CN102355884B - 由晚期糖基化终末产物的蓄积引起的皮肤老化的预防、抑制或改善剂 - Google Patents
由晚期糖基化终末产物的蓄积引起的皮肤老化的预防、抑制或改善剂 Download PDFInfo
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- CN102355884B CN102355884B CN201080012136.4A CN201080012136A CN102355884B CN 102355884 B CN102355884 B CN 102355884B CN 201080012136 A CN201080012136 A CN 201080012136A CN 102355884 B CN102355884 B CN 102355884B
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Abstract
本发明提供以下述成分作为有效成分的AGEs降解剂和由AGEs的蓄积所引起的皮肤衰老的预防、抑制或改善剂:(i)选自于由不饱和脂肪酸及其药学上可接受的盐、酯、酰胺和甘油酯所构成的组中的至少一种,或者(ii)含有选自于由不饱和脂肪酸及其甘油酯所构成的组中的至少一种的植物油(月见草油、巴西油桃木果油、白芒花籽油、乳木果油等)。含有上述(i)或(ii)与选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中至少一种的制剂,是对由AGEs的蓄积所引起的皮肤衰老更加有效的预防、抑制或改善剂。
Description
技术领域
本发明涉及一种作为化妆材料组合物或食品组合物等使用的晚期糖基化终末产物降解剂和由晚期糖基化终末产物的蓄积引起的皮肤衰老的预防、抑制或改善剂。
背景技术
在葡萄糖等还原糖与蛋白质之间,会发生糖化反应(美拉德反应)并形成糖化产物。蛋白质的糖化反应也发生于生物体内,当由于糖尿病等原因而持续高血糖状态或者由于老龄化而难以进行分解反应时,则倾向于形成糖化产物、破坏蛋白质的功能或者蓄积糖化产物。该糖化产物最终形成糖化终末产物(晚期糖基化终末产物;下面有时简称为“AGEs”),但AGEs的生成是不可逆反应。所生成的AGEs通过代谢而排出体外,但伴随着老龄化,代谢速度变慢而使AGEs蓄积于生物体内各组织中。
AGEs在生物体内各组织中蓄积或者与AGEs的受体相结合会导致各种症状。例如,一旦AGEs在皮肤(表皮、真皮)中产生并进行蓄积,就会成为肌肤整体衰老(例如诸如皮肤暗黄之类的皮肤色泽的改变,透明感、紧致感的降低)的原因之一。另外,在糖尿病患者中,因高血糖而产生的AGEs会引起白内障、动脉硬化、肾功能障碍等并发症。从而,为了将产生的AGEs排出体外,使AGEs降解成易于排出体外的形式是重要的。
一直以来,为了作为化妆材料组合物、食品组合物的有效成分,对抑制AGEs产生的成分、分解AGEs的成分进行了探索。例如,在专利文献1中记载,柑橘类的挥发性油状物阻碍了作为AGEs之一的戊糖素(pentosidine)的产生。另外,在专利文献2中记载,橄榄的乙醇水溶液提取物具有分解AGEs的作用并且抑制了肌肤的暗沉。
另外,在专利文献3中公开了一种美白剂,其中选自乳酸、乳酸碱金属盐或碱土类金属盐以及乳酸非金属化合物中的乳酸类的浓度为5v/v%以上并同时含有不饱和脂肪酸。
专利文献
专利文献1:日本特开2004-35424号
专利文献2:日本特开2001-122758号
专利文献3:日本特开平3-106810号
发明内容
本发明以提供新型AGEs降解剂、由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂和皮肤色泽的改善剂作为课题。
本发明人为了解决上述课题进行了反复研究并获得了下述认识。
(1)不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺(下面也简称为“不饱和脂肪酸及其衍生物”),(i)具有AGEs的降解作用,(ii)可改善诸如皮肤暗黄之类的皮肤色泽改变,(iii)可改善皮肤紧致。
(2)含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油,(i)可改善诸如皮肤暗黄之类的皮肤色泽改变,(ii)可改善皮肤紧致。
(3)若并用(a)选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种;以及
(b)选自于上述不饱和脂肪酸及其衍生物中的至少一种,或者,含有它们的植物油、具有AGEs降解效果的植物浸膏(extract)等,则通过协同效应可非常有效地抑制由AGEs蓄积所引起的肌肤衰老;具体而言,(i)可更加有效地改善肌肤紧致,(ii)可更加有效地改善诸如皮肤暗黄之类的皮肤色泽改变。
本发明是基于上述认识并进一步反复进行研究而得以完成的,提供下述AGEs降解剂和由AGEs蓄积所引起的肌肤衰老的预防、抑制或改善剂等。
方案1:一种晚期糖基化终末产物降解剂,其中,所述晚期糖基化终末产物降解剂,含有选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种来作为有效成分。
方案2:如方案1所述的晚期糖基化终末产物降解剂,其中,不饱和脂肪酸是碳原子数为16~20的不饱和脂肪酸。
方案3:如方案2所述的晚期糖基化终末产物降解剂,其中,不饱和脂肪酸是选自于由二烯不饱和脂肪酸和三烯不饱和脂肪酸所构成的组中的至少一种的不饱和脂肪酸。
方案4:一种晚期糖基化终末产物降解剂,其中,作为有效成分含有植物油,所述植物油是含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油。
方案5:如方案4所述的晚期糖基化终末产物降解剂,其中,植物油是选自于由月见草油、巴西油桃木果油、白芒花籽油和乳木果油所构成的组中的至少一种的植物油。
方案6:一种由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,含有选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种来作为有效成分。
方案7:如方案6所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,不饱和脂肪酸是碳原子数为16~20的不饱和脂肪酸。
方案8:如方案7所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,不饱和脂肪酸是选自于由二烯不饱和脂肪酸和三烯不饱和脂肪酸所构成的组中的至少一种的不饱和脂肪酸。
方案9:一种由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,作为有效成分含有植物油,所述植物油是含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油。
方案10:如方案9所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,植物油是选自于由月见草油、巴西油桃木果油、白芒花籽油和乳木果油所构成的组中的至少一种的植物油。
方案11:如方案6所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案12:如方案6所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案13:如方案9所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案14:如方案9所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案15:如方案6所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,还含有选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种。
方案16:如方案9所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂,其中,还含有选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种。
方案17:一种晚期糖基化终末产物的降解方法,其中,将选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种,以有效降解晚期糖基化终末产物的量,对人给药。
方案18:如方案17所述晚期糖基化终末产物的降解方法,其中,还将选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种,以有效降解晚期糖基化终末产物的量,对人给药。
方案19:一种晚期糖基化终末产物的降解方法,其中,将含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油,以有效降解晚期糖基化终末产物的量,对人给药。
方案20:如方案19所述晚期糖基化终末产物的降解方法,其中,还将选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种,以有效降解晚期糖基化终末产物的量,对人给药。
方案21:一种由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,将选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种,以有效预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的量,对人给药。
方案22:如方案21所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案23:如方案21所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案24:如方案21所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,还将选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种,以有效预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的量,对人给药。
方案25:一种由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,将含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油,以有效预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的量,对人给药。
方案26:如方案25所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案27:如方案25所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案28:如方案25所述由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善方法,其中,还将选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种,以有效预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的量,对人给药。
方案29:一种用于降解晚期糖基化终末产物的化合物,其选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种。
方案30:一种用于降解晚期糖基化终末产物的植物油,其含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种。
方案31:一种用于预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的化合物,其选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种。
方案32:如方案31所述化合物,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案33:如方案31所述化合物,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案34:一种用于预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的组合物,其中,含有下述(a)和(b):
(a)选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种的化合物;
(b)选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种的化合物。
方案35:如方案34所述组合物,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案36:如方案34所述组合物,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案37:一种用于预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的植物油,其含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种。
方案38:如方案37所述植物油,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案39:如方案37所述植物油,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案40:一种用于预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的组合物,其含有下述(a)和(b):
(a)选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种的化合物;
(b)含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油。
方案41:如方案40所述组合物,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案42:如方案40所述组合物,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案43:一种用于制造晚期糖基化终末产物降解剂的化合物的应用,所述化合物选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种。
方案44:一种用于制造晚期糖基化终末产物降解剂的植物油的应用,所述植物油含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种。
方案45:一种用于制造由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂的化合物的应用,其中,所述化合物选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种。
方案46:如方案45所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案47:如方案45所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案48:一种用于制造由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂的组合物的应用,其中,所述组合物含有下述(a)和(b):
(a)选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种的化合物;
(b)选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种的化合物。
方案49:如方案48所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案50:如方案48所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案51:一种用于制造由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂的植物油的应用,其中,所述植物油含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种。
方案52:如方案51所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案53:如方案51所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
方案54:一种用于制造由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂的组合物的应用,其中所述组合物含有下述(a)和(b):
(a)选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种的化合物;
(b)含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油。
方案55:如方案54所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤色泽改变。
方案56:如方案54所述应用,其中,由晚期糖基化终末产物的蓄积所引起的肌肤衰老是皮肤紧致的降低。
发明的效果
不饱和脂肪酸及其衍生物,具有降解AGEs的作用。通过该作用,可以改善、抑制和/或预防由AGEs在皮肤中的蓄积引起的肌肤整体的衰老(例如诸如皮肤暗黄之类的皮肤色泽的改变、透明感或紧致感的降低)或者延缓肌肤整体的衰老的进度。
含有大量不饱和脂肪酸及其衍生物的植物油,也具有相同的作用。
针对由AGEs的蓄积所引起的肌肤整体的衰老的改善、抑制和/或预防,具体描述如下:在皮肤上涂敷包含不饱和脂肪酸及其衍生物或者含它们的植物油(例如月见草油、巴西油桃木果油、白芒花籽油、乳木果油(Shea Butter)等)的化妆材料组合物,或者摄取含有它们的食品组合物,由此来抑制肤色发黄、增加透明感、提高皮肤紧致。基于此,可使肌肤整体的印象保持年轻而得到年轻的外貌。
并且,还寄望于预防或改善由AGEs所引发的各种疾病(糖尿病并发症(白内障、动脉硬化、肾功能障碍、视网膜症、神经障碍等)、动脉硬化症、恶性肿瘤、骨病、阿尔茨海默病、帕金森氏病等。
另外,当并用AGEs降解剂和选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种时,皮肤的弹性增强、变形皮肤的恢复良好并且皮肤色泽得到改善。基于此,可使肌肤整体的印象保持年轻而得到年轻的外貌。从而,这些组合物可适于作为化妆材料组合物使用。
附图说明
图1-1是表示涂敷月见草油带来的皮肤的b*值变化的图。
图1-2是表示实施例1-3中的Uf、Ua、Ue、Ur的含义的图。
图1-3是表示涂敷月见草油带来的皮肤的弹性变化的图。
图1-4是表示涂敷月见草油带来的皮肤的水分量变化的图。
图2-1是表示涂敷被检试样带来的皮肤的b*值变化的图。
图2-2是表示实施例2-2中的Uf、Ua、Ue、Ur的含义的图。
图2-3是表示涂敷被检试样带来的皮肤的弹性变化的示图。
图2-4是表示涂敷被检试样带来的皮肤的水分量变化的图。
具体实施方式
下面,对本发明进行详细说明。
(A)本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的
肌肤衰老的预防、抑制或改善剂
本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂,其含有下述(i)或(ii)作为有效成分:
(i)选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种;
(ii)含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油。
换言之,上述(i)、(ii)成分,还是抗糖化剂的有效成分、或者是基于抗糖化作用的抗老化剂或抗老龄化剂的有效成分。
在本发明中还包括:同时含有(i)和(ii)作为有效成分的AGEs降解剂以及由AGEs蓄积所引起的肌肤衰老的预防、抑制或改善剂。
不饱和脂肪酸及其衍生物
作为不饱和脂肪酸,例如,可以举出碳原子数为16~24的不饱和脂肪酸。具体而言,可以举出:诸如巴豆酸(C4:1(2))、肉豆蔻脑酸(9-十四烯酸)(C14:1(9))、棕榈油酸(C16:1(9))、油酸(C18:1(9))、反油酸(C18:1(9))、异油酸(11-十八碳烯酸)(C18:1(11))、鳕油酸(顺9-二十碳烯酸)(C20:1(9))、二十碳一烯酸(C20:1(11))、芥酸(C22:1(13))、神经酸(二十四碳烯酸)(24:1(15))之类的单烯不饱和脂肪酸;诸如亚油酸(C18:2(9,12))、8,11-二十碳二烯酸(C20:2(8,11))、二十二碳二烯酸(C22:2(13,16))之类的二烯不饱和脂肪酸;诸如(9,12,15)-亚麻酸(α-亚麻酸、C18:3(9,12,15))、(6,9,12)-亚麻酸(γ-亚麻酸、C18:3(6,9,12))、桐油酸(9,11,13-十八碳三烯酸)(C18:3(9,11,13))、5,8,11-二十碳三烯酸(C20:3(5,8,11))之类的三烯不饱和脂肪酸;诸如花生四烯酸(C20:4(5,8,11,14)、十八碳四烯酸(C18:4(6,9,12,15))之类的四烯不饱和脂肪酸;诸如二十碳五烯酸(C20:5(5,8,11,14,17))、鱼泡酸(二十二碳五烯酸)(C22:5(7,10,13,16,19))之类的五烯不饱和脂肪酸;二十二碳六烯酸(DHA、C22:6(4,7,10,13,16,19))等。这些脂肪酸均在市售中。
其中,基于AGEs降解活性高的观点,优选为碳原子数为16~20的不饱和脂肪酸,更优选为碳原子数为18~20的不饱和脂肪酸,进一步优选为碳原子数为18的不饱和脂肪酸。对不饱和度而言,基于AGEs降解活性高的观点,优选为二烯不饱和脂肪酸或三烯不饱和脂肪酸。特别优选碳原子数为18的二烯或三烯不饱和脂肪酸。
本发明中,还可使用不饱和脂肪酸的药学上可接受的衍生物。作为衍生物,可以举出:盐、甘油酯、酯和酰胺。
作为不饱和脂肪酸的药学上可接受的盐,可以举出:诸如钠盐、钾盐之类的碱金属盐;诸如钙盐、镁盐之类的碱土类金属盐;铵盐等。
作为不饱和脂肪酸的药学上可接受的甘油酯,可以是甘油一酸酯、甘油二酸酯、甘油三酸酯中的任一种。另外,甘油一酸酯可以是1-酰基甘油酯、2-酰基甘油酯、3-酰基甘油酯中的任一种。甘油二酸酯可以是1,2-酰基甘油酯、1,3-酰基甘油酯、2,3-酰基甘油酯中的任一种。
此外,当不饱和脂肪酸的甘油酯为甘油二酸酯或甘油三酸酯时,只要所构成脂肪酸中至少一个是不饱和脂肪酸即可,构成甘油酯的脂肪酸中的不饱和脂肪酸的比率优选为30重量%以上,更优选为50重量%,进一步优选为65重量%以上。并且,当甘油二酸酯或甘油三酸酯时,不饱和脂肪酸可以相同也可以相异。
作为不饱和脂肪酸的药学上可接受的酯,可以举出与碳原子数为1~20的脂肪醇形成的酯等。
作为不饱和脂肪酸的药学上可接受的酰胺,可以举出:氨、烷基胺(烷基的碳原子数为1~4)、二烷基胺(烷基的碳原子数为1~4)、三烷基胺(烷基的碳原子数为1~4)、烷醇胺(烷基的碳原子数为1~4)等与不饱和脂肪酸形成的酰胺。
不饱和脂肪酸及其衍生物,可单独使用一种或组合使用两种以上。
植物油
植物油是含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油;具体而言,可以举出:月见草油、巴西油桃木果油、白芒花籽油、乳木果油、鳄梨油、橄榄油、桃仁油、石栗子油、葡萄籽油、红花油、杏仁油、玉米油、开心果油、葵花籽油、榛果油、昆士兰果油、玫瑰果油、大豆油、芝麻油、小麦胚芽油、菜籽油、棉籽油、米糠油等。其中,优选为月见草油、巴西油桃木果油、白芒花籽油、乳木果油,更优选为月见草油、巴西油桃木果油,进一步优选为月见草油。月见草油是从月见草(柳叶菜科月见草属)或其同属植物的种子得到的脂肪油,巴西油桃木果油是从巴西油桃木的果肉得到的脂肪油。
这些植物油可采用公知的方法制造。例如,将种子等通过机械压榨来榨出油,进而采用己烷等溶剂提取残余的油,然后通过蒸馏完全去除溶剂,由此获得粗制油。接着,在粗制油中加水、分离胶质并采用离心分离机去除,由此获得原油。在该原油中加入磷酸、去除残余的胶质,加入氢氧化钠以去除游离的脂肪酸,进而进行水洗后,加入活性白粘土等进行搅拌,吸附叶绿素等色素,进行过滤、去除白粘土,接着进行冷却并去除所析出的固体油脂、蜡成分,在高温、真空下通过水蒸气蒸馏除掉有味成分,由此获得精制的植物油。
本发明中,粗制油、原油、精制油的任一种均可用作AGEs降解剂和由AGEs蓄积所引起的肌肤衰老的预防、抑制或改善剂的有效成分。
另外,精制的月见草油,例如,可购自ORYZA油化株式会社(OryzaOil&Fat Chemical Co.,Ltd.)、日清奥利友集团株式会社(The Nisshin OilliOGroup,Ltd.)等;精制的巴西油桃木果油,例如,可购自Croda日本株式会社(Croda Japan KK)。
另外,诸如碳原子数为18的不饱和脂肪酸占脂肪酸总量的比率在90重量%以上的植物油,也可作为AGEs降解、抑制剂的有效成分。作为此类植物油,例如,可以举出月见草油等。
植物油,可单独使用一种或组合使用两种以上。
化妆材料组合物
本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂,可将上述说明的有效成分与作为化妆材料成分可接受的公知的主剂或载体一起混合来制得外用组合物、特别是化妆材料组合物。当本发明的各剂含有两种以上的有效成分时,可作为将各成分相互制备成不同组合物并将这些组合物组合而成的制剂。
对化妆材料组合物的形态没有特别限定,例如,可以举出:诸如化妆水、乳液、乳霜(雪花膏)、美容液、防晒用化妆材料、面膜(pack)、护手霜、身体乳液(body lotion)、身体乳霜(body cream)之类的基础化妆材料;洗面奶、卸妆用品、沐浴液(body shampoo)、洗发剂、漂洗液(rinse)之类的清洗用化妆材料;诸如粉底、底妆用品、润唇膏、口红、腮红之类的化妆品(make-up)化妆材料;沐浴剂(浴用剂)等。
化妆材料组合物中的上述有效成分的含量,只要在例如约0.00001~70重量%即可,优选为约0.0001~50重量%,更优选为约0.001~30重量%。若在上述范围内,则以化妆品的通常用量即可获得充分的AGEs降解效果乃至由AGEs的蓄积引起的肌肤整体的衰老的预防、抑制或改善效果。
作为主剂或载体,可以举出:诸如石蜡、液体石蜡、三十碳烷、白蜡、凝胶化烃(液体石腊和聚乙烯的复合软膏基质(Plastibase(注册商标))等)、地蜡(ozokerite)、纯白地蜡(ceresin)、凡士林、硬脂、微晶蜡、α-烯烃低聚物、轻质液体石蜡之类的烃;月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、山萮酸、异硬脂酸之类的脂肪酸;诸如2-乙基己酸三甘油酯(三辛酸甘油酯(tricaprylin,三2-乙基己酸甘油酯))、辛酸/癸酸甘油三酯(caprylic/caprictriglyceride)之类的三脂肪酸甘油酯;鲸蜡醇、硬脂醇、二十二烷醇之类的高级醇;诸如甲基聚硅氧烷、高聚合甲基聚硅氧烷、二甲基硅氧烷-甲基(聚氧乙烯)硅氧烷-甲基(聚氧丙烯)硅氧烷共聚物、二甲基硅氧烷-甲基(聚氧乙烯)硅氧烷共聚物、二甲基硅氧烷-甲基(聚氧丙烯)硅氧烷共聚物、聚氧乙烯-甲基聚硅氧烷共聚物、聚(氧乙烯-氧丙烯)-甲基聚硅氧烷共聚物、二甲基硅氧烷-甲基十六烷基氧基硅氧烷共聚物、二甲基硅氧烷-甲基硬脂氧基硅氧烷共聚物(硬脂氧聚甲硅氧烷/聚二甲硅氧烷共聚物)、烷基丙烯酸酯共聚物甲基聚硅氧烷酯(丙烯酸(酯)类/聚二甲基硅氧烷共聚物)、交联型甲基聚硅氧烷、交联型甲基苯基聚硅氧烷、交联型聚醚改性聚硅氧烷、交联型烷基聚醚改性聚硅氧烷、交联型烷基改性聚硅氧烷、十甲基环五硅氧烷、乙基三硅氧烷、甲基聚三甲基硅氧烷、甲基硅氧烷网状聚合物、聚氧乙烯-甲基聚硅氧烷共聚物、甲基氢聚硅氧烷、三乙氧基甲硅烷基乙基聚二甲基硅氧乙基己基聚二甲基硅氧烷、二甲基聚硅氧烷之类的硅油;诸如乙二醇单乙酸酯、乙二醇二乙酸酯、三乙二醇二乙酸酯、己二醇二乙酸酯和2-甲基-2-丙烯基-1,1-二醇二乙酸酯之类的二醇乙酸酯(glycol acetate);诸如三乙二醇二戊酸酯、2,2,4-三甲基-1,3-戊二醇单异丁酸酯、2,2,4-三甲基-1,3-戊二醇二异丁酸酯之类的二醇酯;诸如乙二醇二丙烯酸酯、二乙二醇二丙烯酸酯、丙二醇单丙烯酸酯、2,2-二甲基-三亚甲基乙二醇二丙烯酸酯和1,3-丁二醇二丙烯酸酯之类的二醇丙烯酸酯;诸如乙二醇二硝酸脂、二乙二醇二硝酸脂、三乙二醇二硝酸脂和丙二醇二硝酸脂之类的二醇二硝酸脂;2,2’-(1,4-亚苯基双氧)双乙醇;诸如乙基纤维素、羟丙纤维素、羟丙甲基纤维素之类的纤维素衍生物;聚乙烯吡咯烷酮;卡拉胶;聚乙烯醇缩丁醛;聚乙二醇;二噁烷;聚己二酸丁二醇酯;诸如肉豆蔻酸异丙酯、肉豆蔻酸辛基月桂酯、棕榈酸异丙酯、棕榈酸十六酯、异壬酸异壬酯、季戊四醇四(2-乙基己酸)酯之类的酯类;诸如糊精、麦芽糖糊精之类的多糖类;诸如乙醇、异丙醇之类的低级醇;诸如乙二醇单甲醚、乙二醇单乙醚、乙二醇单丙基醚、二乙二醇单甲醚、二乙二醇单乙醚、二乙二醇单丙醚、二乙二醇单丁醚、丙二醇单乙醚、丙二醇单丙醚、二丙二醇单乙醚、二丙二醇单丙醚之类的乙二醇醚;水等水系主剂等。
其中,优选为烃(特别是,α-烯烃低聚物、三十碳烷、轻质液体石蜡、液体石蜡)、三脂肪酸甘油酯(特别是,2-乙基己酸三甘油酯、三(辛酸/癸酸)甘油酯)、高级醇(特别是,鲸蜡醇、硬脂醇、二十二烷醇)、硅油(特别是,甲基聚硅氧烷、烷基丙烯酸酯共聚物甲基聚硅氧烷酯(丙烯酸(酯)类/聚二甲基硅氧烷共聚物)、交联型甲基聚硅氧烷、十甲基环五硅氧烷、乙基三硅氧烷、甲基聚三甲基硅氧烷、甲基硅氧烷网状聚合物、聚氧乙烯·甲基聚硅氧烷共聚物、甲基氢聚硅氧烷、三乙氧基甲硅烷基乙基聚二甲基硅氧乙基己基聚二甲基硅氧烷、二甲基聚硅氧烷)、酯类(特别是,异壬酸异壬酯、季戊四醇四(2-乙基己酸)酯)、多糖类(特别是,糊精、麦芽糖糊精)、乙二醇醚(特别是,二乙二醇单乙醚)、水。
主剂或载体,可单独使用一种或组合使用两种以上。
另外,在不损害本发明的效果的范围内,在化妆材料组合物中,能够添加公知的化妆材料中可添加的添加剂,例如可添加表面活性剂、增粘剂、保存剂、pH调节剂、螯合剂、稳定剂、刺激减轻剂、防腐剂、着色剂、分散剂、香料、珠光剂等。添加剂可单独使用一种或组合使用两种以上。
作为表面活性剂,例如,可以举出:诸如失水山梨醇单异硬脂酸酯、失水山梨醇单月桂酸酯、失水山梨醇单棕榈酸酯、失水山梨醇单硬酸酯、双甘油失水山梨醇五-2-乙基己酸酯、双甘油失水山梨醇四-2-乙基己酸酯之类的失水山梨醇脂肪酸酯类;诸如单硬脂酸甘油酯、单硬脂酸甘油苹果酸酯之类的甘油脂肪酸酯类;单硬脂酸聚甘油酯、单异硬脂酸聚甘油酯、二异硬脂酸聚甘油酯之类的聚甘油脂肪酸酯类;诸如丙二醇单硬脂酸酯之类的丙二醇脂肪酸酯类;聚氧乙烯固化蓖麻油40(HCO-40)、聚氧乙烯固化蓖麻油50(HCO-50)、聚氧乙烯固化蓖麻油60(HCO-60)、聚氧乙烯固化蓖麻油80等固化蓖麻油衍生物;诸如聚氧乙烯(20)失水山梨醇单月桂酸酯(吐温(聚山梨醇酯)20)、聚氧乙烯(20)失水山梨醇单硬脂酸酯(吐温60)、聚氧乙烯(20)失水山梨醇单油酸酯(吐温80)、聚氧乙烯(20)失水山梨醇异硬脂酸酯之类的聚氧乙烯失水山梨醇脂肪酸酯类;椰子油酸聚氧乙烯甘油酯;甘油烷基醚;烷基糖苷;诸如聚氧乙烯鲸蜡醚之类的聚氧亚烷基烷基醚;诸如硬脂酰胺、十八烯胺之类的胺类;聚氧乙烯甲基聚硅氧烷共聚物、月桂醇PEG-9聚二甲基硅氧乙基聚二甲基硅氧烷、PEG-9聚二甲基硅氧乙基聚二甲基硅氧烷之类的聚硅氧烷类表面活性剂等。
其中,优选为甘油脂肪酸类(特别是,单硬脂酸甘油酯)、聚甘油脂肪酸酯类(特别是,单硬脂酸聚甘油酯)、固化蓖麻油衍生物(特别是,聚氧乙烯固化蓖麻油50(HCO-50)、聚氧乙烯固化蓖麻油60(HCO-60))、聚氧乙烯失水山梨醇脂肪酸酯类(特别是,聚氧乙烯(20)失水山梨醇异硬脂酸酯、聚氧乙烯(20)失水山梨醇单硬脂酸酯(吐温60))、聚氧亚烷基烷基醚(特别是,聚氧乙烯鲸蜡醚)、聚硅氧烷类表面活性剂(特别是,聚氧乙烯甲基聚硅氧烷共聚物、月桂醇PEG-9聚二甲基硅氧乙基聚二甲基硅氧烷、PEG-9聚二甲基硅氧乙基聚二甲基硅氧烷)。
作为增粘剂,例如,可以举出:胍尔豆胶(guar gum)、槐树豆胶(locustbean gum)、卡拉胶、黄原胶、葡聚糖、甲基纤维素、乙基纤维素、羧甲基纤维素(carboxymethyl cellulose)、羟甲基纤维素(hydroxymethyl cellulose)、羟乙基纤维素、羟丙纤维素、羟丙甲基纤维素、海藻酸钠、丙二醇藻酸酯、聚乙烯醇、聚乙烯吡咯烷酮、聚乙烯基甲醚、羧基乙烯基聚合物、丙烯酸-甲基丙烯酸烷基酯共聚物、聚丙烯酸钠、聚乙二醇、膨润土、糊精脂肪酸酯、果胶、(丙烯酸羟乙酯/丙烯酰基二甲基牛磺酸钠)共聚物、二硬脂二甲铵锂蒙脱石、(丙烯酰二甲基牛磺酸铵/乙烯吡咯烷酮)共聚物、聚乙二醇二硬脂酸酯、乙二醇三异硬脂酸酯、聚氧乙烯(20)甲基葡萄糖苷三异硬脂酸酯等。其中,优选为黄原胶、丙烯酸-甲基丙烯酸烷基酯共聚物、羟乙基纤维素、羟丙纤维素、羟丙甲基纤维素、聚乙二醇、羧基乙烯基聚合物、(丙烯酸羟乙酯/丙烯酰基二甲基牛磺酸钠)共聚物、二硬脂二甲铵锂蒙脱石、(丙烯酰二甲基牛磺酸铵/乙烯吡咯烷酮)共聚物、聚乙二醇二硬脂酸酯、乙二醇三异硬脂酸酯、聚氧乙烯(20)甲基葡萄糖苷三异硬脂酸酯。
作为保存剂、防腐剂,可以举出:苯甲酸、苯甲酸钠、脱氢醋酸、脱氢醋酸钠、对羟基苯甲酸异丁酯、对羟基苯甲酸异丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸苄酯、对羟基苯甲酸甲酯、苯氧乙醇等。其中,优选为对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、苯氧乙醇。
作为pH调节剂,可以举出:无机酸(盐酸、硫酸、磷酸、多磷酸、硼酸等)、有机酸(乳酸、醋酸、柠檬酸、柠檬酸钠、酒石酸、苹果酸、琥珀酸、琥珀酸钠、草酸、葡糖酸、富马酸、丙酸、醋酸、天冬氨酸、6-氨基己酸、谷氨酸、氨乙基磺酸等)、葡糖酸内酯、醋酸铵、无机碱(碳酸氢钠、碳酸钠、氢氧化钾、氢氧化钠、氢氧化钙、氢氧化镁等)、有机碱(单乙醇胺、三乙醇胺、二异丙醇胺、三异丙醇胺、赖氨酸等)等。其中,优选为琥珀酸、琥珀酸钠、柠檬酸、柠檬酸钠、三乙醇胺、氢氧化钾、氢氧化钠。
作为螯合剂,可以举出:乙二胺四乙酸(依地酸)、乙二胺四乙酸盐(钠盐(依地酸钠:EDTA-2Na等,日本药典(Japanese Pharmacopoeia))、钾盐等)、植酸、葡糖酸、多磷酸、偏磷酸等。其中,优选为依地酸钠。
作为稳定剂,可以举出:聚丙烯酸钠、二丁基羟基甲苯、丁基羟基甲氧基苯(丁羟基茴香醚)等。
作为刺激降低剂,可以举出甘草浸膏、海藻酸钠等。
作为着色剂,可以举出无机颜料、天然色素等。
作为珠光剂,可以举出乙二醇二硬脂酸酯、乙二醇单硬脂酸酯、三乙二醇二硬脂酸酯等。其中,优选为乙二醇二硬脂酸酯。
另外,着眼于进一步增强本发明的效果、即所谓改善、抑制或预防由AGEs在皮肤中的蓄积引起的肌肤整体衰老(例如诸如皮肤暗黄之类的皮肤色泽改变,肌肤紧致或透明感的降低等)或者延缓肌肤整体衰老的进度(速度)的效果,能够将可添加于化妆品中的公知的抗糖化成分与化妆材料组合物相配合。公知的抗糖化成分,可单独使用一种或组合使用两种以上。
作为公知的抗糖化成分,例如,可以举出:余甘子的果实、果汁或它们的提取物(日本特开2006-028090、日本特开2006-62989号等);L-精氨酸、L-赖氨酸、水解酪蛋白(以上参照日本特开2001-039816);水解鞣质(hydrolyzable tannin)(日本特开平9-40519号);肌肽、α硫辛酸(以上,参照《美容のための最新皮膚診断マニユアル(用于美容的最新皮肤诊断指南)》、フレグランスジヤ一ナル(香味期刊)杂志社,2006年8月15日发行);西洋玫瑰的花·子房、杂交月季(hybrid rose)的花·子房·花萼·叶·茎、玫瑰果(蔷薇果)、葡萄叶、柿树叶、苹果叶、万寿菊的花、木兰叶的提取物(以上参照日本特开2006-273811号);牡丹属植物提取物、黄芩属植物提取物、蜜蜂花属植物提取物、向日葵属植物提取物、芦荟属植物提取物、黄精属植物提取物、亚麻属植物提取物、蔷薇属植物提取物、椴树属植物提取物、细辛属植物提取物、鱼腥草属植物提取物、款冬属植物提取物、地榆属植物提取物、薄荷属植物提取物、接骨木属植物提取物(以上参照日本特开2003-212749号);大高良姜的提取物(日本特开2006-62987号);罗汉柏、黑儿茶、虎杖、鹿蹄草、杏(树)、鸡冠花、白花油麻藤、白桦、锐刺山楂、欧蓍草(西洋耆草)、大叶冬青、鱼腥草(蕺菜)、直立委陵菜、麦门冬、罗汉柏、葡萄、扁蓄、无患子、木瓜、荔枝、罗马甘菊的提取物(以上参照日本特开2003-212770号);北美金缕梅、杏(树)、鹿蹄草、熊果、黄连、大花紫薇、黑儿茶树、老鹳草、萍蓬草、石榴、芍药、绣线菊、大黄、茶树(Camellia sinensis)、丁香、番泻叶、甜茶、覆盆子、直立委陵菜、蔷薇(玫瑰)、牡丹、鼠尾草、夜叉五倍子、杨梅、蓝桉树、采木、地榆的提取物(以上参照日本特开2002-241299号);木通、芦荟、杏(树)、桦树、桔梗、五味子、人参三七、狼把草、黄精、繁缕、番杏(滨莴苣)、茯苓、柚子的提取物(以上参照日本特开2002-241293号);玫瑰茄(卡凯蒂(Karkade))、木槿、车前子、桃仁、七叶树、桂皮、五味子、紫草根、番泻叶、菟丝子、白芨的提取物(以上参照日本特开平11-106336号);枣核(酸枣仁)、胖大海果实、南瓜籽、杜仲叶、五层龙根、伞形梅笠草叶的提取物(以上参照日本特开2007-254345号);土常山(茶)、金雀花、雪莲花、南非钩麻、刺五加、红景天(Rhodiola Rosea)、Hercampuri(Gentianella alborosea:一种龙胆科龙胆属植物)的提取物(以上参照日本特开2007-254344号);木瓜的提取物(日本特开2006-298812号);Simonillo(Conyza filaginoides:一种菊科白酒草属植物)的提取物(日本特开2006-219447号);越橘属植物的提取物(日本特开2006-117700号);龙牙草、南非醉茄(ashwagandha,又称印度人参)、大茴香、绞股蓝、甜茶悬钩子、银杏、茴香、金缕梅、姜黄、紫松果菊、刺五加、接骨木、耶巴马黛茶(Yerba Mate)、车前草、橄榄、牛至、柑橘、柿树、连钱草、洋甘菊、瓜拉纳(guarana)、含羞草、菊、匙羹紫藤、猫掌草、猫薄荷、Kilauea(キラウエイ)、金银花、番石榴、枸杞叶、山白竹、猫须草(Kumis kuting)、黑大豆、桑树、肉桂、决明子、苦瓜、可乐果、五加皮、积雪草(gotukola)、芫荽、聚合草(comfrey,紫草科植物)、银叶树、红花、长圆五层龙(Salacia oblonga)、野山楂、人参三七、紫苏、鱼腥草、杜松籽、姜、杉树、问荆、斯特维亚菊、留兰香、鼠尾草、香薄荷、锐刺山楂、仙楂(山楂)、百里香、TAHEEBO(皮蚁木(Tabebuia Avellanedae))、蒲公英、山萝卜、茶树(Camellia sinensis)、粉色西番莲、丁香、雏菊、莳萝、杜仲、肉豆蔻、南姜、荨麻、木槿、白猪母菜(白猪母邱)、白花蛇舌草、羽衣草、罗勒、莲(藕)、半枝莲、欧石楠、桃树、牛膝草、枇杷、小白菊、福木树树、紫藤、洋车前子、蓝莓、紫罗兰、薄荷、红花、薄荷、啤酒花、琉璃苣、圆滑番荔枝(牛心果)、药蜀葵、墨角兰、万寿菊、毛蕊花、小锦葵、欧锦葵、海芒果、奶蓟草、毛果槭、旋果蚊子草(メデウスイ一ト)、木瓜、海巴戟、矢车菊、西洋耆草、桉树、薏苡仁、魁蒿、悬钩子、熏衣草、菩提树、红灌木ROOIBOS(Aspalathus Linearis)、柠檬草、柠檬百里香、柠檬马鞭草、柠檬香蜂草、玫瑰果、玫瑰花蕾(Rose pink buds)、迷迭香、玫瑰红(rose red,药用玫瑰花瓣)、月桂树、罗布麻、野草莓的提取物(以上参照日本特开2004-250445号);赤芽柏、柿树、桑树、贯叶连翘、积雪草、山羊豆、北美圣草、玫瑰果的提取物(以上参照日本特开2004-189663号);樱花、红景天、蓝莓、熊果、蜡杨梅、繁缕、葛缕子(藏茴香)、散沫花、拉瑞阿的提取物(以上参照日本特开2001-316221号);紫杉树、槐花、海桐皮、金樱子、月桂树、交让木、石菖蒲、苍耳、贝母、木天蓼的提取物(以上参照日本特开平8-259431号);胡萝卜叶的提取物(日本特开2004-51580号);黑儿茶树、白桦、锐刺山楂、茶树(Camellia sinensis)、丁香、鱼腥草(蕺菜)、直立委陵菜、蔷薇(玫瑰)、葡萄、七叶树、罗马甘菊的提取物(以上参照日本特开2005-35911号);氨基胍或其盐(《最新医学》,49卷·2号,p78~83,1994);黑大豆种皮、马黛茶叶(绿)、菩提树花、柳叶栎叶、糙米种子、西洋柳树皮(柳皮)·嫩芽、小米草地上部、黑升麻根、西洋牡荆果实(圣洁莓)、洋蓟(Artichoke)叶、荔枝种子、卡杜巴树树皮、燕麦地上部、西番莲叶、柳叶破布木(Cháde Bugre(Cordia salicifolia))叶、荞麦叶、水飞蓟的水飞蓟、明日叶的叶、南非钩麻根、齿叶蚁木(依贝)树皮、姬松茸(巴西蘑菇)菌丝体、珐菲亚(巴西人参:珐菲亚属植物)根、阿萨伊浆果(巴西莓)、海蕴全草和蜂斗菜茎·叶的加工物(以上参照日本特开2008-088102);印楝浸膏;阿利斯丁(Alistin);葡糖胺等。其中,优选为来自余甘子、荔枝、蔷薇(玫瑰)、七叶树、水飞蓟、印楝等植物的成分(特别是,余甘子浸膏、荔枝种子浸膏、蔷薇(玫瑰)花瓣浸膏、七叶树浸膏、水飞蓟浸膏、印楝浸膏);水解鞣质(特别是来自栗内皮的);L-精氨酸或其盐;赖氨酸或其盐;肌肽;α硫辛酸;氨基胍或其盐;阿利斯丁(Alistin);葡糖胺。
使用公知的抗糖化成分时的用量,例如,相对于化妆材料组合物的总量约0.00001~10重量%,优选为约0.0001~5重量%,更优选为约0.001~5重量%。使用植物成分时的用量,以浸膏、精油等提取物来换算,例如,相对于化妆材料组合物的总量约0.00001~20重量%,优选为约0.0001~15重量%,更优选为约0.001~10重量%。
并且,在不妨碍本发明效果的范围内,能够在化妆材料组合物中配合抗氧化成分、防老化成分、抗炎症成分、美白成分、角质软化成分、细胞活化成分、维生素类、血液循环促进成分、保湿成分、具有DNA的损伤的预防和/或修复作用的成分、紫外线吸收成分、紫外线散射成分、清洗成分、抗菌成分、收敛成分等可添加于化妆品中的其它药效成分。对其它药效成分而言,可单独使用一种或组合使用两种以上。
作为抗氧化成分,可以举出:来自植物(例如葡萄、高丽参、聚合草等)的成分;原花色素、生育酚及其衍生物、抗坏血酸及其衍生物、橙皮苷(hesperidin)、葡糖基橙皮苷(glucosyl hesperidin)、硫组氨酸甲基内盐(ergothioneine)、亚硫酸氢钠、异抗坏血酸及其盐、类黄酮、谷胱甘肽、谷胱甘肽过氧化物酶、谷胱甘肽S-转移酶、过氧化氢酶、超氧化物歧化酶、硫氧化还原蛋白、牛磺酸、硫代牛磺酸、亚牛磺酸等。其中,优选为葡萄籽浸膏、葡萄叶浸膏、高丽参浸膏、聚合草叶浸膏、原花色素、生育酚及其衍生物(特别是,δ-生育酚、α-生育酚)、抗坏血酸及其衍生物(特别是,抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯))、橙皮苷、葡糖基橙皮苷、硫组氨酸甲基内盐。
作为使用抗氧化成分时的用量,相对于化妆材料组合物的总量,例如为约0.00001~10重量%,优选为约0.0001~5重量%,更优选为约0.001~5重量%。作为使用植物成分时的用量,以浸膏、精油等提取物来换算,相对于化妆材料组合物的总量,例如为约0.00001~20重量%,优选为约0.0001~15重量%,更优选为约0.001~10重量%。
作为防老化成分,可以举出:水解大豆蛋白、类视黄醇(类维生素A)(维生素A及其衍生物、视黄酸、视黄醇等)、潘氨酸、激动素(kinetin)、熊果酸、姜黄浸膏、鞘氨醇衍生物、硅、硅酸、N-甲基-L-丝氨酸、甲羟戊酸内酯等。其中,优选为水解大豆蛋白、维生素A(视黄醇)、维生素A醋酸酯(视黄醇乙酸酯)、维生素A棕榈酸酯(视黄醇棕榈酸酯)。
作为使用防老化成分时的用量,相对于化妆材料组合物的总量,优选为约0.0001~10重量%,更优选为约0.01~5重量%。
作为抗炎症成分,可以举出:来自植物(例如聚合草)的成分;尿囊素、炉甘石、甘草酸或其衍生物、甘草次酸或其衍生物、氧化锌、愈创蓝油烃、盐酸吡多辛、薄荷醇、樟脑、松节油、吲哚美辛、水杨酸或其衍生物等。其中,优选为聚合草叶浸膏、尿囊素、甘草酸二钾、甘草次酸十八酯。
作为使用抗炎症成分时的用量,相对于化妆材料组合物的总量,优选为约0.0001~10重量%,更优选为约0.01~5重量%。作为使用植物成分时的用量,以浸膏、精油等提取物来换算,相对于化妆材料组合物的总量,例如为约0.00001~20重量%,优选为约0.0001~15重量%,更优选为约0.001~10重量%。
作为美白成分,例如,可以举出熊果苷;氢醌;曲酸;鞣花酸;植酸;4-正丁基间苯二酚;母菊(洋甘菊/春黄菊)提取物;抗坏血酸或其衍生物;维生素E或其衍生物;泛酸或其衍生物;氨甲环酸等;或者具有美白作用的植物成分(例如植物浸膏、精油)。其中,优选为熊果苷、氢醌、曲酸、抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯)、氨甲环酸。
作为使用美白成分时的用量,相对于化妆材料组合物的总量,优选为约0.0001~10重量%,更优选为约0.01~5重量%。作为美白成分使用具有美白作用的植物成分时的用量,以浸膏、精油等提取物来换算,相对于化妆材料组合物的总量,例如为约0.00001~20重量%,优选为约0.0001~15重量%,更优选为约0.001~10重量%。
作为角质软化成分,可以举出羊毛脂、尿素、植酸、乳酸、乳酸盐、乙醇酸、水杨酸、苹果酸、柠檬酸等。其中,优选为乳酸、乳酸钠、乙醇酸、水杨酸、植酸。
作为使用角质软化成分时的用量,相对于化妆材料组合物的总量,例如为0.0001~50重量%,优选为约0.001~50重量%,更优选为约0.05~25重量%。
作为细胞活化成分,可以举出:来自植物(例如越橘(bilberry))的成分;γ-氨基丁酸、ε-氨基己酸等氨基酸类;维生素A及其衍生物、硫胺素、核黄素、盐酸吡多辛、泛酸类等维生素类;乙醇酸、乳酸等α-羟基酸类;鞣质、类黄酮、皂角甙、尿囊素、感光素301号等。其中,优选为越橘叶浸膏、维生素A、维生素A醋酸酯、维生素A棕榈酸酯。
作为使用细胞活化成分时的用量,优选为相对于化妆材料组合物的总量约0.0001~10重量%,更优选为约0.01~5重量%。作为使用植物成分时的用量,以浸膏、精油等提取物来换算,例如,相对于化妆材料组合物的总量,例如为约0.00001~20重量%,优选为约0.0001~15重量%,更优选为约0.001~10重量%。
作为维生素类,可以举出:维生素A,维生素A醋酸酯、维生素A棕榈酸酯等维生素A衍生物,视黄醇、视黄酸、视黄酸甲酯、视黄酸乙酯、视黄醇视黄酸酯、d-δ-生育酚视黄酸酯、α-生育酚视黄酸酯、β-生育酚视黄酸酯等维生素A类;β-胡萝卜素、α-胡萝卜素、γ-胡萝卜素、δ-胡萝卜素、菌脂色素、玉米黄质、隐黄质(玉米黄质)、海胆酮等前维生素A类;δ-生育酚、α-生育酚、β-生育酚、dl-α-生育酚琥珀酸酯、dl-α-生育酚琥珀酸酯钙、δ-生育酚、生育酚烟酸酯等维生素E类;核黄素、黄素单核苷酸、黄素腺嘌呤二核苷酸、核黄素丁酸酯、核黄素四丁酸酯、核黄素5’-磷酸酯钠、核黄素四烟酸酯等维生素B2类;烟酸甲酯、烟酸、烟酸酰胺等烟酸类;抗坏血酸硬脂酸酯、L-抗坏血酸二棕榈酸酯、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯)、抗坏血酸、抗坏血酸钠、脱氢抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸葡糖苷等维生素C类;甲基橙皮苷、钙化醇、胆钙化醇等维生素D类;叶绿醌(维生素K1)、金合欢醌(维生素K2)等的维生素K类;二苯甲酰硫胺素、二苯甲酰硫胺素盐酸盐、硫胺素盐酸盐、硫胺素十六烷基盐酸盐、硫胺素硫氰酸盐、硫胺素月桂基盐酸盐、硫胺素硝酸盐、硫胺素单磷酸盐、硫胺素赖氨酸盐、硫胺素三磷酸盐、硫胺素单磷酸酯磷酸盐、硫胺素单磷酸酯、硫胺素二磷酸酯、硫胺素二磷酸酯盐酸盐、硫胺素三磷酸酯、硫胺素三磷酸酯单磷酸盐等维生素B 1类;盐酸吡多辛、醋酸吡多辛、盐酸吡哆醛、5’-磷酸吡哆醛、盐酸吡哆胺等维生素B6类;氰钴胺素、羟钴胺素、腺苷钴胺酸等的维生素B12类;叶酸、蝶酰谷氨酸等叶酸类;泛酸、泛酸钙、泛醇(泛酰醇)、泛酰巯基乙胺(D-pantetheine)、泛硫乙胺(D-pantethine)、辅酶A、泛醇乙醚等的泛酸类;生物素、生物胞素等生物素类;此外还有肉碱、阿魏酸、α硫辛酸、乳清酸、γ-谷维醇(谷维素)等类似维生素作用的物质等。
其中,优选为维生素A、维生素A醋酸酯、维生素A棕榈酸酯等维生素A类;抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯)等维生素C类;δ-生育酚、生育酚烟酸酯等的维生素E类;烟酸酰胺等烟酸类。
作为使用维生素类成分时的用量,可通过对皮肤的使用感受或效果加以考虑而进行适当选择,相对于化妆材料组合物的总量,例如为约0.001~30重量%,优选为约0.1~25重量%,更优选为约0.5~20重量%。
作为血液循环促进作用成分,可以举出:来自植物(例如高丽参、明日叶、山金车花、银杏、茴香、毛叶香茶菜(延命草)、豆瓣菜、洋甘菊、罗马甘菊、胡萝卜、龙胆根、牛蒡、稻米、野山楂、香菇、锐刺山楂、欧洲杜松、川芎、日本獐牙菜(当药)、百里香、丁香、陈皮、当归、桃仁、橙皮、胡萝卜、大蒜、假叶树、葡萄、牡丹、七叶树、蜜蜂花、柚子、薏苡仁、迷迭香、玫瑰果、陈皮、当归、橙皮、桃、杏、核桃、玉米)的成分;生育酚烟酸酯、葡糖基橙皮苷、橙皮苷。其中,优选为高丽参浸膏、生育酚烟酸酯、葡糖基橙皮苷、橙皮苷。
作为血液循环促进成分的配合量,相对于化妆材料组合物的总量,例如为约0.00001~10重量%,优选为约0.0001~5重量%,更优选为约0.001~4重量%。作为使用植物成分时的用量,以浸膏、精油等提取物来换算,相对于化妆材料组合物的总量,例如为约0.00001~20重量%,优选为约0.0001~15重量%,更优选为约0.001~10重量%。
作为保湿成分,可以举出:来自植物(例如茅草)的成分;诸如丙胺酸、丝氨酸、亮氨酸、异亮氨酸、苏氨酸、甘氨酸、脯氨酸、羟基脯氨酸、葡糖胺、茶氨酸之类的氨基酸及其衍生物;诸如胶原蛋白、明胶、弹性蛋白之类的蛋白质或肽、其水解物;诸如丙三醇、1,3-丁二醇、丙二醇、聚乙二醇、二丙二醇、双甘油等多元醇;山梨醇之类的糖醇;蛋磷脂、氢化卵磷脂之类的磷脂质;透明质酸、透明质酸钠、乙酰基透明质酸、乙酰基透明质酸钠、肝素、软骨素之类的粘多糖;来自乳酸、吡咯烷酮羧酸钠、尿素之类的NMF(naturalmoisturizing factor,天然保湿因子)成分;聚谷氨酸;MPC聚合物(例如LIPIDURE(注册商标)等)等的具有磷脂质极性基的高分子;甲基葡萄糖苷聚氧丙烯醚;三甲基甘氨酸(甜菜碱);羟乙基脲;二甲基二烯丙基氯化铵-丙烯酰胺-丙烯酸共聚物;山梨醇等。其中,优选为茅草根浸膏、水解胶原蛋白、水解弹性蛋白、MPC聚合物丙三醇、1,3-丁二醇、聚乙二醇、二丙二醇、双甘油、甲基葡萄糖苷聚氧丙烯醚、三甲基甘氨酸(甜菜碱)、羟乙基脲、二甲基二烯丙基氯化铵-丙烯酰胺-丙烯酸共聚物、氢化卵磷脂、透明质酸、透明质酸钠、乙酰基透明质酸、乙酰基透明质酸钠、山梨醇。
作为使用保湿成分时的用量,相对于化妆材料组合物的总量,例如为0.001~10重量%,优选为约0.01~5重量%,更优选为约0.1~5重量%。作为使用植物成分时的用量,以浸膏、精油等提取物来换算,相对于化妆材料组合物的总量,例如为约0.00001~20重量%,优选为约0.0001~15重量%,更优选为约0.001~10重量%。
作为具有DNA的损伤的预防和/或修复作用的成分,可以举出:来自动物(例如卤虫)的成分;来自植物(例如猫掌草)的成分;DNA、DNA盐、RNA、RNA盐等的核酸成分。其中,优选为卤虫浸膏、DNA-Na。
作为具有DNA损伤的预防和/或修复作用的成分的配合量,相对于化妆材料组合物的总量,例如为约0.001~3重量%,优选为约0.01~1重量%。作为使用动物成分时的用量,以浸膏等提取物来换算,相对于化妆材料组合物的总量为约0.00001~0.1重量%,优选为约0.0001~0.01重量%。
作为紫外线吸收成分,可以举出:对甲氧基肉桂酸2-乙基己酯、2-[4-(二乙基氨基)-2-羟基苯甲酰]苯甲酸己酯、2,4,6-三[4-(2-乙基己氧基羰基)苯胺基]-1,3,5-三嗪、二甲氧亚苄基氧代咪唑烷基丙酸2-乙基己酯、2,4-双-[{4-(2-乙基己氧基)-2-羟基}-苯基]-6-(4-甲氧基苯基)-1,3,5-三嗪等。其中,优选对甲氧基肉桂酸2-乙基己酯、2-[4-(二乙基氨基)-2-羟基苯甲酰]苯甲酸己酯、2,4,6-三[4-(2-乙基己氧基羰基)苯胺基]-1,3,5-三嗪。
作为使用紫外线吸收成分时的用量,相对于化妆材料组合物的总量,例如为约0.01~20重量%,优选为约0.1~15重量%。
作为紫外线散射成分,可以举出:氧化锌、氧化钛、氧化铁、氧化铈、氧化锆、硅酸钛、硅酸锌、硅酸酐、硅酸铈、水合硅酸等无机化合物,或者使这些无机化合物以水合硅酸、氢氧化铝、云母或滑石等无机粉体来包覆或者与聚酰胺、聚乙烯、聚酯、聚苯乙烯、尼龙等的树脂粉状体发生共轭化而成的物质、进而以硅油或脂肪酸铝盐等处理而成的物质等。其中,优选为氧化锌、氧化钛、氧化铁等无机化合物以及使这些无机化合物以氢氧化铝、水合硅酸、云母或滑石等无机粉体或硅油来包覆而成的物质。
作为使用紫外线散射成分时的用量,例如,相对于化妆材料组合物的总量为约0.001~35重量%,优选为约0.1~25重量%。
作为清洗成分,可以举出:聚氧化亚烷基烷基(或烯基)醚硫酸盐、烷基(或烯基)硫酸盐、高级脂肪酸盐、醚羧酸盐、酰胺醚羧酸盐、烷基磷酸酯盐、N-酰基氨基酸盐、聚氧化亚烷基脂肪酸酰胺醚硫酸盐、酰化羟乙磺酸盐、酰化牛磺酸盐等阴离子表面活性剂;氧化胺、甘油脂肪酸酯、失水山梨醇脂肪酸酯、烷基糖类、聚氧亚烷基烷基醚、脂肪酸烷醇酰胺、聚氧化亚烷基固化蓖麻油等非离子表面活性剂;可加成环氧烷的、具有直链或支链的长链烷基的单长链或双长链烷基季铵盐等阳离子表面活性剂;碳代甜菜碱(carbo-betaine)、硫代甜菜碱(sulfo-betaine)、咪唑啉甜菜碱(imidazoliniumbetaine)、酰胺甜菜碱等两性表面活性剂。
其中,优选为阴离子表面活性剂、非离子表面活性剂、两性表面活性剂。阴离子表面活性剂中,优选为高级脂肪酸盐(特别是,棕榈酸、月桂酸、肉豆蔻酸、硬脂酸等高级脂肪酸的盐)、N-酰基氨基酸盐(特别是,N-月桂酰天冬氨酸钠、氢氧化钾/N-椰子油脂肪酸酰基谷氨酸钾、椰子油脂肪酸酰基甘氨酸钠、肉豆蔻酰谷氨酸)。非离子表面活性剂中,优选为脂肪酸烷醇酰胺(特别是,椰子油脂肪酸二乙醇酰胺、椰子油脂肪酸单乙醇酰胺)、氧化胺(特别是,椰子油烷基二甲基氧化胺、月桂醇二甲基氧化胺)。两性表面活性剂中,优选为咪唑啉甜菜碱(特别是,2-烷基-N-羧甲基-N-羟乙基咪唑啉甜菜碱、N-椰子油脂肪酸酰基-N-羧甲氧基乙基-N-羧甲基乙二胺二钠)。
作为清洗成分的配合量,相对于化妆材料组合物的总量为约0.01~80重量%,优选为约0.1~60重量%。
作为抗菌成分,可以举出:氯己定、水杨酸、苯扎氯铵(氯化苄烷铵)、利凡诺(acrinol)、乙醇、苄索氯铵(氯化苄乙氧铵)、甲酚、葡糖酸及其衍生物、聚乙烯吡酮碘、碘化钾、碘、异丙基甲酚、三氯卡班(Triclocarban)、三氯生(Triclosan)、感光素101号、感光素201号、对羟苯甲酸酯、苯氧乙醇、1,2-戊二醇、盐酸烷基二氨基甘氨酸等。其中,优选为苯扎氯铵、苄索氯铵、葡糖酸及其衍生物、异丙基甲酚、三氯卡班、三氯生、感光素101号、感光素201号、对羟苯甲酸酯、苯氧乙醇、1,2-戊二醇、盐酸烷基二氨基甘氨酸,更优选为苯扎氯铵、葡糖酸及其衍生物、苄索氯铵、异丙基甲酚。
作为使用抗菌成分时的用量,相对于化妆材料组合物的总量,优选为约0.0003~10重量%,更优选为约0.01~5重量%。
作为收敛成分,可以举出:明矾、羟基氯化铝、氯化铝、尿囊素铝盐、硫酸锌、明矾等的金属盐;鞣酸、柠檬酸、乳酸、琥珀酸等有机酸。其中,优选为明矾、羟基氯化铝、氯化铝、尿囊素铝盐、明矾、鞣酸。
作为使用收敛成分时的用量,相对于化妆材料组合物的总量,例如为约0.0003~10重量%,优选为约0.01~5重量%,更优选为约0.01~5重量%。
本发明的化妆材料组合物,可通过采用通常方法对各成分混合搅拌来制备。例如,可以在化妆品主剂中预先混合搅拌不溶性的成分和油性成分,然后配合水性成分并再次混合搅拌。为了在主剂中容易分散不溶性成分,所以可采用均质混合机等搅拌机。
成分的优选组合
作为本发明的有效成分和其它活性成分的优选组合,可以举出下述组合。
当含有公知的抗糖化成分时,可以举出与余甘子浸膏、荔枝种子浸膏、玫瑰花瓣浸膏、七叶树浸膏、水飞蓟浸膏、印楝浸膏、水解鞣质、L-精氨酸或其盐、赖氨酸或其盐、肌肽、α硫辛酸、氨基胍或其盐、阿利斯丁(Alistin)、或葡糖胺的组合;
当含有抗氧化成分时,可以举出与葡萄籽浸膏、葡萄叶浸膏、高丽参浸膏、聚合草叶浸膏、原花色素、δ-生育酚、α-生育酚、抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯)、橙皮苷、葡糖基橙皮苷或硫组氨酸甲基内盐的组合;
当含有防老化成分时,可以举出与水解大豆蛋白、维生素A、维生素A醋酸酯或维生素A棕榈酸酯的组合;
当含有抗炎症成分时,可以举出与聚合草叶浸膏、尿囊素、甘草酸二钾或甘草次酸十八酯的组合;
当含有美白成分时,可以举出与熊果苷、氢醌、曲酸、抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯)或氨甲环酸的组合;
当含有角质软化成分时,可以举出与乳酸、乳酸钠、乙醇酸、水杨酸或植酸的组合;
当含有细胞活化成分时,可以举出与越橘叶浸膏、维生素A、维生素A醋酸酯或维生素A棕榈酸酯的组合;
当含有维生素类时,可以举出与维生素A类(维生素A、维生素A醋酸酯、维生素A棕榈酸酯)、维生素C类(抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯))、维生素E类(δ-生育酚、生育酚烟酸酯)、烟酸类(烟酸酰胺)的组合;
当含有具有血液循环促进作用的成分时,可以举出与高丽参浸膏、生育酚烟酸酯、葡糖基橙皮苷或橙皮苷的组合;
当含有保湿成分时,可以举出与茅草根浸膏、水解胶原蛋白、水解弹性蛋白、MPC聚合物丙三醇、1,3-丁二醇、聚乙二醇、二丙二醇、双甘油、甲基葡萄糖苷聚氧丙烯醚、三甲基甘氨酸(甜菜碱)、羟乙基脲、二甲基二烯丙基氯化铵-丙烯酰胺-丙烯酸共聚物、氢化卵磷脂、透明质酸、透明质酸钠、乙酰基透明质酸、乙酰基透明质酸钠或山梨醇的组合;
当含有具有DNA的损伤的预防和/或修复作用的成分时,可以举出与卤虫浸膏或DNA-Na的组合;
当含有紫外线吸收成分或紫外线散射成分时,可以举出与对甲氧基肉桂酸2-乙基己酯、2-[4-(二乙基氨基)-2-羟基苯甲酰]苯甲酸己酯、或2,4,6-三[4-(2-乙基己氧基羰基)苯胺基]-1,3,5-三嗪、氧化锌、氧化钛、氧化铁或者以无机粉体(氢氧化铝、水合硅酸、云母或滑石)或硅油来包覆这些无机化合物而成的物质的组合;
当含有清洗成分时,可以举出与高级脂肪酸盐(特别是,棕榈酸、月桂酸、肉豆蔻酸、硬脂酸等高级脂肪酸的盐)、N-酰基氨基酸盐(特别是,N-月桂酰天冬氨酸钠、氢氧化钾/N-椰子油脂肪酸酰基谷氨酸钾、椰子油脂肪酸酰基甘氨酸钠、肉豆蔻酰谷氨酸)、脂肪酸烷醇酰胺(特别是,椰子油脂肪酸二乙醇酰胺、椰子油脂肪酸单乙醇酰胺)、氧化胺(特别是,椰子油烷基二甲基氧化胺、月桂醇二甲基氧化胺)、咪唑啉甜菜碱(特别是,2-烷基-N-羧甲基-N-羟乙基咪唑啉甜菜碱、N-椰子油脂肪酸酰基-N-羧甲氧基乙基-N-羧甲基乙二胺二钠)的组合;
当含有抗菌成分时,可以举出与苯扎氯铵、葡糖酸及其衍生物、苄索氯铵或异丙基甲酚的组合;
当含有收敛成分时,可以举出与明矾、羟基氯化铝、氯化铝、尿囊素铝盐、明矾或鞣酸的组合。
其中,优选组合公知的抗糖化成分、抗氧化成分、防老化成分、抗炎症成分、角质软化成分、细胞活化成分、维生素类、血液循环促进作用成分、保湿成分、具有DNA损伤的预防和/或修复作用的成分、紫外线吸收或散射成分以及清洗成分。其中,更优选组合公知的抗糖化成分、防老化成分、抗氧化成分以及具有DNA损伤的预防和/或修复作用的成分,进一步优选组合公知的抗糖化成分、防老化成分和抗氧化成分。
食品组合物
本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂,能够作为食品组合物。
该食品组合物,可适于作为健康食品、营养辅助食品(包括营养平衡食物、补品等)使用。另外,还适于保健功能食品(包括特定保健用食品(包括表明降低疾病风险的特定保健用食品、标准规格型特定保健用食品)、附带条件的特定保健用食品、营养功能食品)。
对剂型并没有特别限定,但由于有效成分是油性成分,所以可以举出软胶囊剂、乳剂等剂型,优选软胶囊剂。根据需要,可以将前述说明的有效成分,与其它油脂、稳定剂、乳化剂、分散剂、悬浮剂、香料、增粘剂、甜味料、着色剂、香料、保存剂、抗氧化剂、有机酸等食品添加剂一起混合后进行制剂化。
制剂化可采用通常的方法来施行。软胶囊,例如按下述方法可获得:采用软胶囊制造机,将作为本发明剂的有效成分的不饱和脂肪酸、其衍生物和/或植物油,根据需要与其它成分混合,将如此形成的混合物,用胶囊皮膜材料包裹、压合成型获得软胶囊。乳剂,例如按下述方法可获得:将作为本发明剂的有效成分的不饱和脂肪酸、其衍生物和/或植物油以及乳化剂,根据需要与其它成分混合备用,将该混合物与纯化水混合搅拌获得乳剂。
作为其它的油脂,可以举出:花生油、可可奶油、稻米胚芽油、紫苏籽油、亚麻仁油等天然植物油等或它们的固化油、脂肪酸(包括中链脂肪酸)的甘油酯(甘油酯、甘油二酸酯、甘油三酸酯等)、蜂蜡等。其中,优选为蜂蜡。
作为乳化剂、分散剂、悬浮剂、稳定剂,可以举出:诸如聚乙二醇、丙二醇、丙三醇、山梨醇之类的多元醇;甘油脂肪酸酯;羧甲基纤维素钠等。其中,优选为丙三醇、甘油脂肪酸酯、羧甲基纤维素钠。
作为增粘剂,可以举出:槐树豆胶、瓜尔胶、黄原胶、罗望子胶、果胶、卡拉胶等。其中,优选为黄原胶。
作为甜味料,可以举出:蔗糖、果糖、麦芽糖、赤藓醇、海藻糖、麦芽糖醇、甘草提取物、斯特维亚菊加工甜味料、阿斯巴特糖、乙酰磺胺酸钾、山梨醇、木糖醇等。
作为保存剂,可以举出:苯甲酸或其盐、山梨酸或其盐、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯、对羟基苯甲酸异丙酯、对羟基苯甲酸乙酯等。
作为抗氧化剂,可以举出:抗坏血酸、抗坏血酸钠、抗坏血酸硬脂酸酯、抗坏血酸硬脂酸钠、抗坏血酸棕榈酸酯、亚硫酸氢盐、次亚硫酸钠、二氧化硫、EDTA二钠钙、异抗坏血酸、异抗坏血酸钠、生育酚等。其中,优选为抗坏血酸、抗坏血酸棕榈酸酯、生育酚。
作为有机酸,可以举出柠檬酸、琥珀酸、酒石酸、天冬氨酸、乳酸、苹果酸、丙二酸、富马酸、马来酸等。
作为食品添加剂,可单独使用一种或组合使用两种以上。
在制剂中,可添加其它活性成分。
作为其它活性成分,以进一步增强上述本发明的效果为目的,即所谓改善、抑制和/或预防由AGEs在皮肤中的蓄积引起的肌肤整体的衰老(例如诸如皮肤暗黄之类的皮肤色泽改变、肌肤紧致或透明感的降低等)或者延缓肌肤整体衰老进度(速度)的目的,食品组合物中能够配合可添加于化妆品中的公知的抗糖化成分。公知的抗糖化成分,可单独使用一种或组合使用两种以上。
作为公知的抗糖化成分,例如,可以举出:余甘子的果实、果汁或它们的提取物(日本特开2006-028090、日本特开2006-62989号等);L-精氨酸、L-赖氨酸、水解酪蛋白(以上参照日本特开2001-039816);水解鞣质(日本特开平9-40519号);肌肽、α硫辛酸(以上,参照《美容のための最新皮膚診断マニユアル(用于美容的最新皮肤诊断指南)》、FRAGRANCEJOURNAL(香味期刊)杂志社,2006年8月15日发行);西洋蔷薇(玫瑰)的花·子房、杂交月季(hybrid rose)的花·子房·花萼·叶·茎、玫瑰果(蔷薇果)、葡萄叶、柿树叶、苹果叶、万寿菊的花、木兰叶的提取物(以上参照日本特开2006-273811号);牡丹属植物提取物、黄芩属植物提取物、蜜蜂花属植物提取物、向日葵属植物提取物、芦荟属植物提取物、黄精属植物提取物、亚麻属植物提取物、蔷薇属植物提取物、椴树属植物提取物、细辛属植物提取物、鱼腥草属植物提取物、款冬属植物提取物、地榆属植物提取物、薄荷属植物提取物、接骨木属植物提取物(以上参照日本特开2003-212749号);大高良姜的提取物(日本特开2006-62987号);罗汉柏、黑儿茶、虎杖、鹿蹄草、杏(树)、鸡冠花、白花油麻藤、白桦、锐刺山楂、欧蓍草(西洋耆草)、大叶冬青、鱼腥草(蕺菜)、直立委陵菜、麦门冬、罗汉柏、葡萄、扁蓄、无患子、木瓜、荔枝、罗马甘菊的提取物(以上参照日本特开2003-212770号);北美金缕梅、杏(树)、鹿蹄草、熊果、黄连、大花紫薇、黑儿茶树、老鹳草、萍蓬草、石榴、芍药、绣线菊、大黄、茶树(Camellia sinensis)、丁香、番泻叶、甜茶、覆盆子、直立委陵菜、蔷薇(玫瑰)、牡丹、鼠尾草、夜叉五倍子、杨梅、蓝桉树、采木、地榆的提取物(以上参照日本特开2002-241299号);木通、芦荟、杏(树)、桦树、桔梗、五味子、人参三七、狼把草、黄精、繁缕、番杏(滨莴苣)、茯苓、柚子的提取物(以上参照日本特开2002-241293号);玫瑰茄(卡凯蒂(Karkade))、木槿、车前子、桃仁、七叶树、桂皮、五味子、紫草根、番泻叶、菟丝子、白芨的提取物(以上参照日本特开平11-106336号);枣核(酸枣仁)、胖大海果实、南瓜籽、杜仲叶、五层龙根、伞形梅笠草叶的提取物(以上参照日本特开2007-254345号);土常山(茶)、金雀花、雪莲花、南非钩麻、刺五加、红景天(RhodiolaRosea)、Hercampuri(Gentianella alborosea:一种龙胆科龙胆属植物)的提取物(以上参照日本特开2007-254344号);木瓜的提取物(日本特开2006-298812号);Simonillo(Conyza filaginoides:一种菊科白酒草属植物)的提取物(日本特开2006-219447号);越橘属植物的提取物(日本特开2006-117700号);龙牙草、南非醉茄、大茴香、绞股蓝、甜茶悬钩子、银杏、茴香、金缕梅、姜黄、紫松果菊、刺五加、接骨木、耶巴马黛茶(Yerba Mate)、车前草、橄榄、牛至、柑橘、柿树、连钱草、洋甘菊、瓜拉纳(guarana)、含羞草、菊、匙羹紫藤、猫掌草、猫薄荷、基拉韦(キラウエイ)、金银花、番石榴、枸杞叶、山白竹、猫须草(Kumis kuting)、黑大豆、桑树、肉桂、决明子、苦瓜、可乐果、五加皮、积雪草(gotukola)、芫荽、聚合草、银叶树、红花、长圆五层龙(Salacia oblonga)、野山楂、人参三七、紫苏、鱼腥草、杜松籽、姜、杉树、问荆、斯特维亚菊、留兰香、鼠尾草、香薄荷、锐刺山楂、仙楂(山楂)、百里香、TAHEEBO(皮蚁木(Tabebuia Avellanedae))、蒲公英、山萝卜、茶树(Camellia sinensis)、粉色西番莲、丁香、雏菊、莳萝、杜仲、肉豆蔻、南姜、荨麻、木槿、白猪母菜、白花蛇舌草、羽衣草、罗勒、莲(藕)、半枝莲、欧石楠、桃树、牛膝草、枇杷、小白菊、福木树树、紫藤、洋车前子、蓝莓、紫罗兰、薄荷、红花、薄荷、啤酒花、琉璃苣、圆滑番荔枝(牛心果)、药蜀葵、墨角兰、万寿菊、毛蕊花、小锦葵、欧锦葵、海芒果、奶蓟草、毛果槭、旋果蚊子草(メデウスイ一ト)、木瓜、海巴戟、矢车菊、西洋耆草、桉树、薏苡仁、魁蒿、悬钩子、熏衣草、菩提树、红灌木ROOIBOS(Aspalathus Linearis)、柠檬草、柠檬百里香、柠檬马鞭草、柠檬香蜂草、玫瑰果、玫瑰花蕾(Rose pink buds)、迷迭香、玫瑰红(rosered,药用玫瑰花瓣)、月桂树、罗布麻、野草莓的提取物(以上参照日本特开2004-250445号);赤芽柏、柿树、桑树、贯叶连翘、积雪草、山羊豆、北美圣草、玫瑰果的提取物(以上参照日本特开2004-189663号);樱花、红景天、蓝莓、熊果、蜡杨梅、繁缕、葛缕子(藏茴香)、散沫花、拉瑞阿的提取物(以上参照日本特开2001-316221号);紫杉树、槐花、海桐皮、金樱子、月桂树、交让木、石菖蒲、苍耳、贝母、木天蓼的提取物(以上参照日本特开平8-259431号);胡萝卜叶的提取物(日本特开2004-51580号);黑儿茶树、白桦、锐刺山楂、茶树(Camellia sinensis)、丁香、鱼腥草(蕺菜)、直立委陵菜、蔷薇(玫瑰)、葡萄、七叶树、罗马甘菊的提取物(以上参照日本特开2005-35911号);氨基胍或其盐(《最新医学》,49卷·2号,p78~83,1994);黑大豆种皮、马黛茶叶(绿)、菩提树花、柳叶栎叶、糙米种子、西洋柳树皮(柳皮)·嫩芽、小米草地上部、黑升麻根、西洋牡荆果实(圣洁莓)、洋蓟(Artichoke)叶、荔枝种子、卡杜巴树树皮、燕麦地上部、西番莲叶、柳叶破布木(Chá de Bugre(Cordia salicifolia))叶、荞麦叶、水飞蓟的水飞蓟、明日叶的叶、南非钩麻根、齿叶蚁木(依贝)树皮、姬松茸(巴西蘑菇)菌丝体、珐菲亚(巴西人参:珐菲亚属植物)根、阿萨伊浆果(巴西莓)、海蕴全草和蜂斗菜茎·叶的加工物(以上参照日本特开2008-088102);印楝浸膏;阿利斯丁(Alistin);葡糖胺等。其中,优选为:来自余甘子、荔枝、蔷薇(玫瑰)、七叶树、水飞蓟、印楝等植物的成分(特别是,余甘子浸膏、荔枝种子浸膏、蔷薇(玫瑰)花瓣浸膏、七叶树浸膏、水飞蓟浸膏、印楝浸膏);水解鞣质(特别是来自栗内皮的);L-精氨酸或其盐;赖氨酸或其盐;肌肽;α硫辛酸;氨基胍或其盐;阿利斯丁(Alistin);葡糖胺。
作为公知的抗糖化成分以外的活性成分,可以举出抗氧化成分、防老化成分、抗炎症成分、美白成分、细胞活化成分、维生素类、血液循环促进作用成分、保湿成分、具有DNA的损伤的预防和/或修复作用的成分等,具体而言,可以举出诸如维生素A类、维生素B类、维生素C类、维生素E类、维生素D类、维生素K类之类的维生素类;诸如苏氨酸、蛋氨酸、苯丙氨酸、色氨酸、赖氨酸、甘氨酸、丙胺酸、天冬酰胺、谷氨酰胺、丝氨酸、半胱氨酸、胱氨酸、酪氨酸、脯氨酸、羟基脯氨酸、天冬氨酸、谷氨酸、羟基赖氨酸、精氨酸、鸟氨酸、组氨酸之类的氨基酸;诸如牛磺酸、胶原蛋白、葡糖胺、乙酰基葡糖胺、透明质酸、异黄酮、聚酚(多元酚)(例如来自栗的内皮、葡萄籽之类植物的聚酚)、生物素、乳清肽、大豆肽、蜂王浆、γ-谷维醇(谷维素)、乳清酸、芸香苷、橙皮苷、肉碱、氯化肉碱、胶原蛋白肽、弹性蛋白肽、神经酰胺、菌脂色素、虾青素、乳酸菌提取物(例如LFK)、谷胱甘肽、芸香苷、来自植物(例如猫掌草、葡萄、姜、莲(藕)、葡萄、甜瓜、雨生红球藻)的成分、泛醌衍生物(例如辅酶Q10)、燕窝末等。
在此,作为维生素A类,可例示视黄醇、维生素A、视黄酸、胡萝卜素、脱氢视黄醛、菌脂色素等;作为维生素B类,可例示二硫胺、二硫化硫胺(硫胺素二硫化物)、硫胺素双十六烷基硫酸酯盐、苯磷硫胺、丙舒硫胺、呋喃硫胺、二苯甲酰硫胺、赛可硫胺、奥托硫胺、蒜硫胺、二硫化丙基硫胺、二硫化四氢糠基硫胺(thiamine tetrahydrofurfuryl disulfide,硫胺四氢糠基二硫化物)、西托硫胺(dicethiamine)、双异丁硫胺(舒布硫胺)、二硫化磷酸硫胺(thiamine monophosphate disulfide)、焦磷酸硫胺素、赛可硫胺、二硫化乙基硫胺、二硫化丙基硫胺(丙硫硫胺)、核黄素、黄素腺嘌呤二核苷酸、吡多辛(吡哆醇)、吡哆醛、羟钴胺素、氰钴胺素、甲基钴胺、腺苷钴胺(deoxyadenosylcobalamin)、叶酸、四氢叶酸、二氢叶酸、烟酸、烟酸酰胺、烟醇、泛酸、泛酰醇、生物素、胆碱、肌醇等;作为维生素C类,可例示抗坏血酸、抗坏血酸钠、抗坏血酸硬脂酸酯、抗坏血酸硬脂酸钠、抗坏血酸棕榈酸酯、异抗坏血酸等;作为维生素D类,可例示钙化醇、胆钙化醇、羟胆钙化醇、二羟胆钙化醇(骨化三醇)、双氢速甾醇等;作为维生素E类,可例示生育酚及其衍生物等。
在其它活性成分之中,优选为聚酚(例如来自诸如栗内皮、葡萄籽之类植物的聚酚)、大豆肽、透明质酸、胶原蛋白肽、弹性蛋白肽、神经酰胺、菌脂色素、辅酶Q10、虾青素、甜瓜提取物、乳酸菌提取物(例如LFK)、谷胱甘肽、芸香苷、猫掌草浸膏、红葡萄叶浸膏、雨生红球藻提取物、姜浸膏、莲胚芽浸膏、抗坏血酸、生育酚。
其它活性成分可单独使用一种或组合使用两种以上。
若针对胶囊制剂的成分进行详述,则对胶囊皮膜的材料没有特别限定,例如,可以举出猪皮明胶、猪骨明胶、鱼明胶、天然亲水性聚合物、牛皮明胶等,可使用它们中的一种以上。其中,优选为猪皮明胶、猪骨明胶、支链淀粉等。可采用公知惯用的方法制备上述胶囊皮膜。
胶囊皮膜中不仅含有来自上述特定动植物等的原料,而且可以含有油脂、多元醇、表面活性剂、抗氧化剂、染料、香料等。作为油脂,例如,可以举出:大豆油、红花油、橄榄油、胚芽油、菜籽油、葵花籽油、花生油、棉籽油、米糠油、可可奶油等天然油或它们的固化油、脂肪酸(包括中链脂肪酸)的甘油酯(甘油酯、甘油二酸酯、甘油三酸酯等)等。作为多元醇,可以举出:聚乙二醇、丙二醇、丙三醇、山梨醇等。作为表面活性剂,可以举出:失水山梨醇脂肪酸酯、聚甘油脂肪酸酯等非离子表面活性剂等。作为染料,可以举出:类胡罗卜素类色素、花色素苷类色素、可可色素、蒽醌(アントラノン)类色素、焦糖色素、红花黄色素、二氧化钛等。其中,基于可进一步提高胶囊制剂稳定性的观点,优选向胶囊皮膜中添加油脂、多元醇、表面活性剂和/或天然色素。
<成分的优选组合>
作为本发明的有效成分与其它成分的优选组合,可以举出下述组合。
当含有其它油脂时,可举出与蜂蜡的组合;
当含有乳化剂、分散剂、悬浮剂或稳定剂时,可举出与丙三醇、甘油脂肪酸酯或羧甲基纤维素钠的组合;
当含有增粘剂时,可举出与黄原胶的组合;
当含有甜味料时,可举出与蔗糖、果糖、麦芽糖、赤藓醇、海藻糖、麦芽糖醇、甘草提取物、斯特维亚菊加工甜味料、阿斯巴特糖、乙酰磺胺酸钾、山梨醇或木糖醇的组合;
当含有保存剂时,可举出与苯甲酸或其盐、山梨酸或其盐、对羟基苯甲酸丁酯、对羟基苯甲酸异丁酯、对羟基苯甲酸异丙酯或对羟基苯甲酸乙酯的组合;
当含有抗氧化剂时,可举出与抗坏血酸、抗坏血酸棕榈酸酯或生育酚的组合;
当含有有机酸时,可举出与柠檬酸、琥珀酸、酒石酸、天冬氨酸、乳酸、苹果酸、丙二酸、富马酸或马来酸的组合;
当含有公知的抗糖化成分时,可举出与余甘子浸膏、荔枝种子浸膏、蔷薇(玫瑰)花瓣浸膏、七叶树浸膏、水飞蓟浸膏、印楝浸膏、水解鞣质、L-精氨酸或其盐、赖氨酸或其盐、肌肽、α硫辛酸、氨基胍或其盐、阿利斯丁(Alistin)、葡糖胺的组合;
当含有其它活性成分时,可举出与来自栗内皮或葡萄籽的聚酚、大豆肽、透明质酸、胶原蛋白肽、弹性蛋白肽、神经酰胺、菌脂色素、辅酶Q10、虾青素、甜瓜提取物、乳酸菌提取物(例如LFK)、谷胱甘肽、芸香苷、猫掌草浸膏、红葡萄叶浸膏、雨生红球藻提取物、姜浸膏、莲胚芽浸膏、抗坏血酸或生育酚的组合。
其中,优选组合其它油脂、乳化剂、分散剂、悬浮剂或稳定剂、增粘剂、公知的抗糖化成分、其它活性成分(抗氧化成分、防老化成分、抗炎症成分、美白成分、细胞活化成分、维生素类、血液循环促进作用成分、保湿成分以及具有DNA损伤的预防和/或修复作用的成分等)。
作为活性成分的组合,优选组合公知的抗糖化成分、防老化成分、抗氧化成分、美白成分以及具有DNA损伤的预防和/或修复作用的成分。
当食品组合物是上述说明的补品等被制剂化的食品组合物时,食品组合物有效成分的含量相对于食品组合物的总量优选为约10~60重量%,更优选为约20~50重量%,进一步优选为约30~40重量%。若在上述范围内,则在可适度摄取的食品组合物中,会含有只获得充分的AGEs降解效果甚至由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善效果的有效成分。
<一般食品组合物>
另外,该食品组合物,可在一般食品中添加上述说明的有效成分来进行制备。作为食品,例如,可以举出:诸如牛奶、乳饮料、乳酸菌饮料、果汁清凉饮料、碳酸饮料、菜汁饮料、茶饮料、果汁饮料、离子饮料(电解质饮料)、运动饮料、功能性饮料、维生素补充饮料、营养补充平衡饮料、果冻饮料、酒精饮料、汤类之类的饮料;诸如可斯德布丁(牛乳布丁)、牛奶布丁、加入果汁的布丁等的布丁类,诸如果冻类、调味汁类、奶油类之类的凝胶状点心,诸如口香糖、泡泡糖之类的口香糖类(板状口香糖、糖衣粒状口香糖等)、巧克力类(纯巧克力、装饰巧克力(coating chocolate)、草莓巧克力、蓝莓巧克力、甜瓜巧克力等有附加风味的巧克力等)、软糖(包括焦糖、果仁奶糖、橡皮糖、棉花软糖等)、乳脂糖(太妃糖)等焦糖类、饼干类(硬饼干、软饼干、软曲奇饼、咸饼干、半生饼干等)、蛋糕类等糕点类;冰淇淋、冰牛奶(ice milk(日式冷饮))、乳酸冰淇淋、水果冰沙、冰点心等冷冻点心类;面包类;面条类;宠物食品等。
当食品组合物是在一般食品中添加了有效成分而成时,对其中有效成分的含量,并没有特别限定。
即,本发明中,(i)选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种的化合物和(ii)含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油,可作为制造用于降解AGEs或者用于预防、抑制或改善由AGEs的蓄积引起的肌肤衰老的食品添加物的有效成分使用。
使用方法
化妆材料组合物,可以按照化妆材料通常的使用方法、使用次数涂敷于人的皮肤(脸面等)。
另外,食品组合物,按每天摄取有效成分的量来计算,例如,可以摄取约50~4000mg,优选为约50~500mg,更优选为约50~180mg。
本发明的AGEs降解剂和由AGEs蓄积所引起的肌肤衰老的预防、抑制或改善剂的使用对象,并没有特别限定,但对于化妆材料组合物而言,优选对象是:高龄者、被确认由AGEs的生成和蓄积所引起的肌肤整体衰老的人、和以AGEs的生成和蓄积为起因而存在肌肤整体衰老趋势的人等。另外,对食品组合物而言,适合的对象是:高龄者、被确认由AGEs的生成和蓄积所引起的肌肤整体的衰老的人、以AGEs的生成和蓄积为起因而存在肌肤整体衰老趋势的人,此外还有糖尿病患者(特别是引发白内障、动脉硬化、肾功能障碍、视网膜症、神经障碍等并发症的患者)、动脉硬化症患者、恶性肿瘤患者、骨病患者、阿尔茨海默病患者、帕金森氏病患者等。另外,化妆材料组合物和食品组合物均能够以健全人为对象,基于此能够预防伴随着老龄化等而来的、由AGEs的生成和蓄积所引起的肌肤整体的衰老或者延缓衰老速度。
从进一步有效发挥本发明效果的观点出发,优选不仅将化妆材料组合物涂敷在肌肤上从而从外侧对肌肤给予有效成分,而且通过摄取食品组合物而经口路径对肌肤提供有效成分。即,特别优选并用本发明的化妆材料组合物和本发明的食品组合物。
即,本发明还包括下述方法。
(i)将选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种,以有效降解晚期糖基化终末产物的量对人给药(包括在人的皮肤上涂敷)的降解晚期糖基化终末产物的方法,或者非治疗性的降解晚期糖基化终末产物的方法。
(ii)将含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油,以有效降解晚期糖基化终末产物的量对人给药(包括在人的皮肤上涂敷)的降解晚期糖基化终末产物的方法,或者非治疗性的降解晚期糖基化终末产物的方法。
(iii)将选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种,以有效预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老(例如皮肤紧致性降低或皮肤色泽改变)的量对人给药(包括在人的皮肤上涂敷)的预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的方法,或者非治疗性的预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的方法。
(iv)将含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油,以有效预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老(例如皮肤紧致性降低或皮肤色泽改变)的量对人给药(包括在人的皮肤上涂敷)的预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的方法,或者非治疗性的预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的方法。
其它
(i)不饱和脂肪酸及其药学上可接受的盐、其药学上可接受的甘油酯、其药学上可接受的酯以及(ii)含有选自于由不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种的植物油,应用于降解晚期糖基化终末产物或者预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤的衰老(例如皮肤紧致性降低或皮肤色泽改变)。另外,还可应用于制造晚期糖基化终末产物的降解剂、或应用于制造由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂。
(B)本发明的第二种由AGEs的蓄积引起的肌肤衰老的预防、抑制或
改善剂、肌肤紧致的改善剂、皮肤色泽的改善剂
本发明的第二种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂和皮肤色泽的改善剂,含有下述(a)和(b)作为有效成分。
(a)选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种
(b)AGEs降解剂
作为(b)AGEs降解剂,可以举出下述(b-i)、(b-ii)或(b-iii)。
(b-i)选自于由不饱和脂肪酸及其药学上可接受的盐、药学上可接受的甘油酯、药学上可接受的酯和药学上可接受的酰胺所构成的组中的至少一种
(b-ii)含有选自于由不饱和脂肪酸及其药学上可接受的衍生物所构成的组中的至少一种的植物油
(b-iii)具有分解AGEs效果的植物浸膏
换言之,上述(a)、(b)的成分,也可以是抗糖化剂或是基于抗糖化作用的抗老化剂或抗老龄化剂的有效成分。
本发明还包括:含有上述(a)与选自于由上述(b-i)、(b-ii)和(b-iii)所构成的组中的两种以上作为有效成分的、由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂和皮肤色泽的改善剂。
乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接
受的盐
作为药学上可接受的盐,可以举出:诸如钠盐、钾盐之类的碱金属盐;诸如钙盐、镁盐之类的碱土类金属盐;铵盐等。在乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐中,优选为乳酸、乳酸钠、乙醇酸、水杨酸、植酸,更优选为乳酸、乳酸钠。
作为乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐,可单独使用一种或组合使用两种以上。
不饱和脂肪酸及其衍生物
不饱和脂肪酸及其衍生物如同针对本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂所述的情形。
植物油
植物油如同针对本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂所述的情形。
具有AGEs降解效果的植物浸膏
作为具有AGEs降解效果的植物浸膏,可没有限制地使用公知的植物浸膏。作为具有AGEs降解效果的公知的植物浸膏,例如,可以举出:橄榄提取物(日本特开2001-122758号);虎耳草提取物(日本特开2001-131051号);菊花科魁蒿属的植物的极性溶剂提取物(日本特开2007-161663号);蔷薇科蚊子草属(日本绣线菊属)的极性溶剂提取物(日本特开2007-161662号);红灌木ROOIBOS(Aspalathus Linearis)的植物体的极性溶剂提取物(日本特开2007-161661号);蔷薇科委陵菜属的植物的植物体的极性溶剂提取物(日本特开2007-161660号);秦椒(zanthoxylum piperitum)软浸膏、姜黄提取液、藏红花酊剂、薄荷软浸膏、姜提取液、胡萝卜提取液、莲叶浸膏、落新妇(红升麻)浸膏、毛喉鞘蕊花浸膏、黄杞叶浸膏、荜拔(piper longum)浸膏、秦椒(zanthoxylum piperitum)花粉、毛叶香茶菜浸膏、扁实柠檬(台湾香檬)浸膏、葛根浸膏、普洱茶浸膏、甘草浸膏、糙米浸膏、月见草浸膏、番石榴叶浸膏、枇杷叶浸膏、洋葱外皮浸膏、青花浸膏、桑叶浸膏、楤木芽浸膏、甘露子(草石蚕)浸膏、白芸豆浸膏、罗布麻浸膏、山白竹浸膏、苦瓜浸膏、菊芋浸膏、大麦嫩叶浸膏、褐藻类浸膏、魔芋浸膏、咖啡豆浸膏、葡萄籽浸膏、苹果浸膏、橄榄叶浸膏、海带浸膏、明日叶粉、儿茶素、金橘软浸膏、枳实浸膏、金橘浸膏、柑橘属果树浸膏、柚子粉和陈皮浸膏(以上参照日本特开2007-119373号);北美金缕梅、杏(树)、鹿蹄草、熊果、黄连、大花紫薇、黑儿茶树、老鹳草、萍蓬草、石榴、芍药、绣线菊、大黄、茶树(Camellia sinensis)、丁香、番泻叶、甜茶、覆盆子、直立委陵菜、蔷薇(玫瑰)、牡丹、鼠尾草、夜叉五倍子、杨梅、蓝桉树、采木、地榆的提取物(以上参照日本特开2002-241299号);柑橘类的挥发性油状物(日本特开2004-35424号)等。其中,优选来自魁蒿、虎耳草、胡萝卜、毛叶香茶菜、褐藻、葡萄籽、苹果、七叶树、印楝等植物的浸膏。
具有AGEs降解效果的植物浸膏可单独使用一种或组合使用两种以上。
化妆材料组合物
本发明的第二种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂和皮肤色泽的改善剂,可将上述说明的有效成分与作为化妆材料成分可接受的公知的主剂或载体一起混合而制成化妆材料组合物。
本发明的各剂,可以是将作为含有上述(a)成分和上述(b)成分的单一组合物进行制剂化而成的制剂,还可以是将上述(a)成分和上述(b)成分作为不同组合物进行制剂化并使这些组合物组合而成的制剂。另外,当使用两种以上的上述(a)成分或使用两种以上的上述(b)成分时,它们也可以相互作为不同组合物。
对化妆材料组合物的形态没有特别限定,例如,可以举出:诸如化妆水、乳液、乳霜、美容液、防晒用化妆材料、面膜(pack)、护手霜、身体乳液(body lotion)、身体乳霜(body cream)之类的基础化妆材料;诸如洗面奶、卸妆用品、沐浴液(body shampoo)之类的清洗用化妆材料;诸如粉底、底妆用品、润唇膏、口红、腮红之类的化妆品化妆材料;沐浴剂(浴用剂)等。
化妆材料组合物中的(a)乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐的含量,只要例如为约0.0001~50重量%即可,优选为约0.001~50重量%,更优选为约0.05~25重量%。
另外,作为含有(a)乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸、植酸和它们的药学上可接受的盐的化妆材料组合物的pH,可以为例如5.5以下,优选为4以下,并且,可以为例如2以上,优选为3以上。当化妆材料组合物含有上述(a)成分和上述(b)成分时,只要该组合物的pH在上述范围即可;当含有上述(a)成分的组合物和含有上述(b)成分的组合物是不同组合物时,只要含有上述(a)成分的组合物的pH在上述范围内即可。
作为化妆材料组合物中的(b)AGEs降解剂的含量,例如,只要设为约0.00001~20重量%即可,优选为约0.0001~10重量%,更优选为约0.001~5重量%。当含有上述(b-i)、(b-ii)和(b-iii)的两种以上时,只要它们的总量在上述范围内即可。
另外,当化妆材料组合物包含(a)乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐和(b)AGEs降解剂时,其比率((a)成分:(b)成分)优选为按重量比计约1∶0.0000002~200000,更优选为约1∶0.000002~10000,进一步优选为约1∶0.00004~100。另外,当将上述(a)成分和上述(b)成分作为不同组合物进行组合时,只要使组合比率((a)成分:(b)成分)在上述范围内即可。
若在上述范围内,则以化妆材料的通常用量即能够获得充分的肌肤紧致的改善效果、皮肤色泽的改善效果。
化妆材料组合物的主剂或载体、添加剂如同针对本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂所述的情形。
另外,以进一步增强本发明的效果为目的,即所谓改善、抑制或预防由AGEs在皮肤中的蓄积引起的肌肤整体的衰老(例如诸如皮肤暗黄之类的皮肤色泽改变、肌肤紧致或透明感的降低等)或者延缓肌肤整体衰老的进度(速度)为目的,能够在化妆材料组合物中配合可添加于化妆品中的公知的抗糖化成分。可单独使用公知的抗糖化成分中的一种或组合使用两种以上。
作为公知的抗糖化成分的种类、特别优选的抗糖化成分的种类和用量(含量),如同针对本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂所述的情形。
并且,在不妨碍本发明效果的范围内,能够在化妆材料组合物中配合抗氧化成分、防老化成分、抗炎症成分、美白成分、角质软化成分、细胞活化成分、维生素类、血液循环促进成分、保湿成分、具有DNA的损伤的预防和/或修复作用的成分、紫外线吸收成分、紫外线散射成分、清洗成分、抗菌成分、收敛成分等可添加于化妆品中的其它药效成分。对其它药效成分而言,可单独使用一种或组合使用两种以上。
关于药效成分的种类、特别优选的药效成分的种类和用量(含量),如同针对本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂所述的情形。
成分的优选组合
作为本发明的第二种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂和皮肤色泽的改善剂中的有效成分与其它活性成分的优选组合,可以举出下述组合。
当含有公知的抗糖化成分时,可以举出与余甘子浸膏、荔枝种子浸膏、蔷薇(玫瑰)花瓣浸膏、七叶树浸膏、水飞蓟浸膏、印楝浸膏、水解鞣质、L-精氨酸或其盐、赖氨酸或其盐、肌肽、α硫辛酸、氨基胍或其盐、阿利斯丁(Alistin)或葡糖胺的组合;
当含有抗氧化成分时,可以举出与葡萄籽浸膏、葡萄叶浸膏、高丽参浸膏、聚合草叶浸膏、原花色素、δ-生育酚、α-生育酚、抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯)、橙皮苷、葡糖基橙皮苷或硫组氨酸甲基内盐的组合;
当含有防老化成分时,水解大豆蛋白、维生素A、维生素A醋酸酯、或维生素A棕榈酸酯的组合;
当含有抗炎症成分时,可以举出与聚合草叶浸膏、尿囊素、甘草酸二钾、或甘草次酸十八酯的组合;
当含有美白成分时,可以举出与熊果苷、氢醌、曲酸、抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯)、或氨甲环酸的组合;
当含有细胞活化成分时,可以举出与越橘叶浸膏、维生素A、维生素A醋酸酯或维生素A棕榈酸酯的组合;
当含有维生素类时,可以举出与维生素A类(维生素A、维生素A醋酸酯、维生素A棕榈酸酯)、维生素C类(抗坏血酸、抗坏血酸磷酸酯钠、抗坏血酸磷酸酯镁、抗坏血酸四异棕榈酸酯(抗坏血酸四2-己基癸酸酯))、维生素E类(δ-生育酚、生育酚烟酸酯)、烟酸类(烟酸酰胺)的组合;
当含有具有血液循环促进作用的成分时,可以举出与高丽参浸膏、生育酚烟酸酯、葡糖基橙皮苷、或橙皮苷的组合;
当含有保湿成分时,可以举出与茅草根浸膏、水解胶原蛋白、水解弹性蛋白、MPC聚合物丙三醇、1,3-丁二醇、聚乙二醇、二丙二醇、双甘油、甲基葡萄糖苷聚氧丙烯醚、三甲基甘氨酸(甜菜碱)、羟乙基脲、二甲基二烯丙基氯化铵-丙烯酰胺-丙烯酸共聚物、氢化卵磷脂、透明质酸、透明质酸钠、乙酰基透明质酸、乙酰基透明质酸钠或山梨醇的组合;
当含有具有DNA的损伤的预防和/或修复作用的成分时,可以举出与卤虫浸膏或DNA-Na的组合;
当含有紫外线吸收成分或紫外线散射成分时,可以举出与对甲氧基肉桂酸2-乙基己酯、2-[4-(二乙基氨基)-2-羟基苯甲酰]苯甲酸己酯或2,4,6-三[4-(2-乙基己氧基羰基)苯胺基]-1,3,5-三嗪、氧化锌、氧化钛、氧化铁、以无机粉体(氢氧化铝、水合硅酸、云母或滑石)或硅油包覆这些无机化合物而成的物质的组合;
当含有清洗成分时,可以举出与高级脂肪酸盐(特别是,棕榈酸、月桂酸、肉豆蔻酸、硬脂酸等的高级脂肪酸的盐)、N-酰基氨基酸盐(特别是,N-月桂酰天冬氨酸钠、氢氧化钾/N-椰子油脂肪酸酰基谷氨酸钾、椰子油脂肪酸酰基甘氨酸钠、肉豆蔻酰谷氨酸)、脂肪酸烷醇酰胺(特别是,椰子油脂肪酸二乙醇酰胺、椰子油脂肪酸单乙醇酰胺)、氧化胺(特别是,椰子油烷基二甲基氧化胺、月桂醇二甲基氧化胺)、咪唑啉甜菜碱(特别是,2-烷基-N-羧甲基-N-羟乙基咪唑啉甜菜碱、N-椰子油脂肪酸酰基-N-羧甲氧基乙基-N-羧甲基乙二胺二钠)的组合;
当含有抗菌成分时,可以举出与苯扎氯铵、葡糖酸及其衍生物、苄索氯铵或异丙基甲酚的组合;
当含有收敛成分时,可以举出与明矾、羟基氯化铝、氯化铝、尿囊素铝盐、明矾或鞣酸的组合。
其中,优选组合公知的抗糖化成分、抗氧化成分、防老化成分、抗炎症成分、细胞活化成分、维生素类和保湿成分。其中,更优选组合公知的抗糖化成分、防老化成分和抗氧化成分。
使用方法
化妆材料组合物,可以按照化妆材料的通常使用方法、使用次数进行涂敷。另外,下述任一种使用方式均优选:(1)使用含有上述(a)成分和上述(b)成分的组合物;(2)并用含有上述(a)成分的组合物和含有上述(b)成分的组合物。
对于本发明的第二种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂和皮肤色泽的改善剂的使用对象,并没有特别限定,但优选对象是:高龄者、被确认由AGEs的生成和蓄积所引起的肌肤整体衰老的人、以AGEs的生成和蓄积为起因而存在肌肤整体衰老趋势的人等。
即,本发明也包括下述方法:将含有上述(a)成分和上述(b)成分的组合物,以有效预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老(例如皮肤紧致性降低或皮肤色泽改变)的量,涂敷于人的皮肤的预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老的方法。
其它
含有上述(a)成分和上述(b)成分的组合物,是用于预防、抑制或改善由晚期糖基化终末产物的蓄积所引起的肌肤衰老(例如皮肤紧致性降低或皮肤色泽改变)的组合物。并且,可应用于制造由晚期糖基化终末产物的蓄积所引起的肌肤衰老(例如皮肤紧致性降低或皮肤色泽改变)的预防、抑制或改善剂。
实施例
下面,通过列举实施例详细说明本发明,但本发明并不局限于这些实施例。
下述实施例1-1~1-4是本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂的实施例。
实施例1-1(AGEs降解性能的测定)
(1)被检试样(植物油·脂肪酸)
月见草油,购自ORYZA油化株式会社和日清奥利友集团株式会社。巴西油桃木果油,购自Croda日本株式会社。γ-亚麻酸、α-亚麻酸,购自CaymanChemical Co.。亚油酸、油酸,购自和光纯药工业株式会社。二十二碳六烯酸(DHA),购自ChromaDex,Inc.。月见草浸膏,购自ORYZA油化株式会社。
(2)测定方法
已知有通过切断AGEs中存在的α-二酮结构的酮间C-C键来分解AGEs。参考日本特开2007-161662号公报所述的方法,通过测定具有α-二酮结构的1-苯基-1,2-丙二酮(下面简称PPD)的酮间C-C键的可切断性能,测定了AGEs降解性能。
将1ml的溶解了PPD的乙醇溶液与1ml的使植物油或脂肪酸试样以成为后述表2所列浓度的方式溶解了的PBS混合,并且以最终浓度成为22mM的PPD的方式来制备反应液。使该反应液在37℃反应15小时。在反应后,采用HPLC定量反应液中作为PPD降解物的苯甲酸的量。
HPLC的分析条件如下所述。
检测器:紫外吸光光度计(测定波长:260nm)
色谱柱:Inertsil ODS-3(4.6×250mm)
柱温:30℃附近的一定温度
流量:1.20mL/min
流动层:流动相A 用水稀释的三氟乙酸(1→1000)溶液
流动相B 用乙腈混合液稀释的三氟乙酸(1→1000)溶液
梯度程序如下表1-1所示。
[表1-1]
时间(分钟) | 流量(mL/min) | 流动相A(%) | 流动相B(%) |
0.00 | 1.200 | 60.0 | 40.0 |
15.00 | 1.200 | 60.0 | 40.0 |
15.01 | 1.200 | 20.0 | 80.0 |
25.00 | 1.200 | 20.0 | 80.0 |
25.01 | 1.200 | 60.0 | 40.0 |
35.00 | 1.200 | 60.0 | 40.0 |
(3)结果
PPD切断率(AGEs降解率),设定为与被检材料实际发生反应后生成的苯甲酸的量相对于理论上从PPD生成的苯甲酸的总量的比率(百分率)。结果示于下列表1-2中。
[表1-2]
根据表1-2可知,碳原子数为18和20的不饱和脂肪酸和月见草油,显示出非常强的AGEs降解性能。另外,碳原子数为18的不饱和脂肪酸所含的双键越多AGEs降解性能就越高。另一方面,用含水乙醇提取月见草种子得到的月见草浸膏的AGEs降解活性非常弱。
实施例1-2(对肤色产生的影响的研究)
月见草油是采用购自日清奥利友集团株式会社(The Nisshin OilliOGroup,Ltd.)的月见草油。
在20~40几岁成人(四人一组)的前臂部的4个部位划分出2cm×2cm的区域来作为试验部位。按每天两次(早晚)以0.05ml/区域的方式,对4个部位的试验部位涂敷月见草油。将各个被试验者中未施以任何涂敷的前臂部位作为对照。在涂敷开始前和涂敷28天后,采用分光比色计(CM-2002,美能达株式会社(Minolta Co.,Ltd.)制造)测定肤色(b*值)。b*值是色度指标,值越大则表示黄色越强而值越小则表示青色越强。
在28天期间涂敷被检试样所获得的b*值变化量,示于下列表1-3和图1-1中。表1-3和图1-1中的数值,是来自4位被试验者的4个部位测定值(合计16个测定值)的b*值变化量的平均值。
[表1-3]
0天 | 28天 | b*值的变化量 | |
月见草油 | 19.40 | 19.22 | 0.18 |
对照 | 19.05 | 19.05 | 0 |
根据表1-3和图1-1可知,通过涂敷月见草油,明显减小了b*值,降低了皮肤的黄色。
实施例1-3(对皮肤弹性产生的影响的研究)
与实施例1-1同样地进行操作,在被试验者的前臂部涂敷被检试样。在涂敷28天后,采用皮肤弹性测量仪(Integral Corporation制造,CutometerSEM575),以300mbar压力对皮肤的涂敷部吸引2秒之后释放2秒,测定皮肤的高度变化,由此评价皮肤的弹性。
将通过释放而引起的高度的恢复部分(Ua)相对于最大吸引时的皮肤高度(Uf)的比(Ua/Uf),作为表示皮肤弹性的指标。另外,将释放0.1秒后的高度的恢复部分(Ur)相对于吸引0.1秒后的皮肤高度(Ue)的比(Ur/Ue),作为表示在吸引和释放下皮肤状态的易恢复程度的指标。Uf、Ua、Ue、Ur的含义图示于图1-2中。
涂敷28天后的各组的平均值示于图1-3中。根据图1-3可知,皮肤的弹性(Ua/Uf)和皮肤状态的易恢复程度(Ur/Ue)均高于对照。
实施例1-4(对皮肤水分量产生的影响的研究)
与实施例1-2同样地进行操作,在被试验者的前臂部涂敷月见草油。在涂敷开始前和涂敷14天后,采用阻抗计(Skicon-200,IBS社制造)测定涂敷部分的皮肤的水分量。
结果如图1-4所示。由此可知:通过涂敷月见草油,皮肤的水分量增大(保湿)。
下述实施例2-1~2-3是本发明的第二种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂、皮肤色泽的改善剂的实施例。
被检试样
采用通常的方法制备出下列表2-1所示组成的、含有乳酸和乳酸钠的化妆水。
[表2-1]
成分 | 浓度(w/w%) |
乳酸 | 2.6 |
乳酸钠 | 2.4 |
二丙二醇 | 10 |
三乙醇胺 | 0.5 |
纯化水 | 余量 |
乳酸和乳酸钠,购自Purac日本株式会社(Purac Japan K.K.)。另外,月见草油,购自日清奥利友集团株式会社。
在下述实施例中,设置了只涂敷上述化妆水的组、只涂敷月见草油的组和涂敷上述化妆水后涂敷月见草油的组。
实施例2-1(对肤色产生的影响的研究)
在20~40几岁成人(四人一组)的前臂部的4个部位划分出2cm×2cm的区域来作为试验部位。按每天两次(早晚)并分别以0.05ml化妆水/区域、以0.05ml月见草油/区域的方式,对4个部位的试验部位涂敷被检试样。将各被试验者中未施以任何涂敷的前臂部位作为对照。在涂敷开始前和涂敷28天后,采用分光比色计(CM-2002,美能达株式会社制造)测定肤色(b*值)。b*值是色度指标,值越大则表示黄色越强而值越小则表示青色越强。
在28天期间涂敷被检试样所获得的b*值变化量,示于下列表2-2和图2-1中。表2-2和图2-1中的数值,是来自4位被试验者的4个部位测定值(合计16个测定值)的b*值变化量的平均值。
[表2-2]
0天 | 28天 | b*值的变化量 | |
月见草油+乳酸(钠) | 19.53 | 19.12 | 0.41 |
月见草油 | 19.40 | 19.22 | 0.18 |
乳酸(钠) | 19.17 | 19.16 | 0.01 |
对照 | 19.05 | 19.05 | 0 |
根据表2-2和图2-1可知,通过并用乳酸(钠)和月见草油,b*值大幅减少,皮肤的黄色降低。并且,还确认:与分别单独使用月见草油和乳酸(钠)时相比,当并用乳酸(钠)和月见草油时,根据b*的减少幅度具有协同效应。
实施例2-2(对皮肤弹性产生的影响的研究)
与实施例2-1同样地进行操作,在被试验者的前臂部涂敷被检试样。在涂敷开始前和涂敷14天后,采用皮肤弹性测量仪(Integral Corporation制造,Cutometer SEM575),以300mbar压力对皮肤的涂敷部吸引2秒之后释放2秒,测定皮肤的高度变化,由此评价皮肤的弹性。
将通过释放而引起的高度的恢复部分(Ua)相对于最大吸引时的皮肤高度(Uf)的比(Ua/Uf),作为表示皮肤弹性的指标。另外,将释放0.1秒后的高度的恢复部分(Ur)相对于吸引0.1秒后的皮肤高度(Ue)的比(Ur/Ue),作为表示在吸引和释放下皮肤状态的易恢复程度的指标。Uf、Ua、Ue、Ur的含义图示于图2-2中。另外,在涂敷14天后各组的平均值示于下列表2-3和图2-3中。
[表2-3]
Ua/Uf | Ur/Ue | |
月见草油+乳酸(钠) | 0.878 | 0.903 |
月见草油 | 0.836 | 0.813 |
乳酸(钠) | 0.851 | 0.821 |
对照 | 0.831 | 0.836 |
根据表2-3和图2-3可知,通过并用月见草油和乳酸(钠),皮肤弹性(Ua/Uf)和皮肤状态的易恢复程度(Ur/Ue)均高于对照。并且还确认:与分别单独使用月见草油和乳酸(钠)时相比,具有协同效应。
实施例2-3(对皮肤水分量产生的影响的研究)
与实施例2-1同样地进行操作,在被试验者的前臂部涂敷被检试样。在涂敷开始前和涂敷14天后,采用阻抗计(Skicon-200,IBS社制造)测定涂敷部分的皮肤的水分量。
结果如图2-4所示。由此可知:通过涂敷含有乳酸和月见草油的化妆水,皮肤的水分量比对照增大。
配方例
下述配方例1-1~1-21为本发明的AGEs降解剂和本发明的第一种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂的配方例。
(1)化妆材料组合物
下述化妆品组合物的配方例中的数值的单位是“重量%”。
配方例1-1透明洗液
配方例1-2透明洗液
配方例1-3乳化洗液
配方例1-4乳化洗液
配方例1-5乳化洗液
配方例1-6乳液
配方例1-7乳液
配方例1-8乳霜
配方例1-9乳霜
配方例1-10乳霜
配方例1-11乳霜
配方例1-12清洁霜(cleansing cream)
配方例1-13清洁霜(cleansing cream)
配方例1-14洗面奶
配方例1-15洗面奶
(2)食品组合物
下述食品组合物的配方例中的数值的单位是“重量份”。
配方例1-16软胶囊
胶囊内容物
胶囊皮膜
配方例1-17软胶囊
胶囊内容物
胶囊皮膜
明胶 100
丙三醇 30
染料 4
配方例1-18软胶囊
胶囊内容物
胶囊皮膜
支链淀粉 100
丙三醇 40
染料 2
配方例1-19软胶囊
胶囊内容物
胶囊皮膜
配方例1-20软胶囊
胶囊内容物
胶囊皮膜
明胶 100
丙三醇 40
染料 3
配方例1-21软胶囊
胶囊内容物
胶囊皮膜
下述配方例2-1~2-6为本发明的第二种由AGEs的蓄积引起的肌肤衰老的预防、抑制或改善剂、肌肤紧致的改善剂、皮肤色泽的改善剂的配方例。
下述化妆品组合物的配方例中的数值的单位是“重量%”。
配方例2-1乳液
配方例2-2透明洗液
配方例2-3乳液
配方例2-4乳霜
配方例2-5
含有(b)成分的乳液
并用上述透明洗液和乳液。
配方例2-6
含有(a)成分的美容液
含有(b)成分的乳霜
并用上述美容液和乳霜。
工业实用性
不饱和脂肪酸及其药学上可接受的衍生物以及含有它们的植物油,具有AGEs降解活性,因此,通过将其添加于化妆材料组合物、食品组合物中使用,能够改善、抑制和/或预防由AGEs在皮肤中的蓄积引起的肌肤整体的衰老(例如诸如皮肤暗黄之类的皮肤色泽改变、肌肤紧致或透明感的降低)或者延缓肌肤整体的衰老速度。并且,能够预防或改善由AGEs所引发的各种疾病(白内障、动脉硬化、肾功能障碍、视网膜症、神经障碍之类的糖尿病并发症、动脉硬化症、恶性肿瘤、骨病、阿尔茨海默病、帕金森氏病等)。
并且,(a)乳酸和/或其盐与(b)AGEs降解剂的混合物,可提高皮肤弹性、使变形皮肤恢复良好、改善诸如皮肤暗黄之类的皮肤色泽、提升皮肤水分量。从而,含有上述混合物的组合物,可适于作为化妆材料组合物来使用。
Claims (16)
1.一种选自于由碳原子数16~24的不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种在制备晚期糖基化终末产物降解剂中的用途。
2.如权利要求1所述的用途,其中,不饱和脂肪酸是碳原子数为16~20的不饱和脂肪酸。
3.如权利要求2所述的用途,其中,不饱和脂肪酸是选自于由二烯不饱和脂肪酸和三烯不饱和脂肪酸所构成的组中的至少一种的不饱和脂肪酸。
4.一种植物油在制备晚期糖基化终末产物降解剂中的用途,所述植物油是选自于月见草油、白芒花籽油、鳄梨油、橄榄油、桃仁油、石栗子油、葡萄籽油、红花油、杏仁油、玉米油、葵花籽油、榛果油、昆士兰果油、玫瑰果油、大豆油、芝麻油、小麦胚芽油、菜籽油和棉籽油所构成的组中的至少一种的植物油。
5.如权利要求4所述的用途,其中,植物油是选自于由月见草油、和白芒花籽油所构成的组中的至少一种的植物油。
6.一种选自于由碳原子数16~24的不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种在制备由晚期糖基化终末产物的蓄积所引起的皮肤色泽改变的改善剂中的用途。
7.如权利要求6所述的用途,其中,不饱和脂肪酸是碳原子数为16~20的不饱和脂肪酸。
8.如权利要求7所述的用途,其中,不饱和脂肪酸是选自于由二烯不饱和脂肪酸和三烯不饱和脂肪酸所构成的组中的至少一种的不饱和脂肪酸。
9.一种植物油在制备由晚期糖基化终末产物的蓄积所引起的皮肤色泽改变的改善剂中的用途,所述植物油是选自于月见草油、白芒花籽油、鳄梨油、橄榄油、桃仁油、石栗子油、葡萄籽油、红花油、杏仁油、玉米油、葵花籽油、榛果油、昆士兰果油、玫瑰果油、大豆油、芝麻油、小麦胚芽油、菜籽油和棉籽油所构成的组中的至少一种的植物油。
10.如权利要求9所述的用途,其中,植物油是选自于由月见草油、和白芒花籽油所构成的组中的至少一种的植物油。
11.一种选自于由碳原子数16~24的不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种、以及选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种的组合在制备由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂中的用途。
12.一种选自于由月见草油、白芒花籽油、鳄梨油、橄榄油、桃仁油、石栗子油、葡萄籽油、红花油、杏仁油、玉米油、葵花籽油、榛果油、昆士兰果油、玫瑰果油、大豆油、芝麻油、小麦胚芽油、菜籽油和棉籽油所构成的组中的至少一种的植物油、以及选自于由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种的组合在制备由晚期糖基化终末产物的蓄积所引起的肌肤衰老的预防、抑制或改善剂中的用途。
13.如权利要求1所述的用途,其中,选自于由碳原子数16~24的不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种与由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种相组合而使用。
14.如权利要求4所述的用途,其中,选自于月见草油、白芒花籽油、鳄梨油、橄榄油、桃仁油、石栗子油、葡萄籽油、红花油、杏仁油、玉米油、葵花籽油、榛果油、昆士兰果油、玫瑰果油、大豆油、芝麻油、小麦胚芽油、菜籽油和棉籽油所构成的组中的至少一种的植物油与由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种相组合而使用。
15.如权利要求6所述的用途,其中,选自于由碳原子数16~24的不饱和脂肪酸及其药学上可接受的甘油酯所构成的组中的至少一种与由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种相组合而使用。
16.如权利要求9所述的用途,其中,选自于月见草油、白芒花籽油、鳄梨油、橄榄油、桃仁油、石栗子油、葡萄籽油、红花油、杏仁油、玉米油、葵花籽油、榛果油、昆士兰果油、玫瑰果油、大豆油、芝麻油、小麦胚芽油、菜籽油和棉籽油所构成的组中的至少一种的植物油与由乳酸、乙醇酸、水杨酸、苹果酸、柠檬酸和植酸以及它们的药学上可接受的盐所构成的组中的至少一种相组合而使用。
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JP5938193B2 (ja) * | 2011-11-10 | 2016-06-22 | ポーラ化成工業株式会社 | 抗老化剤のスクリ−ニング方法 |
JP6347611B2 (ja) * | 2013-07-19 | 2018-06-27 | 白井松新薬株式会社 | メイラード反応抑制機能または抗酸化機能を有する機能剤 |
CN103961276A (zh) * | 2014-01-08 | 2014-08-06 | 片仔癀(上海)生物科技研发有限公司 | 抗糖化化妆品组合物及含其的抗糖化化妆品 |
JP2016006036A (ja) * | 2014-05-26 | 2016-01-14 | アークレイ株式会社 | AGEs分解剤およびその用途 |
KR102554508B1 (ko) * | 2014-08-20 | 2023-07-13 | 가부시기가이샤하야시바라 | 경구 미용제 |
KR102716629B1 (ko) * | 2015-09-02 | 2024-10-15 | 나가세비타 가부시키가이샤 | 황변 현상 저감용 피부외용제 |
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