CN102548529B - 胶原生成促进组合物 - Google Patents
胶原生成促进组合物 Download PDFInfo
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- CN102548529B CN102548529B CN201080043687.7A CN201080043687A CN102548529B CN 102548529 B CN102548529 B CN 102548529B CN 201080043687 A CN201080043687 A CN 201080043687A CN 102548529 B CN102548529 B CN 102548529B
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Abstract
开发一种具有胶原生成促进作用的新颖组合物,且无类维生素A类的副作用而且光稳定性强的组合物。本发明提供一种胶原生成促进组合物,其含有由D-天冬氨酸和D-丙氨酸及其衍生物和/或盐组成的组中的1种或2种以上的化合物。所述组合物根据情况为了抑制和/或改善皮肤状态而被使用。所述皮肤状态包括光老化和/或皱纹,但并不限定于这些。所述组合物根据情况被用作皮肤外用剂或食品。所述组合物根据情况为I型胶原生成促进组合物。
Description
技术领域
本发明涉及包括选自由D-天冬氨酸和D-丙氨酸及其衍生物和/或盐组成的组中的1种或2种以上的化合物的胶原生成促进组合物及包括投与所述化合物的步骤的抑制和/或改善皮肤状态的方法。
背景技术
I型胶原为皮肤的主要蛋白质之一,是由2条α1(I)肽链和1条α2(I)肽链组成的3条肽链蛋白质。I型胶原被生成于皮肤的真皮层的成纤维细胞,形成嵌入该成纤维细胞的细胞外基质。不论是通常(intrinsic)老化还是光老化,都伴随着胶原生成的减少及胶原分解酶活性的增加(非专利文献1-3)。在此,已意识到促进胶原生成与抑制和/或改善由于通常老化和光老化导致的皮肤状态之间,例如皱纹形成之间的相关性。实际上,已知作为维生素A的衍生物的类维生素A类在适用于发生了通常老化及光老化的面部及上臂皮肤具有药效(非专利文献4-5)。但是,类维生素A类具有光敏化、作为类维生素A反应而周知的炎症性反应这样的副作用(非专利文献6)。还有,类维生素A类一般光反应性强,为了稳定保存需要遮光,在通常的生活条件下投与皮肤后易被透过到体内的光分解(非专利文献3)。
现有技术文献
非专利文献
非专利文献1:Takeda,K.等,J.Cell.Physiol.,153:450(1992)
非专利文献2:Varani,J.等,Am.J.Pathol.,158:931(2001)
非专利文献3:Varani,J.等,Am.J.Pathol.,168:1861(2006)
非专利文献4:Kligman,A.M.等,J.Am.Acad.Dermatol.,15:836(1986)
非专利文献5:Kligman,A.M.等,J.Am.Acad.Dermatol.,29:25(1993)
非专利文献6:Mukherjee,S.等,Clin.Interv.Aging1:327(2006)
发明内容
发明要解决的问题
在此,需要开发具有胶原生成促进作用的新颖组合物,该组合物无类维生素A类的副作用且光稳定性强。
用于解决问题的方案
本发明提供一种胶原生成促进组合物,其含有选自由D-天冬氨酸和D-丙氨酸及其衍生物和/或盐组成的组中的1种或2种以上的化合物。
本发明的胶原生成促进组合物根据情况为了抑制和/或改善皮肤状态而被使用。
在本发明的胶原生成促进组合物中,所述皮肤状态包括光老化和/或皱纹,但并不限定于这些。
本发明的胶原生成促进组合物根据情况被用作皮肤外用剂。
本发明的胶原生成促进组合物根据情况被用作食品。
本发明的胶原生成促进组合物根据情况为I型胶原生成促进组合物。
本发明提供一种抑制和/或改善皮肤状态的方法,其包括投与胶原生成促进组合物的步骤,所述胶原生成促进组合物包含选自由D-天冬氨酸和D-丙氨酸及其衍生物和/或盐组成的组中的1种或2种以上的化合物。
通过本发明的方法抑制和/或改善的皮肤状态包括光老化和/或皱纹,但并不限定于这些。
本发明的方法中,所述胶原生成促进组合物根据情况为皮肤外用剂。
本发明的方法中,所述胶原生成促进组合物根据情况为食品组合物。
本发明的方法中,所述胶原生成促进组合物根据情况为I型胶原生成促进组合物。
本说明书中,D-天冬氨酸和D-丙氨酸的“盐”是指:在不损害D-天冬氨酸和D-丙氨酸的促进胶原生成的效果的条件下,包括金属盐、胺盐等在内的任意的盐。前述金属盐可以包括碱金属盐、碱土金属盐等。前述胺盐可以包括三乙胺盐、苄胺盐等。
本说明书中,D-天冬氨酸和D-丙氨酸的“衍生物”是指:在不损害D-天冬氨酸和D-丙氨酸的促进胶原生成的效果的条件下,D-天冬氨酸和D-丙氨酸分子在氨基、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。(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-丝氨酸和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)。但是在皮肤中的D-天冬氨酸和D-丙氨酸的生理作用尚不明确。
如以下的实施例所示的那样,D-天冬氨酸和D-丙氨酸的增大胶原生成量的效果迄今未曾被知晓。因此,本发明的含有D-天冬氨酸和/或D-丙氨酸的胶原生成促进组合物为新颖发明。
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克湿质量为2-500nmol(Morikawa,A.等,Amino Acids,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-天冬氨酸及D-丙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-天冬氨酸在0.01~320μM的浓度范围下对培养的人成纤维细胞具有促进胶原生成的效果。因此,本发明的组合物中所含的D-天冬氨酸的量只要满足该浓度范围的D-天冬氨酸能够送达至生物体皮肤组织的成纤维细胞的条件,则可以为任意含量。本发明的组合物为外用剂时,在本发明的组合物的全量中D-天冬氨酸的含量为0.0000001质量%到50质量%或可配合的最大质量浓度范围即可。即所述组合物在为外用剂时的D-天冬氨酸的含量,优选为0.000001质量%~30质量%、最优选为0.00001质量%~3质量%。本发明的组合物为口服剂时的D-天冬氨酸的含量为0.0000001质量%~100质量%的范围即可。本发明的组合物为口服剂时的D-天冬氨酸的含量,优选为0.0000002质量%~80质量%、最优选为0.000001质量%~60质量%。再者,本发明的组合物中所含的D-天冬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。
如以下的实施例所示的那样,本发明的D-丙氨酸在0.01~1000μM的浓度范围下对培养的人成纤维细胞具有促进胶原生成的效果。因此,本发明的皮肤症状改善剂、皮肤外用剂、食品组合物中所含的D-丙氨酸的量只要满足该浓度范围的D-丙氨酸能够送达至生物体皮肤组织的成纤维细胞的条件,则可以为任意含量。本发明的组合物为外用剂时,在本发明的组合物的全量中D-丙氨酸的含量为0.000001质量%到50质量%或可配合的最大质量浓度范围即可。即所述组合物在为外用剂时的D-丙氨酸的含量,优选为0.00001质量%~30质量%、最优选为0.0001质量%~10质量%。本发明的组合物为口服剂时的D-丙氨酸天的含量为0.000001质量%~100质量%的范围即可。本发明的组合物为口服剂时的D-丙氨酸的含量,优选为0.00001质量%~80质量%、最优选为0.0001质量%~60质量%。再者,本发明的组合物中所含的D-丙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。
本发明的组合物除了含有D-天冬氨酸和D-丙氨酸及D-天冬氨酸和D-丙氨酸的盐和/或能够在生物体内通过药物代谢酶等释放D-天冬氨酸和D-丙氨酸的衍生物之外,在不损害D-天冬氨酸和D-丙氨酸的促进胶原生成的效果的条件下,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物添加剂,但不限于这些。
本发明的组合物还可以仅使用D-天冬氨酸和D-丙氨酸、D-天冬氨酸和D-丙氨酸的盐和/或能够在生物体内通过药物代谢酶等释放D-天冬氨酸和D-丙氨酸的衍生物作为有效成分进行制备,但通常在不损害本发明的效果的范围内,可根据需要适当配合包括准药物在内的化妆品、药物等皮肤外用剂等中使用的其他成分。作为前述其他成分(任意配合成分),例如可列举出油分、表面活性剂、粉末、着色材料、水、醇类、增稠剂、螯合剂、硅酮类、抗氧化剂、紫外线吸收剂、保湿剂、香料、各种药效成分、防腐剂、pH调节剂、中和剂等。
本发明的为了抑制和/或改善皮肤状态而被使用的胶原生成促进组合物(以下称为“皮肤状态改善剂”)的剂型只要是以往的准药物组合物及医药组合物中所用者即可,包括例如软膏、乳霜、乳液、化妆水、面膜、凝胶剂,贴剂等外用剂及例如、粉末、颗粒、软胶囊、片剂等的口服剂和例如入鼻雾状液体等的入鼻剂及注射剂。
本发明的皮肤外用剂的剂型只要是以往的皮肤外用剂中所用者即可,包括例如软膏、乳霜、乳液、化妆水、面膜、凝胶剂、贴剂等。
本发明的食品组合物除了含有D-天冬氨酸和D-丙氨酸、D-天冬氨酸和D-丙氨酸的盐和/或能够在生物体内通过药物代谢酶等释放D-天冬氨酸和D-丙氨酸的衍生物之外,在不损害D-天冬氨酸和D-丙氨酸的促进胶原生成效果的条件下,还可以含有调料、着色材料、保存料等作为食品所允许的成分。
本发明的食品组合物只要是例如糖果、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、醪黑醋等使用于以往食品组合物中即可,但不限于前述例示。
附图说明
图1为显示D-天冬氨酸在正常人真皮成纤维细胞中对I型胶原生成的效果的坐标图。
图2为显示D-丙氨酸在正常人真皮成纤维细胞中对I型胶原生成的效果的坐标图。
图3为显示L-和D-天冬氨酸在正常人真皮成纤维细胞中对I型胶原生成的效果的坐标图。
图4为显示L-和D-丙氨酸在正常人真皮成纤维细胞中对I型胶原生成的效果的坐标图。
图5为显示D-天冬氨酸和D-丙氨酸在正常人真皮成纤维细胞中对I型去端肽胶原生成的效果的坐标图。
图6为显示D-丙氨酸在正常人真皮成纤维细胞中对I型去端肽胶原生成的效果的坐标图。
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,不会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所限定。
在本说明书中所言及的所有的文献通过其整体引用被纳入本说明书。
实施例1
D-天冬氨酸的促进I型胶原生成的效果
方法
细胞培养
细胞使用市售的人新生儿真皮成纤维细胞(CryoNHDF-Neo,三光纯药)。所述细胞按照每个孔2×105个的方式接种于市售的24孔细胞培养板,使用于细胞培养用培养基(D-MEM(1g/L葡萄糖)和光纯药)中添加了10%胎牛血清的培养基(以下称为“普通培养基”。)进行培养。所述细胞在37℃、5%CO2及饱和水蒸气条件下培养4小时。
添加氨基酸
之后,将用于培养所述细胞的培养基更换为于市售的细胞培养用培养基(D-MEM(1g/L葡萄糖)、和光纯药)中添加了0.5%胎牛血清的培养基(以下称为“低血清培养基”。),在37℃、5%CO2及饱和水蒸气条件下培养约1天。在此,将D-天冬氨酸(和光纯药工业,018-04821)分别以0.01μM、0.1μM、10μM、100μM和320μM的浓度添加至所述低血清培养基中。将维生素C的前体L-抗坏血酸磷酸酯镁(L-Ascorbic Acid Phosphate MagnesiumSalt n-Hydrate、以下称为“APM”、和光纯药工业,013-19641)分别以150μM、250μM或500μM的浓度添加至所述低血清培养基作为阳性对照。另,将不添加APM和D-天冬氨酸的所述低血清培养基作为阴性对照。
I型胶原生成量的定量
经过2天培养之后,采集培养上清,使用Procollagen typeI C-peptide EIA kit(宝生物工程公司制造),按照制造商的说明书测定由人新生儿真皮成纤维细胞生成的I型前胶原的C末端肽(以下称为“PIP”。)的浓度。
定量结果
图1示出了调查在人新生儿真皮成纤维细胞中添加D-天冬氨酸对I型胶原生成的效果的实验结果。各实验条件的误差柱表示在同一条件下重复4-6次的实验结果的测定值的标准偏差。另外,Bonferroni/Dunn检验中,星号(**)表示p值不足1%。
阴性对照的PIP浓度为583ng/mL。添加了150μM,250μM和500μM浓度的APM时(阳性对照)的PIP浓度分别增大至1183ng/mL、1666ng/mL或1416ng/mL。添加了0.01μM、0.1μM,10μM、100μM或320μM浓度的D-天冬氨酸时的PIP浓度分别为1286ng/mL、1159ng/mL、1117ng/mL、1119ng/mL或1007ng/mL。添加了APM及D-天冬氨酸的培养基中在所有浓度条件下与阴性对照相比较对促进I型胶原生成的效果具有在统计学意义上的显著差异。再者,0.01-100μM的浓度的D-天冬氨酸对促进I型胶原生成的效果和APM的最低浓度150μM相同,D-天冬氨酸示出了具有远比APM更强的促进I型胶原生成的效果。
实施例2
D-丙氨酸的促进胶原生成的效果
方法
细胞培养、添加氨基酸及I型胶原生成量的定量和实施例1同样进行。氨基酸使用0.01μM、0.1μM、10μM、1000μM、17400μM的浓度的D-丙氨酸(肽研究所,2801)。再者,使用不添加APM和D-丙氨酸的所述低血清培养基作为阴性对照。
定量结果
图2示出了调查在人新生儿真皮成纤维细胞中添加D-丙氨酸对I型胶原生成的效果的实验结果。各实验条件的误差柱表示在同一条件下重复4-6次的实验结果的测定值的标准偏差。另外,Bonferroni/Dunn检验中,星号(*)表示p值不足5%。星号(**)表示p值不足1%。
阴性对照的PIP浓度为551ng/mL。添加150μM,250μM或500μM的浓度的APM时(阳性对照)的PIP浓度分别增大至1183ng/mL,1666ng/mL或1416ng/mL,I型胶原的生成被促进了。添加了0.01μM、0.1μM、10μM、1000μM或17400μM的浓度的D-丙氨酸时的PIP浓度分别为750ng/mL、789ng/mL、876ng/mL、823ng/mL或799ng/mL。添加APM及D-丙氨酸的培养基中在所有浓度条件下与阴性对照相比较对促进I型胶原生成的效果具有在统计学意义上的显著差异。
实施例3
L-及D-天冬氨酸的促进胶原生成的效果
方法
细胞培养、添加氨基酸及I型胶原生成量的定量和实施例1同样进行。氨基酸使用0.1μM浓度的D-天冬氨酸(和光纯药工业,018-04821)和0.1μM浓度的L-天冬氨酸(和光纯药工业,013-04832)。再者,使用不添加L-及D-天冬氨酸的所述低血清培养基作为阴性对照。
定量结果
图3示出了调查在人新生儿真皮成纤维细胞中添加L-和D-天冬氨酸对I型胶原生成的效果的实验结果。各实验条件的误差柱表示在同一条件下重复6-12次的实验结果的测定值的标准偏差。另外,Bonferroni/Dunn检验中,星号(**)表示p值不足1%。
阴性对照的PIP浓度为361ng/mL。添加0.1μM的L-和D-天冬氨酸时的PIP浓度分别为406ng/mL和456ng/mL。以上的结果显示了,通过添加0.1μM的D-天冬氨酸对促进I型胶原生成具有在统计学意义上的显著差异。另一方面,添加0.1μM的L-天冬氨酸对促进I型胶原生成无效果。
实施例4
L-和D-丙氨酸的促进胶原生成的效果
方法
细胞培养、添加氨基酸及I型胶原生成量的定量和实施例1同样进行。氨基酸使用0.1μM及150μM的D-丙氨酸(肽研究所,2801)和0.1μM及150μM的L-丙氨酸(肽研究所,2701)。再者,使用不添加L-和D-丙氨酸的所述低血清培养基作为阴性对照。
定量结果
图4示出了调查在人新生儿真皮成纤维细胞中添加L-和D-丙氨酸对I型胶原生成的效果的实验结果。各实验条件的误差柱表示在同一条件下重复6-12次的实验结果的测定值的标准偏差。另外,Bonferroni/Dunn检验中,星号(*)及星号(**)分别表示p值不足5%及1%。
阴性对照的PIP浓度为361ng/mL。添加0.1μM和150μM的D-丙氨酸时的PIP浓度分别为502ng/mL及450ng/mL。添加0.1μM及150μM的L-丙氨酸时的PIP浓度分别为405ng/mL及413ng/mL。以上的结果显示了,通过添加0.1μM和150μM的D-丙氨酸对促进I型胶原生成具有在统计学意义上的显著差异。另一方面,添加0.1μM及150μM的L-丙氨酸对促进I型胶原生成无效果。
实施例5
D-天冬氨酸和D-丙氨酸的促进胶原生成的效果
方法
细胞培养、添加氨基酸和实施例1同样进行。氨基酸使用0.1μM的D-天冬氨酸(和光纯药工业,018-04821)、0.1μM和0.001μM的D-丙氨酸(肽研究所,2801)。再者,使用不添加D-天冬氨酸及D-丙氨酸的所述低血清培养基作为阴性对照。将APM调制至250μM添加于所述低血清培养基作为阳性对照。为了评价I型胶原生成量,将人新生儿真皮成纤维细胞生成的I型前胶原及原胶原经胃蛋白酶(800-2500Unit/mg,SIGMA,P7000)处理后,按照制造商的说明书,依据人类胶原类型IELISA(酶联免疫吸附法)(EC1-E105,AC生物技术股份有限公司)测定I型去端肽胶原的浓度。
定量结果(1)
图5示出了调查在人新生儿真皮成纤维细胞中添加D-天冬氨酸和D-丙氨酸对I型去端肽胶原生成的效果的实验结果。各实验条件的误差柱表示在同一条件下重复5-6次的实验结果的测定值的标准偏差。另外,Bonferroni/Dunn检验中,星号(*)及星号(**)分别表示p值不足5%及1%。
阴性对照的I型去端肽胶原浓度为1.8μg/mL。添加250mM的APM时(阳性对照)的I型去端肽胶原浓度增大至3.9μg/mL,I型胶原的生成被促进了。添加0.1μM的D-丙氨酸时的I型去端肽胶原浓度为4.0μg/mL。添加0.1μM的D-天冬氨酸时的I型去端肽胶原浓度为3.8μg/mL。以上的结果显示了,通过添加0.1μM的D-天冬氨酸和D-丙氨酸对促进I型胶原生成具有在统计学意义上的显著差异。
定量结果(2)
图6示出了调查在人新生儿真皮成纤维细胞中添加D-丙氨酸对I型去端肽胶原生成的效果的实验结果。各实验条件的误差柱表示在同一条件下重复2次的实验结果的测定值的标准偏差。
阴性对照的I型去端肽胶原浓度为1.7μg/mL。添加250mM的APM时(阳性对照)的I型去端肽胶原浓度增大至2.6μg/mL,I型胶原的生成被促进了。添加0.001μM的D-丙氨酸时的I型去端肽胶原浓度为2.1μg/mL。
实施例6
以下示出基于本发明的含有D-天冬氨酸及/或D-丙氨酸的乳液制剂、贴剂、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、醪黑醋、乳霜、身体用乳霜、凝胶剂、剥离型面膜、浸渗型面膜、乳液、化妆水及气雾剂的的配合例。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(乳液制剂)
配合例2(乳液制剂)
配合例3(贴剂)
配合例4(贴剂)
配合例5(片剂)
配合例6(片剂)
配合例7(软胶囊)
配合例8(软胶囊)
配合例9(颗粒)
配合例10(饮料)
配合例11(饮料)
配合例12(糖果)
配合例13(饼干)
配合例13(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-天冬氨酸和/或D-丙氨酸及香料并搅拌。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℃下烘焙15分钟制成饼干。
配合例14(味噌)
配合例14(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-天冬氨酸和/或D-丙氨酸使其浓度为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-天冬氨酸和/或D-丙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-天冬氨酸和/或D-丙氨酸而使用产生大量D-天冬氨酸和/或D-丙氨酸的米曲。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-天冬氨酸和/或D-丙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-天冬氨酸和/或D-丙氨酸或其盐。
配合例15(法式色拉调味汁)
配合例16(法式色拉调味汁)
配合例15及16(法式色拉调味汁)的制造方法
向醋中加入氯化钠及D-天冬氨酸或D-丙氨酸后,充分搅拌并溶解。加入色拉油,充分搅拌并添加胡椒。
配合例17(蛋黄酱)
配合例18(蛋黄酱)
配合例17及18(蛋黄酱)的制造方法
向鸡蛋黄(室温)中加入醋、氯化钠、D-天冬氨酸或D-丙氨酸及胡椒,用打蛋器充分搅拌。然后,一边一点点加入色拉油一边继续搅拌,直至制成乳化液。最后加入砂糖进行搅拌。
配合例19(法式面包)
配合例20(法式面包)
配合例19和配合例20(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、5g砂糖和D-天冬氨酸或D-丙氨酸放入钵中,向其中加入前发酵过的酵母。充分揉和后,形成球状,在30℃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℃的烤箱中烘焙30分钟。
配合例21(酱油)
配合例22(酱油)
配合例21和配合例22(酱油)的制造方法
向市售的酱油中添加D-天冬氨酸或D-丙氨酸并充分搅拌。此外,也可以代替添加D-天冬氨酸或D-丙氨酸或其盐而使用产生大量D-天冬氨酸或D-丙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-天冬氨酸或D-丙氨酸进行定量从而挑选。
配合例23(酸奶)
配合例24(酸奶)
配合例23和配合例24(酸奶)的制造方法
在40℃~45℃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-天冬氨酸或D-丙氨酸。另外,也可以代替添加D-天冬氨酸或D-丙氨酸及其盐而使用产生大量D-天冬氨酸或D-丙氨酸的菌。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-天冬氨酸或D-丙氨酸进行定量从而挑选。
配合例25(撒在饭上的粉状食品)
配合例26(调料·纳豆的佐料汁)
配合例27(调料·纳豆的佐料汁)
配合例28(纳豆)
配合例28(内豆)的制造方法
也可以代替添加D-天冬氨酸和/或D-丙氨酸及其盐而使用产生大量D-天冬氨酸和/或D-丙氨酸的菌来制作纳豆。为了得到前述菌,可通过利用日本特开2008-185558中记载的方法对D-天冬氨酸和/或D-丙氨酸进行定量从而挑选。
配合例29(醪黑醋)
配合例30(醪黑醋)
配合例29和配合例30(醪黑醋)的制造方法
也可以代替添加D-天冬氨酸或D-丙氨酸及其盐而使用产生大量D-天冬氨酸或D-丙氨酸的菌来制作醋、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-天冬氨酸或D-丙氨酸进行定量从而挑选。
配合例31(乳霜)
配合例32(乳霜)
配合例33(身体用乳霜)
配合例34(身体用乳霜)
配合例35(凝胶剂)
配合例36(凝胶剂)
配合例37(剥离型面膜)
配合例38(剥离型面膜)
配合例39(浸渗型面膜)
配合例40(浸渗型面膜)
配合例41(乳液)
配合例42(乳液)
配合例43(乳液)
配合例44(乳液)
配合例45(化妆水)
配合例46(化妆水)
配合例47(化妆水)
配合例48(化妆水)
配合例49(气雾尿素外用剂原液)
配合例50(气雾尿素外用剂原液)
配合例51(气雾尿素喷剂)
配合例51(气雾尿素喷剂)的填充方法
将气雾尿素外用剂原液及二甲醚填充至内表面被teflon(注册商标)涂布处理过的耐压气溶胶铝罐中,制备气雾剂。
Claims (5)
1.选自由D-天冬氨酸和D-丙氨酸及其盐组成的组中的1种或2种以上的化合物的、用于制备胶原生成促进组合物的用途。
2.根据权利要求1所述的用途,其特征在于,所述胶原生成促进组合物为了抑制和/或改善皮肤状态而被使用。
3.根据权利要求2所述的用途,其特征在于,所述皮肤状态为光老化和/或皱纹。
4.根据权利要求1至3中任一项所述的用途,其特征在于,所述胶原生成促进组合物被用作皮肤外用剂。
5.根据权利要求1至3中任一项所述的用途,其特征在于,所述胶原生成促进组合物被用作食品。
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- 2010-09-27 CN CN201080043687.7A patent/CN102548529B/zh active Active
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- 2010-09-27 KR KR1020167032981A patent/KR101788101B1/ko active IP Right Grant
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US8637572B2 (en) | 2014-01-28 |
AU2010301764A1 (en) | 2012-04-12 |
CN102548529A (zh) | 2012-07-04 |
RU2526199C2 (ru) | 2014-08-20 |
KR101780658B1 (ko) | 2017-09-21 |
RU2012113314A (ru) | 2013-11-10 |
TW201117735A (en) | 2011-06-01 |
BR112012007598A2 (pt) | 2016-08-23 |
US20120184619A1 (en) | 2012-07-19 |
TWI519241B (zh) | 2016-02-01 |
KR101788101B1 (ko) | 2017-10-19 |
KR20120084718A (ko) | 2012-07-30 |
JP5826032B2 (ja) | 2015-12-02 |
ES2733537T3 (es) | 2019-11-29 |
HK1168036A1 (zh) | 2012-12-21 |
EP2484340B1 (en) | 2019-04-17 |
JPWO2011040363A1 (ja) | 2013-02-28 |
KR20160137696A (ko) | 2016-11-30 |
WO2011040363A1 (ja) | 2011-04-07 |
EP2484340A1 (en) | 2012-08-08 |
EP2484340A4 (en) | 2014-05-07 |
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