其中具有轻微的弯曲部。
按照如图10中所示的一个实施例,射流元件100的盘绕部分106基本上与进口部分104和输出口部分108位于同一平面中。进口部分104、盘绕部分106及输出口部分108的长度将依据在系统10内希望的最优化背压而变化。管状部件102的进口部分104优选地附接到进口配合组件140上,该进口配合组件140从泵送单元50和阀组件60接收液体组分26。输出口配合组件142将射流元件100连接到浮质产生单元90上。
按照另一个实施例,如图11中所示,管状部件102的盘绕部分106具有螺旋形状。管状部件102也包括大致为直线的进口部分104和大致为直线的输出口部分108。射流元件100也具有呈进口配合组件142形式的壳体146,该壳体146用于射流元件100,该进口配合组件142适于配合在壳体146内。壳体146在一个端部处连接到泵送单元50和阀组件60上,并且在另一个端部处连接到浮质产生单元90上。进口配合组件140可包括外部环或凸缘,以帮助进口配合组件142在壳体146内的配合。输出口配合组件142接纳射流元件100,并且将射流元件100连接到浮质产生单元90上。壳体146也优选地包括螺纹紧固件或其它适当的环元件144,该螺纹紧固件或其它适当的环元件144附接到输出口配合组件142上。
按照另一个实施例,如图12中所示,射流元件100可包括圆盘或板状元件160,该圆盘或板状元件160中具有沟道164。沟道164优选地呈螺旋线的形式,具有适于从泵送单元50和阀组件60接收液体组分的进口162。沟道164优选地从圆盘或板状元件160的外部部分延伸到内部部分,该内部部分中具有输出口166。输出口166优选地穿过圆盘或板状元件160延伸到通向浮质产生单元90的入口。
射流元件100也优选地包括射流元件壳体170,该射流元件壳体170包括外壳部件172和基础单元174,该基础单元174具有适于接收圆盘或板状元件160的外部远侧表面176。O形圈或密封圈180绕圆盘或板状元件160的外边缘配合。O形圈180优选地是具有圆形(O形)的横截面的弹性体材料,它形成用于射流元件100的机械密封,该射流元件100配合在射流元件壳体170的外壳部件172和基础单元174内。
图13是浮质产生系统10的原理图。如图13中所示,浮质产生系统10包括组分或剂量包350、热板/搅拌器300、泵送单元50、阀组件60、浮质产生单元90、射流元件100、过渡适配器190以及冷凝阱200,该浮质产生单元90中具有毛细管。系统10也可包括CPAP适配器310、空气过滤器330(如HEPA过滤器)、空气源(CPAP)320以及控制单元340,该CPAP适配器310用来将浮质输送到病人。空气源320优选地来自医院的压缩空气管线或加压空气源,如具有用于实现希望空气流量的适当阀装置的压缩空气罐。
按照一个实施例,包含在组分或剂量包350内的液体材料或液体组分26(如肺脏表面活性剂)通过最初在热板/搅拌器300上加热包350以将组分26液化到用于输送到泵送单元50的希望粘度(即,高粘性组分),而准备用于输送到病人。泵送单元50和阀组件60按恒定和连续速率将组分26供给到浮质发生器(或浮质产生单元)90,该浮质发生器90包括毛细通道,在该毛细通道中,液体组分至少部分地被汽化。加热器块将毛细通道加热到对于至少部分地使在毛细通道或管内的液体组分挥发成浮质有效的温度范围。浮质发生器90还优选地包括至少一个空气通道,该空气通道布置成,空气源由加热器本体或块加热,并且其中,被加热的空气或暖空气与由浮质发生器90产生的浮质相混合。可认识到,作为代替或除了使用在毛细管处或附近产生的热量之外,系统10可包括呈分立空气加热器形式的单独的空气加热器312,该分立空气加热器远离毛细管。
过渡适配器或浮质约束部件190捕获由浮质发生器90和毛细管产生的浮质,并且将浮质引导到流动管中,以便经CPAP适配器310输送到病人。CPAP适配器310优选地在约35℃至38℃下并且对于婴幼儿更优选地在约37℃下将浮质输送到病人。可认识到,通过改变输送软管或管件104的长度,浮质的输送温度可在适当或希望的温度下被输送。浮质约束部件190优选地对于浮质产生单元90的毛细管被密封,这防止环境空气(与输送到过渡适配器的被加热的空气不同)与由浮质发生器或毛细管产生的浮质相混合。过渡适配器或浮质约束部件190可包括冷凝阱200,该冷凝阱200中具有至少一个隔板和/或在其下端部处的排出端口,该排出端口适于附接到冷凝收容装置或排出管组件上。被加热的空气或暖空气与由组分产生的浮质的混合减少来自毛细管的冷凝量,以能够将浮质输送到位于离系统10和浮质产生单元90较远位置处的病人。
优选地在药品输送用途中的系统10适于提供浮质,该浮质具有小于2微米的平均质量中间颗粒直径,以便于较深的肺脏透入。也希望的是,在一定药品输送用途中,按大流量(例如在1毫克每秒以上)输送药物。可认识到,液体组分源优选地包含适于作为浮质输送到婴幼儿肺脏的肺脏表面活性剂。
尽管已经描述了各个实施例,但要理解,本领域的技术人员显然可以采取各种变更和修改。这样的变更和修改应落入在所附的权利要求书的权限和范围内。
Claims (20)
1.一种浮质产生系统,包括:
浮质发生器,其中,液体组分至少部分地在毛细通道中汽化,并且从所述毛细通道排出,以形成浮质;
泵送单元,适于将液体组分供给到所述浮质发生器;及
射流元件,布置在所述泵送单元与所述毛细通道之间,其中,当所述液体组分进入所述毛细通道时,所述射流元件增大所述液体组分的压力。
2.根据权利要求1所述的系统,其中,所述射流元件在所述液体组分进入所述毛细通道之前,减小在所述液体组分中的颗粒尺寸。
3.根据权利要求1所述的系统,其中,所述射流元件减小所述毛细通道的堵塞和/或在所述毛细通道内的压力尖峰。
4.根据权利要求1所述的系统,其中,所述射流元件是管状部件。
5.根据权利要求4所述的系统,其中,所述管状部件具有的长度为100mm至300mm。
6.根据权利要求4所述的系统,其中,所述毛细通道是毛细管,并且其中,所述管状部件的内径小于所述毛细管的内径。
7.根据权利要求1所述的系统,其中,所述射流元件是盘绕式管状元件。
8.根据权利要求7所述的系统,其中,所述盘绕式管状元件具有螺旋形状。
9.根据权利要求1所述的系统,其中,所述射流元件是板状元件,该板状元件中具有非直线沟道。
10.根据权利要求1所述的系统,其中,在20微升每秒(μl/s)的液体流量下,所述射流元件将在所述泵送单元与所述毛细通道的输出口之间的压力增大1MPa至7MPa。
11.根据权利要求1所述的系统,其中,所述毛细通道是具有输出口的毛细管,该输出口的尺寸比所述毛细通道的内径小,并且其中,所述液体组分至少部分地由加热器块汽化,所述加热器块布置在所述毛细通道附近。
12.根据权利要求1所述的系统,还包括液体组分源,该液体组分源包含适于作为浮质输送到婴幼儿肺脏的肺脏表面活性剂。
13.一种生产浮质的方法,包括:
将液体材料通过射流元件泵送到浮质产生单元的被加热的毛细通道,所述射流元件在泵送单元的阀组件与所述毛细通道的进口之间增大所述液体材料的压力,从而在通向所述毛细通道的进口处的所述液体材料的压力至少为1000psi;和
用所述被加热的毛细通道产生浮质。
14.根据权利要求13所述的方法,还包括将被加热的空气与所产生的浮质相混合,从而产生流量增大的被加热的浮质。
15.根据权利要求14所述的方法,还包括将所述被加热的浮质沿所述毛细通道传送到远处位置。
16.根据权利要求13所述的方法,其中,所述液体材料在7.9MPa至10MPa的压力下进入所述毛细通道的所述进口。
17.根据权利要求13所述的方法,其中,所述液体材料在进入所述毛细通道的所述进口之前,被泵送穿过减小尺寸的射流元件。
18.根据权利要求13所述的方法,其中,所述液体材料在所述毛细通道中至少部分地挥发,并且挥发的液体通到所述毛细通道的输出口外,所述毛细通道沿其长度具有均匀的横截面,并且所述输出口小于所述进口。
19.根据权利要求13所述的方法,其中,所述液体材料按18至22微升每秒(μl/s)的流量连续地泵送到所述毛细通道的所述进口。
20.根据权利要求13所述的方法,其中,所述液体材料穿过所述射流元件的直线或者非直线通道泵送,该直线或者非直线通道的内径小于所述毛细通道的所述进口的直径。
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AU2008306584A1 (en) | 2009-04-09 |
US20090310950A1 (en) | 2009-12-17 |
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US8634709B2 (en) | 2014-01-21 |
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BRPI0818296A2 (pt) | 2017-08-22 |
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KR20100068408A (ko) | 2010-06-23 |
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