CN1420755A - 用于治疗疤痕的方法和组合物 - Google Patents
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Abstract
一种用于治疗肥大性疤痕从而减小疤痕和改善疤痕的外观的方法和组合物,包括向疤痕上施用组合物,所述组合物包括膜形成载体如火棉胶,它包含一种或多种活性成分如局部类固醇、硅硐胶和维生素E。利用火棉胶膜形成载体的新颖组合物还可用于治疗多种皮肤病。
Description
本发明涉及用于治疗疤痕的方法,具体地说,涉及用于改善疤痕组织的大小和外观的方法。本发明还涉及用于治疗疤痕和其他皮肤症状和疾病的新颖的局部用组合物。
发明背景
当皮肤或表皮受到切割或烧灼伤害时,将形成疤痕组织。大多数情况下,小的切割或烧伤区域将导致相应少量的疤痕组织,这对于不经意的观察者来说通常不易察觉。在另一些情况下,当创伤区域较大和/或太长时,疤痕和疤痕组织对于不经意的观察者来说都十分明显。这不仅对于带有疤痕的患者来说是一件很困窘的事,而且对于不经意的观察者来说也很不舒服。这个问题随着时间变得更严重,疤痕组织倾向于变黑,变厚并从皮肤表面向外凸起,因此变得更明显。
在正常的创伤-愈合或溃疡-愈合过程中,在创伤或溃疡的成熟期有丰富的血管网再生,并且胶原纤维聚集成大束。如果创伤和溃疡愈合期间的生长、发育和修复期间结缔组织基质的形状改变,则需要在胶原合成和降解之间有精细的平衡。在正常环境下,胶原的合成和降解保持平衡。然而,有时这种成熟过程不能发生,于是疤痕组织保持在上皮细胞下面一段相对长的时间,并且甚至发展和变得很大。这是肥大性疤痕的临床特点。
尽管在皮肤创伤愈合过程中平衡的疤痕形成和重塑是基本过程,但过度的疤痕形成的紊乱也十分常见并且是很难控制的临床问题。肥大性疤痕是疤痕过度,这定义为疤痕生长的大小超过正常创伤愈合中所需的疤痕大小。肥大性疤痕可出现在很多创伤类型,如烧伤和锐器切割伤。肥大性疤痕增高、发红和发痒增大。疤痕可能对于触摸和其他外部压力敏感,并可形成于身体每个令人痛苦的地方。
肥大性疤痕常常保持很长时间,有时甚至折磨人整整一生。在成人的情况下,肥大性疤痕通常在一年左右变形成典型的发软和苍白的疤痕。除了发痒和相对难看以外,如果肥大性疤痕碰巧延伸在骨关节处,关节的运动时常常疼痛并受到限制。在过去,这种并发症通过用衣物、化妆品覆盖,或避免与其他人接触来克服。这种方法通常不可能也是不希望的。疤痕组织和邻近组织通常与衣物接触时变得过度敏感,患者常常不遮盖疤痕组织从而有损社交形象。在某些情况下,患者可能不能忍受使用化妆品来遮盖疤痕组织,这也有损社交形象。在其他一些情况下,患者可能需要穿着某种类型或式样的衣服,而这种衣服不能遮盖疤痕组织的位置。
很多医护人员已经认识到与疤痕组织相关的问题,并且目前已经将疤痕组织处理作为患者的整个治疗的一部分。
已经推荐了很多用于改善疤痕的技术。这些包括应用压力和用例如氢化可的松、胶原、维生素如维生素E和A,以及植物和动物源的提取物治疗。这些治疗中的一些有一定作用,但所有这些治疗都很麻烦、不方便甚至疼痛。
压力敷料的使用被认为是最确实有效的疤痕治疗方法。应用压力明显增加胶原酶的活性,这种酶是能够降解和重塑疤痕组织,并在体内被用于维持伤口愈合期间胶原的形成和降解之间的平衡。然而,压力敷料很笨重,使得穿戴者非常不舒服,并且将它保持在患有疤痕组织的位置常常很不方便。
应用类固醇,如可的松也可以增强胶原酶的胶原降解活性。对于大量的过大疤痕组织,如肥大性疤痕或疤痕疙瘩,根据严重程度,医生常常推荐可的松注射。在不太严重的情况下,可的松药膏或可的松胶布显示有中度作用。然而,药膏使用起来常常不方便,因为会弄得很脏,并且会粘在衣服上和使衣服褪色。使用胶布也有缺点,因为这种胶布经常使病变区域潮湿和从该区域掉落。另外,可的松药膏需要摩擦或按摩于疤痕上。对一些人来说可能很疼。可的松注射对于病人来说也是一件痛苦的事。
维生素如维生素E治疗被认为能够在创伤愈合期间降低胶原粘合并已经被用于软化疤痕。从维生素E胶囊的半中间切开并将油挤出是将维生素E涂抹到伤口上的最常见方式。显然,维生素E油会弄脏周围并且从半中间切割胶囊是件很烦人的事。将维生素A和E加入到霜剂和洗液中也是公知的,但是这种霜剂和洗液摸起来常常是油性的并且不会变干,因此常保持油性状态,或者需要花费很长时间去彻底擦涂进皮肤。再者,将霜剂或油在某一疤痕组织上和/或内擦涂或按摩对一些人来说很痛苦。
近几年已经发现在疤痕上应用硅硐胶片或膜可增加肥大性的疤痕的皱缩。然而,硅硐胶与这类疤痕的相互作用的准确机制尚不清楚。市售的许多产品用于这个目的,例如Dow鸡眼硅橡胶(Dow Corning Silastic)片,Cica-Care(Smith & Nephew),Epi-Derm(Biodermis),Nagosil(Nagor)等等产品。这些产品具有模塑的硅硐胶膜的形式,具有2-4毫米厚。在治疗肥大性疤痕中,将这些膜置于疤痕上并戴相对较长的时间,常常是3-12个月,直到疤痕即不缩小也不再生为止。最近公开的这类硅硐胶膜的专利包括美国专利号5,759,560;5,891,076;5,895,656和5,919,476。
已知的硅硐胶膜相对较硬,在贴附于疤痕上后没有足够的粘合力,所以没有一些辅助形式很难保持固定在原位上。结果,需要用固定、袜套、绷带、自粘胶布或一些装置将这些膜牢牢贴在皮肤上。这些膜经常吸收太多潮气引起病损区域的刺激。适用硅硐胶类型的胶膜摸起来粘乎乎的,在内部主体,主体的接触面和外表面都是这样。使主体的接触面摸起来发粘是有利并是所希望的。然而,不希望主体的外表面摸起来发粘。外部发粘的不利原因是衣物容易粘在胶膜上。这存在几个问题。一个问题是常常出现胶膜粘着衣物的力量大于粘着在皮肤上的力。因此,当脱下衣物时,胶膜也从身体上脱落。另一个问题是衣物粘着到胶膜上,并妨碍了正常范围的运动。摸起来发粘的胶膜遇到的另一个问题是它们很容易被迅速弄脏。
可用的其他物理治疗包括手术、X线疗法和冷冻疗法。这类治疗价格昂贵或具有潜在危险,通常不推荐使用。
因此,物理治疗、在减少、软化和减轻肥大性疤痕方面有中度的作用的包含药剂的组合物和/或物品,这些现有的方法价格昂贵、使用不方便、应用困难或仅仅是在取得期望的目的上没有明显效果。
发明概述
如上所述,用于肥大性疤痕和疤痕疙瘩的现有疗法包括手术、机械压迫、X线照射、冷冻疗法和各种药物,如类固醇、维生素,以及植物和动物提取物的应用。这些方法的每一种都有许多缺点。因此,手术切除疤痕组织经常不完全,并且可能导致切口处和缝合点的肥大性疤痕和疤痕疙瘩的发展。X线疗法是截至目前唯一预言有效的疗法,然而,由于它有潜在诱发癌症的可能,因此X线疗法一般不推荐使用或被接受。最常用的控制肥大性疤痕和疤痕疙瘩的疗法是施加压力,这在很多情况下似乎都有效。然而,这种疗法的用途有限,因为一般要根据身体上疤痕组织的大小和位置而定。类固醇注射作用不肯定,并常导致皮肤脱色。含硅硐胶凝胶如硅硐胶片的应用一般引起受治疗的疤痕的外观和大小的改善,但这种愈合的机理还不清楚,并且如上面所讨论的,这种硅硐胶胶片不太方便。
因此,本发明的主要目标是提供一种能够改善瘢痕,尤其是肥大性疤痕的大小和外观的有效,且使用方便的组合物。
在它的最广的方面来讲,本发明涉及一种使用能够缩小疤痕的尺寸或改善它的外观的药剂来治疗肥大性疤痕的方法,其中该药剂包含于膜形成载体中,这种载体可以准确并直接涂抹在病变疤痕组织上,干燥后变成基本上透明的膜,使得药剂保持在原位上。本发明的膜成型载体包括是火棉胶,它包括火棉(硝化纤维)于25/75的乙醇和乙醚的混合物中的溶液,或包括火棉胶与樟脑和蓖麻油的混合物的弹性火棉胶。这种膜成型载体不是油性或脂性的,其特征在于该载体与应用维生素或其他植物或动物的提取物或类固醇共同使用,本发明的膜成型载体可以不需要摩擦或施加压力而直接应用于要治疗的疤痕上,这与应用油性或脂性载体时常引起接受疤痕治疗的病人疼痛所不同。
本发明的另一个方面是提供一种组合物,它能够有效减小增生性疤痕的大小和外观,和能够容易并准确直接地应用的疤痕上而没有油和脂,或包扎和膜相关的问题,应用时仅仅施加压力或与硅硐胶接触。在本发明的这个方面,提供一种包括火棉胶或弹性火棉胶膜形成载体,这种载体包括一种皮肤病学有效的类固醇如皮质类固醇,它可以直接应用到疤痕组织上,干燥后形成包含类固醇药剂的透明膜。
在上面描述的本发明的另一种组合物中,将皮质类固醇、硅硐胶胶或维生素E,或它们的混合物提供在火棉胶或弹性火棉胶膜形成载体中,并用于治疗不仅疤痕而且包括许多皮肤症状和疾病。
本发明的还一各方面是用于治疗增生性疤痕从而减小疤痕的大小并改善它的外观的组合物是通过与皮肤病学有效的类固醇例如氢化可的松、硅硐胶胶和任选地维生素E结合成一单一载体中,它能够直接应用到疤痕组织上,并第一次以与已经被单独使用的成分的有效特性结合的多成分药剂组合物出现。已经发现类固醇、硅硐胶胶和维生素E能够有效地混合到膜形成载体如火棉胶或弹性火棉胶中,并且不需要涂擦该组合物进入疤痕而直接以方便的方式应用到疤痕组织。组合物干燥后形成透明膜,不需要包扎、胶布,并且没有油性或脂性药剂引起衣物褪色并需要摩擦或按摩到并进入疤痕的缺点而保留于受治疗的区域上。发明详述
本发明的方法是涉及应用膜形成载体到病变疤痕组织的方法。膜形成载体包含一种或多种可以应用到疤痕组织上并通过膜形成载体保持在原位的药物(活性成分),并可以减小肥大性疤痕组织的大小和/或改善它的外观。因此,本发明的方法是应用膜形成载体和一种或多种有效的疤痕治疗药物于增生性疤痕上的方法。当膜形成载体干燥后,它在应用药物的位置上形成保护膜以保持活性成分与疤痕接触并防止活性成分从原位移开。用于本发明的方法中的膜形成物优选是火棉胶或弹性火棉胶。火棉胶是4克火棉(主要是硝化纤维)于100毫升25毫升乙醇和75毫升乙醚的混合物中的溶液。火棉胶是无色或淡黄、透明或淡乳白色糖浆样液体。弹性火棉胶包括单火棉胶加上樟脑和3%的蓖麻油(按重量计)。弹性火棉胶是淡黄色并且包含67%乙醚和大约22%无水乙醇(按体积计)的糖浆样液体。当火棉胶或弹性火棉胶蒸发后形成有韧性并无色的膜。本发明的局部组合物还包括添加到载体中用于溶解活性成分的溶剂。可以使用的溶剂的实例是丙酮。
在本发明的方法中,能有效治疗增生性疤痕的活性成分被包含于火棉胶或弹性火棉胶膜形成载体中。任何有效的、目前已知或未知的活性成分都可以用于本发明的方法中。这种活性成分包括皮肤病学活性类固醇,例如皮质类固醇、维生素和其它已知的治疗疤痕的植物和动物提取物,以及硅硐胶,包括已经用于硅硐胶膜和片中的硅硐胶。
在制备用于本发明的方法的局部组合物中,可以加入常规的佐剂如丙酸、丙二醇、丙酮和乳酸,常规的渗透增强剂如芥子酸、油酸和红果榄仁树(bahemic)酸;常规的缓冲液、防腐剂、亲水性乳化剂、亲脂性乳化剂、防晒剂、香味剂、润肤剂、除臭剂、保湿剂等。色素也可以任意地加入到本发明的组合物中。显然,应该避免对疤痕组织或周围皮肤有害的佐剂,以及那些可能与掺入到膜形成载体中的活性成分发生反应和/或降低活性成分的效力的佐剂。当前的基于火棉胶的FDA专著认可的配方可用于这样的局部液体组合物中。
在本发明的方法中,优选使用任何常用的将组合物涂抹到皮肤上的涂药器如刷子、辊或滴眼装置以利于将基于火棉胶的组合物施用到要治疗的疤痕组织上。还可以通过将多孔的基底材料上充满组合物并将组合物涂抹到疤痕上来应用组合物,或者多孔基底材料包括将多孔基底材料固定到靠近疤痕的皮肤的粘合剂,并且其中膜成形物和活性成分放置在要治疗的疤痕上。用于本发明的方法中的组合物是相对粘性的液体,它可以直接并准确地应用到疤痕组织上而不需要如以前使用的一些油性或油脂性一样施加额外的力或摩擦。因此,相信带有一种或多种治疗增生性疤痕的药物的基于火棉胶的膜形成物的用途是一种新颖的用途。
本发明的第二个方面是提供一种组合物,用于治疗增生性疤痕从而减小疤痕的大小或改善疤痕的外观。在本发明的这个方面,将以类固醇形式的一种活性成分加入到火棉胶型的膜形成载体中。因此,已经发现可以将能够局部应用的如氢化可的松、倍他米松和任何其它已知的皮质类固醇等的皮肤病学活性成分,以及它的可药用盐,包括氯化物、醋酸盐等以按重量计约0.25%~约70%的量加入到火棉胶膜形成载体中,以产生可方便并直接地应用到要治疗的疤痕组织上的组合物。该组合物干燥后形成透明的膜,并保持类固醇活性成分与疤痕组织接触,和提供有益的和连续的类固醇治疗效应。如前所述,可以添加通常用于局部组合物中的佐剂,包括溶剂、渗透增强剂、润肤剂、缓冲剂等,只要这种添加没有负面干扰类固醇的效果即可。
本发明还涉及一种局部用组合物,它可用于方便并有效地治疗不良的皮肤症状,包括肥大性疤痕、湿疹、牛皮癣、遗传性过敏性皮炎和其他免疫性皮肤病。在本发明的这个方面,将局部活性成分,如类固醇,包括皮质类固醇、硅硐胶,即,不挥发性聚硅氧烷,维生素包括维生素A和E,或它们的混合物掺入到火棉胶或弹性火棉胶膜形成载体中。每种活性成分的浓度将根据要治疗的皮肤病而变化,并可以从包含于其它载体,例如洗液、油脂、油或多孔结构例如绷带、纱布等中的活性成分的已知剂型中很容易地确定。一般来说,最实用的是0.25wt%~75wt%的浓度,但在本发明范围内的变化是允许的。
本发明还一个方面是提供用于改善肥大性疤痕的大小和外观的组合物。这种组合物也是基于火棉胶型膜形成载体。在本发明的这个方面,对改善增生性疤痕有活性的并且已经被用于个体基础上的三种成分与火棉胶型膜形成载体结合,其中的膜形成载体干燥后成为透明膜覆盖在接受治疗的区域,并提供使三种成分作用于疤痕组织并提供所期望的改善的基底。因此,根据本发明,火棉胶型载体中掺入了皮肤病学活性类固醇、硅硐胶和任选地加入维生素E。
可以使用的皮肤病学活性类固醇是如上所述的那些,具体地说,皮质类固醇如氢化可的松、倍他米松等,包括它们的可药用盐。
另外,发现可以通过除 了皮肤病学活性类固醇成分外进一步向该组合物种加入硅硐胶而使火棉胶型载体仍可以保持膜形成作用,并形成特别优势的组合物。可加入到本发明的组合物中的硅硐胶是已经发现对改善肥大性疤痕的外观和大小有效的那些。硅硐胶是一组完全合成的聚合物,它包括重复基-SiR2O-,其中R是可以被取代或不被取代的例如烷基、苯基或乙烯基。较简单的硅硐胶是熔点非常低的油,而在物理特性规格的另一极端是高度交联的可以形成刚性固体的硅硐胶。中间体的物理特性是硅硐胶弹性体,如硅硐胶和橡胶。很多硅硐胶被用作创伤敷料,如转让给Johnson和Johnson的美国专利No.4,838,253和转让给Dow的美国专利No.4,991,574中公开的一样。市售的可用的硅硐胶实例的商标名为SILASTIC。
还没有最后证明硅硐胶是如何作用在疤痕组织上以改善它们的,根据包括与施用这种硅硐胶相关的物理参数的测定,调查者的结论是硅硐胶的作用模式和疤痕治疗不包括压力、温度、氧、张力或包藏。如所报道的,更合适的机制可能包括角质层的水合作用和从凝胶中的低分子量的硅硐胶液体的释放这两个原因。
如上所述在以前曾被用作创伤敷料的任何已知的硅硐胶都可用于本发明的组合物中。一般来说,在25℃下硅硐胶具有100-30000厘泊的粘度。优选可使用苯基三甲基硅氧烷如Dow Corning556液体或非挥发性聚二甲基硅氧烷。
尽管是任选的,但优选在组合物中包括维生素E(α-生育酚)。在这个最优选的实施例中,已知在个体基础上治疗肥大性疤痕的三种活性成分以组合形式在单一的膜形成载体中非常有用,在各成分之间没有不利的相互作用。有用的组合物可包括大约0.25-50%重量的类固醇如氢化可的松,优选大约0.5-5%的类固醇;2-70%,优选5-25%硅硐胶和0-25%,优选10%的维生素E。余量是火棉胶型膜形成载体,无论火棉胶或弹性火棉胶均可。尽管优选火棉胶膜形成载体,但也可以使用其它的膜形成载体。这些例子包括聚乙烯-吡咯烷酮聚合物和共聚物,聚酰化聚合物和共聚物等。
如上所述,也可以添加其它佐剂以增强活性成分的渗透,控制疤痕组织上的湿度,提供防腐剂和抗菌效果等。在最优选的实施方案中,可以添加少量的黄原胶,它既可以提供增稠性又可用作包括类固醇如氢化可的松和硅硐胶成分的活性物质的分散增强剂。如果加入黄原胶,它的含量应该是大约0.5-4%,优选大约0.75-2.5%重量。
本发明的组合物被认为是新颖的组合物。因为载体系统,含有类固醇和硅硐胶的火棉胶型膜形成材料还没有被用作治疗肥大性疤痕。氢化可的松可用作局部药膏或霜,硅硐胶可用以液体、油膏或作为绷带(它必须被剪断并用胶布或其它机构粘着在皮肤上)形式施用,本发明的组合物将这两种活性成分组合并将这种药剂分散到包藏敷料的基质上,当涂抹或用其它方法施用到皮肤上后,立即干燥,保持活性成分与皮肤接触以发挥它们的预计作用,并可以在治疗结束后或者施用后面的药剂时很容易地揭下。本发明的组合物不需要其它机构,如粘合绷带、纱布或浸药的盖片的帮助。通过刷涂该医用粘性基质到疤痕区域并使其干燥而很方便地完成操作。液体基质在一分钟内完全干燥,产生透明、柔性的封闭绷带盖膜。在可以很容易地将该组合物刷涂于皮肤上以外,也可以使用其它方法,包括分散性装置,它可以将材料滚涂于疤痕上,以及滴眼型装置。重要的是包含本发明的活性成分的载体不需要在疤痕区域上摩擦或按摩(摩擦或按摩在某些情况下可能会很痛)。另外,载体干燥后形成完全干燥的膜,它不会粘在衣服上。发现本发明的组合物当每天施用一到两次持续3-4个月时可产生最佳的软化、皱缩和减轻肥大性疤痕的效果。
实施例
配制下列组合物作为治愈疤痕组合物和代表本发明的优选实施方案。通过向载体基质(在该例中是弹性火棉胶,USP)中加入以下所示的成分制备该组合物:
10wt% 硅硐胶556
1wt% 氢化可的松盐酸盐
0.5wt% α-生育酚(维生素E)
1.2wt% 黄原胶
余量弹性火棉胶 USP
该实施例不是意在严格地将本发明限制于所示的实施方案中。应该明白前面所进行的详细描述仅仅是为了说明的目的。显然,在不背离本发明的精神和范围的情况下,在上文中的任何修改和变化都是允许的。因此,只有附加的权利要求中所指的这些限制条件应该被遵守。
Claims (20)
1.一种治疗肥大性疤痕从而减小疤痕和/或改善其外观的方法包括:在肥大性疤痕上施用一种组合物,该组合物包括其中含有能够减小疤痕或改善其外观的活性成分的火棉胶膜形成载体。
2.权利要求1的方法,其中火棉胶膜形成载体包括火棉胶或弹性火棉胶。
3.权利要求1的方法,其中所述组合物通过刷子、辊将组合物施用到疤痕上或将所述组合物滴加到疤痕上。
4.权利要求3的方法,其中所述组合物通过刷子涂抹到疤痕上。
5.权利要求1的方法,其中所述活性成份包括局部类固醇、硅硐胶或维生素中的至少一种。
6.权利要求5的方法,其中所述活性成分包括氢化可的松或它的可药用盐。
7.权利要求5的方法,其中所述活性成分包括局部类固醇和硅硐胶的组合。
8.权利要求7的方法,其中所述局部类固醇是氢化可的松或它的可药用盐。
9.权利要求7的方法,其中所述组合物进一步包括维生素E。
10.一种用于治疗皮肤疾病的组合物包括火棉胶膜形成载体和活性成分,其中的活性成分包括局部活性类固醇、硅硐胶、维生素或所述活性成分的混合物。
11.权利要求10的组合物,其中所述活性成份是局部活性类固醇,它包括氢化可的松或它的可药用盐。
12.权利要求10的组合物,其中所述活性成分是硅硐胶。
13.权利要求12的组合物,其中所述硅硐胶是苯基三甲基硅氧烷。
14.权利要求10的组合物,其中所述活性成分包括维生素E。
15.权利要求10的组合物,其中所述活性成分包括局部类固醇、硅硐胶和任选的维生素E的混合物。
16.权利要求15的组合物,其中所述局部类固醇是氢化可的松或其可药用盐,并且所述硅硐胶具有在25℃下100-30000厘泊的粘度。
17.权利要求16的组合物,其中所述硅硐胶包括苯基三甲基硅氧烷。
18.权利要求15的组合物,其中所述膜形成载体是火棉胶或弹性火棉胶。
19.一种用于减小肥大性疤痕的大小或改善其外观的组合物,包括在膜形成载体中的局部类固醇和硅硐胶的混合物,所述载体干燥后在疤痕的表面形成覆盖膜。
20.权利要求19的组合物进一步包括维生素E。
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CY (2) | CY1113841T1 (zh) |
DK (2) | DK1231887T3 (zh) |
ES (2) | ES2435499T3 (zh) |
HK (1) | HK1048949B (zh) |
PT (2) | PT1231887E (zh) |
WO (1) | WO2001037782A2 (zh) |
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2003
- 2003-02-18 HK HK03101230.5A patent/HK1048949B/zh not_active IP Right Cessation
- 2003-11-17 US US10/715,183 patent/US20040096487A1/en not_active Abandoned
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2004
- 2004-04-21 US US10/829,316 patent/US7833542B2/en not_active Expired - Lifetime
- 2004-04-21 US US10/829,315 patent/US7731983B2/en not_active Expired - Fee Related
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2010
- 2010-09-28 US US12/892,482 patent/US8178115B2/en not_active Expired - Lifetime
-
2012
- 2012-04-05 US US13/440,182 patent/US20120190658A1/en not_active Abandoned
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2013
- 2013-03-20 CY CY20131100237T patent/CY1113841T1/el unknown
- 2013-10-21 CY CY20131100926T patent/CY1115642T1/el unknown
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN108778234A (zh) * | 2016-03-18 | 2018-11-09 | 小林制药株式会社 | 用于减轻皮肤摩擦的外用制剂 |
CN113453670A (zh) * | 2018-09-28 | 2021-09-28 | 乔·斯图丁 | 类固醇和大分子的透孔递送 |
CN113557061A (zh) * | 2018-12-03 | 2021-10-26 | 乔·斯图丁 | 用于治疗皮肤缺陷的化妆品组合物 |
CN110200988A (zh) * | 2019-06-17 | 2019-09-06 | 瑞希(重庆)生物科技有限公司 | 一种疤痕修复剂及其制备方法 |
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