CN101632627B - 涂指甲及甲周的溶液 - Google Patents
涂指甲及甲周的溶液 Download PDFInfo
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- CN101632627B CN101632627B CN2009101641308A CN200910164130A CN101632627B CN 101632627 B CN101632627 B CN 101632627B CN 2009101641308 A CN2009101641308 A CN 2009101641308A CN 200910164130 A CN200910164130 A CN 200910164130A CN 101632627 B CN101632627 B CN 101632627B
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- Prior art keywords
- solution
- acid
- fingernail
- carbamide
- activating agent
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Abstract
本发明涉及一种涂指甲及甲周的溶液，以及一种起协同作用的助渗透剂在制备皮肤病学或化妆用的涂指甲和甲周溶液中的用途。
Description
本申请是申请日为2003年9月1日、发明名称为“涂指甲及甲周的溶液”的发明专利申请的分案申请，原申请的中国专利申请号为03821214.5。
技术领域
本发明涉及起协同作用的助渗透(pro-penetrating)剂的用途，它们用于制备有皮肤病学或化妆品用途的涂指甲及甲周溶液，本发明还涉及由此得到的溶液。
背景技术
指甲可以是有不同性质和起因的紊乱、缺乏或病理学客体(BaranR.等人，《指甲疾病及其处理(Diseases of the nails and theirmanagement)》，第3版，2001年)。例如可以提到甲沟炎，其起因可能是细菌、真菌、寄生物或病毒，或者来自皮肤性疾病或全身疾病，或者可能源于药物治疗。真菌病理可能专门位于指甲内部，例如甲真菌病，或者像疱疹或梅毒，会影响身体的其他部位，但也能影响指甲的生理机能。通常指甲真菌感染由皮肤真菌引起，但也可能由霉菌、真菌和酵母菌引起。
现在采用的治疗或者是局部治疗，或者是常规治疗，这两种方法通常结合在一起，以达到最佳的疗效。事实上，为了使治疗有效，看到指甲再生的时间应该很长。另外，真菌病可位于指甲内或甲床内，这就需要活性剂渗透到整个指甲中。
常规治疗经常有不利的副作用，而局部治疗只因难以渗透到指甲中而疗效往往不好。
目前，指甲油或成膜溶液更特别地用于治疗甲真菌病和人类或哺乳动物指甲的类似真菌感染。文献已描述了许多用于预防和治疗这些病症的组合物，这些组合物含有具有抗真菌活性的活性剂，例如像在非水溶性成膜剂中的1-羟基-2-吡啶酮(US 4 957 730)，在含有作为助渗透剂的2-正壬基-1，3-二氧戊环的组合物中的活性剂(WO99/39680)，特比萘芬(US 6 214 360)，伊曲康唑(US 4 267 179)，盐酸阿莫罗芬(EP 0 389 778)或噻康唑(US 5 916 545)。
Marty在《J.Eur.Acad.Dermatol.Venerol.》，4(suppl.l)，S17-S21，(1995)中描述了作为输送载体用于活性剂局部涂敷的指甲油的疗效。这篇文章研究了抗真菌剂盐酸阿莫罗芬的输送问题。如在该文献中所描述，由溶剂、增塑剂和成膜剂组成的指甲油基组合可惜没有使活性剂最佳渗透到指甲中。
因此，证明研制例如涂指甲和甲周溶液这类皮肤病学或化妆品组合物是必要的，它应能使活性剂更好地渗透到指甲中，由此使活性剂的疗效更好，敷用时间缩短。
目前，尿素用作角质溶解剂是已知的事实。尿素还曾是有关它渗透到皮肤中(Wohlrab W.《J.Appl.Cosmetol.》9，1-7(1991年1月，3月))以及与硫醇结合渗透到指甲内的助渗透能力(US 5 696 164)的研究课题。Malhotra G.G.和Zatz J.L.(《J.Pharm.Sciences》，vol 91，2，(2002))描述了含有作为角质溶解剂的尿素和N-(2-巯基丙酰基)甘氨酸的组合，使活性剂能非常好地渗透到指甲中。
还没有现有技术描述过在涂指甲和甲周的溶液中使用酸或乙氧基二甘醇作为助渗透剂。此外，在现有技术描述的组合物中，还没有任何东西能促使本领域的技术人员将尿素与酸或尿素与乙氧基二甘醇混合起来，制备出涂指甲和甲周溶液，其中这种混合物对活性剂渗透到指甲中具有协同作用。
现在，本申请人出乎意料地发现，含有至少尿素和酸，或至少尿素和乙氧基二甘醇的适当助渗透剂混合物的存在，由于它们的协同作用有可能使活性剂在指甲内具有更好的生物利用率。
术语“协同作用”意指其效果高于每一种助渗透剂单独达到的效果之和。
发明内容
因此，本发明涉及一种起协同作用的助渗透剂的混合物在制备药用或化妆用的涂指甲和甲周溶液中的用途，这些助渗透剂选自尿素、酸和乙氧基二甘醇。因此，本发明的溶液可以含有至少两种这样的助渗透剂，即尿素和酸，或尿素和乙氧基二甘醇，或酸和乙氧基二甘醇，以及这三种试剂的混合物。
术语“涂指甲和甲周溶液”表示涂敷到指甲及其周围的溶液，这种溶液可以是，也可以不是成膜溶液(或指甲油)。
本发明优选地涉及一种助渗透剂混合物在制备药用或化妆用的涂指甲和甲周溶液中的用途，该助渗透剂至少含有尿素和酸。
本发明还涉及一种助渗透剂混合物在制备药用或化妆用的涂指甲和甲周溶液中的用途，该助渗透剂至少含有尿素和乙氧基二甘醇。
一种有协同作用的助渗透剂混合物的用途是更具体地用于制备抗真菌的涂指甲和甲周溶液。
术语“酸”意指“有机酸”，特别是指一元或多元的C1-C18羧酸及其衍生物，例如羟基单羧酸、羟基二羧酸，或游离酸。在本发明的范围内，还可使用由其衍生的内酯、盐和酯。优选地，本发明的酸不是含巯基的氨基酸。
优选地使用C1-C12脂族羧酸，尤其是羟基酸。作为非限制性的实例，可以列举甲酸、2-甲基丁酸、丙酸、2-甲基丙酸、2，2-二甲基丙酸、癸酸、辛酸、己-2-烯酸、庚酸、6-甲基庚酸、3-乙基戊酸、3-氯戊酸、2-羟基丙酸、2-氯-4-羟基己酸、己二酸、十八烷酸、4-氧代戊酸、6-羟基-4-氧代壬酸(6-hydroxy-4-oxononoic acid)、2-酮基丙酸、丙醇二酸、苹果酸、酒石酸、葡糖二酸、柠檬酸、乳酸、羟基乙酸、异柠檬酸、托品酸、5-羟基月桂酸、3-羟基-4-甲氧基扁桃酸或其混合物。
特别地，本发明的溶液可以含有脂族羧酸、乳酸或柠檬酸，优选乳酸。
为了得出一个数量级，本发明使用的涂指甲和甲周溶液，特别是指甲油，优选地以该组合物非挥发性组分重量计包含浓度小于15重量％的尿素，特别地，以该组合物的非挥发性组分重量计包含浓度小于14重量％，优选地，以该组合物的非挥发性组分重量计尿素浓度为7-14重量％，更特别地为9-13重量％。
以该组合物总重量计，酸的重量比例是0.01-15％(重量/重量)，优选地为1-10％，特别地为1-7％。
以该组合物总重量计，乙氧基二甘醇的重量比例是0.01-20％(重量/重量)，优选地为1-10％。
本发明还涉及涂指甲和甲周溶液，该溶液含有助渗透剂混合物，该混合物至少含有尿素和乙氧基二甘醇。
本发明还涉及涂指甲和甲周溶液，该溶液含有助渗透剂混合物，该混合物至少含有尿素和酸，其特征在于它呈非水成膜溶液形式，其特征还在于它含有以该组合物的非挥发性组分重量计15重量％以下的尿素。
术语“非水成膜溶液(指甲油)”意指含有成膜剂的溶液，所述的溶液无添加的水。但是，该溶液含有的残留水量可以不超过该组合物溶剂/助溶剂总浓度的5％。
优选地，这种酸是脂族羧酸，尤其是乳酸。
在本发明的一个实施方案中，如上定义的涂指甲和甲周溶液还含有：
a)至少一种活性剂，
b)有机溶剂/助溶剂混合物，和，
c)一种任选的增塑剂。
溶剂和助溶剂可选自有机溶剂类，并且根据ICH标准(杂质：残留溶剂准则，国际协调会议)，是低毒性的3级溶剂，例如乙醇、乙醇100或乙醇95、丙酮、乙酸甲酯、乙酸乙酯、乙酸丁酯，如二甲基亚砜之类的烷基甲基亚砜、2-丙醇、甲基异丁基酮、1-丁醇、二氯甲烷或其混合物。
在这些上述溶剂/助溶剂中，优选地使用挥发性的有机溶剂/助溶剂，更优选地使用由乙醇、乙酸乙酯和乙酸丁酯组成的混合物。
溶剂/助溶剂的优选使用浓度是以该组合物总重量计分别为30-90重量％和0-30重量％，更优选地以该组合物总重量计分别为35-60重量％和10-25重量％。
为了制备本发明的指甲油组合物，该组合物要求存在成膜剂，所述成膜剂有利地是水不溶性的，并选自：
-聚乙烯基甲醚与苹果酸的单烷基酯的共聚物，如ISP公司以商品名Gantrez ES 425销售的聚乙烯基甲醚与苹果酸的丁酯的共聚物(PVM/MA的丁酯共聚物)，
-丙烯酸与甲基丙烯酸的酯的共聚物，其中由丙烯酸衍生的季铵基团含量很低，例如
Pharma公司以商品名Eudragit RL 100销售的丙烯酸酯和甲基丙烯酸铵的共聚物(丙烯酸酯/甲基丙烯酸铵共聚物)，
-或纤维素衍生物，例如Aqualon公司销售的硝基纤维素或乙基纤维素，
-聚氨酯衍生物，例如Noveon公司销售的Avalures。
上述成膜剂的优选使用浓度是以该组合物总重量计0.01-20重量％。
增塑剂的浓度优选地是以该组合物总重量计0.001-10.00重量％，更特别地为0.01-5.00重量％。在这些增塑剂中，不受所列限制使用诸如邻苯二甲酸酯、三乙酸酯、柠檬酸酯或其混合物之类的化合物。
作为非限制性实例，这种活性剂可以是抗生素、抗菌剂、甾体消炎剂、非甾体消炎剂、抗寄生虫剂、抗病毒剂、免疫抑制剂、核受体调节剂、抗真菌剂或其混合物。
在抗生素中，可以提到例如氟喹诺酮类、利福霉素、交沙霉素、磺胺嘧啶、维及尼霉素、夫西地酸或其混合物。
在抗菌剂中，可以提到例如过氧化苯甲酰。
在甾体消炎剂中，可以提到例如丁氯倍他松、氢化可的松、醋酸氟轻松、地奈德、倍他米松、地塞米松或其混合物。
在非甾体消炎剂中，可以提到吲哚衍生物、芳基数酸衍生物、昔康类(oxicams)、吡唑衍生物或其混合物。
在抗寄生虫剂中，可以提到例如克罗他米通。
在抗病毒剂中，可以提到例如阿糖腺苷。
在免疫抑制剂中，可以提到例如氨甲喋呤、环孢霉素、他克莫司或其混合物。
在核受体调节剂中，可以提到例如类视色素、或维生素D及其同功异质体或其混合物。
在抗真菌剂中，可以提到例如属咪唑类的益康唑、酮康唑或密康唑；吡咯化合物，例如伊曲康唑或克霉唑之类；双三唑化合物，例如氟康唑；烯丙基胺族化合物，例如特比萘芬；吡啶酮类，例如环吡酮胺；吗啉类，例如阿莫罗芬及其盐；多烯化合物，例如两性霉素B；灰黄霉素，或其混合物。
该活性剂优选地选自抗真菌剂。
因此，本发明的涂指甲和甲周溶液优选地是抗真菌溶液，特别地，它们含有阿莫罗芬或它的盐中的一种。
以该组合物总重量计，活性剂的优选浓度是0.001-20重量％。
本发明的涂指甲和甲周溶液还可以含有在化妆品或药物领域中通常使用的添加剂，如多价螯合剂、润湿剂、粘合剂、涂铺剂、抗氧化剂、防晒剂、防腐剂、填料、电解质、保湿剂、颜料、染料，通常的无机或有机碱或酸类、精油、化妆活性剂、保湿液、维生素、必需脂肪酸或神经鞘脂。当然，本领域技术人员会谨慎选择这种或这些任选的补充化合物和/或它(们)的量，以便本发明组合物的有利性质不会或基本不会受到损害。
本发明的涂指甲和甲周溶液特别适合于下述的皮肤病学治疗领域：甲癣、chloronychia、甲沟炎、类丹毒、脆甲症、淋病、游泳池肉芽肿、蠕虫蚴行症、麻风、羊痘疮结(orf nodule)、乳牛结(milkers′nodules)、疱疹性瘭疽、急性细菌性甲周炎、慢性甲周炎、孢子丝菌病、梅毒、疣状皮肤结核、土拉菌病、潜蚤病、甲周疣和甲下疣、带状疮疹、20指甲营养不良(trachyonychia)，以及影响指甲的皮肤病，如牛皮癣、脓疱性银屑病、斑秃、角化不全性银屑病(parakeratosis pustulosa)、接触性职业皮肤病、瑞特综合症、牛皮癣状肢端皮炎psoriasiform acral dermatitis)、扁平苔藓、指甲中特发性萎缩、光泽苔藓、条纹状苔藓、炎症性线状疣状表皮痣(ILVEN)、脱发、天疱疮、大疱性类天疱疮、后天性大疱性表皮松解症、毛囊角化症、毛发红糠疹、掌跖角化病、接触性皮炎、多形性红癍、疥疮、Bazex综合征、全身性硬皮病、全身性红斑狼疮、慢性红斑狼疮、皮肌炎。
本发明的涂指甲和甲周溶液更特别适合于治疗和预防甲癣。
本发明的目的还涉及如上所述的涂指甲和甲周溶液在制备意欲治疗诸如甲癣之类真菌病药品中的用途。
本发明的涂指甲和甲周溶液还应用于化妆品领域，特别用于治疗指甲不齐、匙状甲、博氏线、纵脊、嵌甲。
具体实施方式
下面的实施例能说明本发明，而不限制其范围。在这些配方实施例中(实施例1-9)，除非另外说明，这些组分的量都是以该组合物的总重量计以重量％表示的。
还描述了一些说明本发明组合物中活性剂释放-渗透作用的实施例。
实施例1：
| 组分 | ％ |
| 乙醇 | 43.85 |
| 乙酸乙酯 | 17.00 |
| 乙酸丁酯 | 6.00 |
| 尿素 | 2.50 |
| 乳酸 | 4.25 |
| 盐酸阿莫罗芬 | 6.40 |
| PVM/MA丁酯共聚物 | 20.00 |
这种溶液可涂于足部趾甲，在9个月内每周一次，用于治疗甲癣。
实施例2：
| 组分 | ％ |
| 乙醇 | 51.90 |
| 乙酸乙酯 | 17.00 |
| 乙酸丁酯 | 6.00 |
| 三乙酸甘油酯 | 1.20 |
| 尿素 | 2.5 |
| 乙氧基二甘醇 | 5.00 |
| 盐酸阿莫罗芬 | 6.40 |
| 丙烯酸酯/甲基丙烯酸铵共聚物 | 10.00 |
该溶液可涂于指甲，在9个月内每周一次，用于治疗甲癣。
实施例3：
| 组分 | ％ |
| 乙醇 | 53.85 |
| 乙酸乙酯 | 17.00 |
| 乙酸丁酯 | 6.00 |
| 尿素 | 2.50 |
| 乳酸 | 4.25 |
| 密康唑 | 6.40 |
| 丙烯酸酯/甲基丙烯酸铵共聚物 | 10.00 |
该溶液可涂于指甲，在1-2个月内每天两次，用于治疗急性细菌性甲周炎。
实施例4：
| 组分 | ％ |
| 乙醇 | 43.10 |
| 乙酸乙酯 | 17.00 |
| 乙酸丁酯 | 6.00 |
| 尿素 | 2.50 |
| 乙氧基二甘醇 | 5.00 |
| 盐酸阿莫罗芬 | 6.40 |
| PVM/MA丁酯共聚物 | 20.00 |
该溶液可涂于手指甲，在6个月内一周一次，用于治疗甲癣。
实施例5：
| 组分 | ％ |
| 乙醇 | 48.10 |
| 丙酮 | 28.00 |
| 尿素 | 2.50 |
| 乙氧基二甘醇 | 5.00 |
| 盐酸阿莫罗芬 | 6.40 |
| 丙烯酸酯/甲基丙烯酸铵共聚物 | 10.00 |
该溶液可涂于足部趾甲，在9个月内每周一次，用于治疗甲癣。
实施例6：
| 组分 | ％ |
| 乙醇 | 45.65 |
| 丙酮 | 20.00 |
| 三乙酸甘油酯 | 1.20 |
| 尿素 | 2.50 |
| 乳酸 | 4.25 |
| 盐酸阿莫罗芬 | 6.40 |
| PVM/MA丁酯共聚物 | 20.00 |
该溶液可涂于指甲，在6-8个月内每周一次，用于治疗甲癣。
实施例7：
| 组分 | ％ |
| 二氯甲烷 | 52.65 |
| 乙酸乙酯 | 17.00 |
| 乙酸丁酯 | 6.00 |
| 三乙酸甘油酯 | 1.20 |
| 尿素 | 2.50 |
| 柠檬酸 | 4.25 |
| 盐酸阿莫罗芬 | 6.40 |
| 丙烯酸酯/甲基丙烯酸铵共聚物 | 10.00 |
该溶液可涂于足部趾甲，在9个月内每周二次，用于治疗甲癣。
实施例8：
| 组分 | ％ |
| 二氯甲烷 | 66.85 |
| 丙酮 | 20.00 |
| 甘油 | 5.00 |
| 尿素 | 2.50 |
| 乳酸 | 4.25 |
| 盐酸阿莫罗芬 | 8.00 |
该溶液可涂于足部趾甲，在6-12个月内每周一次，用于治疗甲癣。
实施例9：
| 组分 | ％ |
| 乙醇 | 37.39 |
| 乙酸乙酯 | 17.00 |
| 乙酸丁酯 | 6.00 |
| 尿素 | 2.50 |
| 乳酸 | 4.25 |
| PVM/MA丁酯共聚物 | 20.00 |
| 盐酸阿莫罗芬 | 12.86 |
该溶液可涂于足部趾甲，在6-12个月内每周一次，用于治疗甲癣。
实施例10：物理和化学稳定性
将本发明组合物置于各种温度下，进行随着时间流逝的物理评定(该组合物的颜色和物理结构)。
*RAS：该薄膜没有浑浊和破裂，没有发黄，也没有再结晶。
化学稳定性
在室温和40℃下，在时间为0和2个月时通过测定这种活性剂来评定所述活性剂的降解作用。
在进行的试验中稳定性检测结果表明，从颜色和物理结构来看，本发明组合物在所有试验温度下随着时间变化都是稳定的。
使用的活性剂没有显示出任何重结晶迹象，并且在所有温度下随着时间变化也都是稳定的。
实施例11：释放-渗透作用
方法
使用扩散池，更具体地Frantz(Pittrof F等人，《Clin.Exp.Dermatol.》17(suppll)：26-28，(1992))，在猪趾甲上进行活性剂释放-渗透作用的研究。
根据本发明，将活性剂加入指甲油中。
每天往1cm2趾甲表面积上涂敷10ul待试验指甲油(含有放射性同位素标记的活性剂)，连续涂3天。
然后，通过使用闪烁计数器测定其放射性来评定趾甲中的活性剂。
这个试验在6个池中并行地进行，参比指甲油作为对照。这种参比指甲油(参比)不含任何助渗透剂，它由55.20％乙醇、17.20％乙酸乙酯、5.70％乙酸丁酯、1.20％三乙酸甘油酯、14.30％Eudragit R1 100、6.40％盐酸阿莫罗芬组成。
对照指甲油仅含有一种助渗透剂，该助渗透剂是尿素或者乳酸或者乙氧基二甘醇。
结果
| 组合物 | 参照e | 对照1 | 对照2 | 对照3 | 实施例1 | 实施例4 |
| 乙醇乙酸乙酯乙酸丁酯 | 55.2017.205.70 | 44.4017.006.00 | 54.4017.006.00 | 54.4017.006.00 | 43.8517.006.00 | 43.1017.006.00 |
| 三乙酸甘油酯 | 1.20 | 1.20 | - | - | - | - |
| 乙氧基二甘醇尿素乳酸 | 5.00-- | -2.50- | --4.25 | -2.504.25 | 5.002.50- | |
| Eudragit R1 100Gantrez ES 425 | 14.30- | -20.00 | 10.00- | 10.00- | 20.00 | 20.00 |
| 盐酸阿莫罗芬 | 6.40 | 6.40 | 6.40 | 6.40 | 6.40 | 6.40 |
| 释放-渗透增加 | 1 | 1 | 1 | 1 | 3.06 | 2.16 |
与参比指甲油相比，本发明指甲油能明显提高活性剂渗透到指甲中(实施例4为2倍以上，实施例1为3倍以上)，而单独试验的各种助渗透剂(对照组合物)根本没有提高活性剂渗透到猪趾甲中(与参比指甲油相比，释放-渗透差异不明显)。
这些结果明确表明，本发明的尿素和乙氧基二甘醇，或尿素与酸，助渗透剂组合能以协同方式提高活性剂渗透到指甲中。
Claims (8)
1.用于涂指甲和甲周的成膜溶液，该溶液含有助渗透剂混合物，该助渗透剂混合物至少含有尿素和乙氧基二甘醇，其中，该成膜溶液还含有：
a)至少一种活性剂，
b)有机溶剂，
其中所述活性剂是抗真菌剂。
2.根据权利要求1的溶液，其特征在于其含有尿素、乳酸和乙氧基二甘醇。
3.根据权利要求1或2的溶液，其特征在于其是指甲油。
4.根据权利要求1或2的溶液，其中它还含有助溶剂。
5.根据权利要求1或2的溶液，其特征在于它还含有增塑剂。
6.根据权利要求1或2的溶液，其特征在于抗真菌剂选自阿莫罗芬或阿莫罗芬的一种盐。
7.根据权利要求1-6任一项的溶液在制备治疗真菌病药品中的用途。
8.根据权利要求7的用途，其中所述真菌病是甲癣。
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| Application Number | Priority Date | Filing Date | Title |
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| FR0211023 | 2002-09-05 | ||
| FR0211023A FR2844197B1 (fr) | 2002-09-05 | 2002-09-05 | Solution pour application ungueale et peri-ungeale |
| US41134902P | 2002-09-18 | 2002-09-18 | |
| US60/411349 | 2002-09-18 | ||
| US60/411,349 | 2002-09-18 |
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| CNB038212145A Division CN100542610C (zh) | 2002-09-05 | 2003-09-01 | 涂指甲及甲周的溶液及其在制备治疗真菌病药品中的用途 |
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| CN101632627A CN101632627A (zh) | 2010-01-27 |
| CN101632627B true CN101632627B (zh) | 2013-01-16 |
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| CN2009101641308A Expired - Fee Related CN101632627B (zh) | 2002-09-05 | 2003-09-01 | 涂指甲及甲周的溶液 |
| CNB038212145A Expired - Fee Related CN100542610C (zh) | 2002-09-05 | 2003-09-01 | 涂指甲及甲周的溶液及其在制备治疗真菌病药品中的用途 |
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| Country | Link |
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| CN (2) | CN101632627B (zh) |
| AR (1) | AR041146A1 (zh) |
| FR (1) | FR2844197B1 (zh) |
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| WO2007102241A1 (ja) * | 2006-03-08 | 2007-09-13 | Nihon Nohyaku Co., Ltd. | 外用の医薬組成物 |
| GB2478159A (en) * | 2010-02-26 | 2011-08-31 | Lrc Products | Composition for the treatment of fungal nail infection |
| FR2976808B1 (fr) * | 2011-06-22 | 2013-06-28 | Urgo Lab | Composition filmogene et son utilisation pour le traitement de l'herpes |
| CN105106179A (zh) * | 2015-08-28 | 2015-12-02 | 江苏福邦药业有限公司 | 一种盐酸阿莫罗芬搽剂的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US5891428A (en) * | 1995-08-04 | 1999-04-06 | Sederma S.A. | Physically active antimicrobial gel for cosmetic products |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| SE325667B (zh) * | 1968-03-06 | 1970-07-06 | Medisan Ab | |
| JPS58150509A (ja) * | 1982-03-03 | 1983-09-07 | Taisho Pharmaceut Co Ltd | 白癬症治療剤 |
| DE3210138A1 (de) * | 1982-03-19 | 1983-09-22 | Röhm Pharma GmbH, 6100 Darmstadt | Antimykotische, therapeutische zubereitungen auf creme- und salbenbasis |
| JPS60174716A (ja) * | 1984-02-21 | 1985-09-09 | Yamanouchi Pharmaceut Co Ltd | パツチ剤 |
| SE462139B (sv) * | 1986-02-04 | 1990-05-14 | Sven Moberg | Farmaceutisk komposition, innehaallande propylenglykol och karbamid, foer behandling av bl.a. nagelsvamp och seborroiskt eksem |
| FR2613227B1 (fr) * | 1987-04-01 | 1990-12-28 | Oreal | Compositions pharmaceutiques a base de nitrate de miconazole ou de nitrate d'econazole dans le traitement des infections fongiques des ongles |
| CN1032116C (zh) * | 1989-06-23 | 1996-06-26 | 铁汉 | 病甲剥脱剂的制造方法 |
| CN1063820A (zh) * | 1991-01-30 | 1992-08-26 | 樊芝芹 | 灰指甲溶解膏的制造方法 |
| FR2673537B1 (fr) * | 1991-03-08 | 1993-06-11 | Oreal | Utilisation d'agents de penetration hydrophiles dans les compositions dermatologiques pour le traitement des onychomycoses, et compositions correspondantes. |
| DE4137544C2 (de) * | 1991-11-12 | 1998-07-30 | Kramer Axel | Antimikrobielle Wirkstoffkombination auf der Basis von Sauerstoff abspaltenden Verbindungen |
| NL9401095A (nl) * | 1994-06-30 | 1996-02-01 | Drs Erwin Philip Balthazar Pli | Kosmetisch preparaat voor de verbetering van de eigenschappen van nagels, werkwijze voor het aanbrengen hiervan en toepassing hiervan. |
| US5696164A (en) * | 1994-12-22 | 1997-12-09 | Johnson & Johnson Consumer Products, Inc. | Antifungal treatment of nails |
| US6162419A (en) * | 1996-11-26 | 2000-12-19 | Nicholas V. Perricone | Stabilized ascorbyl compositions |
| US5993790A (en) * | 1997-08-04 | 1999-11-30 | Pedinol Pharmacal Inc. | Nail evulsion compositions and method for evulsing nails and treating nail and nail bed infections |
| US6740326B1 (en) * | 1998-09-10 | 2004-05-25 | Bioequal Ag | Topical nail care compositions |
| ATE320250T1 (de) * | 2000-01-03 | 2006-04-15 | Karl Kraemer | Zubereitungen zur atraumatischen nagelentfernung |
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2002
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5891428A (en) * | 1995-08-04 | 1999-04-06 | Sederma S.A. | Physically active antimicrobial gel for cosmetic products |
Non-Patent Citations (1)
| Title |
|---|
| 马道铭.新的吗啉类抗真菌药-阿莫罗芬.《国外医学皮肤性病学分册》.1994,第20卷(第5期), * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101632627A (zh) | 2010-01-27 |
| CN100542610C (zh) | 2009-09-23 |
| AR041146A1 (es) | 2005-05-04 |
| FR2844197B1 (fr) | 2006-06-23 |
| CN1703246A (zh) | 2005-11-30 |
| FR2844197A1 (fr) | 2004-03-12 |
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