CN102099002A - 指/趾甲外观的改善 - Google Patents
指/趾甲外观的改善 Download PDFInfo
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- CN102099002A CN102099002A CN2009801034553A CN200980103455A CN102099002A CN 102099002 A CN102099002 A CN 102099002A CN 2009801034553 A CN2009801034553 A CN 2009801034553A CN 200980103455 A CN200980103455 A CN 200980103455A CN 102099002 A CN102099002 A CN 102099002A
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Classifications
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- A—HUMAN NECESSITIES
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
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Abstract
本发明提供改善患者的指/趾甲外观的方法,其中将组合物局部施加至呈现至少一种选自由甲剥离、甲分裂或脆甲症所组成群组的病症的症状的患者指/趾甲上,且其中所述组合物含有至少两种生物相容性有机溶剂、极性脂质、表面活性剂、水、尿素和增稠剂,其中所述有机溶剂包含酯且提供二元和、或多元醇。
Description
技术领域
本揭示内容涉及用于改善指/趾甲外观的组合物。根据本揭示内容已发现,局部微乳液能够改善表现甲剥离、甲分裂或脆甲症和/或指/趾甲分裂症状的手指甲和脚趾甲的外观。
背景技术
甲剥离是皮肤科医生经常遇到的指/趾甲病况。甲剥离的特征在于甲板自远端游离缘开始自发性分离并向近端发展。甲板与下伏和/或侧面支撑结构分离甲板分离通常不始于近端指/趾甲且延伸至游离缘,此最常见于指/趾甲牛皮癣(称作脱甲病)中。很少有病例限定于指/趾甲外侧缘。
患有甲剥离的指甲通常是平滑坚硬且无炎性反应。其并非甲母质疾病,但在指/趾甲下面可能因继发感染而出现甲变色。在发生甲剥离时,会同时出现酵母感染。治疗使病症恶化的主要和次要因素具有重要意义。始终不治疗的甲剥离严重病例可导致指甲床结疤。
内源性、外源性、遗传性、和特发性因素可导致甲剥离。接触刺激物、创伤、和潮湿是最常见的甲剥离原因,但也存在其它关联。内源性因素源于全身性疾病和病症,例如:淀粉样蛋白和多发性骨髓瘤、贫血(缺铁)、支气管扩张症、糖尿病、红细胞生成性卟啉病、组织细胞增多症X、甲状腺功能亢进症、甲状腺功能减退症、缺血(外周循环损坏)、麻疯病、红斑狼疮、神经炎、糙皮病、寻常型天疱疮、胸腔积液、迟发性皮肤卟啉病、妊娠、牛皮癣关节炎、莱特尔综合症(Reiter syndrome)、结节病、硬皮病、贝壳甲综合症、梅毒、和黄甲综合症。其也可源于皮肤病,例如:牛皮癣、扁平苔藓、皮炎、多汗症、甲肥厚、先天性外胚层缺损、增殖型天疱疮、条纹状苔藓、特应性皮炎、和指/趾甲先天性畸形。
外源性因素包含微生物因素,例如皮肤癣菌病(即,红色毛癣菌(Trichophyton rubrum)、须毛癣菌(Trichophyton mentagrophytes)感染)、酵母(念珠菌属(Candida)感染)、细菌(假单胞菌属(Pseudomonas)感染)、或病毒(单纯疱疹感染)。
外源性因素也可归因于非微生物因素(此可在工作场所遇到,即,呈职业性甲剥离形式);且再分成机械因素(机械力(创伤)、重复性微创伤、或浸软)或化学因素(源于以下的过敏性接触性皮炎:各种指/趾甲美容品(甲基丙烯酸甲酯单体、1-2%甲醛、指/趾甲底油/硬化剂、用于人工指/趾甲中的聚合2-乙基氰基丙烯酸酯黏着剂、指/趾甲胶)、汽油、脱漆剂、双氰胺、巯基乙酸盐、溶剂、和显色剂中的硫酸羟胺;或源于以下的刺激性接触性皮炎:在水中延长浸渍指/趾甲、甜食制造者/面包师的糖性甲剥离、和暴露于高破坏性毒素(例如,氢氟酸)中)。
指/趾甲分裂在医学上称作甲分裂(若水平分裂)或称作脆甲症(若垂直分裂),其为导致甲板内发生分裂的病症。此两种病症也称作“脆指/趾甲综合症”。
发明内容
在测试含有抗真菌剂的调配物的临床试验中,已发现,媒剂调配物本身能够改善患者的甲剥离外观。此结果非常令人意外,因为业内还没有已知的局部疗法可有效治疗甲剥离。
业内也已使用与显示可治疗甲剥离的调配物相似的调配物来治疗已显示分裂的指/趾甲。在每一情形下,在每日于洗手后施加调配物并持续少至5天后,已改善指/趾甲分裂。
本揭示内容也涉及改善显示甲剥离、甲分裂或脆甲症的手指甲或脚趾甲外观的方法,其包括向人类或动物的指/趾甲局部施加某些组合物。
所述组合物包括一或多种生物相容性有机溶剂、极性脂质、至少一种表面活性剂、水、尿素和增稠剂。所述有机溶剂包括酯和/或二元和/或多元醇。所述组合物包括约2重量%至约30重量%的酯和约2重量%至约20重量%的二元和/或多元醇。
所属领域技术人员根据下列详细说明可容易地了解本揭示内容的其它目的和优点,其中仅通过简单地阐释实施本揭示内容所涵盖的最佳模式来展示并阐述优选实施例。应了解,本揭示内容能够具有其它实施例和不同实施例,并且可在各个重要方面对其多个细节进行改变并且不背离本揭示内容。因此,应将本说明视为阐释性而非限定性。
具体实施方式
本文所用的“局部投与”意指直接涂抹或涂敷于表皮组织、尤其手指甲和脚趾甲(包含所述指/趾甲周围的皮肤区域)上。
本文所用术语“包括”意指各种其它相容组份(例如惰性成份、闭塞剂、和美容媒剂)、美容品和/或药剂可联合用于本发明的组合物和方法中。因此,术语“包括”涵盖并且包含限制性更强的术语“由……组成”和“基本由……组成”,其描述以本文所揭示方式来使用基本成份的特征。
本文所用的“受影响位点”意指指/趾甲上不美观的局部区域和紧邻区域。
本文所用的“施加位点”意指适于通过机械释放装置或敷裹来施加的位点,例如指/趾甲远端、指/趾甲顶部、指/趾甲近端区域等。
本文所用的“基本不含”意指本发明组合物含有小于约10%、优选地小于3.5%、更优选地小于约1%、并且最优选地小于约0.5%的所述术语描述的任一特定化合物、或化合物群组的任一特定成员。
除非另有说明,否则本文所用的所有百分比和比率都是以组合物的总重量计。
此揭示内容中所用的组合物包括极性脂质(例如卵磷脂或磷脂酰胆碱)、和两种生物相容性有机溶剂(一种选自酯群组且另一种选自液体二元醇和多元醇群组)、表面活性剂、水、和尿素,其pH为约5至约8.5且优选地为约6至约7.5。此揭示内容的组合物可另外含有其它可减少皮肤刺激、或增加其美容吸引力或可接受性的可选组份,例如,润肤剂、颜料、日用香料(frangrance)、香料(perfume)、防腐剂和诸如此类。此揭示内容的组合物可含有或可不含有能够以此揭示内容的组合物作为载剂而产生或具有局部活性的美容剂和/或医药活性剂。
所用典型极性脂质为卵磷脂和磷脂酰胆碱。优选地,卵磷脂或磷脂酰胆碱是具有高质量的医药级。适宜卵磷脂和磷脂酰胆碱可以市售大豆卵磷脂或大豆磷脂酰胆碱形式获得。优选地,在此揭示内容的组合物中使用大豆卵磷脂。
生物相容性有机酯溶剂可为可溶解极性脂质和尿素的任一无毒酯。通常,所述酯是脂肪单酯,其结构可通过以下方式来获得:使用一元醇的烷基来代替具有4至22个碳原子并且更通常地具有8至18个碳原子的脂肪酸(特定实例具有12个碳原子)的活性氢。脂肪酸可为饱和或不饱和脂肪酸,且更通常为饱和脂肪酸。一元醇通常含有2至8个碳原子且更通常含有2至5个碳原子,特定实例具有3个碳原子。
用于此目的的可接受酯包含但不限于异丙酯。优选地,所述酯为肉豆蔻酸异丙酯或棕榈酸异丙酯,其中特别优选者为肉豆蔻酸异丙酯。
生物相容性有机二元和多元醇溶剂可为可溶解极性脂质和尿素的任一无毒二元醇或多元醇。用于此目的的可接受二元醇和多元醇包含但不限于二元和三元烷醇。通常,所述醇含有3至8个碳原子且更通常含有3至5个碳原子,并且是饱和醇。优选地,多元醇为丙二醇或甘油,其中特别优选者是丙二醇。
本揭示内容的组合物通常含有约2重量%至30重量%且更通常4重量%至10重量%的酯和约2重量%至约20重量%且更通常2重量%至约10重量%的二元/多元醇。
在制备此揭示内容的组合物时,极性脂质通常以约5∶1∶1至约1∶5∶5的质量比率溶于有机酯溶剂和二元或多元醇溶剂中。优选地,极性脂质与有机酯溶剂和多元醇溶剂是以等质量比率进行混合。因此,在本揭示内容的一实施例中,以等质量比率混合大豆卵磷脂、肉豆蔻酸异丙酯、和丙二醇并且混合至卵磷脂均匀分布为止。此称作溶剂-极性脂质混合物。
调配物中通常以占最终组合物质量约0.5%至约20%的浓度包含表面活性剂。在包含聚阳离子活性剂的调配物中,根据此揭示内容已发现,优选者为非离子性或阳离子性表面活性剂。另一方面,在其它活性成份或没有活性成份的情形下,完全可接受阴离子性、阳离子性或非离子性表面活性剂。优选地,表面活性剂是适合活体内投与并且不会引起不期望副作用者。一种优选表面活性剂为多库酯钠和其水溶性更高的形式-多库酯钠苯甲酸盐(docusate sodium benzoat)。其它适宜离子性或非离子性表面活性剂为(例如)聚山梨醇酯80、Tween 80、泊洛沙姆(poloxamer)、布洛芬(ibuprofen)、多库酯钙、十四烷基三甲基溴化铵、五氧基乙二醇单十二烷基醚、或三乙醇胺月桂醇聚醚硫酸酯。一旦表面活性剂完全分散于溶剂-极性脂质混合物中,若需要可立即添加并溶解美容或医药活性化合物。所述活性化合物的实例包含抗增殖/消炎化合物,其可改善导致手指甲和脚趾甲外观不美观的其它促进因素或减少组合物的反应时间。然而,此揭示内容的组合物并不需要所述活性剂且优选地不含所述活性剂。
添加美容或医药活性化合物(若使用)后,可将一定量尿素(优选地呈增稠水溶液形式)添加至表面活性剂-溶剂-极性脂质混合物中。通常,所添加尿素可使尿素浓度占最终组合物质量的约1质量%至约20质量%、更通常约1质量%至约15质量%、且甚至更通常约5质量%至10质量%。
增稠剂是选自常用的国家处方集(National formulary)增稠剂,包含但不限于具有适宜聚合物分子量的聚乙二醇、聚乙烯吡咯烷酮、卡波姆(carbomer)、藻酸盐、树胶和甲基纤维素。增稠剂的量通常为约0.01重量%至约5重量%且更通常约0.05重量%至约5重量%。
因此,在一具体实例中,将约5克10%的尿素水溶液(含有0.9%卡波姆974P)添加至约100克表面活性剂-溶剂-极性脂质混合物中。在任一情形下,所属领域技术人员在了解本揭示内容后都可根据所制备特定调配物容易地作出此选择。
调配上述组合物后,通常将pH调节至pH为约5至约8.5并且更通常为6至7.5。在组合物最初倾向于具有酸性pH时,此可通过(例如)添加氢氧化钠水溶液来达成。然而,若医药活性剂倾向于产生强碱性溶液,则期望添加酸来降低pH。此可通过添加柠檬酸或诸如碳酸钠或磷酸钾等生物缓冲液来达成。在组合物的pH介于约5.5至7.5之间时,调配物变稠并形成用于局部投与的稳定微乳液。
所属领域技术人员在了解本揭示内容后将能通过常规实验使用此组合物的所述要素来制备特定凝胶,所述凝胶也可包含用于各种消炎或抗微生物应用的活性成份或其组合。此外,应理解,所述组合物可含有辅助剂,包含业内通常已知和/或常用者,例如但不限于防腐剂和日用香料。
为便于制备,可便捷地制备第一凝胶组合物(在本文中称作“MQX-凝胶”),其可用于添加至局部投与用最终组合物的调配物中的其它组份中。可能存在若干种MQX-凝胶调配物。例如,可通过以下方式来制备MQX-凝胶:混合卵磷脂有机凝胶(L.O.)(卵磷脂、肉豆蔻酸异丙酯与丙二醇的1∶1∶1(m/m/m)混合物)与LID油(L.O.与多库酯钠的1∶1[m/m]混合物),将其它表面活性剂和/或多库酯钠粉末溶于此混合物中,且然后添加增稠尿素水溶液。
在MQX-凝胶调配物的一实施例中,最终浓度为:L.O.=30%;多库酯钠=9%;尿素=5%;增稠剂=1%;且水=55%。这些比率可容易地改变以使每一组份的最终量如下:L.O.=15-50%;多库酯钠和/或另一表面活性剂=3-20%;尿素=1-15%;增稠剂=0.5-5%;且水=40-65%。然后可将溶解的活性成份添加至MQX-凝胶中。可用于溶解活性成份的赋形剂(若使用)包含L.O.、丙二醇、肉豆蔻酸异丙酯、柠檬烯、薄荷油、甘油、和/或聚乙二醇。然后通过仔细掺和各种组份来制备均匀混合物。
制得上述调配物后,可如下所述简单地使用调配物:将调配物施加至受影响区域,其中期望经皮递送。因此,在甲裂的情形下,将上述调配物擦抹于手指或脚趾的受影响指/趾甲区域上。在使用根据本发明制得的调配物时,可在五日内通过每日施用恢复成未分裂指/趾甲的正常外观。在症状再次出现时重复进行治疗。
同样,在甲剥离的情形下,将上述调配物擦抹于手指或脚趾的受影响指/趾甲区域上。在使用根据本发明制得的调配物时,可在四个月内通过每日施用恢复指/趾甲的正常外观。在症状再次出现时重复进行治疗。
预计只要不出现局部反应问题,即可按照需要频繁地局部施加本发明组合物。
尽管前文中的说明概述了如何实施本揭示内容,但仍提供下列实例来更具体地指出如何实践本发明。然而,应清楚地理解,由本文随附权利要求书所界定的本发明范围并不限于下列实例的细节。另外,应理解,在所阐述和所主张的具体组合物中,即便各成份的百分比数量相差至少10%也仍可达成与明确揭示的组合物等效的目的。
通常,调配物具有下列成份范围:
调配物范围----------------------> | 低 | 高 |
纯化水,USP | 30 | 65 |
尿素,USP | 1 | 20 |
增稠剂(下列实例) | 0.01 | 5 |
卡波普(Carbopol)974P,NF | 0.01 | 5 |
甲基纤维素(各种等级) | 0.01 | 5 |
聚乙二醇 | 0.01 | 5 |
聚维酮(Povidone) | 0.01 | 5 |
异丙酯 | 2 | 30 |
肉豆蔻酸异丙酯,NF | 2 | 30 |
多元醇 | 0.5 | 20 |
丙二醇,USP | 0.5 | 20 |
极性脂质 | 5 | 30 |
卵磷脂,NF | 5 | 30 |
表面活性剂 | 0.5 | 20 |
多库酯钠 | 0.5 | 20 |
聚山梨醇酯80,NF | 0.5 | 20 |
使用下列物质将pH调节至: | 5 | 8.5 |
氢氧化钠,NF(1N) | 0 | QS |
三乙醇胺,NF | 0 | QS |
所测试的具体调配物为:
调配物----------------------> | A | B |
纯化水,USP | 60.4 | 60.4 |
尿素,USP | 10 | 10 |
·卡波普934,NF | 0.05 | 0.00 |
·卡波普974P,NF | 0.00 | 0.05 |
三乙醇胺,NF | 0.07 | 0.07 |
肉豆蔻酸异丙酯,NF | 6.53 | 6.53 |
甲基纤维素,USP | 0 | 0 |
卵磷脂,NF | 7.31 | 7.31 |
多库酯钠,USP | 14.36 | 14.36 |
丙二醇,USP | 0.98 | 0.98 |
聚山梨醇酯80,NF | 0.3 | 0.3 |
氢氧化钠,NF(1N) | 0 | 0 |
100 | 100 |
已研究的其它调配物为:
调配物----------------------> | C | D |
纯化水,USP | 50.68 | 50.68 |
尿素,USP | 10 | 10 |
·卡波普934,NF | 0 | 0 |
卡波普974P,NF | 0.07 | 0.05 |
三乙醇胺,NF | 0.06 | 0.06 |
肉豆蔻酸异丙酯,NF | 8.7 | 8.7 |
甲基纤维素,USP | 0.03 | 0.03 |
卵磷脂,NF | 9.75 | 9.75 |
多库酯钠,USP | 19.14 | 19.14 |
丙二醇,USP | 9 | 12 |
聚山梨醇酯80,NF | 0.4 | 0.4 |
氢氧化钠,NF(1N) | 0.48 | 0.48 |
100 | 100 |
调配物----------------------> | E | F |
纯化水,USP | 62.25 | 48.4 |
尿素,USP | 10 | 10.68 |
·卡波普934,NF | 0 | 0 |
卡波普974P,NF | 0.05 | 0.07 |
三乙醇胺,NF | 0.07 | 0.07 |
肉豆蔻酸异丙酯,NF | 6.09 | 8.7 |
甲基纤维素,USP | 0.05 | 0.05 |
卵磷脂,UP | 6.83 | 9.75 |
多库酯钠,USP | 13.4 | 19.14 |
丙二醇,USF | 0.98 | 0.98 |
聚山梨醇酯80,NF | 0.28 | 0.4 |
氢氧化钠,NF(1N) | 0.3 | 0 |
100 | 100 |
提供下列非限制性实例以进一步阐释本揭示内容:
实例1--MQX-凝胶的制备
*LID油为卵磷脂有机凝胶∶多库酯钠的1∶1混合物(以质量计)。
**L.O.为卵磷脂、肉豆蔻酸异丙酯与丙二醇的1∶1∶1混合物。
1.将LID添加至L.O.中并加热。
2.添加多库酯钠粉末,且搅拌混合物直至均匀。
3.将增稠剂和尿素完全溶于水中,加热,并在搅拌下添加至步骤2的混合物中。
4.将pH调节至介于6.5至6.9之间。
可如下所述容易地制备MOX-凝胶:
加热L.O.且在搅拌下将多库酯钠苯甲酸盐粉末添加至加热L.O.中直至制得均匀溶液。加热水并将增稠剂和尿素溶于水中,且然后将增稠尿素溶液与含有多库酯钠的L.O.溶液充分混合。结果得到pH为约6.0的均匀透明琥珀色凝胶。
制备MQX-凝胶的另一方法如下:
将LID和L.O.充分混合且制备水、增稠剂和尿素的加热溶液并将所述溶液添加至LID-L.O.溶液中。结果得到pH为约6.0的均匀透明琥珀色凝胶。
使用与实例2中所述相同的组合各成份的方法。
也可以其它比率使用卵磷脂有机凝胶的三种成份来制备MQX-凝胶。在下列实例中,卵磷脂有机凝胶(2号L.O.)的比率为卵磷脂、肉豆蔻酸异丙酯和丙二醇的1∶0.9∶0.1(m/m/m)混合物,并且LID油为2号L.O.和多库酯钠的1∶1[m/m]混合物,将其它表面活性剂和/或多库酯钠粉末溶于此混合物中,且然后添加增稠尿素水溶液。
在MQX-凝胶调配物的此实施例中,最终浓度为:2号L.O.=25%;多库酯钠=10%;尿素=10%;增稠剂=1%;且水=54%。这些比率也可容易地改变以使每一组份的最终量如下:2号L.O.=15-50%;多库酯钠和/或另一表面活性剂=3-15%;尿素=1-15%;增稠剂=0.5-5%;且水=40-65%。若需要,然后可向MQX-凝胶中添加溶解的活性成份。可用于溶解活性成份的赋形剂(若使用)包含2号L.O.、丙二醇、肉豆蔻酸异丙酯、薄荷油、甘油、和/或聚乙二醇。然后通过仔细地掺和各种组份来制备均匀混合物。
实例3-另一MOX-凝胶的制备
使用与实例2中所述相同的组合各成份的方法。
实例4-另一MQX-凝胶的制备
在此实例中使用与前一实例相同的制备方法。
实例5-另一MOX-凝胶的制备
1.将丙二醇添加至2号L.O.中并搅拌以获得澄清溶液。
2.将多库酯钠添加至来自步骤1的溶液中并搅拌以获得澄清溶液。
3.将尿素添加至蒸馏水中,同时加热并搅拌以获得均匀溶液。
4.添加卡波姆974P和甲基纤维素以使步骤3的尿素-水变稠。
5.合并来自步骤2的溶液与来自步骤4的增稠尿素水溶液以形成均匀混合物。
6.使用稀NaOH水溶液将pH调节至6.5以形成精细的粘稠微乳液。
上述说明阐释并阐述了本揭示内容。此外,本揭示内容仅展示和阐述本揭示内容的优选实施例,但如上所述,应理解,能够在本文所表达的概念范围中作出与上述教示内容和/或相关领域的技术或知识一致的改变和修改。上述实施例另外意欲阐释实践本发明的已知最佳模式,并且意欲使其它所属领域技术人员能够利用所述实施例或其它实施例中的揭示内容,并且根据本文所揭示的特定应用或用途的需要做出各种修改。因此,本说明并非意欲将本发明限于本文所揭示的形式。另外,随附权利要求书意欲理解为包含替代实施例。
本说明书中引用的所有公开案、专利和专利申请案都以引用方式并入本文中,且出于任何和所有目的,其并入程度如同明确地和单独地指出将每一个别公开案、专利和专利申请案以引用方式并入一般。如果出现不一致的情形,以本揭示内容为准。
Claims (14)
1.一种改善患有甲剥离的患者的指/趾甲外观的方法,其包括向呈现至少一种选自由甲剥离、甲分裂或脆甲症所组成群组的病症的症状的所述患者指/趾甲局部施加组合物,所述组合物包括两种生物相容性有机溶剂、极性脂质、至少一种或多种表面活性剂、水、尿素和增稠剂;其中所述有机溶剂包括酯和二元醇和/或多元醇;且其中所述组合物包括约2%至约30%的所述酯和约0.5%至约20%的所述二元醇和/或多元醇。
2.如权利要求1所述的方法,其中所述酯为脂肪单酯。
3.如权利要求2所述的方法,其中所述酯可通过使用具有2个至约8个碳原子的一元醇的烷基代替具有4至22个碳原子的脂肪酸的活性氢来获得。
4.如权利要求2所述的方法,其中所述酯为异丙酯。
5.如权利要求1所述的方法,其中所述酯为肉豆蔻酸异丙酯或棕榈酸异丙酯中的至少一者。
6.如权利要求1所述的方法,其中所述酯为肉豆蔻酸异丙酯。
7.如权利要求1所述的方法,其中所述二元或多元醇为烷醇且含有3至8个碳原子。
8.如权利要求1至6中任一权利要求所述的方法,其中所述醇为丙二醇或甘油中的至少一者。
9.如权利要求1至6中任一权利要求所述的方法,其中所述醇为丙二醇。
10.如权利要求1所述的方法,其中所述极性脂质为卵磷脂或磷脂酰胆碱中的至少一者。
11.如权利要求1所述的方法,其中至少一种表面活性剂是选自由以下组成的群组:多库酯钠、多库酯钠苯甲酸盐(docusate sodium benzoate)、多库酯钙、泊洛沙姆(poloxamer)、布洛芬(ibuprofen)、十四烷基三甲基溴化铵、五氧基乙二醇单十二烷基醚、和三乙醇胺月桂醇聚醚硫酸酯。
12.如权利要求2所述的方法,其中所述增稠剂是选自聚乙二醇、甲基纤维素、和卡波姆(carbomer)的群组。
13.如权利要求1所述的方法,其中所述极性脂质的量为约5重量%至约30重量%;所述表面活性剂的量为约0.5重量%至约20重量%,水的量为约30重量%至约65重量%,且所述增稠剂的量为约0.01重量%至约5重量%。
14.如权利要求1所述的方法,其中尿素的量为约5重量%至约10重量%;所述表面活性剂的量为约0.5重量%至约20重量%,水的量为约35重量%至约65重量%,且所述增稠剂的量为约0.05重量%至约5重量%。
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US7740875B2 (en) * | 2004-10-08 | 2010-06-22 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
US20130045503A1 (en) * | 2010-03-12 | 2013-02-21 | Riken | Clearing reagent for biological material, and use thereof |
WO2012147965A1 (ja) * | 2011-04-28 | 2012-11-01 | 独立行政法人理化学研究所 | 生物材料を透明化する方法、及びその利用 |
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JP6433901B2 (ja) | 2013-08-14 | 2018-12-05 | 国立研究開発法人理化学研究所 | 光透過性に優れた生物材料を調製するための組成物およびその利用 |
US10058159B2 (en) * | 2016-12-01 | 2018-08-28 | Richard L. Kronenthal | Sterile compositions for human cosmetic products |
EP3603650A1 (fr) | 2018-08-01 | 2020-02-05 | Edix O Sarl | Compositions injectables et a duree d'action prolongee pour leur utilisation dans le traitement de maladies de l'ongle et/ou pour accelerer la croissance de l'ongle |
WO2020025683A1 (fr) | 2018-08-01 | 2020-02-06 | Edix-O Sarl | Compositions injectables a duree d'action prolongee pour leur utilisation dans le traitement de maladie de l'ongle et/ou pour accelerer la croissance de l'ongle |
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US3646049A (en) * | 1970-03-05 | 1972-02-29 | Merck & Co Inc | Acylaminobenzimidazole derivatives |
US5861142A (en) * | 1996-03-25 | 1999-01-19 | Schick; Mary Pichler | Method for promoting hair, nail, and skin keratinization |
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US6585963B1 (en) * | 2001-02-15 | 2003-07-01 | Watson Pharmaceuticals, Inc. | Nail compositions and methods of administering same |
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US6908941B2 (en) * | 2002-06-06 | 2005-06-21 | Nicholas V. Perricone | Hair and nail treatments using alkanolamines |
US20070014743A1 (en) * | 2002-09-27 | 2007-01-18 | Birnbaum Jay E | Subunguicide, and method for treating onychomycosis |
US7740875B2 (en) * | 2004-10-08 | 2010-06-22 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
US20060078580A1 (en) * | 2004-10-08 | 2006-04-13 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
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Application publication date: 20110615 |