CN105873634A - 透皮释放活性物质的系统 - Google Patents
透皮释放活性物质的系统 Download PDFInfo
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- CN105873634A CN105873634A CN201480070086.3A CN201480070086A CN105873634A CN 105873634 A CN105873634 A CN 105873634A CN 201480070086 A CN201480070086 A CN 201480070086A CN 105873634 A CN105873634 A CN 105873634A
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Abstract
本发明涉及一种用于释放药物活性物质的透皮治疗系统(TTS),其包括背衬层(7)和至少一种含活性物质的载体材料(1),其中,至少一个固定元件(6a‑6d)位于含活性物质的载体材料和背衬层之间,通过该固定元件将含活性物质的载体材料固定在背衬层上。本发明还涉及一种用于在钩和环带节段存在的情况下将含活性物质的载体材料固定到TTS的背衬层上的方法,并涉及钩和环带在将药物或治疗活性物质透皮或离子电渗给药至患者的方法中的用途。
Description
本发明涉及用于释放治疗有效量的药物活性物质至生物体的新系统。
本发明优选涉及一种易于操作的系统,所述系统用于以治疗有效量透皮释放溶解在液体中的药物活性物质,更优选用于通过离子电渗疗法透皮释放阳离子活性物质。
肠胃外给药的透皮途径与其它给药途径相比提供了许多优点。通过皮肤施用药物的方法和系统在药学领域是众所周知的。透皮给药通常利用被动透皮系统(例如,透皮的、治疗系统,TTS),其借助扩散将确定量的药物活性物质透过皮肤供给生物体。
具体地说,溶解在液体中的活性物质的透皮传输存在以下问题:由无纺布或海绵布或凝胶构成的含有活性物质的载体材料必须保持与背衬层分开,在TTS中的活性物质连同背衬层一起被固定到皮肤上,其原因在于否则不能保证长时间的储存稳定性,或者其原因在于活性物质可能必须保持冷却,或者其原因在于活性物质可能对氧化敏感。医药贴剂的使用者必须就此从事先通过除去封闭薄膜而开启的、通常是密封的并因此不透液体的包装中将含活性物质的载体材料转移至透皮治疗系统(TTS)的背衬层上并在其上固定。然而,使用者在此因沾染菌落的风险,应尽可能不用手指接触含活性物质的载体材料并尽可能也不使用其他额外的用于转移的辅助手段。
因此,通常将TTS背衬层以其下侧面放置到含活性物质的载体材料的上侧面的开启的包装上,并在此将载体材料按在TTS背衬层上。当此后再次将TTS从打开的包装中取出时,含活性物质的载体材料被保持附着于TTS背衬层,并与TTS背衬层结合以形成在实际意义上的TTS,但是这并不总是可靠地发生的。经常或至少偶尔发生的是,含活性物质的载体材料仍只是被留在包装中。
尤其是在采用离子电渗疗法的方法时发生这种问题。当被动透皮药物释放对于某些类型的药物非常低效时则采用离子电渗疗法。特别是离子化的药物往往不能以治疗有效量被动地透过皮肤。
离子电渗疗法的方法最初是由勒杜克在1908年和甚至更早地在US 222276(1879)和US 486902(1892)中描述的。自此,离子电渗疗法在商业上被用于离子带电治疗活性分子,如毛果芸香碱,利多卡因,地塞米松,利多卡因和芬太尼的透皮应用。
离子电渗疗法一般是基于以下的基本原理的释放方法:电流的应用提供外部能量,借助于提高的活性物质药物透过皮肤膜的渗透力使得能够产生活性物质粒子透过皮肤的改善的穿透性。
当带有正电荷(例如,阳离子活性物质)的离子置于离子电渗系统的阳极中或离子电渗系统的阳极下方时,在电流的应用下脉冲将作用到这些离子上,所述脉冲在向阴极的电场的方向上移动这些离子并使其远离阳极,所述阴极被置于无间质的皮肤近旁。在此过程中,阳离子药物通过皮肤的输送被改善或促进。
可以以活性药物成分的各种形式进行离子电渗,最有利的是具有电荷并且由此在电场中发展出克服障碍(例如,皮肤)的能力的那些。
典型的离子电渗药物释放系统包括由阳极和阴极构成的电解电系统,身上阳极和阴极被置于患者的不同(优选相邻的)皮肤区域,在此每个电极通过导线连接到外部电源。在一般情况下,这是一个微处理器控制的电子仪器。这种类型的装置是已知的,包括非常简单的设计(例如,US 5685837或US 6745071)或其他更复杂的系统,其中本领域的技术人员具有所述系统的原理知识。利多卡因和芬太尼的透皮离子电渗系统已经在美国被成功推出。通过离子电渗疗法释放药物的系统的非常特别详细的描述在WO 2012/071175中被找到。
US 5558633涉及离子电渗疗法的装置,其特别适用于从液体或从凝胶化水性制剂释放药物。然而,在这种装置中,药物活性物质的离子电渗给药可以被存在的“背景”电解质严重破坏(例如参见Luzardo-Alvarez,A.,等人,Proceedings of the International Symposium on Controlled Release ofbioactive Materials(2000),第27版,第159至160页)。离子电渗装置的构造,还导致本身并不作为“背景”抗衡离子的医药凝胶或液体的不足。
尽管仍然存在各种不足之处,离子电渗疗法已经被证明在所有这些情况(其中常规的TTS不足以确保这种活性物质的治疗有效剂量的快速给药)下是有用的释放方法。然而,存在采用离子电渗疗法的固有风险,即副作用如皮肤刺激,皮肤发红,灼热或其他皮肤坏死可以特别在增加电流强度中或在长时间实施离子电渗治疗中发生。另一方面,在电流强度的增加对于更高剂量治疗活性物质的施用可以是完全理想的,因为运输的离子数目与的每单位时间的电流的水平成正比。
因此鉴于上述,本发明解决的问题是提供一种方法,通过所述方法,含有活性物质的载体材料可以从它的包装可靠地取出并固定到用于随后应用(无论该应用是否通过离子电渗的增强)的目的的TTS背衬层上,而不需要用手或额外的辅助的碰触来转移含活性物质的载体材料。
这个问题是由文端所述类型的TTS来解决的,所述TTS包括背衬层和至少一种含活性物质的载体材料,其中所述含活性物质的载体材料和背衬层之间具有至少一个固定元件,其用于将含活性物质的载体材料固定到背衬层上。
根据本发明优选固定元件被构造为钩和环带(Klettband)的伸长成型的节段。
根据本申请,钩和环带被理解为纺织品,其为任意地经常被解除的闭合介质,其基于牛蒡果(Klettfrüchten)的原理。仿生学转化以典型的形式由两个纺织的纤维带构成,其一个具有柔韧的倒钩或蘑菇头,另一个却表现为环。一起按压使之或多或少地具有负荷能力,但无论如何是可逆的快速闭合。纺织的钩和环带由聚酰胺、聚酯或聚烯烃纤维构成。对于钩带,钩可以在织造过程中或以后被引入。钩和环带和压敏闭合也可以在其背面用粘附剂自粘性地进行层贴。
根据本发明,设置在TTS的背衬层上的钩和环带形成钩侧,而含活性物质的载体材料料承担环侧的功能。通过按压置于TTS的背衬层上的该固定原件到朝上地通过事先去除封闭膜而开启的其中有含活性物质的载体材料的包装的上侧面,使之根据本发明产生所述钩和环带与载体材料的挂钩作用,当TTS从包装取出时附着至TTS的固定元件,而当包装随后再次被除去时不被留在包装中。
一般情况下,含活性物质的载体材料在包装中,其恰在将载体材料加上活性物质转移至TTS的背衬层前通过除去封闭膜,打开所述包装。
通过将含活性物质的载体材料用液体浸渍,其粘附在包装膜上。为了奖载体材料从包装膜上解除,因此需要力(X1)。现在,如果在没有额外辅助如,例如,手指或用于转移的夹持元件的情况下,将载体材料转移到TTS上,则将TTS平放到载体材料上和被按下。就此所述液体浸渍的载体材料还附着到按下的TTS(塑料膜/聚酯膜)上。然而,附着至TTS的附着力(=Ftts)近似于附着至包装的附着力(=F包装)。在TTS已被按下后,在再次除去TTS时,两个附着力的大小决定了含活性物质的载体材料是否保持附着在TTS上或另一种情况地附着在包装上。除非附着至TTS的附着力(Ftts)比附着至包装膜的附着力(F包装)显著更大,否则存在以下风险:液体浸渍的载体材料仍然保留在包装中,而不是象所希望的附着在TTS上。
为了从包装膜中可靠地转移含活性物质的载体材料至TTS,附着力必须被改变,使得它们显著不同:
Ftts>>F包装
含活性物质的载体材料附着至包装膜的附着力几乎不能降低。即使抗粘涂层减小这种附着力,因液体粘度也不会显著。即使表面的轮廓化(Profilierung)也不引起附着力的任何变化,其原因在于液体填充表面轮廓和挤出空气泡。
因此,提供增加的对TTS的附着力(Ftts)以保证转移过程的可靠性是问题的解决方案。
根据本发明采用钩和环带来增加附着TTS的附着力(Ftts)。由于钩和环带,含活性物质的载体材料(Ftts)的附着力显著增加。这是因为,钩和环带甚至可以在潮湿状态下发挥功能。在将含活性物质的载体材料按压在钩和环带上的情况下,使得载体材料的纤维与钩和环带的钩发生挂钩。所以钩和环带即使在潮湿的环境中也显著增大附着力(Ftts),保证了液体浸渍的载体材料从包装转移到TTS的背衬层。
作为背衬层,根据本发明描述的是基本上自支撑的面片体,其覆盖发生药物活性物质透皮释放至生物体的皮肤位点。如果所述TTS不是通过粘附性配置的覆盖性贴剂固定到皮肤上的,则所述背衬层还有利地具有将系统固定到皮肤上的功能,其通过背衬层面朝皮肤的一侧的平面粘贴或图案形粘贴的构造实现的,其中一种或多种含活性物质的载体材料的一个或多个区域至少是无粘贴剂的。
在本发明的进一步的实施方案,背衬层是闭合背衬层。闭合背衬层特别是用于液体和水蒸汽、防止液体或水蒸汽通过背衬层逸出到外部的阻挡层,所述逸出在待释放的药物活性物质是液体或溶解在液体的情况下将导致系统脱水。本发明中的闭合背衬层可以由塑料(如聚乙烯或聚丙烯或聚酯或聚氨酯或聚酰胺)膜构成,其基本特性是,它构成了水、水蒸汽或水混合的有机溶剂的充分可靠的阻断物。所述塑料构成的适宜的膜的厚度范围为5至300μm,优选10至200μm,更优选12至150μm。
闭合背衬层可另外还包含或结合到用于加强的非闭合载体层。作为非闭合载体层,织物(ein textiles Gewebe)可以是适宜的,或者是无纺布或毡材料或其它含纤维素的材料。非闭合性载体层和闭合背衬层之间的结合可以通过在压力下的层压或通过挤出或通过用合适的粘合剂粘结来建立。合适的粘合剂可以包括聚异戊二烯或聚异丁烯或聚丙烯酸酯或其他的聚硅氧烷共聚物。
作为闭合背衬层还可以在其下侧面,即,面朝皮肤的侧面,设计有自粘性层。作为自粘性材料适宜的是上述粘合剂,优选丙烯酸系粘合剂。
在进一步的实施方案中,所述含活性物质的载体材料是水凝胶,或被撒上粉状活性物质的或采用液体浸渍的载体材料。本发明中的液体可以理解为活性物质在溶剂(优选含水溶剂)中的溶液,否则,可以替代地理解为活性物质在合适的分散介质或乳化介质中的分散体或乳液。作为载体材料在此考虑无纺布型材料或织物材料或针织物或海绵状材料,有利地是采用或任选地还有形成凝胶的聚合物。
在本发明的一个优选实施方案中,伸长成型的钩和环带的形状与含活性物质的载体材料的形状相匹配。当含活性物质的载体材料具有矩形形状时,所述伸长成型的钩和环带的长度优选相应于矩形形状的含活性物质的载体材料的多个侧边中的一个的长度。当含活性物质的载体材料具有圆形或椭圆形时,所述伸长成型的钩和环带的形状优选是弓形环段的形状,所述弓形环段具有相应于圆形或椭圆形的含活性物质的载体材料的半径的半径。
根据本发明所适宜的钩和环带是自粘性的,即它们以其自粘性背面粘附到背衬层上。但也有可能采用合适的粘合剂,例如丙烯酸系粘合剂或双组分粘合剂或热熔粘合剂用于将钩和环带固定到背衬层上。
所述伸长成型的钩和环带的宽度可以在宽的范围内变化。钩和环带不必覆盖整个区域(TTS中所述含活性物质的载体材料通过所述钩和环带在所述区域上伸展),当所述伸长成型的钩和环带不取决于含活性物质的载体材料的几何形状,仅覆盖所述区域的一部分,这就足够了。还可能的是,钩和环带仅位于靠近侧边缘的区,或者是作为环绕带构造的,其具有宽度范围为2至15毫米,优选3至10毫米。
本发明还可以包括两个或多个钩和环带,所述钩和环带被放置例如,在区域的相对两侧,在所述区域中含活性物质的载体材料被固定到TTS或将被固定到TTS。
本发明还提供在钩和环带节段的存在下将含活性物质的载体材料固定于TTS背衬层的方法。这涉及使在通过预先除去封闭膜而向上打开的包装中的含活性物质的载体材料接近闭合背衬层和设置在其上的钩和环带节段。然后,将包装与存在于其中的含活性物质的载体材料通过压力一起按在闭合背衬层上的钩和环带节段上。此后,可以将包装解开并除去,含活性物质的载体材料固定地留存在钩和环带节段以及闭合背衬层上。
本发明还提供了一种使用钩和环带作为透皮治疗系统(TTS)的组成部分或作为离子电渗透皮治疗系统的组成部分的方法。
本发明进一步包括钩和环带在将阳离子活性物质透皮或离子电渗给药至需要采用这种活性物质治疗的患者的方法中的用途。
本发明的系统特别是与具有阳离子结构的治疗活性物质相结合是特别有用的,特别是在其分子中具有氨基或亚氨基基团的活性物质。
因此本发明适于透皮给药,特别是通过离子电渗疗法给药止痛剂如芬太尼或吗啡,止吐剂如格拉司琼或其他作用于中枢神经系统的药物如利凡斯的明或加兰他敏。
当本发明的系统被用于这样的活性物质的透皮给药时,液体浸渍的载体材料用作基质或储库,阳离子活性物质从基质或储库中被释放到皮肤,然后被动地或在离子电渗协助下通过皮肤。
具有阳离子结构的活性物质通常是如下活性物质:是在带正电荷的离子(阳离子)的形式中的活性物质,或能够在水性介质中形成带正电的离子的活性物质。例如许多生物活性剂具有在水性介质中容易解离成带正电荷的离子和抗衡离子的官能团,其实例是碱性活性物质的可溶性盐。
术语“活性物质”具体包括治疗活性剂,药理活性剂或当给予人或动物时具有有利的效果的其它试剂。
术语“活性物质”一般指药物活性物质或药物,即,治疗性活性物质。表达“活性物质”也进一步包括兽药中使用的试剂。
本发明特别适用于透皮给药,特别是通过离子电渗疗法给药的活性物质,所述活性物质例如
-阿片样激动剂,包括镇痛剂,如芬太尼,舒芬太尼,吗啡,吗啡衍生物如可待因或如海洛因,二氢可待因,氢化吗啡,羟考酮,氢可酮(二氢可待因酮),哌替啶,洛哌丁胺,地芬诺酯,美沙酮,曲马多或替利定;
-阿片样拮抗剂如纳洛酮,纳曲酮;
-混合阿片激动剂/拮抗剂,如丁丙诺啡,喷他佐辛,纳布啡;
-止吐剂包括5-HT3受体拮抗剂,例如格拉司琼,来立司琼,昂丹司琼,多拉司琼,甲氧氯普胺和也包括抗多巴胺能药物如多潘立酮,并且还包括H1受体拮抗剂,诸如,例如,异丙嗪或美克洛嗪以及毒蕈碱拮抗剂,例如东莨菪碱;
-作用于中枢神经系统的药物化合物,如利斯的明,加兰他敏,他克林,多奈哌齐,并且还例如普拉克索,肾上腺素,多巴胺,罗匹尼罗,尼古丁,氟奋乃静,氯丙嗪,苯并二氮类,单胺再摄取抑制剂如阿米替林,抗抑郁剂如米安色林;
-生物碱,如麦角胺,双氢麦角胺,美西麦角或利舒脲,颠茄生物碱;
-肽,特别是肽类激素,如胰岛素和催产素或凝血因子和生长激素;
-阳离子活性吲哚化合物,例如N-二甲基色胺,舒马曲坦或赛洛新;
-局部麻醉剂如利多卡因,buprivacaine,阿替卡因,普鲁卡因;
-胃肠道活性治疗剂,如肉碱氯化物或甲氧氯普胺;
-肌肉松弛剂,如泮库溴铵(vancuronium bromide);
-抗生素如四环素,基于四环素的制剂,卡那霉素,基于卡那霉素的制剂,庆大霉素,基于庆大霉素的制剂或奎宁;
-减食欲剂如芬氟拉明或麻黄碱;
-抗糖尿病药物诸如二甲双胍;
-血小板聚集抑制剂,例如,噻氯匹定或氯吡格雷;
-抗心律失常药,如奎尼丁或利多卡因;
-心脏或心血管药物如多巴胺,去甲肾上腺素,甲氧明,肾上腺素,维拉帕米,地尔硫卓,普萘洛尔,可乐定,妥拉唑啉;
-拟交感神经剂例如沙丁胺醇或特布他林;
-抗组胺药,如氯马斯汀,西替利嗪或氯苯沙明。
在一个优选实施方案中,活性物质来自以下组成的组:阳离子吲哚化合物,特别是选自以下组成的组:阳离子吲哚化合物,N-二甲基-色胺和赛洛新,前述组也包括这些阳离子活性吲哚化合物的药学上适宜的盐。
上述阳离子活性物质也可以存在于药学上合适的盐的形式。药学上合适的盐的实例包括盐酸盐,氢溴酸,氢碘酸,硫酸盐,磷酸盐,乳酸盐,柠檬酸盐,酒石酸盐,水杨酸盐,琥珀酸盐,马来酸盐,葡糖酸盐,甲磺酸盐,月桂酸盐,十二烷酸盐,肉豆蔻酸盐,棕榈酸盐和硬脂酸盐,但不限于这些。
离子电渗疗法期间的电流的强度应理想地不超过600μA/cm2的值,从而避免烧皮肤或皮肤上的烧灼感。起动电压一般是在0.5至10伏的范围,这取决于两个电极和皮肤在两者之间的区域之间的电阻,其可以通常为50kΩ或更大。
在进一步的实施方案中,液体浸渍的载体材料含有阳离子活性物质或其盐,所述阳离子活性物质或其盐的含量为0.1至20wt%,优选0.2至10wt%,更优选为2至10wt%,,最优选3至5wt%,基于载体材料中液体的总重量。
在本发明的液体浸渍的载体材料的液体优选为水或含水溶剂混合物。溶剂混合物中水的比例优选为至少15wt%,更优选至少40wt%,基于液体的总重量。
在本发明的进一步的实施方案中,溶剂混合物的水含量或比例是在80至99wt%的范围内。
术语“含水溶剂混合物”通常包含液体混合物,其中含有水和至少一种另外的溶剂,所述另外的溶剂是极性水混溶的有机溶剂,例如,醇如乙醇,异丙醇或甘油。
本发明还包含以下应用:其中将阳离子活性物质与至少一种另外的活性物质相组合使用,所述是另外的活性物质选自包括具有中性电荷的活性剂的组,并甚至可能还包括阴离子活性物质。
本发明的系统通常采用能够通过被动扩散通过皮肤或适于皮肤离子电渗渗透的活性物质。
在进一步的实施方案中,液体浸渍的载体材料可以是水凝胶组合物,在这种情况下,额外地存在形成凝胶的聚合物,其可从由聚丙烯酸酯或盐和纤维素衍生物,如羟基丙基甲基纤维素,羟丙基纤维素或羟基乙基纤维素组成的组中选择。
在离子电渗疗法中使用水凝胶制剂是特别有利的,因为,在这种情况下,离子强度可以通过改变水凝胶中的水的比例进行调整。因此,容易的是,调节离子强度以在任何特定的情况下优化离子电渗过程的效力。
在进一步的实施方案中,在液体浸渍的载体材料中的液体的pH在以下范围内:3至8,优选5.5至7,更优选为约6。
通常优选的是,建立当TTS施加到皮肤时与皮肤pH无显著差异的pH。在进一步的实施方案中,皮肤pH值变化±4.0或更小,约±3.5或更小,约±3.0或更小,约±2.5或更小,约±2.0或更小,约±1.5或更小、,约±1.0或更小,或约±0.5或更小。用于调节或建立pH的物质和缓冲剂是本领域的技术人员已知的。
液体浸渍的载体材料可以任选含有其它的添加剂,在这种情况下,添加剂可选自增溶剂,皮肤渗透增强剂,防腐剂和抗微生物剂。
在此背景下,作为一般含义,术语“溶解度改进剂”应被理解为能够有助于提高阳离子活性剂在液体中的溶解度的化合物。这是可以通过以下实现:调节存在于液体中的阳离子活性物质和其它成分之间可能的相互作用,或者额外掺入合适的辅助材料。
可替代地,通过改变晶型实现活性物质的溶解度。
增溶剂的实例包括水,二醇,如丙二醇和甘油,一元醇如乙醇,丙醇和高级醇,二甲基亚砜(DMSO),二甲基甲酰胺,N,N-二甲基乙酰胺,N-取代烷基氮杂环烷基-2-酮。
术语“皮肤渗透增强剂”进一步包含,其中增加活性物质、特别是阳离子活性物质的皮肤的渗透性的具体化合物。由于这种皮肤透过性的增强,活性物质通过皮肤而进入血液循环的速率增加。
渗透增强剂的实例包括二甲基亚砜(DMSO),N,N-二甲基乙酰胺(DMA),癸基甲基亚砜(C 10MSO),聚乙二醇单月桂酸酯(PEGML),丙二醇(PG),丙二醇单月桂酸酯(PGML),甘油单月桂酸酯(GML),卵磷脂,1-取代的烷基氮杂环烷基-2-酮,特别是Indodecylcyl氮杂环庚烷-2-酮,醇等。
渗透增强剂也可以选自植物油,例如,红花油,棉籽油或玉米油。
含两种或多种不同渗透增强剂的组合是同样可用的。
作为一般含义,术语“抗微生物剂”是进一步应被理解为适合于防止微生物在药物制剂中、特别是在本发明的液体浸渍的载体材料的液体中的生长的试剂。
合适的抗微生物剂的实例包括氯己定的盐,例如碘代丙炔丁基氨基甲酸酯或盐,尿素醛(Diazolidinyl-Harnstoff),氯己定二葡糖酸盐,氯己定醋酸盐,氯己定异硫化羟酸盐或氯己定盐酸盐。其它阳离子抗微生物剂也同样可以使用,例如苯扎氯铵,苄索氯铵,三氯卡班(Triclocarbon),聚六亚甲基双胍,氯化鲸蜡基吡啶鎓,氯化甲苄乙氧铵(Methylbenzethoniumchlorid)。
其他抗微生物剂包括卤代酚类化合物,如2,4,4′-三氯-2-羟基二苯醚(三氯生),对氯间二甲苯酚(parachlorometa Xylenol)(PCMX),对羟基苯甲酸甲酯和短链醇,如乙醇,丙醇等。抗微生物剂的总浓度优选在0.01至2wt%的范围内,基于其中存在抗微生物剂的液体的总重量。
适宜的载体材料可以是纤维板层,纺织物,针织物,海绵,海绵布,针织-无纺布或毡织物或毡样材料等。
本发明进一步提供了使用上述系统作为离子电渗贴剂的整体组成部分、优选作为贴剂的阳极储库的方法。
实施例
现在将通过举例的方式参考附图说明本发明及其效果,其中
图1以示意形式表示从下面的、即从皮肤侧的视角中的根据本发明的TTS;
图2以示意性的形式示出从上面的、即从背向皮肤侧的根据本发明的TTS;
图3a,3b,3c和3d以示意形式示出,在分步骤中,含活性物质的载体材料如何从其分开储存的包装中取出并固定至TTS的背衬层。
图1表示,1为含活性物质的载体材料,其具有圆形形状并且已经被放到TTS的左手区域的位置,而具有在右手侧的开口3的覆盖膜2给出了电极4的视图,线上电器5和四个弧形(弓形)钩和环带6a、6b、6c和6d。然后,将含有活性物质的载体材料(未示出)进一步在接下来的步骤中压在钩和环带6a、6b、6c和6d上,并使其与钩和环带6a、6b、6c和6d牢牢固定。
图2基本上示出背衬层7,电流供给5和5′通过所述背衬层7并且分别在左侧和右侧是可见的。可以在描绘的中心发现具有电池和电子控制的电流供给单元8。
图3a在顶部示出背衬层7,在背衬层7上设置有两个钩和环带节段6a和6c,并在底部示出含活性物质的载体材料1,所述含活性物质的载体材料1处于向上打开的包装10中,由被预先剥离的封闭膜打开所述包装10(未描述)。
图3b示出含活性物质的载体材料1如何在仍然在打开的包装10中的同时接近背衬层7以及钩和环带节段6a和6c。
图3c显示了含活性物质的载体材料1如何与包装10一起从下面在箭头方向上被按在钩和环带节段6a和6c上以及背衬层7上。
图3d示出如何向下去除包装10,而保持含活性物质的载体材料1固定至所述钩和环带节段6a和6c,并且由此保持含活性物质的载体材料1固定到背衬层上7。
Claims (16)
1.一种用于药物活性物质的释放的透皮治疗系统(TTS),其包含背衬层和至少一种含活性物质的载体材料,其中所述含活性物质的载体材料和背衬层之间具有至少一个固定元件,其用于将含活性物质的载体材料固定到背衬层上。
2.根据权利要求1所述的TTS,其特征在于,所述固定元件是钩和环带的伸长成型的节段的钩侧。
3.根据权利要求1或2所述的TTS,其特征在于,所述TTS在皮肤上的固定是通过粘贴性配置的覆盖贴剂进行的,或者通过背衬层面朝皮肤的一侧的平面粘贴或图案形粘贴的构造,其中一种或多种含活性物质的载体材料的一个或多个区域至少是无粘贴剂的。
4.根据权利要求1至3中一项或多项所述的TTS,其特征在于,所述背衬层是闭合背衬层,其是液体和水蒸汽的阻挡层。
5.根据权利要求4所述的TTS,其特征在于,所述闭合背衬层由塑料薄膜如聚乙烯或聚丙烯或聚酯或聚氨酯或聚酰胺构成,并具有范围是5至300μm,优选10至200μm,更优选12至150μm的厚度。
6.根据权利要求1至5中一项或多项所述的TTS,其特征在于,所述伸长成型的钩和环带的形状与含活性物质的载体材料的形状相匹配。
7.根据权利要求1至6一项或多项所述的TTS,其特征在于所述含活性物质的载体材料具有圆形或椭圆形形状,并且所述伸长成型的钩和环带具有弓形环段的形状,所述弓形环段具有相应于圆形或椭圆形的液体浸渍的载体材料的半径的半径。
8.根据权利要求1至7一项或多项所述的TTS,其特征在于所述伸长成型的钩和环带的宽度可以改变,其中,所述钩和环带不覆盖所述背衬层的整个区域,在TTS中所述含活性物质的载体材料在所述区域上伸展。
9.根据权利要求8所述的TTS,其特征在于,所述伸长成型的钩和环带仅覆盖所述区域的一部分,优选被设置在所述区域靠近侧边缘的区,在TTS中所述含活性物质的载体材料在所述区域上伸展。
10.根据权利要求1至9一项或多项所述的TTS,其特征在于,包含设置在所述区域的对侧的多个钩和环带,在TTS中所述含活性物质的载体材料在所述区域上伸展。
11.根据权利要求1至10一项或多项所述的TTS,其特征在于,所述含活性物质的载体材料是液体浸渍的载体材料,其中所述载体材料是无纺布、纺织材料、织物、针织物或者海绵状的材料、海绵布或者形成凝胶的聚合物。
12.在钩和环带节段的存在下将含活性物质的载体材料固定于TTS背衬层的方法,其中将在向上地通过预先剥离封闭膜而打开包装中的含活性物质的载体材料接近背衬层和设置在其上的钩和环带节段,然后,将包装与存在于其中的含活性物质的载体材料通过压力一起按在背衬层上的钩和环带节段上,此后将包装解开并除去,含活性物质的载体材料固定地留存在钩和环带节段以及背衬层。
13.钩和环带在将治疗活性物质透皮或离子电渗给药至需要采用这种活性物质治疗的患者的方法中的用途,其用于将含活性物质的载体材料固定到闭合背衬层上。
14.根据权利要求13所述的用途,其特征在于,具有阳离子结构的治疗活性物质是在其分子中具有氨基或亚氨基基团的活性物质。
15.根据权利要求13或14所述的用途,其用于透皮离子电渗给药镇痛剂如芬太尼或吗啡,止吐剂如格拉司琼或其他作用于中枢神经系统的药物如利凡斯的明或加兰他敏或肽,特别是肽类激素,如胰岛素和催产素或凝血因子和生长激素。
16.根据权利要求13至15任一项所述的用途,其特征在于,所述含活性物质的载体材料是液体浸渍的载体材料,其用作为基质或储库,治疗活性物质从中释放到皮肤上,然后被动地或经由离子电渗增强地透过皮肤。
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- 2014-12-17 CN CN201480070086.3A patent/CN105873634A/zh active Pending
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- 2014-12-17 RU RU2016129497A patent/RU2687090C1/ru not_active IP Right Cessation
- 2014-12-17 AU AU2014365899A patent/AU2014365899B2/en not_active Ceased
- 2014-12-17 BR BR112016013278-5A patent/BR112016013278B1/pt active IP Right Grant
- 2014-12-17 EP EP14815239.0A patent/EP3082942B1/de active Active
- 2014-12-17 ES ES14815239.0T patent/ES2661836T3/es active Active
- 2014-12-17 CA CA2934318A patent/CA2934318C/en active Active
- 2014-12-17 KR KR1020167019531A patent/KR20160102002A/ko not_active Application Discontinuation
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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CN108159563A (zh) * | 2016-12-07 | 2018-06-15 | 恩客斯(上海)商贸有限公司 | 电皮肤裹布 |
CN107670022A (zh) * | 2017-09-06 | 2018-02-09 | 华中农业大学 | 一种催产素透皮剂及其制备方法和应用 |
CN107670022B (zh) * | 2017-09-06 | 2020-07-10 | 华中农业大学 | 一种催产素透皮剂及其制备方法和应用 |
CN111417429A (zh) * | 2017-10-12 | 2020-07-14 | 瑞士Spa系统有限公司 | 可持在手中的用于电辅助的皮肤治疗的装置、用于该装置的备件和用于该备件的泡罩 |
CN111417429B (zh) * | 2017-10-12 | 2024-04-09 | 瑞士Spa系统有限公司 | 可持在手中的用于电辅助的皮肤治疗的装置、用于该装置的备件和用于该备件的泡罩 |
WO2020143633A1 (zh) * | 2019-01-08 | 2020-07-16 | 上海肤泰科技有限公司 | 一种用于透皮离子电渗给药的皮肤贴膜 |
CN110694036A (zh) * | 2019-08-21 | 2020-01-17 | 云南中医药大学 | 一种具有缓释功能的三伏贴及其制备方法 |
Also Published As
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JP2016540818A (ja) | 2016-12-28 |
EP3082942B1 (de) | 2018-02-28 |
ES2661836T3 (es) | 2018-04-04 |
KR20160102002A (ko) | 2016-08-26 |
US20160303361A1 (en) | 2016-10-20 |
US10485967B2 (en) | 2019-11-26 |
CA2934318A1 (en) | 2015-06-25 |
US20200046963A1 (en) | 2020-02-13 |
HK1223583A1 (zh) | 2017-08-04 |
AU2014365899B2 (en) | 2019-03-14 |
MX2016008138A (es) | 2016-09-16 |
EP2886153A1 (de) | 2015-06-24 |
CN112206223A (zh) | 2021-01-12 |
RU2016129497A (ru) | 2018-01-26 |
BR112016013278A2 (zh) | 2017-08-08 |
AU2014365899A1 (en) | 2016-07-07 |
US11439807B2 (en) | 2022-09-13 |
WO2015090583A1 (de) | 2015-06-25 |
JP6560679B2 (ja) | 2019-08-14 |
EP3082942A1 (de) | 2016-10-26 |
RU2687090C1 (ru) | 2019-05-07 |
CA2934318C (en) | 2022-02-22 |
BR112016013278B1 (pt) | 2021-09-08 |
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