CN101384265A - 新颖的营养药物性组合物和药物组合物，及其用于治疗、辅助治疗或预防炎性病症的用途 - Google Patents
新颖的营养药物性组合物和药物组合物，及其用于治疗、辅助治疗或预防炎性病症的用途 Download PDFInfo
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Abstract
本发明涉及包含酚类化合物的新颖组合物以及这些组合物作为药物的用途，尤其是用于制造营养药物性组合物或药物组合物的用途，所述营养药物性组合物或药物组合物用于治疗、辅助治疗或预防炎性病症，例如关节炎、哮喘、炎性肠疾病、炎性皮肤疾病(例如银屑病、湿疹、特应性皮炎、晒伤)和慢性炎性病症，例如动脉粥样硬化、心脏病、代谢综合征X、癌症、Alzheimer’s病及其前期阶段(如轻度认知缺损)。本发明还涉及包含酚类化合物的组合物用于美容治疗、辅助治疗或预防皮肤炎症的用途，尤其是用于美容治疗、辅助治疗或预防晒伤或不纯皮肤的用途。
Description
本发明涉及包含酚类化合物的新颖组合物，以及这些组合物作为药物的用途，尤其是作为治疗、辅助治疗或预防炎性病症的药物的用途。
炎性病症(Inflammatory disorder)是世界上最重要的健康问题之一。炎症一般是身体组织对外界材料或伤害性刺激的宿主侵入的一种局部的保护性应答。炎症的起因可以是传染剂如细菌、病毒和寄生虫；或物理因素如烧灼或辐射；或化学品如毒素、药物或工业试剂；或免疫反应如***反应和自身免疫应答或与氧化应激相关的病症。
炎症的特征在于被感染区域的疼痛、发红、肿胀、发热和最终丧失功能。这些症状是在细胞和免疫***之间发生的一组复杂的相互作用的结果。细胞的应答导致若干组炎症介质的相互作用网络，所述炎症介质为：蛋白质(例如细胞因子、酶(例如蛋白酶、过氧化物酶)、主要碱性蛋白、黏附分子(ICAM，VCAM))，脂质介质(例如类花生酸、***素、白细胞三烯、血小板活化因子(PAF))，活性氧物质(例如过氧化氢、超氧化物阴离子O2 -、一氧化氮(NO)等)。然而，许多这类炎症介质也是正常细胞活性的调节子。因此，炎症反应的不足导致缺乏抵抗力的宿主(即感染)，而不受控制的并且因此是慢性的炎症导致炎性疾病，所述炎性疾病部分地由若干种上述介质的过量生产介导。
炎性介质过量生物合成导致的急性和慢性炎症涉及大量炎性病症，如关节炎(例如骨关节炎、类风湿性关节炎)、哮喘、炎性肠疾病、炎性皮肤疾病(例如银屑病、湿疹、特应性皮炎、晒伤)和慢性炎性病症，例如动脉粥样硬化、心脏病、代谢综合征X、癌症、Alzheimer’s病及其前期阶段(如轻度认知缺损)。
类风湿性关节炎是关节的慢性炎性疾病。例如，关节炎包括类风湿性关节炎、脊椎关节病、痛风性关节炎、骨关节炎、***性红斑狼疮和幼年型关节炎。哮喘和类风湿性关节炎的特征在于细胞因子、趋化因子、激肽及其受体、黏附分子和炎性酶长期失衡表达导致的分子水平。
银屑病是最常见的问题之一，影响1-3％的人群。炎性肠病是用于描述胃肠道疾病如溃疡性结肠炎和Crohn’s疾病的一个通用术语。
除了血管内脂质沉积的过程之外，内皮(即血管壁)的炎性反应被认为关键性地引起动脉粥样硬化，即粥样斑形成。引发炎症的血管损伤导致动脉粥样硬化。活化的巨噬细胞、T-淋巴细胞和肥大细胞存在于动脉粥样硬化斑块中。单核细胞/巨噬细胞和淋巴细胞活化导致类花生酸和细胞因子的释放，所述类花生酸和细胞因子涉及内皮损伤以及动脉粥样硬化斑块的形成和最后破裂。最后，在高冠状动脉疾病(CAD)风险的组中，循环炎性标记物(circulating inflammatory markers)如C-反应性蛋白(CRP)、血纤蛋白原(fibrinogen)和白细胞介素提高。若干临床试验指出提高的CRP浓度与提高的冠状和血管事件风险相关。因此，看起来炎症在粥样斑形成的开始和发展中起重要作用。
炎性病症还与Alzheimer’s疾病的病理生理学相关。在患有Alzheimer’s疾病的患者大脑中存在炎症的迹象，因为其特征是提高的细胞因子和活化的小神经胶质细胞水平。因此，炎症不仅涉及经典的炎性病症(例如关节炎、哮喘、肠病)，而且与许多慢性炎性病症相关(例如动脉粥样硬化、心脏病、代谢综合征X、癌症、Alzheimer’s疾病)。
炎性事件还与不同类型癌症(例如胃和肠癌、黑色素瘤)的病例生理学相关。在人的乳腺、结肠、肺和胰腺癌中已经发现提高的***素水平。
两种主要的药物种类，皮质类固醇和非类固醇消炎药(NSAID)被用于治疗炎性病症。NSAID和皮质类固醇事实上提供了症状缓解。出于对长期使用的严重副作用的越来越多的考虑，皮质类固醇的使用已减少。
NSAID是最广泛使用的药物之一，主要用于治疗疼痛和炎性病症，尤其是用于治疗关节炎。
流行病学研究已提出摄取NSAID的患者具有比不摄取NSAID的患者更低的发生Alzheimer’s疾病的风险。NSAID的保护性作用提示环氧合酶可能涉及神经变性过程。
流行病学研究显示与不摄取NSAID的人群相比，在摄取非类固醇消炎药(NSAID)的人群中结肠直肠癌、胃癌、食管癌和乳腺癌的风险显著降低。在动物模型中，NSAID显著降低肿瘤发生。
然而，治疗慢性疾病如关节炎时，NSAID的慢性使用受到严重的副作用的限制，如严重的胃肠并发症、肾毒性或哮喘反应。
因此，需要具有弱副作用或无副作用的新的消炎剂。患有炎性疾病的患者对被认为是“天然的”疗法具有特殊的兴趣，所述疗法具有温和的消炎作用并且不具有大的副作用，所述疗法可以被用于疾病预防和作为辅佐疗法。
致力于这类需要是本发明的一个目的。
本发明通过包含式(1)
的酚类化合物的组合物达成了该目的，其中R1表示H、OH或甲氧基，其中R2表示H或COOH，其中R3表示饱和的、单不饱和或多不饱和的C14、C15、C16或C17烷基链。如果烷基链是单不饱和的，则双键可以是(E)或(Z)构型。如果烷基链是多不饱和的，则各双键可各自独立地是(E)或(Z)构型之一。优选地，在本发明的所有实施方案中，R3代表饱和的、单不饱和或多不饱和的烷基链，其为结构(a)-(k)之任一：
在本发明的范围内，用＊表示R3基团与式(1)的结合点。
令人惊奇地发现式(1)的酚类化合物是一种消炎剂。因此，本发明的组合物可特别适用于治疗、辅助治疗和预防炎性病症，如心脏病、多发性硬化、骨关节炎和类风湿性关节炎、动脉粥样硬化和骨质疏松。
本发明的组合物特别适用于治疗、辅助治疗和预防关节炎，尤其是骨关节炎和类风湿性关节炎。因此，本发明的组合物可具有一个或多个以下特性：其降低关节炎症、其维持和/或促进关节健康、其预防关节僵直、其促进灵活性(mobility)、其提供柔软的和/或柔韧的关节、其润滑关节、其缓解关节炎疼痛、其缓解与关节炎症相关的疼痛、其减轻关节肿胀、其减少关节问题、其提供关节护理。
更优选的，式(1)的酚类化合物选自银杏酸(I)、槚如三烯(Cardoltriene)(II)、槚如二烯(Cardoldiene)(III)、(15:3)-漆树酸(Anacardic acid)(IV)和(15:2)-漆树酸(V)。化合物(I)、(II)、(III)、(IV)、(V)可见图1。
进一步更优选的，式(1)的酚类化合物选自槚如三烯(II)和槚如二烯(III)。更优选的，酚类化合物为槚如二烯(III)。
式(1)的酚类化合物优选地以下述浓度使用，所述浓度使得成人(体重约70kg)的每日消耗在从1mg/天到2000mg/天、优选地从5mg/天到500mg/天的范围内。食物或饮料优选地每份含有0.2mg和1000mg之间的式(1)的酚类化合物。如果营养药物性组合物是药物配制剂，则该配制剂可优选地以每剂量单位(例如每粒胶囊或片剂)0.5mg和2000mg之间的量含有式(1)的酚类化合物，或是介于1mg每日剂量和3000mg每日剂量之间的液体配制剂。
因此，本发明还涉及下述组合物，所述组合物包含0.5mg和3000mg之间、优选1和2000mg之间、更优选1和500mg之间的式(1)的酚类化合物。
本发明的组合物清楚地还包括包含式(1)的酚类化合物的萃取物，例如槚如树(cashew)植物或槚如树植物的部分(例如槚如树果)的萃取物，优选有机相萃取物或超临界流体萃取物。另外，本发明还包括下述组合物，所述组合物包含具有上文给定的定义和优选级的本发明式(1)的酚类化合物，所述组合物以萃取物的形式，尤其是可得自植物材料(槚如树植物或槚如树植物的部分，例如槚如树果)的萃取物例如有机相萃取物的形式。
式(1)的酚类化合物可以通过本领域技术人员已知的方法被合成或萃取和/或纯化。
式(1)的酚类化合物优选地得自槚如树植物，所述槚如树植物可以从常规和商业可获得的来源(例如栽培者)获得。
大量式(1)的酚类化合物在Anacardium occidentale中、槚如树坚果、槚如树坚果壳、槚如树果和多种Toxicodendron物种如T.radicans、T.diversilobum中被发现。例外，一些式(1)的酚类化合物可在Rhusverniciflua、Melanorrhoea usitata、Amorpha fruticosa或Cajanus cajan中被发现，并可以通过本领域技术人员已知的方法被分离。银杏酸(I)也可例如得自Ginkgo bilbo(如叶和果实)。
本文使用的酚类化合物可以通过本领域已知的大量方法制备。可以通过任何合适的手段加工上述植物以获得所述的组合物。例如，可以萃取槚如树果以获得混合物。酚类化合物可以从该混合物中直接获得，或可以通过本领域技术人员已知的大量方法将该混合物分级和/或纯化。分级方法的实例包括用有机溶剂、色谱法例如高压液相色谱(HPLC)或使用超临界流体来分离。
图1中提到的所有化合物可例如如下获得：用甲醇:MTB(9:1)萃取Anacardium occidentale的干燥植物材料，并在缓冲的溶剂体系中通过制备HPLC随后分级由此得到的粗萃取物。
本发明在一个不同的方面还涉及用作药物的式(1)的酚类化合物和/或本发明的组合物。本发明更尤其涉及该化合物和/或组合物用于制造营养药物性组合物(nutraceutical composition)或药物组合物的用途，所述营养药物性组合物或药物组合物用于治疗、辅助治疗或预防炎性病症，更优选关节炎，最优选类风湿性关节炎或骨关节炎。本发明还涉及用于在动物(包括人)中治疗、辅助治疗和预防炎性病症(优选关节炎，最优选骨关节炎)的方法，所述方法包括对有需要的动物(包括人)施用有效量的式(1)的酚类化合物和/或根据本发明的组合物的步骤。
在本发明的范围中，动物表示所有的动物，包括哺乳动物，其例子包括人。除人以外优选的哺乳动物的例子包括犬、单峰骆驼(dromedary)、骆驼、大象和马。
本发明另一方面涉及式(1)的酚类化合物和/或根据本发明的组合物用于制造营养药物性组合物或药物组合物的用途。
本发明还在另一方面涉及根据本发明的组合物，其中该组合物为食物或饮料或用于食物或饮料的补剂组合物。
本发明另一方面涉及根据本发明的组合物，其中该组合物是还包含可药用载体的药物组合物。
根据本发明的营养药物性组合物和药物组合物可以是适用于施用给动物体(包括人体)的任何盖伦形式(galenic form)，更尤其是口施用中常规的任何形式，例如固体形式，例如作为食物或饲料(用的添加剂/补充剂)、食物或饲料预混物、强化的食物或饲料、片剂、丸剂、颗粒剂、锭剂、胶囊和泡腾配制剂(如粉末和片剂)，或液体形式，例如溶液、乳剂或悬浮液的形式，例如作为饮料、糊剂和油悬浮液。糊剂可以被填充进硬或软壳胶囊中。其它应用形式的例子是用于经皮、肠胃外、局部或可注射施用的形式。营养药物性组合物和药物组合物可以是受控(延迟)释放的配制剂的形式。药物组合物的例子也包括适用于局部应用和酚类化合物经皮吸收的组合物，如霜剂、凝胶、喷雾、干燥胶棒、粉末等。
另外，可以向本发明的营养药物性组合物中添加多种维生素和矿物补剂，以获得一些膳食中缺乏的足够量的必需养分。多种维生素和矿物补剂也可以适用于疾病预防和防止生活方式引起的营养丧失和缺乏。
本领域技术人员知道何种载体可以被用作可药用载体。这类可药用载体的例子为适用于口/肠胃外/可注射施用的无机和有机载体材料，并且包括水、明胶、***胶、乳糖、淀粉、硬脂酸镁、滑石、植物油等等。
除了式(1)的酚类化合物和可药用的载体外，根据本发明的药物组合物可还含有常规的药物添加剂和佐剂、赋形剂或稀释剂，包括但不限于水、任何来源的明胶、植物胶、木质素磺酸盐、滑石、糖、淀粉、***胶、植物油、聚乙二醇、聚亚烷基二醇、调味剂、防腐剂、稳定剂、乳化剂、缓冲液、润滑剂、着色剂、湿润剂、填充剂等等。
强化食物的例子是谷物棒、口香糖和烘焙物体，如蛋糕和曲奇。
饮料包括无酒精饮品和酒精饮品，以及要被添加进饮用水和液体食物中的液体制剂。无酒精饮品为例如软饮、运动饮品、果汁如橙汁、苹果汁和葡萄汁；柠檬水、茶、接近水的饮品(near-water drink)和基于乳的饮品，如酸乳饮品。液体食物的例子包括糖和乳制品，例如酸乳。
可以通过在施用式(1)的酚类化合物之前、同时或之后施用，而将式(1)的酚类化合物与本领域技术人员已知用于治疗或预防炎性病症的其它营养药物性组合物或治疗剂组合施用。
在本发明的另一实施方案中，式(1)的酚类化合物可以被掺入化妆品或皮肤病学组合物(后一组合物为药物组合物的特定类型)中，如用于治疗、辅助治疗或预防皮肤炎症(尤其是UV-辐射引起的晒伤)的皮肤护理制剂，或例如用于治疗、辅助治疗或预防不纯皮肤的皮肤护理制剂。不纯皮肤的例子包括脓疱、座疮和具有炎性方面的其它皮肤不纯。
因此，本发明还涉及化妆品组合物用于美容治疗、辅助治疗或预防皮肤炎症的用途，尤其是用于美容治疗、辅助治疗或预防晒伤的用途。本发明还涉及式(1)的酚类化合物和/或根据本发明的组合物用于制造皮肤病学组合物的用途，所述皮肤病学组合物用于治疗、辅助治疗或预防皮肤炎症，尤其是晒伤或不纯的皮肤。本发明还涉及用于治疗、辅助治疗或预防皮肤炎症(尤其是人晒伤或不纯皮肤，如座疮)的方法，所述方法包括对有需要的人施用有效量的根据本发明的皮肤病学组合物的步骤。本发明还涉及通过根据本发明的化妆品组合物用于美容治疗、辅助治疗或预防皮肤炎症(尤其是晒伤或不纯皮肤)的方法。晒伤预防优选地通过局部应用式(1)的多酚化合物或根据本发明的组合物达成，所述化合物或组合物优选地与合适的遮光剂组合。
根据本发明的化妆品或皮肤病学组合物可以是溶剂或脂肪物质中悬浮液或分散液的形式，或者是乳剂或微乳剂(尤其是O/W或W/O型，O/W/O或W/O/W-型，其中O表示有机相，W表示水相)的形式，如霜剂、糊剂、乳液、增稠的乳液或乳、软膏剂形式的小泡分散液、凝胶、固体管胶棒或气溶胶摩丝，并可以以摩丝、泡沫或喷雾泡沫、喷雾、管棒或气溶胶或擦拭物(wipe)的形式被提供。化妆品或皮肤病学组合物的例子是皮肤护理制剂，尤其是身体油、身体乳液、身体凝胶、治疗霜剂、皮肤保护软膏、保湿凝胶、保湿喷雾、醒肤身体喷雾和晒后制剂或防晒配制物。
用于治疗、辅助治疗或预防皮肤炎症(例如晒伤或不纯皮肤)的化妆品或皮肤病学组合物可以是用于口施用的常规方式，其例子在上文中描述，并还包括美容食物和补剂。
本发明的化妆品或皮肤病学组合物(例如防晒配制物或晒后制剂)可进一步分别包含常用的化妆品或皮肤病学佐剂和/或添加剂，例如防腐剂/抗氧化剂，脂肪物质/油，水，有机溶剂，硅酮，增稠剂，软化剂，乳化剂，其它遮光剂，抗泡剂，湿润剂，香料，表面活性剂，填充剂，掩蔽剂，阴离子、阳离子、非离子或两性多聚物，或其混合物，推进剂，酸化或碱化剂，染料，着色剂，色素或纳米色素，光稳定剂，抗虫剂，皮肤美黑剂，皮肤增白剂，抗菌剂，防腐剂或通常被配制进化妆品中的任何其它成分。
可被掺入本发明的化妆品或皮肤病学组合物(例如防晒配制剂)中的遮光剂有利地选自UV-A、UV-B、UV-C和/或光谱遮光剂。UV-B或广谱遮光剂(即具有约290和340nm之间吸收最大值的物质)的例子可以是有机或无机化合物。有机UV-B或光谱遮光剂为例如丙烯酸酯，例如2-氰基-3，3-二苯基丙烯酸2-乙基己基酯(奥克立林(octocrylene)，
340)，2-氰基-3，3-二苯基丙烯酸乙酯等等；樟脑衍生物，例如4-甲基亚苄基樟脑(
5000)、3-亚苄基樟脑、甲基硫酸樟脑苯甲烷铵(camphor benzalkonium methosulfate)、聚丙烯酰胺基甲基亚苄基樟脑、磺基亚苄基樟脑、磺基甲基亚苄基樟脑、对苯二亚甲基二樟脑酰胺磺酸等等；肉桂酸酯衍生物，例如甲氧基肉桂酸乙基己基酯(
MCX)、甲氧基肉桂酸乙氧基乙基酯、甲氧基肉桂酸二乙醇胺酯(Hydro)、甲氧基肉桂酸异戊酯等等，以及键合到硅氧烷上的肉桂酸衍生物；对氨基苯甲酸衍生物，例如对氨基苯甲酸、对二甲基氨基苯甲酸2-乙基己基酯、N-氧丙烯化的对氨基苯甲酸乙酯、对氨基苯甲酸甘油酯；二苯甲酮，例如二苯甲酮-3、二苯甲酮-4、2，2′，4，4′-四羟基-二苯甲酮、2，2′-二羟基-4，4′-二甲氧基二苯甲酮等等；亚苄基丙二酸酯，例如4-甲氧基亚苄基丙二酸二-(2-乙基己基)酯；2-(4-乙氧基-苯胺亚甲基)丙二酸酯，例如欧洲专利公开EP 0895 776中所述的2-(4-乙氧基-苯胺亚甲基)丙二酸二乙酯；如欧洲专利公开EP 0358584 B1、EP 0538431 B1和EP0709080A1中所述的含有苯丙二酸基的有机硅氧烷化合物如聚硅氧烷-15(
SLX)；甲酚曲唑三硅氧烷(Drometrizole trisiloxane(MexorylXL))；咪唑衍生物，例如2-苯基苯并咪唑磺酸及其盐(
HS)。2-苯基苯并咪唑磺酸的盐为例如碱金属盐(如钠盐或钾盐)、铵盐，吗啉盐，伯、仲和叔胺盐(例如单乙醇胺盐、二乙醇胺盐)等等；水杨酸酯衍生物，例如水杨酸异丙基苄酯、水杨酸苄酯、水杨酸丁酯、水杨酸乙基己基酯(
EHS，NEO Heliopan OS)、水杨酸异辛酯或水杨酸高薄荷酯(homosalate，
HMS，Heliopan OS)等等；三嗪衍生物，例如辛基三嗪酮(UVINUL T-150)、二辛基丁酰胺基三嗪酮(UVASORB HEB)。如例如EP1471995中所述的被封装的UV-遮光剂如被封装的甲氧基肉桂酸乙基己基酯(Eusolex UV-pearls)或装有UV-遮光剂的微胶囊等等。无机化合物为色素，如微粒化的ZnO、TiO2等等。术语“微粒化的”是指从约5nm到约200nm，尤其是从约15nm到约100nm的颗粒尺寸。TiO2颗粒也可用金属氧化物(例如氧化铝或氧化锆)或有机涂层(例如多元醇、甲基硅酮、硬脂酸铝、烷基甲硅烷)包覆。这类涂层为本领域熟知。
广谱的或UV A遮光剂(即在约320nm到400nm之间有最大吸收的物质)可以是有机或无机化合物，例如二苯甲酰甲烷衍生物，例如4-叔丁基-4′-甲氧基二苯甲酰甲烷(
1789)、二甲氧基二苯甲酰甲烷、异丙基二苯甲酰甲烷等等；苯并***衍生物，例如2，2′-亚甲基-二-(6-(2H-苯并***-2-基)-4-(1，1，3，3，-四甲基丁基)-苯酚)(TINOSORB M)等等；二-乙基己基氧代苯酚甲氧基苯基三嗪(Tinosorb S)等等；亚苯基-1，4-二-苯并咪唑磺酸或盐，例如2，2-(1，4-亚苯基)二-(1H-苯并咪唑-4，6-二磺酸)(Neoheliopan AP)；经氨基取代的羟基二苯甲酮，例如如欧洲专利公开EP1046391中所述的2-(4-二乙氨基-2-羟基-苯甲酰基)-苯甲酸己酯(UvinulA plus)；如国际专利公开WO2005080341A1中所述的离子UV-A遮光剂。色素，例如微粒化的ZnO或TiO2等等。术语“微粒化的”是指从约5nm到约200nm，尤其是从约15nm到约100nm的颗粒尺寸。颗粒也可用金属氧化物(例如氧化铝或氧化锆)或有机涂层(例如多元醇、甲基硅酮、硬脂酸铝、烷基甲硅烷)包覆。这类涂层为本领域熟知。
因为二苯甲酰甲烷衍生物具有有限的光稳定性，所以其可以适当地光稳定这些UV-A遮光剂。因此，术语“常规的UV-A遮光剂”也指被以下物质稳定的二苯甲酰甲烷衍生物(例如
1789)：如欧洲专利公开EP 0 514 491 B1和EP 0 780 119 A1中描述的3，3-二苯基丙烯酸酯衍生物；如US专利No.5,605,680中描述的亚苄基樟脑；如欧洲专利公开EP0358584B1、EP 0538431 B1和EP 0709080 A1中描述的含苯丙二酸酯基的有机硅氧烷。
可以包含在本发明的化妆品或皮肤病学组合物中的活性成分为例如维生素及其衍生物，例如生育酚，醋酸生育酚，抗坏血酸，抗坏血酸磷酸盐，维生素Q、D和K，视黄醇，视黄醛，视黄酸，视黄醇醋酸酯，视黄醇棕榈酸酯，生物素，类胡萝卜素衍生物如β-胡萝卜素、番茄红素、虾青素，植物提取物，抗菌成分，包含二肽、寡肽和多肽的不稳定的氨基酸如甲硫氨酸、半胱氨酸、胱氨酸、色氨酸、苯丙氨酸、酪氨酸，酚类、多酚或类黄酮，没药醇，尿囊素，植烷三醇，泛醇，AHA酸，泛醌如辅酶Q10，神经酰胺酶，假神经酰胺，精油，植物提取物过氧核糖核酸。
化妆品和皮肤病学佐剂、添加剂和/或其它活性成分的必需量可以以期望的产物为基础，由本领域技术人员容易地选择，并将在实施例中阐述，但不仅限于此。
在另一方面，本发明也涉及本发明的组合物，其中所述组合物为分别包含化妆品或皮肤病学佐剂和/或化妆品或皮肤病学添加剂和/或化妆品或皮肤病学的其它活性成分的化妆品或皮肤病学组合物。
化妆品或皮肤病学组合物以有效量包含式(1)的酚类化合物。术语“有效量”优选按重量计占组合物的至少0.01％。优选地，组合物以0.01重量％和20重量％之间、更优选0.05和10重量％之间、还更优选0.1和5重量％之间的量包含式(1)的酚类化合物。
本发明将借助于以下的实施例来阐述，然而不仅限于此。
实施例1
软明胶胶囊
通过常规工序来制备软明胶胶囊，所述软明胶胶囊提供50mg式(1)的酚类化合物剂量。合适的每日剂量为1到5粒胶囊。
其它成分：甘油。水、明胶、植物油
实施例2
硬明胶胶囊
通过常规工序来制备硬明胶胶囊，所述硬明胶胶囊提供20mg式(1)的酚类化合物剂量。合适的每日剂量为1到5粒胶囊。
其它组分：
填料：适量的乳糖或纤维素或纤维素衍生物
润滑剂：如果需要的话，硬脂酸镁(0.5％)
实施例3
药片
通过常规工序来制备药片，每片提供20mg式(1)的酚类化合物作为活性成分，和微晶纤维素、二氧化硅(SiO2)、硬脂酸镁、交聚维酮NF(一种崩解剂)总计500mg作为赋形剂。
实施例4
软饮
可以如下制备含COMPOUND的软饮：
从以下的成分制备软饮：
混合果汁浓缩物和水溶性香料而不掺入空气。将色素溶于去离子水中。将抗坏血酸和柠檬水溶于水中。将苯甲酸钠溶于水中。果胶在搅拌下被添加并在煮沸时溶解。冷却溶液。预混合橙油和油溶性香料。将F下提到的活性成分搅拌进A的果汁浓缩物混合物中。
为了制备软饮，将所有的组分A-F混合在一起后使用Turrax和随后使用高压匀化器(p1＝200bar，p2＝50bar)匀化。
实施例5
制备包含式(1)的酚类化合物的皮肤病学组合物(治疗霜剂)，其可以被用
于(美容)治疗晒伤引起的皮肤炎症
可以用以下量的以下成分制备治疗霜剂：
| 成分 | INCI命名法 | ％w/w | |
| A | 肉豆蔻酸甘油酯 | 肉豆蔻酸甘油酯 | 2.00 |
| 式(1)的酚类化合物 | 0.05-25 | ||
| 十六醇 | 十六醇 | 0.50 | |
| Myritol318 | 辛酸/癸酸甘油三酯 | 5.00 | |
| Crodamol DA | 己二酸二异丙基酯 | 5.00 |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 2.00 | |
| 丁基化的羟基甲苯 | BHT | 0.05 | |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | 0.60 | |
| Edeta BD | EDTA二钠 | 0.10 | |
| Amphisol K | 十六烷基磷酸钾 | 2.00 | |
| B | 去离子水 | 水 | 加至100 |
| 1，2-丙二醇 | 丙二醇 | 2.00 | |
| D-泛醇75L | 泛醇 | 2.00 | |
| 乙醇 | 乙醇 | 5.00 | |
| 尿囊素 | 尿囊素 | 0.20 | |
| Carbopol ETD 2001 | 卡波姆 | 0.30 | |
| C | KOH10％溶液 | 氢氧化钾 | 1.50 |
| D | 香料 | 香料 | 适量 |
步骤：
搅拌下将A)和B)部分加热至85℃。均匀时在搅动下向A)中加入B)部分。搅拌下冷却至约45℃。添加C)部分。在11000rpm匀化以得到小颗粒尺寸。搅拌下冷却至室温。然后添加D)部分。
实施例6
抑制炎性介质的生产
在细胞学实验中测定A.occidentale(槚如树果)的结构相关物质如槚如二烯、槚如三烯、漆树酸和银杏酸的消炎作用。从Anacardiumoccidentale的萃取物中分离这些物质。
如下获得萃取物：用甲醇:甲基叔丁基醚(MTB)(9:1)从Anacardiumoccidentale的干燥植物材料中萃取并随后在缓冲的溶剂体系中通过制备HPLC分级由此获得的萃取物。在细胞学炎性体系中测试这些萃取物，并测定物质混合物的IC50(见下文)。
然后在细胞学细胞体系中进一步体外测定纯净的物质。测量化合物对一氧化氮和/或促炎症反应***素(PG)合成的抑制。PGE2在炎症过程中起关键作用，而一氧化氮(NO)是多种慢性炎性疾病(包括多种形式的关节炎、胃肠疾病和代谢综合征X)中的标志。
使用鼠巨噬细胞指示细胞系RAW267.4在细胞学实验中测试化合物对炎性应答的作用。该细胞购自ATCC(Manassas，VA，USA)并在含有链霉素/青霉素、非必需氨基酸和10％胎牛血清(FCS)的DMEM中培养。为了测试大范围的化合物浓度，将细胞(～50’000/孔)接种进平底的微孔滴定板中并培养一天。然后在含0.25％FCS(D-025)的完全培养基中使细胞饥饿。过夜培养后，去除培养基并用含有两倍最终浓度测试化合物的100μL D-025代替。然后添加含有2μg/ml LPS的100μL D-025(即最终LPS浓度为1μg/ml)并将细胞培养24小时。
在两倍稀释步骤中在0.2到50μM的浓度范围内测试物质。测试从0.2到50mg/L的萃取物。所有的处理一式两份完成，并对每个处理进行若干个实验系列。通过Griess反应，使用亚硝酸钠作为标准物，测定由细胞释放的一氧化氮快速形成的亚硝酸盐浓度。简言之，将50μL的上清液与Griess试剂1(25μL)和Griess试剂2(25μL)混合、离心，并测定540nm处的光密度。通过得自Cayman Chemicals(Ann Harbor，WI，USA)并根据制造商的说明书使用的EIA测定被分泌进细胞培养基中的PGE2。所有的测定一式两份并在培养物上清液的多种稀释度下进行。使用两参数最小二乘法拟合等式[y＝A+((B-A)/(1+((C-x)＾D))]针对最佳拟合曲线(Excel拟合软件程序)计算IC50值。
化合物对两种炎性参数的抑制作用在下表中给出。A.occidentale的萃取物有效地抑制一氧化氮和PGE2生产；观察到的IC50值反映了提高的生物活性化合物浓度。在A.occidentale萃取物中鉴定的五种物质中的三种(即槚如二烯、槚如三烯、[15:3]漆树酸)有效地以<～20μmol/L的IC50降低一氧化氮(NO)的生产。在槚如二烯和槚如三烯的情况下，对PGE2生产的影响甚至更加重要。被测试的物质显示比白藜芦醇或EGCG更好或类似的生物活性，所述白藜芦醇或EGCG具有被广泛证明的消炎作用。
表:A.occidentale萃取物的IC50值
| 萃取物 | IC50一氧化氮 | IC50PGE2 | |
| A.occidentale | 2.2mg/L | 0.7mg/L |
表:单一物质的IC50值
| 化合物 | IC50一氧化氮 | IC50PGE2 |
| 槚如二烯 | 8.9±1.5μmol/L | 2.5±1.4μmol/L |
| 槚如三烯 | 4.9±0.8μmol/L | 0.9±0.2μmol/L |
| (15:3)-漆树酸 | 7.4±0.4μmol/L | 26.6±21.1μmol/L |
| (15:2)-漆树酸 | 82.4±6.7μmol/L | 43.1±5.5μmol/L |
| 银杏酸 | >100μmol/L | 57.8μmol/L |
| 白藜芦醇 | 31±2μmol/L | 24±2μmol/L |
| EGCG | 33±2μmol/L | 35+/-3μmol/L |
实施例7
炎性基因表达水平的调控
已经评价了这些化合物对涉及炎性应答的基因的表达水平的作用。这些包括例如以下的基因TNF-α、IL-6、MIP1β和NF-κB1和NF-κBp49，其中后两个是涉及炎性基因表达调节的转录因子。在存在不同浓度物质(图中示出)时刺激RAW264.7细胞。4小时后，提取RNA并如(Richard，N.，Porath，D.，Radspieler，A.and Schwager，J.Effects of resveratrol，piceatannol，tri-acetoxystilbene，and genistein on the inflammatory response of humanperipheral blood leukocytes.Mol Nutr Food Res 2005.49:431-442)所述通过定量RT-PCR测定基因的表达。作为例子，显示针对(15:3)漆树酸的数据，其显著降低TNF-α和MIP-1β。总而言之，结果显示了这些化合物对炎性介质和对涉及炎性应答的不同基因的作用。
表：(15:3)漆树酸对炎性基因(TNF-α、IL-6、巨噬细胞炎性蛋白1[MIP-1]、涉及炎性基因表达调节的转录因子[NF-κB1、NF-κBp49])表达的影响。给定基因的mRNA水平以相对于在仅用LPS刺激的细胞中观察到的水平来表述。低于100％的值表示物质对相关基因的表达具有抑制作用。
实施例8
槚如二烯对大鼠中角叉菜胶诱导的爪水肿(paw edema)的作用
在角叉菜胶诱导的足水肿模型中体内评价槚如二烯的消炎活性。该模型已经长期被用于评价抑制***素的试剂的消炎特性，所述试剂如非类固醇消炎药(NSAID)。该模型在向大鼠爪的下跖面(subplantar surface)中施用角叉菜胶之后引起时间依赖性的水肿。
将重量在120到150g的二十只雄性Wistar(Han)大鼠随机分为两组。使他们居住在控制为(21±3℃)温度和(30-80％)相对湿度、具有12-h光/暗周期的房间中。在整个研究中它们可以随意取用经过滤的自来水和标准的成粒的实验室食物(standard pelleted laboratory chow)，以每笼4到5只居住，并在任何测试之前观察至少5天的习服周期。
在禁食过夜后，以编码和随机顺序通过口途径施用溶解在玉米油(以5mL/kg的体积)中的槚如二烯(200mg/kg)或单独的载剂。三十分钟后，通过下跖注射0.05ml的1.5％角叉菜胶悬浮液进入右后爪来诱导炎症。用0.05ml生理盐水注射左后爪。在两个时间点(一次在注射角叉菜胶后1.5h，一次在3.5h)以mL为单位测量每只大鼠的爪体积。通过右后爪体积(发炎的爪)和左(未发炎的)后爪体积之间的差异测定右爪水肿体积。处理组中对水肿体积的消炎作用被表示为抑制百分比(％)[(载剂处理组爪水肿体积的均值—处理组爪水肿体积的均值)/(载剂处理组爪水肿体积的均值)x100]。结果见下表。
表：口服槚如二烯对大鼠中角叉菜胶诱导的爪水肿的药物学作用
爪水肿体积的所有数据作为每组中10只大鼠均值以mL为单位表示。
％抑制相对于载剂处理组来计算。
上表显示与用载剂处理的对照组相比，槚如二烯(200mg/kg)抑制角叉菜胶注射后1.5h和3.5h的平均爪水肿体积。因此，槚如二烯在哺乳动物中具有消炎作用。
实施例9
O/W防晒乳
| 成分 | INCI命名法 | ％w/w | |
| A) | PARSOL SLX | 二甲基硅氧烷亚苄基丙二酸二乙基酯聚硅氧烷-15 | 6.00 |
| Neo Heliopan AP | 3.00 | ||
| Tinosorb S | 氢化的可可酸甘油酯 | 3.00 | |
| Lanette O | 鲸蜡硬脂醇 | 2.00 | |
| Myritol 318 | 辛酸/癸酸甘油三酯 | 6.00 | |
| 矿物油 | 矿物油 | 2.00 |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 1.00 | |
| Prisorine3515 | 异硬脂醇 | 4.00 | |
| B) | Edeta BD | EDTA二钠 | 0.10 |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | 0.60 | |
| Amphisol K | 十六烷基磷酸钾 | 2.00 | |
| 去离子水 | 水(Aqua) | 加至100 | |
| 1，2-丙二醇 | 丙二醇 | 5.00 | |
| Carbopol 981 | 卡波姆(Carbomer) | 0.30 | |
| Tinosorb M | 亚甲基二(苯并***基四甲基丁基苯酚) | 6.00 | |
| KOH 10％溶液 | 氢氧化钾 | 2.10 | |
| C) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
步骤：
搅拌下将A)和B)部分加热至85℃。均匀时在搅动下向A)中加入B)部分。搅拌下冷却至环境温度并加入C)部分。匀化以得到小颗粒尺寸。
实施例10
防水型防晒乳
| 成分 | INCI命名法 | ％w/w | |
| A) | PARSOL SLX | 聚硅氧烷-15 | 6.00 |
| PARSOL 1789 | 丁基甲氧基二苯甲酰甲烷 | 2.00 | |
| PARSOL 5000 | 4-甲基亚苄基樟脑 | 4.00 | |
| Uvinul T150 | 乙基己基三嗪酮 | 2.00 | |
| 硅酮DC200/350cs | 二甲基硅氧烷(Dimethicone) | 1.00 |
| Lanette O | 鲸蜡硬脂醇 | 2.00 | |
| Softisan100 | 氢化可可酸甘油酯 | 3.00 | |
| Tegosoft TN | 苯甲酸C12-15烷基酯 | 6.00 | |
| Cetiol B | 己二酸二丁酯 | 7.00 | |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 2.00 | |
| BHT | BHT | 0.05 | |
| Edeta BD | EDTA二钠 | 0.10 | |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | 0.60 | |
| Amphisol | 十六烷基磷酸DEA | 2.00 | |
| B) | 去离子水 | 水(Aqua) | 加至100 |
| 丙二醇 | 丙二醇 | 5.00 | |
| Carbopol 980 | 卡波姆 | 0.30 | |
| KOH(10％溶液) | 氢氧化钾 | 1.50 | |
| C) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
步骤：
搅拌下将A)和B)部分加热至85℃。均匀时在搅动下向A)中加入B)部分。搅拌下冷却至环境温度并加入C)部分。匀化以得到小颗粒尺寸。
实施例11
婴儿和儿童用防晒乳
| 成分 | INCI命名法 | ％w/w | |
| A) | Tegosoft TN | 苯甲酸C12-15烷基酯 | 5.00 |
| 硅酮2503化妆品蜡 | 硬脂基二甲基硅氧烷 | 2.00 | |
| 十六烷醇 | 十六烷醇 | 1.00 | |
| 丁基化的羟基甲苯 | BHT | 0.05 | |
| Estol GMM 3650 | 肉豆蔻酸甘油酯 | 4.00 |
| Edeta BD | EDTA二钠 | 0.10 | |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | 0.60 | |
| Amphisol A | 磷酸十六烷基酯 | 2.00 | |
| B) | 去离子水 | 水(Aqua) | 加至100 |
| Carbopol 980 | 卡波姆 | 0.6 | |
| 甘油 | 甘油 | 3.00 | |
| KOH溶液10％ | 氢氧化钾 | 2.4 | |
| C) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
步骤：
搅拌下将A)和B)部分加热至85℃。均匀时在搅动下向A)中加入B)部分。搅拌下冷却至环境温度并加入C)部分。匀化以得到小颗粒尺寸。
实施例12
高保护性防晒乳
| 成分 | INCI命名法 | ％w/w | |
| A) | PARSOL SLX | 聚硅氧烷-15二甲基硅氧烷亚苄基丙二酸二乙基酯 | 6.00 |
| PARSOL 1789 | 丁基甲氧基二苯酰甲烷 | 2.00 | |
| PARSOL 5000 | 4-甲基亚苄基樟脑 | 4.00 | |
| Uvinul T150 | 2.00 | ||
| 硅酮DC 200/350cs | 二甲基硅氧烷 | 1.00 | |
| Lanette O | 鲸蜡硬脂醇 | 2.00 | |
| Softisan 100 | 氢化的可可酸甘油酯 | 3.00 | |
| Tegosoft TN | 苯甲酸C12-15烷基酯 | 6.00 | |
| Cetiol B | 己二酸二丁酯 | 7.00 |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 2.00 | |
| BHT | BHT | 0.05 | |
| Edeta BD | EDTA二钠 | 0.10 | |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | 0.60 | |
| Amphisol K | 十六烷基磷酸钾 | 2.00 | |
| B) | 去离子水 | 水(Aqua) | 加至100 |
| 丙二醇 | 丙二醇 | 5.00 | |
| Carbopol 980 | 卡波姆 | 0.30 | |
| KOH(10％溶液) | 氢氧化钾 | 1.50 | |
| C) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
| D) | 香料 | 香料 | 适量 |
步骤：
搅拌下将A)和B)部分加热至85℃。均匀时在搅动下向A)中加入B)部分。搅拌下冷却至环境温度并加入C)和D)部分。匀化以得到小颗粒尺寸。
实施例13
无水防晒凝胶
| 成分 | INCI命名法 | ％w/w | |
| A) | PARSOL MCX | 甲氧基肉桂酸乙基己基酯 | 6.00 |
| PARSOL 1789 | 丁基甲氧基二苯酰甲烷 | 4.00 | |
| PARSOL 5000 | 4-甲基亚苄基樟脑 | 4.00 | |
| Uvasorb HEB | 二乙基己基丁酰胺基三嗪酮 | 1.50 | |
| Uvinul A plus | 2.00 |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 1.50 | |
| Tegosoft TN | C12-15烷基苯甲酸酯 | 9.00 | |
| Elefac I-205 | 新戊酸乙基己基十二烷基酯 | 2.00 | |
| 醇 | 醇 | 加至100 | |
| 异丙醇 | 异丙醇 | 20.00 | |
| B) | Klucel MF | 羟丙基纤维素 | 2.00 |
| C) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
| D) | 香料 | 适量 |
步骤：
搅拌下将A)和B)部分混合。均匀时在搅动下加入C)和D)部分。
实施例14
防晒凝胶
| 成分 | INCI命名法 | ％w/w | |
| A) | Pemulen TR-2 | 丙烯酸酯/丙烯酸C10-30烷基酯交叉聚合物 | 0.60 |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | 0.60 | |
| Edeta BD | EDTA二钠 | 0.1 | |
| 水 | 水 | 加至100 | |
| B) | PARSOL 1789 | 丁基甲氧基二苯酰甲烷 | 4.00 |
| PARSO L340 | 奥克立林(Octocrylene) | 3.00 | |
| Tegosoft TN | 苯甲酸C12-15烷基酯 | 15.00 | |
| Antaron V-216 | PVP/十六碳烯共聚物 | 1.00 | |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 0.50 |
| 丁基化的羟基甲苯 | BHT | 0.05 | |
| Cremophor RH 410 | PEG-40氢化的蓖麻油 | 0.50 | |
| Tris Amino | 氨丁三醇(Tromethamine) | 0.50 | |
| C) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
| D) | 香料 | 适量 |
步骤：
搅拌下将A)和B)部分加热至85℃。均匀时在搅动下向A)中加入B)部分。搅拌下冷却至环境温度，并加入C)和D)部分。匀化以得到小颗粒尺寸。
实施例15
高保护WO防晒乳
| 成分 | INCI命名法 | ％w/w | |
| A) | PARSOL 1789 | 丁基甲氧基二苯酰甲烷 | 2.00 |
| PARSOL 5000 | 4-甲基亚苄基樟脑 | 4.00 | |
| Uvinul T 150 | 乙基己基三嗪酮 | 2.00 | |
| Uvinul TiO2 | 二氧化钛和三甲氧基辛酰甲硅烷(Trimethoxycaprylylsilane) | 5.00 | |
| Arlacel P 135 | PEG-30二聚羟基硬脂酸酯(Dipolyhydroxystearate) | 2.00 | |
| Tegosoft TN | 苯甲酸C12-15烷基酯 | 5.00 | |
| Cosmacol EMI | 苹果酸二C12-13烷基酯 | 6.00 | |
| Miglyol 840 | 二辛酸/二癸酸丙二醇酯 | 6.00 | |
| 丁基化的羟基甲苯 | BHT | 0.05 | |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | 0.60 | |
| B) | 去离子水 | 水 | 加至100 |
| 甘油 | 甘油 | 5.00 | |
| Edeta | EDTA二钠 | 0.1 | |
| NaCl | 氯化钠 | 0.30 | |
| C) | PARSOL HS | 苯基苄基咪唑磺酸 | 4.00 |
| 水 | 水 | 20.00 | |
| 三乙醇胺99％ | 三乙醇胺 | 2.50 | |
| D) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
| E) | 香料 | 适量 |
步骤：
搅拌下将A)、B)和C)部分加热至85℃。均匀时在搅动下向A)中加入B)和C)部分。搅拌下冷却至环境温度，并加入D)和E)部分。匀化以得到小颗粒尺寸。
实施例16
含颜料的W/O乳
| 成分 | INCI命名法 | ％w/w | |
| A) | Cremophor WO7 | PEG-7氢化蓖麻油 | 6.00 |
| Elfacos ST9 | PEG-45/十二烷基二醇共聚物 | 2.00 | |
| PARSOL 1789 | 丁基甲氧基二苯酰甲烷 | 3.00 | |
| Tinosorb S | 5.00 | ||
| PARSOL 5000 | 4-甲基亚苄基樟脑 | 4.00 | |
| 精细ZnO | 氧化锌 | 2.00 | |
| 微晶蜡 | 微晶蜡 | 2.00 | |
| Miglyol 812 | 辛酸/癸酸甘油三酯 | 5.00 | |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 1.00 | |
| 霍霍巴油 | 霍霍巴树种子油 | 5.00 | |
| Edeta BD | EDTA二钠 | 0.10 | |
| 丁基化的羟基甲苯 | BHT | 0.05 | |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯 | 0.60 |
| &对羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | |||
| B) | 去离子水 | 水 | 加至100 |
| 甘油 | 甘油 | 5.00 | |
| C) | Neo Heliopan AP | 2.00 | |
| 去离子水 | 水 | 20.00 | |
| KOH10％溶液 | 氢氧化钾 | 4.00 | |
| D) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
| E) | 香料 | 香料 | 适量 |
步骤：
搅拌下将A)、B)和C)部分加热至85℃。均匀时在搅动下向A)中加入B)和C)部分。搅拌下冷却至环境温度，并加入D)和E)部分。匀化以得到小颗粒尺寸。
实施例17
带有维生素C的保护性日霜
| 成分 | INCI术语 | ％w/w | |
| A) | PARSOL SLX | 聚硅-15二甲基硅氧亚苄基丙二酸二乙基酯 | 4.00 |
| PARSOL 1789 | 丁基甲氧基二苯酰甲烷 | 1.50 | |
| 肉豆蔻酸甘油酯 | 肉豆蔻酸甘油酯 | 2.00 | |
| 十六醇 | 十六醇 | 0.50 | |
| Myritol 318 | 辛酸/癸酸甘油三酯 | 5.00 | |
| Crodamol DA | 己二酸二异丙基酯 | 5.00 | |
| 维生素E醋酸酯 | 生育酚醋酸酯 | 2.00 | |
| 丁基化的羟基甲苯 | BHT | 0.05 | |
| Phenonip | 苯氧乙醇&对羟基苯甲酸甲酯&对 | 0.60 |
| 羟基苯甲酸乙酯&对羟基苯甲酸丙酯&对羟基苯甲酸丁酯 | |||
| Edeta BD | EDTA二钠 | 0.10 | |
| Amphisol K | 十六烷基磷酸钾 | 2.00 | |
| B) | 去离子水 | 水 | 加至100 |
| 1，2-丙二醇 | 丙二醇 | 2.00 | |
| D-泛醇75L | 泛醇 | 2.00 | |
| 乙醇 | 乙醇 | 5.00 | |
| 尿囊素 | 尿囊素 | 0.20 | |
| Carbopol ETD 2001 | 卡波姆 | 0.30 | |
| KOH 10％溶液 | 氢氧化钾 | 1.50 | |
| C) | 水 | 水 | 10.00 |
| Stay-C 50 | 抗坏血酸磷酸钠 | 0.50 | |
| D) | 酚类化合物 | 例如图1中给出的结构 | 0.05-25 |
| E) | 香料 | 香料 | 适量 |
Claims (20)
1.包含式(1)
的酚类化合物的组合物，其中R1表示H、OH或甲氧基，其中R2表示H或COOH，其中R3表示饱和的、单不饱和或多不饱和的C14、C15、C16或C17烷基链。
2.根据权利要求1的组合物，其中R3代表饱和的、单不饱和或多不饱和的烷基链，其为结构(a)-(k)中任意一个：
3.根据权利要求1或2的组合物，其中式(1)的所述酚类化合物选自银杏酸(I)、槚如三烯(II)、槚如二烯(III)、(15:3)-漆树酸(IV)和(15:2)-漆树酸(V)。
4.根据权利要求1-3中任一项的组合物，其中式(1)的所述酚类化合物选自槚如三烯(II)和槚如二烯(III)。
5.根据权利要求1-4中任一项的组合物，其中式(1)的所述酚类化合物的剂量在0.2mg到3000mg之间。
6.作为药物使用的根据权利要求1-5中任一项的组合物。
7.式(1)
的酚类化合物和/或根据权利要求1-5中任一项的组合物用于制造营养药物性组合物或药物组合物的用途，所述式(1)中R1表示H、OH或甲氧基，其中R2表示H或COOH，其中R3表示饱和的、单不饱和或多不饱和的C14、C15、C16或C17烷基链，所述营养药物性组合物或药物组合物用于治疗、辅助治疗或预防炎性病症。
8.根据权利要求7的用途，其中R3代表饱和的、单不饱和或多不饱和的烷基链，其为结构(a)-(k)中任意一个：
9.根据权利要求7或8的用途，其中所述炎性病症为关节炎。
10.根据权利要求1-5中任一项的组合物用于制造营养药物组合物或药物组合物的用途。
11.根据权利要求1-5中任一项的组合物，其中所述组合物是食物或饮料或用于食物或饮料的补剂。
12.根据权利要求1-5中任一项的组合物，其中所述组合物是还包含可药用载体的药物组合物。
13.根据权利要求1-5中任一项的组合物，其中所述组合物是化妆品或皮肤病学组合物，其还分别包含化妆品或皮肤病学佐剂和/或分别包含化妆品或皮肤病学添加剂和/或分别包含化妆品或皮肤病学的其它活性成分。
14.权利要求13的化妆品组合物用于美容治疗、辅助治疗或预防皮肤炎症的用途，尤其是用于美容治疗、辅助治疗或预防晒伤或不纯皮肤的用途。
15.式(1)
的酚类化合物或根据权利要求1-5中任一项的组合物用于制造皮肤病学组合物的用途，所述式(1)中R1表示H、OH或甲氧基，其中R2表示H或COOH，其中R3表示饱和的、单不饱和或多不饱和的C14、C15、C16或C17烷基链，所述皮肤病学组合物用于治疗、辅助治疗或预防皮肤炎症的用途，尤其是用于治疗、辅助治疗或预防晒伤或不纯皮肤。
16.根据权利要求15的用途，其中R3代表饱和的、单不饱和或多不饱和的烷基链，其为结构(a)-(k)中任意一个：
17.用于在动物中治疗、辅助治疗或预防炎性病症的方法，所述方法包括对有需要的动物施用有效量的式(1)
的酚类化合物或根据权利要求1-5中任一项的组合物，所述式(1)中R1表示H、OH或甲氧基，其中R2表示H或COOH，其中R3表示饱和的、单不饱和或多不饱和的C14、C15、C16或C17烷基链，所述动物包括人。
18.根据权利要求17的方法，其中R3代表饱和的、单不饱和或多不饱和的烷基链，其为结构(a)-(k)中任意一个：
19.根据权利要求17或18的方法，其中所述炎性病症为关节炎。
20.根据权利要求17或18的方法，其中所述炎性病症为皮肤炎症，尤其是晒伤或痤疮。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06003156 | 2006-02-16 | ||
| EP06003156.4 | 2006-02-16 |
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| Publication Number | Publication Date |
|---|---|
| CN101384265A true CN101384265A (zh) | 2009-03-11 |
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| CNA2007800058867A Pending CN101384265A (zh) | 2006-02-16 | 2007-02-13 | 新颖的营养药物性组合物和药物组合物，及其用于治疗、辅助治疗或预防炎性病症的用途 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20090186942A1 (zh) |
| EP (1) | EP1984000A1 (zh) |
| JP (1) | JP2009526797A (zh) |
| KR (1) | KR20080093441A (zh) |
| CN (1) | CN101384265A (zh) |
| WO (1) | WO2007093375A1 (zh) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102641278A (zh) * | 2012-04-06 | 2012-08-22 | 王青 | 银杏酚酸在治疗关节炎中的用途 |
| CN107072903A (zh) * | 2014-10-30 | 2017-08-18 | 欧莱雅 | 亲脂性水杨酸衍生物的用途 |
| CN111057531A (zh) * | 2019-12-25 | 2020-04-24 | 华鼎鸿基采油技术服务（北京）有限公司 | 增效剂以及复合驱油体系 |
| CN111249262A (zh) * | 2020-02-07 | 2020-06-09 | 北京工商大学 | 烷基间苯二酚类化合物在制备预防或治疗阿兹海默症的药物的应用 |
| CN111574339A (zh) * | 2020-04-30 | 2020-08-25 | 广州医科大学附属第三医院（广州重症孕产妇救治中心、广州柔济医院） | 一种新的烷基间苯二酚化合物及其制备方法和应用 |
| CN111991405A (zh) * | 2020-08-28 | 2020-11-27 | 广州中医药大学第一附属医院 | 莪术二酮联合白果新酸在制备促进骨形成药物中的应用 |
| CN113876756A (zh) * | 2021-09-17 | 2022-01-04 | 温州医科大学 | 银杏酸c15:1在药物制备中的应用 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120051725A (ko) * | 2009-07-30 | 2012-05-22 | 이데미쓰 고산 가부시키가이샤 | 코트 제제 |
| JP6144564B2 (ja) * | 2013-07-23 | 2017-06-07 | 株式会社日清製粉グループ本社 | 炎症予防剤 |
| FR3036034B1 (fr) * | 2015-05-13 | 2018-10-12 | L'oreal | Composition comprenant des derives d'acide salicylique et un solvant particulier |
| KR101758153B1 (ko) | 2016-03-10 | 2017-07-17 | 재단법인 임실치즈앤식품연구소 | 옻씨 추출물을 첨가한 발효유 |
| US11700869B2 (en) * | 2018-06-27 | 2023-07-18 | Pepsico, Inc. | Mouthfeel enhancing composition |
| JP2021087380A (ja) * | 2019-12-03 | 2021-06-10 | 出光興産株式会社 | 腸管細胞の炎症抑制剤 |
| IT202000031544A1 (it) * | 2020-12-18 | 2022-06-18 | Metabolic Insights Ltd | Composizioni di pesticidi comprendenti cardol triene |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0781137B2 (ja) * | 1990-01-24 | 1995-08-30 | 御木本製薬株式会社 | 酸化防止剤 |
| JP2511163B2 (ja) * | 1990-02-20 | 1996-06-26 | 御木本製薬株式会社 | ニキビ治療用皮膚外用剤 |
| JPH0436238A (ja) * | 1990-06-01 | 1992-02-06 | Takasago Internatl Corp | 尋常性▲ざ▼瘡用皮膚外用剤 |
| BRPI0406040B1 (pt) * | 2004-10-21 | 2018-09-11 | Fundacao Univ De Brasilia | compostos capazes de absorver radiação ultravioleta, composições contendo os mesmos e processos para sua preparação |
-
2007
- 2007-02-13 JP JP2008554660A patent/JP2009526797A/ja not_active Withdrawn
- 2007-02-13 US US12/279,516 patent/US20090186942A1/en not_active Abandoned
- 2007-02-13 WO PCT/EP2007/001227 patent/WO2007093375A1/en active Application Filing
- 2007-02-13 EP EP07722810A patent/EP1984000A1/en not_active Withdrawn
- 2007-02-13 KR KR1020087019835A patent/KR20080093441A/ko not_active Application Discontinuation
- 2007-02-13 CN CNA2007800058867A patent/CN101384265A/zh active Pending
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| CN102641278A (zh) * | 2012-04-06 | 2012-08-22 | 王青 | 银杏酚酸在治疗关节炎中的用途 |
| CN107072903A (zh) * | 2014-10-30 | 2017-08-18 | 欧莱雅 | 亲脂性水杨酸衍生物的用途 |
| CN111057531A (zh) * | 2019-12-25 | 2020-04-24 | 华鼎鸿基采油技术服务（北京）有限公司 | 增效剂以及复合驱油体系 |
| CN111057531B (zh) * | 2019-12-25 | 2021-11-26 | 华鼎鸿基采油技术服务（北京）有限公司 | 增效剂以及复合驱油体系 |
| CN111249262A (zh) * | 2020-02-07 | 2020-06-09 | 北京工商大学 | 烷基间苯二酚类化合物在制备预防或治疗阿兹海默症的药物的应用 |
| CN111249262B (zh) * | 2020-02-07 | 2021-04-09 | 北京工商大学 | 烷基间苯二酚类化合物在制备预防或治疗阿兹海默症的药物的应用 |
| CN111574339A (zh) * | 2020-04-30 | 2020-08-25 | 广州医科大学附属第三医院（广州重症孕产妇救治中心、广州柔济医院） | 一种新的烷基间苯二酚化合物及其制备方法和应用 |
| CN111574339B (zh) * | 2020-04-30 | 2022-06-24 | 广州医科大学附属第三医院（广州重症孕产妇救治中心、广州柔济医院） | 一种新的烷基间苯二酚化合物及其制备方法和应用 |
| CN111991405A (zh) * | 2020-08-28 | 2020-11-27 | 广州中医药大学第一附属医院 | 莪术二酮联合白果新酸在制备促进骨形成药物中的应用 |
| CN111991405B (zh) * | 2020-08-28 | 2021-10-29 | 广州中医药大学第一附属医院 | 莪术二酮联合白果新酸在制备促进骨形成药物中的应用 |
| CN113876756A (zh) * | 2021-09-17 | 2022-01-04 | 温州医科大学 | 银杏酸c15:1在药物制备中的应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1984000A1 (en) | 2008-10-29 |
| KR20080093441A (ko) | 2008-10-21 |
| JP2009526797A (ja) | 2009-07-23 |
| US20090186942A1 (en) | 2009-07-23 |
| WO2007093375A1 (en) | 2007-08-23 |
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