CN1819824B - 抗氧化剂在皮肤病和/或化妆品组合物中的用途 - Google Patents

抗氧化剂在皮肤病和/或化妆品组合物中的用途 Download PDF

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CN1819824B
CN1819824B CN2004800191677A CN200480019167A CN1819824B CN 1819824 B CN1819824 B CN 1819824B CN 2004800191677 A CN2004800191677 A CN 2004800191677A CN 200480019167 A CN200480019167 A CN 200480019167A CN 1819824 B CN1819824 B CN 1819824B
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吉恩-诺埃尔·托雷尔
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Abstract

本发明涉及一种用于治疗痤疮、脂溢性皮炎和与粉刺形成相关的皮肤疾病的皮肤病和/或化妆品组合物。本发明的特征是，它含有：选自棓酸酯、类黄酮、丁基化羟基甲苯(BHT)、丁基羟基苯甲醚(BHA)、十八烯二酸和羟基癸酸的至少一种亲脂性抗氧化剂作为其活性要素；以及至少一种第二活性要素，其形式为选自甘露醇、维生素C、壬二酸赖氨酸、芸香苷和槲皮素的亲水性抗氧化剂。

Description

抗氧化剂在皮肤病和/或化妆品组合物中的用途
本发明涉及痤疮和与粉刺形成相关的皮肤疾病的治疗。
粉刺是寻常痤疮的主要损伤，该损伤由毛囊管壁的细胞阻塞，阻止皮脂细胞(皮脂腺的细胞)生产的皮脂到达皮肤表面引起。皮脂和细胞的混合物形成栓塞，称为粉刺，在如此栓塞的毛孔中造成通常靠皮肤生活的细菌，如痤疮丙酸杆菌(Propionibacterium acnes)和颗粒丙酸杆菌(Propionibacterium granulosum)以及酵母，具体是皮屑芽孢菌(Malassezia furfur)的繁殖。这些细菌具有不同的代谢皮脂甘油三酯和释放脂肪酸的特征，这引起组织发炎。
由此引起的脂溢性皮炎反映为长出红斑或疙瘩，覆有淡黄色油性鳞屑，或多或少地发痒，主要发生在富含皮脂腺的区域。在面部，该损伤的区域分布是提示性的：鼻子和嘴唇之间的沟、眉毛根、头皮、鼻翼、耳廓褶、耳甲、外耳道。在头皮上，或多或少的脂溢性头屑症状反映了它常常发作。在躯干上，在男性中注意到两处频发区域：胸骨和两块肩胛骨之间的区域。
皮脂是富含脂肪酸，和尤其是角鲨烯、含有30个碳原子的脂肪烃即胆固醇前体的油脂分泌的产物。皮脂，尤其在保护皮肤方面起到重要的积极作用，但自1969年以来，人们确定，在皮脂分泌水平和痤疮的严重程度之间存在关联(Cunliffe，W.J.等，Lancet，I，685，1969，The Pathogenesis of Acne)。
因此，在现代化妆业和皮肤学中，在为减少和控制皮脂腺过度分泌，尤其是为减少难看的后果，如皮肤和头皮的油脂性外观，而且也为降低粉刺的形成和产生的发炎而开发组合物方面进行了很多研究。
由于去除了皮脂，使它们不能再起到保护性作用，所以这些组合物具有明显副作用，如皮肤干燥、紧绷感、甚至发炎。
关于治疗毛发，将提及FR 2 099 582中揭示的毛发组合物，它在溶液中至少包括一种酚衍生物，所述组合物用于使毛发脱臭，但除此脱臭作用之外，它还减慢皮脂分泌，施用它似乎具有强烈减慢分泌或改善较低流动性的效果。
近年来的科学研究显示，皮脂的一种组分，角鲨烯尤其是角鲨烯的氧化产物具有粉刺发生性和刺激性(Saint-Léger等，British J.of Dermatology，114，543-552，1986；Chiba K.等，The J.of Toxicological Sciences，25，77-83，2000和Uchino.T.等，Biol.Pharm.Bulletin，25(5)，605-610，2002)。
更具体说，已确定，患痤疮的病人的皮脂组合物高度富含角鲨烯。
本申请公司也指出，构成皮脂的脂类物质的氧化导致所述皮脂的粘度增加，并增加粉刺形成，流动性较低的皮脂不再可能从毛囊管流出，该氧化可能由细菌组分和紫外线辐射引起，导致形成使皮脂变稠和高度致粉刺发生的粘稠聚合物。
因此，本发明涉及通过阻止皮脂变稠来提高皮脂质量从而降低对角质细胞增殖的诱导，导致降低粉刺发生的组合物。
令人惊讶的是，在没有改变皮脂流动，即没有影响所产生皮脂量的情况下，而通过降低粉刺发生性、通过校正其质量和通过防止其变稠得到关于患有痤疮的皮肤的结果。
本发明更具体地涉及使维持皮脂流动性成为可能的组合物，更具体涉及用于治疗痤疮、脂溢性皮炎和与粉刺形成相关的皮肤疾病的皮肤病和/或化妆品用途的组合物，其特征是它包含选自棓酸酯、类黄酮、丁基化羟基甲苯(BHT)、丁基化羟基苯甲醚(BHA)、十八烯二酸和羟基癸酸的至少一种亲脂性抗氧化剂作为其活性要素。
也涉及如上所述的组合物，其特征是它还包含至少一种第二活性要素、选自甘露醇、维生素C、壬二酸赖氨酸、芸香苷和槲皮素的亲水性抗氧化剂。
本发明也涉及其中亲脂性抗氧化剂是棓酸十二烷酯的组合物。
本发明也涉及其中亲脂性抗氧化剂是棓酸丙酯的组合物。
本发明也涉及其中亲脂性抗氧化剂是棓酸辛酯的组合物。
类黄酮可以，例如，由植物萃取物如白果或绿茶萃取物提供。
活性要素的量，即亲水性或亲脂性抗氧化剂的量或两种抗氧化剂的总量在组合物重量的0.0001和20％之间，优选在组合物重量的0.0001和10％之间。
上述量优选在组合物重量的0.001和2％之间。
本发明也涉及使皮脂流动的方法，其特征是它包括将上述的本发明组合物施用于皮肤或头皮。
在药学上可接受的介质中，该组合物包含至少一种活性要素，即一种亲脂性抗氧化剂。
药学上可接受的介质，即剂型环境，必须是既不可氧化也不具氧化性，即所用赋形剂在施用于皮肤的条件下必须是不可氧化且稳定的，并且必须不引起氧化反应。
因此，本发明涉及如上所述的组合物，其特征是它不含在使用条件下能够氧化的赋形剂。
本发明组合物可任选地含有各种不可氧化的添加剂，如悬浮剂，乳化剂，阴离子、阳离子、非离子性或两性聚合物，蛋白质，维生素，表面活性剂，矿物或植物油，硅氧烷蜡，树胶和/或树脂，增稠剂，酸化或碱化剂，溶剂，pH稳定剂，UV稳定剂，防腐剂，抗菌剂和抗真菌剂，香料或化妆品中或皮肤病学中常用的其它佐剂。
优选地，以适合通过局部皮肤途径给药的形式和覆盖所有化妆品或皮肤病学的形式提供本发明组合物。这些组合物含有化妆品中和/或皮肤病学上可接受的介质，即与皮肤或毛发，包括头发相容的介质。这些组合物具体可以呈适合施用于皮肤、嘴唇和/或毛发的乳膏，O/W、W/O乳剂或多相乳剂，溶液，悬液，凝胶，乳液、洗剂、粘着剂或粉剂的形式。
本发明也涉及在用于治疗痤疮和/或由粉刺形成引起的皮肤疾病的皮肤病和/或化妆品组合物的制备中至少一种亲脂性抗氧化剂的用途。
更具体地涉及如上所述的用途，其特征是该亲脂性抗氧化剂选自棓酸酯和类黄酮。
在另一形式中，该亲脂性抗氧化剂选自丁基化羟基甲苯(BHT)、丁基化羟基苯甲醚(BHA)、十八烯二酸和羟基癸酸。
本发明也涉及当亲脂性抗氧化剂是棓酸十二烷酯时的所述用途。
本发明也涉及当亲脂性抗氧化剂是棓酸丙酯时的所述用途。
本发明也涉及当亲脂性抗氧化剂是棓酸辛酯时的所述用途。
类黄酮可以，例如，由植物萃取物如白果或绿茶萃取物提供。
本发明也涉及在用于治疗痤疮和/或由粉刺形成引起的皮肤疾病的皮肤病和/或化妆品组合物的制备中亲水性抗氧化剂与亲脂性抗氧化剂结合的用途。
也涉及如上所述的用途，其特征是亲水性抗氧化剂选自甘露醇和维生素C。
在另一形式中，该亲水性抗氧化剂选自壬二酸赖氨酸、芸香苷和槲皮素。
根据本发明，所用亲水性或亲脂性抗氧化剂的量或两种抗氧化剂的总量在组合物重量的0.0001和20％之间，优选在组合物重量的0.0001和10％之间。
上述量优选在组合物重量的0.001和2％之间。
阅读以例子方式给出并且不包含限制意思的实施例后，本发明的其它优点和特征将变得更加显而易见。
实施例1-制备活性混合物
Sepigel 305(聚丙烯酰胺和C13-14异链烷烃和月桂基聚氧乙烯(7)醚)    2％
棓酸十二烷酯                                  0.0001％
甘露醇                                        0.50％
防腐剂(对羟基苯甲酸酯类)                      0.20％
EDTA(螯合剂)                                  0.10％
水                                            足量至100％
实施例2-本发明组合物的效果
在一组约30位志愿者中测试了含有棓酸十二烷酯、甘露醇和白果萃取物作为活性要素的本发明组合物。
试验对象平均年龄为23岁(18-34岁)，具有中度多形青春痘，即平均具有约40个保留性或炎性损伤。
在除鼻锥体的整个面部仅观察计数保留性损伤，即小囊和粉刺。
将本发明组合物施用于面部，每天两次，共8周。
施用8周后，记录显示至少40％对象的保留性损伤减少，20％对象显示出小囊减少50-90％，15％对象显示出粉刺减少50-90％，10％对象粉刺完全消失。
实施例3-制备组合物
通过简单地混合各种组分获得这些组合物。所示量以重量百分数表示。
水包油乳剂
Montanov 68(十六/十八醇和十六/十八烷基葡糖苷(Cetearyl glucoside)) 5.00％
霍霍巴油                                                          5.00％
BHT                                                               0.05％
棕榈酸异丙酯                                                      7.00％
甘油                                                              5.00％
尿囊素                                                            0.10％
甘露醇                                                            3.00％
Sepigel 305(聚丙烯酰胺和C13-14异链烷烃和月桂基聚氧乙烯(7)醚)      0.30％
Phenonip                                                          0.50％
香料                                                              0.50％
水                                                                足量至100％
凝胶
Carbopol Ultrez 10(溶液，2％)                                     25％
三乙醇胺                                                          0.50％
甘露醇                                                            2.00％
棓酸十二烷酯                                                      0.0001％
防腐剂                                                            0.20％
EDTA(螯合剂)                                                      0.10％
香料                                                              0.50％
水                                                                足量至100％
洗剂
单丙二醇                                                          1.00％
尿囊素                                                            0.30％
甘油                                                              1.00％
Cetiol HE(聚氧乙烯(7)甘油醚椰油酸酯)                              1.00％
壬二酸赖氨酸                                                      5.00％
BHA                                                               0.01％
防腐剂                                                            0.20％
香料                                                              0.50％
水                                                                足量至100％
用于脂溢性油性皮肤的发泡凝胶
化合物(90％甘露醇和10％棕榈酸抗坏血酸酯)                          2.00％
香料                                                              0.30％
氯化钠                                                            1.00％
57％乙醇酸的水溶液                                                0.50％
氧乙烯化(60EO)氢化牛油醇和十四烷二醇的共聚物                      0.90％
甘油                                                              3.00％
38％氨基乙酸N-二钠N-羧基乙氧基乙基-N-(椰油基酰氨基乙基)酯的水溶液 5.00％
28％月桂醚硫酸钠(C12-1470/30)(2.2EO)的水溶液                      14.30％
椰油脂肪酸二乙醇酰胺                                              0.70％
氧乙烯化(26EO)/氧丙烯化(26PO)丁醇、
氧乙烯化(40EO)氢化蓖麻油的混合物水溶液                  1.00％
软化水                                                  足量至100％
用于脂溢性皮肤的治疗性凝胶
棕榈酸抗坏血酸酯                                        1.00％
香料                                                    0.20％
黄原胶                                                  1.00％
甘油                                                    2.00％
乙醇                                                    20.00％
芸香苷                                                  0.10％
氧乙烯化(26EO)/氧丙烯化(26PO)丁醇、
氧乙烯化(40EO)氢化蓖麻油的混合物水溶液                  1.00％
软化水                                                  足量至100％
用于患有痤疮的皮肤和头屑症状的纯化洗剂
BHA                                                     0.05％
棓酸丙酯                                                0.0005％
香料                                                    0.20％
乙醇                                                    20.00％
甘油                                                    2.00％
氧乙烯化(26EO)/氧丙烯化(26PO)丁醇、
氧乙烯化(40EO)氢化蓖麻油的混合物水溶液                  1.00％
Octopirox                                               0.20％
软化水                                                  足量至100％
为了补充本发明组合物的作用并增加其有效性和耐受性，可以将其它活性要素与抗氧化剂结合。
这导致，该作用的各组分使组合物可能满足有痤疮倾向的皮肤的复杂要求。
本发明组合物还可包含具有角质层分离活性的选自α-羟酸和/或水杨酸的酯的活性要素，该要素使得清除和防止形成也可促进粉刺形成的角质细胞团成为可能。
它们还可包含锌盐，例如葡糖酸锌，它由于对5α-还原酶的抑制作用而具有皮脂分泌调节作用，而且在高浓度时，具有对痤疮丙酸杆菌的杀菌作用，而粉刺中这种细菌的繁殖是痤疮的特有的。
向本发明组合物中加入高浓度的含锌活性要素使得在局部或全身施用中补充抗生素治疗，如红霉素治疗的作用成为可能。
本发明组合物也可含有消炎或润肤活性要素，如18β-甘草亭酸(甘草次酸)，其内源性消炎作用是由于它抑制了造成将皮质醇转化成可的松的酶，或者描述为炎症级联反应抑制剂的白果萃取物。
通过剂型基料含有因其增湿性选出的甘油和木糖醇来补充这些活性要素的作用。

Claims (1)

1.包含棓酸十二烷酯、甘露醇和白果类黄酮作为活性药物的组合物在制备局部施用来治疗痤疮和/或由于粉刺形成引起的皮肤疾病的皮肤病和/或化妆品组合物中的应用。
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