CN1250171C - 利用微凸起刺入皮肤的装置和方法 - Google Patents
利用微凸起刺入皮肤的装置和方法 Download PDFInfo
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Abstract
本发明公开了一种用于形成一个或多个通过角质层的微裂口的装置,通过这些微裂口可以输送或取样介质,这种装置包括:一敷贴器,其包括:一装置主体,一可运动地安装在所述装置主体内的活塞,一设于所述装置主体上以便致动敷贴器从而利用一微凸起构件冲击角质层的盖件,一环绕所述活塞的杆定位并相对于装置主体向下偏压所述活塞的弹簧,一接触表面;以及一具有一个或多个角质层刺入微凸起的微凸起构件,微凸起构件可释放地安装于所述敷贴器上,其中,所述敷贴器的构形做成通过所述接触面施加一个冲击于所述微凸起构件上,使得所述微凸起构件以在10毫秒或者更短时间内每平方厘米微凸起构件至少0.05焦耳的能量冲击角质层。
Description
技术领域
本发明涉及一种用于通过冲击将刺入构件施加到角质层的装置和方法,并且更具体而言,本发明涉及一种敷贴器装置的使用,该装置利用一种微凸起阵列来提供冲击以便可重复地刺入角质层,从而输送或采样介质。
背景技术
随着市场上日益增加的可大量得到的纯态的医用肽和蛋白质,对于将肽和蛋白质通过皮肤输送到人体的兴趣也持续增长。通过皮肤输送肽和蛋白质仍然面临很显著的问题。在许多场合,由于多肽具有较大的尺寸和分子量,因此通过皮肤输送多肽的速度和流量不足以产生所需治疗效果。另外,在刺入皮肤期间和之后并且到达目标细胞之前,多肽和蛋白质容易降级。同样,许多低分子量的化合物的被动地通过皮肤的流量太低,因而不能达到治疗效果。
一种增强通过皮肤输送介质的量的方法是依赖于使用皮肤渗入增强器,通过对皮肤进行预处理或与有益介质一起输送的方式进行。渗入增强器物质在施加到输送介质的身体表面时,将会增强介质通过皮肤的流量。通过这些增强器的作用,就可以增强身体表面的选择刺入性和/或刺入性,并且/或者减小介质的降级。
增强介质流量的另一方法涉及在身体表面上施加电流并称之为“电迁移”。“电迁移”通常指的是有益介质,例如药物或药引,通过身体表面,例如皮肤、黏膜、指甲和类似物。介质的传输通过施加电位而引起或得以增强,该电位通过施加用于输送介质或增强介质的输送的电流产生。电迁移输送方式增强了介质的输送量并降低了通过皮肤输送期间的多肽的降级。
已经进行了许多尝试以便通过机械方式刺入或穿过皮肤从而增强通过皮肤的流量,例如授予Godshall等人的US5,879,326,授予Ganderton等人的US3,814,097,授予Gross等人的US5,279,544,授予Lee等人的US5,250,023,授予Gerstel等人的US3,964,482,授予Kravitz等人的Reissue25,637,和PCT公开号WO96/37155,WO96/37256,WO96/17648,WO97/03718,WO98/11937,WO98/00193,WO97/48440,WO97/48441,WO97/48442,WO98/00193,WO99/64580,WO98/28037,WO98/29298,WO98/29365。这些装置使用不同形状和尺寸的穿刺元件刺透皮肤的最外层(即,角质层)。这些参考文件所公开的刺入元件通常从一个薄平构件,例如垫或片,垂直延伸。刺入元件通常被称作“微刀片”,在某些这种装置中尺寸极小。有些这些微刀片尺寸(微刀片长度和宽度)只有大约25~400μm,而微刀片厚度大约为5~50μm。其他的刺入元件有空心针,具有大约10μm或更小的直径以及大约50~100μm的长度。这些微小的角质层穿刺/切割元件用于在角质层内形成相应小的微切口/微裂口,以便通过其中增强介质通过皮肤的输送量,或者增强身体分析物通过皮肤的流量。被穿过的皮肤提供得以改进的流量以便通过皮肤持续地进行介质输送或者采样。在许多场合,角质层内的微切口/微裂口具有小于150μm的长度和显著小于其长度的宽度。
当微凸起阵列用来改进通过皮肤输送或采样介质时,需要通过微凸起阵列实现连续、完整和可重复的刺入。用手施加皮肤贴片包括微凸起经常导致穿刺深度跨过微凸起阵列而存在显著变化。另外,由于使用者施加阵列的方式的原因,用手施加操作还会导致不同施加次数之间的穿刺深度存在很大变化。因此,希望能够使用自动或半自动装置来将微凸起阵列施加到角质层上,从而提供以连续和可重复的方式提供微凸起皮肤刺穿操作。
因此,需要提供一种用于将微凸起阵列连续、可重复地施加于皮肤上的敷贴器,通过敷贴器施加一个能够利用微凸起阵列实现有效刺穿角质层的冲击。
发明内容
本发明涉及一种用于形成一个或多个通过角质层的微裂口的装置,通过这些微裂口可以输送或取样介质,这种装置包括:一敷贴器,其包括:一装置主体,一可运动地安装在所述装置主体内的活塞,一设于所述装置主体上以便致动敷贴器从而利用一微凸起构件冲击角质层的盖件,一环绕所述活塞的杆定位并相对于装置主体向下偏压所述活塞的弹簧,一接触表面;以及一具有一个或多个角质层刺入微凸起的微凸起构件,微凸起构件可释放地安装于所述敷贴器上,其中,所述敷贴器的构形做成通过所述接触面施加一个冲击于所述微凸起构件上,使得所述微凸起构件以在10毫秒或者更短时间内每平方厘米微凸起构件至少0.05焦耳的能量冲击角质层。
附图说明
本发明现在将参考附图中所示的优选实施例进行更详细的描述,其中相同元件具有相同的参考标号,并且附图中:
图1是在击发之前处于初始构型的敷贴器装置的侧剖视图;
图2是在击发位置上的图1的敷贴器装置的侧剖视图,其中贴片保持环连接在敷贴器上;
图3是在为施加贴片活塞已经释放之后,带有图2的贴片保持环的图1的敷贴器装置的侧剖视图;
图4是敷贴器装置的一个备选实施例的透视图;
图5是微凸起阵列的一个实例的一部分的透视图;
图6是一种压力驱动的敷贴器装置的侧剖视图;以及
图7是来自使用手指压力(无阴影的条)和使用根据本发明的自动敷贴器(带阴影的条)施加的干燥涂敷的微凸起阵列的经过两个时限(5秒和1小时)输送的卵清蛋白剂量M(单位为微克)的图。
具体实施方式
图1示出了一种敷贴器装置10,用于将一个微凸起阵列可重复地冲击施加于角质层。敷贴器装置10的构型配置使得包括一个微凸起阵列的微凸起构件能够实现对角质层进行预定的、连续的冲击,以便利用微凸起可接受地刺穿角质层。特别地,敷贴器装置10的设计使每单位冲击面积的能量得以优化以便利用微凸起实现对角质层的有效刺穿。
如下文中将要进行更详细的描述,已经确定敷贴器装置10应当在每单位面积的微凸起构件输送一定范围的能量以便有效地刺穿角质层。每单位面积的能量范围表示成在最大值的时间内输送至皮肤位置的每单位面积的最小能量。
如图1-3中所示,敷贴器装置10的一个实施例包括装置主体12和可在装置主体内运动的活塞14。盖件16提供于装置主体12上以便致动敷贴器从而利用微凸起构件(在图1中未示出)冲击角质层。冲击弹簧20环绕着活塞14的杆22定位并相对于装置主体12向下偏压活塞。活塞14具有下表面18,该表面大致为平或构造成一身体表面。一旦致动敷贴器装置之后,冲击弹簧20就移动活塞14并使得微凸起构件,例如包括微凸起阵列的通过皮肤的贴片,冲击并刺入角质层。
图1示出的活塞14处于未击发位置,而图2示出的活塞14处于击发位置。当敷贴器装置10击发时,活塞14在装置主体12的内部向上受压并通过锁定机构锁定就位。锁定机构包括杆22上的卡扣26和位于装置主体12上并具有相应锁栓30的柔性指部28。当活塞14向装置主体12运动从而压缩冲击弹簧20时,卡扣26使指部28发生挠曲并卡扣在柔性指部28的相应锁栓30上。击发步骤可以只需通过同时能够将活塞14击发和锁定在击发位置的单次压缩运动实现。
图2示出的敷贴器装置10中活塞14处于击发构型。如图2中所示,当装置处于击发位置时,卡扣26和活塞14上的锁栓30以及装置主体12可释放地接合以防止活塞在装置主体内向下运动。
图2还示出了安装在装置主体12上的一个保持环34。保持环34具有摩擦接合于装置主体12上的第一端40。保持环34的第二端42提供了角质层接触表面。包括多个微凸起的微凸起构件44安装于保持环34的第一和第二端40、42之间。微凸起构件44悬置在保持环34内。微凸起构件44在保持环34内的安装方式以及微凸起构件的位置可以变化。举例来说,微凸起构件44的位置可以邻近保持环34的第二端42。
根据一个实例,微凸起构件44通过底部材料的脆弱部分连接到粘接于保持环件34上的底部材料的环形件上。当敷贴器装置10的活塞14释放时,微凸起构件44在活塞14的向下力作用下从保持环34上分开。备选地,微凸起构件44可以可释放地连接到活塞14上或者定位于活塞之下的皮肤上。
在击发活塞14之后,保持环34被连接于装置主体12上。保持环34的连接通过搭扣连接、销钉配合或者滑动配合而实现,从而使得保持环34可以沿垂直于敷贴器的轴线的方向而在装置主体12上滑动。
按照所述,敷贴器装置10可使用微凸起构件44,例如通过皮肤的贴片。可以用于本发明的通过皮肤的贴片通常包括一个微凸起阵列、一个介质储槽和一个衬垫。然而,敷贴器装置10同样可以使用没有介质储槽的微凸起构件。在这种情况下,微凸起构件用作预处理,随后通过通过一个独立装置施加或采样介质。作为选择,例如对于通过皮肤输送疫苗,微凸起构件可将介质作为涂层结合在这些微凸起上。
由释放锁定机构而致动敷贴器装置10通过在利用压紧力将保持环34的第二端42压靠皮肤的同时施加在敷贴器盖件16的向下力来实现。盖件16通过位于装置主体12和盖件之间的压紧弹簧24而向上偏压。盖件16包括从盖件向下延伸的销46。当盖件16向下受压以克服压紧弹簧24的偏压时,销46接触柔性指部28上的斜面48以便使柔性指部向外运动并将柔性指部28的锁栓30从卡扣26释放。当达到预定的压紧力时,活塞14释放并向下运动,从而利用微凸起构件44冲击角质层。图3示出了装置已经致动并且微凸起构件已经对角质层进行冲击之后的敷贴器装置10。
选择的压紧弹簧24使得在敷贴器装置10致动之前必须达到预定的压紧力。该压紧力使得角质层在保持环34的表面42的作用下而延展,从而使得皮肤在微凸起构件44冲击皮肤时处于最佳的张力下。
由压紧弹簧24施加的压紧力优选进行选择以便使保持环34的第二端42对皮肤施加大约0.01~10Mpa范围内的张力,更优选为大约0.05至2Mpa。当活塞14释放时保持环34的皮肤接触表面42压靠在皮肤上的压紧力优选为至少0.5kg,更优选为至少1.0kg。
压紧弹簧24和冲击弹簧20之间的平衡使得可以通过按压盖件16击发活塞14而不会使得指部46释放锁定机构。换句话说,当对敷贴器装置10施加击发力时,冲击弹簧20将在压紧弹簧24偏斜之前发生偏斜。
冲击弹簧20的选择使得可以对活塞施加一个力,以实现微凸起构件44对角质层的预定冲击。微凸起构件44冲击时所用的能量能够利用微凸起提供所需的皮肤刺穿。冲击弹簧20还优选地进行选择以便实现所需的皮肤刺穿而不会超过引起病人感到不适的冲击。
微凸起构件对角质层的冲击根据敷贴器装置的以下特征确定:1)活塞14从击发和锁定位置(图2中所示)到皮肤行进的距离(x):2)当活塞14处于击发和锁定位置时冲击弹簧20中的压缩量;3)冲击弹簧20在其从击发和锁定位置移至皮肤冲击位置时的速率(k);4)冲击弹簧20的势能(PE)作为动能(KE)给予皮肤经过的时间(t);5)运动的冲击活塞和贴片及微凸起阵列的质量(m);6)与用于将贴片保持于保持器上的脆弱连接的摩擦和断裂相关的能量损失(L);7)冲击面积(A)。冲击还收到敷贴器装置的外部条件的影响,包括微凸起构件的构型和受冲击的皮肤的条件(例如是否延展)。在确定所需的冲击能量时已经将这些敷贴器装置的外部条件考虑在内。
每微凸起阵列单位面积(A)的冲击能量(P)根据下式确定:
P/A=(KE)/(A)(t)
其中:PE=KE+L
PE=0.5(k)(x)2
KE=0.5(m)(v)2
P=(KE)/(t)
P/A=(KE)/(A)(t)
实例
以下为具有冲击弹簧的敷贴器系统的几个实例,这些冲击弹簧能够提供每单位面积的大小可以接收的能量以便输送微凸起构件,它们在人体皮肤上进行试验。先前所述的敷贴器10在这里配置为带有三个具有不同弹簧常数和长度的不同的冲击弹簧,如下所示。这三个敷贴器/弹簧构型经证明可用于输送具有下列三种不同面积的微刀片阵列。所输送的微凸起装置大致与图5中所示的装置相似,具有长度约为250微米的微刀片。
微刀片阵列面积 | 弹簧 | 弹簧常数(K) | 弹簧长度(L) | 输送的总能量 | 能量/面积 |
1平方厘米 | #71512 | 9.3磅/英寸 | 1.75英寸 | 0.36焦耳 | 0.36焦耳/平方厘米 |
2平方厘米 | #71526 | 14磅/英寸 | 1.75英寸 | 0.63焦耳 | 0.32焦耳/平方厘米 |
3.3平方厘米 | #71527 | 12磅/英寸 | 2.00英寸 | 1.07焦耳 | 0.32焦耳/平方厘米 |
冲击弹簧20优选选择成输送的能量最小值为每平方厘米0.05焦耳,并且在低于10毫秒时间内完成输送。优选的能量值最小为每平方厘米0.10焦耳,在低于1毫秒的时间内完成输送。由冲击弹簧20输送的能量最大值约为每平方厘米0.3焦耳。所输送的最大能量值根据使用附加能量来实现附加刀片刺穿操作与要求防止由于利用微凸起构件冲击角质层而产生的不适(例如疼痛和擦伤)之间的权衡来确定。
图4示出了一个具有不同形状和一个用于手动致动的释放按钮86的敷贴器80的备选实施例。根据本实施例,使用者抓住敷贴器装置80的手柄82并且将装置的下端84压向角质层。敷贴器装置80的致动通过按压释放按钮86手动实现并且压紧力的大小手动控制而不受按压释放按钮86的时间的影响。图4的敷贴器80可以包括一个位于敷贴器手柄82上的压紧指示器,用于(例如通过听觉、触觉或视觉信号)在已达到预定压紧力以及需要按压释放按钮86时向使用者发出指示。
根据本发明的敷贴器装置10、80相对于直立方位进行描述,其中微凸起构件44从装置的活塞侧施加,在图中示于装置的底部。应当理解敷贴器装置可以在其它方位使用。
尽管敷贴器装置10和80使用弹簧加载,但是本领域的普通技术人员应当理解可以使用其它已知的能量源(例如,除了压缩弹簧例如拉簧/牵引弹簧和橡皮带之外还可使用压力、电力、磁力或其它偏压构件)来取代弹簧20,并且只要这些备选能量源在冲击时能够提供所规定的最小能量就认为与其等价。
图6中示出了压力驱动的敷贴器装置的一个实例。压力驱动的敷贴器60具有一个管状主体61,管状体61带有一个凹槽式盖件63。凹槽式盖件具有一个中心孔64,活塞杆单元65的杆67通过其中放置。在杆67的上端置有一个活塞66,它与主体61的内表面滑动、密封地接合。可以看到,活塞66还将主体61内的内部空间分成一个上腔室71和一个下腔室72。杆67也是滑动、密封地与凹槽式盖件63中的中心孔64接合。冲击头68置于杆67的下端,它适于使在本文其它部分所述的皮肤刺入微凸起构件对着病人的皮肤冲击。为了操作敷贴器60,通过按压冲击头68而将活塞66从邻近凹槽式盖件63的位置移出并向着孔69向上滑动。随着活塞66在主体61内部向上移动,腔室71内的空气通过孔69排出。另外,由于活塞66与主体内表面为密封接触并且杆67与孔64为密封接触,就在腔室72内形成一个局部真空。当冲击头68与凹槽式盖件63的下表面接合时,推压滑动卡扣74通过主体61中的开口73。任选地,在开口73’中还置有一个第二滑动卡扣74’。这样,滑动卡扣74和74’就起克服腔室72内的局部真空施加的力而将冲击头68保持压靠于盖件63上的作用。一旦通过滑动卡扣74和74’固定好,微凸起构件就可以安装于冲击头68的下表面上。一旦完成这项工作,就将敷贴器60贴在病人的皮肤上,通过边缘62与皮肤接触。随后拉出滑动卡扣74,使得冲击头68对着皮肤冲击已安装好的微凸起构件,使微凸起刺入皮肤。
任选地,孔69可以去掉。在这种构型中,活塞杆单元65不仅受到腔室72内形成的局部真空的驱动,还受到腔室71内的正压力(即,大于大气压)的驱动。
图5示出了用于刺入角质层的微凸起构件的一个实施例的一部分,它可用于本发明。图5中示出了多个呈微刀片90形式的微凸起。微刀片90从具有开口94的薄板92上大致成90°角延伸。薄板92可以结合于包括介质储槽和用于将贴片粘合于角质层上的粘合剂的介质输送贴片或介质采样贴片上。结合有微凸起阵列的介质输送和采样贴片的实例见于专利WO97/48440、WO97/48441和WO97/48442中。图5的不带储槽的微凸起阵列也可单独用作皮肤预处理。
这里使用的术语“微凸起”指的是非常小的角质层穿刺元件,其长度通常小于500μm,优选小于250μm,并穿透角质层。为了刺入角质层,微凸起优选具有至少10μm的长度,更优选至少50μm的长度。微凸起可形成不同形状,例如针、空心针、刀片、销、冲头及其组合。
这里使用的术语“微凸起构件”指的是包括多个用于刺入角质层的微凸起的构件。该微凸起构件可以通过由薄片上切割多个刀片并将每个刀片从薄板平面向外折弯以形成图5中的构型从而形成。微凸起构件同样可以其他已知方式形成,例如通过连接多个沿每个条带的边缘具有微凸起的条带而形成,如专利Zuck WO99/29364中所公开,其内容在此作为参考。微凸起构件可包括注射液体制剂的空心针。
微凸起阵列的实例的描述见于美国专利,包括授予Godshall等人的US5,879,326,授予Ganderton等人的US3,814,097,授予Gross等人的US5,279,544,授予Lee等人的US5,250,023,授予Gerstel等人的US3,964,482,授予Kravitz等人的Reissue25,637,和PCT公开,包括WO96/37155,WO96/37256,WO96/17648,WO97/03718,WO98/11937,WO98/00193,WO97/48440,WO97/48441,WO97/48442,WO98/00193,WO99/64580,WO98/28037,WO98/29298,WO98/29365,所有这些专利的全部内容在此作为参考。
本发明的装置可与介质输送、介质采样或两者结合使用。特别是,本发明的装置与通过皮肤输送药物、通过皮肤采样分析物或两者结合使用。可以输送的介质的实例包括药物和疫苗。可以采样的身体分析物的实例为葡萄糖。使用本发明的通过皮肤输送的装置包括,但不局限于,被动装置、刺入装置、压力驱动装置和电迁移装置。使用本发明的通过皮肤采样的装置包括,但不局限于被动装置、负压驱动装置、刺入装置和反向电迁移装置。本发明的通过皮肤的装置可以与例如皮肤刺入增强器的其它增强介质流量的方法结合使用。
本发明的装置可以使用微凸起构件,例如具有将贴片连接到皮肤上的粘合剂的通过皮肤的输送或采样贴片。作为选择,微凸起构件和输送或采样贴片可以是两个分开的元件,而微凸起构件用于在施加输送或采样贴片之前进行预处理。
实例1
钛微凸起构件包括一个具有多个形状和构型如图5中所示的微凸起(微凸起长度为360微米,而微凸起密度为190个微凸起/平方厘米)的圆形薄板(薄板面积为2平方厘米),它涂有模型蛋白质疫苗卵清蛋白。荧光素标记的卵清蛋白的200毫克/毫升的水涂敷溶液已制备好。为了进行涂敷,将微凸起构件短暂地浸入该溶液中,吹干,并在室温下干燥一夜。随后的分析表明微凸起构件上涂有200至250微克/平方厘米的卵清蛋白。
在无毛豚鼠(HGP)上进行了研究以便评价在短时间内(5秒)施加微凸起构件之后吸入皮肤的卵清蛋白。所应用的系统包括一个涂敷过的微凸起构件,它利用丙烯酸脂粘合剂(8平方厘米圆盘)粘合于低密度聚乙烯衬垫(LDPE)的中心。在一组五个HGP中,系统利用冲击敷贴器而施加。冲击敷贴器在少于10毫秒内以0.42焦耳的冲击能量将系统冲击于动物的皮肤上,并且系统在与皮肤接触5秒后即除去。在第二组五个HGP中,使用2千克/平方厘米的手动压力将系统施加于皮肤上,保持就位5秒钟,然后除去。在两组中,刺穿情况相似,这可以通过微凸起良好地保留于皮肤中而得到证明。在除去系统之后,将残余的药物完全从皮肤上洗掉,在施加微凸起构件的位置进行8毫米的皮肤活体检查。输送入皮肤中的卵清蛋白的总量通过将皮肤活体检查样品溶解于J.T.Baker(NJ,USA)所售的酒精中的氢氧化铵化合物,(二异丁基甲苯氧基乙氧乙基)(二甲基)苯甲基氢氧化铵,1M中而确定,并且通过荧光测定法进行定量。结果表明,冲击施加方法得到的平均输送量为30.1微克卵清蛋白,而手动施加方法平均输送的卵清蛋白只有6.6微克。
实例2
使用干燥涂敷的卵清蛋白进行了第二个实验以便比较利用不同的钛微凸起构件和更长的施加时间时在冲击和手动施加后的输送情况。荧光素标记的卵清蛋白的200毫克/毫升的水涂敷溶液已制备好。将微凸起构件(微凸起长度为214微米,没有保持特征,292个微凸起/平方厘米,2平方厘米圆盘)短暂地浸入该溶液中,吹干,并在室温下干燥一夜。随后的分析表明微凸起构件上涂有200至250微克/平方厘米的卵清蛋白。
输送研究在无毛豚鼠(HGP)上进行。所应用的系统包括一个涂敷过的微凸起构件,它利用丙烯酸脂粘合剂(8平方厘米圆盘)粘合于LDPE衬垫的中心。在一组五个HGP中,微凸起构件的施加利用冲击敷贴器(在低于10毫秒内以0.2焦耳/平方厘米)进行,并且系统在与皮肤接触5秒后即除去。在第二组五个HGP中,使用2千克/平方厘米的手动压力将系统施加于皮肤上,保持就位5秒钟,然后除去。除了在施加之后系统与皮肤保持接触1小时之外,完全按照上述方式对另外两组无毛豚鼠进行处理。在除去系统之后,将残余的药物完全从皮肤上洗掉,并在施加微凸起构件的位置进行8毫米的皮肤活体检查。输送入皮肤中的卵清蛋白的总量通过将皮肤活体检查样品溶解于氢氧化铵化合物而确定,并且通过荧光测定法进行定量。两个时限(t)的卵清蛋白输送量(M)的结果示于图7中,并且结果表明,不管施加时间如何,冲击施加方法得到的输送量高于手动施加方法。
实例1和实例2表明,不管微凸起构件设计、涂敷类型以及施加时间如何,使用冲击施加方法输送的卵清蛋白的量高于手动施加方法。
尽管本发明参考其优选实施例进行了详细描述,但是对于本领域普通技术人员来说,很显然,可进行多种变型和改型以及采用等同结构,而不偏离本发明。
Claims (18)
1.一种用于形成一个或多个通过角质层的微裂口的装置,通过这些微裂口可以输送或取样介质,这种装置包括:
一敷贴器,其包括:
一装置主体,
一可运动地安装在所述装置主体内的活塞,
一设于所述装置主体上以便致动敷贴器从而利用一微凸起构件冲击角质层的盖件,
一环绕所述活塞的杆定位并相对于装置主体向下偏压所述活塞的弹簧,
一接触表面;以及
一具有一个或多个角质层刺入微凸起的微凸起构件,微凸起构件可释放地安装于所述敷贴器上,
其中,所述敷贴器的构形做成通过所述接触面施加一个冲击于所述微凸起构件上,使得所述微凸起构件以在10毫秒或者更短时间内每平方厘米微凸起构件至少0.05焦耳的能量冲击角质层。
2.根据权利要求1所述的装置,其特征在于,所述敷贴器通过选自偏压构件、压力、电力和磁力中的能量源而驱动。
3.根据权利要求2所述的装置,其特征在于,所述偏压构件包括弹簧。
4.根据权利要求3所述的装置,其特征在于,所述弹簧为冲击弹簧,并且在10毫秒或者更短时间内施加具有每平方厘米微凸起构件至少0.05焦耳的能量的冲击。
5.根据权利要求1所述的装置,其特征在于,所述微凸起为微刀片。
6.根据权利要求1所述的装置,其特征在于,所述敷贴器还包括一第二弹簧,用于在致动之前达到一定的压紧力。
7.根据权利要求6所述的装置,其特征在于,所述第二弹簧需要至少为0.5千克的压紧力以在致动敷贴器之前施加于敷贴器上。
8.根据权利要求7所述的装置,其特征在于,其还包括用于在已将预定压紧力施加于敷贴器上时发出指示的指示器。
9.根据权利要求8所述的装置,其特征在于,所述指示器用于提供听觉、触觉或视觉信号以在已施加预定压紧力时发出指示。
10.根据权利要求1所述的装置,其特征在于,所述敷贴器使得微凸起构件以在10毫秒或者更短时间内每平方厘米微凸起构件至少0.1焦耳的能量冲击角质层。
11.根据权利要求1所述的装置,其特征在于,当敷贴器以至少0.5千克的作用力压在角质层上时,所述敷贴器就会致动。
12.根据权利要求1所述的装置,其特征在于,所述敷贴器使得微凸起构件以在1毫秒或者更短时间内每平方厘米微凸起构件至少0.05焦耳的能量冲击角质层。
13.根据权利要求1所述的装置,其特征在于,所述微凸起构件包括一衬底,其中所述一个或多个微凸起从所述衬底上延伸,所述一个或多个微凸起的长度小于500微米。
14.根据权利要求1所述的装置,其特征在于,其还包括一介质。
15.根据权利要求14所述的装置,其特征在于,所述介质为药物或疫苗。
16.根据权利要求14所述的装置,其特征在于,所述介质包括位于微凸起构件上的涂层。
17.根据权利要求14所述的装置,其特征在于,所述介质包括身体分析物,并且这种装置还包括一用于收集所述身体分析物的介质储槽。
18.根据权利要求14所述的装置,其特征在于,所述介质包括一有益介质,并且所述装置还包括一在其中容放所述介质的储槽,所述储槽能够与角质层形成介质输送关系。
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- 2001-10-12 DE DE60138411T patent/DE60138411D1/de not_active Expired - Lifetime
- 2001-10-12 US US09/976,798 patent/US7131960B2/en not_active Expired - Lifetime
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- 2001-10-12 KR KR10-2003-7005187A patent/KR20030068136A/ko active IP Right Grant
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- 2001-10-12 PL PL01360998A patent/PL360998A1/xx not_active Application Discontinuation
- 2001-10-12 AU AU9682801A patent/AU9682801A/xx active Pending
- 2001-10-12 AT AT01977734T patent/ATE428357T1/de not_active IP Right Cessation
- 2001-10-12 AU AU2001296828A patent/AU2001296828B2/en not_active Ceased
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- 2001-10-12 WO PCT/US2001/031936 patent/WO2002030301A1/en active IP Right Grant
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- 2003-05-12 ZA ZA200303633A patent/ZA200303633B/en unknown
- 2003-05-12 MA MA27151A patent/MA26057A1/fr unknown
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CA2425315C (en) | 2010-01-12 |
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HUP0303558A2 (en) | 2004-01-28 |
NO20031681D0 (no) | 2003-04-11 |
NZ525294A (en) | 2005-02-25 |
PL360998A1 (en) | 2004-09-20 |
ATE428357T1 (de) | 2009-05-15 |
KR20030068136A (ko) | 2003-08-19 |
CN1479590A (zh) | 2004-03-03 |
JP2004510535A (ja) | 2004-04-08 |
CA2425315A1 (en) | 2002-04-18 |
EP1341453B1 (en) | 2009-04-15 |
MA26057A1 (fr) | 2004-04-01 |
EP1341453A1 (en) | 2003-09-10 |
US20050234401A1 (en) | 2005-10-20 |
ES2324461T3 (es) | 2009-08-07 |
DE60138411D1 (de) | 2009-05-28 |
US20020123675A1 (en) | 2002-09-05 |
RU2275871C2 (ru) | 2006-05-10 |
AU9682801A (en) | 2002-04-22 |
ZA200303633B (en) | 2004-05-12 |
WO2002030301A1 (en) | 2002-04-18 |
NO20031681L (no) | 2003-06-13 |
CZ20031037A3 (cs) | 2003-10-15 |
BR0114629A (pt) | 2004-01-20 |
US7798987B2 (en) | 2010-09-21 |
JP4659332B2 (ja) | 2011-03-30 |
IL155374A0 (en) | 2003-11-23 |
US7131960B2 (en) | 2006-11-07 |
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