CN102711905B - 流电皮肤治疗装置 - Google Patents
流电皮肤治疗装置 Download PDFInfo
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- CN102711905B CN102711905B CN201080060622.3A CN201080060622A CN102711905B CN 102711905 B CN102711905 B CN 102711905B CN 201080060622 A CN201080060622 A CN 201080060622A CN 102711905 B CN102711905 B CN 102711905B
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- skin
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Abstract
本发明提供了用于治疗皮肤的流电装置。所述装置包括具有多个分立电偶的基底,各个电偶均包括与第二导电电极电子连通的第一导电电极,所述第一导电电极为阳极而所述第二导电电极为阴极。
Description
相关专利申请的交叉引用
本专利申请要求2009年11月13日提交的美国临时专利申请Serial No.61/261,084的优先权。上述相关专利申请的全部公开内容据此以引用方式并入本文,用于所有目的。
背景技术
在离子电渗装置中使用电偶作为电源为本领域所周知。参见(例如)美国专利No.5,147,297、No.5,162,043、No.5,298,017、No.5,326,341、No.5,405,317、No.5,685,837、No.6,584,349、No.6,421,561和No.6,653,014。制备电偶的典型材料包括银/锌供体电极和银/氯化银反电极。这种组合产生约一伏的电势并且在体组织和/或流体与系统形成完整电路时自动起作用而产生电。
美国专利申请公布No.US2007/0060862公开了用于治疗各种组织和病症的含电偶装置。在一个实施例中,这种装置可包括位于载体层中的两个不同的导电电极,所述导电电极通过连接导线或通过直接物理接触彼此连接而形成多个电偶电源。如图8-11所示,导电电极为跨载体层的连续结构形式(例如锌导线),所述导电电极彼此通过若干位置处的连接导线进行接触。
美国专利No.7,457,667以及美国专利申请公布No.US2006/0015052和No.US2006/0015053公开了据称使用流电电流的伤口敷料。伤口敷料包括基底材料,所述基底材料保持两种相异金属的区域或颗粒,这些区域或颗粒彼此靠近但不接触。
申请人目前已发现包括多个分立电偶的流电皮肤治疗装置,所述分立电偶包括在基底上彼此电子连通的导电电极。这种电偶彼此分离、通常具有小尺寸和可变形状并且设置在基底上。在一个实施例中,所述基底为纸制。
有利的是,在基底上使用多个电偶,即电偶阵列,这使多个正电极和负电极在治疗区域上的定制和受控的分布成为可能,并因此能够得到非常均一的对于治疗中的组织的电流分布。对于仅提供一个阳极和一个阴极的常规电气装置或者包含分散的金属颗粒的装置,这是不可能实现的。由于各个电偶独立于周围电偶起作用,因此各个电偶仅治疗与其直接相邻的皮肤。因此,多个电偶将均匀分布的电流剂量提供至治疗区域。这种效果的另一个优点在于可通过各个电偶的输出来控制最大电流剂量。如果治疗区域的一部分具有变化的导电性或受损的皮肤完整性(例如具有伤口),则尤为有利(例如所提供的最大电流被限于仅为由那些局部电偶提供的电流)。本发明的装置还能给用户带来形状和尺寸上的灵活性。例如,护士可从本发明的装置制备所需尺寸和形状的伤口敷料以适配于慢性伤口/病灶(其可能具有任何形状或尺寸),而不会使电偶损坏。
发明内容
本发明提供了用于治疗皮肤的装置,其包括具有多个分立电偶的基底,各个电偶包括与第二导电电极即阴极电子连通的第一导电电极即阳极。
本发明还提供了治疗皮肤的方法,其包括将上述装置施用于所述皮肤。
本发明还提供了皮肤治疗产品,其包括面膜和上述装置,其中所述装置具有适于在使用期间(即,在将面膜和装置施用于皮肤时)盖在面膜上面或置于其下面的形状或尺寸。
通过本发明的具体实施方式和权利要求书,本发明的其他特征和优点将显而易见。
附图说明
图1为根据本发明的单个电偶的俯视图,其中导电电极140和240通过包含导电材料的连接桥350实现电气连通。
图2为根据本发明的装置的俯视图,所述装置包括具有多个分立电偶的基底160,各个电偶包括通过包含导电材料的连接桥350实现电气连通的第一导电电极140和第二导电电极240。
图3为根据本发明的单个电偶的俯视图,所述电偶包括通过具有第二导电电极的延伸部240A的连接桥实现电气连通的导电电极140和240。
图4为根据本发明的装置的俯视图,所述装置包括具有多个分立电偶的基底160,各个电偶包括通过具有第二导电电极的延伸部240A的连接桥实现电气连通的第一导电电极140和第二导电电极240。
图5为具有波状H形的根据本发明的单个电偶的俯视图。
图6为包括多个如图5所示的分立电偶的根据本发明的装置的俯视图。
图7为包括呈套叠构型的多个如图1所示的分立电偶的根据本发明的装置的俯视图。
图8为可用作强化贴片的根据本发明的装置的俯视图。在强化贴片的周边内包括释放缝450以增强其适形于皮肤表面的能力。
图9为根据本发明的皮肤治疗产品的俯视图,所述皮肤治疗产品包括盖在靠贴于皮肤650的面膜550上的装置750。
具体实施方式
据信,本领域的技术人员可根据本文的描述最大限度地利用本发明。以下特定实施例应被解释为仅仅是说明性的,而不以任何方式限制本公开内容的其余部分。
除非另有规定,否则本文使用的所有技术和科学术语都具有本发明所属技术领域普通技术人员公知的相同含义。此外,将本文提及的所有出版物、专利申请、专利和其他参考文献以引用方式并入本文中。除非另外指明,文中百分比均指重量百分比(即,重量%)。
尽管本发明就皮肤治疗而描述,但本发明的装置、方法和产品可应用于任何人或动物隔膜,包括皮肤或眼(角膜、视网膜等)、口腔、颊面、鼻腔、阴道、胃肠道、或直肠粘膜、或者伤口、病灶、或指甲。
“产品”是指成品包装形式的产品。在一个实施例中,所述产品包括指导使用者将所述装置施用于隔膜(例如,为了治疗皮肤病症)的说明书。这种说明书可印刷在产品上、标签插页或任何其它包装上。
在一个方面,本发明的特征为促进本发明的装置或产品用于其预期用途。所谓“促进”是指促销、宣传和推销。促销的实例包括(但不限于)关于产品或在商场、杂志、报纸、广播、电视、互联网等中作出的文字、视像或口头陈述。
如本文所用,“药学上可接受”是指适用于与隔膜(例如,皮肤或粘膜)接触而没有不适当的毒性、不相容性、不稳定性、刺激性、过敏反应等。
如本文所用,“安全有效量”意指足以达到所期望程度的理想有益效果、但又低至足以避免严重副作用的量。所述安全有效量将根据正在治疗的部位、最终使用者的年龄和皮肤类型、治疗的持续时间和性质、所用的特定成分或组成、特定的可药用的所用载体等因素而改变。
如本文所用,术语“医治”或“治疗”是指治疗(例如症状的缓和或消除和/或治愈)和/或预防或抑制病症(例如皮肤病症)。
“皮肤病症”是指皮肤学疾病或病症(包括(但不限于)痤疮、红斑痤疮、特应性皮炎、或皮肤感染或炎症)、或者皮肤特征(包括(但不限于)色素沉着(例如,老年斑或皮肤的色素沉着过度)、毛发生长调节(增加头发生长)、皮肤肌理和光滑度(例如,皮肤的皱纹和细纹)、皮肤硬度、皮肤弹性(例如,眼周围的浮肿和/或黑眼圈)、皮肤脉管和循环、脂肪团、皮脂调节、和皮肤光泽)。皮肤感染和炎症的实例包括(但不限于)因感染性病原体产生的那些,例如,痤疮、红斑痤疮、脓疱病、毛囊炎、疖病、深脓疱、湿疹、牛皮癣、特应性皮炎、疱疹、大疱性表皮松解症、鱼鳞癣、和感染的外伤性损伤(例如,溃烂、轻度烧伤、切口、擦伤、裂伤、创口、活组织检查部位、外科切口和虫咬)。
本发明涉及用于将电流(例如,诱导所需的生物学反应)和/或活性剂递送到隔膜(例如皮肤)中的装置。
本装置包括具有多个分立电偶的基底,各个电偶包括与第二导电电极即阴极电子连通的第一导电电极即阳极。如本文所述,“电子连通”是指自由电子可在第一和第二导电电极之间直接通过。电子连通不同于离子连通。“离子连通”是指电子可通过接触元件(例如,第一和第二导电电极、载体和皮肤)的离子(作为“电子运载者”)的迁移在这些元件中传送(例如,电子通过电解质的离子转运(例如,通过载体)在导电电极和皮肤之间传送)。
在一个实施例中,第一和第二导电电极通过彼此之间的直接物理接触而处于电子连通状态。在另一个实施例中,第一和第二导电电极通过至少一种导电材料、优选惰性导电材料而处于电子连通状态。优选的导电材料包括(但不限于)银、铜以及导电碳或石墨。
在一个实施例中,所述装置还包括载体以及与载体离子连通的第一和第二导电电极,所述载体优选地包含电解质(例如,载体中的一种或多种电解质的离子与第一和第二导电电极接触)。载体又与皮肤离子连通。
在另一个实施例中,所述装置为强化贴片。这种强化贴片可直接靠贴在皮肤上。作为另外一种选择,这种强化贴片可(例如)与面膜结合使用。将面膜和强化贴片一起施用于皮肤。所述装置盖在面膜上面或置于其下面。这种面膜可为常规类型,即包含各种皮肤有益剂和载体的湿面膜或干面膜。作为另外一种选择,面膜可另外包括导电电极以施用电流或递送活性剂。这种导电电极可为流电型、或者可连接至单独电源,如在(例如)美国专利申请公布No.US2007/0060862中所述,该专利申请的全部内容以引用方式并入本文。
在一个实施例中,所述装置包括发光二极管以使得来自发光二极管的光与皮肤连通。这样,光也可被施用于皮肤。
在一个实施例中,所述装置将活性剂递送至皮肤。活性剂可加入基底、载体中、单独地设置在皮肤上、或者由所述装置在使用过程中以电化学方式产生。如本文所用,“以电化学方式产生的”是指通过因流过导电电极的电流引起的电化学反应产生,例如从反应性导电电极释放的化学物质(例如,得自锌电极的以电化学方式产生的锌离子)、以电化学方式产生在惰性电极表面上的化学物质、或者作为这种以化学方式产生的物质的后续反应产物的化学物质。
电偶
所述装置包括至少两个分立电偶作为电源。优选地所述装置包括至少2个、更优选地至少4个分立电偶。各个电偶均包括作为阳极的第一导电电极和作为阴极的第二导电电极。第一和第二导电电极彼此物理接触。电子在各个电偶的第一和第二导电电极之间通过。电子是由于第一和第二导电电极的标准电势上存在差异而产生的(例如,电流并非由外部电池或其他电源(例如AC电源)产生的)。
构成电偶的材料的实例包括(但不限于)锌-铜、锌-铜/卤化铜、锌-铜/氧化铜、镁-铜、镁-铜/卤化铜、锌-银、锌-银/氧化银、锌-银/卤化银、锌-银/氯化银、锌-银/溴化银、锌-银/碘化银、锌-银/氟化银、锌-金、镁-金、铝-金、镁-银、镁-银/氧化银、镁-银/卤化银、镁-银/氯化银、镁-银/溴化银、镁-银/碘化银、镁-银/氟化银、镁-金、铝-铜、铝-银、铝-银/氧化银、铝-银/卤化银、铝-银/氯化银、铝-银/溴化银、铝-银/碘化银、铝-银/氟化银、铜-银/卤化银、铜-银/氯化银、铜-银/溴化银、铜-银/碘化银、铜-银/氟化银、铁-铜、铁-铜/氧化铜、铁-铜/卤化铜、铁-银、铁-银/氧化银、铁-银/卤化银、铁-银/氯化银、铁-银/溴化银、铁-银/碘化银、铁-银/氟化银、铁-金、铁-导电碳、锌-导电碳、铜-导电碳、镁-导电碳、和铝-碳。用于构成电偶的材料也可以用作装置的导电电极,如锌用作导电阳极而银/氯化银用作导电阴极,或锌用作导电阳极而铜用作导电阴极。用作导电电极的金属也可为合金。合金的非限制性实例包括用作阳极材料的锌、铜、铝、镁合金,以及用作阴极材料的银、铜、金合金。
在一个实施例中,第一导电电极包括锌、镁、铁、铝、它们的合金、或者它们的混合物,并且第二导电电极包括铜、铁、金、银、铂、碳、它们的合金、它们的氧化物、它们的卤化物、或者它们的混合物。
在一个实施例中,可将一种或多种导电材料加入第一导电电极和第二导电电极中的任一者或两者中以增加电极导电性。
在一个实施例中,构成电偶的材料具有等于或大于约0.1伏的标准电势差,如大于约0.2伏,如大于约0.5伏。在一个实施例中,构成电偶的材料具有等于或小于约3伏的标准电势差。
各个电偶的电流输出可根据治疗持续时间和电偶尺寸而不同。通常,对于较长的治疗持续时间,可使用较低的电流输出。另外,电偶的尺寸越大,则电流输出越高。
在一个实施例中,所述装置产生和/或能够产生进入皮肤或其他隔膜的约1nA/cm2至约1000μA/cm2的电流,例如约1μA/cm2至约500μA/cm2。
在另一个实施例中,尤其是对于疼痛治疗而言,由包括单个电偶或多个电偶的装置提供的穿透皮肤的总电流可为约20至约2000μA、优选地约50μA至约1000μA、并且更优选地约100μA至约500μA。
可利用本领域已知的多种沉积技术中的任何一种来使导电电极附着于基底。例如,第一和第二导电电极中的一者或两者可为一件金属片、金属丝或金属网、或者涂布金属的织物或其他材料(例如,涂布金属及其氧化物、卤化物、和硫化物的织物(例如,涂布银、银/氧化银、银/卤化银、锌、镁、铜、铜/卤化铜、铜/氧化铜的织物))。这种材料可任选为穿孔的。例如,锌网片(或电池和抗腐蚀领域中通常所称的“扩展锌”)可以用具有机械穿孔的薄锌箔制成,随后将其扩展成网状图案。锌网片或其他网片的主要优点为其形成和保持形状、可朝任何方向拉伸、以及透气的能力。
作为另外一种选择,可通过化学或电化学沉积(例如本领域已知的用于化学沉积的化学镀以及用于电化学沉积的电镀)将第一和第二导电电极沉积到基底上。可通过物理沉积(例如,丝网印刷、喷涂、凹版印刷、激光喷墨打印、移印、针式打印、浸涂、真空沉积、或者其他的印刷或转移方法)将第一和第二导电电极沉积到基底上。
在一个实施例中,导电电极可通过将流电材料配制到为沉积所述材料的方法所专用的油墨(例如,用于丝网印刷的丝网印刷油墨、或者用于激光喷墨打印的激光喷墨打印油墨)中来制备,并且可包含诸如溶剂、粘结剂、或增塑剂之类的成分。这些制剂在干燥时必须为可药用的,即所有的非挥发性成分必须对于接触隔膜是安全的。粘结剂可包括水溶性的和水不溶性的那些。可药用的粘结剂的实例包括(但不限于)聚乙烯、聚丙烯、聚氯乙烯、聚苯乙烯、丙烯腈丁二烯苯乙烯、聚对苯二甲酸乙二酯、聚氨酯、羟丙基甲基纤维素、聚乙烯吡咯烷酮、聚乙二醇、羟丙基纤维素、羟乙基纤维素、甲基纤维素、泊洛沙姆、和反式泊洛沙姆。
电偶的尺寸可根据所述装置的施用而改变。在其中所述装置用于美容的一个实施例中,各个电偶占据的面积不超过约4cm2,例如2×2平方厘米。在更优选的实施例中,各个电偶占据的面积不超过约1cm2,例如1×1平方厘米。各个电偶的整体尺寸的变化范围可为约0.01cm2至约10cm2。
在其中所述装置用于疼痛治疗的替代实施例中,可使用较大的电极以提供较长效的电流治疗以及可能较高的电流电平。各个电偶占据的面积为约10至约400cm2,例如15×15平方厘米。在更优选的实施例中,各个电偶占据的面积为约20至约200cm2,例如10×10平方厘米。在此实施例中,各个电偶的整体尺寸的变化范围可为约10cm2至约400cm2。
各个电偶可以多种方式设置,前提条件是它们彼此分立,即各个电偶彼此分离并且不接触。可根据需要来设置电偶以增加或降低电流密度。
在一个实施例中,电偶彼此间隔(例如)以规则或重复图案而均匀地分布在基底上,如图2、4和6所示。在另一个实施例中,电偶不规则地间隔分布在基底上,如图8所示。在另一个实施例中,电偶可间隔分布在基底上以在基底上形成图样、图案、标志、或字母。
在一个实施例中,电偶为套叠的以致它们的周边彼此重叠。套叠电偶的一个实例示于图7中。
在一个实施例中,电偶可被取向成使阴极或阳极治疗会聚到基底上的点以放大这种阴极或阳极的作用。
作为另外一种选择,电偶可在基底上布置成可最佳地适应预期治疗。
可使用单个电偶、或者可使用形成阵列的多个电偶。电偶在阵列中的取向可为相对于彼此的任何方向,或者电偶可设置成某些图案(例如,平行或非平行的阵列、以及交叉或套叠的图案)以包括预期治疗区域的某一部分或全部。
电极间距将取决于应用。在电极间距增大的情况下,电流较深地穿透到组织内。设置成过于靠拢的电极不可能将电流传送至引起疼痛的组织深部。在一个实施例中,就背痛而言,所述装置能够被设计成使得电偶的电极间隔跨越整个疼痛区域。例如,对于背痛的治疗而言,电极可能被优选地布置成隔开至少5cm、更优选地隔开至少10cm。
在一个实施例中,对于膝痛而言,电偶可间隔开而覆盖膝部的两侧。
在任何情况下,在基底上使用多个电偶允许在治疗区域上对多个正极和负极进行定制分布。对于仅提供一个阳极和一个阴极的常规电气装置或者包含分散的金属颗粒的装置,这是不可能实现的。由于各个电偶独立于周围电偶起作用,因此各个电偶仅治疗与其直接相邻的皮肤,以致将均匀的电流剂量递送至治疗区域。这种效果的另一个优点在于可通过各个电偶的输出来控制最大电流剂量。如果治疗区域的一部分具有变化的导电性或受损的皮肤完整性(例如具有伤口),则尤为有利(例如所提供的最大电流被限于仅为由那些局部电偶提供的电流)。
第一和第二导电电极可在各个电偶内以多种方式布置。优选的是,第一和第二导电电极被布置成等距迹线(即,阳极和阴极之间沿单一笛卡尔轴具有固定距离),使得电极间的电流分布均匀。优选的是,第一导电电极即阳极和第二导电电极即阴极之间的间隔等于或接近相邻电偶之间的间隔,以均匀地分布送至皮肤的电流。
阳极和阴极迹线(第一和第二导电电极)必须电子连通以产生流电电流。换句话讲,第一和第二导电电极必须通过易于传导自由电子渡越的介质(例如金属或碳)以电子方式桥接。
在一个实施例中,第一和第二导电电极通过包含导电材料的连接桥实现接触,所述导电材料例如为惰性导电材料,所述惰性导电材料例如为(但不限于)银或碳。
在另一个实施例中,第一和第二导电电极通过包括第一导电电极、第二导电电极、或这两者的延伸部的连接桥实现接触。
优选的是,连接桥在不损失导电性的情况下尽可能薄,以使沿桥的电化学反应受到限制。用于连接桥的最小可实现厚度取决于沉积方法。例如,在丝网印刷中可实现0.1mm的迹线厚度。连接桥的厚度优选地为约0.01至约10mm并且更优选地为约0.1至约2.0mm。
连接桥在电偶的性能中起到重要的作用,因为其可充当电阻器并且调节电流。因此,可通过调节由连接桥构成的电阻来控制电流的大小和持续时间。可通过改变连接桥材料以及连接桥的几何参数来控制连接桥的电阻。与较短、较宽的连接桥相比,较长且较窄的连接桥提供较大的电阻。
在一个实施例中,连接桥可具有波状或锯齿状图案,这种图案具有长于直线的路径长度,因此增加了连接桥的电阻。在一个实施例中,连接桥可位于电极之间的间隔之外。在一个实施例中,连接桥可连接第一和第二导电电极的外边缘,以使其设置在电极之间的间隔之外。
在一个实施例中,电偶包括不止一个连接桥。
在一个实施例中,连接桥水平地设置在平行的第一和第二导电电极之间,使得电偶为基本上H形的。在另一个实施例中,连接桥水平地设置在平行的第一和第二电极之间,使得电偶为基本上U形的。在另一个实施例中,连接桥对角地设置在第一和第二导电电极之间,使得电偶为基本上N形的。连接桥可设置成任何取向或者可具有任何形状,使得第一和第二导电电极实现电气连通。优选的是,连接桥提供范围为0.1-1,000,000欧姆的电阻,这取决于所需的电流。
对称电偶设计的优点在于所得电场和电流的均匀分布。然而,也可通过向上或向下移动(即,远离竖直腿的中间位置移动)连接桥而成为不对称设计,以实现非均匀电流分布。通常,水平连接桥的形状或位置或者长度/宽度可被设计为实现所需的电流强度和分布,例如使其倾斜而成为“N”形而非“H”形。作为另外一种选择,“H”形的第一和第二导电电极的相对位置也可改变而成为不对称性并且实现不均匀的电分布。
各个电偶独立于周围的电偶起作用。因此,可将包括电偶阵列的基底切割成小片而不失去其作用,前提条件是至少一些单独电偶在所得的基底小片上仍保持完整。因此,在一个实施例中,所述装置可被构造为使得使用者可将所述装置切割成多个较小部分,以使所述装置个性化或者定制为贴合使用者的皮肤。
所述装置的电流规格,例如电流强度、电流密度、和电流持续时间,可根据预期的效果而改变。
例如,不同的应用可以需要不同的治疗时间。丘疹治疗可以需要仅20分钟,伤口治疗应能在24小时或更长时间内完成,而用于疼痛或其他感觉不适治疗的持续时间可能在20分钟至48小时的范围内。因此,在设计特定应用的装置时必须考虑电输出的控制。可通过若干手段来控制电偶提供的电流。可通过调节下述参数来控制电输出的持续时间和强度:沉积为第一和第二导电电极的阳极和阴极材料的量、第一和第二导电电极以及连接桥的电阻、第一和第二导电电极之间的间隙宽度、外加载体的导电性、外加载体的体积、以及邻近所述装置的基底或其他材料的吸收性。对于具有不利的低导电性的油墨而言,可通过如下方式来增强由这种油墨制成的导电电极的整体导电性,即在导电电极的迹线下印刷导电层,该导电层最好为化学惰性的。
由于电偶产生的电流源于电化学反应,因此在各个电极处可能存在pH变化。阴极处的pH往往会增加而阳极处的pH往往会降低。由于pH的变化速率取决于电流的大小,因此在某些实施例中,可能有利的是设计具有自停止或自减缓机制的电偶以在pH水平一旦超出所需范围时就终止或减缓pH的变化速率。这可通过将第一和/或第二导电电极配制成包含pH依赖性聚合物(在明确限定的pH范围下溶胀)来实现。这种聚合物在pH一旦达到特定值时将膨胀并且沿电极降低导电性,由此阻止电化学反应。pH依赖性溶胀聚合物包括(但不限于)在碱性环境中溶胀的聚丙烯酸(例如Eudragit S、Eudragit L、Eudragit FS、和Eudragit E)和在酸性环境中溶胀的脱乙酰壳多糖。
第一和第二导电电极可为反应性导电电极或惰性导电电极。“反应性导电电极”为如下电极:其化学组成通过在电流通过电极时发生的电极化学反应而变化。在一个实施例中,反应性导电电极为由反应性材料制成的阳极,如纯金属或金属合金,包括但不限于锌、铝、铜、镁、锰、银、钛、锡、铁以及它们的合金。用于构成上文所述的电偶的材料也可用作反应性导电电极。电流通过各个阳极进入载体并被送入皮肤中时,金属离子(例如锌、铜、镁、锰和/或铝阳离子)从阳极释放。此类离子可以提供治疗有益效果,如抗微生物作用、免疫调节、酶调控和/或抗炎作用。
在一个实施例中,反应性导电电极由金属卤化物这样的反应性材料制成,所述金属卤化物例如是银-氯化银(Ag/AgCl)、银-溴化银、和银-碘化银。在这种情况下,阴极表面的主要电化学反应为固体卤化银转换为金属银,对由阳极生成的氧化剂存在极少不想要的消耗。释放的卤离子随后可被氧化成氧化剂,如氯离子转换为氯气(Cl2)、次氯酸(HClO)和次氯酸根离子(ClO-),碘离子转换为碘。
“惰性导电电极”在电子从中通过期间不发生化学组成的变化。在一个实施例中,阳极由惰性导电电极制成,以使得阳极表面处的电化学过程生成氧化剂,例如初生态氧(例如通过水的电解)和/或含氯氧化剂,如氯气、次氯酸盐、氯酸盐和高氯酸盐以及二氧化氯。初生态氧为可抑制痤疮丙酸杆菌(P.acnes)的氧化剂,含氯氧化剂为具有杀菌活性的强效抗微生物剂。
在一个实施例中,导电电极由惰性材料制成或表面上涂覆惰性材料,所述惰性材料如贵金属(例如,金、铂或镀金导电金属)、导电碳(例如,玻璃碳或石墨)、嵌碳聚合物(例如,碳硅橡胶)、导电碳聚合物泡沫或海绵、镀卤化银的银(例如,涂覆氯化银的银、涂覆溴化银的银以及涂覆碘化银的银)、以及耐蚀合金。
在一个实施例中,用作第一导电电极的所述装置的阳极由上述反应性的可氧化的导电金属制成,所述金属如锌、钙、镁、铝、铁、锡、铜或它们的合金,而用作第二导电电极的阴极由上述反应性的可还原的导电材料制成,所述材料如化学上更稳定的金属及其金属卤化物、氧化物、硫化物或其他金属盐,如银和卤化银(例如氯化银、溴化银、碘化银、氟化银)、氧化银、硫化银。在一个实施例中,可还原的导电材料直接接触良好的电导体,如:金属银上的氯化银、氧化银或硫化银薄层;具有粘结剂的氯化银粉末(例如氯化银油墨);和/或用粘接剂保持在一起的基质形式的氯化银粉末与银或导电碳粉的混合物(例如银-氯化银油墨和氯化银-碳油墨)。
在另一个实施例中,所述装置的阳极由上述反应性的可氧化的导电金属制成,而阴极由上述化学上更稳定的电极材料制成,所述材料如导电碳、金属银、金或铂、或基质形式的导电碳与贵金属的粉末混合物,如美国专利No.5,162,043所公开。
在一个实施例中,本发明的装置允许将有益的锌通过毛囊靶向递送至毛囊皮脂腺单位(即,皮脂腺和相关的毛囊)以治疗痤疮或红斑痤疮。锌为人体的必要金属,因为其参与体内的各种生物学活动(例如,重70Kg的人体内含有约2.3克锌)。已知体内缺少锌会导致皮肤病,例如痤疮。
在另一个实施例中,本发明的装置能够通过使用由含少量的其他有益金属的锌合金制成的阳极将其他有益金属靶向递送到毛囊和毛囊皮脂腺中。这种有益金属包括(但不限于)人体必需的某些金属,例如铁、铜、镁、锰、钙、钾、铝、和硒。当锌合金阳极氧化时,其将锌离子和锌合金中的其他有益金属释放到载体中,所述成分随后在施加于皮肤上的电势下迁移到毛囊中。在一个实施例中,阳极中的锌合金的含量大于约50重量%,例如大于90重量%。
在一个实施例中,测得的(i)载体和(ii)用此载体水化的皮肤的第一导电电极与第二导电电极之间的电导系数的比率(其中基本上所有的电流均通过皮肤在电极之间流动)在约10000:1至约1:100的范围内。换句话讲,I载 体与I皮肤之间的电流分布使得I载体/I皮肤值在约10,000和约0.01之间。I载体是通过装置的总电流(I总)的一部分,其只经过阳极与阴极之间的载体层,不流经皮肤,而I皮肤则是I总中经过皮肤的那部分,也就是说,I总=I载体+I皮 肤。
载体电导系数与皮肤电导系数的比率减小会使更大百分比的电流通过皮肤,从而增强如此递送进皮肤的任何活性剂的离子电泳递送。可通过将不太导电的材料添加到载体中非排他性地降低载体的导电性。此类不太导电的材料的实例包括但不限于:油,如硅油或烃油;气穴,如半固体载体中的气泡或气穴;或者聚合物或粘土小珠。在一个主要旨在于载体中电化学地生成物质的实施例中,I载体/I皮肤值在约10,000与约1之间。在主要目的为将电流和/或活性剂递送到皮肤中的另一个实施例中,I载体/I皮肤值在约10与约0.01之间。对于具体的应用,也可以通过改变第一电极与第二电极之间的距离或两个导电电极与皮肤之间的距离来调节I载体/I皮肤值。例如,当两个导电电极之间的距离减小时,在两个电极之间测得的电导系数增大,并因此使I载体也增大,从而导致I载体/I皮肤值增大。在另一方面,如果两个导电电极与皮肤之间的距离增大,则I皮肤增大,从而导致I载体/I皮肤值减小。
基底
所述装置包括有电偶位于其上或其中的基底。基底可制成各种形状和尺寸以适配于皮肤或其他隔膜的各种解剖表面的外形。例如,基底被制成以下形状:具有开口/孔以露出眼、眉毛、鼻和嘴的完整面膜;只覆盖脸的上半部或下半部的局部面膜;或只覆盖前额或眼部区域下方、颌腭区域、颈、背、伤口、痤疮病灶或丘疹或者需要治疗的隔膜的其他具体区域的贴片。
基底可由多种材料制成,例如纸、塑料或水不溶性聚合物、织造材料(例如,织造织物)、和非织造材料(非织造织物)。基底可包括“可透气”材料,例如(但不限于)棉或合成的织造和非织造纤维层(例如,通常用于绷带和体育绷带的那些纤维材料)。基底可包括导电材料,例如导电塑料、织造材料、非织造材料、或纸。
在一个实施例中,基底包括流体吸收材料,例如通常视为纸的材料,包括(但不限于)薄棉纸、滤纸、复印纸、铜版纸、氢粘合纸(hydrogenbonded paper)、碎木料造的纸、纤维浆造的纸、木浆造的纸、非木浆造的纸、回收纸、不含机械木浆纸(freesheet paper)、具有涂层(包括(但不限于)丙烯酸涂层、硅树脂涂层)的纸、压延纸、具有添加剂以提高湿强度的(例如,但不限于的纸、具有低分子量聚丙烯酰胺添加剂以提高干强度的纸、具有水溶性或水不溶性粘接剂以提高机械强度、可印刷性和手控便利的纸、含颜料的纸、吸收纸或者由导电纤维构成的纸。所述纸对于施用于人体皮肤应为安全的,并且所述纸的组分应对皮肤为无毒的、非刺激性的和非致敏的。所述纸可为导电的或非导电的。
对于可制造性而言,优选的是所述纸在干燥时为足够刚性的以使得所述纸在其上印刷电偶过程中可易于搬运和加工,但在使用期间由使用者润湿时应极大地降低刚性以使其可易于贴合并粘附于隔膜(例如,皮肤)。对于具有陡变曲率的某些解剖特征的隔膜(例如颊骨或鼻子周围的皮肤)的治疗而言,隔膜接触表面的适形能力和接触解剖外形的能力尤为重要。在润湿时,这些表面必须提供足够的柔性和适形能力以适配于皮肤,同时保持特定的结构完整性以使得其在使用时不易撕裂或破碎。
在一个实施例中,流体吸收材料可以被处理以防止或延缓使用期间的水分蒸发。例如,非织造材料或纸可在一个侧面上涂布硅以形成不渗水阻挡层。
流体吸收材料的实例包括(但不限于):交联和非交联的聚合物;溶胀性聚合物,如水溶胀纤维素衍生物(例如,甲基纤维素(MC)、羟乙基甲基纤维素(HEMA)、羟丙基甲基纤维素(HPMC)、乙基羟乙基纤维素(EHEC)、羟乙基纤维素(HEC)、羟丙基纤维素(HPC)、和羧甲基纤维素(CMC)及其盐);聚乙烯醇(PVA);聚乙烯吡咯烷酮(PVP);聚环氧乙烷(PEO);通过单体制备的聚合物,如甲基丙烯酸羟乙酯(HEMA)、甲基丙烯酸羟乙氧基乙酯(HEEMA)、甲基丙烯酸羟二乙氧基乙酯(HDEEMA)、甲基丙烯酸甲氧基乙酯(MEMA)、甲基丙烯酸甲氧基乙氧基乙酯(MEEMA)、甲基丙烯酸甲二乙氧基乙酯(MDEEMA)、乙二醇二甲基丙烯酸酯(EGDMA)、n-乙烯基-2吡咯烷酮(NVP)、甲基丙烯酸(MA)和乙酸乙烯酯(VAC);聚丙烯酰胺;明胶;树胶和多糖,如阿拉伯树胶、刺梧桐树胶、黄蓍树胶、瓜尔胶、安息香树胶和藻酸及其盐;聚乙二醇(PEG);聚丙二醇(PPG);以及粘土或其他溶胀性矿物,如膨润土和蒙脱石。载体中的流体吸收性材料的量的范围可为载体的约0.1重量%至约95重量%,例如约1重量%至约20重量%。
在本发明的一个实施例中,基底包括水不溶性基底。“水不溶性的”是指基底在25℃的蒸馏水中浸渍后不轻易溶解或不轻易裂开。然而,水不溶性基底可以缓慢破碎和/或溶解,即在若干小时长至若干天内。多种材料都可以用作水不溶性基底。合适的基底的实例包括(但不限于)非织造基底、织造基底、水刺基底、喷气交缠基底、天然海绵、合成海绵和聚合网眼。
水不溶性基底可以是可冲入抽水马桶的。如本文所用,“可冲入抽水马桶的”是指基底在两次马桶冲水中将通过至少10英尺的污水管。该材料也可进行生物降解。
在一个实施例中,基底包含非织造材料。“非织造”是指基底或基底的层由未织成织物而是形成为片层、簇层或垫层的纤维构成。纤维可为无规的(即,无规排列),或者它们可为梳理成网的(即,被梳理成主要沿一个方向取向。此外,非织造基底可以由一组无规的并被梳理成网的纤维的层构成)。
非织造基底可由多种天然和/或合成材料构成。所谓“天然的”是指得自植物、动物、昆虫或植物、动物和昆虫的副产物的材料。所谓“合成的”是指主要得自各种人造材料或已进行了进一步改变的天然材料的材料。可用于本发明的天然材料的非限制性实例为丝纤维、角蛋白纤维(例如羊毛纤维、驼毛纤维)和纤维素纤维(例如木浆纤维、棉纤维、大麻纤维、黄麻纤维和亚麻纤维)。
合成材料的实例包括(但不限于)选自乙酸酯纤维、丙烯酸类纤维、纤维素酯纤维、棉纤维、改良丙烯酸类纤维、聚酰胺纤维、聚酯纤维、聚烯烃纤维、聚乙烯醇纤维、人造丝纤维、聚氨酯泡沫以及它们的混合物中的合成材料。
可用于本发明的由一种或多种天然和合成材料制成的基底可以从多种商业来源获得,如·弗罗伊登贝克公司(美国北卡罗来纳州德罕市)(Freudenberg & Co.(Durham,N.C.USA))、美国田纳西州那什维尔市BBA无纺布公司(BBA Nonwovens(Nashville,Tenn.USA))、美国南卡罗来纳州北查尔斯顿市PGI无纺布公司(PGI Nonwovens (North Charleston,S.C.USA))、美国田纳西州孟菲斯市博凯技术/沃奇索公司(BuckeyeTechnologies/Walkisoft(Memphis,Tenn.USA))、以及美国伊利诺伊州迪尔菲尔德市Fort James公司(Fort James Corporation(Deerfield,Ill.USA))。
制备非织造基底的方法也是本领域所熟知的。这些方法包括(但不限于)气流成网法、水流成网法、熔喷法、纺粘法或粗梳法。无论其制备方法或组成如何,随后都使所得的基底经受几种类型粘结操作中的至少一种,以将单独的纤维锚定在一起,从而形成自支承幅材。可通过多种方法(包括水缠结法、热粘结法以及这些方法的组合)制备非织造基底。此外,基底可以具有单层或多层。另外,多层基底可以包括薄膜层(例如有孔或无孔薄膜层)和其他非纤维材料。
非织造材料的强度或硬度可具有理想的属性。这可(例如)通过添加粘结材料(例如湿强度树脂)来实现,或者该材料可由聚合物粘结剂涂层、(例如)基于棉布、羊毛、亚麻布的短纤维制得。湿强度树脂的实例包括(但不限于)醋酸乙烯-乙烯(VAE)和乙烯-氯乙烯(EVCL)Airflex乳液(宾夕法尼亚州利哈伊县空气产品公司(Air Products,Lehigh,Pa.))、Flexbond丙烯酸聚合物(宾夕法尼亚州利哈伊县空气产品公司(Air Products,Lehigh,Pa.))、Rhoplex ST-954丙烯酸粘结剂(宾夕法尼亚州费城罗门哈斯公司(Rohm and Haas,Philadelphia,Pa.))、和乙烯-醋酸乙烯(EVA)乳液以得自(新泽西州桥水市国家淀粉化学品公司(National StarchChemicals,Bridgewater,N.J.))。基底中粘结材料的量可占基底重量的约5%至约20%。
增加强度的非织造材料还可通过使用所谓的射流喷网成布或水缠结技术来获得。在此技术中,将单独的纤维扭结在一起,以使得在无需使用粘结材料的情况下获得合格的强度或硬度。后一技术的优点在于非织造材料的优异柔软性。
在一个实施例中,非织造材料包括超吸收聚合物。就本发明的目的而言,术语“超吸收聚合物”是指在0.5磅/平方英寸的压力下能够吸收和保持至少约10倍于其重量的体液的材料。本发明的超吸收聚合物颗粒可为无机或有机交联的亲水性聚合物,例如聚乙烯醇、聚乙烯氧化物、交联淀粉、瓜耳胶、黄原胶以及吸收制品制造领域中已知的其他材料。
也可在制造过程中将活性剂复合到基底中,或随后在应用于隔膜之前施加到基底中(例如以可湿润基底的包含电解质或活性剂的液体喷剂的形式)。
另外还可加入添加剂以便增加基底的柔软性。此类添加剂的实例包括但不限于诸如甘油、丙二醇和聚乙二醇的多元醇、邻苯二甲酸酯衍生物、柠檬酸酯、诸如聚氧乙烯(20)山梨糖醇酯之类的表面活性剂、以及乙酰化单酸甘油酯。
也可将感觉属性掺入基底中。此类感觉属性的实例包括(但不限于)颜色、纹理、图案以及压花。
载体
所选装置任选地包括载体。载体可为在使用过程中能够从导电电极导电(例如,载体包含一种或多种电解质、有机溶剂、和水)的液体(例如可任选地固定在吸收材料(例如纱布或非织造垫)内的溶液、悬浮液或乳液)、半固体(例如凝胶、霜膏、洗剂、微乳、或水凝胶)或固体(例如可任选地包含活性剂的冻干组合物,其可以在使用前通过添加液体再造)。在一个实施例中,在将所述装置施用于皮肤之前,使用者将载体(例如,液体或半固体)添加至所述装置。在另一个实施例中,首先将载体施用于皮肤,然后施用所述装置。
在一个实施例中,以使用前基底的总重量计,载体的含量为至少约50重量%,如至少约75重量%。在另一个实施例中,以水不溶性基底的总重量计(例如,所述装置在使用前可不含任何载体),液体载体的含量小于约10重量%,如小于约1重量%。在另一个实施例中,产品包含使用说明,其中包括(i)在应用前润湿基底或(ii)在应用前用水和/或另一种液体润湿隔膜(例如皮肤)。
用于载体中的电解质的实例包括(但不限于)可药用的有机盐和有机盐以及缓冲剂。盐的实例包括但不限于氯化物盐(例如氯化钠、氯化钾、氯化锂、氯化钙、氯化锶、氯化镁或其他氯化物盐),以及钠、钾、锂、钙、镁、锶的氟化物盐、碘化物盐、溴化物盐。缓冲剂的实例包括但不限于磷酸盐、柠檬酸盐、乙酸盐、乳酸盐和硼酸盐。
在一个实施方案中,电解质为活性剂,或者在电流流经载体之后变成活性剂。此类电解质-活性剂的实例包括(但不限于)水杨酸、水杨酸盐、以及其他弱酸或弱碱活性剂。
在一个实施例中,载体为水或包含水。在进一步的实施方案中,载体还可包含一种或多种有机溶剂。有机溶剂的实例包括(但不限于):异山梨醇二甲基醚;豆蔻酸异丙酯;阳离子、阴离子和非离子性质的表面活性剂;植物油;矿物油;蜡;树胶;合成和天然的胶凝剂;链烷醇;二元醇和多元醇。
二元醇的实例包括(但不限于)甘油、丙二醇、丁二醇、戊二醇、己二醇、聚乙二醇、聚丙二醇、二甘醇、三甘醇、丙三醇和已三醇以及它们的共聚物或混合物。链烷醇的实例包括(但不限于)那些具有约2个碳原子至约12个碳原子(例如,约2个碳原子至约4个碳原子)的链烷醇,如异丙醇和乙醇。多元醇的实例包括(但不限于)那些具有约2个碳原子至约15个碳原子(例如,约2个碳原子至约10个碳原子)的多元醇,如丙二醇。
基于载体的总重量计,载体中的有机溶剂的含量可为约1重量%至约90重量%(例如,载体的约5重量%至约50重量%)。基于载体的总重量计,载体(使用前)中水的含量可为约5%至约95%(例如,约50%至约90%)。
载体还可包含:防腐剂(例如,甲酚、氯甲酚、苄醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、酚、乙基汞硫代水杨酸钠、苯扎氯铵、苄索氯铵、和硝酸苯汞);稳定剂或抗氧化剂(例如,抗坏血酸、抗坏血酸酯、丁基羟基苯甲醚、丁基羟基甲苯、半胱氨酸、N-乙酰半胱氨酸、亚硫酸氢钠、焦亚硫酸钠、甲醛次硫酸氢钠、丙酮亚硫酸氢钠、生育酚和去甲二氢愈创木酸);螯合剂(例如,乙二胺四乙酸及其盐);缓冲剂(例如,乙酸、柠檬酸、磷酸、谷氨酸及其盐);以及张力调节剂(例如,氯化钠、硫酸钠、右旋糖和甘油)。
在一个实施例中,载体还可包含悬浮材料和/或流体吸收材料(例如,用于物理地稳定载体的成分),例如所描述的用于基底中的那些。在一个实施例中,载体包含流体吸收材料,其包括纸,例如结合基底描述的那种纸。用于载体中的纸也应适用于皮肤,并且纸的组分应对皮肤为无毒的、非刺激性的和非致敏的。
本发明的另一个实施例涉及将一个或多个惰性导电电极配对以便在载体中从电化学反应性材料就地以电化学方式产生氧化剂或还原剂。这种氧化剂或还原剂可用作活性剂以治疗隔膜病症。
根据本发明的载体中的电化学反应性材料的实例包括(但不限于)水以及包含选自元素周期表VIB和VIIB(例如氧、硫、氟、氯、溴、和碘)的元素的化合物。
在一个实施例中,反应性材料与惰性电极反应而形成氧化剂。这种反应性材料的实例包括(但不限于)离子OH-、Cl-、I-、Br-、SO3 2-、和HCO3 -。本装置因而能够产生氧化剂,例如初生态氧(例如,单态氧)、氯气和二氧化氯气体,这些均难以在常规局部用产品中配制。
在一个实施例中,反应性材料与惰性阴极反应而形成还原剂。这种反应性材料的实例包括(但不限于)具有一个或多个巯基官能团的硫代化合物的氧化形式或二硫化物形式、含硫氨基酸及其盐或酯、以及硫化物。这种硫代化合物的实例包括(但不限于)巯基乙酸及其盐,例如钙、钠、锶、钾、铵、锂、镁的巯基乙酸盐、以及其他金属盐;硫代乙二醇;硫甘油;硫代乙醇;硫代乙酸;和硫代水杨酸;以及它们的盐。含硫氨基酸的实例包括(但不限于)L-半胱氨酸、D-半胱氨酸、DL-半胱氨酸、N-乙酰基-L-半胱氨酸、DL-高半胱氨酸、L-半胱氨酸甲酯、L-半胱氨酸乙酯、N-氨甲酰基半胱氨酸、谷胱甘肽、和半胱胺。硫化物的实例包括(但不限于)钙、钠、钾、锂和锶的硫化物以及谷胱甘肽二硫化物。惰性阴极将含硫化合物的上述反应性氧化形式或二硫化物形式转化成含硫化合物或含巯基化合物。这种转化的实例为胱氨酸到半胱氨酸的转化以及谷胱甘肽的氧化形式到谷胱甘肽的转化。
在一个实施例中,载体中的反应性材料的浓度范围可为载体的约0.01重量%至约25重量%,例如约0.1重量%至约10重量%。载体的pH值范围可为约pH 1.5至约pH 9、优选地为pH 2至pH 7、并且最优选地为约pH 3至pH 5。
在一个实施例中,载体或基底包含粘接剂。粘结剂可用来将所述装置附着在皮肤上。疏水性粘接剂的实例包括(但不限于)硅树脂、聚异丁烯及其衍生物、丙烯酸类、天然橡胶、以及它们的组合。硅树脂粘结剂的实例包括(但不限于)得自密歇根州米德兰市道康宁公司(Dow Corning(Midland,Mich.))的Dow Corning 355;Dow Corning X7-2920;DowCorning X7-2960;以及得自纽约州沃特福德市通用电气公司(GeneralElectric Company(Waterford,N.Y.))的GE 6574。丙烯酸类粘接剂的实例包括(但不限于)乙烯基(D醋酸酯-丙烯酸酯)共聚物,例如得自密苏里州圣路易斯市孟山都公司(Monsanto Company(St.Louis,Mo.))的Gelva 7371;Gelva 7881;Gelva 2943;以及得自俄亥俄州佩恩斯维尔市艾利丹尼森公司(Avery Dennison(Painesville,Ohio))的1-780医学级粘接剂。亲水性粘接剂的实例包括(但不限于)番木瓜树树胶和其他天然树胶、MC、HEMA、HPMC、EHEC、HEC、HPC、CMC、PVA、PVP、PEO、HEMA、HEEMA、HDEEMA、MEMA、MEEMA、MDEEMA、EGDMA、NVPMA、VAC、聚丙烯酰胺、明胶、阿拉伯树胶、刺梧桐胶、黄蓍胶、瓜耳胶、安息香树胶、和藻酸及其盐、聚乙二醇(PEG)、和聚丙二醇(PPG)。
在一个实施例中,载体中的粘接剂的浓度范围可为载体的约0.1重量%至约95重量%,例如约1重量%至约20重量%。
所述装置可任选地包括可移除的隔离衬片,所述可移除的隔离衬片(例如)覆盖包含粘接剂(例如粘接剂水凝胶)的基底或载体。隔离衬片通常为聚合物片材或者涂布有聚合物的纸或织物,所述隔离衬片对粘接剂水凝胶具有弱粘合力,由此允许其易于在使用前移除而不损坏所述装置。通常用于隔离衬片的聚合物的实例为硅树脂和聚乙烯。作为另外一种选择,可用蜡取代聚合物来涂布隔离衬片。
除使用粘接剂之外或者取代使用粘接剂,所述装置可用胶带、松紧带、带有扣环的带(类似于皮表带)、或尼龙表带固定于皮肤。
为了使用所述装置,剥离掉任选的可移除隔离衬片,并且将任选的载体设置到所述装置上或使用者的皮肤上。然后可将所述装置直接附着于皮肤。
在另一个实施例中,所述装置包括背衬层,例如未打孔或打孔的聚合物膜(即,聚对苯二甲酸乙二醇酯)或吸收材料(例如纸)。
本发明的一个实施例为双包装系统,其中所述装置和载体(或载体的一部分)单独进行包装。载体的一部分可为无水的固液基质(例如干的织造或非织造织物、海绵、或脱水水凝胶层(例如,冷冻干燥的水凝胶)),而载体的液体部分(例如包含活性剂的溶液、凝胶、或霜膏)包装在单独的液体容纳隔室(例如单位剂量小袋、易破容器或小瓶)中。使用之前,打破液体容纳隔室并且将载体的液体或半固体部分施加于固液基质,以启动施用于皮肤的电流的生成。将活性剂加入固液基质或液体/半固体组合物中。
在一个实施例中,所述装置为自停装置。所述装置使用包含水的载体。随着载体组合物中的水蒸发,电导系数和电流减小。最终,电流显著减小,这实际上提供了自停装置以用作使用者的安全措施,由此防止对皮肤的任何无意的过度电流施用以及可能导致的皮肤损伤。
活性剂
在一个实施例中,基底或载体包含一种或多种活性剂。可将活性剂以溶解的分子和离子、分散的固体颗粒、或液滴(例如霜膏、洗剂、乳液、微乳、和/或脂质体组合物)加入基底或载体中。
“活性剂”是指对隔膜和周围组织(例如能够对人体施加生物学效应的材料)具有美容或治疗作用的化合物(例如合成化合物或从自然来源提取的化合物),例如治疗药物,包括(但不限于)有机和大分子化合物。这类治疗药物的实例包括肽、多肽、蛋白和包括DNA的核酸物质;以及营养物质。多肽和蛋白质活性剂的实例包括促甲状腺激素释放激素(TRH)、后叶加压素、促性腺激素释放激素(GnRH或LHRH)、促黑色素细胞激素(MSH)、降钙素、生长激素释放激素(GRF)、胰岛素、促红细胞生成素(EPO)、α干扰素、β干扰素、催产素、卡托普利、缓激肽、心钠素、胆囊收缩素、内啡肽、神经生长因子、黑素细胞抑制剂-I、胃泌素拮抗剂、生长抑素、脑磷脂、褪黑激素、疫苗、肉毒素(肉毒神经毒素)、环孢菌素及其衍生物(例如生物活性碎片或类似物)。其他活性剂包括麻醉剂;镇痛剂(例如芬太尼及其盐,例如柠檬酸芬太尼);用于治疗精神障碍、癫痫和偏头痛的药物;用于抑制药物成瘾和滥用的药物;抗炎剂;用于治疗高血压、心血管疾病、胃酸和溃疡的药物;用于激素替代疗法和避孕的药物,例如雌激素和雄激素;抗生素、抗真菌剂、抗病毒剂和其他抗微生物剂;抗瘤剂、免疫抑制剂和免疫促进剂;以及作用于血液和造血器官的药物,包括造血剂和抗凝血剂、溶解血栓剂和抗血小板药物。可使用本发明的剪切装置递送到体内的其他活性剂包括多种疾病的疫苗,例如用于流行性感冒、艾滋病、肝炎、麻疹、腮腺炎、风疹、狂犬病、风疹、avercella、破伤风、低丙种球蛋白血症、Rh疾病、白喉、肉毒杆菌中毒、蛇咬、黑寡妇蜘蛛咬伤及其他昆虫咬/叮、特发性血小板减少性紫癜(ITP)、慢性淋巴细胞白血病、细胞巨化病毒(CMV)感染、急性肾排异、口服脑灰质炎、肺结核、百日咳、嗜血杆菌b、肺炎球菌、和金黄色葡萄球菌的疫苗。
在一个实施例中,基底或载体包含抗痤疮和/或抗红斑痤疮药剂。抗痤疮和抗红斑痤疮药剂的实例包括(但不限于):维甲酸类,例如维甲酸、异维甲酸、莫维A胺、阿达帕林、他佐罗汀、壬二酸和视黄醇;水杨酸;过氧化苯甲酰;间苯二酚;硫;磺胺醋酰;尿素;抗生素,例如四环素、克林霉素、甲硝唑、和红霉素;抗炎剂,例如皮质类固醇(例如氢化可的松)、布洛芬、萘普生、和酮洛芬;以及咪唑类,例如酮康唑和二氯苯基咪唑二氧戊环;及其盐和前体药物。抗痤疮活性剂的其它实例包括精油、α-红没药醇、甘草酸二钾盐、樟脑、β-葡聚糖、尿囊素、龙牙草、黄酮类化合物(例如大豆异黄酮)、沙巴棕、螯合剂(例如EDTA)、脂肪酶抑制剂(例如银和铜离子)、水解植物蛋白、氯、碘、氟的无机离子及氯、碘、氟的非离子衍生物和其他共价物、合成磷脂及天然磷脂,例如ArlasilkTM磷脂(CDM,SV,EFA,PLN)和GLA(英国威尔顿市ICI集团Uniqema公司(Uniqema,ICI Group of Companies,Wilton,UK))。
在一个实施例中,所述装置包含抗衰老剂。合适的抗衰老剂的实例包括(但不限于)无机防晒剂,例如二氧化钛和氧化锌;有机防晒剂,例如甲氧基肉桂酸辛酯;维甲酸类;二甲氨基乙醇(DMAE)、含铜肽、维生素(例如维生素E、维生素A、维生素C、和维生素B)和维生素盐或衍生物(例如抗坏血酸二葡糖苷和维生素E醋酸酯或棕榈酸酯);α-羟基酸和它们的前体,例如乙醇酸、柠檬酸、乳酸、苹果酸、扁桃酸、抗坏血酸、α-羟基丁酸、α-羟基异丁酸、α-羟基异己酸、阿卓乳酸、α-羟基异戊酸、丙酮酸乙酯、半乳糖醛酸、葡庚糖酸、葡庚糖酸內酯、葡萄糖酸、葡萄糖酸内酯、葡萄糖醛酸、葡萄糖醛酸内酯、丙酮酸异丙酯、丙酮酸甲酯、粘酸、丙酮酸、葡糖二酸、糖质酸-1,4-内酯、酒石酸和丙醇二酸;β-羟基酸,例如β-羟基丁酸、β-苯基乳酸和β-苯基丙酮酸;锌和含锌化合物(例如氧化锌);以及植物提取物,例如绿茶、大豆、乳蓟、海藻、芦荟、当归、酸橙、咖啡、黄连、葡萄柚、hoellen、金银花、薏仁、紫草、桑椹、芍药、葛根、大米、莳萝、黑莓、和红花;以及它们的盐和前体药物。
在一个实施例中,基底或载体包含脱色素剂。合适的脱色素剂的实例包括(但不限于):大豆异黄酮;类视黄醇,例如视黄醇;曲酸;曲酸二棕榈酸酯;对苯二酚;熊果苷;氨甲环酸;维生素,例如烟酸和维生素C;壬二酸;亚麻酸和亚油酸;placertia;甘草;以及提取物,例如春黄菊和绿茶;及其盐和前体药物。
在一个实施例中,基底或载体包含植物提取物。植物提取物的实例包括(但不限于)龙牙草、大豆、野生大豆、燕麦片、小麦、芦荟、越橘、金缕梅、赤杨皮、山金车酊、茵陈蒿、细辛根、桦树、金盏花、春黄菊、蛇床属植物、聚合草、茴香、五倍子、山楂、鱼腥草、金丝桃属植物、枣子、猕猴桃、甘草、木兰、橄榄、胡椒薄荷、喜林芋属植物、鼠尾草属植物、日本纹竹(sasa albo-marginata)、天然类异黄酮、大豆异黄酮、和天然精油。
在一个实施例中,基底或载体包含金属,例如金属离子、金属盐、金属络合物、细金属粉末、细金属涂布的合成或天然的纤维和织物、或者细金属纤维。这种金属的实例包括(但不限于)锌、铜、铝、金、银、钛。金属离子提供有益效果,例如抗微生物、抗炎、和/或皮脂减少作用。与电流通过同时发生的电化学氧化反应,可使得从金属阳极释放有益的金属离子(例如,从锌阳极以电化学方式产生的锌离子)。
在另一个实施例中,可在电极表面处由电化学反应间接地产生有益离子,例如,在惰性电极处产生氢或氢氧根离子,其随后导致产生有益离子的过程。例如,本发明的装置可包括惰性阳极(例如,铂、铂涂布的导电电极、金、或金涂布的导电电极)、反应性阴极(例如,银/氯化银电极)、和包含(除其他活性剂之外)氧化物(例如,氧化锌粒子)的水性载体组合物。在施用于皮肤期间,惰性阳极处的水的电解产生过量的氢离子而使载体酸化至较低的pH值,然而反应性阴极处的电化学反应(例如,氯化银转化成银离子)不影响pH。当溶液成为更加酸性时,氧化物开始溶解以释放离子(例如,锌离子)从而发挥其对隔膜的有益效果。
其他活性剂包括通常用于局部治疗和皮肤组织的美容治疗的那些,例如用于伤口的局部用抗生素、用于治疗皮肤和指甲的真菌感染的局部用抗真菌药、以及用于治疗皮肤和银屑病指甲的银屑病病灶的抗银屑病药。
抗真菌药的实例包括(但不限于)咪康唑、益康唑、酮康唑、丝他康唑、伊曲康唑、氟康唑、伏立康唑、氯碘羟喹、比佛那唑(bifoconazole)、特康唑、布康唑、噻康唑、奥苷康唑、硫康唑、沙康唑、克霉唑、十一烯酸、卤普罗近、布替萘芬、托萘酯、制霉菌素、环吡酮胺、特比萘芬、阿莫罗芬、萘替芬、二氯苯基咪唑二氧戊环、灰黄霉素及其药用盐和前体药物。在一个实施例中,抗真菌药为唑、烯丙胺、或它们的混合物。
抗生素(或防腐剂)的实例包括(但不限于)莫匹罗星、硫酸新霉素、杆菌肽、多粘菌素B、1-氧氟沙星、四环素(盐酸氯四环素、盐酸氧四环素和盐酸四环素)、磷酸克林霉素、硫酸庆大霉素、甲硝唑、己基间苯二酚、甲苄索氯铵、酚、季铵化合物、茶树油、以及它们的药用盐和前体药物。
抗微生物剂的实例包括但不限于氯己定的盐,例如碘代丙炔基丁基氨基甲酸酯、双咪唑烷基脲、葡萄糖酸氯己定、醋酸氯己定、羟乙基磺酸氯己定和盐酸氯己定。还可使用其他阳离子抗微生物剂,例如苯扎氯铵、苄索氯铵、三氯卡班、聚六亚甲基双胍、十六烷基氯化吡啶鎓、甲苄索氯铵。其他抗微生物剂包括(但不限于):卤代酚类化合物,例如2,4,4,-三氯-2'-羟基二苯基醚(三氯生);对氯间二甲苯酚(PCMX);和短链醇类,例如乙醇、丙醇等。在一个实施例中,所述的醇优选地为低浓度(例如小于载体的约10重量%,如小于载体的5重量%),以使其不会造成隔膜的过度干燥。
抗银屑病药或者用于皮脂溢性皮炎治疗的药物的实例包括(但不限于)皮质类固醇(例如,倍他米松二丙酸酯、倍他米松戊酸酯、丙酸氯倍他索、二乙酸二氟拉松、卤贝他索丙酸酯、曲安奈德、地塞米松、氟轻松醋酸酯、氟轻松、哈西奈德、曲安西龙醋酸酯、氢化可的松、戊酸氢化可的松、丁酸氢化可的松、阿氯米松双丙酸酯、氟氢缩松、糠酸莫米松、醋酸甲基氢化甲泼尼龙)、甲氨蝶呤、环孢菌素、卡泊三烯、蒽林、页岩油及其衍生物、二氯苯基咪唑二氧戊环、酮康唑、柏油、水杨酸、1-氧-2-巯基吡啶锌、硫化硒、氢化可的松、硫、薄荷醇和盐酸普莫卡因、以及它们的盐和前体药物。
用于病毒感染(例如疱疹和肝炎)的抗病毒剂的实例包括(但不限于)咪喹莫特及其衍生物、普达非洛、盾页鬼臼树脂、干扰素α、阿昔洛韦、泛昔洛韦、伐昔洛韦、reticulos和西多福韦、以及它们的盐和前体药物。
抗炎剂的实例包括但不限于合适的甾族抗炎剂,例如皮质类固醇,例如氢化可的松、羟基去炎松α甲基地塞米松、磷酸地塞米松、二丙酸倍氯米松、戊酸氯倍他索、地奈德、脱氧米松、醋酸去氧皮质酮、地塞米松、二氯松、二乙酸二氟拉松、戊酸二氟可龙、fluadrenolone、氟氯奈德、氟氢可的松、新戊酸氟米松、氟轻松、氟轻松醋酸酯、氟可丁酯、氟可龙、醋酸氟泼尼定(氟强的松)、氟氢缩松、哈西奈德、乙酸氢化可的松、丁酸氢化可的松、甲基强的松龙、曲安奈德、可的松、可托多松、flucetonide、氟氢可的松、醋酸双氟拉松、fluradrenalone acetonide、甲羟松、amciafel、安西非特、倍他米松、氯泼尼松、乙酸氯泼尼松、氯可托龙、clescinolone、二氯松、二氟泼尼酯、氟二氯松、氟尼缩松、氟甲去氧泼尼松龙、氟培龙、戊酸氢化可的松、氢化可的松环戊丙酸酯、氢可松氨酯、甲泼尼松、帕拉米松、氢化泼尼松、泼尼松、二丙酸倍氯米松、二丙酸倍他米松、氟羟氢化泼尼松及其盐和前体药物。用于本发明的优选的甾族抗炎剂为氢化可的松。可用于本发明的组合物中的第二类抗炎剂包括非甾族抗炎剂。
其他活性剂包括(但不限于)伤口愈合促进剂,例如重组人类血小板衍生生长因子(PDGF)和其他生长因子、酮色林、伊洛前列素、前列腺素E1和透明质酸、去疤剂(例如甘露糖-6-磷酸)、止痛剂、麻醉剂、毛发生长促进剂(例如敏乐啶)、毛发生长抑制剂(例如盐酸依氟鸟氨酸)、降压剂、治疗冠心病的药物、抗癌剂、内分泌和代谢药物、神经病学药物、化学剂成瘾戒除药物、运动病、蛋白质和肽药物。
在一个实施例中,基底或载体包含芳香剂以有效用于减小压力、镇静、和/或影响睡眠,例如薰衣草和春黄菊。
所述装置中的活性剂的量总是取决于活性剂和/或所述装置的预期用途。在一个实施例中,所述装置包含安全有效量的活性剂,例如,占基底或载体的约0.001重量%至约20重量%,如约0.01重量%至约5重量%。
在一个实施例中,基底或载体包含至少两种带相反电荷的活性剂。一个这种组合物的实例包含约0.5至约2%的水杨酸和约0.01至约0.2%的阳离子季铵抗微生物剂(例如,苯扎氯铵、苄索氯铵、甲基苄索氯铵、和鲸蜡基氯化吡啶鎓)、酚、和/或洗必太葡糖酸酯。所述装置可同时将两种带相反电荷的活性剂递送进隔膜内。
一般用途
所述装置可用于治疗隔膜病症(例如,将活性剂、光、和/或电流递送到皮肤或粘膜组织中)。在一个实施例中,所述装置用于治疗皮肤病症。此类治疗的实例包括(但不限于):治疗痤疮、红斑痤疮、或皮肤的其他微生物感染;减少可见的皮肤老化迹象(例如,皱纹、松垂、和老年斑);治疗毛囊炎和须部假性毛囊炎;治疗伤口和病灶(例如,促进愈合和减少疤痕);调节皮脂(例如,减少皮脂和/或抑制或控制油性/光亮皮肤外观);调节色素沉着(例如,减少浅色皮肤的色素沉着过度或色素沉着);延缓毛发生长(例如,腿上的皮肤)或刺激毛发(例如,头皮);以及治疗皮炎(例如,特应性、接触性、或皮脂溢性皮炎)和/或银屑病。
在另一个实施例中,所述装置用于治疗粘膜病症(例如,口腔或阴道腔内的粘膜)。此类治疗的实例包括(但不限于):对于阴道念珠菌病和阴道炎、生殖器和口腔疱疹、感冒疮、口腔溃疡、口腔卫生、牙周病、和粘膜的其他微生物感染的治疗。
在另一个实施例中,所述装置诱导某些所需生物学反应以促进隔膜病症的治疗。在隔膜病症的治疗中,可通过穿过隔膜的电流、和/或以电化学方式产生的氧化物质、以及从所述装置通过离子电渗法递送的活性剂来诱导这些所需的生物反应。隔膜的所需反应的实例包括(但不限于)皮脂调节(例如,降低皮脂腺活力)、抑制厌氧性微生物生长和建立较健康的膜微生物群落(例如,降低痤疮丙酸杆菌的生长和产生刺激性脂肪酸)、血管收缩(由此促进活性剂的局部积聚或者移除因脱氧血红蛋白导致的眼下的黑眼圈)、增强的组织免疫活性(例如,增强杀灭组织自身的防御系统上的病原微生物)、改善的组织修复(例如,增强愈合并且减少病灶(例如痤疮病灶)的瘢痕)、以及改善的角质层分离活性(例如,软化痤疮的白头和黑头中的粉刺的角质栓以及促进其移除)。
在一个实施例中,所述装置用于消除或减轻各种类型的疼痛或其他感觉不适,包括(但不限于)背痛、关节疼痛、颈痛、肩痛、皮肤的发麻或麻木、手术后疼痛、肌痛、肌肉痉挛、经期痉挛、关节僵直、头痛或胃痛。当用于除皮肤之外的较深组织或器官的疼痛时,电偶的电极具有较大的尺寸并且隔开较远距离以较深地递送电刺激并覆盖人体的较大区域,例如在治疗背痛、膝痛、肩痛或颈痛时。
在另一方面,本发明的特征还在于通过惰性电极的氧化或还原将活性剂从较低活性的形式转化成较高活性的形式(例如,胱氨酸转化成半胱氨酸、二硫化乙酰基-半胱氨酸转化成乙酰基-半胱氨酸、和视黄醇转换成视黄酸)的方法。因此,不稳定的试剂可以较稳定的形式贮存并在施用前转化成其活性形式。在另一方面,通过本发明的装置产生的还原剂可用于稳定氧不稳定的活性剂。这种氧不稳定的活性剂的实例包括(但不限于)维甲酸类、抗坏血酸、和过氧化苯甲酰。
在一个实施例中,本发明的特征还在于通过反应性阳极(例如由锌、镁、铜、铝、这些金属的合金或混合物制成的阳极)处的氧化将活性剂从较低活性的形式转化成较高活性的形式的方法。例如,由锌制成的阳极在电流通过该电极时释放锌离子。然后通过带正电荷的阳极的电斥力将由这种电化学反应产生的锌离子递送至隔膜中。在一个实施例中,这种离子沉积到毛囊和/或皮脂腺中,以抑制痤疮丙酸杆菌生长和/或抑制因治疗前过度生长的痤疮丙酸杆菌导致的皮肤组织炎症。类似地,锌-铜合金阳极或另一种锌-有益金属合金分别将锌离子和铜离子或其他有益离子释放到毛囊和皮脂腺中以用于痤疮治疗和预防。
在一个实施例中,本发明的装置用于通过递送活性剂(包括载体中预配制的活性剂和通过电极以电化学方式产生的活性剂(例如,有益的金属离子))和/或通过将电刺激加到皮肤组织来治疗皮肤病症,例如:痤疮(例如,黑头和白头)和痤疮相关的皮肤病症(例如红斑痤疮和结节囊肿);色素沉着过度,例如雀斑、黑斑、光化性和老年性着色斑、老人斑、炎症后过度黑素沉着病、Becker's痣、眼下的黑眼圈、和面部黑变病;牵拉痕;以及皮肤上的皮肤年龄效应(例如由光损伤引起的那些),包括起皱、粗糙、色素改变、灰黄、细纹、和松弛。
在一个实施例中,所述装置提供多种作用机制来治疗这些病症:即,(a)通过离子电渗法和电渗透法将预配制的活性剂靶向递送到毛囊皮脂腺单位中;(b)以电化学方式产生新活性剂(例如,得自反应性阳极的有益金属离子)并且将新产生的活性剂(例如,有益离子,例如已知可增强皮肤自身的免疫系统的锌和铜)靶向递送到毛囊皮脂腺单位中;和/或(c)将电刺激加到毛囊皮脂腺单位及其周围皮肤组织以增强血液循环、通过减少炎症来治疗皮肤、促进伤口愈合、和/或增加皮肤脱落。
在一个实施例中,本发明的装置可用作伤口敷料或绷带或者可结合到伤口敷料或绷带中以提供电治疗,由此促进愈合和防治疤痕。在一个实施例中,伤口渗出液和/或伤口清洗液用于激活流电伤口敷料/绷带,以递送预加入伤口敷料/绷带中的活性剂和/或以电化学方式产生有益金属离子并随后将有益金属离子递送进伤口。所述装置还利用治疗电流来治疗伤口,所述治疗电流可增加血液循环、刺激组织免疫反应、和/或抑制组织炎症,由此可导致加速愈合和减少疤痕形成。
在一个实施例中,本发明的装置以干擦拭物、毛巾、或者全面膜或局部面膜(例如,具有约20cm2至约10,000cm2的表面积)的形式使用,这种装置可在临使用前通过将水施用于所述装置或皮肤来进行润湿(例如,用自来水清洗)。在另一个实施例中,本发明的装置以治疗贴片或面膜(例如,具有约1cm2至约600cm2的表面积)的形式使用以施用于面部的一部分或基本全部上。
强化贴片
在一个特定实施例中,所述装置被构造为与其他皮肤治疗(例如面膜)结合使用的强化贴片。因此,所提供的皮肤治疗产品包括面膜(优选地为润湿面膜)和本发明的装置。
在另一个实施例中,所述装置被构造为可通过使用载体而直接施用于皮肤的强化贴片。
在一个实施例中,强化贴片的基底为非吸收性的(例如,基底包括PET膜)并且使强化贴片的印刷表面朝向皮肤。
在另一个实施例中,强化贴片的基底为吸收材料(例如为纸,但不限于纸)并且电流可流过基底以及面膜和皮肤。因此,强化贴片的任一表面可取向为面向皮肤。对于其中吸收性强化贴片和面膜结合使用的应用而言,优选的是其上设置电偶的表面(即,其上印刷第一和第二导电电极的表面)被面向面膜施用。对于其中单独使用吸收性强化贴片而不存在面膜的应用而言,优选的是使强化贴片的未印刷表面靠贴于皮肤。
在一个实施例中,可将活性成分沉积到干燥的强化贴片上,例如基底上。
强化贴片和面膜或皮肤之间的粘合至关重要,并可通过若干方法来实现。优选的是,包含在面膜内的流体与强化贴片基底之间的表面力足够大,使得强化贴片能够轻易地粘附于润湿面膜或皮肤。如果情况并非这样,则可改变强化贴片的基底、面膜液体、或面膜材料的表面特性以便于充分粘合。在一个实施例中,可通过对强化贴片的基底或面膜材料进行电晕处理来表面改性以改变表面张力,从而使表面粘合力增大。在另一个实施例中,可通过将粘接剂或溶解聚合物添加至干燥的强化贴片或面膜材料来增强粘合力,以使得所述制剂在润湿时变得具有粘性。在另一个实施例中,面膜可包含配制有粘性物质(例如聚丙烯酸钠和/或丙烯酸酯/C10-30烷基丙烯酸酯交联聚合物)的液体。
在另一个实施例中,可将机械特征附加于强化贴片以增强与面膜的粘合力。这种特征包括(但不限于):1)强化贴片上的吊钩、倒钩、或其他凸起以对面膜基底产生类似于效果的机械连接;2)强化贴片的表面的纹理化以增加其表面粗糙度,以使得在强化贴片和面膜之间用于增加吸引的表面积增大;3)将释放缝引入到强化贴片中以便增加围绕解剖学上陡变表面贴合的柔性和适形性。
图1示出了根据本发明的单个电偶的俯视图。电偶包括基底160上的第一导电电极140和第二导电电极240。第一和第二导电电极通过含有导电材料的连接桥350实现电气连通。图2为根据本发明的装置的俯视图,所述装置包括具有多个图1的分立电偶的基底160。
图3为根据本发明的包括第一导电电极140和第二导电电极240的单个电偶的俯视图,所述第一导电电极140和第二导电电极240通过包括第二导电电极240的延伸部的连接桥240A实现电气连通。图4为根据本发明的装置的俯视图,所述装置包括具有多个图3的分立电偶的基底160。
图5为具有波状H形的根据本发明的单个电偶的俯视图。所述电偶包括第一导电电极140和第二导电电极240,所述第一导电电极140和第二导电电极240通过包括第二导电电极的延伸部的连接桥240A实现电气连通。图6为根据本发明的装置的俯视图,所述装置包括具有多个如图5所示的分立电偶的基底160。
图7为根据本发明的装置的俯视图,所述装置包括呈套叠构型的多个如图1所示的分立电偶。在该装置中,在基底160上设置电偶阵列以增加其表面密度。六个电偶的第一导电电极140取向为将单一极性向所述装置的中心会聚。
图8为根据本发明的用作强化贴片的装置的俯视图。强化贴片包括弧形的基底160,所述基底160包括沿周边的释放缝450以增强对皮肤表面的适形能力。强化贴片包括具有波状H形的电偶,各个电偶均包括与第二导电电极240电子连通的第一导电电极140。
图9为根据本发明的皮肤治疗产品的俯视图,所述皮肤治疗产品包括盖在靠贴于皮肤650的面膜550上的装置750。面膜550包含吸湿材料,其可载有包含活性剂的制剂。在一个实施例中,所述皮肤为面部皮肤。在一个实施例中,吸收材料为滤纸。在另一个实施例中,吸收材料为非织造材料。在一个实施例中,吸收材料具有全面膜形状。然后将强化贴片750施用于面膜,其中导电电极面向皮肤,所述强化贴片750包括基底160上的多个分立电偶,所述分立电偶包括通过连接桥350而处于电子连通状态的第一导电电极140和第二导电电极240。吸收材料内吸收的润湿制剂提供强化贴片的粘合力。
实例1
按下述步骤制备根据本发明的电偶。将包含锌的第一导电电极和包含银/氯化银的第二导电电极丝网印刷到包括麦拉膜的基底上。将包含可药用的粘结剂、增塑剂、溶剂和金属锌的油墨制剂用作第一导电电极的材料。将包含可药用的粘结剂、增塑剂、溶剂和氯化银的油墨制剂用作第二导电电极的材料。将金属银粉添加到这两种油墨以增强印刷迹线的导电性。
印刷的锌迹线为1mm宽×10mm长并且是通过195目的聚酯网进行印刷的。银/氯化银迹线为2mm宽×10mm长,通过255目的聚酯网印刷。所述电极被取向成使得所述10mm轴线彼此平行并且隔开4mm的间隙。锌和银/氯化银电极的端到端迹线电阻小于100欧姆。
电极通过导电碳的印刷迹线实现电气连通,所述导电碳的印刷迹线印制于(位于)锌和银/氯化银迹线之前(下面)。导电碳和印刷尺寸被修改成可在电极之间的整个4mm间隙上提供2000欧姆的电阻。包含可药用的粘结剂、增塑剂、溶剂和碳的油墨制剂被用作导电碳迹线的材料。
电偶具有图1所示的设计,所述设计由H形图案构成,其中代表‘H’的直腿的锌导电电极240和银/氯化银电极140和代表作为横杆的连接碳迹线350的碳形成完整的电偶电源。
电偶具有约10mm×7mm的尺寸并且覆盖约1cm2。
这些电偶的阵列用DEK Horizon 03i商用丝网印刷机印制。电偶之间的水平间距设为4mm,使得所有锌和银/氯化银迹线之间的间距均被固定,即电偶内锌和银/氯化银之间的间隙与电偶之间的间隙具有相同的尺寸。因此,可将均匀分布的电流递送至治疗区域。电偶之间的垂直间距为2mm。
通过将非织造材料的一部分设置在电偶的印刷表面上来测试电偶的电流输出。用电导率为1300微西门子的美容制剂来润湿非织造材料并且用万用表和PC数据采集站来测量电流。这些样品的电流范围为每电偶80-120A并且持续20-30分钟。
通过对美容制剂掺加UV荧光分子水杨酸并且将所述装置靠着自愿受试者的面部皮肤放置20分钟来确认活性化合物到皮肤中的增强递送。所述产品一经移除即清洗皮肤,皮肤的UV照片显示出由明亮的矩形构成的阵列,这些明亮的矩形表明水杨酸已经以离子电渗方式进入了皮肤。
实例2
在此实例中,将由锌(阳极)和银/氯化银(阴极)油墨构成的多个分立电偶丝网印刷到麦拉膜上,如实例1所述。然而,这些电极通过锌迹线的凸起来实现接触和电气连通,所述锌迹线的凸起也由锌油墨构成并且连接至银/氯化银迹线。该凸起(锌桥)具有0.25mm的宽度和5mm的长度,并且产生约20欧姆的跨越电偶的电阻。整个设计由‘H’图案构成,所述‘H’图案具有代表‘H’的直腿的锌和银/氯化银和代表连接杆的锌,如图3所示。实际上,锌为旋转90度的“T”形。相比于实例1中所述的三步骤电偶,该电偶以两个步骤进行印刷。在银/氯化银迹线之前印刷锌‘T’。
例如用如实例1中所述的商用丝网印刷机来印刷这些电偶的阵列。按实例1中的描述测试了电偶的电流输出。这些样品的电流范围为每电偶300-500μA并且持续20-30分钟。
按照实例1中所述利用水杨酸来确认活性化合物到皮肤中的增强递送。移除产品时,洗涤皮肤并且皮肤的UV照片显示出亮矩形阵列,这表明水杨酸以离子电渗方式递送进了皮肤。
实例3
制备了根据本发明的包括锌和银/氯化银波状电极的装置。这样做是为了增加阵列内电偶的美观。尽管电极为波状的,但锌和银/氯化银迹线之间沿各个电偶长轴的所有点处的间距均固定不变,以确保电流均匀地分布在电极之间。电学性能和化合物进入皮肤的递送均与实例2的类同。
实例4
为了增加某些区域中的电偶密度并且为了将负极向皮肤上的斑点会聚以增加电流强度或电流密度,制备如图7所示的装置。利用实例1中所述的方法将六个各自包括第一导电电极140和第二导电电极240的电偶沉积到基底160上。第一和第二导电电极通过包含导电材料的连接桥350实现电气连通。另外,电偶交错套叠以使得银/氯化银电极向阵列的中心会聚。相邻的电偶相交插,以增加治疗部位处的电流密度。电偶以此方式进行套叠可为斑点治疗应用形成优选的电极性,以及增加被治疗组织表面的电流密度。可根据所需效果以任何取向来实现套叠的电偶。它们也可被设置为将正极向一个斑点会聚。
实例5
下述实例描述被设计成可粘附于包括非织造材料的面膜的强化贴片。
将十二个双油墨电偶丝网印刷到2密耳的麦拉膜上,然后将所述麦拉膜切割成具有如图8所示的形状。在强化贴片的周边中实施四个机械应力释放凹槽以增强柔性。
十五个自愿受试者按如下步骤对于面膜使用强化贴片。首先,使用者将润湿的非织造面膜施用于其面部。然后各个使用者将强化贴片施用于面膜,其中印刷的侧面(即包括电偶的一侧)朝向面膜。强化贴片通过仅与表面张力相关的力轻易地粘附于润湿的面膜。在强化贴片施用20分钟之后,移除面膜和强化贴片。
由自愿受试者评价耐用性和强化贴片的粘合力。对于10个自愿受试者,强化贴片在完整的20分钟治疗中保持在润湿面膜上且未出现剥离。两个自愿受试者报告贴片在15分钟之后轻度剥离并且三个受试者报告不到15分钟的治疗就出现剥离。
通过对面膜中的制剂掺加水杨酸并且针对7个自愿受试者按上文所述将强化贴片靠着面膜进行设置来确认活性化合物到皮肤中的增强递送。所述产品一经移除,就用肥皂和水清洗皮肤。皮肤的紫外线照片显示出对应于锌电极的亮区阵列,这表明水杨酸以离子电渗方式递送进了皮肤。
实例6
针对两个非织造基底来比较锌导电油墨的印刷质量,其中一个基底由开孔的纯人造丝料构成并且一个基底由聚乙烯/纸浆的50/50共混物构成。对于两个基底,在相同的印刷条件下完成印刷。印刷图案由2mm×10mm矩形的阵列组成。对于人造丝基底而言,在矩形迹线的长端之间测得印刷迹线的电导率小于100欧姆。显微图像显示非织造样品的纤维被油墨均匀地涂布,这表明具有相同的表面能。印刷在聚乙烯/纸浆非织造材料上的迹线显示出散在的电阻值,其中多个迹线完全不导电。显微图像指示出非织造材料的纤维未被油墨涂布。然而,油墨以微珠形式沉积进非织造基质中。这导致沿印刷迹线的不连续性,其转变成高电阻值。
实例7
按照实例1中所述将由锌、银/氯化银、和碳油墨制成的电偶印刷到开孔人造丝非织造材料上。显微镜检查显示油墨可轻易涂布在非织造材料的人造丝纤维上,这表明油墨-人造丝系统的润湿性。银/氯化银和锌电极的电阻均小于100欧姆。碳的电阻为1000欧姆。通过将电导率为1300微西门子的导电性美容溶液添加到经印刷的非织造材料来测量电流输出。每个电偶产生的电流在100-150μA的范围内。
在人体皮肤上来测试所得产品以评价带电荷的UV-荧光化合物、水杨酸到皮肤的离子电渗递送。自愿受试者利用电导率为1300微西门子的掺加有水杨酸的美容凝胶来润湿非织造材料并且将非织造材料的未印刷侧面靠着颊部皮肤放置20分钟。然后移除所述产品,并用温和的肥皂清洗皮肤。皮肤的紫外线照片显示出对应于锌电极的亮区阵列,这表明水杨酸以离子电渗方式递送进了皮肤。
应当了解,虽然已结合本发明的具体实施方式描述了本发明,但是前述描述旨在说明而非限制由随附权利要求书所限定的本发明的范围。其他方面、优点和修改均在权利要求书内。
Claims (15)
1.一种用于治疗皮肤的装置,包括具有多个均匀分布且彼此分立的电偶的基底,各电偶彼此分离并且不接触,各个电偶均包括与第二导电电极电子连通的第一导电电极,所述第一导电电极为阳极而所述第二导电电极为阴极,所述第一和第二导电电极都含有油墨。
2.根据权利要求1所述的装置,其中各个电偶具有0.01cm2至10cm2的尺寸。
3.根据权利要求1所述的装置,其中各个电偶具有10cm2至400cm2的尺寸。
4.根据权利要求1所述的装置,其中所述第一和第二导电电极通过包含至少一种导电材料的连接桥实现电子连通。
5.根据权利要求1所述的装置,其中所述第一和第二导电电极通过包括所述第一或第二导电电极的延伸部的连接桥实现电子连通。
6.根据权利要求1所述的装置,其中各个电偶的形状选自基本上H形、基本上U形和基本上N形。
7.根据权利要求1所述的装置,其中所述电偶在所述基底上相套叠。
8.根据权利要求1所述的装置,其中所述基底包括的材料选自纸和塑料。
9.根据权利要求1所述的装置,其中所述基底包括的材料选自织造材料和非织造材料。
10.根据权利要求1所述的装置,还包括载体,所述载体适于接触皮肤并且与所述第一和第二导电电极离子连通。
11.根据权利要求1所述的装置,其中所述第一和第二导电电极的标准电势差为至少0.2V。
12.根据权利要求1所述的装置,还包括所述基底中的活性剂。
13.根据权利要求10所述的装置,还包括所述载体中的活性剂。
14.根据权利要求1所述的装置,其中所述第一导电电极包括锌、镁、铁、铝和/或它们的合金,并且所述第二导电电极包括铜、铁、金、银、铂、碳、它们的合金、它们的氧化物和/或它们的卤化物。
15.一种皮肤治疗产品,包括面膜和下述装置,所述装置包括具有多个均匀分布且彼此分立的电偶的基底,各电偶彼此分离并且不接触,各个电偶均包括与第二导电电极电子连通的第一导电电极,所述第一导电电极为阳极而所述第二导电电极为阴极,所述第一和第二导电电极都含有油墨,所述装置具有适于在将所述面膜和所述装置施用于皮肤期间盖在所述面膜上面或下面的形状和尺寸。
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- 2010-11-08 CN CN201080060622.3A patent/CN102711905B/zh not_active Expired - Fee Related
- 2010-11-08 AU AU2010319733A patent/AU2010319733B2/en not_active Ceased
- 2010-11-08 WO PCT/US2010/055819 patent/WO2011059915A1/en active Application Filing
- 2010-11-08 BR BR112012011411A patent/BR112012011411A2/pt not_active IP Right Cessation
- 2010-11-08 KR KR1020127014808A patent/KR20120091335A/ko active IP Right Grant
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- 2010-11-08 CA CA2780537A patent/CA2780537A1/en not_active Abandoned
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ES2617760T3 (es) | 2017-06-19 |
CN102711905A (zh) | 2012-10-03 |
RU2012124042A (ru) | 2013-12-20 |
US8744567B2 (en) | 2014-06-03 |
EP2498867B1 (en) | 2016-12-21 |
AU2010319733B2 (en) | 2014-08-07 |
KR20120091335A (ko) | 2012-08-17 |
US20110118655A1 (en) | 2011-05-19 |
CA2780537A1 (en) | 2011-05-19 |
AU2010319733A1 (en) | 2012-05-31 |
BR112012011411A2 (pt) | 2017-12-12 |
EP2498867A1 (en) | 2012-09-19 |
RU2548824C2 (ru) | 2015-04-20 |
WO2011059915A1 (en) | 2011-05-19 |
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