CN104853745A - 用于治疗口疮的局部用药物 - Google Patents
用于治疗口疮的局部用药物 Download PDFInfo
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- CN104853745A CN104853745A CN201380065380.0A CN201380065380A CN104853745A CN 104853745 A CN104853745 A CN 104853745A CN 201380065380 A CN201380065380 A CN 201380065380A CN 104853745 A CN104853745 A CN 104853745A
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Abstract
本发明涉及用于治疗口疮的局部用药物，其中，所述局部用药物为膜状剂型的形式，所述局部用药物包含由可水溶胀的或水溶性聚合物或者聚合物混合物制成的膜和至少一种选自鞣剂和精油的活性成分。
Description
技术领域
本发明涉及用于治疗口疮的局部用药物，并且特别地，涉及以膜状形式提供的局部用药物。
背景技术
“口疮”指以发炎的边缘为界限的疼痛的黏膜损伤。口疮是具有白色纤维蛋白覆盖层的溃疡。小口疮的直径小于一厘米并且通常在一至两周内愈合。在极少情况下，口疮直径可大于一厘米，多达3cm。这些称为重度型的口疮可持续数周或甚至数月，并且仅以伤痕形成来愈合。口疮主要发生于牙龈、扁桃体和舌头的黏膜。不常见生殖区的黏膜被口疮感染。
口疮是疼痛的。口疮的疼痛与它的大小关系较小，其在一定程度上取决于所述口疮发生的位置。特别在说话、吃和吞咽期间，所述疼痛变得明显。因此，口疮显著影响那些被感染的人的健康。在这方面，即使他们能够通过自己愈合，但是为了更快地免于疼痛，仍需要口疮的治疗。以喷雾剂、含漱液、凝胶剂或软膏的形式提供用于口疮的症状治疗的止痛药，如利多卡因、聚乙二醇单十二醚或苄达明。也可施用收敛剂，如大黄根提取物、没药酊、硝酸银、苯酚磺酸化合物、甲酚磺酸缩合聚甲酚磺醛、硫酸锌或过氧化氢溶液。作为一种用于治疗口疮的处方剂可以提及抗炎曲安奈德。可供选择的用于治疗口疮的抗炎剂是，例如，澳大利亚茶树油、蜂花提取物和黄春菊或鼠尾草茶。
未经审查的专利公布DE 10 2004 002 001 A1公开了用于炎性疾病治疗的透明质酸的用途。除其他施用的形式外，还提及闭合膜(occlusive film)。这些包含透明质酸的闭合膜施用于皮肤上以覆盖发炎的区域。作为一种用透明质酸可治疗的炎性疾病而提及口疮。
文献WO 90/01046 A1描述了喷在黏膜上以便在那里形成膜的制剂。
文献DE 696 13 840 T1涉及包含提供有麻醉包衣的显示长期效应的非麻醉活性成分片心的片剂。所述片心可具有可包含亲水聚合物(如聚羧乙烯)的亲水糖层。除所述片剂外，提及用于口疮治疗的包含活性成分的聚合物膜，其从颊黏膜吸收水分并且黏附于所述膜表面。但是，所描述的不利是，如果通过这样的聚合物膜来进行施用，当施用导致刺激的活性成分时，治疗位置的刺激较重。当所述治疗位置是疼痛的炎症，因为疼痛增加，所以该效果是特别有问题的。
专利文献DE 694 29 964 T2公开了用于治疗黏膜疾病的固体制剂。这些固体制剂是含有丙烯酸、纤维素醚和明胶的均聚物或共聚物的丸。
在文献US 2007/0104783 A1中，提及了口腔分散片的用途，所述口腔分散片直接黏附于黏膜的损伤以致它们的施用对患者将无疑是疼痛的。
文献WO 2003/039465 A2公开了用于治疗口疮的贴剂，其中，在口中通过一种覆盖贴剂固定膜状药物。
文献US 2007/0248655 A1描述了在口中用于施用局部有效药物的贴剂，其中，使用专门的植物聚合物。用于生产所述贴剂的材料仍然固定在口中，并且是适合于在唾液中缓慢溶解的。
现有技术中已知的用于治疗口疮的药物在各方面不是最佳的。因此，软膏、漱口液、酊剂和糊剂的缺点在于，它们仅在所述口疮上黏附短时间。粘合片剂的缺点在于，它们的施用对于患者来说是疼痛的，因为它们是在所述口疮上施加压力的硬丸。因此，需要适合易于施用的局部用药物，其在所述口疮上具有长停留时间，并且其施用不会对患者导致更多疼痛。
发明内容
因此，本发明的目的是提供一种用于治疗口疮的局部用药物，其连续施予一种或多种活性成分，不在口中溶化，并且确保所述一种活性成分或所述多种活性成分充分地分散于口腔黏膜中，并且其在它的施用中最大可能的避免皮肤刺激。
所述目的通过包含可水溶胀的或水溶性聚合物或者聚合物混合物和至少一种适合治疗口疮的活性成分的膜状剂型形式的局部用药物来实现。根据本发明的膜状剂型能容易地施用于口疮，可在那里停留然后连续释放其中含有的活性成分，因为其溶解周期时间较长，即，周期多于一小时。令人惊讶地，根据本发明的剂型的施用不会引起患者额外的疼痛。
在第一方面，本发明涉及一种用于治疗口疮的局部用药物，其作为膜状剂型提供。
在第二方面，本发明涉及一种制备用于治疗口疮的所述膜状剂型的方法。
在第三方面，本发明涉及用于治疗口疮的所述膜状剂型的用途。
在第四方面，本发明涉及一种通过所述膜状剂型治疗口疮的方法。
根据本发明的第一方面，所述用于治疗口疮的局部用药物以膜状剂型的形式提供。所述膜状剂型包含可水溶胀的或水溶性聚合物或者可水溶胀的或水溶性聚合物混合物。此外，所述膜状剂型包含至少一种用于治疗口疮的活性成分，即，至少一种适合治疗口疮的活性成分。
根据本发明的膜状剂型具有这样的固有粘合性：保证与黏膜持续接触。因为黏膜的湿气由膜状剂型的聚合物吸收，所以提供所述固有粘合性。因此，它们开始溶胀。此外，所述膜状剂型包含可延展的聚合物膜，其中，所述至少一种活性成分以溶解的或很好的分散的形式存在于所述聚合物或聚合物混合物中。
所述可水溶胀的或水溶性聚合物可以是天然聚合物，即，一种能够在自然界中发现的聚合物。本说明书的上下文中的天然聚合物还包括以能够在自然界中发现的聚合物为基础并通过化学和/或物理处理改性的聚合物。根据膜状剂型的另一个实施方式，所述可水溶胀的或水溶性剂型为一种全合成聚合物。如果某些膜状剂型的实施方式具有特定的特征，则相对天然聚合物而言，由于全合成聚合物的溶胀和/或溶解性，可以优选全合成聚合物。
在所述膜状剂型包括可水溶胀的或水溶性聚合物混合物的实施方式中，聚合物混合物的聚合物中的至少一种是可水溶胀的或水溶性聚合物。优选地，所述可水溶胀的或水溶性聚合物混合物中的至少一种可水溶胀的或水溶性聚合物是全合成聚合物。在另一个和/或另外的实施方式中，所述可水溶胀的或水溶性聚合物混合物可包括多种可水溶胀的或水溶性聚合物，优选多种全合成可水溶胀的或水溶性聚合物。
在一个实施方式中，所述膜状剂型可包括选自如下聚合物中至少一种可水溶胀的或水溶性聚合物：葡聚糖、纤维素衍生物、聚丙烯酸、聚丙烯酸酯、聚环氧乙烷聚合物、聚丙烯酰胺、聚乙二醇、胶原、藻酸盐、果胶、黄蓍胶、脱乙酰壳多糖、藻酸、阿拉伯半乳聚糖、半乳甘露聚糖、琼脂、琼脂糖、卡拉胶和天然树胶。所述纤维素衍生物可以选自羧甲基纤维素、乙基纤维素和丙基纤维素。
在另外的和/或备选的实施方式中，所述膜状剂型可包含选自如下聚合物中的至少一种水溶性或至少部分水溶性聚合物：聚乙烯醇、纤维素衍生物、淀粉、淀粉衍生物、明胶、聚乙烯吡咯烷酮、阿拉伯树胶、支链淀粉和丙烯酸酯类。所述纤维素衍生物优选选自羟丙基纤维素、羟丙基甲基纤维素、羧基甲基纤维素钠、甲基纤维素、羟乙基纤维素和羟丙基乙基纤维素。所述淀粉或淀粉衍生物可选自麦芽糖糊精、直链淀粉、支链淀粉、玉米淀粉、马铃薯淀粉、米淀粉、木薯淀粉、豌豆淀粉、甘薯淀粉、大麦淀粉、小麦淀粉、蜡质种玉米淀粉和改性淀粉。
膜状剂型的物理性质，如黏膜粘合性、挠性、溶解性能、溶胀性能等，可以根据想要和需要通过结合上述聚合物的两种或更多种来调节。
膜状剂型的物理性质还可以通过聚合物含量来调节。所述膜状剂型的聚合物含量为至少5wt％，优选至少10wt％，尤其优选至少30wt％。所述膜状剂型的聚合物含量不超过90wt％，优选不超过70wt％，并且尤其优选不超过60wt％。
根据本发明的剂型包含至少一种适合治疗口疮的活性成分。所述至少一种活性成分以溶解的或很好的分散的形式存在于所述聚合物或聚合物混合物中。
在另外的和/或备选的实施方式中，所述至少一种活性成分可以是鞣剂。鞣剂指化学物质相当复杂的结构，其能够在许多植物中发现。包含鞣剂并且可以用于生产含有鞣剂的提取物的植物和/或植物机体结构可以，例如，选自棓子、金缕梅叶、核桃叶、栎树皮、迷迭香根、血根根、越橘、黑莓、鹤金梅、草莓叶、龙牙草、斗篷草、阔叶车前叶、长叶车前叶、玫瑰叶和地榆叶。
鞣剂与黏膜上层反应并形成一种固化皮肤蛋白(鞣革(tanning))。当鞣剂与蛋白接触时，鞣剂与蛋白结合。在蛋白中结合的水可以由鞣剂取代，从而引起脱水。生物活性蛋白可以通过鞣剂来变性，以便它们不再具有生物活性。
在另外的和/或备选的实施方式中，所述鞣剂可以为儿茶，即，鞣剂选自儿茶素类的鞣剂。术语儿茶实际上是“树汁”的印度语表达。关于在此描述的剂型，儿茶指包含儿茶素类的高含量浓缩鞣剂的染料植物的提取物。作为所述鞣剂儿茶，以下儿茶素种类可被考虑：
1.来自于格伯金合欢(Gerber acacia)(豆科金合欢属植物儿茶(Acaciacatechu))、苏马儿茶(Acacia suma)或槟榔(areca palm)的红心材的孟加拉儿茶(Bengal catechu)；
2.来自于儿茶钩藤(Uncaria gambirer bush)的叶和茎的干巴儿茶(Gambi(e)r catechu)，当其用1％重碳酸钾熔化时被称为制备儿茶；
3.来自于细芯红树(mangrove Ceriops candolleana)的红树儿茶(Mongrove catechu)；
4.来自于欧洲软木的新儿茶；
5.来自于阿拉伯金合欢(Acacia nilotica)的“Khair”，其在印度用于丝绸的直接褐变。
儿茶通常通过煮沸木头或植物机体结构来获得，以便获得非常鞣质的树脂提取物。儿茶在沸水中是可溶的，并且一般含有大约2-10％的儿茶素，25-35％的儿茶素鞣剂，20-30％的槲皮素和黏胶及树脂。因此，儿茶不指单一的、特定的化合物，而是一种多种化合物的组合物。
在另一个和/或附加的实施方式中，所述至少一种活性成分可以是精油。精油指具有可接受的固有气味的挥发性的、亲脂性的植物化合物。精油具有抗微生物活性。在一个实施方式中，所述精油可以选自包含在春黄菊酊、鼠尾草酊、蜂花酊或山金车酊中的精油。
在另外的和/或备选的实施方式中，所述膜状剂型可包括至少0.1wt％，优选至少0.5wt％的活性成分含量。所述膜状剂型包括不超过50wt％，优选不超过20wt％的活性成分含量。
单个剂型优选包括至少0.5mg的活性成分，优选包括至少1mg的活性成分。单个剂型包括不超过20mg的活性成分，优选包括不超过10mg的活性成分。
在另外的和/或备选的实施方式中，所述膜状剂型可包含一种或多种制药上可接受的赋形剂。赋形剂的种类和含量还取决于所述剂型包含的所述聚合物或聚合物混合物，如同取决于所述至少一种活性成分。
至少一种制药上可接受的赋形剂可选自增塑剂、稳定剂、载体、调味剂和填料。
在另外的和/或备选的实施方式中，所述膜状剂型可包含至少一种作为赋形剂的增塑剂。所述至少一种增塑剂可选自如下增塑剂：甘油、高级醇(如，十二烷醇)、羧酸酯(尤其是其中醇组分为聚乙氧基化醇的羧酸酯、二羧酸酯和甘油三酯(尤其是椰子油的辛酸和/或癸酸的中链甘油三酯))、1,2-丙二醇。其他聚乙二醇在药典中提及。术语“高级醇”指室温下(即，在18℃至22℃的温度下)是固体的醇。从本发明的意义上说的高级醇优选为生理上无害的醇。与甘油三酯有关的术语“中链”为脂肪酸残基的长度。在此，中链甘油三酯包括中等长度的脂肪酸残基，即，基于包括6至12个碳原子的脂肪酸的脂肪酸残基。
在所述膜状剂型中的至少一种制药上无害的赋形剂的含量可以为大于1wt％且多达10wt％、多达20wt％或多达30wt％。
在另外的和/或备选的实施方式中，所述膜状剂型可具有范围在10μm至500μm、优选范围在20μm至300μm的均匀厚度。
所述独立剂型具有范围在1cm2和10cm2之间，优选范围在5cm2和8cm2之间的表面积。
在另外的和/或备选的实施方式中，所述局部用药物可包括一种可再分离的保护层，在该保护层上搁置所述膜状剂型。所述可再分离的保护层可为硅化的纸。
在另外的和/或备选的实施方式中，所述膜状剂型可直接搁置在包装的内侧上，即，在提供用于膜状剂型的、包裹所述膜状剂型的包装的内部区域的包装装置的表面上。
在另外的和/或备选的实施方式中，与所述膜状剂型接触的所述可分离的保护层可以例如通过硅化由与用于生产工艺衬垫相同的材料制成，只要使后者可分离即可。工艺衬垫为一种膜，其用于平面医药剂型的制造工艺，但不存在于终产物中，因为其已经根据本工艺移除。所述可分离的保护膜可为一种聚四氟乙烯、经处理的纸、玻璃纸、聚氯乙烯等的层。
在另外的和/或备选的实施方式中，所述可分离的保护层的表面积大于大小和形式适合于治疗的膜状剂型的表面积。优选地，配制所述可分离的保护层的较大表面积以便其在一端超过膜状剂型的表面大大地伸出。可分离的保护层的这个伸出区域能够使所述保护膜较容易的从所述膜状剂型上撕下，尤其在所述膜状剂型的施用期间。
在另外的和/或备选的实施方式中，所述剂型在边缘密封袋中以单独给药的剂量包装。根据另一个实施方式，在一个共用包装中提供数个剂型。
作为一种用于膜状剂型的包装材料，优选使用可密封的复合包装材料。优选的密封介质为聚丙烯腈和聚对苯二甲酸乙二醇酯，这是因为在包装的膜状剂型的储存期间，它们不吸收精油或仅仅吸收极少量的精油，其中，所述优选的密封介质在它们的侧边(其形成后续包装的内部)上包含所述可密封的复合包装材料。
根据本发明的第二方面提供一种用于制备上述膜状剂型的方法。
在一个实施方式中，根据本发明的膜状剂型可以通过在溶剂或悬浮剂中的聚合物或聚合物混合物的溶液或悬浮液中均匀分散所述至少一种活性成分来制备。
在另外的和/或备选的实施方式中，所述至少一种活性成分与所述至少一种制药上可接受的赋形剂一起可以均匀地分散在溶剂或悬浮剂中的聚合物或聚合物混合物的溶液或悬浮液中。
所得聚合物或聚合物混合物、至少一种活性成分和非必须的至少一种制药上可接受的赋形剂的混合物可以在载体材料上涂布。然后，所述溶剂或悬浮剂可以从涂布的混合物中移除，以便获得聚合物膜，从其中可以分离所述膜状剂型。
根据本发明的第三方面包括上述膜状剂型用于治疗口疮的用途。为此，膜状剂型中的一个可以施用于待治疗的口疮，以便所述口疮由所述膜状剂型覆盖。由于它的粘膜黏合性能，所述膜状剂型持续与黏膜接触并释放其所包含的所述至少一种活性成分至感染的黏膜和口疮的附近。所述膜状剂型经过较长时间溶解。
根据本发明的第四方面还包括用于治疗口疮的方法，尤其是用于治疗口腔中的口疮的方法，其中，将由可溶胀或水溶性聚合物或者聚合物混合物的膜和至少一种选自鞣剂和精油的活性成分组成的膜状剂型施用于待治疗的口疮，以便所述膜状剂型覆盖所述口疮。
以下就仅用于解释并不意欲限制本发明的示例性的实施方式举例说明了本发明。本发明仅由权利要求定义。
具体实施方式
实施例1
在300ml 45％的乙醇中搅拌溶解40g儿茶(粉末状的)、10g肉桂粉和150g聚乙烯吡咯烷酮K 90。固体完全溶解后，获得粘性液体，其通过挤压轮涂抹于硅化的纸上。通过温和干燥，大部分水和乙醇从所述粘性液体中移除，从而获得膜。接着，通过采用冲孔机，冲出具有大约1cm2面积的圆形结构，并且将它们的膜的侧边放在复合包装材料的密封介质上。然后，移除所述硅化的纸，并且在圆形膜上放置复合包装材料的另外一层，以使两个复合包装材料层的密封表面面对彼此。通过密封罩，结合所述复合包装材料层以获得包含含有所述活性成分的膜的边缘密封袋。
实施例2
制备根据实施例1的膜状剂型，其中，所述膜包含以下组分：
1.0mg儿茶酊
6.5mg聚羧乙烯
2.5mg淀粉。
Claims (16)
1.用于治疗口疮的局部用药物，其包含膜状剂型，所述膜状剂型包含可水溶胀的或水溶性聚合物或者可水溶胀的或水溶性聚合物混合物的膜和用于治疗口疮的至少一种活性成分。
2.根据权利要求1所述的局部用药物，其特征在于，所述可水溶胀的或水溶性聚合物或者可水溶胀的或水溶性聚合物混合物中的至少一种可水溶胀的或水溶性聚合物为全合成聚合物。
3.根据权利要求1所述的局部用药物，其特征在于，所述膜状剂型包含选自葡聚糖、纤维素衍生物、聚丙烯酸、聚丙烯酸酯、聚环氧乙烷聚合物、聚丙烯酰胺、聚乙二醇、胶原、藻酸盐、果胶、黄蓍胶、脱乙酰壳多糖、藻酸、阿拉伯半乳聚糖、半乳甘露聚糖、琼脂、琼脂糖、卡拉胶和天然树胶中的至少一种可水溶胀的或水溶性聚合物。
4.根据权利要求1或3所述的局部用药物，其特征在于，所述膜状剂型包含选自聚乙烯醇、纤维素衍生物、淀粉、淀粉衍生物、明胶、聚乙烯吡咯烷酮、阿拉伯树胶、支链淀粉和丙烯酸酯中的至少一种水溶性或至少部分水溶性聚合物。
5.根据前述权利要求中的任意一项所述的局部用药物，其特征在于，所述膜状剂型中的聚合物含量为至少5wt％，优选至少10wt％，尤其优选至少30wt％，并且不超过90wt％，优选不超过70wt％，并且尤其优选不超过60wt％。
6.根据前述权利要求中的任意一项所述的局部用药物，其特征在于，所述至少一种活性成分选自鞣剂和精油。
7.根据权利要求6所述的局部用药物，其特征在于，所述鞣剂选自儿茶素鞣剂。
8.根据权利要求6或7所述的局部用药物，其特征在于，所述鞣剂为儿茶。
9.根据权利要求6所述的局部用药物，其特征在于，所述精油选自包含在春黄菊酊、鼠尾草酊、蜂花酊或山金车酊中的精油。
10.根据前述权利要求中的任意一项所述的局部用药物，其特征在于，所述膜状剂型具有至少0.1wt％，优选至少0.5wt％，并且不超过50wt％，优选不超过20wt％的活性成分含量。
11.根据前述权利要求中的任意一项所述的局部用药物，其特征在于，所述膜状剂型包含至少一种制药上可接受的赋形剂，所述制药上可接受的赋形剂优选选自增塑剂、稳定剂、载体、调味剂和填料。
12.根据权利要求11所述的局部用药物，其特征在于，所述增塑剂选自如下增塑剂：甘油；在室温下为固体的醇，如，十二烷醇；羧酸酯，尤其是其中醇组分为聚乙氧基化醇的羧酸酯、二羧酸酯和甘油三酯，尤其是椰子油的辛酸和/或癸酸的中链甘油三酯；1,2-丙二醇和其他聚乙二醇。
13.根据权利要求11或12所述的局部用药物，其特征在于，所述至少一种制药上可接受的赋形剂的含量超过1wt％且多达30wt％。
14.根据前述权利要求中的任意一项所述的局部用药物，其特征在于，其包含可分离的保护层，在该保护层上搁置所述膜状剂型。
15.制备根据权利要求1至14中的任意一项所述的局部用药物的方法，其特征在于，在所述方法中，将所述至少一种活性成分和非必须的所述至少一种赋形剂均匀地分散在溶剂或悬浮剂中的聚合物或聚合物混合物的溶液或悬浮液中，将所得的混合物涂布在载体材料上，接着，移除所述溶剂或悬浮剂，以便获得聚合物膜，并且从其中分离所述剂型。
16.根据前述权利要求中的任意一项所述的局部用药物用于治疗口疮的用途。
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| Application Number | Priority Date | Filing Date | Title |
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| EP12197073.5 | 2012-12-13 | ||
| EP12197073.5A EP2742931A1 (de) | 2012-12-13 | 2012-12-13 | Topisches Arzneimittel zur Behandlung von Aphten |
| PCT/EP2013/076497 WO2014090981A1 (de) | 2012-12-13 | 2013-12-13 | Topisches arzneimittel zur behandlung von aphten |
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| EP (2) | EP2742931A1 (zh) |
| JP (1) | JP2016506392A (zh) |
| CN (1) | CN104853745A (zh) |
| BR (1) | BR112015013959A2 (zh) |
| CA (1) | CA2892105A1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070104783A1 (en) * | 2001-02-28 | 2007-05-10 | Axiomedic Ltd. | Double-Layered Absorbable Solid Compositions for the Topical Treatment of Oral Mucosal Disorders |
| US20070248655A1 (en) * | 2006-04-21 | 2007-10-25 | Haley Jeffrey T | Lenticular shaped protective mouth sore discs |
| US20070292487A1 (en) * | 2006-06-20 | 2007-12-20 | Izun Pharmaceuticals Corporation | Anti-Inflammatory Dissolvable Film |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1989010745A1 (en) * | 1988-05-02 | 1989-11-16 | Pomerantz, Edwin | Compositions and in situ methods for forming films on body tissue |
| FR2712807B1 (fr) | 1993-11-24 | 1996-02-23 | Vetoquinol Sa | Composition solide mucoadhésive, thérapeutique ou hygiénique, pour administration par application sur la muqueuse buccale ou nasale . |
| US5713852A (en) | 1995-06-07 | 1998-02-03 | Alza Corporation | Oral dosage and method for treating painful conditions of the oral cavity |
| CN1309425C (zh) * | 2001-11-05 | 2007-04-11 | 奥拉黑尔斯公司 | 用贴片治疗口腔溃疡以加速痊愈和缓解疼痛的方法 |
| DE102004002001A1 (de) | 2004-01-14 | 2005-08-11 | Reinmüller, Johannes, Dr.med. | Mittel zur Behandlung von entzündlichen Erkrankungen |
-
2012
- 2012-12-13 EP EP12197073.5A patent/EP2742931A1/de not_active Withdrawn
- 2012-12-13 US US14/652,079 patent/US20150320676A1/en not_active Abandoned
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- 2013-12-13 EP EP13815436.4A patent/EP2931254A1/de not_active Withdrawn
- 2013-12-13 BR BR112015013959A patent/BR112015013959A2/pt not_active IP Right Cessation
- 2013-12-13 HK HK15111404.0A patent/HK1210693A1/zh unknown
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- 2013-12-13 WO PCT/EP2013/076497 patent/WO2014090981A1/de active Application Filing
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070104783A1 (en) * | 2001-02-28 | 2007-05-10 | Axiomedic Ltd. | Double-Layered Absorbable Solid Compositions for the Topical Treatment of Oral Mucosal Disorders |
| US20070248655A1 (en) * | 2006-04-21 | 2007-10-25 | Haley Jeffrey T | Lenticular shaped protective mouth sore discs |
| US20070292487A1 (en) * | 2006-06-20 | 2007-12-20 | Izun Pharmaceuticals Corporation | Anti-Inflammatory Dissolvable Film |
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| Title |
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| 常忆凌: "《药剂学》", 30 June 2008, 中国医药科技出版社 * |
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| HK1210693A1 (zh) | 2016-05-06 |
| CA2892105A1 (en) | 2014-06-19 |
| BR112015013959A2 (pt) | 2017-07-11 |
| JP2016506392A (ja) | 2016-03-03 |
| US20150320676A1 (en) | 2015-11-12 |
| EP2931254A1 (de) | 2015-10-21 |
| EP2742931A1 (de) | 2014-06-18 |
| WO2014090981A1 (de) | 2014-06-19 |
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