CN102686224B - 减轻皮肤粗糙的口服组合物 - Google Patents
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- CN102686224B CN102686224B CN201080043067.3A CN201080043067A CN102686224B CN 102686224 B CN102686224 B CN 102686224B CN 201080043067 A CN201080043067 A CN 201080043067A CN 102686224 B CN102686224 B CN 102686224B
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Abstract
本发明开发一种作用于皮肤屏障功能、能够减轻和/或预防皮肤粗糙、稳定且安全的口服组合物。本发明提供一种用于减轻皮肤粗糙的口服组合物,其含有选自由D-谷氨酸和其衍生物和/或盐所组成组中的1种或2种以上的化合物。本发明提供一种用于预防皮肤粗糙的口服组合物,其含有选自由D-谷氨酸和其衍生物和/或盐所组成组中的1种或2种以上的化合物。本发明提供一种药品组合物和/或食品组合物,其含有本发明的用于减轻皮肤粗糙的口服组合物或用于预防皮肤粗糙的口服组合物。
Description
技术领域
本发明涉及含有选自由D-谷氨酸和其衍生物和/或盐所组成组中的1种或2种以上的化合物的用于减轻皮肤粗糙的口服组合物和用于预防皮肤粗糙的口服组合物,还涉及包括投与所述化合物的步骤的减轻皮肤粗糙的方法和预防皮肤粗糙的方法。
背景技术
引起了皮肤粗糙的皮肤的表皮水分丧失度(TEWL)增加,因此认为皮肤屏障功能的降低为皮肤粗糙的原因之一。
现有技术文献
非专利文献
非专利文献1:标准皮肤科学第7版(医学书院)
发明内容
发明要解决的问题
以往用于减轻和/或预防皮肤粗糙的组合物外用于皮肤,具有助于保湿皮肤的作用,但并非通过口服投与而抑制皮肤屏障功能的降低的组合物。
因此,需要开发一种作用于皮肤屏障功能、能够减轻和/或预防皮肤粗糙、稳定且安全的口服组合物。
用于解决问题的方案
本发明提供一种用于减轻皮肤粗糙的口服组合物,其含有选自由D-谷氨酸和其衍生物和/或盐所组成组中的1种或2种以上的化合物。
本发明提供一种用于预防皮肤粗糙的口服组合物,其含有选自由D-谷氨酸和其衍生物和/或盐所组成组中的1种或2种以上的化合物。
本发明提供一种药品组合物,其含有本发明的用于减轻皮肤粗糙的口服组合物或用于预防皮肤粗糙的口服组合物。
本发明提供一种食品组合物,其含有本发明的用于减轻皮肤粗糙的口服组合物或用于预防皮肤粗糙的口服组合物。
本发明提供一种减轻皮肤粗糙的方法,其包括投与用于减轻皮肤粗糙的口服组合物的步骤,所述用于减轻皮肤粗糙的口服组合物含有选自由D-谷氨酸和其衍生物和/或盐所组成组中的1种或2种以上的化合物。
本发明提供一种预防皮肤粗糙的方法,其包括投与用于预防皮肤粗糙的口服组合物的步骤,所述用于预防皮肤粗糙的口服组合物含有选自由D-谷氨酸和其衍生物和/或盐所组成组中的1种或2种以上的化合物。
在本发明的减轻皮肤粗糙的方法和/或预防皮肤粗糙的方法中,所述用于减轻皮肤粗糙的口服组合物和/或用于预防皮肤粗糙的口服组合物有时为药品组合物。
在本发明的减轻皮肤粗糙的方法和/或预防皮肤粗糙的方法中,所述用于减轻皮肤粗糙的口服组合物和/或用于预防皮肤粗糙的口服组合物有时为食品组合物。
本说明书中,“皮肤粗糙”是皮肤问题的一种,是指由皮肤表面的干燥、皮沟·皮丘所规定的纹理紊乱的状态。引起了皮肤粗糙的皮肤表面由于纹理紊乱而产生鳞屑,变得光学上不规则,可通过目视确认其紊乱。
本说明书中,“皮肤屏障功能”是使皮肤保持正常状态的功能,是指用于防止异物侵入体内、或防止水分从体内丧失的功能。
本说明书中,D-谷氨酸的“盐”是指在不损害D-谷氨酸的改善皮肤粗糙的效果的条件下,包括金属盐、胺盐等在内的任意的盐。所述金属盐可以包括碱金属盐、碱土金属盐等。所述胺盐可以包括三乙胺盐、苄胺盐等。
本说明书中,D-谷氨酸的“衍生物”是指在不损害D-谷氨酸的改善皮肤粗糙的效果的条件下,D-谷氨酸分子在氨基、或羧基、或侧链上与任意的原子团共价结合而成的化合物。所述任意原子团包括像N-苯基乙酰基、4,4’-二甲氧基三苯甲基(DMT)等这样的保护基,像蛋白质、肽、糖、脂质、核酸等这样的生物高分子,像聚苯乙烯、聚乙烯、聚乙烯基化合物、聚酯等这样的合成高分子,像酯基等这样的官能团,但不限定于这些。所述酯基可以包括例如甲酯、乙酯等脂肪族酯,或芳香族酯。
氨基酸中存在作为光学异构体的L-体和D-体,天然的蛋白质为L-氨基酸以肽键键合而成的蛋白质,除了细菌的细胞壁等例外情况外仅L-氨基酸被利用,因此认为以人类为首的哺乳类中仅存在L-氨基酸并且仅利用L-氨基酸。按照(木野内忠稔等,蛋白质核酸酶,50:453-460(2005),Lehninger的新生物化学[上]第2版pp132-147(1993)广川书店,哈珀·生物化学原文书22版pp21-30(1991)丸善)。因此,一直以来,学术上也好产业上也好,作为氨基酸主要仅使用L-氨基酸。
作为例外地使用D-氨基酸的例子,有用作使细菌中产生抗生物质的原料的情况;以及为了节省从化学合成氨基酸时等量获得的L-氨基酸与D-氨基酸混合物中仅分离提取L-氨基酸的成本,而直接以DL-氨基酸混合物的形式使用D-氨基酸的食品添加物的例子。然而,从来没有在产业中仅使用D-氨基酸作为具有生理活性的物质的实例。
D-丝氨酸、D-天冬氨酸由于D-体的比例高,因此研究进展较快。D-丝氨酸局部存在于大脑、海马中,已清楚其为脑内的NMDA受体的调控因子。确认到D-天冬氨酸局部存在于精巢、松果体中,显示参与控制激素的分泌(日本特开2005-3558号公报)。但是D-谷氨酸的减轻皮肤粗糙的效果尚不明确。
以下实施例所示的D-谷氨酸的减轻皮肤粗糙的效果至今未曾被知晓。因此,含有D-谷氨酸的本发明的口服组合物为新型发明。
近年来,有报道显示,使ddY小鼠两周内自由摄入10mM的D-氨基酸水溶液,然后测定各器官中的D-氨基酸浓度,结果:松果体中,D-氨基酸浓度相对于1个作为分泌器官的松果体为3-1000pmol;脑组织中,D氨基酸浓度相对于1克湿重量为2-500nmol(Morikawa,A.等,AminoAcids,32:13-20(2007))。基于此,算出以下说明的本发明的组合物中所含有的D-谷氨酸的一日摄入量的下限。
如以下的实施例所示的那样,本发明的D-谷氨酸以1~10mM的水溶液浓度的口服组合物对小鼠具有减轻皮肤粗糙的效果。因此,本发明的用于改善皮肤粗糙的口服组合物和食品组合物中所含的D-谷氨酸的量只要满足D-谷氨酸可送达至生物体皮肤组织的条件,则可以为任意含量。本发明的组合物为口服剂时,D-谷氨酸的含量为0.00001重量%~100重量%的范围即可。本发明的组合物为口服剂时,D-谷氨酸的含量优选为0.00002重量%~80重量%,最优选为0.0002重量%~60重量%。另外,本发明的组合物中所含的D-谷氨酸的一日摄入量的下限只要每1kg体重为0.01ng即可,优选为0.1ng,更优选为1ng。
本发明的药品组合物除了含有D-谷氨酸、D-谷氨酸的盐和/或能够在生物体内通过药物代谢酶等释放D-谷氨酸的衍生物之外,在不损害D-谷氨酸的减轻皮肤粗糙的效果的条件下,还可含有1种或2种以上药学上允许的添加物。所述添加物可以包括稀释剂及膨胀剂、粘合剂及粘接剂、润滑剂、助流剂、增塑剂、崩解剂、载体溶剂、缓冲剂、着色材料、香料、甜味剂、防腐剂及稳定化剂、吸附剂、本领域技术人员所知的其他药品添加剂,但不限于这些。
本发明的食品组合物除了含有D-谷氨酸、D-谷氨酸的盐和/或能够在生物体内通过药物代谢酶等释放D-谷氨酸的衍生物之外,在不损害D-谷氨酸的改善皮肤粗糙的效果的条件下,还可以含有调料、着色材料、保存材料等作为食品所允许的成分。
本发明的食品组合物只要为例如糖果、饼干、味噌、法式色拉调味汁、蛋黄酱、法式面包、酱油、酸奶、撒在饭上的粉状食品、调料·纳豆的佐料汁、纳豆、醪黑醋等以往食品组合物中使用的物质则可以为任意,但不限定于所述例示。
附图说明
图1表示口服投与11天D-谷氨酸对SDS处理小鼠的皮肤屏障功能的效果的坐标图。
图2表示口服投与28天D-谷氨酸对SDS处理小鼠的皮肤屏障功能的效果的坐标图。
具体实施方式
以下说明的本发明的实施例仅以例示为目的,不限定本发明的保护范围。本发明的保护范围仅受权利要求书的记载范围所限定。
本说明书中言及的全部文献以引用其整体的方式引入本说明书中。
以下的实施例中说明的实验依据美国国立卫生研究所(National Institutes of Health(NIH))的准则并得到资生堂研究中心的伦理委员会认可后实施。
实施例1
通过短期投与D-谷氨酸获得的皮肤粗糙减轻效果
方法
实验动物
对于小鼠,向试验供给HR-1无毛小鼠(雄性,7周龄,星野试验动物饲育所股份有限公司)。各实验条件各使用了7~8只小鼠。
氨基酸的投与
为了调查氨基酸对皮肤粗糙的效果,给水投与了1mM或10mM的D-谷氨酸。作为阴性对照,使用了不含D-谷氨酸的饮用水。
皮肤粗糙实验
在开始投与D-谷氨酸的第10天及第11天,将浸渍了10%SDS溶液的无纺布接触到麻醉下的小鼠的背部的单侧5分钟(以下,称为”SDS处理”。)。对于SDS处理次数,直至引起皮肤粗糙为止在2~5次的范围内实施。本实施例中,将开始投与D-谷氨酸的第10天及第11天的SDS处理分别称为第1次及第2次的SDS处理。另外,在以下的表皮水分丧失度的测定中,将实施了SDS处理的部位称为”SDS处理部位”,未实施SDS处理的相反侧部位称为”SDS未处理部位”。
表皮水分丧失度的定量
为了定量皮肤粗糙状态,在正要进行第1次的SDS处理之前(SDS处理前)和第1次及第2次的SDS处理的2小时后,使用水分丧失度测定装置(Tewameter TM-300,Courage+Khazaka公司制造),按照制造者的说明书确定表皮水分丧失度。此处,将SDS处理部位的表皮水分丧失度减去SDS未处理部位的表皮水分丧失度的测定值作为”TEWLΔ值”。
结果
图1表示调查了口服投与D-谷氨酸11天对小鼠的SDS处理的效果的实验结果。各实验条件的误差柱表示在同一条件下反复操作7~8次的实验结果的测定值的标准偏差。另外,星号(*)表示在Dunnett检验中p不足5%。
进行第1次的SDS处理之前(SDS处理前)的TEWLΔ值在阴性对照组中为0.7g/m2/h、在1mM的D-谷氨酸投与组中为0.4g/m2/h、在10mM的D-谷氨酸投与组中为0.1g/m2/h。第1次的SD S处理的2小时后(第1次处理)的TEWLΔ值在阴性对照组中为2.2g/m2/h、在1mM的D-谷氨酸投与组中为1.5g/m2/h、在10mM的D-谷氨酸投与组中为1.2g/m2/h。第2次的SDS处理的2小时后(第2次SD S处理)的TEWLΔ值在阴性对照组中为7.0g/m2/h、在1mM的D-谷氨酸投与组中为3.2g/m2/h、在10mM的D-谷氨酸投与组中为3.8g/m2/h。关于第2次的SDS处理的2小时后的TEWLΔ值,确认1mM及10mM的D-谷氨酸投与组相对于阴性对照组有显著差异。从以上的结果表明,重复SDS处理时,小鼠发生皮肤粗糙,通过事前投与D-谷氨酸可以预防和/或减轻皮肤粗糙。
实施例2
通过长期投与D-谷氨酸获得的皮肤粗糙减轻效果
方法
氨基酸的投与、皮肤粗糙实验及表皮水分丧失度的定量使用所述HR-1无毛小鼠,与实施例1同样进行。氨基酸使用10mM的L-或D-谷氨酸,或者L-或D-谷氨酰胺。使用不含有氨基酸的饮用水作为阴性对照。SDS处理在开始投与所述氨基酸的第27天及第28天进行。本实施例中,将开始投与所述氨基酸的第27天及第28天的SDS处理分别称为第1次的SDS处理及第2次的SDS处理。表皮水分丧失度的定量在第2次的SDS处理的2小时后进行。
结果
图2表示调查了口服投与D-谷氨酸28天对小鼠的SDS处理的效果的实验结果。各实验条件的误差柱表示在同一条件下反复操作5次的实验结果的测定值的标准偏差。另外,星号(*)表示在Dunnett检验中p不足5%。
第2次的SDS处理的2小时后(第2次SDS处理)的TEWLΔ值在阴性对照组中为2.4g/m2/h、在D-谷氨酸投与组中为-0.9g/m2/h、在L-谷氨酸投与组中为1.1g/m2/h、在D-谷氨酰胺投与组中为3.3g/m2/h、在L-谷氨酰胺投与组中为2.3g/m2/h。关于第2次的SD S处理的2小时后的TEWLΔ值,确认10mM的D-谷氨酸投与组相对于阴性对照组有显著差异,另一方面,没有确认到L-谷氨酸、L-谷氨酰胺及D-谷氨酰胺的投与组相对于阴性对照组有显著差异。从以上的结果表明,在SDS处理前长期投与D-谷氨酸时,可以显著预防和/或减轻皮肤粗糙。因此表明,D-谷氨酸的持续摄入对维持和/或促进皮肤的屏障功能是有效的。
以下示出基于本发明的含有D-谷氨酸的片剂、软胶囊、颗粒、饮料、糖果、饼干、味噌、法式色拉调味汁、蛋黄酱、法式面包、酱油、酸奶、撒在饭上的粉状食品、调料·纳豆的佐料汁、纳豆及醪黑醋的配合例。这些配合例以例示为目的而被列举,并不意图限定本发明的保护范围。
配合例1(片剂)
配合例2(片剂)
配合例3(软胶囊)
配合例4(软胶囊)
配合例5(颗粒)
配合例6(饮料)
配合例7(糖果)
配合例8(饼干)
配合例8(饼干)的制造方法
边搅拌黄油边缓慢地添加细砂糖,添加鸡蛋、D-谷氨酸钠及香料并搅拌。充分混合后,加入摇匀的低筋面粉,在低速度下搅拌,以块状在冰箱中存放。之后,进行成型,在170°C下烘焙15分钟制成饼干。
配合例9(味噌)
配合例9(味噌)的制造方法
将米曲和盐充分混合。将洗净的大豆在3倍量的水中浸泡一夜,然后去除水,边添加新的水边煮熟,过筛。收集煮出来的汤汁(原汁),溶解D-谷氨酸使其浓度为10%w/v。立即将煮好的豆捣碎,加入混有盐的米曲,边加入所述溶解有D-谷氨酸的原汁边均匀混合至如粘土那样的硬度。将揉成的团状物以无间隙的状态紧密地填塞到桶中直至各个角落也填满,使表面平整后,用包裹物覆盖并密封。3个月后更换容器,使表面平整后,用包裹物覆盖。另外,也可以代替向原汁中加入D-谷氨酸而使用产生大量D-谷氨酸的米曲。为了得到所述米曲,可通过利用日本特开2008-185558中记载的方法对D-谷氨酸进行定量从而挑选。另外,也可以向市售的味噌中添加D-谷氨酸或其盐。
配合例10(法式色拉调味汁)
配合例10(法式色拉调味汁)的制造方法
向醋中加入氯化钠及D-谷氨酸后,充分搅拌并溶解。加入色拉油,充分搅拌并添加胡椒。
配合例11(蛋黄酱)
配合例11(蛋黄酱)的制造方法
向鸡蛋黄(室温)中加入醋、氯化钠、D-谷氨酸及胡椒,用打蛋器充分搅拌。一边一点点加入色拉油一边继续搅拌,制成乳化液。最后加入砂糖进行搅拌。
配合例12(法式面包)
配合例12(法式面包)的制造方法
向温水中加入1g砂糖及干酵母进行前发酵。将高筋面粉、低筋面粉、氯化钠和5g砂糖以及D-谷氨酸钠放入钵中,向其中加入前发酵过的酵母。充分揉和后,形成球状,在30°C下进行主发酵中的第一次发酵。再次揉和面团,稍后,整形至适当的形状,使用电子发酵机进行后发酵。于面团表面划切痕后,在220°C的烤箱中烘焙30分钟。
配合例13(酱油)
配合例13(酱油)的制造方法
向市售的酱油中添加D-谷氨酸钠并充分搅拌。此外,也可以代替添加D-谷氨酸或其盐而使用产生大量D-谷氨酸的米曲来酿造酱油。为了得到所述米曲,可通过利用日本特开2008-185558中记载的方法对D-谷氨酸进行定量从而挑选。
配合例14(酸奶)
配合例14(酸奶)的制造方法
在40°C~45°C下进行发酵。可以使用其他市售的种菌,也可以向市售的酸奶中加入D-谷氨酸钠。另外,也可以代替添加D-谷氨酸或其盐而使用产生大量D-谷氨酸的菌。为了得到所述菌,可通过利用日本特开2008-185558中记载的方法对D-谷氨酸进行定量从而挑选。
配合例15(撒在饭上的粉状食品)
配合例16(调料·纳豆的佐料汁)
配合例17(纳豆)
配合例17(纳豆)的制造方法
也可以代替添加D-谷氨酸或其盐而使用产生大量D-谷氨酸的菌来制作纳豆。为了得到所述菌,可通过利用日本特开2008-185558中记载的方法对D-谷氨酸进行定量从而挑选。
配合例18(醪黑醋)
配合例18(醪黑醋)的制造方法
也可以代替添加D-谷氨酸或其盐而使用产生大量D-谷氨酸的菌来制作醋、黑醋、醪。为了得到所述菌,可通过利用日本特开2008-185558中记载的方法对D-谷氨酸进行定量从而挑选。
Claims (4)
1.选自由D-谷氨酸和其盐所组成组中的1种或2种以上的化合物在制备减轻皮肤粗糙的口服组合物中的用途。
2.选自由D-谷氨酸和其盐所组成组中的1种或2种以上的化合物在制备预防皮肤粗糙的口服组合物中的用途。
3.根据权利要求1或2所述的用途,其中,口服组合物为药品组合物。
4.根据权利要求1或2所述的用途,其中,口服组合物为食品组合物。
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---|---|---|---|---|
US5091171B2 (en) * | 1986-12-23 | 1997-07-15 | Tristrata Inc | Amphoteric compositions and polymeric forms of alpha hydroxyacids and their therapeutic use |
JP4643800B2 (ja) * | 2000-06-16 | 2011-03-02 | エム・ディジャパン株式会社 | プロテアーゼ阻害剤 |
AU3946402A (en) * | 2000-11-01 | 2002-05-27 | Sention Inc | Methods and compositions for regulating memory consolidation |
JP3439199B2 (ja) * | 2001-05-07 | 2003-08-25 | 憲司 中村 | 保湿組成物 |
EP1521735A2 (en) * | 2001-05-25 | 2005-04-13 | Ceremedix, Inc | Single amino acid based compounds for counteracting effects of reactive oxygen species and free radicals |
JP4291967B2 (ja) * | 2001-11-08 | 2009-07-08 | 雪印乳業株式会社 | 皮膚コラーゲン産生促進剤 |
JP2005041861A (ja) * | 2003-07-09 | 2005-02-17 | Takeda Chem Ind Ltd | 皮膚角層水分量低下抑制剤 |
JP4838537B2 (ja) * | 2005-05-25 | 2011-12-14 | 株式会社 資生堂 | 不全角化抑制剤、毛穴縮小剤又は肌荒れ防止・改善剤及び皮膚外用組成物 |
KR100628413B1 (ko) * | 2005-12-29 | 2006-09-26 | 주식회사 바이오리더스 | 폴리감마글루탐산―비타민c 복합체를 함유하는 콜라게나제저해제 및 그 용도 |
JP2008285472A (ja) * | 2007-04-16 | 2008-11-27 | Sapporo Breweries Ltd | 細胞外マトリックス分解酵素阻害剤 |
JP5374058B2 (ja) * | 2008-03-12 | 2013-12-25 | 株式会社 資生堂 | グルタミン酸誘導体、不全角化抑制剤、毛穴縮小剤、肌荒れ防止・改善剤及び皮膚外用組成物 |
-
2010
- 2010-09-06 KR KR1020127005294A patent/KR20120080164A/ko active Search and Examination
- 2010-09-06 WO PCT/JP2010/065198 patent/WO2011040185A1/ja active Application Filing
- 2010-09-06 US US13/261,200 patent/US20120165408A1/en not_active Abandoned
- 2010-09-06 EP EP10820305.0A patent/EP2484357A4/en not_active Withdrawn
- 2010-09-06 CN CN201080043067.3A patent/CN102686224B/zh not_active Expired - Fee Related
- 2010-09-06 JP JP2011534160A patent/JP5636370B2/ja active Active
- 2010-09-16 TW TW099131491A patent/TWI461219B/zh not_active IP Right Cessation
Non-Patent Citations (5)
Title |
---|
DOMINIC RAJ,et al..Regulatory responses to an oral D-glutamate load:formation of D-pyrrolidone carboxylic acid in humans.《Am J Physiol Endocrinol Metab》.2001,第280卷E214-220. |
JP特开2001-354582A 2001.12.25 |
JP特开2008-285472A 2008.11.27 |
JP特开2009-215268A 2009.09.24 |
Regulatory responses to an oral D-glutamate load:formation of D-pyrrolidone carboxylic acid in humans;DOMINIC RAJ,et al.;《Am J Physiol Endocrinol Metab》;20011231;第280卷;E214-220 * |
Also Published As
Publication number | Publication date |
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CN102686224A (zh) | 2012-09-19 |
KR20120080164A (ko) | 2012-07-16 |
EP2484357A4 (en) | 2013-11-20 |
US20120165408A1 (en) | 2012-06-28 |
WO2011040185A1 (ja) | 2011-04-07 |
TWI461219B (zh) | 2014-11-21 |
JP5636370B2 (ja) | 2014-12-03 |
TW201117831A (en) | 2011-06-01 |
JPWO2011040185A1 (ja) | 2013-02-28 |
EP2484357A1 (en) | 2012-08-08 |
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