CN101301297A - 皮肤光老化预防剂 - Google Patents
皮肤光老化预防剂 Download PDFInfo
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- CN101301297A CN101301297A CNA2008100961499A CN200810096149A CN101301297A CN 101301297 A CN101301297 A CN 101301297A CN A2008100961499 A CNA2008100961499 A CN A2008100961499A CN 200810096149 A CN200810096149 A CN 200810096149A CN 101301297 A CN101301297 A CN 101301297A
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- extract
- acid
- prophylactic agent
- skin
- ester
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Abstract
本发明的目的是提供一种新颖成分的皮肤光老化预防剂以及使用该皮肤光老化预防剂的食品、包括人类在内的哺乳类动物用的药品和皮肤外用剂、以及哺乳类动物用饲料。本发明的皮肤光老化预防剂的特征在于以列当科植物的提取物为有效成分。所述皮肤光老化预防剂优选含有苯乙醇苷类化合物为有效成分。另外,该皮肤光老化预防剂优选含有松果菊苷和类叶升麻苷中的至少一种作为所述苯乙醇苷类化合物。此外,该皮肤光老化预防剂优选含有松果菊苷和类叶升麻苷两者作为所述苯乙醇苷类化合物。而且,上述皮肤光老化预防剂可以用作包括人在内的哺乳类动物的药品、皮肤外用剂、饮用食品、哺乳类动物用饲料。
Description
技术领域
本发明涉及一种使用新颖成分的皮肤光老化预防剂。本发明可以广泛用于包括人类在内的哺乳类动物用的药品、皮肤外用剂、食品等中。
背景技术
自古以来就已经知道,列当科(Cistanche)草本植物的新鲜茎对于不孕症、阳痿、便秘等的治疗是有效的(参考专利文献1)。而且,由这些多年生草本植物的新鲜茎所制得的制备物可作为血液和肾脏的营养。这些多年生寄生草本植物在中国西北地区广泛栽培,有些地方将它们称作“沙漠人参”。其中列当科的全寄生植物管花肉苁蓉Cistanche tubulosa(Schrenk.)Wight为列当科(Cistanche)中栽培产量最大的一种。
日本学者等对列当科(Cistanche)植物的化学成分和药理活性进行了系统的研究,结果发现苯乙醇苷类化合物是这些多年生草本植物的主要活性成分(例如,参考非专利文献1-3)。这些活性成分可作为有效的抗氧化剂、代谢促进剂、记忆改善剂、性欲促进剂等。很多研究者对多种苯乙醇苷类化合物的医学特性进行了深入研究。
专利文献1:日本特开2004-250449号公报
非专利文献1:Sato T,et al.Yakugaku Zasshi,1985,105(12):1131
非专利文献2:Jimenez C.,et al.Nat.Prod.Rep.,1994,11(6):591
非专利文献3:Cometa F.,et al.Fitoterapia,1993,64(3):195
非专利文献4:DengMin et al.Acta Pharmacoe Sin,2004,25(10)1276-1284
另一方面,一般来说,皮肤老化是指伴随着年龄的增长而产生的生理性老化与暴露于日光下(紫外线)而引起的光老化相互影响而形成的一种生理现象,但是现在特别是光老化与皱纹、皮肤粗糙、色斑、雀斑等色素沉着之间的关系受到人们的关注(Gilchrest编著Photodamage:BlackwellScience公司,1995)。也就是说,已经知道,如果长时间暴露于太阳(紫外线)下,会使脸、脖子上的深皱纹增加,而且还会引起皮肤粗糙以及色斑、雀斑等色素沉着,由光老化造成的皮肤问题已引起人们的注意。
迄今为止,为了防止由紫外线而引起皮肤光老化的加速,已经开发出并使用配伍有各种可以吸收、散射、遮挡紫外线的物质(如,氧化钛、氧化锌、对甲氧基肉桂酸酯、对氨基苯甲酸酯等)的化妆产品(防晒霜、防晒化妆品)。但是,即使使用了这些化妆产品,要完全控制由于日光暴露而引起的皮肤问题也是很困难的。另外,作为上述皮肤光老化症状的改善方法,众所周知采用外用涂抹的全反式视黄酸是有效的方法(参考Gilchrest编著Photodamage:Blackwell Science公司,1995等),但是由于全反式视黄酸存在着可引起皮肤粗糙等香料化妆品科学上的问题、而且还存在安全性问题,所以在日本只限定于根据医生的指导才能使用,因此人们热切盼望开发出一种有效的而且安全性高的防止/改善光老化的药物以及皮肤外用剂。
发明内容
发明所要解决的问题
在这样的背景下,本发明人发现给光老化小鼠(用紫外线照射的裸鼠)摄食松果菊苷和类叶升麻苷以及含有松果菊苷和类叶升麻苷的列当科(Cistanche)植物后,评价它们对皱纹形成的影响以及对皮肤老化相关酶(透明质酸酶、胶原酶)的影响,结果发现松果菊苷和类叶升麻苷以及含有松果菊苷和类叶升麻苷的列当科(Cistanche)植物具有预防皮肤光老化的作用,从而完成本发明。换言之,本发明的目的是提供一种使用新颖成分的皮肤光老化预防剂以及使用该皮肤光老化预防剂的食品、包括人类在内的哺乳类动物用的药品和皮肤外用剂以及哺乳类动物用饲料。
解决问题的手段
为了解决上述问题,本发明为具有如下所示的特征的皮肤光老化预防剂。
1.一种以苯乙醇苷类化合物为有效成分的皮肤光老化预防剂。
2.如前所述的皮肤光老化预防剂,其特征在于,该药物含有松果菊苷和类叶升麻苷中的至少一种作为所述苯乙醇苷类化合物。
3.如前所述的皮肤光老化预防剂,其特征在于,该药物含有松果菊苷和类叶升麻苷作为所述苯乙醇苷类化合物。
4.一种以列当科植物的提取物为有效成分的皮肤光老化预防剂。
5.如前所述的皮肤光老化预防剂,其特征在于,所述提取物中含有苯乙醇苷类化合物作为有效成分。
6.如前所述的皮肤光老化预防剂,其特征在于,所述提取物中含有松果菊苷和类叶升麻苷中的至少一种作为所述苯乙醇苷类化合物。
7.如前所述的皮肤光老化预防剂,其特征在于,所述提取物中含有松果菊苷和类叶升麻苷作为所述苯乙醇苷类化合物。
8.一种可用于包括人在内的哺乳类动物的药品,该药品以上述1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
9.一种可用于包括人在内的哺乳类动物的皮肤外用剂,该皮肤外用剂以上述1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
10.一种饮用食品,该饮用食品以上述1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
11.一种哺乳类动物用饲料,其以上述1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
附图说明
图1为本实施例中裸鼠紫外线照射与皱纹面积之间的关系的图。
图2为本实施例对透明质酸酶基因表达的影响的图。
图3为本实施例对胶原酶基因表达的影响的图。
具体实施方式
下面详细说明本发明。本发明的皮肤光老化预防剂的特征在于以苯乙醇苷类化合物为有效成分。
此处,所述“苯乙醇苷类化合物”是指下面的化学式(1)所表示的化合物。
对所述苯乙醇苷类化合物不特别限定,例如,可以列举松果菊苷、类叶升麻苷、2′-乙酰基类叶升麻苷(2′-acetylacteoside)、campneoside I、campneoside II、管花肉苁蓉苷A(cistantubuloside A)、管花肉苁蓉苷B1、管花肉苁蓉苷B2、管花肉苁蓉苷C1、管花肉苁蓉苷C2、crenatoside、去咖啡酰基类叶升麻苷(decaffeoylacteoside)、异类叶升麻苷(isoacteoside)、红景天苷(rhodioloside)、syringalide A 3′-α-L-rhamnopyranoside和管花苷A(tubuloside A)等成分。另外,这些化合物可以只使用一种,也可以2种以上合用。
另外,上述皮肤光老化预防剂含有松果菊苷和类叶升麻苷中的至少一种作为所述苯乙醇苷类化合物,而且优选含有松果菊苷和类叶升麻苷两者作为所述苯乙醇苷类化合物,这是因为其具有更高的预防皮肤光老化的作用。
对获得苯乙醇苷类化合物的方法没有特别的限定,可以通过合成得到,也可以通过从植物中提取得到。另外,在从植物中提取的情况下,对作为原料的植物没有特别的限定,例如,可以列举生药地黄、唇形科植物水苏、胡椒科胡椒属橄榄的果实、列当科的草本植物等。另外,可以只使用1种所述植物来提取苯乙醇苷类化合物,也可以合用2种以上植物来提取苯乙醇苷类化合物。在这些植物中,最优选使用列当科的植物。这是因为在列当科的植物中,作为苯乙醇苷类化合物,除了松果菊苷和类叶升麻苷之外,还含有2′-乙酰基类叶升麻苷(2′-acetylacteoside)、campneoside I、campneoside II、管花肉苁蓉苷A(cistantubuloside A)、管花肉苁蓉苷B1、管花肉苁蓉苷B2、管花肉苁蓉苷C1、管花肉苁蓉苷C2、去咖啡酰基类叶升麻苷(decaffeoylacteoside)、异类叶升麻苷(isoacteoside)、红景天苷(rhodioloside)、syringalide A 3′-α-L-rhamnopyranoside和管花苷A(tubuloside A)等,所以具有更高的皮肤光老化预防活性。此处,对用作原料的列当科植物没有特别的限定,例如,可以列举全寄生植物管花肉苁蓉(Cistanche tubulosa)、盐生肉苁蓉(Cistanche salsa)、野菰(Aeginetia indica)、草苁蓉(Boschniakia rossica)等,但并不只限于这些植物。另外,这些植物可以只使用一种,也可以2种以上合用。在这些植物中,优选使用全寄生植物管花肉苁蓉(Cistanche tubulosa)。
以下示出上述苯乙醇苷类化合物中的成分与所述化学式(1)之间的关系。但是,crenatoside的结构式如下面的化学式(2)所示。在所述制备物中基本上只含有少量或微量的除了上述成分中的松果菊苷和类叶升麻苷之外的其它成分。
皮肤光老化预防剂中的主要成分
注:Ac:乙酰基;Cf:反式咖啡酰基;Cm:反式香豆酰基(trans-Coumaroyl);c-Cm:顺式香豆酰基(cis-Coumaroyl);Glc:β-D-吡喃葡萄糖;Rha:α-L-鼠李糖(Rhamnopyranose)
上述表1中所示化合物均可以通过高效液相色谱法(HPLC)确认。此时,高效液相色谱法的条件如下所示。固定相为C18烷基硅烷键合硅胶,流动相为乙腈-0.05M磷酸水溶液(洗脱梯度为4∶96→15∶85),流速为1毫升/分钟,检测波长为330nm。
本发明的第二种皮肤光老化预防剂的特征在于以从列当科植物中所提取的提取物作为有效成分。
此处,对用作原料的列当科的植物没有特别的限定,例如,可以列举全寄生植物管花肉苁蓉(Cistanche tubulosa)、盐生肉苁蓉(Cistanchesalsa)、野菰(Aeginetia indica)、草苁蓉(Boschniakia rossica)等,但并不只限于这些植物。另外,这些植物可以只使用一种,也可以2种以上合用。另外,在这些列当科植物中,优选使用全寄生植物管花肉苁蓉(Cistanchetubulosa)。
更进一步来说,所述“提取物”中优选含有苯乙醇苷类化合物。此处,对所述“苯乙醇苷类化合物”没有特别的限定,可以列举松果菊苷、类叶升麻苷、2′-乙酰基类叶升麻苷(2′-acetylacteoside)、campneoside I、campneoside II、管花肉苁蓉苷A(cistantubuloside A)、管花肉苁蓉苷B1、管花肉苁蓉苷B2、管花肉苁蓉苷C1、管花肉苁蓉苷C2、crenatoside、去咖啡酰基类叶升麻苷(decaffeoylacteoside)、异类叶升麻苷(isoacteoside)、红景天苷(rhodioloside)、syringalide A 3′-α-L-rhamnopyranoside和管花苷A(tubuloside A)等成分。此时,所述提取物中可以只含有一种上述成分,也可以含有2种以上成分的混合物。其中,特别优选含有松果菊苷和类叶升麻苷中的至少一种。
此时,对松果菊苷的含量没有特别的限定,以列当科植物(例如,全寄生植物管花肉苁蓉(Cistanche tubulosa))的提取物的总质量作为100质量%时,松果菊苷的含量为10质量%~70质量%、优选为15质量%~50质量%、更优选为20质量%~40质量%、进一步优选为23质量%~38质量%。另外,对类叶升麻苷的含量没有特别的限定,以列当科植物的提取物的总质量作为100质量%时,类叶升麻苷的含量为1质量%~40质量%、优选为5质量%~30质量%、更优选为7质量%~20质量%、进一步优选为8质量%~10质量%。
此时,对列当科植物的被提取部位没有特别的限定,可以使用叶、根、茎等,只要可以达到所期望的效果即可。优选的是,从列当科植物的茎、特别是新鲜的茎中提取。
对从作为原料的列当科植物中获得提取物的方法没有特别的限定,例如,可以列举溶剂提取法、超临界提取法等。
另外,采用溶剂提取法来进行提取时,对所使用的溶剂没有特别的限定,但是优选使用极性溶剂。另外,对所述极性溶剂没有特别的限定,例如,可以列举水、甲醇、乙醇、异丙醇、丙酮、1,3-丁二醇、乙二醇、丙二醇、甘油、醋酸、醋酸乙酯、醚等。这些溶剂可以只使用一种,也可以2种以上合用。优选的是,随后进行稀释、浓缩、干燥、纯化等处理,因为通过这样的处理可以获得含有高浓度的苯乙醇苷类化合物的提取物。另外,作为纯化方法,例如,可以列举活性炭处理、树脂吸附处理、离子交换树脂、液-液逆流分配等方法。
下面详细描述上述提取物的具体制造方法的一个实施方案,但提取物的制造方法并不限于以下的实施方案。
所述提取物的制造方法由提取和纯化2个阶段构成。在第一个阶段中,将列当科植物(例如,全寄生植物管花肉苁蓉(Cistanche tubulosa))的茎(更优选为该植物的新鲜的茎)切成薄片,或者粉碎成微粒或粉末状。接下来,将如此得到的薄片、或者微粒或粉末浸渍在水或者甲醇、乙醇等低级脂肪醇等溶剂、或者它们的混合溶液中。此时,在室温下进行提取。接着,过滤该混合溶液,并在减压条件下或者真空条件下浓缩该滤液,得到提取物。接下来,在第二阶段中,将所述提取物在水中加热后,通过将该提取物转移至填充有D-101型或AB-8型大孔吸附树脂的吸附柱中对所述提取物进行纯化。此时,使用水、甲醇、乙醇、水与甲醇的混合液、或者水与乙醇的混合液等作为洗脱溶剂,对所述吸附柱进行洗脱。洗脱时,可以将上述洗脱溶剂以一定浓度的溶液的形式来洗脱,也可以将上述洗脱溶剂按照浓度梯度来洗脱。收集洗脱液,经浓缩后,采用公知的干燥方法来进行干燥。待洗脱液干燥完成后,得到上述提取物。如此得到的提取物中含有苯乙醇苷类化合物。
本发明中的皮肤光老化预防剂可以用作各种饮用食品的原材料。作为所述饮用食品,例如,可以列举以食用油(色拉油)、点心类(口香糖、糖果、焦糖、巧克力、饼干、零食、果冻、咀嚼片、小甜点等)、面类(荞麦面、乌冬面、拉面等)、乳制品(牛奶、雪糕、酸乳酪等)、调味品(味噌、大酱等)、汤类、饮料(果汁、咖啡、红茶、茶、碳酸饮料、运动饮料等)为代表的一般食品、或者健康食品(片剂、胶囊等)、营养补品(营养饮料等)。在这些饮用食品中可以适当配有本发明的皮肤光老化预防剂。
根据这些饮用食品的种类,可以在其中加入各种成分,例如可以使用葡萄糖、果糖、蔗糖、麦芽糖、山梨糖醇、甜叶菊甙(Stevioside)、玉米糖浆、乳糖、柠檬酸、酒石酸、苹果酸、琥珀酸、乳酸、L-抗坏血酸、dl-α-维生素E、异抗坏血酸钠、甘油、丙二醇、甘油脂肪酸酯、聚甘油脂肪酸酯、蔗糖脂肪酸酯、山梨聚糖脂肪酸酯、丙二醇脂肪酸酯、阿拉伯胶、角叉菜聚糖(carrageenan)、酪蛋白、明胶、果胶、琼脂、维生素B类、烟酰胺、泛酸钙、氨基酸类、钙盐类、色素、香料、保存剂等食品原材料。另外,在具有维持健康功能的本发明的皮肤光老化预防剂中也可以加入其它的抗氧化物质或健康食品原材料等辅剂,所述辅剂例如有抗氧化物质、还原型抗坏血酸(维生素C)、维生素E、还原型谷胱甘肽、生育三烯酚、维生素A衍生物、番茄红素、β-玉米黄质、虾青素、玉米黄质、岩藻黄、尿酸、泛醌、辅酶Q10、叶酸、大蒜提取物、大蒜素、芝麻素、木质素类、儿茶素、异黄酮、查尔酮、鞣质类、黄酮类、香豆素、异香豆素类、越橘提取物、熊果苷、丹宁、花青苷、苹果多酚、葡萄籽提取物、鞣花酸、曲酸、沙棘提取物保健食品原材料、V.(维生素)A、V.B1、V.B2、V.B6、V.B12、V.C、V.D、V.E、V.P、胆碱、烟酰胺、泛酸、叶酸钙、EPA、低聚糖、食物纤维、角鲨烯、大豆卵磷脂、牛磺酸、杜氏藻(Dunaliella)、蛋白质、二十八烷醇、DHA、蛋黄卵磷脂、亚油酸、乳铁蛋白、镁、锌、铬、硒、钾、亚铁血红素、牡蛎肉提取物、脱乙酰壳多糖、几丁质低聚糖、胶原蛋白、软骨素、郁金、甘草、枸杞子、桂皮、山楂、生姜、灵芝、蚬贝提取物、甲鱼、甘草、枸杞子、桂皮、山楂、生姜、灵芝、车前草、黄花菊、洋甘菊、蒲公英、扶桑花、蜂蜜、ボ一レン、蜂王浆、莱檬、薰衣草、野玫瑰果、迷迭香、鼠尾草、双歧杆菌、杆菌(faecalis)、有胞子性乳酸菌、小麦胚芽油、蓖麻油、紫苏油、大豆油、中链脂肪酸、姬松茸(Agaricus)、银杏叶提取物、郁金、软骨素、糙米胚芽提取物、灵芝、洋葱、DHA、EPA、DPA、甜茶、冬虫夏草、大蒜、蜜蜂籽、番木瓜、普洱茶、蜂胶、千里眼树、ャブシタケ、蜂王浆、锯叶棕提取物、透明质酸、胶原蛋白、GABA、海豹油、鲨鱼软骨、葡萄糖胺、卵磷脂、磷脂酰丝氨酸、三七、桑叶、大豆提取物、紫锥菊属植物、西伯利亚人参(ェゾゥコギ)、大麦提取物、橄榄叶、橄榄果实、匙羹藤(Gymnema)、大花紫薇、五层龙属植物(Salacia)、藤黄属植物(Garcinia)、脱乙酰壳多糖、贯叶连翘、大枣、人参、西番莲、青菜花、胎盘、薏苡、葡萄种子、花生皮、越橘、黑升麻、水飞蓟、月桂、鼠尾草、迷迭香、罗布麻、黑醋、ゴ一ャ一茶、玛珈、红花、亚麻、乌龙茶、花棘豆、咖啡因、辣椒碱(capsaicin)、木寡糖、葡萄糖胺、荞麦、柑橘属植物、食物纤维、蛋白质、梅干、螺旋藻、大麦嫩叶、核酸、酵母、香菇、梅肉、氨基酸、深海鲨鱼提取物、诺丽(noni)、牡蛎肉、甲鱼、蘑菇(シャンピニォン)、车前草、樱桃(ァセロラ)、菠萝、香蕉、桃、杏、哈密瓜、草莓、树莓、橘子、岩藻依聚糖、桑黄、鹤莓、硫酸软骨素、锌、铁、神经酰胺、silk peptide、甘氨酸、烟酸、蔓荆子、神经酰胺、L-半胱氨酸、L-肉碱、红葡萄叶、黍、问荆、生物素、积雪草、蓝靛果忍冬、碧萝芷(PYCNOGENOL)、蜂斗菜、大黄、丁香、迷迭香、儿茶素、普洱茶、柠檬酸、啤酒酵母、メリロ一ト、黑大豆、生姜、莪术、纳豆菌、红曲、生育三烯酚、乳铁蛋白、肉桂、鞑靼荞麦、可可粉、柚子籽提取物、紫苏籽提取物、荔枝籽提取物、月见草提取物、糙米提取物、α-硫辛酸、GABA、生咖啡豆提取物、蜂斗菜提取物、猕猴桃籽提取物、温州桔提取物、生姜提取物、虾青素等。
作为具体的制造方法,采用喷雾干燥或者冷冻干燥的方法,可以直接将本发明的皮肤光老化预防剂(如果是提取物,则将该提取物与糊精一起)制成粉末、颗粒、片剂或溶液,从而容易地将它们包含在食品(速食食品等)中。另外,根据需要,也可以将本发明的皮肤光老化预防剂或提取物与阿拉伯胶等粘合剂混合,制成粉末状或者颗粒状,然后添加到固型食品中。另外,在提取物的情况下,可以直接将该提取物添加到饮料中,也可以将该提取物分散溶解于(例如)水、乙醇、甘油或它们的混合物中,然后再添加到饮料中。
本发明的皮肤光老化预防剂也可以用作药品(包括医药品及医药部外品,其中所述医药外部品(quasi drug)又称作准药物,详见http://www.ipss.go.jp/site-ad/yougo/gyousei.html)的原材料。可以通过在药品制剂用的原料中适当加入本发明的皮肤光老化预防剂来制造所述药品。另外,所述药品可以用于人类,也可以用于除了人类以外的哺乳类动物。作为可以与本发明的皮肤光老化预防剂配伍的制剂原料,例如,可以列举赋形剂(葡萄糖、乳糖、白糖、氯化钠、淀粉、碳酸钙、高岭土、结晶纤维素、可可脂、植物硬化油、高岭土、滑石粉等)、粘合剂(蒸馏水、生理盐水、乙醇水、白糖浆、葡萄糖液、淀粉液、明胶溶液、羧甲基纤维素、磷酸钾、聚乙烯吡咯烷酮等)、崩解剂(藻酸钠、琼脂、碳酸氢钠、碳酸钙、月桂基硫酸钠、单硬脂酸甘油酯、淀粉、乳糖、阿拉伯胶粉末、明胶、乙醇等)、崩解抑制剂(白糖、硬脂酸、可可脂、氢化油等)、吸收促进剂(季铵碱、月桂基硫酸钠等)、吸附剂(甘油、淀粉、乳糖、高岭土、皂土、硅酸等)、润滑剂(精制滑石粉、硬脂酸盐、聚乙二醇等)等。
作为本发明的皮肤光老化预防剂的给药方法,一般来说,可以采用片剂、丸剂、软胶囊剂、硬胶囊剂、微粒剂、散剂、颗粒剂等形式经口给药。另外,作为液体制剂,水溶性制剂可以经口给药,也可以非经口给药。作为非口服制剂而给药时,可以将本发明的皮肤光老化预防剂分散于乙醇或水等合适的可溶试剂中,然后以巴布剂、洗剂、软膏剂、酊剂、乳剂等剂型来使用。另外,本发明的皮肤光老化预防剂的水溶性制剂可以直接使用,也可以向该水溶性制剂中加入分散剂、悬浊剂、稳定剂等,然后以巴布剂、洗剂、软膏剂、酊剂、乳剂等剂型来使用。
给药剂量可以根据给药方法、病情、患者的年龄等而变化,但是一般来说,成年人可以按照1天给予的有效成分为5mg~400mg、儿童按照1天给予的有效成分为0.5mg~200mg左右的剂量来给药。
本发明的皮肤光老化预防剂作为药品而使用时,其加入的比例可以根据剂型来适当改变。一般来说,口服给药或者通过粘膜吸收而给药时,皮肤光老化预防剂的加入比例可以为大约0.01重量%~10重量%,而非口服给药时,皮肤光老化预防剂的加入比例可以为0.01重量%~20重量%左右。另外,由于给药剂量根据各种条件的不同而不同,所以有的时候即使给予的剂量小于上述给药剂量范围时也足够,而有的时候给药剂量则需要超过上述剂量范围。医药组合物中除了含有上述皮肤光老化预防剂外,也可以含有医药领域中常用的已知的其它化合物、以及可以含有在适合于经口给药的形式时成型所需要的化合物。作为这样的化合物,例如可以列举乳糖、淀粉、羟丙基纤维素、高岭土、滑石粉、碳酸钙等。
另外,在哺乳类动物用的饲料中也可以含有本发明的皮肤光老化预防剂。可以采用与上述饮用食品相同的方法,将本发明的皮肤光老化预防剂包含在所述动物用饲料中。另外,对可使用所述动物用饲料的动物没有特别的限定,例如,该饲料可用于牛、猪等家畜动物、狗、猫、仓鼠等陪伴动物(作为宠物而饲养的动物)等。另外,例如,作为所述陪伴动物的饲料,可以使用面粉、食用肉等。此时,作为所述面粉,例如有小麦粉、米粉、黑麦粉、燕麦粉、稗麦粉、谷子粉、玉米粉、大豆粉等,这些面粉也可以2种以上合用。通过使用所述面粉,可以给所述陪伴动物提供碳水化合物等营养素。所述面粉中,最优选使用小麦粉。作为所述小麦粉,可以单独或者适当组合使用强力粉、中力粉、薄力粉,另外所述小麦粉也可以与其它的面粉合用。另外,为了调节经加热处理后的动物用饲料的弹性,也可以使小麦粉与小麦麸、大豆蛋白质等组合使用。而且,小麦粉中所含有的麸皮的网状结构在加热处理后会形成膨化的组织结构,有助于改善口感。
对本发明中所使用的食用肉没有特别的限定,可以使用鸡肉、猪肉、牛肉、羊肉、山羊肉、兔肉、火鸡肉、马肉等,从口味上考虑最佳使用鸡肉。可以通过采用常用的方法来宰杀家畜类动物并解剖后得到所述食用肉。而且,中间水分产品或低水分状态的产品发生质量恶化主要是由于脂肪的氧化而引起的,所以所使用的食用肉最好是脂肪含量少的或者是除去了脂肪的瘦肉。另外,在饲料中含有食用肉,不仅可以给动物提供优良的动物性蛋白质,而且还可以改善所述陪伴动物的嗜好。
虽然可以采用各种方法来配制所述陪伴动物的饲料,但是优选的方法例如有这样的方法:配制含有面粉(优选为小麦粉)和食用肉的拌和好的原料混合物(下文中称为“生面团”),待成形后再进行加热处理。对所述生面团中的面粉和食用肉的组成没有特别的限定,一般来说,配制成由5%~60%左右、优选为10%~50%左右的面粉,5%~80%左右、优选为20%~50%左右的食用肉以及必需量的水分所组成的生面团。而且,在使用水活性值(Aw,water activity)调节剂的情况下,该Aw调节剂的添加量为5%~30%左右、优选为10%~20%左右。另外,水的用量可以根据所述生面团的混合搅拌、成形的程度以及面粉、食用肉、Aw调节剂等的用量来适当调节。对所述生面团的配制方法没有特别的限定,优选的是,首先用斩拌机、切碎机等将所述食用肉制成肉馅。此时,为了在制成肉馅的食用肉中充分含有气泡,优选将所述食用肉细切。然后,向所述制成肉馅的食用肉中加入面粉、水以及根据需要还可以加入Aw调节剂等,充分搅拌使其中含有气泡,从而配制成含有气泡的生面团。在配制生面团时,也可以加入发泡剂,特别是在除了小麦粉以外的其它面粉用作所述面粉的情况下,优选使用发泡剂。通过加入发泡剂,可以使生面团中均匀地含有微小气泡。作为所述发泡剂,可以使用各种发泡剂,但是从气泡的稳定性等方面考虑,优选使用大豆蛋白类发泡剂和/或酶分解的大豆蛋白类发泡剂。
使如此制得的生面团成型并经过加热处理后,得到本发明的所述陪伴动物用的饲料。在生面团的成型时,根据所述陪伴动物在吃食时的容易程度、饲养人操作的容易程度等,可以将本发明的所述陪伴动物用饲料制成合适的形状,例如所述形状为片状、棒状、圆片状、环状、心型等。另外,可以将由相同的配合组分所制备的生面团用各种不同色调的色素染色、或者加入蔬菜或水果等,从而制成具有不同外观的多种生面团,将这些生面团组合成多层的形状或者同心圆的形状,从而成型。对成型后的生面团的加热手段没有特别的限定,例如,所述加热手段可以列举烘箱加热、微波加热等。这些加热方法都是公知的,可以按照常用的方法进行加热处理。经过加热处理后的饲料中的水分含量一般为20%~40%左右。经过所述加热处理后,由于水分的蒸发以及气泡的膨胀,所述生面团膨化,另外由于是在短时间内使水分蒸发,所以Aw降低,从而提高了保存性。另外,在小麦粉用作所述面粉的情况下,通过加热处理,小麦粉中所含有的麸皮的网状结构被固定,从而改善口感。而且,在采用烘箱加热的情况下,具有在所述饲料中产生独特的色调(狐色,即类似于狐狸背部的黄褐色的颜色)或香气的优点,而在采用微波加热的情况下,由于是在生面团的内部开始加热,所以可以使生面团均匀膨化,具有可以得到含有均匀气泡的饲料这样的优点。在进行所述加热处理时,优选的是,使所得到的饲料中Aw调节在0.6~0.9的范围内。如上所述,通过将Aw调节在此范围内,可以显著提高饲料的保存性。
如此制得的所述陪伴动物的饲料为具有面包的性状的饲料,由于该饲料具有柔软的口感以及合适的柔软性和弹性,所以适合用作幼犬、老龄犬或猫等牙齿能力弱的陪伴动物的饲料、点心等。将上述动物用饲料以合适的量容纳在包装容器内,密封后制成产品。作为所述包装容器,优选使用不透氧气的包装材料。作为包装的形式,可以列举真空包装、填充有活性炭的包装等,但是优选的是同时填充有去氧剂(例如,ェ一ジレスTM等)和活性炭的包装。采用相关的包装形式,在保存期间可以防止由于氧气而引起的质量恶化以及微生物的繁殖。
本发明的皮肤光老化预防剂也可以用作皮肤外用剂(包括化妆品、医药品以及医药部外品),期待该皮肤外用剂具有皮肤光老化预防作用。另外,所述皮肤外用剂可以用于人类,也可以用于除了人类以外的其它哺乳类动物。作为可以配伍有本发明的皮肤光老化预防剂的皮肤外用剂的形式,例如,可以列举乳液、肥皂、洗面剂、洗澡剂、护肤霜、乳液、化妆水、花露水、剃须用乳膏、剃须用洗液、化妆油、防晒用化妆水、粉饼、粉底、香水、面膜(pack)、指甲膏、指甲油(enamel)、指甲油洗液、眉墨、胭脂、眼霜、眼影、染睫毛油、眼线、口红、唇膏、洗头液、护发素、染发剂、分散液、洗涤剂。另外,作为可以配伍有本发明的皮肤光老化预防剂的医药品或医药部外品的形式,可以列举软膏剂、乳剂、外用液等。
在上述形式的皮肤外用剂中,除了含有本发明的皮肤光老化预防剂之外,在不损害皮肤光老化预防作用的范围内,也可以加入下述物质,所述物质为可以加入到化妆品、医药部外品等皮肤外用剂中的成分,包括油类成分、高级醇、脂肪酸、紫外线吸收剂、粉末、颜料、表面活性剂、多元醇、糖类、高分子、生理活性物质、溶剂、抗氧化剂、香料、防腐剂等。以下虽然罗列出这些物质的例子,但是本发明并不只限于这些例子。
(1)油类成分的例子 酯类的油类成分举例有:三2-乙基己酸甘油酯、2-乙基己酸十六醇酯、肉豆蔻酸异丙酯、肉豆蔻酸丁酯、棕榈酸异丙酯、硬脂酸乙酯、棕榈酸辛酯、异硬脂酸异十六醇酯、硬脂酸丁酯、肉豆蔻酸丁酯、亚油酸乙酯、亚油酸异丙酯、油酸乙酯、肉豆蔻酸异十六醇酯、肉豆蔻酸异十八醇酯、棕榈酸异十八醇酯、肉豆蔻酸辛基十二醇酯、异硬脂酸异十六醇酯、癸二酸二乙酯、己二酸二异丙酯、新戊酸异廿十醇酯、三(辛基癸酸)甘油酯、三2-乙基己酸三羟甲基丙酯、三异硬脂酸三羟甲基丙酯、四2-乙基己酸季戊四醇酯、辛酸十六醇酯、月桂酸癸酯、月桂酸己酯、肉豆蔻酸癸酯、肉豆蔻酸肉豆蔻醇酯、肉豆蔻酸十六醇酯、硬脂酸十八醇酯、油酸癸酯、蓖麻醇酸十六醇酯、月桂酸异十八醇酯、肉豆蔻酸异三癸酯、肉豆蔻酸异十六醇酯、肉豆蔻酸异十八醇酯、棕榈酸异十六醇酯、棕榈酸异十八醇酯、硬脂酸辛酯、硬脂酸异十六醇酯、油酸异癸酯、油酸辛基十二醇酯、亚油酸辛基十二醇酯、异硬脂酸异丙酯、2-乙基己酸十八醇十六醇酯、2-乙基己酸十八醇酯、异硬脂酸己酯、二辛酸乙二醇酯、二油酸乙二醇酯、二癸酸丙二醇酯、二(辛基癸酸)丙二醇酯、二辛酸丙二醇酯、二癸酸新戊二醇酯、二辛酸新戊二醇酯、三辛酸甘油酯、三(十一酸)甘油酯、三异棕榈酸甘油酯、三异硬脂酸甘油酯、新戊酸辛基十二醇酯、辛酸异十八醇酯、异壬酸辛酯、新癸二酸己基十二醇酯、新癸二酸辛基十二醇酯、异硬脂酸异十六醇酯、异硬脂酸异十八醇酯、异硬脂酸辛基十二醇酯、聚甘油油酸酯、聚甘油异硬脂酸酯、碳酸二丙酯、碳酸二烷基(C12-C18)酯、柠檬酸三异十六醇酯、柠檬酸三异廿十醇酯、柠檬酸三异辛酯、乳酸月桂酯、乳酸肉豆蔻酯、乳酸十六醇酯、乳酸辛基十二醇酯、柠檬酸三乙酯、柠檬酸乙酰基三乙酯、柠檬酸乙酰基三丁酯、柠檬酸三辛酯、苹果酸二异十八醇酯、羟基硬脂酸2-乙基己酯、琥珀酸二2-乙基己酯、己二酸二异丁酯、癸二酸二异丙酯、癸二酸二辛酯、硬脂酸胆甾醇酯、异硬脂酸胆甾醇酯、羟基硬脂酸胆甾醇酯、油酸胆甾醇酯、油酸二氢胆甾醇酯、异硬脂酸植物甾醇酯、油酸植物甾醇酯、12-硬脂酰基羟基硬脂酸异十六醇酯、12-硬脂酰基羟基硬脂酸十八醇酯、12-硬脂酰基羟基硬脂酸异十八醇酯等。烃类的油类成分举例有:角鲨烯、液态石蜡、α-烯烃低聚物、异石蜡、白地蜡、石蜡、液态异石蜡、聚丁烯、微晶蜡、凡士林等。动植物油及其硬化油、以及天然的蜡举例有:牛脂、硬化牛脂、猪脂、硬化猪脂、马油、硬化马油、貂油、ォレンジラフィ一(棘鲷科的一种鱼)油、鱼油、硬化鱼油、蛋黄油等动物油及其硬化油;鳄梨油、杏仁油、橄榄油、可可脂、猕猴桃种子油、杏仁油、木立芦荟油、芝麻油、小麦胚芽油、米胚芽油、玄米油、红花油、牛油果脂、豆油、月见草油、紫苏油、茶籽油、山茶油、玉米油、菜籽油、硬化菜籽油、棕榈核油、硬化棕榈核油、花生油、硬化花生油、蓖麻油、硬化蓖麻油、向日葵油、葡萄籽油、霍霍巴油、硬化霍霍巴油、澳洲坚果油、メドホ一ム油、棉籽油、硬化棉籽油、椰子油、硬化椰子油等植物油及其硬化油;蜂蜡、高酸价蜂蜡、羊毛脂、还原羊毛脂、硬化羊毛脂、液状羊毛脂、巴西棕榈蜡、褐煤蜡等蜡。硅氧烷类的油类成分举例有:二甲基聚硅氧烷、甲基苯基聚硅氧烷、甲基环聚硅氧烷、八甲基聚硅氧烷、十甲基聚硅氧烷、十二甲基聚硅氧烷、甲基氢聚硅氧烷、聚醚改性有机聚硅氧烷、二甲基硅氧烷·甲基十六烷基羟基硅氧烷共聚物、二甲基硅氧烷·甲基十八烷基羟基硅氧烷共聚物、烷基改性有机聚硅氧烷、末端改性有机聚硅氧烷、氨基改性硅酮油、氨基改性有机聚硅氧烷、二甲基硅氧烷醇(Dimethiconol)、硅酮胶、丙烯基硅酮、三甲基甲硅烷氧基硅酸、硅酮RTV胶等。氟类的油类成分举例有:全氟聚醚、氟改性有机聚硅氧烷、氟化沥青、氟化碳、氟代醇、氟代烷基·聚羟基亚烷基共改性有机聚硅氧烷等。
(2)高级醇的例子有:月桂基醇、肉豆蔻醇、鲸蜡醇、十八烷醇、异十八烷醇、油醇、二十二醇、2-乙基己醇、十六烷醇、辛基十二烷醇等。
(3)脂肪酸的例子有:辛酸、癸酸、十一碳烯酸、月桂酸、肉豆蔻酸、棕榈酸、棕榈油酸、硬脂酸、异硬脂酸、油酸、亚油酸、亚麻酸、花生酸、花生四烯酸、二十二酸、芥子酸、2-乙基己酸等。
(4)紫外线吸收剂的例子有:对氨基安息香酸、对氨基安息香酸戊酯、对氨基安息香酸乙基二羟基丙酯、对氨基安息香酸甘油酯、对氨基安息香酸乙酯、对氨基安息香酸辛酯、对氨基安息香酸辛基二甲酯、水杨酸乙二醇酯、水杨酸辛酯、水杨酸三乙醇胺、水杨酸苯酯、水杨酸丁基苯酯、水杨酸苄酯、水杨酸同孟酯、桂皮酸苄酯、对甲氧基桂皮酸辛酯、对甲氧基桂皮酸2-乙基己酯、二对甲氧基桂皮酸单2-乙基己酸甘油酯、对甲氧基桂皮酸异丙酯、对甲氧基桂皮酸二乙醇胺、二异丙基·二异丙基桂皮酸酯混合物、尿刊酸、尿刊酸乙酯、羟基甲氧基苯甲酮、羟基甲氧基苯甲酮磺酸及其盐、二羟基甲氧基苯甲酮、二羟基甲氧基苯甲酮磺酸钠、二羟基苯甲酮、二羟基二甲氧基苯甲酮、羟基辛氧基苯甲酮、四羟基苯甲酮、丁基甲氧基二苯甲酰基甲烷、2,4,6-三苯胺基-对-(2-乙基己基-1-羧基)-1,3,5-三嗪、2-(2-羟基-5-甲基苯基)苯并三唑、邻-氨基苯甲酸甲酯、2-氨基-3,3-二苯基丙烯酸2-乙基己酯、苯基苯并咪唑硫酸、3-(4-甲基苯亚甲基)樟脑、异丙基二苯甲酰基甲烷、4-(3,4-二甲氧基苯基亚甲基)-2,5-二氧代-1-咪唑烷基丙酸2-乙基己酯等,以及这些物质的高分子衍生物或硅烷衍生物等。
(5)粉末、颜料的例子有:红色104号、红色201号、黄色4号、蓝色1号、黑色401号等色素;黄色4号AL沉淀色料、黄色203号BA沉淀色料等沉淀色素;尼龙粉、丝粉、氨基甲酸乙酯粉、特氟隆(注册商标)粉、硅酮粉、聚甲基丙烯酸甲酯粉、纤维素粉、淀粉、硅酮球状弹性体粉末、聚乙烯粉等高分子;黄色氧化铁、红色氧化铁、黑色氧化铁、氧化铬、炭黑、群青、深蓝等有色颜料;氧化锌、氧化钛、氧化铈等白色颜料;滑石粉、云母、白铅矿、高岭土、板状硫酸钡等体质颜料;云母钛等珠光颜料;硫酸钡、碳酸钙、碳酸镁、硅酸铝、硅酸镁等金属盐;硅、氧化铝等无机粉末;硬脂酸铝、硬脂酸镁、棕榈酸锌、肉豆蔻酸锌、肉豆蔻酸镁、月桂酸锌、十一烯酸锌等金属肥皂;膨润土、蒙脱石、氮化硼等。对这些粉末的形状(球形、棒状、针状、板状、不定型、鳞片状、纺锤状等)和粒径没有特别的限定。另外,也可以采用已知的表面处理方法(如,氟化合物处理方法、硅酮处理法、硅树脂处理法、悬垂处理法、硅烷耦合剂处理法、钛耦合剂处理法、油剂处理法、N-酰基化树脂处理法、聚丙烯酸处理法、金属皂化处理法、氨基酸处理法,卵磷脂处理法、无机化合物处理法、等离子体处理法、机械化学处理法等)对这些粉末预先进行表面处理。
(6)表面活性剂的例子 阴离子型表面活性剂可以列举有:脂肪酸皂、α-酰基磺酸盐、烷基磺酸盐、烷基烯丙基磺酸盐、烷基萘磺酸盐、烷基硫酸盐、POE烷基醚硫酸盐、烷基氨基硫酸盐、烷基磷酸盐、POE烷基磷酸盐、烷基氨基磷酸盐、烷酰基烷基牛磺酸盐、N-酰基氨基酸盐、POE烷基醚羧酸盐、烷基磺基琥珀酸盐、烷基磺基醋酸钠、酰基化水解胶原蛋白肽盐、全氟烷基磷酸酯等。阳离子型表面活性剂可以列举有:烷基三甲基氯化铵、硬脂酰基三甲基氯化铵、硬脂酰基三甲基溴化铵、十八碳酰基十六碳酰基三甲基氯化铵、二硬脂酰基二甲基氯化铵、硬脂酰基二甲基苄基氯化铵、二十二碳酰基三甲基溴化铵、氯化新洁尔灭、二十二酸氨基丙基二甲基羟基丙酯氯化铵、硬脂酸二乙基氨基乙酰胺、硬脂酸二甲基氨基丙酰胺、羊毛脂衍生物季铵盐等。两性表面活性剂可以列举有:羧基甜菜碱型、酰胺基甜菜碱型、磺基甜菜碱型、羟基磺基甜菜碱型、酰胺基磺基甜菜碱型、磷酸甜菜碱型、氨基羧酸盐型、咪唑啉衍生物型、酰胺基胺型等。非离子型表面活性剂可以列举有:丙二醇脂肪酸酯、甘油脂肪酸酯、聚甘油脂肪酸酯、山梨糖醇脂肪酸酯、POE脱水山梨醇脂肪酸酯、POE山梨糖醇脂肪酸酯、POE甘油脂肪酸酯、POE烷基醚、POE脂肪酸酯、POE硬化蓖麻油、POE·POP共聚物、POE·POP烷基醚、聚醚改性硅氧烷月桂酸烷基醇酰胺、烷基氧化胺、氢化大豆卵磷脂等。天然表面活性剂可以列举有:卵磷脂、皂苷、糖类表面活性剂等。
(7)多元醇、糖的例子可以列举有:乙二醇、二乙二醇、聚乙二醇、丙二醇、二丙二醇、聚丙二醇、甘油、二甘油、聚甘油、3-甲基-1,3-丁二醇、1,3-丁二醇、山梨醇、甘露醇、蜜三糖、赤藓糖醇、葡萄糖、蔗糖、果糖、木糖、乳糖、麦芽糖、麦芽糖醇、海藻糖、烷基化海藻糖、混合异性糖、硫酸化海藻糖、支链淀粉等。另外也可以使用它们的化学修饰物等。
(8)高分子的例子有:丙烯酸酯/甲基丙烯酸酯共聚物(プラスサィズ、互应化学株式会社制造)、醋酸乙烯酯/巴豆酸共聚物(レジン 28-1310、NSC株式会社制造)、醋酸乙烯酯/巴豆酸/新癸酸乙烯酯共聚物(28-2930、NSC株式会社制造)、甲基乙烯基醚马来酸半酯(ガントレッッES、ISP株式会社制造)、丙烯酸叔丁酯/丙烯酸乙酯/甲基丙烯酸共聚物(ルビマ一、BASF株式会社制造)、乙烯基吡咯烷酮/乙酸乙烯酯/丙酸乙烯酯共聚物(ルビスコ一ルVAP、BASF株式会社制造)、乙酸乙烯基酯/巴豆酸共聚物(ルビセットCA、BASF株式会社制造)、乙酸乙烯基酯/巴豆酸/乙烯基吡咯烷酮共聚物(ルビセットCAP、BASF株式会社制造)、乙烯基吡咯烷酮/丙烯酸酯共聚物(ルビフレックス、BASF株式会社制造)、丙烯酸酯/丙烯酰胺共聚物(ゥルトラホ一ルド、BASF株式会社制造)、乙酸乙烯基酯/马来酸丁酯/丙烯酸异冰片酯共聚物(ァドバンテ一ジ、ISP株式会社制造)、羧基乙烯基聚合物(カ一ボポ一ル、BFGoodrich公司制造)、丙烯酸·甲基丙烯酸烷基共聚物(ペミュレン、BFGoodrich公司制造)等阴离子型高分子化合物;或者甲基丙烯酸二烷基氨基乙酯聚合物的乙酸两性化合物(ュカフォ一マ一、三菱化学株式会社制造)、丙烯酸辛基丙烯酰胺/丙烯酸羟基丙酯/甲基丙烯酸丁基氨基乙酯共聚物(AMPHOMER、NSC株式会社制造)等两性高分子化合物;乙烯基吡咯烷酮/甲基丙烯酸二甲基氨基乙酯的季碳化物(GAFQUAT、ISP公司制造)、甲基乙烯基氯化咪唑鎓/乙烯基吡咯烷酮共聚物(ルビコ一ト、BASF株式会社制造)等阳离子型高分子化合物;聚乙烯吡咯烷酮(ルビスコ一ルK、BASF株式会社制造)、乙烯吡咯烷酮/醋酸乙烯基酯共聚物(ルビスコ一ルVA、BASF株式会社制造)、乙烯吡咯烷酮/甲基丙烯酸二甲基氨基乙酯共聚物(コポリマ一937、ISP公司制造)、乙烯基己内酰胺/乙烯吡咯烷酮/甲基丙烯酸二甲基氨基乙酯共聚物(コポリマ一VC713、ISP公司制造)等非离子型高分子化合物等。另外,下列来源于天然的高分子化合物也是适用的:纤维素及其衍生物、角蛋白及胶原蛋白或它们的衍生物、海藻酸钙、普鲁兰多糖、琼脂、明胶、罗望子种子多糖、黄原胶、角叉菜聚糖、高甲氧基果胶、低甲氧基果胶、瓜尔胶、阿拉伯胶、结晶纤维素、阿拉伯半乳聚糖、刺梧桐树胶、黄耆胶、海藻酸、白蛋白、酪蛋白、凝胶多糖、结冷胶、葡聚糖等。
(9)生理活性成分的例子作为生理活性成分,在涂敷于皮肤上的情况中,可以列举那些可以给皮肤带来某种生理活性的物质。例如,可以列举美白成分、免疫活化剂、抗老化剂、防紫外线剂、瘦身剂、拉伸剂、抗氧化剂、增毛剂、育毛剂、保湿剂、促进血液循环剂、抗菌剂、杀菌剂、干燥剂、冷感剂、温感剂、维生素类、氨基酸、创伤治愈促进剂、刺激缓和剂、镇痛剂、细胞活化剂、酶成分等。作为与这些生理活性成分配伍的合适的成分的例子,例如有:返阳草提取物、鳄梨提取物、土常山提取物、蜀葵提取物、山金车提取物、芦荟提取物、杏提取物、杏核提取物、银杏提取物、茴香提取物、郁金提取物、乌龙茶提取物、营实提取物、松果菊叶提取物、黄芩提取物、黄檗提取物、黄连提取物、大麦提取物、小连翘提取物、野芝麻提取物、豆掰菜提取物、橘子提取物、海水干燥物、海藻提取物、水解弹性蛋白、水解麦子粉末、水解丝、洋甘菊提取物、胡萝卜提取物、茵陈蒿提取物、甘草提取物、扶桑提取物、火棘提取物、金鸡纳提取物、黄瓜提取物、鸟苷、栀子提取物、山白竹提取物、苦参提取物、胡桃提取物、葡萄柚提取物、绣球藤提取物、螺旋藻提取物、桑提取物、龙胆草提取物、红茶提取物、酵母提取物、牛蒡提取物、玄米发酵提取物、米胚芽油、聚合草提取物、骨胶原、越橘提取物、细辛提取物、柴胡提取物、脐带提取液、鼠尾草提取物、肥皂草提取物、小竹提取物、山楂提取物、花椒提取物、香菇提取物、地黄提取物、紫根提取物、紫苏提取物、椴树提取物、绣线菊提取物、芍药提取物、菖蒲根提取物、白桦提取物、问荆提取物、常春藤提取物、西洋山楂提取物、接骨木提取物、西洋蓍草提取物、西洋薄荷提取物、鼠尾草提取物、锦葵提取物、川芎提取物、獐牙菜提取物、大豆提取物、大枣提取物、百里香提取物、茶提取物、丁香提取物、茅草提取物、陈皮提取物、当归提取物、金盏菊提取物、桃仁提取物、桧树提取物、鱼腥草提取物、西红柿提取物、纳豆提取物、人参提取物、蒜提取物、野蔷薇提取物、扶桑提取物、麦门冬提取物、欧芹提取物、蜂蜜、金缕梅提取物、夏白菊提取物、香茶菜提取物、红没药醇、枇杷提取物、蒲公英提取物、蜂斗菜提取物、茯苓提取物、假叶树提取物、葡萄提取物、蜂胶、丝瓜提取物、红花提取物、胡椒薄荷提取物、菩提树提取物、牡丹提取物、啤酒花提取物、松提取物、欧洲七叶树提取物、水芭蕉提取物、无患子提取物、香蜂花提取物、桃提取物、矢车菊提取物、桉树提取物、虎耳草提取物、薏苡仁提取物、艾蒿提取物、薰衣草提取物、苹果提取物、莴苣提取物、柠檬提取物、紫云英提取物、蔷薇提取物、迷迭香提取物、罗马甘菊提取物、蜂王浆提取物等。另外、还可以列举:脱氧核糖核酸、粘多糖类、透明质酸钠、硫酸软骨素钠、骨胶原、弹性蛋白、几丁质、脱乙酰壳多糖、水解卵壳膜等生物高分子;氨基酸、水解肽、乳酸钠、尿素、吡咯烷酮羧酸钠、甜菜碱、乳清、三甲基甘氨酸等保湿成分;神经脂质、神经酰胺、植物鞘氨醇、胆固醇、胆固醇衍生物、磷脂等油性成分;ε-氨基己酸、甘草酸、β-甘草次酸、氯化溶菌酶、愈创蓝油烃、ヒドロコ一ルチゾン等免疫活化剂;维生素A、维生素B2、维生素B6、维生素C、维生素D、维生素E、泛酸钙、生物素、烟酸酰胺、维生素C酯等维生素类;尿囊素、二氯乙酸二异丙胺、4-氨基甲基环己酸等活性成分;生育酚、类胡萝卜素、黄酮、鞣质、木质素、皂苷等抗氧化剂;α-羟酸、β-羟酸等细胞活化剂;γ-谷维素、维生素E衍生物等血液循环促进剂;视黄醇、视黄醇衍生物等创伤治愈剂;白蛋白、曲酸、胎盘提取物、硫磺、鞣花酸、亚油酸、凝血酸、谷胱甘肽等美白剂;风箱树苷、甘草提取物、辣椒素、桧醇、碘化蒜提取物、盐酸吡哆醇、DL-α-生育酚、醋酸DL-α-生育酚、烟酸、烟酸衍生物、泛酸钙、D-泛醇、乙酰基泛酰乙基醚、生物素、尿囊素、异丙基甲基苯酚、雌二醇、乙炔基雌二醇、卡普氯铵、苯扎氯铵、盐酸苯海拉明、タカナ一ル、樟脑、水杨酸、壬酸香子兰酰胺、壬烷酸香子兰酰胺、ピロクトンォラミン、十五烷酸甘油酯、L-薄荷醇、单硝基愈创木酚、间苯二酚、γ-氨基丁酸、苄索氯铵、盐酸美西律、植物生长素、雌激素、斑蝥酊、环孢菌素、吡啶硫酮锌、ヒドロコ一ルチゾン、米诺地尔、单硬脂酸聚氧乙烯山梨聚糖、薄荷油、ササニシキ米提取物等育毛剂等。
(10)抗氧化剂的例子可以列举:亚硫酸氢钠、亚硫酸钠、异抗坏血酸、异抗坏血酸钠、硫代二丙酸二月桂酯、生育酚、甲苯基双胍、去甲二氢愈创木酸、对羟基苯甲醚、丁基羟基苯甲醚、二丁基羟基甲苯、硬脂酸抗坏血酸酯、棕榈酸抗坏血酸酯、没食子酸辛酯、没食子酸丙酯、类胡萝卜素、黄酮、鞣质、木质素、皂苷、苹果提取物和丁香提取物等具有抗氧化效果的植物提取物等。
(11)溶剂的例子可以列举:纯化水、乙醇、低级醇、醚类、LPG、碳氟化合物、N-甲基吡咯烷酮、氟取代醇、具有挥发性的直链硅氧烷、次生氟利昂等。
实施例
虽然对本发明的实施例进行说明,但是本发明并不限于这些实施例。
实施例
本发明的皮肤光老化预防剂的制备实施例1:列当科全寄生植物管花肉苁蓉(Cistanche tubulosa)(下文中简称为“管花肉苁蓉”)提取物的制备
[提取工艺]
将管花肉苁蓉新鲜茎的薄片10kg浸渍于该薄片8倍量的水中。将薄片在水中浸渍1小时后,用水煎煮2小时。将如此煎煮后的混合物进行过滤,得到第一滤液。接下来,将煎煮后的混合物的残渣与该残渣4倍量的40%乙醇混合后,煎煮4小时,将煎煮后的混合物进行过滤,得到第二滤液。对于第二滤液的残渣,按照与上述同样的操作重复进行2次,得到第三滤液和第四滤液。合并上述4种滤液,真空浓缩至浓缩液的比重为1.05(50℃),从而得到最终提取物。如此得到的所述最终提取物的重量为6.2kg。
[纯化工艺]
将上述最终提取物6kg在边加热的条件下溶解于该最终提取物一半重量的水中。接下来,将该提取物溶液上样于已填充有预先处理过的D-101型大孔吸附树脂的吸附柱中。首先用水洗脱该吸附柱,得到所述新鲜茎的2倍量的水洗脱液,再用20%的乙醇洗脱该吸附柱,得到所述新鲜茎的2倍量的20%乙醇第一洗脱液。将上述水洗脱液再次重复进行吸附-洗脱这样的操作,得到20%乙醇第二洗脱液。合并这2种20%乙醇洗脱液,通过浓缩、干燥,得到含有苯乙醇苷类化合物的制备物(实施例1)。如此得到的制备物的重量为0.865kg。
通过高效液相法(HPLC)来测定松果菊苷和类叶升麻苷的含量。此时,HPLC的条件如下:固定相为C18烷基硅烷键合硅胶,流动相为甲醇-0.15%醋酸水溶液(30∶70),流速为1毫升/分钟,检测波长为330nm。
称取在60℃真空中干燥24小时后的松果菊苷和类叶升麻苷,溶解于50%的甲醇中,配制成对照品溶液(1ml溶液中含有0.1mg的溶质)。
边用超声波处理,边将含有苯乙醇苷类化合物的制备物50mg溶解于25ml容量瓶中的适量的50%甲醇中。向上述溶液中再加入50%甲醇,调节至25ml的刻度。精密量取该溶液约1ml,置10ml的容量瓶中,加入50%甲醇直至刻度。经0.45μm的膜过滤该溶液后,制得样品溶液。
分别量取5μl的对照品溶液和样品溶液,注入高效液相色谱仪中,分别测定松果菊苷和类叶升麻苷的峰面积。根据它们的峰面积计算其含量。其结果为,松果菊苷在制备物(实施例1)中的含量为37.5质量%、类叶升麻苷在制备物(实施例1)中的含量为9.0质量%。
实施例2和实施例3
实施例2中使用松果菊苷纯品(杏辉药品工业股份有限公司制造),实施例3中使用类叶升麻苷纯品(杏辉药品工业股份有限公司制造)。
试验例1
方法:将裸鼠分为下述3组(n=4)。
·无UV组
·UV+给予溶剂组
·UV+给予管花肉苁蓉200mg/kg组
此处,对于上述“UV+给予管花肉苁蓉200mg/kg组”,给裸鼠强制性地经口给予上述实施例1的制备物的水溶液200mg/kg,1日1次连续给药6周。对于“UV+给予溶剂组”,用蒸馏水代替上述实施例1的制备物的水溶液,强制性经口给予,1日1次连续给药6周。对于“无UV组”,不进行强制性经口给药。此处,对于上述“UV+给予管花肉苁蓉200mg/kg组”和“UV+给予溶剂组”,每周用UV照射3次,共照射6周(第1周:50mJ/cm2,第2周:70mJ/cm2,第3周和第4周:80mJ/cm2,第5周和第6周:200mJ/cm2)。另外,“无UV组”不进行UV照射,并且除了不强制性经口给予上述实施例1的制备物和蒸馏水之外,在与“UV+给予管花肉苁蓉200mg/kg组”和“UV+给予溶剂组”同样的环境下饲养6周。
在给药后第6周,用SKIN CAST获取上述各组裸鼠背部的复制品(replica)。用USB Microscope M2在一定条件下对所获取的复制品进行照相,然后用图像分析软件(NIH Image)测定给药前后的皱纹面积“NIHImage分析面积值”,并进行评价。结果如图1所示。另外,“NIH Image分析面积值”是指在本试验例所使用的图像分析软件中所示出的皱纹的面积的值,该数值越大表示皱纹占皮肤的面积越大。另外,在图1中,“NO-UV”表示无UV组的结果,“对照(UV)”表示UV+给予溶剂组的结果,“200”表示UV+给予管花肉苁蓉200mg/kg组的结果。
试验例1中实施例的效果
根据图1,关于对皱纹形成的影响,可以发现“UV+给予管花肉苁蓉200mg/kg组”具有抑制由紫外线照射而引起的皱纹形成的趋势。由此可以确认本实施例的制备物可以有效地防止由紫外线照射而引起的皱纹形成。
试验例2
方法:对于上述试验例1中所使用的各组裸鼠,分别采集给药6周后各组裸鼠的皮肤,提取皮肤的RNA,逆转录反应后用RT-PCR来比较各组中透明质酸酶基因和胶原酶基因的表达量。结果如图2(透明质酸酶基因表达)和图3(胶原酶基因表达)所示。另外,在图2和图3中,“无UV”表示无UV组的结果,“对照(UV)”表示UV+给予溶剂组的结果,“200”表示UV+给予管花肉苁蓉200mg/kg组的结果。
试验例2中实施例的效果
根据图2和图3,用RT-PCR来比较透明质酸酶基因和胶原酶基因的表达量,结果发现管花肉苁蓉提取物(200mg/kg)组可以抑制由UV引起的透明质酸酶基因(图2)和胶原酶基因(图3)的表达量。该结果与图1所示的对皱纹形成的影响具有相同的趋势。因此可以认为管花肉苁蓉提取物通过抑制皮肤老化基因的表达,从而抑制皱纹的形成。由以上结果可以确认,管花肉苁蓉提取物可以抑制由紫外线照射而引起的皮肤老化现象。
下面列举本发明的皮肤光老化预防剂的配方例,但是这些配方例并不用于限定本发明。
配方例1:口香糖
砂糖 53.0重量%
胶基 20.0
葡萄糖 10.0
水饴 16.0
香料 0.5
皮肤光老化预防剂 0.5
100.0重量%
配方例2:咀嚼片
麦芽糖醇 40.0重量%
砂糖 20.0
葡萄糖 20.0
明胶 4.7
水 9.68
葡萄汁 4.0
葡萄调味料 0.6
色素 0.02
皮肤光老化预防剂 1.0
100.0重量%
配方例3:糖果
砂糖 50.0重量%
麦芽糖 33.0
水 14.4
有机酸 2.0
香料 0.2
皮肤光老化预防剂 0.4
100.0重量%
配方例4:酸乳酪(硬式·软式)
牛奶 41.5重量%
脱脂奶粉 5.8
砂糖 8.0
琼脂 0.15
明胶 0.1
乳酸菌 0.005
皮肤光老化预防剂 0.4
香料 微量
水 补足
100.0重量%
配方例5:清凉饮料
果糖葡萄糖的糖液 30.0重量%
乳化剂 0.5
皮肤光老化预防剂 0.05
香料 适量
纯化水 补足
100.0重量%
配方例6:小甜点
砂糖 76.4重量%
葡萄糖 19.0
蔗糖脂肪酸酯 0.2
皮肤光老化预防剂 0.5
纯化水 3.9
100.0重量%
配方例7:软胶囊
葡萄籽油 87.0重量%
乳化剂 12.0
皮肤光老化预防剂 1.0
100.0重量%
配方例8:片剂
乳糖 54.0重量%
结晶纤维素 30.0
淀粉分解物 10.0
甘油脂肪酸酯 5.0
皮肤光老化预防剂 1.0
100.0重量%
配方例9:颗粒内服剂(医药品)
皮肤光老化预防剂 1.0重量%
乳糖 30.0
玉米淀粉 60.0
结晶纤维素 8.0
聚乙烯吡咯烷酮 1.0
100.0重量%
配方例10:化妆膏
角鲨烷 20.0重量%
蜂蜡 5.0
精制荷荷芭油 5.0
甘油 5.0
甘油单硬脂酸酯 2.0
聚氧乙烯(20)山梨聚糖单硬脂酸酯 2.0
皮肤光老化预防剂 2.0
防腐剂 适量
香料 适量
纯化水 补足
100.0重量%
配方例11:化妆水
乙醇 5.0重量%
甘油 2.0
1,3-丁二醇 2.0
聚乙烯油醚 0.5
柠檬酸钠 0.1
柠檬酸 0.1
皮肤光老化预防剂 0.1
纯化水 补足
100.0重量%
配方例12:润体乳
澳洲坚果油 2.0重量%
肉豆蔻酸辛基十二烷基酯 10.0
甲基苯基聚硅氧烷 5.0
二十二烷醇 3.0
硬脂酸 3.0
鲨肝醇 1.0
单硬脂酸甘油酯 1.0
四油酸聚氧乙烯山梨糖醇 2.0
氢化大豆磷脂 1.0
神经酰胺 0.1
棕榈酸视黄醇酯 0.1
防腐剂 适量
积雪草提取物 1.0
皮肤光老化预防剂 1.0
1,3-丁二醇 5.0
纯化水 补足
100.0重量%
配方例13:乳液
角鲨烷 4.0重量%
凡士林 2.5
鲸蜡醇 2.0
甘油 2.0
亲油型单硬脂酸甘油酯 1.0
硬脂酸 1.0
L-精氨酸 1.0
皮肤光老化预防剂 0.5
氢氧化钾 0.1
香料 微量
纯化水 补足
100.0重量%
配方例14:洗浴用剂(液状)
丙二醇 50.0重量%
乙醇 20.0
硫酸钠 5.0
皮肤光老化预防剂 0.5
羊毛脂 0.5
牛油果油 0.5
色素 1.5
香料 22.0
100.0重量%
配方例15:猫食
玉米粉 34.0重量%
小麦粉 35.0
肉粉 15.0
牛脂 8.9
食盐 1.0
鰜鱼提取物 4.0
皮肤光老化预防剂 1.0
牛磺酸 0.1
维生素类 0.5
矿物质类 0.5
100.0重量%
配方例16:狗食
玉米粉 30.0重量%
肉类(鸡肉) 15.0
脱脂大豆 10.0
小麦粉 25.0
麸糠类 5.0
皮肤光老化预防剂 5.0
动物性油脂 8.9
寡糖 0.1
维生素 0.5
矿物质 0.5
100.0重量%
工业适用性
如上所述,本发明可以抑制紫外线照射的裸鼠的皱纹形成,而且可以抑制紫外线照射的裸鼠的皮肤老化相关基因(透明质酸酶、胶原酶)的表达,所以可以提供一种新型的皮肤光老化预防剂,并且可以提供使用了该皮肤光老化预防剂的食品、包括人类在内的哺乳类动物用的药品和皮肤外用剂、以及哺乳类动物用饲料。
Claims (11)
1.一种以苯乙醇苷类化合物为有效成分的皮肤光老化预防剂。
2.权利要求1所述的皮肤光老化预防剂,其特征在于,该药物含有松果菊苷和类叶升麻苷中的至少一种作为所述苯乙醇苷类化合物。
3.权利要求2所述的皮肤光老化预防剂,其特征在于,该药物含有松果菊苷和类叶升麻苷作为所述苯乙醇苷类化合物。
4.一种以列当科植物的提取物为有效成分的皮肤光老化预防剂。
5.权利要求4所述的皮肤光老化预防剂,其特征在于,所述提取物中含有苯乙醇苷类化合物作为有效成分。
6.权利要求5所述的皮肤光老化预防剂,其特征在于,所述提取物中含有松果菊苷和类叶升麻苷中的至少一种作为所述苯乙醇苷类化合物。
7.权利要求6所述的皮肤光老化预防剂,其特征在于,所述提取物中含有松果菊苷和类叶升麻苷作为所述苯乙醇苷类化合物。
8.一种可用于包括人在内的哺乳类动物的药品,该药品以权利要求1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
9.一种可用于包括人在内的哺乳类动物的皮肤外用剂,该皮肤外用剂以权利要求1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
10.一种饮用食品,该饮用食品以权利要求1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
11.一种哺乳类动物用饲料,其以权利要求1至7中任意一项所述的皮肤光老化预防剂作为有效成分。
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