CN115243669A - 溶解度提高的包含4-羟基苯酮的燕麦蒽酰胺组合物 - Google Patents
溶解度提高的包含4-羟基苯酮的燕麦蒽酰胺组合物 Download PDFInfo
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- CN115243669A CN115243669A CN202080098186.2A CN202080098186A CN115243669A CN 115243669 A CN115243669 A CN 115243669A CN 202080098186 A CN202080098186 A CN 202080098186A CN 115243669 A CN115243669 A CN 115243669A
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- Medicines Containing Plant Substances (AREA)
Abstract
本发明总体上涉及:一种溶解度提高的、包含至少一种燕麦蒽酰胺或其类似物和4‑羟基苯乙酮的组合物或由其组成的组合物;其护肤品或医疗用途;此类组合物用于制备食品、食品补充剂、护肤品、药物或兽药制剂的用途;和包含此类组合物的食品、食品补充剂、护肤品、药物或兽药制剂。最后,本发明涉及用于提高燕麦蒽酰胺或其类似物的溶解度的4‑羟基苯乙酮。
Description
技术领域
本发明总体上涉及:一种溶解度提高的、包含至少一种燕麦蒽酰胺(燕麦生物碱)或其类似物和4-羟基苯乙酮的组合物或由其组成的组合物;其护肤品或医疗用途;此类组合物用于制备食品、食品补充剂、护肤品、药物或兽药制剂的用途;和包含此类组合物的食品、食品补充剂、护肤品、药物或兽药制剂。最后,本发明涉及用于提高燕麦蒽酰胺或其类似物的溶解度的4-羟基苯乙酮。
背景技术
燕麦蒽酰胺(以下简称Avns或Avn表示单一的燕麦蒽酰胺化合物)是含有邻氨基苯甲酸和具有酰胺键的羟基肉桂酸部分的低分子量酚酰胺,是燕麦(包括皮燕麦(A.sativa)和裸燕麦(A.nuda)中天然存在的一组酚酰胺。它们最初被鉴定为植物在暴露于病原体(诸如真菌)后产生的植物抗毒素。燕麦含有一组独特的大约40种不同类型的燕麦蒽酰胺,它们存在于燕麦粒和燕麦叶之中。最丰富的是Avn A(N-(4′-羟基肉桂酰基)-5-羟基邻氨基苯甲酸)、Avn B(N-(4′-羟基-3′-甲氧基肉桂酰基)-5-羟基邻氨基苯甲酸)和Avn C(N-(3′-4′-二羟基肉桂酰基)-5-羟基邻氨基苯甲酸),它们分别是5-羟基邻氨基苯甲酸与对香豆酸、阿魏酸和咖啡羟基肉桂酸的酰胺。这些燕麦蒽酰胺在谷仁中进行组成型表达,几乎出现在所有碾磨部分中,但其在谷仁的麸皮和外层中浓度最高(Boz H,Czech Journal of FoodSciences[捷克食品科学杂志]2015,33(5):399-404)。已经发现,根据培育品种和农艺处理,燕麦粒中燕麦蒽酰胺(Avn)的总含量约为2mg/kg至700mg/kg(0.0002%至0.07%)(Maliarova M等人,Journal of the Brazilian Chemical Society[巴西化学学会杂志]2015,26(11),2369-2378)。
燕麦蒽酰胺从燕麦中的提取使用各种溶剂组合物(诸如纯的或稀释的乙醇和甲醇)进行。在室温或受控加热下,在不同的时间使用诸如裸燕麦、50%乙醇水溶液等完成提取程序(Tong L等人,Journal of Integrative Agriculture[农业科学学报]2014,13,1809)。
Maliarova,M.等人(Journal of the Brazilian Chemical Society[巴西化学学会杂志]2015,26(11),2369–2378)比较了甲醇、乙醇和异丙醇从裸燕麦麸皮中提取燕麦蒽酰胺的效率。实现燕麦蒽酰胺最高产率的最佳条件为70%甲醇浓度、55℃提取温度和165分钟提取时间。
在治疗学中,燕麦蒽酰胺的应用是一个不断发展的领域,因为许多研究已表明燕麦蒽酰胺在体外和体内都具有出色的抗氧化活性,以及抗炎、抗刺激、抗动脉粥样硬化和抗增殖活性,这些活性可以预防和限制细胞氧化功能障碍和氧化应激相关疾病(诸如神经退行性疾病和心血管疾病)的发展,并且可以提供额外的保护,防止皮肤刺激、老化、冠心病(CHD)和癌症(Perrelli A等人,Oxidative Medicine and Cellular Longevity[氧化药物与细胞寿命]2018,DOI:10.1155/2018/6015351)。
已发现,与典型的谷物成分阿魏酸、龙胆酸、对羟基苯甲酸、原儿茶酸、丁香酸、香草酸和香草醛相比,燕麦蒽酰胺的抗氧化活性要高出10倍至30倍。燕麦蒽酰胺具有不同的抗氧化活性,Avn C具有最高活性,其次是Avn B和Avn A。富含燕麦蒽酰胺的燕麦提取物可抑制低密度脂蛋白(LDL)在体外的氧化。动物研究和人体临床试验均证明,燕麦抗氧化剂有潜力通过降低血清胆固醇、抑制LDL胆固醇氧化和过氧化来降低心血管风险。另一项研究表明,食用燕麦和燕麦麸皮可以降低患结肠癌的风险,这不仅是因为燕麦和燕麦麸皮具有较高的纤维含量,还归因于燕麦蒽酰胺。此外,富含燕麦蒽酰胺的燕麦提取物已被证明可抑制动脉粥样硬化和NF-kB转录因子的激活,NF-kB转录因子是感染和炎症的调节因子(HüseyinBoz,Phenolic Amides(Avenanthramides)in Oats-A Review[燕麦中的酚酰胺(燕麦蒽酰胺)——综述],Czech J.Food Sci.[捷克食品科学杂志],33,2015(5),399-404)。
WO 2004/047833 A1描述了对组胺在物质P的诱导下从肥大细胞中的释放进行抑制,以及通过燕麦蒽酰胺和燕麦蒽酰胺类似物物质对发痒进行治疗和预防。
WO 2017/159964 A1描述了包含作为活性成分的燕麦蒽酰胺或其衍生物的组合物用于预防和治疗听力损失。
EP 0 157 420A2描述了作为5-脂氧合酶抑制剂的燕麦蒽酰胺,其包含结构上与燕麦蒽酰胺L相关的化合物。
Lotts T等人(Experimental Dermatology[实验皮肤病学]2017,26(8):739-742)描述了二氢燕麦蒽酰胺D(CAS 697235-49-7,INCI名称:羟苯基丙酰胺基苯甲酸;Symrise提供的中的活性成分)如何抑制肥大细胞脱粒以及如何通过与神经激肽-1受体的相互作用展现出抗炎作用。
燕麦蒽酰胺具有强大的有益生物活性,这使其成为了有价值且高度有意义的天然活性成分,适于人类和动物的口腔和/或局部应用的营养、护肤品和健康用途。
因此,在食品、护肤品、药物和兽药行业,对开发基于天然存在的、耐受性良好的、且可生物降解的物质的新制剂或惯用配制剂,尤其是对这些物质在皮肤保护以及预防和/或治疗皮肤病中的使用有着持续的需求和消费需求,这些物质具有稳定性,分别在加工步骤、储存或运输期间以及在光和UV照射、金属阳离子、空气和某些酶的影响下不会发生降解。
氧化降解过程和自氧化过程对制剂的稳定性起着重要的作用,因为这些过程会破坏所需的成分使其之后消失不见,能够产生不良或不希望的降解产物或不利地影响产品的物理性能特征(例如,颜色),因此通常会降低产品的价值。
然而,在营养、护肤品、药物或兽药行业中应用的燕麦蒽酰胺在有机溶剂、水性有机溶剂或水性溶剂中的溶解度较差。这限制了它们在具有透明外观的溶液中的浓度,或者使其在储存期间发生絮凝或沉淀,这对于组合物本身或其所掺入的最终产品而言是不利的。溶剂一般为液体,可以是纯物质,也可以是两种或多种溶剂物质的混合物。由于发生絮凝或沉淀,燕麦蒽酰胺不再作为活性物质存在,或者仅以溶解形式在降低的浓度下存在,这降低了其生物利用度。在燕麦蒽酰胺化合物中,尤其是燕麦蒽酰胺A和L的溶解度较低。
溶解度是在相应的组织或体循环中达到活性物质或药物的所需浓度以实现所需的生物学或药理学反应的重要参数之一。难溶性物质通常需要较高的剂量才能在施用后达到生物学相关或治疗浓度。低溶解度、最重要的是低水溶度,是新化学实体配制剂开发和仿制药开发中遇到的主要问题。任何待吸收的活性物质或药物必须以溶解的形式存在于吸收部位。难溶性物质会导致生物利用度不足和多变。对于局部和口服施用的药物或活性物质,溶解度是达到其生物学或药理学反应所需浓度或生物利用度的最重要参数。任何待吸收的药物或活性物质必须以溶液形式存在于吸收部位。溶解度问题是配制剂科学家面临的主要挑战。
因此,为了保持燕麦蒽酰胺的良好溶解度及使组合物中的燕麦蒽酰胺达到生物学相关或治疗浓度或生物利用度,需要提高燕麦蒽酰胺化合物的溶解度。
相应地,本发明的目的是提供一种包含燕麦蒽酰胺或其类似物的组合物,该组合物展现出燕麦蒽酰胺、特别是燕麦蒽酰胺A或燕麦蒽酰胺L或二氢燕麦蒽酰胺D的溶解度得到改善。
特别地,本发明的目的是提出天然的、可生物降解的、在护肤品或药学上耐受性良好的、安全的、易用且稳定的物质,这些物质能够提高组合物中的燕麦蒽酰胺的溶解度,并且不会干扰燕麦蒽酰胺的有益生物活性或本身的制剂或惯用配制剂特性。尤其是,本发明的目的是提出天然的、可生物降解的、在护肤品或药学上耐受性良好的、安全的、易用且稳定的物质,这些物质能够提高组合物或惯用配制剂中的燕麦蒽酰胺A、或燕麦蒽酰胺L、或二氢燕麦蒽酰胺D的溶解度。
令人惊讶地,事实证明,采用4-羟基苯乙酮,特别是在低浓度下,可以显著提高燕麦蒽酰胺或其类似物的溶解度,特别是提高燕麦蒽酰胺中溶解度最差的燕麦蒽酰胺A、或燕麦蒽酰胺L、或二氢燕麦蒽酰胺D的溶解度。在其中该至少一种燕麦蒽酰胺类似物为二氢燕麦蒽酰胺D的情况下特别如此。
发明内容
根据本发明的第一方面,上述目的是通过以下方式实现的:提供一种组合物,所述组合物包含或由以下组成:
-至少一种燕麦蒽酰胺或其类似物;和
-4-羟基苯乙酮。
在第二方面,本发明涉及所述组合物作为护肤品的用途,特别是在皮肤护理、头皮护理、头发护理、指甲护理或在预防和/或治疗皮肤病状、皮肤不耐受和敏感、皮肤刺激、皮肤发红、风团、瘙痒(发痒)、皮肤老化、皱纹形成、皮肤体积损失、皮肤弹性丧失、色素斑、色素异常、或皮肤干燥(即用于皮肤保湿)中用作皮肤病护肤品。
在第三方面,本发明涉及所述组合物作为药剂的用途,特别是用于预防和/或治疗皮肤病或角化病,特别是具有与屏障相关的、炎症性、免疫过敏性、致动脉粥样硬化性、干燥性或过度增殖性组分的皮肤病或角化病,或在预防和/或治疗与ROS产生增加相关的皮肤病中,或在预防和/或治疗心血管疾病、过敏反应、冠心病中的用途,用于降低血清中的LDL胆固醇和脂质水平,用于降低血压,用于提高对胰岛素的敏感性以及用于使得能够对血糖水平进行控制。
在第四方面,本发明涉及所述组合物用于制备食品、食品补充剂、护肤品、药物或兽药制剂的用途。
在第五方面,本发明涉及包含根据本发明的组合物的食品、食品补充剂、护肤品、药物或兽药制剂。
最后,本发明涉及4-羟基苯乙酮用于提高燕麦蒽酰胺或燕麦蒽酰胺类似物化合物、特别是燕麦蒽酰胺A或燕麦蒽酰胺L或二氢燕麦蒽酰胺D(2-[(3-(4-羟苯基)丙酰基]氨基)苯甲酸;INCI:羟苯基丙酰胺苯甲酸;CAS 697235-49-7)的溶解度的用途。
本发明在所附权利要求中进行详细说明。然而,结合所附实施例和附图,本发明本身及其优选变型、其他方面和优势在以下具体实施方式中将变得显而易见。
附图说明
图1是含燕麦蒽酰胺A的溶液的图像。
图2a和图2b是含燕麦蒽酰胺L的溶液的图像。
图3是含燕麦蒽酰胺A和B共混物的溶液的图像。
图4是含燕麦蒽酰胺B、C和D共混物的溶液的图像。
图5a和图5b是含二氢燕麦蒽酰胺D的溶液的图像。
具体实施方式
在第一方面,本发明涉及一种组合物,该组合物包含或由以下组成:
-至少一种燕麦蒽酰胺或其类似物;和
-4-羟基苯乙酮。
根据本发明第一方面的组合物的第一主要成分是至少一种燕麦蒽酰胺或其类似物。
如本文中所使用的,短语“至少一种”意指组合物可以包含例如一种燕麦蒽酰胺或多于一种燕麦蒽酰胺。另外,当应用于列表时,短语“至少一种”意指列表中指定项目的任何一种组合。
根据本发明第一方面的组合物是通过组合指定的成分而制备的,如以下进一步详细描述的。
在本发明的上下文中,术语“燕麦蒽酰胺”(邻氨基苯甲酸酰胺)被理解为意指尤其是一组酚类生物碱的成员,即天然存在的燕麦蒽酰胺,其主要存在于燕麦(皮燕麦)中但也存在于菜粉蝶卵(Pieris brassicae和P.rapae)和真菌感染的康乃馨(Dianthuscaryophyllus)中,如下文详述的;或非天然存在的人造燕麦蒽酰胺类似物,如下文详述的。
本发明组合物的燕麦蒽酰胺天然存在于燕麦中,并且可以从燕麦中富集、分离出来并纯化。燕麦的两个主要的物种是皮燕麦(Avena sativa L.)和裸燕麦(Avena nuda L.)(同义词包括依据Gillet&Magne的Avena sativa subsp.nuda(L.),和依据的Avenasativa var.nuda(L.)),其中燕麦蒽酰胺看似最集中出现在外围区域、外壳、毛状体或秸秆中。已经从燕麦粒中分离出50多种不同的燕麦蒽酰胺(Collins,Journal of Agriculturaland Food Chemistry[农业与食品化学杂志],37(1989),60-66)。
燕麦蒽酰胺可以由以下通式1表示:
下表1显示了基于通式1的天然存在的燕麦蒽酰胺的示例。
表1:
*)柯林斯缩写(de Bruijn等人,Food Chemistry[食品化学](2018),doi:https://doi.org/10.1016/j.foodchem.2018.11.013,补充信息表S1)
**)更常用的非柯林斯缩写
许多研究表明,所述燕麦蒽酰胺具有抗炎、抗氧化、止痒、抗刺激和抗动脉粥样硬化的活性。
对于如上所述的天然存在的燕麦蒽酰胺或燕麦蒽酰胺的混合物,可以通过提取从燕麦属植物中获得、富集和分离,特别是从新鲜或干燥的任何燕麦物种或其部分获得、富集和分离,诸如皮燕麦或裸燕麦等燕麦物种的碾磨的谷粒、非碾磨的谷粒、外壳、毛状体或燕麦秸秆。
用于有利地提取燕麦蒽酰胺L的提取溶剂(提取剂)选自由以下组成的组:水和有机溶剂的混合物,其中该有机溶剂优选为适用于食品或护肤品或药物制剂的溶剂。毋庸置疑,此类溶剂需要适用于食品、护肤品或药物制剂的制备并与之相容。
在一个更优选的变型中,提取溶剂包含水和醇或丙酮的混合物。醇优选选自由以下组成的组:甲醇、乙醇、正丙醇、异丙醇、正丁醇、异丁醇、叔丁醇以及它们的混合物即它们的组合。用于本发明的提取步骤的最优选的提取溶剂(提取剂)为甲醇、乙醇、正丙醇、异丙醇或丙酮,或所述溶剂各自组合的任何混合物,各自与水混合。由于甘油三酯的共提取,使用纯有机溶剂是不利的。
在提取溶剂中,在每种情况下按所得提取溶剂计,水与有机溶剂、优选水与醇或水与丙酮的混合比为10:90至90:10(v/v),优选在20:80至80:20(v/v)的范围内,并且最优选在30:70至70:30(v/v)的范围内。
特别优选的提取溶剂(提取剂)为:甲醇/水(3:7)、甲醇/水(1:1)、甲醇/水(7:3)、乙醇/水(3:7)、乙醇/水(1:1)、乙醇/水(1:4)、乙醇/水(7:3)、异丙醇/水(3:7)、异丙醇/水(1:1)、异丙醇/水(7:3)、丙酮/水(3:7)、丙酮/水(1:1)、丙酮/水(7:3)。
为了提高提取率,燕麦源的提取温度范围为30℃至80℃、优选40℃至70℃并且更优选50℃至60℃。碾磨的燕麦粒的提取产率随着温度在40℃至70℃之间的升高而增加。
除了从天然来源富集、分离和纯化的燕麦蒽酰胺化合物外,还可以通过有机合成生产天然存在的燕麦蒽酰胺化合物。本领域已知的合成方法例如在美国专利第6,096,770号和第6,127,392号、日本专利第J60019 754 A号以及匈牙利专利第HU 200 996 B号中进行了说明。
所述合成制备的燕麦蒽酰胺物质与如从燕麦中分离或提取的对应的天然存在的燕麦蒽酰胺化合物相同。
根据本发明的组合物中的非天然存在的燕麦蒽酰胺类似物在下文中又称“类似物”或“类似燕麦蒽酰胺化合物”,已经通过有机合成方法(诸如,例如WO 2004/047833 A1或WO 2007/062957 A1中给出的那些)人工生产,其符合下式2并被赋予重要生物学特性,:
其中m=0、1、2或3,p=0、1或2,且n=0、1或2,
条件是如果n=1或2,则p+m>0,
并且如果n=1或2,则R1和R2在各自的对中分别表示H或一起表示另一个化学键(例如在肉桂酸衍生物中),
并且如果m=1、2或3,则X各自独立地表示OH、氧烷基或氧酰基,
并且如果p=1或2,则Y各自独立地表示OH、氧烷基或氧酰基,
并且如果p+m>0,则X和Y中的至少一者选自由以下组成的组:OH和氧酰基,
并且其中R3为-H或烷基(特别是-CH3,或具有2至30个C原子的其他直链或支链烷基链;在这一上下文中,对于对应的药学上可接受的盐,R3也是-H)。
根据本发明的特别优选的式2化合物是以下那些:
n=1或2并且p+m>0;和/或
p+m>0并且X或Y、X和Y中的至少一者选自由以下组成的组:OH和氧烷基。
特别优选地,使用式2的化合物,其中n=1并且p+m>2,条件是X和Y中的至少两者一起选自由以下组成的组:OH和氧烷基。
还优选使用式2化合物,其中n=1并且m=1、2或3,条件是至少一个X选自由以下组成的组:OH和氧烷基,和/或P=1或2,条件是至少一个Y选自由以下组成的组:OH和氧烷基。
如果n的值为1,则R1和R2各自优选为H,尽管R1和R2也能够一起构成另一个化学键。
关于式2的定义和WO 2004/047833 A1或WO 2007/062957 A1中公开的具体燕麦蒽酰胺化合物,所述文献中的对应披露内容通过引用并入本文。
式2的燕麦蒽酰胺类似物化合物优选选自由以下组成的组:
以上说明主要涉及其中n=1的式2化合物。
然而,也经常优选使用其中n=0的式2化合物,在这种情况下,优选保持m+p=0,或m+p>1或2,条件是取代基X和Y中的至少两个选自由以下组成的组:OH和氧烷基。
特别优选使用选自包括以下的组的式2(其中n=0)化合物:
在被描述为特别优选且由其结构式表示的化合物中,R3始终为H。
代替这些优选化合物,在每种情况下还优选使用其中R3为CH3或为具有2至30个C原子的直链或支链烷基的对应化合物。
在以上燕麦蒽酰胺类似物中,特别优选的是8号化合物(二氢燕麦蒽酰胺D(2-[(3-(4-羟苯基)丙酰基]氨基)苯甲酸;INCI:羟苯基丙酰胺苯甲酸;CAS 697235-49-7)和27号化合物。
除了以上天然存在的燕麦蒽酰胺和非天然存在的燕麦蒽酰胺类似物之外,还在重组酵母中生成了新的燕麦蒽酰胺类似物,包括N-(4′-羟基肉桂酰基)-3-羟基邻氨基苯甲酸(YAvn I)和N-(3′-4′-二羟基肉桂酰基)-3-羟基邻氨基苯甲酸(YAvn II),它们是通过采用两个编码参与酚酯生物合成的关键蛋白质的植物基因(来自烟草的4cl-2,来自球洋蓟的hct)对酿酒酵母(Saccharomyces cerevisiae)菌株进行工程改造而产生的。值得注意的是,YAvn I和YAvn II分别与Avn A和Avn C具有结构相似性。
在本发明的上下文中,优选的是从天然来源获得的天然存在的燕麦蒽酰胺或合成产生的天然存在的燕麦蒽酰胺,并且二者用法相似。
术语“燕麦蒽酰胺或其类似物”还旨在包括其存在的各种异构体,特别是(天然存在的)反式异构体以及顺式异构体,诸如,例如由曝光所致光异构化而诱导的、具有顺势异构化双键(式1或2,n=1)或1或2个顺式异构化双键(式1或2,n=2)的燕麦蒽酰胺。
特别地,在本发明的上下文中,燕麦蒽酰胺是由通式1表示并在表1中定义的燕麦蒽酰胺化合物中的任何一种或其任何异构体,或者燕麦蒽酰胺类似物是如上所述的、由通式2及其定义表示的燕麦蒽酰胺类似物化合物中的任何一种或其任何异构体。
在根据第一方面的本发明的优选变型中,该组合物包含至少一种燕麦蒽酰胺,该燕麦蒽酰胺选自由以下组成的组:燕麦蒽酰胺A、B、C、G、H、K、L和R,又更优选燕麦蒽酰胺A或燕麦蒽酰胺L。
在根据第一方面的本发明的优选变型中,该组合物至少包含燕麦蒽酰胺类似物化合物二氢燕麦蒽酰胺D。
在另一个变型中,本发明的组合物包含两种、三种、四种或者甚至更多种不同燕麦蒽酰胺的混合物,这些燕麦蒽酰胺选自由以下组成的组:燕麦蒽酰胺A、B、C、G、H、K、L(非柯林斯缩写;CAS号172549-38-1)(又称O或2pd)和R。因此,这些燕麦蒽酰胺的组合/混合物可以包括以下燕麦蒽酰胺组合中的任一种:A/B;A/C;A/G;A/H;A/K;A/L;A/R;B/C;B/G;B/H;B/K;B/L;B/R;C/G;C/H;C/K;C/L;C/R;G/H;G/K;G/L;G/R;H/K;H/L;H/R;K/L;K/R;L/R;A/B/C;A/B/G;A/B/H;A/B/K;A/B/L;A/B/R;A/C/G;A/C/H;A/C/K;A/C/L;A/C/R;A/G/H;A/G/K;A/G/L;A/G/R;A/H/K;A/H/L;A/H/R;A/K/L;A/K/R;A/L/R;B/C/G;B/C/H;B/C/K、B/C/L;B/C/R;C/G/H;C/G/K、C/G/L;C/G/R、G/H/K;G/H/L;G/H/R;H/K/L、H/K/R;K/L/R;A/B/C/G;A/B/C/H;A/B/C/K;A/B/C/L;A/B/C/R;A/C/G/H;A/C/G/K;A/C/G/L;A/C/G/R;A/G/H/K;A/G/H/L;A/G/H/R;A/H/K/L;A/H/K/R;A/K/L/R;B/C/G/H;B/C/G/K;B/C/G/L;B/C/G/R;C/G/H/K;C/G/H/L;C/G/H/R;G/H/K/L;G/H/K/R和H/K/L/R。
然而,根据本发明的最优选的燕麦蒽酰胺的混合物是A/B、A/C、A/L、B/C和A/B/C。
除了以上燕麦蒽酰胺化合物或燕麦蒽酰胺组合之外,该组合物还可以包含除燕麦蒽酰胺A、B、C、G、H、K、L(非柯林斯缩写;CAS号172549-38-1)(又称O或2pd)和R以外的一种或多种燕麦蒽酰胺,诸如燕麦蒽酰胺D、E、F U、X、Y(也称2)、AA、CC或OO,或者表1指定的剩余燕麦蒽酰胺化合物中的任何一种。
在另一个变型中,本发明的组合物包含至少一种(即,一种、两种或者甚至更多种)燕麦蒽酰胺与燕麦蒽酰胺类似物化合物二氢燕麦蒽酰胺D的组合,该燕麦蒽酰胺选自由以下组成的组:燕麦蒽酰胺A、B、C、G、H、K、L(非柯林斯缩写;CAS号172549-38-1)(又称O或2pd)和R。因此,燕麦蒽酰胺的混合物可以包括以下组合中的任一种:A/二氢燕麦蒽酰胺D;B/二氢燕麦蒽酰胺D;C/二氢燕麦蒽酰胺D;G/二氢燕麦蒽酰胺D;H/二氢燕麦蒽酰胺D;K/二氢燕麦蒽酰胺D;L/二氢燕麦蒽酰胺D;或R/二氢燕麦蒽酰胺D;A/B/二氢燕麦蒽酰胺D;A/C/二氢燕麦蒽酰胺D;A/D/二氢燕麦蒽酰胺D;A/G/二氢燕麦蒽酰胺D;A/H/二氢燕麦蒽酰胺D;A/K/二氢燕麦蒽酰胺D;A/L/二氢燕麦蒽酰胺D;A/R/二氢燕麦蒽酰胺D;B/C/二氢燕麦蒽酰胺D;B/D/二氢燕麦蒽酰胺D;B/G/二氢燕麦蒽酰胺D;B/H/二氢燕麦蒽酰胺D;B/K/二氢燕麦蒽酰胺D;B/L/二氢燕麦蒽酰胺D;B/R/二氢燕麦蒽酰胺D;C/D/二氢燕麦蒽酰胺D;C/G/二氢燕麦蒽酰胺D;C/H/二氢燕麦蒽酰胺D;C/K/二氢燕麦蒽酰胺D;C/L/二氢燕麦蒽酰胺D;C/R/二氢燕麦蒽酰胺D;G/H/二氢燕麦蒽酰胺D;G/K/二氢燕麦蒽酰胺D;G/L/二氢燕麦蒽酰胺D;G/R/二氢燕麦蒽酰胺D;H/K/二氢燕麦蒽酰胺D;H/L/二氢燕麦蒽酰胺D;H/R/二氢燕麦蒽酰胺D;K/L/二氢燕麦蒽酰胺D;K/R/二氢燕麦蒽酰胺D;或L/R/二氢燕麦蒽酰胺D,又更优选A/二氢燕麦蒽酰胺D或燕麦蒽酰胺L/二氢燕麦蒽酰胺D。
除了以上燕麦蒽酰胺组合物之外,该组合物还可以包含与除燕麦蒽酰胺A、B、C、G、H、K、L(非柯林斯缩写;CAS号172549-38-1)(又称O或2pd)和R以外的一种或多种燕麦蒽酰胺的组合,诸如与燕麦蒽酰胺D、E、F U、X、Y(也称2)、AA、CC或OO或者表1指定的剩余燕麦蒽酰胺化合物中的任何一者与二氢燕麦蒽酰胺D的组合。
在另一个变型中,本发明的组合物包含一种燕麦蒽酰胺类似物化合物、优选二氢燕麦蒽酰胺D,或燕麦蒽酰胺类似物化合物、优选二氢燕麦蒽酰胺D与通式2表示的及以上指定的任何一种或多种不同燕麦蒽酰胺类似物化合物的组合。
按组合物的总重量计,如上所述的至少一种燕麦蒽酰胺或燕麦蒽酰胺类似物化合物、或燕麦蒽酰胺或燕麦蒽酰胺类似物化合物的混合物可以以0.0001wt%至5.0wt%的浓度或总量存在于组合物中。在一个优选变型中,按组合物的总重量计,该组合物包含浓度或总量为0.0005wt%至2.0wt%、又更优选0.001wt%至1.0wt%的至少一种燕麦蒽酰胺或燕麦蒽酰胺类似物化合物、或者燕麦蒽酰胺或燕麦蒽酰胺类似物化合物的混合物。
根据本发明第一方面的组合物的第二主要成分是下式3表示的4-羟基苯乙酮(INCI:羟基苯乙酮;CAS 99-93-4)或对羟基苯乙酮:
4-羟基苯乙酮是一种天然等同成分。虽然它是合成生产的,但在自然界也发现存在于挪威云杉树中。
在护肤品或药物制剂中,4-羟基苯乙酮是一种合成的抗氧化剂和皮肤调理成分。具体的抗氧化剂化合物实际上被称为对羟基苯乙酮,这是一种酚类抗氧化剂,能够中和几种不同类型的自由基。它的另一个好处是提升护肤品的防腐体系。这是有利的,因为它使护肤品化学家能够使用较少量的防腐剂而不会令功效丧失,又有利于降低过敏反应的风险。4-羟基苯乙酮还具有舒缓作用,因为它可以抑制皮肤表面的一种会造成刺激症状的酶(被称为COX-2)。另外,该产品是在FEMA/GRAS中列出的一种天然等同成分。4-羟基苯乙酮在高、低pH值和温度下都表现出出色的稳定性。此外,羟基苯乙酮易于配制,适用于诸如洗发水、湿巾和乳液等冷加工配制剂,它无色、气味淡,可溶于乙醇和乙二醇,并且属于食用级,这使其成为一种适用于口腔护理的化合物。另外,4-羟基苯乙酮是已知的、可用于提高例如调味剂和香料的溶解度的化合物,特别是用于溶解亲脂性化合物,如EP 2 962 678 A1中所述。然而,由于物质的化学性质不同,一种化合物与其他物质组合的效果不能简单地被概括并应用于其他化合物。
令人惊讶地,事实证明,与4-羟基苯乙酮组合有利于提高燕麦蒽酰胺、或燕麦蒽酰胺类似物在溶剂中或在包含一种或多种燕麦蒽酰胺或燕麦蒽酰胺类似物的组合物中的溶解度。根据其浓度,4-羟基苯乙酮甚至可以完全溶解一种或多种燕麦蒽酰胺、或一种或多种燕麦蒽酰胺类似物化合物。
更令人惊讶地,事实证明,添加4-羟基苯乙酮特别有效地增加了燕麦蒽酰胺A、或燕麦蒽酰胺L、或二氢燕麦蒽酰胺D的溶解度,这三者在燕麦蒽酰胺或燕麦蒽酰胺类似物之中分别具有最差的溶解度。
用于提高溶解度的化合物是指用于提高另一种难溶性组分或物质在溶剂或组合物中的溶解度、并用于防止所述组分或物质发生絮凝或沉淀的化合物。通过增加难溶性组分或物质的溶解度,提高了其在溶剂中或在其中掺入该组分的组合物中的所需浓度,或提高了其对生物学或药理学反应的生物利用度。另外,通过增加难溶性组分或物质的溶解度,可以使包含所述难溶性组分或物质的液体组合物或溶液在储存期间保持稳定。
因此,在本发明的上下文中,4-羟基苯乙酮是一种用于提高活性组分(即,一种或多种燕麦恩酰胺)在溶剂中或在组合物中的溶解度的物质,从而提高该活性物质在组合物中或在掺入其的最终产品中的生物利用度。
通过添加4-羟基苯乙酮,可以显著增加燕麦恩酰胺的溶解度,即,燕麦恩酰胺不会发生絮凝或沉淀。特别地,包含一种或多种燕麦恩酰胺的液体组合物溶液因此可以在储存期间保持稳定。以下示例证明了这一效果:添加4-羟基苯乙酮会使溶液更加透明,沉淀更少。
按组合物的总重量计,在根据本发明的组合物中存在的4-羟基苯乙酮的总量可以在0.005wt%和2.0wt%之间。在一个优选变型中,稳定剂在组合物中的总浓度按组合物的总重量计为0.01wt%至1.5wt%,甚至优选地按组合物的总重量计可以在0.1wt%和1.0wt%之间。
在根据本发明的组合物中存在的4-羟基苯乙酮的浓度最优选为0.1wt%至1.0wt%:该组合物呈透明状且不混浊。这表明燕麦蒽酰胺完全溶解在组合物中。
从以下示例中可以明显看出,4-羟基苯乙酮可以有效提高一种或多种燕麦蒽酰胺的溶解度:在0.01wt%的浓度下,4-羟基苯乙酮已提高了一种或多种燕麦蒽酰胺、特别是燕麦蒽酰胺A的溶解度,并且在0.50wt%的浓度下,4-羟基苯乙酮即使在低浓度下也能使一种或多种燕麦蒽酰胺完全溶解。以上浓度对应于其中羟基苯乙酮通常用作护肤品或药物制剂中的抗氧化剂或抗微生物剂时的浓度。
根据本发明的特别优选的混合物是其中组合物包含或由以下组成的那些混合物:按组合物的总重量计,
-0.0001wt%至5.0wt%、特别是0.0005wt%至2.0wt%、仍更优选0.001wt%至1.0wt%的至少一种燕麦蒽酰胺或其类似物;和
-0.005wt%至2.0wt%、特别是0.01wt%至1.5wt%、仍更优选0.1wt%至1.0wt%的4-羟基苯乙酮。
特别地,如果根据本发明的组合物中存在的至少一种燕麦蒽酰胺与4-羟基苯乙酮的比率为1:1至1:50、更优选的比率为1:1.5至1:40,或者如果该至少一种燕麦蒽酰胺类似物、特别是二氢燕麦蒽酰胺D的比率为1:0.2至1:30、特别是1:0.5至1:20,则获得了良好的溶解度,如表8中所证实的。该组合物的外观良好,并且燕麦恩酰胺或燕麦恩酰胺类似物化合物没有发生絮凝或沉淀。
根据本发明的组合物、特别是那些表征为优选组合物的组合物拥有良好溶解度的燕麦蒽酰胺或燕麦蒽酰胺类似物化合物,特别是燕麦恩酰胺A、燕麦蒽酰胺L或二氢燕麦蒽酰胺D。令人惊讶地,根据本发明的组合物的溶解度优于仅包含一种或多种燕麦恩酰胺或燕麦蒽酰胺类似物化合物但不含4-羟基苯乙酮的组合物的溶解度。展现出具有重大意义的生物学益处(诸如抗炎、抗氧化、止痒、抗刺激和抗动脉粥样硬化活性)的护肤或药物活性物质(即燕麦蒽酰胺或燕麦蒽酰胺类似物、特别是二氢燕麦蒽酰胺D)没有发生絮凝或沉淀,因此能够以治疗有效量持续更长有效时间,从而更好地达到其预期目的。
根据本发明的组合物也特别有效并且不含任何毒理学或皮肤病学上可能有危险的次级组分;因此,使用该组合物时没有护肤品和药物制剂中的其他担忧。
根据本发明的组合物可以在将其添加到最终配制剂之前制备成溶解度提高的液体组合物的形式,或者可以将单独的组合物成分分别添加到最终配制剂中,从而提高其中的至少一种燕麦蒽酰胺或燕麦恩酰胺类似物化合物的溶解度。
应当记住,在组合物和最终制剂中使用的4-羟基苯乙酮
-在毒理学上可接受,
-具有良好的皮肤耐受性、
-稳定性(特别是在惯用配制剂中),
-优选无味且
-能够廉价生产(即使用标准工艺和/或从标准前体开始)并且
处于与活性和施用相关的浓度范围内。
由于燕麦蒽酰胺或燕麦恩酰胺类似物化合物的抗炎症、抗氧化、止痒、抗刺激和抗动脉粥样硬化活性与4-羟基苯乙酮的上述特性相结合,使燕麦蒽酰胺或燕麦恩酰胺类似物针对生物学或药理学反应达到所需的浓度或生物利用度,因此,根据本发明的组合物有益于皮肤保护以及皮肤病的预防和/或治疗。
因此,本发明的另一方面涉及根据本发明的第一方面的组合物作为护肤品的用途,特别是用于皮肤护理、头皮护理、头发护理、指甲护理或用于预防和/或治疗皮肤病状、皮肤不耐受和敏感、皮肤刺激、皮肤发红、风团、瘙痒(发痒)、皮肤老化、皱纹形成、皮肤体积损失、皮肤弹性丧失、色素斑、色素异常、或皮肤干燥(即用于皮肤保湿)。
本发明的另一方面涉及根据本发明的第一方面的组合物用作药剂。
由于其前述优越特性,根据本发明的第一方面的组合物在以下方面特别有用:预防和/或治疗皮肤病或角化病、特别是具有与屏障相关的、炎症性、免疫过敏性、致动脉粥样硬化性、干燥性或过度增殖性组分的皮肤病或角化病,或预防和/或治疗心血管疾病、过敏反应、冠心病,以降低血清中的LDL胆固醇和脂质水平,降低血压,提高对胰岛素的敏感性以及使得能够对血糖水平进行控制。
由于燕麦蒽酰胺的特定抗氧化作用,本发明还涉及根据本发明的第一方面的组合物用于预防和/或治疗与ROS产生增加有关的皮肤病。
此类皮肤病或角化紊乱的示例包括:湿疹、牛皮癣、皮脂溢、皮肤炎、红斑、瘙痒(发痒)、耳炎、炎症、刺激、纤维化、扁平苔藓、玫瑰糠疹、花斑糠疹、自身免疫性大疱病、荨麻疹、血管水肿性和过敏性皮肤反应和伤口愈合,并且与ROS产生增加相关的皮肤病的示例选自由以下组成的组:特应性皮炎、神经性皮炎、牛皮癣、红斑痤疮、痤疮样皮疹、皮脂腺活性降低和干燥病。
在本发明的一个特别优选的变型中,根据本发明的包含至少一种燕麦蒽酰胺或其类似物或由其组成的组合物有益地用于预防和/或治疗瘙痒(发痒)。
慢性瘙痒是与各种皮肤病状和全身性疾病相关的常见症状,在某些情况下已知没有潜在病状。慢性瘙痒按临床表现(例如,与患病/发炎或正常/非发炎的皮肤相关和/或与存在继发性划痕损伤相关)和潜在原因(例如,皮肤病、全身性、神经性、心身性、混合性或未确定性起因)进行分类。
将燕麦蒽酰胺或其类似物用于这些相应目的的用途对应于以下方法:通过添加治疗有效量的活性物质或组合物,赋予活性物质的各自的治疗活性。
在本发明的上下文中,组合物的有效量是每种活性组分(即燕麦蒽酰胺)足以表现出益处(诸如,减少与待治疗的紊乱、疾病或病状相关的症状)的量。当应用于组合或组合物时,如在本案中,该术语是指组合的活性成分带来益处的量。
相应地,本发明涉及一种方法,该方法用于在有需要的受试者中预防和/或治疗皮肤病或角化病、特别是具有屏障相关、炎症性、免疫过敏性、致动脉粥样硬化性、干燥性或过度增殖性组分的皮肤病或角化病,或在预防和/或治疗心血管疾病、过敏反应、冠心病中,用于降低血清中的LDL胆固醇和脂质水平,用于降低血压,用于提高对胰岛素的敏感性以及用于使得能够对血糖水平进行控制,其中该方法包括向受试者施用治疗有效量的包含至少一种燕麦蒽酰胺或其类似物和4-羟基苯乙酮或由其组成的组合物,该组合物包含至少一种燕麦蒽酰胺或其类似物和4-羟基苯乙酮的量足以预防和/或治疗皮肤病或角化病、特别是具有屏障相关、炎症性、免疫过敏性、致动脉粥样硬化性、干燥性或过度增殖性组分的皮肤病或角化病,或在预防和/或治疗心血管疾病、过敏反应、冠心病中,用于降低血清中的LDL胆固醇和脂质水平,用于降低血压,用于提高对胰岛素的敏感性以及用于使得能够对血糖水平进行控制。
由于其如上所述的显著效果,根据本发明的第一方面的组合物有益地适用于制备食品、食品补充剂、护肤品、药物或兽药制剂。
根据本发明的组合物可以轻松地掺入常规食品、食品补充剂、护肤品、药物或兽药制剂中。
因此,本发明的又一方面涉及包含根据本发明的组合物的食品、食品补充剂、护肤品、药物和兽药制剂。在本发明的优选变型中,包含该组合物的功能性食品被提供为用于皮肤护理和/或预防或改善以上皮肤病或角化病的有效成分。
在一个优选变型中中,该食品、食品补充剂、护肤品、药物或兽药制剂按其重量计以0.0001%至5.0%、更优选0.0005%至2.0%、最优选0.001wt%至1.0wt%的量包含根据本发明的组合物。
在这一上下文中,还可行并且在某些情况下有利的是,将根据本发明的组合物与其他活性化合物组合,例如其他协同增强的物质(诸如抗炎剂、抗细菌剂或抗真菌剂)、具有减轻发红或止痒作用的物质、缓和物质、保湿剂和/或清凉剂和/或抗氧化剂、防腐剂、(金属)螯合剂、渗透促进剂和/或护肤或药学上可接受的赋形剂,如以下详细描述和举例说明的。
活性物质意指为赋予组合物或制剂/惯用配制剂主要效用的物质或化合物。此类活性物质的示例包括抗氧化剂、防腐剂、(金属)螯合剂、渗透促进剂等。赋形剂是指用于配制作为加工或制造的结果的护肤品或药物的非活性物质。
由于皮肤病状或疾病通常与皮肤干燥、皮肤擦伤、皮肤损伤或甚至炎症有关,因此根据本发明的组合物或护肤品和/或药物制剂特别有利地含有皮肤保湿和/或水分保持物质,清凉剂,渗透剂,角质层溶解物质,滋养物质,抗炎、抗细菌或抗真菌物质,和/或具有减轻发红或减轻骚痒作用的物质,和/或缓和物质。
皮肤干燥时,发痒会发生得特别强烈。在护肤品和药物制剂中使用皮肤保湿和/或水分保持物质或调节剂可以显著减轻发痒。因此,根据本发明的护肤品或药物制剂也可以特别有利地与一种或多种皮肤保湿和/或水分保持物质或调节剂组合。因此,根据本发明的护肤品或药物制剂还可以有利地含有以下保湿和/或水分保持物质或调节剂:乳酸钠,尿素,尿素衍生物,醇,丙三醇,二醇(诸如丙二醇、己烯乙二醇、1,2-戊二醇、1,2-己二醇、1,2-庚二醇、1,2-辛二醇、1,2-壬二醇、1,2-癸二醇或所述二醇的混合物,特别是1,2-己二醇和1,2-辛二醇的混合物),胶原蛋白,弹性蛋白或透明质酸,己二酸二辛酯,矿脂,尿刊酸,卵磷脂,泛醇,植烷三醇,番茄红素,(类)神经酰胺,鞘糖脂,胆固醇,植物甾醇,壳聚糖,硫酸软骨素,羊毛脂,羊毛脂酯类,氨基酸,α-羟基酸(例如柠檬酸、乳酸、马来酸)及其衍生物,单糖、二糖及寡糖(诸如葡萄糖、半乳糖、果糖、甘露糖、果糖和乳糖),多糖(诸如R-葡聚糖,特别是来自燕麦的1,3-1,4-β-葡聚糖)、α羟基脂肪酸、三萜酸(诸如桦木酸和熊果酸),以及藻类提取物。
根据物质的不同,按即用型护肤品或药物最终产品的总重量计,所使用的水分保持调节剂的浓度在0.1%和10%(m/m)之间、优选在0.5%和5%(m/m)之间。这些数据特别适用于被有利地使用的此类二醇,诸如己烯乙二醇、1,2-戊二醇、1,2-己二醇、1,2-辛二醇和1,2-癸二醇,以及1,2-己二醇和1,2-辛二醇的混合物。
在该组合物或含有根据本发明的组合物的护肤品和药物制剂中使用清凉剂可以减轻发痒。因此,根据本发明的制剂也可以特别有利地与一种或多种清凉剂组合。以下列出了在本发明范围内使用的优选的个别清凉剂。本领域技术人员可以向该列表中添加许多其他清凉剂;所列出的清凉剂也可以相互组合使用:l-薄荷醇、d-薄荷醇、外消旋薄荷醇、薄荷酮甘油缩醛(商品名: MGA)、乳酸薄荷酯(商品名:ML;乳酸薄荷酯优选为l-乳酸薄荷酯、特别是l-薄荷基l-乳酸酯)、取代的薄荷基-3-甲酰胺(诸如薄荷基-3-甲酸N-乙基酰胺)、2-异丙基-N-2,3-三甲基丁酰胺、取代的环己烷羧酰胺、3-薄荷氧基丙烷-1,2-二醇、2-羟乙基碳酸薄荷酯、2-羟丙基碳酸薄荷酯、N-乙酰甘氨酸薄荷酯、异胡薄荷醇、乙基氨基草酸薄荷酯(商品名:X-cool)、羟基羧酸薄荷酯(诸如3-羟基丁酸薄荷酯)、琥珀酸单薄荷酯、2-巯基环癸酮、2-吡咯烷酮-5-甲酸薄荷酯、2,3-二羟基-对薄荷烷、3,3,5-三甲基环己酮甘油缩酮、3-薄荷基-3,6-二和三氧杂链烷酸酯、3-甲氧基乙酸薄荷酯和冰素。
由于其特别的协同作用而被优选的清凉剂为:l-薄荷醇、d-薄荷醇、外消旋薄荷醇、薄荷酮甘油缩醛(商品名: MGA)、乳酸薄荷酯(优选l-乳酸薄荷酯,特别是l-薄荷基l-乳酸酯(商品名:ML)、取代的薄荷基-3-甲酰胺(诸如薄荷基-3-羧酸N-乙基酰胺)、2-异丙基-N-2,3-三甲基丁酰胺、取代的环己烷甲酰胺、3-薄荷氧基丙烷-1,2-二醇、2-羟乙基碳酸薄荷酯、2-羟丙基碳酸薄荷酯、乙基氨基草酸薄荷酯(商品名:X-cool)和异胡薄荷醇。
特别优选的清凉剂为:l-薄荷醇、外消旋薄荷醇、薄荷酮甘油缩醛(商品名: MGA)、乳酸薄荷酯(优选l-乳酸薄荷酯,特别是l-薄荷基l-乳酸酯(商品名:ML)、乙基氨基草酸薄荷酯(商品名:X-cool)、3-薄荷氧基丙烷-1,2-二醇、2-羟乙基碳酸薄荷酯和2-羟丙基碳酸薄荷酯。
根据物质的不同,按即用型护肤品或药物最终产品的总重量计,所使用的清凉剂的浓度优选地在0.01wt%和20wt%之间,并且特别优选地在0.1wt%和5wt%之间。
该组合物或含有根据本发明的组合物的护肤品或药物制剂也可以与一种或多种渗透剂一起使用。此处会提及的渗透剂的示例包括来自包括以下的组的物质:糖醇(肌醇、甘露醇、山梨醇),季胺(诸如牛磺酸、胆碱、甜菜碱、甜菜碱甘氨酸、四氢嘧啶、磷酸二甘油酯、磷酸胆碱或甘油磷酸胆碱),氨基酸(诸如谷氨酰胺、甘氨酸、丙氨酸、谷氨酸、天冬氨酸或脯氨酸),磷脂酰胆碱,磷脂酰肌醇、无机磷酸盐和所述化合物的聚合物,诸如蛋白质、肽、聚氨基酸和多元醇。所有渗透剂同时具有皮肤保湿作用。
优选地,角质层溶解物质还可以与根据本发明的组合物组合。角质层溶解化合物包括一大组α-羟基酸。例如,优选使用水杨酸。
在用于例如干燥和/或发痒皮肤的局部护肤或药物治疗的根据本发明的组合物或含有该组合物的护肤品或药物制剂中,特别是滋养物质占据大比例也是特别有利的,因为减少了由亲脂性组分造成的经表皮水分流失。在一个优选的实施方案中,护肤品或药物制剂含有一种或多种滋养性动物和/或植物脂肪和油类,诸如橄榄油、葵花油、精制大豆油、棕榈油、芝麻油、菜籽油、杏仁油、琉璃苣油、月见草油、椰子油、乳木果油、荷荷巴油、鲸油、兽脂、牛脚油和猪油,以及任选地其他滋养组分,诸如具有8至30个C原子的脂肪醇。此处使用的脂肪醇可以是饱和或不饱和的,也可以是直链或支链的。特别地,可以特别优选地与根据本发明的混合物组合的滋养物质还包括:神经酰胺,在此理解为意指N-酰基鞘氨醇(鞘氨醇的脂肪酸酰胺)或此类脂质的合成类似物(所谓的类神经酰胺),其可显著提高角质层的保水能力;磷脂,诸如大豆卵磷脂、鸡蛋卵磷脂和脑磷脂;和矿脂、石蜡油和硅油,后者尤其包括二烷基芳基硅氧烷和烷基芳基硅氧烷,诸如二甲基聚硅氧烷和甲基苯基聚硅氧烷及其烷氧基化和季铵化衍生物。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以含有其他抗炎活性化合物、或展现出抗发红和抗发痒活性的活性化合物。在这一上下文中,可以使用任何抗炎活性化合物、以及减轻发红和发痒并且适用于或惯用于护肤品和/或皮肤病学应用的活性化合物。有利地,所使用的抗炎活性化合物以及减轻发红和/或发痒的活性化合物是皮质类固醇类型的甾体抗炎物质,诸如,例如氢化可的松、地塞米松、磷酸地塞米松、甲基强的松龙或可的松,其中这一列表可以通过添加其他甾体抗炎剂进行扩展。也可以使用非甾体抗炎剂,例如:昔康类,诸如吡罗昔康或替诺昔康;水杨酸类,诸如阿司匹林、 或芬度柳;乙酸衍生物类,诸如双氯芬酸、芬氯芬酸、吲哚美辛、舒林酸、托美汀或环氯茚酸(clindanac);芬那酸类,诸如甲芬那酸、甲氧芬那酸、氟芬那酸或尼氟酸;丙酸衍生物,诸如布洛芬、萘普生、苯恶洛芬;或吡唑类,诸如保泰松、羟布宗(oxyphenylbutazone)、非普拉宗(feprazone)或阿扎丙宗(azapropazone)。另选地,可以使用天然抗炎物质和减轻发红和/或发痒的物质。可以使用植物提取物、特制高活性植物提取物馏分,还有从植物提取物中分离的高纯度活性物质。特别优选的是来自甘菊、芦荟、没药属、茜草属、柳树、柳草、生姜、万寿菊、山金车、甘草属、紫锥菊属、悬钩子属和纯物质中的提取物、馏分和活性物质,诸如尤其是红没药醇、芹菜素、芹菜素-7-葡萄糖苷、姜酚(诸如[6]-姜酚)、姜酮酚(诸如[6]-姜酮酚)、乳香脂酸、植物甾醇、甘草甜素、光甘草定或甘草查耳酮A。含有组胺释放抑制剂的制剂也可以含有两种或更多种抗炎活性化合物的混合物。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以含有用于防腐目的的活性化合物,其中可以使用适用于或惯用于护肤品和/或皮肤病学应用、并且有利地选自由以下防腐剂组成的组的任何防腐剂:诸如尤其是苯甲酸、其酯类和盐类;丙酸及其盐类;水杨酸及其盐类;2,4-己酸(山梨酸)及其盐类;甲醛和多聚甲醛;2-羟基联苯醚及其盐类;2-锌硫代吡啶N-氧化物;无机亚硫酸盐类和亚硫酸氢盐类;碘酸钠;氯丁醇;4-羟基苯甲酸及其盐类和酯类;脱氢乙酸;甲酸;1,6-双(4-脒基-2-溴苯氧基)-正己烷及其盐类;乙基汞-(II)-硫代水杨酸的钠盐;苯汞及其盐类;10-十一碳烯酸及其盐类;5-氨基-1,3-双(2-乙基己基)-5-甲基六氢嘧啶;5-溴-5-硝基-1,3-二恶烷;2-溴-2-硝基-1,3-丙二醇;2,4-二氯苄醇;N-(4-氯苯基)-N'-(3,4-二氯苯基)脲;4-氯间甲酚;2,4,4'-三氯-2'-羟基-二苯醚;4-氯-3,5-二甲基苯酚;1,1'-亚甲基-双(3-(1-羟甲基-2,4-二氧咪唑烷-5-基)脲);聚(六亚甲基双胍)盐酸盐;2-苯氧乙醇;六亚甲基四胺;1-(3-氯丙烯)-3,5,7-三氮杂-1-氮鎓金刚烷氯化物;1-(4-氯-苯氧基)-1(1H-咪唑-1-基)-3,3-二甲基-2-丁酮;1,3-双(羟甲基)-5,5-二甲基-2,4-咪唑烷二酮;苄醇;1,2-二溴-2,4-二氰基丁烷;2,2'-亚甲基-双(6-溴-4-氯-苯酚);溴氯酚;5-氯-2-甲基-3(2H)-异噻唑啉酮和2-甲基-3(2H)异噻唑啉酮与氯化镁和硝酸镁的混合物;2-苄基-4-氯苯酚;2-氯乙酰胺;氯己定;乙酸氯己定;葡萄糖酸氯己定;盐酸氯己定;1-苯氧基-丙烷-2-醇;N-烷基(C12-C22)三甲基溴化和氯化铵;4,4-二甲基-1,3-恶唑烷;N-羟甲基-N-(1,3-二(羟甲基)-2,5-二氧咪唑烷-4-基)-N'-羟甲基脲;1,6-双(4-脒基苯氧基)-正己烷及其盐类;戊二醛5-乙基-1-氮杂-3,7-二氧杂双环(3.3.0)辛烷;3-(4-氯苯氧基)-1,2-丙二醇;季铵盐;烷基(C8-C18)二甲基苄基氯化铵;烷基(C8-C18)二甲基苄基溴化铵;烷基(C8-C18)二甲基苄基糖精铵;苄基半缩甲醛;3-碘-2-丙炔基丁基氨基甲酸酯;或((羟甲基)氨基)乙酸钠。
其他抗细菌或抗真菌活性物质还可以特别有利地用于根据本发明的组合物或含有该组合物的护肤品或药物制剂中,其中可以使用适用于或惯用于护肤品和/或皮肤病学应用的任何抗细菌或抗真菌活性物质。除了一大组常规抗生素,在此有利的其他产品包括与护肤品相关的那些产品,诸如特别是三氯生、氯咪巴唑、辛氧基甘油、(1-羟基-4甲基-6-(2,4,4-三甲基戊烷基)-2(1H)-吡啶酮2-乙醇胺盐)、壳聚糖、法尼醇、单月桂酸甘油酯或所述物质的组合,这些尤其是用于预防狐臭、脚臭或头皮屑。
根据本发明的组合物或含有该组合物的护肤品和/或药物制剂还可以含有一种或多种缓和物质,其中可以使用任何适用于或惯用于护肤品和/或药物应用的任何缓和物质,诸如α-红没药醇,甘菊环烃,愈创蓝油烃,18-β-甘草次酸,尿囊素,芦荟汁或凝胶,金缕梅(Hamamelis virginiana)、紫锥菊属、积雪草、洋甘菊物提取物,山金车、甘草属、藻类、海藻和金盏花提取物,以及植物油(诸如甜杏仁油、猴面包树油、橄榄油)、泛醇、月桂醇聚醚-9、十三烷醇聚醚-9和4-叔丁基环己醇。
另外,根据本发明的组合物或护肤品或药物制剂还可以特别有利地与用于控制体臭的抑制排汗的活性化合物(止汗剂)组合使用。使用的抑制排汗的活性化合物特别包括铝盐,诸如氯化铝、氢氯酸铝、硝酸铝、硫酸铝、乙酸铝等。然而,使用锌、镁或锆化合物也可以是有利的。铝盐以及在某种较小程度上铝/锆盐组合已被证明可有效用于护肤和皮肤病学止汗剂。还值得注意的是,部分中和的羟基氯化铝因此对皮肤更加耐受,但效果不够有效。还可以使用除铝盐之外的物质,诸如,例如:(a)蛋白质沉淀物质,诸如特别是甲醛、戊二醛、天然和合成鞣剂和三氯乙酸,其会导致汗腺表面闭合;(b)局部麻醉剂,包括例如利多卡因、丙胺卡因或它们的混合物的稀释溶液,其通过阻断周围神经通路来关闭汗腺的交感神经供应;(c)X、A或Y型沸石,其会减少汗液分泌并且还用作不良气味吸附剂;以及(d)肉毒杆菌毒素(细菌肉毒杆菌(Chlostridium botulinum)的毒素),其也用于多汗症(汗液分泌的病理性增加),并且其作用是基于不可逆地阻断与汗液分泌相关的递质物质乙酰胆碱的释放。
在根据本发明的组合物或含有该组合物的护肤品或药物制剂中,与(金属)螯合剂的组合也可以是有利的,其中可以使用适用于或惯用于护肤品和/或皮肤病学应用的任何金属螯合剂。优选的(金属)螯合剂包括α-羟基脂肪酸、植酸、乳铁蛋白、α-羟基酸,诸如尤其是葡萄糖酸、甘油酸、乙醇酸、异柠檬酸、柠檬酸、乳酸、马来酸、扁桃酸、酒石酸,以及腐植酸、胆汁酸、胆汁提取物、胆红素、胆绿素或EDTA、EGTA及其衍生物。
使用时,以使用护肤品或皮肤病学产品的惯用方式,将根据本发明的组合物或含有该组合物的护肤品或药物制剂以足够的量涂抹于皮肤、头皮、头发和/或指甲上。在这一上下文中,含有根据本发明的组合物并且另外用作防晒剂的护肤品和皮肤病学制剂提供了特别的优势。有利地,这些制剂含有至少一种UVA过滤剂和/或至少一种UVB过滤剂和/或至少一种无机色素。在这一上下文中,该制剂可以采用各种形式,诸如,例如惯用于此类制剂的形式,诸如,例如溶液、油包水(W/O)乳液、水包油(O/W)乳液或多重乳液(诸如水包油包水(W/O/W)乳液、凝胶、水分散体、固体棒或气溶胶。
根据本发明的组合物或含有该组合物的护肤品或药物制剂可以有利地与吸收UVB范围内的UV辐射的物质组合,按制剂的干重计,过滤物质的总量为例如0.01%至40%(m/m)、优选0.1%至10%(m/m)、特别是1.0%至5.0%(m/m),从而提供保护头发和/或皮肤免受整个范围的紫外线辐射的护肤品制剂。它们还可以用作头发的防晒剂。如果根据本发明的制剂含有UVB过滤物质,则这些物质可以是油溶性的或水溶性的。有利的油溶性UVB过滤剂包括:3-亚苄基樟脑的衍生物,优选3-(4-甲基亚苄基)樟脑、3-亚苄基樟脑;4-氨基苯甲酸的衍生物,优选2-乙基己基-4-(二甲氨基)苯甲酸酯、4-(二甲氨基)苯甲酸戊酯;肉桂酸的酯类,优选2-乙基己基-4-甲氧基肉桂酸酯、4-甲氧基肉桂酸异戊酯;水杨酸的酯类,优选2-水杨酸乙基己酯、4-水杨酸异丙基苄酯、水杨酸高薄荷酯;二苯甲酮衍生物,优选2-羟基-4-甲氧基二苯甲酮、2-羟基-4-甲氧基-4'-甲基二苯甲酮、2,2'-二羟基-4-甲氧基二苯甲酮;亚苄基丙二酸酯,优选二(2-乙基己基)4-甲氧基亚苄基丙二酸酯、2,4,6-三苯胺基-(对-碳基-2'-乙基-1'-己氧基)-1,3,5-三嗪。有利的水溶性UVB过滤剂包括:2-苯基苯并咪唑-5-磺酸的盐类,诸如其钠盐、钾盐或三乙醇铵盐,以及磺酸本身;二苯甲酮的磺酸衍生物,优选2-羟基-4-甲氧基二苯甲酮-5-磺酸及其盐;3-亚苄基樟脑的磺酸衍生物,诸如,例如4-(2-氧代-3-亚冰片基甲基)苯磺酸、2-甲基-5-(2-氧代-3-亚冰片基-甲基)磺酸及其盐,还有1,4-二(2-氧代-10-磺基-3-亚冰片基甲基)-苯及其盐(对应的10-硫酸根化合物,诸如对应的钠盐、钾盐和三乙醇铵盐),以及苯-1,4-二(2-氧代-3-亚冰片基甲基)-10-磺酸。
还可能有利的是采用UVA过滤剂,诸如惯常包含在护肤品制剂中的UVA过滤剂。优选地,这些物质是二苯甲酰甲烷的衍生物,特别是1-(4'-叔丁基苯基)-3-(4'-甲氧基苯基)丙烷-1,3-二酮和1-苯基-3-(4'-异丙基苯基)丙烷-1,3-二酮。可以类似地使用用于UVB组合的量。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以有利地与诸如惯用于此类制剂中的其他助剂或赋形剂组合,诸如,例如抗氧化剂、芳香油、消泡剂、着色剂、具有着色作用的色素、增稠剂、表面活性物质、乳化剂、增塑物质、保湿和/或水分保持物质、脂肪、油、蜡或护肤品制剂的其他常规成分,诸如醇、多元醇、聚合物、泡沫稳定剂、电解质、有机溶剂或有机硅衍生物。根据本发明,在此可以使用任何可想到的、适用于或惯用于护肤品和/或皮肤病学应用的抗氧化剂、芳香油、消泡剂、着色剂、具有着色作用的色素、增稠剂、表面活性物质、乳化剂、增塑物质、保湿和/或水分保持物质、脂肪、油、蜡、醇、多元醇、聚合物、泡沫稳定剂、电解质、有机溶剂或硅酮衍生物。
在含有根据本发明的组合物的用于皮肤的局部预防或护肤处理的制剂中,高含量的处理物质通常是有利的。根据一个优选的实施方案,组合物含有一种或多种动物和/或植物处理脂肪和油类,例如橄榄油、葵花油、纯化大豆油、棕榈油、芝麻油、菜籽油、杏仁油、琉璃苣油、月见草油、椰子油、乳木果油、荷荷巴油、鲸油、牛油、牛蹄油和猪油,以及任选的其他处理成分,诸如,例如C8-C30脂肪醇。此处使用的脂肪醇可以是饱和的或不饱和的和直链的或支链的,其中示例包括:癸醇、癸烯醇、辛醇、辛烯醇、十二烷醇、十二烯醇、辛二烯醇、癸二烯醇、十二碳二烯醇、油醇、蓖麻醇、芥酸醇、硬脂醇、异硬脂醇、鲸蜡醇、月桂醇、肉豆蔻醇、花生醇、正辛醇、正癸醇、亚麻醇、次亚麻醇和山嵛醇,以及它们的格尔伯特醇;该列表可以根据需要扩展以包括结构上化学相关的其他醇。优选地,脂肪醇来源于天然脂肪酸并且通常由对应的脂肪酸酯通过还原制备。还可以使用通过从天然存在的脂肪和脂肪油(诸如,例如牛油、花生油、菜油、棉籽油、大豆油、葵花油、棕榈仁油、亚麻籽油、玉米油、蓖麻油、菜籽油、芝麻油、可可油和可可脂还原而形成的脂肪醇部分。
可以优选地与根据本发明的组合物组合的处理物质还可包括:神经酰胺,理解为N-酰基鞘氨醇(鞘氨醇的脂肪酸酰胺)或此类脂质的合成类似物(所谓的类神经酰胺),其可明显提高角质层的保水能力;磷脂,例如大豆卵磷脂、鸡蛋卵磷脂和脑磷脂;和凡士林、石蜡油和硅油,后者尤其包括二烷基芳基硅氧烷和烷基芳基硅氧烷,诸如二甲基聚硅氧烷和甲基苯基聚硅氧烷,以及其烷氧基化和季铵化衍生物。
有利地,还可以向含有根据本发明的组合物的制剂中添加水解的动物和/或植物蛋白。在这一方面,有利的示例特别地包括:弹性蛋白、胶原蛋白、角蛋白、乳蛋白、大豆蛋白、燕麦蛋白、豌豆蛋白、杏仁蛋白和小麦蛋白部分或对应的水解蛋白,以及它们与脂肪酸的缩合产物;并且还包括季铵化水解蛋白,其中优选使用水解植物蛋白。
如果含有根据本发明的组合物的护肤品或皮肤病学制剂是溶液或洗剂,则可以使用的溶剂包括:水或水溶液;脂肪油、脂肪、蜡和其他天然和合成脂肪体,优选脂肪酸与具有低C数的醇(诸如异丙醇、丙二醇或丙三醇)的酯,或脂肪醇与具有低C数的链烷酸或与脂肪酸的酯;具有低C数的醇、二醇或多元醇,以及它们的醚类,优选乙醇,异丙醇,丙二醇,丙三醇,乙二醇,乙二醇单乙基或单丁基醚,丙二醇单甲基、单乙基或单丁基醚,二甘醇单甲基或单乙基醚和类似产品。特别地,使用上述溶剂的混合物。在醇类溶剂的情况下,水可以是附加成分。
根据本发明的组合物或含有该组合物的的护肤品或药物制剂还可以含有抗氧化剂,其中可以使用适用于或惯用于护肤品和/或皮肤病学应用的任何抗氧化剂。有利地,抗氧化剂选自由以下组成的组:氨基酸(例如,甘氨酸、组氨酸、酪氨酸、色氨酸)及其衍生物,咪唑(例如,尿刊酸)及其衍生物,肽(诸如,D,L-肌肽、D-肌肽、L-肌肽)及其衍生物(例如,鹅肌肽),类胡萝卜素,胡萝卜素(例如,α-胡萝卜素、β-胡萝卜素、番茄红素)及其衍生物,硫辛酸及其衍生物(例如,二氢硫辛酸),金硫代葡萄糖,丙基硫代尿嘧啶和其他硫醇(例如,硫氧还原蛋白、谷胱甘肽、半胱氨酸、胱氨酸、胱胺及其糖基、N-乙酰基、甲基、乙基、丙基、戊基、丁基和月桂基、棕榈酰基、油基、γ-亚油基、胆甾醇基和甘油酯)及其盐类,二月桂基硫代二丙酸酯,二硬脂基硫代二丙酸酯,硫代二丙酸及其衍生物(酯类、醚类、肽类、脂质类、核苷酸类、核苷类和盐类)以及极低耐受剂量的亚砜亚胺化合物(例如,丁硫氨酸亚砜亚胺、高半胱氨酸亚砜亚胺、丁硫氨酸砜、五-、六-、七-亚硫氨酸亚砜亚胺);和(金属)螯合剂,例如α-羟基脂肪酸、棕榈酸、植酸、乳铁蛋白、α-羟基酸(例如,柠檬酸、乳酸、马来酸)、腐殖酸、胆汁酸、胆汁提取物、胆红素、胆绿素、EDTA、EGTA及其衍生物,不饱和脂肪酸及其衍生物(例如,γ-亚麻酸、亚油酸、油酸),叶酸及其衍生物,泛醌和泛醇及其衍生物,维生素C及其衍生物(例如,抗坏血酸棕榈酸酯、磷酸抗坏血酸镁、乙酸抗坏血酸酯),生育酚及其衍生物(例如,乙酸维生素E),维生素A及其衍生物(例如维生素A棕榈酸酯);以及安息香树脂的苯甲酸松柏酯,芦丁酸及其衍生物,阿魏酸及其衍生物,丁基羟基甲苯,丁基羟基苯甲醚,去甲二氢愈创木脂酸,去甲二氢愈创木酸,三羟基苯丁酮,尿酸及其衍生物,甘露糖及其衍生物,锌及其衍生物(例如,ZnO、ZnSO4),硒及其衍生物(诸如蛋氨酸硒),二苯乙烯及其衍生物(诸如二苯乙烯氧化物、反式二苯乙烯氧化物),以及所述活性化合物的如适合于本发明的衍生物(诸如盐类、酯类、醚类、糖类、核苷酸类、核苷类、肽类和脂质类)。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以含有维生素和维生素前体,其中可以使用适用于或惯用于护肤品和/或皮肤病学应用的任何维生素和维生素前体。在此可以特别提及的是维生素和维生素前体,诸如生育酚、维生素A、烟酸和烟酰胺、其他复合维生素B,特别是生物素和维生素C。在该组中优选使用的其他示例包括泛醇及其衍生物,特别是其酯类和醚类,以及以阳离子方式获得的泛醇衍生物,诸如,例如泛醇三乙酸酯、泛醇单乙醚及其单乙酸酯以及阳离子泛醇衍生物。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以含有具有亮肤作用的活性化合物,其中可以根据本发明使用适用于或惯用于护肤品和/或皮肤病学应用的任何亮肤活性化合物。在这一方面,有利的亮肤活性化合物包括曲酸、对苯二酚、熊果苷、抗坏血酸、抗坏血酸磷酸酶、间苯二酚、甘草根提取物及其成分光甘草定或甘草查耳酮A,或来自酸模属和小枝属物种的提取物、来自松树物种(Pinus)的提取物或来自葡萄属物种的提取物,其尤其含有亮肤二苯乙烯衍生物。
根据本发明的组合物或含有该组合物的护肤品制剂还可以含有具有美黑作用的活性化合物,其中可以使用适用于或惯用于护肤品和/或皮肤病学应用的美黑活性化合物。在此可以通过示例的方式提及二羟基丙酮(DHA;1,3-二羟基-2-丙酮)。DHA可以单体或二聚体的形式提供,二聚体主要以晶体形式存在。
根据本发明的组合物或含有该组合物的护肤品和药物制剂还可以含有单糖、二糖和寡糖,诸如,例如葡萄糖、半乳糖、果糖、甘露醇和乳糖。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以含有植物提取物,其通常通过提取整个植物而制备,但在个别情况下也仅由植物的花朵和/叶子、木材、树皮或根而制备。关于可以根据本发明使用的植物提取物,特别参考Leitfaden zurInhaltsstoffdeklaration kosmetischer Mittel[化妆品制剂成分声明指南](Industrieverband und Waschmittel e.V.(IKW)[盥洗用品和洗涤剂工业协会]出版,法兰克福)第三版第44页开始的表格中列出的提取物。特别有利的提取物包括:芦荟、金缕梅、藻类、橡树皮、柳草、荨麻、野芝麻、啤酒花、甘菊、耆草、山金车、金盏花、牛蒡根、马尾、山楂、菩提花、黄瓜、杏仁、松针、七叶树、檀香、杜松、椰子、芒果、杏、橙、柠檬、青柠、葡萄柚、苹果、绿茶、葡萄柚籽、小麦、燕麦、大麦、鼠尾草、百里香、罗勒、迷迭香、桦木、锦葵、苦木薯、柳树皮、匍匐芒柄花、款冬、蜀葵、人参和姜根。在这些之中,特别优选的提取物包括芦荟、甘菊、藻类、迷迭香、金盏花、人参、黄瓜、鼠尾草、荨麻、菩提花、山金车和金缕梅。还可以采用两种或更多种植物提取物的混合物。可用于制备所述植物提取物的提取剂包括水、醇及其混合物。在这一上下文中,优选的醇为低级醇(诸如乙醇和异丙醇),还有多羟基醇(诸如乙二醇、丙二醇和丁二醇),特别是二者作为单一提取剂以及与水的混合物。根据本发明,植物提取物可以以纯形式或稀释形式使用。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以含有阴离子、阳离子、非离子和/或两性表面活性剂,在结晶或微晶固体(例如无机微色素)将被掺入到根据本发明的制剂中的情况下尤为如此。表面活性剂是能够在水中溶解有机、非极性物质的两亲性物质。表面活性剂一般根据分子的亲水部分的性质和电荷进行分类。这里可以分成四组:阴离子表面活性剂、阳离子表面活性剂、两性表面活性剂和非离子表面活性剂。
阴离子表面活性剂通常含有羧酸根、硫酸根或磺酸根作为官能团。在水溶液中,它们在酸性或中性介质中形成带负电荷的有机离子。阴离子表面活性剂几乎完全由存在的季铵基团表征。在水溶液中,它们在酸性或中性介质中形成带正电荷的有机离子。两性表面活性剂同时含有阴离子和阳离子基团,相应地在水溶液中表现得像阴离子或阳离子表面活性剂,这取决于pH值。它们在强酸性介质中带正电荷,而在碱性介质中带负电荷。相反,在中性pH值范围内,它们是两性离子型。聚醚链是典型的非离子表面活性剂。非离子表面活性剂不会在水性介质中形成离子。
可以有利地使用的阴离子表面活性剂包括:酰基氨基酸(及其盐类),诸如:酰基谷氨酸盐,例如酰基谷氨酸钠、二-TEA-棕榈酰基天冬氨酸和辛酸/癸酸谷氨酸钠;酰基肽,例如棕榈酰基-水解乳蛋白、椰油酰基水解大豆蛋白钠和椰油酰基水解胶原蛋白钠/钾;肌氨酸盐,例如肉豆蔻酰基肌氨酸盐、TEA-月桂酰基肌氨酸盐、月桂酰基肌氨酸钠和椰油酰基肌氨酸钠;牛磺酸盐,例如月桂酰基牛磺酸钠和甲基椰油酰基牛磺酸钠;酰基乳酸盐,例如月桂酰基乳酸盐和己酰基乳酸盐;丙氨酸盐;羧酸及其衍生物,诸如,例如月桂酸、硬脂酸铝、链烷醇镁和十一碳烯酸锌;羧酸酯,例如硬脂酰基乳酸钙、月桂醇聚醚-6柠檬酸盐和PEG-4月桂酰胺羧酸钠;羧酸醚,例如月桂醇聚醚-13羧酸钠和PEG-6椰油酰胺羧酸钠;磷酸酯和磷酸盐,例如DEA-油醇聚醚-10磷酸盐和二月桂醇聚醚-4磷酸盐;磺酸和盐,诸如酰基羟乙基磺酸盐,例如椰油酰基羟乙基磺酸钠/铵;烷基芳基磺酸盐;烷基磺酸盐,例如椰油酸单甘油酯磺酸钠、C12-14烯烃磺酸钠、月桂基磺基乙酸酯钠和PEG-3椰油酰胺硫酸镁;磺基琥珀酸盐,例如二辛基磺基琥珀酸钠、月桂醇聚醚磺基琥珀酸二钠、月桂基磺基琥珀酸二钠和十一碳烯酰胺MEA-磺基琥珀酸二钠;和硫酸酯,诸如烷基醚硫酸盐,例如钠、铵、镁、MIPA、TIPA月桂醇聚醚硫酸盐、肉豆蔻醇聚醚硫酸钠和C12-13烷醇聚醚硫酸钠;以及烷基硫酸盐,例如钠、铵和TEA月桂基硫酸盐。
可以有利地使用的阳离子表面活性剂包括:烷基胺、烷基咪唑、乙氧基化胺和季铵表面活性剂。
季铵表面活性剂含有至少一个N原子,该N原子与四个烷基或芳基基团共价键合。无论pH值如何,这都会产生正电荷。烷基甜菜碱、烷基酰胺丙基甜菜碱和烷基酰胺丙基羟基磺基甜菜碱(alkyl amidopropyl hydroxysulphaine)是有利的。优选地,所使用的阳离子表面活性剂还可以选自下组:季铵化合物,特别是苄基三烷基氯化铵或苄基三烷基溴化铵,诸如,例如苄基二甲基硬脂醇氯化铵;以及烷基三烷基铵盐,例如十六烷基三甲基氯化铵或十六烷基三甲基溴化铵、烷基二甲基羟乙基氯化铵或烷基二甲基羟乙基溴化铵、二烷基二甲基氯化铵或二烷基二甲基溴化铵、烷基酰胺乙基三甲基铵醚硫酸盐;烷基吡啶鎓盐,例如月桂基或十六烷基氯化吡啶鎓;咪唑啉衍生物和阳离子性质的化合物,诸如氧化胺,例如烷基二甲基氧化胺或烷基氨基乙基二甲基氧化胺。特别有利地,可以使用十六烷基三甲基铵盐。
可以有利地使用的两性表面活性剂包括:酰基/二烷基乙二胺,例如酰基两性乙酸钠、酰基两性二丙酸二钠、烷基两性二乙酸二钠、酰基两性羟丙基磺酸钠、酰基两性二乙酸二钠和酰基两性丙酸钠;N-烷基氨基酸,例如氨丙基烷基谷氨酰胺、烷基丙氨酸、烷基亚氨基二丙酸钠和月桂基两性羧基甘氨酸。
可以有利地使用的非离子表面活性剂包括:醇类;链烷醇酰胺,诸如椰油酰胺MEA/DEA/MIPA,氧化胺,诸如椰油酰胺丙基氧化胺;羧酸与环氧乙烷、丙三醇、脱水山梨糖醇或其他醇类进行酯化反应形成的酯类;醚类,例如乙氧基化/丙氧基化醇、乙氧基化/丙氧基化酯、乙氧基化/丙氧基化丙三醇酯、乙氧基化/丙氧基化胆固醇、乙氧基化/丙氧基化甘油三酯、乙氧基化/丙氧基化羊毛脂、乙氧基化/丙氧基化聚硅氧烷、丙氧基化POE醚,以及烷基多糖苷类,诸如月桂基葡糖苷、癸基糖苷和椰油糖苷;蔗糖酯类和醚类;聚甘油酯、二甘油酯、单甘油酯;甲基葡萄糖酯,羟基酸的酯。
使用阴离子和/或两性表面活性剂与一种或多种非离子表面活性剂的组合是有利的。按制剂的干重计,表面活性物质在根据本发明的含有组胺释放抑制剂的制剂中的浓度可以在1%和98%(m/m)之间。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以配制成适用于局部应用的形式,例如配制为洗剂、水性或水-醇凝胶、囊泡分散体,或配制为单纯或复方乳液(O/W、W/O、O/W/O或W/O/W)、液体、半液体或固体(诸如乳、霜、凝胶、霜-凝胶、糊剂或棒),并且可以任选地包装成气溶胶并采用慕斯或喷雾的形式。这些组合物根据常规方法进行制备。
为了制备乳液,油相可以有利地选自下组物质:矿物油、矿物蜡;脂肪油、脂肪、蜡以及其他天然和合成脂肪体,优选脂肪酸与具有低C数的醇(例如,与异丙醇、丙二醇或丙三醇)的酯,或脂肪醇与具有低C数的链烷酸、或与脂肪酸的酯;苯甲酸烷基酯;硅油,诸如二甲基聚硅氧烷、二乙基聚硅氧烷、二苯基聚硅氧烷及其混合形式。有利地,可以使用链长为3至30个C原子的饱和和/或不饱和、支链和/或直链链烷羧酸与链长为3至30个C原子的饱和和/或不饱和、支链和/或直链醇的酯,其选自芳族羧酸与链长为3至30个C原子的饱和和/或不饱和、支链和/或直链醇的酯的组。优选的酯油包括肉豆蔻酸异丙酯、棕榈酸异丙酯、硬脂酸异丙酯、油酸异丙酯、硬脂酸正丁酯、月桂酸正己酯、油酸正癸酯、硬脂酸异辛酯、硬脂酸异壬酯、异壬酸异壬酯、2-棕榈酸乙基己酯、2-月桂酸乙基己酯、2-硬脂酸己基癸酯、2-棕榈酸辛基十二烷酯、油酸油酯、芥酸油酯、油酸芥酸酯、芥酸芥酸酯以及此类酯的合成、半合成和天然混合物,例如荷荷巴油。
油相还可以有利地选自包含以下的组:支链和直链烃和蜡、硅油、二烷基醚,该组包括饱和/或不饱和的、支链或直链醇,以及脂肪酸甘油三酯,尤其是链长为8至24个、特别是12至18个C原子的的饱和和/或不饱和、支链和/或直链链烷羧酸的甘油三酯。例如,脂肪酸甘油三酯可以有利地选自包括以下的组:合成、半合成和天然油,例如橄榄油、葵花油、大豆油、花生油、菜籽油、杏仁油、棕榈油、椰子油、棕榈仁油等。有利地,还可以使用此类油和蜡组分的任一混合物。在某些情况下,使用蜡(例如,棕榈酸鲸腊酯)作为油相的唯一脂质组分也是有利的;有利地,油相选自由以下组成的组:2-异硬脂酸乙基己酯、辛基十二烷醇、异壬酸异十三烷基酯、异二十烷、2-椰油酸乙基己酯、C12-15苯甲酸烷基酯、辛酸-癸酸甘油三酯和二辛基醚。特别有利的是C12-15苯甲酸烷基酯和2-异硬脂酸乙基己酯的混合物、C12-15苯甲酸烷基酯和异壬酸异十三烷基酯的混合物以及C12-15苯甲酸烷基酯和、2-异硬脂酸乙基己酯和异壬酸异十三烷基酯的混合物。有利地,还可以使用烃类石蜡油、角鲨烷和角鲨烯。有利地,油相还可以含有环状或线性硅油或完全由其组成,尽管优选使用的是除硅油或油类之外的附加含量的其他油相组分。有利地,可以将环甲硅油(例如,十甲基环五硅氧烷)作为硅油使用。然而,有利地,还可以使用其他硅油,诸如,例如十一甲基环三硅氧烷、聚二甲基硅氧烷和聚(甲基苯基硅氧烷)。环甲硅油与异壬酸异十三烷基酯的混合物以及环甲硅油与2-异硬脂酸乙基己酯的混合物也是特别有利的。
含有根据本发明的组合物并且以乳液的形式提供的制剂的水相可以包括:具有低C数的醇、二醇或多元醇,以及它们的醚类,优选乙醇、异丙醇、丙二醇、丙三醇、乙二醇、乙二醇单乙基或单丁基醚、丙二醇单甲基、单乙基或单丁基醚、二甘醇单甲基或单乙基醚和类似产品;以及具有低C数的醇,诸如乙醇、异丙醇、1,2-丙二醇、丙三醇,并且特别是一种或多种增稠剂,其可以有利地选自包括以下的组:二氧化硅、硅酸铝、多糖及其衍生物(诸如透明质酸、黄原胶、羟丙基甲基纤维素),并且特别有利地选自包括以下的组:聚丙烯酸酯,优选选自包括所谓的卡波姆(诸如980、981、1382、2984、5984型卡波姆)的组的聚丙烯酸酯,每一种均单独使用或组合使用。
有利地,以乳液形式提供的、根据本发明的组合物或含有该组合物的护肤品或药物制剂含有一种或多种本领域常用于制备护肤品或药物制剂的乳化剂。
根据本发明的组合物或含有该组合物的护肤品或药物制剂还可以包含护肤品或药学上可接受的载体,诸如(但不限于)本领域常用的以下一种:乳糖、右旋糖、蔗糖、山梨糖醇、甘露醇、淀粉、阿拉伯胶、磷酸钙、藻酸盐、明胶、硅酸钙、微晶纤维素、聚乙烯吡咯烷酮、纤维素、水、糖浆、甲基纤维素、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石粉、硬脂酸镁、矿物油等。除了以上组分之外,护肤品或药物制剂还可以包括润滑剂、润湿剂、甜味剂、调味剂、乳化剂、混悬剂、防腐剂等。合适的药学上可接受的载体和制剂在Remington'sPharmaceutical Sciences[雷明顿药学大全](第19版,1995)中进行了详细描述。
药物制剂可以局部、口服或肠道外施用。
根据本发明的药物制剂的合适剂量可以根据诸如患者的年龄、体重、性别或病状、食品、施用时间、施用途径、排泄率和反应敏感性等因素进行不同的规定。
根据本发明的药物组合物可以根据本发明所属领域的普通技术人员可易于执行的方法,通过使用药学上可接受的载剂和/或赋形剂进行配制,而制备成单位剂量的形式。
在又一方面,本发明涉及4-羟基苯乙酮用于提高燕麦蒽酰胺或其类似物、或包含燕麦蒽酰胺或其类似物、特别是燕麦蒽酰胺A或燕麦蒽酰胺L或二氢燕麦蒽酰胺D的组合物的溶解度的用途。
最后,本发明涉及一种用于提高组合物中至少一种燕麦蒽酰胺或燕麦蒽酰胺类似物化合物、优选燕麦蒽酰胺A或燕麦蒽酰胺L或二氢燕麦蒽酰胺D的溶解度的方法,其中向该组合物中添加4-羟基苯乙酮。
尽管本发明已经参考优选的变型进行了具体示出和描述,但本领域技术人员将理解,在不背离本发明的精神和范围的情况下,可以对其进行各种形式和细节上的改变。而且,除非另有明确说明,否则本发明涵盖上述元素所有可能变化中的任何组合。
另外,在按照马库什组对本发明的特征或方面进行描述的情况下,本领域技术人员将认识到本发明因此也按照马库什组的任何个体成员或成员的子组进行了描述。
现在将参考以下实施例对本发明进行详细描述,这些实施例仅用于例示说明本发明,因此本发明的内容不受以下实施例的限制或不限制于以下实施例。
实施例
实施例1:4-羟基苯乙酮对燕麦蒽酰胺A、B、C、D或L和二氢燕麦蒽酰胺D的溶解度的影响
相比于不含4-羟基苯乙酮的燕麦蒽酰胺A、B、C、D和L的溶液,评价了燕麦蒽酰胺A、B、C、D或L和二氢燕麦蒽酰胺D在与不同浓度的4-羟基苯乙酮组合的溶液中的溶解度。
将对应的燕麦蒽酰胺预溶解在乙醇或乙二醇中。边搅拌边加入水和4-羟基苯乙酮,并将溶液加热至60℃。根据下表1,在22℃下评价溶液的外观:
表2:外观编码
沉淀 | 混浊度 |
透明(C) | 透明(C) |
沉淀(P) | 混浊(T) |
大量沉淀(P+) | 高度混浊(T+) |
极大量沉淀(P++) | 极高度混浊(T++) |
表3:含燕麦蒽酰胺A的溶液
图1示出了不同溶液的外观。
表4:含燕麦蒽酰胺L的溶液
表4a:
可以明显观察到,Avn L的溶解度随着4-羟基苯乙酮的浓度的增加而升高。通过进一步将浓度增加到如表4b中的0.5%,获得了透明溶液。
表4b:
图2a和图2b示出了不同溶液的外观。
表5:含燕麦蒽酰胺A和B共混物的溶液
图3示出了不同溶液的外观。
表6:含燕麦蒽酰胺B、C和D共混物的溶液
图4示出了不同溶液的外观。
表7:含二氢燕麦蒽酰胺D的溶液
表7a:
图5a示出了不同溶液的外观。
表7b:
图5b示出了不同溶液的外观。
表8
表3至表7中的结果清晰地表明,向燕麦蒽酰胺或二氢燕麦蒽酰胺D溶液中添加4-羟基苯乙酮,产生了更加透明且沉淀更少的溶液。
特别地,以0.1wt%或0.5wt%的浓度向燕麦蒽酰胺A(表3)和燕麦蒽酰胺L(表4b)溶液中添加4-羟基苯乙酮,产生了没有浑浊或沉淀的透明溶液。
此外,特别地,以0.5%至1.0%的浓度向二氢燕麦蒽酰胺D溶液(表7a和表7b)中添加4-羟基苯乙酮,产生了没有浑浊或沉淀的透明溶液。
表8中的结果还表明,燕麦蒽酰胺与4-羟基苯乙酮的优选比率为1:1至1:50,更优选的比率为1:1.5至1:40,并且二氢燕麦蒽酰胺D与4-羟基苯乙酮的优选比率为1:0.2至1:2,更优选的比率为1:0.5.
实施例2:配制剂实施例
表9:芳香油1(PO1)(用量单位:重量‰)
表10:芳香油2(PO2)(用量单位:重量‰)
表11:芳香油3(PO3)(用量单位:重量‰)
表12:芳香油4(PO4)(用量单位:重量‰)
表13:芳香油5(PO5)(用量单位:重量‰)
上述芳香油PO1、PO2、PO3、PO4或PO5在每种情况下分别加工成以下所示制剂/配制剂。
护肤品制剂/配制剂(所有制剂/配制剂的量按重量百分比计)
表14:霜(o/w)
表15:护手霜和润肤霜
表16:日常面霜SPF 20
表17:晚霜,w/o
表18:润肤露
表19:喷雾型抗细菌润肤露
表20:无菌创伤霜
表21:抗痘膏
表22:屏障修护霜
表23:皮肤舒缓乳
表24:婴儿尿布疹霜(w/o)
表25:皮肤提亮日霜(o/w)
表26:洗发水
表27:去屑洗发水
表28:二合一洗发水
表29:沐浴液
表30:沐浴露
表31:护理清洁露
表32:透明液体肥皂
表33:合成洗涤皂液
表34:去痘液
表35:矿物质洗面清洁凝胶
表36:须后水
表37:冲洗型含甘宝素护发素
表38:冲洗型UV-B/UV-A防护头皮舒缓护发素
表39:防UV护发素
表40:免洗型护发素
表41:免洗型止痒护发素
表42:免洗型含吡啶硫酮锌的可喷雾护发素
表43:头发定型凝胶
表44:除臭棒
表45:锆悬胶止汗棒
表46:止汗/除臭滚珠
表47:除臭配制剂滚珠凝胶
成分 | 用量 |
1,3-丁二醇 | 2.0 |
2-甲基5-环己基戊醇 | 0.1 |
PEG-40氢化蓖麻油 | 2.0 |
羟乙基纤维素 | 0.5 |
戊二醇 | 1.0 |
芳香油PO1、PO2、PO3、PO4或PO5 | 0.3 |
1,3-丙二醇 | 0.5 |
SymGuard CD(3-苯基丙醇、o-伞花烃-3-醇、癸二醇) | 0.4 |
乙基己基甘油 | 0.1 |
SymSave H(羟基苯乙酮) | 0.5 |
燕麦蒽酰胺L | 0.001 |
燕麦蒽酰胺B | 0.004 |
水 | ad 100 |
表48:清透去味止汗滚珠
表49:SymClariol除臭泵式喷雾
表50:美白除臭喷雾
成分 | 用量 |
PEG-40氢化蓖麻油 | 3.0 |
乙基己基甘油(辛氧基甘油) | 0.2 |
Symbright 2036(香紫苏内酯) | 0.1 |
乙醇 | 40.0 |
柠檬酸盐缓冲液 | 0.5 |
1,2-己二醇、1,2-辛二醇(SymDiol 68) | 0.3 |
SymOcide C(o-伞华烃-5-醇) | 0.05 |
2-苄基庚烷-1-醇(茉莉醇) | 0.1 |
芳香油PO1、PO2、PO3、PO4或PO5 | 0.75 |
苯氧乙醇 | 0.4 |
燕麦蒽酰胺L | 0.001 |
SymSave H(羟基苯乙酮) | 0.5 |
水 | ad 100 |
表51:除臭气溶胶喷雾
表52:防晒乳液(o/w,广谱防护)
表53:UV-A/B广谱防护乳
表54:防晒软霜(w/o;SPF40)
表55:防晒乳(w/o)
表56:低油UV-A/B广谱保护型防晒喷雾
表57:防晒喷雾(o/w;SPF 15-20)
表58:晒后凝胶
表59:晒后乳
成分 | 用量 |
丙烯酸酯/C10-30烷基丙烯酸酯交联聚合物 | 0.4 |
十六烷基乙基己酸酯 | 15.0 |
红没药醇 | 0.2 |
生育酚乙酸酯 | 1.0 |
泛醇 | 1.0 |
醇 | 15.0 |
丙三醇 | 3.0 |
芳香油PO1、PO2、PO3、PO4或PO5 | 0.30 |
1,2-己二醇(Hydrolite-6) | 1.0 |
三乙醇胺 | 0.2 |
戊二醇(绿色Hydrolite-5) | 4.0 |
脱矿水 | ad 100 |
4-羟基苯乙酮(SymSave H) | 0.3 |
燕麦蒽酰胺A | 0.005 |
表60:抗菌合成皂条
表61:合成皂条
表62:剃须泡沫
成分 | 用量 |
脱矿水 | ad 100 |
三乙醇胺 | 4.0 |
Edenor L2 SM(硬脂酸、棕榈酸)(Cognis) | 5.3 |
月桂醇聚醚-23 | 3.0 |
硬脂醇 | 0.5 |
燕麦蒽酰胺L | 0.001 |
SymSave H(羟基苯乙酮) | 0.3 |
燕麦蒽酰胺B | 0.003 |
月桂基硫酸钠 | 3.0 |
海藻提取物(水、丙二醇、碘化钾、墨角藻提取物) | 1.0 |
Dragosantol(红没药醇,法尼醇) | 0.1 |
芳香油PO1、PO2、PO3、PO4或PO5 | 1.0 |
丙烷,丁烷4.2Bar | 4.0 |
表63:可喷雾消毒凝胶
表64:湿巾溶液
表65:不含月桂基醚硫酸钠(SLES)的进一步优选的清洁配制剂(%(w/w))。
1:温和头发身体沐浴液
2:洗发水
3:抗痘洗面奶
4:护色洗发水
5:女性洗液
6:胶束水
7:肥皂液
8:去头屑洗发水
9:婴儿洗发水
10:固体洗发水
表66:凝胶牙膏
成分 | I(%) | II(%) | III(%) |
羧甲基纤维素钠 | 0.40 | 0.40 | 0.40 |
山梨糖醇70%,于水中 | 72.00 | 72.00 | 72.00 |
聚乙二醇(PEG)1500 | 3.00 | 3.00 | 3.00 |
糖精钠 | 0.07 | 0.07 | 0.07 |
氟化钠 | 0.24 | 0.24 | 0.24 |
对羟基苯甲酸(PHB)乙酯 | 0.15 | 0.15 | |
馨二醇68 | 0.5 | ||
SymSave H | 0.2 | 0.02 | 0.25 |
薄荷味 | 1.00 | 1.00 | 1.00 |
燕麦蒽酰胺A和B1:1(w/w) | 0.03 | ||
燕麦蒽酰胺L | 0.01 | ||
双蒽胺B | 0.005 | ||
磨料二氧化硅 | 11.00 | 11.00 | 11.00 |
增稠二氧化硅 | 6.00 | 6.00 | 6.00 |
十二烷基硫酸钠(SDS) | 1.40 | 1.40 | 1.40 |
蒸馏水 | ad 100.00 | ad 100.00 | ad 100.00 |
表67:即用型含氟漱口水
Claims (15)
1.一种组合物,所述组合物包含或由以下组成:
至少一种燕麦蒽酰胺或其类似物;和
4-羟基苯乙酮。
2.根据权利要求1所述的组合物,其中所述至少一种燕麦蒽酰胺选自由以下组成的组:燕麦蒽酰胺A、B、C、G、H、K、L和R或这些燕麦蒽酰胺的混合物,特别是其中所述至少一种燕麦蒽酰胺选自由以下组成的组:燕麦蒽酰胺A和燕麦蒽酰胺L。
3.根据权利要求1所述的组合物,其中所述至少一种燕麦蒽酰胺类似物是二氢燕麦蒽酰胺D。
4.根据权利要求1或权利要求2所述的组合物,其中所述至少一种燕麦蒽酰胺是从皮燕麦Avena sativa或裸燕麦Avena nuda物种、特别是碾磨或非碾磨麦粒或燕麦秸秆的燕麦源中获得的。
5.根据权利要求1至4中任一项所述的组合物,按所述组合物的总重量计,所述组合物包含:
0.0001wt%至5.0wt%、特别是0.001wt%至1.0wt%的所述至少一种燕麦蒽酰胺或其类似物;和
0.005wt%至2.0wt%、特别是0.1wt%至1.0wt%的4-羟基苯乙酮;和/或
其中所述至少一种燕麦蒽酰胺、特别是燕麦蒽酰胺A或燕麦蒽酰胺L与所述4-羟基苯乙酮的比率为1:1至1:50、特别是1:1.5至1:40,或者其中所述至少一种燕麦蒽酰胺类似物、特别是二氢燕麦蒽酰胺D的比率为1:0.2至1:30、特别是1:0.5至1:20。
6.根据权利要求1至5中任一项所述的组合物用于皮肤护理、头皮护理、头发护理、指甲护理或在预防和/或治疗皮肤病状、皮肤不耐受和敏感、皮肤刺激、皮肤发红、风团、瘙痒(发痒)、皮肤老化、皱纹形成、皮肤体积损失、皮肤弹性丧失、色素斑、色素异常、或皮肤干燥即用于皮肤保湿的非治疗或护肤品用途。
7.根据权利要求1至5中任一项所述的组合物,所述组合物用作药剂。
8.根据权利要求7所述的组合物,所述组合物在预防和/或治疗皮肤病或角化病,特别是具有与屏障相关的、炎症性、免疫过敏性、致动脉粥样硬化性、干燥性或过度增殖性组分的皮肤病或角化病中,或在预防和/或治疗与ROS产生增加相关的皮肤病中,或在预防和/或治疗心血管疾病、过敏反应、冠心病中的用途,用于降低血清中的LDL胆固醇和脂质水平,用于降低血压,用于提高对胰岛素的敏感性以及用于使得能够对血糖水平进行控制。
9.根据权利要求8所述的组合物,其中所述皮肤病或角化病选自由以下组成的组:湿疹、牛皮癣、皮脂溢、皮肤炎、红斑、瘙痒(发痒)、耳炎、炎症、刺激、纤维化、扁平苔藓、玫瑰糠疹、花斑糠疹、自身免疫性大疱病、荨麻疹、血管水肿性和过敏性皮肤反应和伤口愈合,和/或其中所述与ROS产生增加相关的皮肤病选自由以下组成的组:特应性皮炎、神经性皮炎、牛皮癣病、红斑痤疮、痤疮样皮疹、皮脂腺活性降低或干燥病。
10.根据权利要求1至5中任一项所述的组合物在制备食品、食品补充剂、护肤品、药物或兽药制剂,特别是皮肤病制剂或角化病制剂中的用途。
11.一种包含根据权利要求1至5中任一项所述的组合物的食品、食品补充剂、护肤品、药物或兽药制剂,按所述组合物的重量计,所述食品、食品补充剂、护肤品、药物或兽药制剂特别地以0.0001%至5.0%、更优选0.0005%至2.0%、最优选0.001%至1.0%的量包含所述组合物。
12.根据权利要求1至5中任一项所述的组合物或根据权利要求11所述的食品、食品补充剂、护肤品、药物或兽药制剂,还包含选自由以下组成的组中的一种或多种活性物质:皮肤保湿和/或水分保持物质、清凉剂、渗透剂、皮肤病物质、滋润物质、抗炎、抗细菌或抗真菌物质、具有减轻发红或减轻瘙痒作用的物质、缓和物质、以及这些物质的任何混合物;和/或选自由以下组成的组中的护肤或药学上可接受的赋形剂:抗氧化剂、防腐剂、(金属)螯合剂、渗透促进剂、表面活性物质、乳化剂、芳香油、消泡剂、着色剂、具有着色作用的色素、增稠剂、增塑剂、脂肪、油、蜡、或护肤品组合物的其他常规组分诸如醇、多元醇、聚合物、泡沫稳定剂、电解质、有机溶剂或聚硅氧烷衍生物,以及这些的任何混合物。
13.根据权利要求11或权利要求12所述的护肤品或药物制剂,所述护肤品或药物制剂以流体、酊剂、洗剂、乳液、凝胶、乳霜、软膏、喷雾或洗发水的形式提供。
14.一种4-羟基苯乙酮用于提高燕麦蒽酰胺、特别是燕麦蒽酰胺A或燕麦蒽酰胺L,或其类似物、特别是二氢燕麦蒽酰胺D的溶解度的用途。
15.一种用于提高至少一种燕麦蒽酰胺、特别是燕麦蒽酰胺A或燕麦蒽酰胺L,或至少一种燕麦蒽酰胺类似物、特别是二氢燕麦蒽酰胺D在组合物中的溶解度的方法,其中向所述组合物或制剂加入4-羟基苯乙酮。
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PCT/EP2020/056123 WO2021175454A1 (en) | 2020-03-06 | 2020-03-06 | Avenanthramide compositions with improved solubility comprising 4-hydroxyphenone |
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EP (1) | EP4114354A1 (zh) |
JP (1) | JP2023516454A (zh) |
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CN (1) | CN115243669A (zh) |
BR (1) | BR112022017607A2 (zh) |
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- 2020-03-06 BR BR112022017607A patent/BR112022017607A2/pt unknown
- 2020-03-06 EP EP20710137.9A patent/EP4114354A1/en active Pending
- 2020-03-06 CN CN202080098186.2A patent/CN115243669A/zh active Pending
- 2020-03-06 KR KR1020227034640A patent/KR20220150945A/ko not_active Application Discontinuation
- 2020-03-06 JP JP2022553579A patent/JP2023516454A/ja active Pending
- 2020-03-06 WO PCT/EP2020/056123 patent/WO2021175454A1/en unknown
- 2020-03-06 US US17/909,343 patent/US20230129036A1/en active Pending
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EP4114354A1 (en) | 2023-01-11 |
MX2022010949A (es) | 2022-10-18 |
US20230129036A1 (en) | 2023-04-27 |
BR112022017607A2 (pt) | 2022-10-18 |
CA3172764A1 (en) | 2021-09-10 |
JP2023516454A (ja) | 2023-04-19 |
KR20220150945A (ko) | 2022-11-11 |
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