CN1085523C - 表皮用制剂和其制备方法 - Google Patents

表皮用制剂和其制备方法 Download PDF

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CN1085523C
CN1085523C CN94106507A CN94106507A CN1085523C CN 1085523 C CN1085523 C CN 1085523C CN 94106507 A CN94106507 A CN 94106507A CN 94106507 A CN94106507 A CN 94106507A CN 1085523 C CN1085523 C CN 1085523C
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井垣孝久
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Abstract

本发明提供了一种表皮用制剂及其制备方法，该制剂包含曲酸和/或其衍生物，和一种或多种HLB值调至12或更小的表面活性剂。该制剂优选为O/W乳剂或W/O乳剂，后一种优选采用凝胶乳化方法形成。表面活性剂的作用是抑制曲酸和/或其衍生物的色变或分解，并改善制剂在使用时的感觉。

Description

表皮用制剂和其制备方法
本发明涉及一种包含曲酸和/或其衍生物的表皮用制剂及其制备方法。随着时间变化，该制剂中的曲酸和/或其衍生物是稳定的，将该制剂施加到皮肤上时感觉令人愉快。更具体地说，本发明涉及一种表皮用制剂和其制备方法，该制剂包含有曲酸和/或其衍生物，还包含一种具有特定HLB值的表面活性剂。表面活性剂的作用是抑制曲酸和/或其衍生物的色变或分解，并改善制剂在使用时的感觉。
表皮制剂的形式通常有两种：O/W乳剂(水包油)和W/O乳剂(油包水)，它们的水与油的比例不同且物理性能有异，但是，借助于表面活性剂，可以稳定地乳化和分散油相或水相，从而两种制剂均为均匀的制剂。
O/W乳剂和W/O乳剂在施用感觉上及物理性能上差异很大。也就是说，O/W乳剂非常适于皮肤，不发粘，从而带来良好的施用感觉，但会损坏水溶性成分的稳定性。因此，O/W乳剂存在设计制剂形式的问题。
另一方面，W/O乳剂保护皮肤性能优良，并能确保成分的持久效能，但它不适于皮肤，并且更粘一些。而就物理性能而言，在较低或较高的温度下，W/O乳剂易于发生油相分离，因而难于获得乳剂稳定性。因此，就需要大量的表面活性剂或稳定助剂，这又会引起皮肤的安全问题。
对曲酸和其衍生物本发明人进行过长期的研究，它们是公知的具有各种优异性能的有用试剂，如下文献均有报导：日本未审专利公开号S55-157509，日本审查专利公开号S56-18569，S58-22151，S58-22152，S58-34446，S60-7961，S60-9722和S60-10005，日本未审专利公开号S60-137253，日本审查专利公开号S61-10447和S61-60801，日本未审专利公开号S62-5909，日本审查专利公开号S62-3820和S63-27322，日本未审专利公开号H1-132502和日本审查专利公开号H5-30422。
但是，曲酸和其衍生物(以下有时仅称之为曲酸)也是公知的自身稳定性较差的试剂。特别是，当曲酸被掺入上述O/W乳剂或W/O乳剂中时，需要相当复杂的技术来设计一种适宜的配方。因此，对于配制含曲酸的制剂来说，一个紧迫的任务是发展以下一种技术：该技术可使含曲酸的制剂具有足够的稳定性以耐受严重的分布机制，且当将其于皮肤上时不会有令人不快的感觉。
在O/W乳剂中含有曲酸且它们溶于外层水相中时，这些制剂被置于可能暴露于紫外线的条件至变化程度，紫外线可能是其变色或分解的外部原因。因此，可推断出应混合一种适量的紫外线吸收剂来抑制由紫外线辐射造成的损害。
例如，以下文献给出了相应的实例，日本未审专利公开号S62-108804和S64-83008，日本审查专利公开号H4-46924。
然而，曲酸变色不仅是因其受到紫外线的照射，而且还因其受热等原因。因此，上述技术仍然不是非常足够的，故而一直试图使用其它的稳定剂。例如下述文献给出了这些技术的实例，日本审查专利公开号S63-24968和H2-27963，日本未审专利公开号H3-101609，H3-188011，H3-193712。
在将曲酸掺入W/O乳剂中时，曲酸是溶解在内层的水相中的，因而与O/W乳剂相比，因紫外线照射造成曲酸的色变或分解情形发生的可能要小许多。但是，在某些情形下，随着时间变化，曲酸会与基质成分相互作用而发生变化。为了抑制这种变化，业已采用了多种特殊添加剂，如日本未审专利公开号H2-28105所述。
上述现有技术的效能有限，并没有完全解决该问题。
由于两种乳剂均存在如下问题：随时间变化曲酸变色或分解至某种程度；不能提供各种可供选择的施用感觉，因此一直希望能提供一种制剂，它的配方中不含大量的各种稳定剂，能使曲酸稳定以及易于提供理想的施加感觉。
因而，本发明的一个目的就是提供一种表皮用制剂，该制剂能解决传统的O/W或W/O乳剂型制剂存在的上述问题，即该制剂不会发生因时间变化曲酸或其衍生物的色变或分解。
本发明的其它目的，特征及优点通过以下对本发明优选实施方式的详细描述将充分展现出来。
为了解决上述问题，本发明人经过广泛的研究后发现，在O/W或W/O乳剂中必要的表面活性剂是破坏曲酸稳定的原因之一。通过不断的研究后发现，表面活性剂的HLB值与曲酸的稳定剂之间存在某种关系，具有特定HLB值的表面活性剂可以解决上述问题，从而完成了本发明的内容。
本发明提供了一种表皮用制剂，它包含有曲酸和/或其衍生物，还包含一种HLB值调至12或更低的表面活性剂。这种制剂几乎不存在曲酸和/或其衍生物随时间变化而发生的色变或分解，并且提供令人愉快的施用感觉。
图1为45℃下色变(ΔE)随时间变化的示意图，试样为PH4.5，含1％曲酸的洗剂，图中给出了名种不同HLB值的表面活性剂的情形。
图2为45℃下色变(ΔE)随时间变化的示意图，试样为PH4.5，含1％曲酸的洗剂，图中给出了不同HLB值的表面活性剂的情形。
图3为色变(ΔE)随时间变化的示意图，试样为PH4.5，含1％曲酸的乳油。
本发明所采用的曲酸(5-羟基-2-羧甲基-γ-吡酮)为第一种成分，它可为5-羟基-2-羟甲基-γ-吡酮的纯产物，包含曲酸作主要成分且通过培养已知的能产生曲酸的细菌菌株而得到的发酵液，发酵液的浓缩液，由发酵液中提取曲酸并使提取物结晶获得的产物，等等。
曲酸衍生物可单独使用，或者两种或多种组合使用，曲酸衍生物公开于例如以下的文献中：日本审查专利公开号S60-10005，H1-45472和H3-74229，曲酸和其衍生物的酯化产物公开于例如以下的文献中：日本审查专利公开号S58-22151和S58-22152，上述酯化产物中，糖被键合到曲酸2-位的-CH2OH基团上。
曲酸和/或其衍生物在制剂中的掺入量为0.001～10％(wt)，优选0.1～5％(wt)，以外用制剂总量计。
HLB(亲水-采油平衡)值代表构成非离子表面活性剂的亲水基团与亲油基团强度间的平衡程度，该值可通过实验测定。以表面活性剂的结构为基础可以近似计算HLB值，已知的这些计算式为Griff-in公式和Kawakami公式。通常，HLB值可被看作特定配方的设计参考，必须通过实验测定亲水性和亲油性间的最佳平衡。在本发明中，HLB值即用作曲酸色变的参考，也是设计稳定配方的参考。
本发明中，术语“优选HLB值调至12或更小的表面活性剂”是指HLB值为12或更小的一种或多种表面活性剂。任何非离子表面活性剂可以单独使用或以两种或多种组合使用。此外，其它类型的表面活性剂如阴离子表面活性剂、阳离子表面活性剂和两性表面活性剂也可以组合使用。
进而，HLB值大于12的非离子表面活性剂也可与HLB值为12或更小的表面活性剂组合使用，以使整个表面活性剂化合物的HLB值为12或更小。
此外，HLB值为HLBA含量为X％的乳剂A与HLB值为HLBB含量为(100-X)％的乳剂B的混合物，其HLB值即HLBAB可以按照下式近似计算其算术平均值：HLBAB＝HLBA X/100+HLBB(100-X)/100，上式已为许多实验证实。
作为本发明所采用的表面活性剂其HLB值为12或更小，特别优选的是HLB值较低的非离子表面活性剂。以下给出这些表面活性剂的实例和HLB值(括号内)：脱水山梨醇脂肪酸酯，如脱水山梨醇单月桂酸酯〔8.6〕，脱水山梨醇单棕榈酸酯〔6.7〕，脱水山梨醇单硬脂酸酯〔4.7〕，脱水山梨醇倍半油酸酯〔4.2〕，脱水山梨醇三硬脂酸酯〔2.1〕，脱水山梨醇单油酸酯〔4.3〕，脱水山梨醇倍半油酸酯〔3.7〕，脱水山梨醇三油酸酯〔1.7〕，脱水山梨醇单异硬脂酸酯〔5.0〕，脱水山梨醇倍半异硬脂酸酯〔4.5〕；甘油脂肪酸酯，如甘油单肉豆蔻酸酯〔3.5〕，甘油单硬脂酸酯〔4.5〕，可自乳化甘油单硬脂酸酯〔6.0〕，甘油单油酸酯〔2.5〕，甘油单异硬脂酸酯〔4.0〕；聚甘油脂肪酸酯，如：二甘油单硬脂酸酯〔5.0〕，二甘油单油酸酯〔5.5〕，二甘油二油酸酯〔7.0〕，二甘油单异硬脂酸酯〔5.5 〕，四甘油单硬脂酸酯〔6.0〕，四甘油单油酸酯〔6.0〕，六甘油单硬脂酸酯〔9.0〕，六甘油单油酸酯〔9.0〕，六甘油三硬脂酸酯〔2.5〕，十甘油三硬脂酸酯〔7.5〕，十甘油三油酸酯〔7.0〕，十甘油三异硬脂酸酯〔7.0〕，十甘油五硬脂酸酯〔3.5〕，十甘油三异硬脂酸酯〔7.0〕，十甘油五硬脂酸酯〔3.5〕，十甘油五油酸酯〔3.5〕，十甘油五异硬脂酸酯〔3.5〕；聚氧乙烯山梨醇脂肪酸酯，如：聚氧乙烯(6)山梨醇六硬脂酸酯〔3.0〕，聚氧乙烯(6)山梨醇四油酸酯〔8.5〕；聚乙二醇脂肪酸酯，如：聚乙二醇(1EO)单硬脂酸酯〔2.0〕，聚乙二醇(2EO)单硬脂酸酯〔4.0〕，聚乙二醇(4EO)单硬脂酸酯〔6.5〕，聚乙二醇(2EO)单油酸酯〔4.5〕，聚乙二醇(6EO)单油酸酯〔8.5〕，乙二醇单硬脂酸酯〔3.5〕，二乙二醇硬脂酸酯〔4.5〕，聚乙二醇二硬脂酸酯〔8.5〕；聚氧乙烯烷基醚，如：聚氧乙烯(2)鲸蜡基醚〔8.0〕，聚氧乙烯(2)硬脂酰醚〔8.0〕，聚氧乙烯(4)硬脂酰醚〔9.0〕，聚氧乙烯(2)油基醚〔7.5〕，聚氧乙烯(5)山萮醚〔7.0〕；聚氧乙烯烷基苯基醚，如聚氧乙烯(2)壬基苯基醚〔4.5〕，聚氧乙烯(3)辛基苯基醚〔6.0〕；聚氧乙烯蓖麻油硬化蓖麻油，如聚氧乙烯(3)蓖麻油〔3.0〕，聚氧乙烯(10)蓖麻油〔6.5〕，聚氧乙烯(5)硬化蓖麻油〔6.0〕，聚氧乙烯(10)硬化蓖麻油〔6.5〕；聚氧乙烯蜂蜡衍生物，如聚氧乙烯(6)山梨醇蜂蜡〔7.5〕，聚氧乙烯(20)山梨醇蜂蜡〔9.5〕；聚氧乙烯烷基醚磷酸酯，如二聚氧乙烯(2)烷基醚磷酸酯〔6.5〕，三聚氧乙烯(2)烷基醚磷酸酯〔7.0〕，三聚氧乙烯(6)烷基醚磷酸酯〔8.0〕，二聚氧乙烯(4)壬基苯基醚磷酸酯〔5.5〕；丙二醇脂肪酸酯，如丙二醇单硬脂酸酯〔3.5〕，可自乳化丙二醇单硬脂酸酯〔4.0〕；聚氧乙烯聚氧丙烯二醇醚，如：Poloxamer331〔4.5〕，Poloxamer 401〔5.0〕，Poloxamer 181〔5.8〕，Poloxamer 182〔6.2〕， Poloxamer 101〔7.0〕，Poloxamer 333〔9.0〕；蔗糖脂肪酸酯，如：蔗糖硬脂酸酯〔高至1.0，1.0，2.0，3.0，5.0，7.0，9.0〕，蔗糖棕榈酸酯〔高至1.0，约1.0〕，蔗糖油酸酯〔约1.0，2.0〕，和蔗糖月桂酸酯〔约1.0，5.0〕。优选使用上述表面活性剂，但并不仅限于这些。
HLB值大于12的表面活性剂可以为：聚甘油脂肪酸酯，聚氧乙烯脱水山梨醇脂肪酸酯，聚氧乙烯山梨醇脂肪酸酯，聚乙二醇脂肪酸酯，聚氧乙烯蓖麻油，聚氧乙烯硬化蓖麻油，聚氧乙烯烷基醚，聚氧乙烯植物甾醇，polyoxyethylene phytostanols，聚氧乙烯聚氧丙烯烷基醚，聚氧乙烯烷基苯基醚，聚氧乙烯羊毛脂，聚氧乙烯羊毛脂醇，聚氧乙烯蜂蜡衍生物，聚氧乙烯烷基胺，聚氧乙烯脂肪酸酰胺，聚氧乙烯聚氧丙烯二醇醚，蔗糖脂肪酸酯，聚氧乙烯烷基醚磷酸酯和其盐。
这些表面活性剂的用量根据其种类不同而变化，但一般说来，其用量为5～50％(wt)，优选10～20％(wt)，以制剂中油相总量计。
采用本发明的技术按已知方法制得的表皮用制剂可使人们获得优良的使用感觉，而曲酸和/或其衍生物的稳定性不会破坏。
O/W乳剂基本上能在施加至皮肤上带来良好的感觉。采用增稠剂或润湿剂，O/W乳剂可使人们易于得到理想的施用感觉，使用它们的条件是要保证曲酸或其衍生物能随时间变化保持稳定。
由于W/O乳剂具有粘着性，因而其施用感觉要比O/W乳剂要差，但可改进W/O乳剂以去除这一缺陷。可以使用小量的油相成分按近来发展的乳化技术制备W/O乳剂。典型的方法为凝胶乳化法。令人惊异的是，业已发现，由凝胶乳化法制备的乳剂其施用感觉得到改善，掺入乳剂中的曲酸或其衍生物的稳定性得到了增强。凝胶乳化法包括：将多元醇(如1，3-丁二醇、甘油等)或糖(如山梨醇、麦芽糖醇等)或氨基酸(或其盐)的水溶液与具有特定化学结构的亲油表面活性剂混合以生产一种凝胶，其中，表面活性剂形成外层相，多元醇、糖或氨基酸(或其盐)的水溶液形成内层相。当该凝胶分散在油相中时，随之向其中加入水相，从而得到一种含水量可在很大范围内的相当稳定的W/O乳剂。
当然，所获得的含曲酸的W/O制剂具有与一般W/O乳剂相同的特征。即，当将该乳剂施加至皮肤上时，包含在乳剂中的有效成分不会立刻吸收，而是在一段确定的时间内不断地吸收，这是与O/W制剂不同的。
进而，本发明相应于O/W乳剂和W/O乳剂的上述技术也可用于多层乳剂，如W/O/W乳剂，和O/W/O乳剂，从而增强乳剂中曲酸和/或其衍生物的稳定性。此外，本发明也可用作微生物制剂的基本技术。
本发明的表皮用制剂并不特别限制其使用方式，它可以以已知的药物、准药物和化妆品的使用方式使用，如泥敷剂、糊剂、膏剂、霜剂、软膏剂、气雾剂、乳剂、洗剂、油剂(essence)、润肤膏、胶凝剂、粉剂、粉底(foundation)、防晒剂(suncare)、浴盐(bathsalts)等。
在本发明的制剂制备过程中，各种已知的常用有效成分也可选择性地加入，但要求其量不会损坏本发明的目的。这些已知的有效成分的实例包括：毛细血管扩张剂，如氯化三甲胺丁酸甲酯、顶花防己碱、维生素E、烟酸维生素E、烟酸、烟酸酰胺、烟酸苯甲酯、姜酊和辣椒酊(ginger tincture，chill tincturc)；冷却剂如樟脑、薄荷醇和薄荷油；抗微生物剂如：4-异丙基环庚二烯酚酮，苯扎氯铵、十一碳烯酸；抗炎剂如肾上腺皮质激素，氨基己酸、溶菌酶氯化物、甘草、尿囊素；皮肤白嫩剂(fairness impartingagents)，如：抗坏血酸和熊果苷；各种动植物或微生物提取物，如胎盘提取物、肝提取物，lithospermum根提取物，乳酸菌培养液提取物。
此外，可以使用适当选择的已知紫外线吸收剂或光散射剂来增强本发明的效果。优选的实例包括：二苯酮衍生物如：羟苯酮(oxy-benzone)，羟苯酮磺酸，羟基甲氧基二苯酮磺酸钠和二羟基二甲氧基二苯酮；水杨酸衍生物如：水杨酸乙二醇酯，水杨酸单酯和水杨酸苯酯；尿刊酸和尿刊酸乙酯；肉桂酸衍生物如：对甲氧基肉桂酸2-乙基己酯和甲氧基肉桂酸辛酯；对氨基苯甲酸衍生物如：对氨基苯甲酸甘油酯和对二甲基氨基苯甲酸2-乙基己酯；二苯甲酰甲烷衍生物如4-叔丁基-4′-甲氧基二苯甲酰甲烷；苯并三唑衍生物如2-(2-羟基-5-甲苯基)苯并三唑。
除了已知的有效成分，各种添加剂均可使用，如润湿剂、防腐剂、抗氧化剂、螯合剂、PH调节剂、香料、着色剂，以及基底成分如脂肪和油，只要它的加入不会损坏本发明上述药物、准药物和化妆品的应用方式。
通过下述实例和配方对本发明进行更为详细的描述，它们不是对本发明的限制。
实施例1
曲酸的色变或分解抑制实验：
制备洗剂型样品和霜剂型样品作为测试的典型样品。1)洗剂型样品：实验方法：
根据表1所示配方来制备各种洗剂。将它们置于4盎司的蜡瓶后，用铝箔避光包装将这些瓶在恒温室中保持45℃30天，并且每10天测定色差(ΔE)(运用色差仪，MINOLTA CT-210)。
                            表1测试样品
  配方序号   表面活性剂种类(量：4.2×10-4mol)   曲酸(g)   乙醇(ml)   纯水(ml)     HLB值
  1234   聚乙二醇单硬脂酸酯(55EO)聚乙二醇单硬脂酸酯(25EO)聚乙二醇单硬脂酸酯(10EO)聚乙二醇单硬脂酸酯(4EO) 1.0 10   加至总量达100(PH调至4.5)柠檬酸(PH调节剂)     18.015.011.06.7
  5678   POE(20)脱水山梨醇单月桂酸酯POE(20)脱水山梨醇单棕榈酸酯POE(20)脱水山梨醇单硬脂酸酯POE(6)脱水山梨醇单硬脂酸酯     16.915.614.99.6
实验结果：
图1和2表示含1％曲酸且具有不同调节的HLB值的溶液随时间的颜色变化(ΔE)(简单的洗剂，pH4.5)。作为表面活性剂，聚乙二醇脂肪酸酯和聚氧乙烯脱水山梨醇脂肪酸酯被用作典型的表面活性剂。可以看到HLB值较低的表面活性剂导致形成较小的色变或较少的曲酸分解，当HLB值达12上时可获得特别显著的效果。2)霜剂型样品
按表2所示配方制备各种霜剂型样品。将它们置于4盎司的蜡瓶中后，用铝箔避光包装。将这些瓶于恒温室中保持45℃30天，并且每10天测定一次色差(ΔE)(运用色差仪，Z-100IDP，由Nihon Denshoku Kogyo制造)。
                          表2测试样品
组份         O/W制剂           W/O制剂
  配方1   配方2     配方3     配方4     配方5*
  1.聚氧乙烯鲸蜡醚(25EO)2.亲油性甘油硬脂酸酯3.聚氧乙烯脱水山梨醇单月桂酸酯(20EO)4.亲油性甘油单油酸酯5.聚乙二醇(40EO)单硬脂酸酯6.可自身乳化的甘油硬脂酸酯7.聚氧乙烯脱水山梨醇单油酸酯(20EO)8.二甲基氧烷甲基(聚氧乙烯-聚氧丙烯)共聚物   3.001.50------   --2.002.00----     ----2.005.00--     ---3.50--1.00-     -------3.00
(续)
  9.微晶纤维素蜡10.石蜡11.凡士林12.蜂蜡13.还原羊毛脂14.鲸蜡醇15.十八烷醇16.山萮醇17.辛基十二烷醇18.硬脂酸19.角鲨烷20.液体石蜡21.三辛酸甘油酯22.脂肪酸甘油酯23.己二酸十六烷基酯24.蔗糖脂肪酸酯     ----2.00-7.00-6.002.005.00-----   ---6.008.005.00----37.50--4.00--     -------1.00-5.00-10.0010.00---   9.002.005.003.008.00-----34.00---0.00-   ----------5.00-3.00--0.20
  25.丙二醇26.甘油27.十甲基环戊硅氧烷28.八甲基环丁硅氧烷29.二甲基聚硅氧烷30.曲酸31.纯化水     5.00----1.00*1   5.00----1.00*1     5.00----1.00*1   2.00----1.00*1   -12.003.003.005.001.00*1
  表面活性剂的HLB值     13.70   10.45     9.29   5.28   6.33
5*：凝胶乳剂
*1：足以使总量达100.00的量实验结果：
图3显示了含1％曲酸的霜剂样品随时间的颜色变化(ΔE)。可以看出，无论在O/W制剂和W/O制剂中，HLB值较低的表面活性剂导致形成较小的色变和较少的曲酸分解。与O/W制剂相比，W/O制剂倾向于形成较小的色变和较少的曲酸分解。十分明显，使用凝胶乳化方法时，该趋势有所增强。
应用试验
进行下列器官感觉测试来测定本发明表皮用制剂的应用感觉。实验方法：
由20名女性专业评审员依下列标准测定表3所示以普通方式得到的W/O霜剂和凝胶乳化法得到的W/O霜剂样品的渗透皮肤感(皮肤舒适)、覆盖感、粘着感和湿润感。表4表示了如此得到的结果。
                        表3测试样品
组份   普通型W/O制剂(％)   凝胶乳化型W/O制剂(％)
  1.亲油性甘油单油酸酯2.聚氧乙烯脱水山梨醇单油酸酯(20EO)3.二甲基硅氧烷甲基(聚氧乙烯-聚氧丙烯)共聚物   3.501.00-   --3.00
  4.微晶纤维素蜡   9.00   -
(续)
  5.石蜡6.凡士林7.蜂蜡8.还原羊毛脂9.角鲨烷10.三辛酸甘油酯11.己二酸十六烷基酯12.蔗糖脂肪酸酯     2.005.003.008.0034.00-10.00-     ----5.003.00-0.20
  13.丙二醇14.甘油15.十甲基环戊硅氧烷16.八甲基环丁硅氧烷17.二甲基聚硅氧烷18.曲酸19.纯化水     3.00----1.00*1     -12.003.003.005.001.00*1
*1：足以使总量达100.00的量检测标准：◎：20名评审员中至少有15人评好。△：20名评审员中至少有10人评好。×：20名评审员中只有5人或不足5人评好。试验结果：
可以从表4中看出，用凝胶乳化方法得到的本发明的W/O霜剂表现出良好的皮肤应用感觉。
                        表4
                    器官感觉检测结果
器官感觉检测项目     普通型W/O制剂   用凝胶乳化法的W/O制剂
1.渗透皮肤感2.覆盖感3.粘着感4.湿润感 ×××◎ ◎△◎◎
配制实施例1：W/O霜剂
                                      重量(％)A.1.二甲基硅氧烷甲基(聚氧乙烯/聚氧丙烯)   3.00共聚物2.单油酸二甘油酯                        1.003.脱水山梨醇单硬脂酸酯                  0.20B 4.角鲨烷                                5.005.甘油三甲酸酯                          3.006.天然维生素E                           0.047.4-叔丁基-4 ′-甲氧基-二苯甲酰甲烷     0.50C 8.甘油                                  10.009.山梨醇                                2.0010.十甲基环戊硅氧烷                     3.0011.八甲基环丁硅氧烷                     3.0012.二甲基聚硅氧烷                       5.0013.乙二胺四乙酸二钠                     0.0114.曲酸                                 5.00  15.纯化水加至                           100.00配制实施例2：O/W霜剂
                                      重量(％)A 1.聚氧乙烯鲸蜡醚(25EO)                  2.502.亲油性甘油单硬脂酸酯                  2.503.还原羊毛脂                            2.004.硬脂酸                                2.005.十八烷醇                              7.006.辛基十二烷醇                          6.007.角鲨烷                                5.008.天然维生素E                           0.049.羟苯酮磺酸(Oxybenzonesulfonic         0.50acid)10.对羟苯甲酸酯                         0.20B 11.丙二醇                               5.0012.乙二胺四乙酸二钠                     0.0113.曲酸                                 3.0014.纯化水加至                           100.00配制实施例3：O/W乳剂                      (重量％)A 1.聚氧乙烯脱水山梨醇单硬脂酸酯(20EO)    2.002.聚氧乙烯山梨醇四油酸酯(60EO)          0.503.亲油性甘油单硬脂酸酯                  1.00  4.硬脂酸                                0.505.山萮醇                                0.506.鳄梨油                                4.007.甘油三辛酸酯                          4.008.天然维生素E                           0.049.水杨酸乙二醇酯                        0.1010.对羟苯甲酸酯                         0.20B 11.1，3-丁二醇                          5.0012.黄原胶                               0.1413.乙二胺四乙酸二钠                     0.0114.曲酸                                 0.5015.纯化水加至                           100.00配制实施例4：O/W霜剂润肤膏
                                      (重量％)A 1.聚乙二醇单硬脂酸酯(40EO)              2.002.可自身乳化的甘油单硬脂酸酯            5.003.硬脂酸                                5.004.山萮醇                                0.505.角鲨烷                                15.006.辛酸鲸蜡酯                            5.007.天然维生素E                           0.048.4-叔丁基-4′-甲氧基-二苯甲酰甲烷      0.509.对羟苯甲酸酯                          0.20B 10.1，3-丁二醇                          5.0011.乙二胺四乙酸二钠                     0.0112.曲酸葡糖苷                           2.0013.纯化水加至                           100.00配制实施例5：O/W香精
                                      (重量％)A 1.聚氧乙烯脱水山梨醇单硬脂酸酯(20EO)    1.002.聚氧乙烯山梨醇四油酸酯(60EO)          0.503.亲油性单硬脂酸甘油酯                  1.004.硬脂酸                                0.505.山萮醇                                0.506.鳄梨油                                2.007.角鲨烷                                3.008.三辛酸甘油酯                          3.009.天然维生素E                           0.0410.羟基苯酮(Oxybenzone)                 0.5011.对羟苯甲酸酯                         0.20B.12.1，3-丁二醇                          5.0013.黄原胶                               0.1414.乙二胺四乙酸二钠                     0.1015.曲酸                                 1.0016.纯化水加至                           100.00
已经证实上述配制实施例1～5提供了具有同样令人满意效果的制剂。
在不背离本发明精神和基本特征的前提下，本发明可以其它形式来实现。因此本发明的具体方案从各方面均旨在说明而非限制，本发明的范围是通过附录的权利要求而不是前面的描述来指明，并且包括了在与权利要求相当的方法和范围内发生的全部变化。

Claims (3)

1.表皮用制剂，是O/W或W/O型制剂，其特征在于配合有曲酸和/或其衍生物与HLB值12以下的表面活性剂。
2.根据权利要求1的表皮用制剂，所述制剂是乳剂。
3.根据权利要求2的表皮用制剂，其中所述W/O乳剂是通过凝胶乳化法制备的。
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KR950007832A (ko) 1995-04-15
CN1106661A (zh) 1995-08-16
GB2282325B (en) 1997-12-10
GB9411941D0 (en) 1994-08-03
MY115306A (en) 2003-05-31
JPH07101822A (ja) 1995-04-18
US5599528A (en) 1997-02-04
TW291437B (zh) 1996-11-21
KR100309399B1 (ko) 2002-02-19
GB2282325A (en) 1995-04-05
JP3566739B2 (ja) 2004-09-15

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