CN113693965A - 用于改善皱纹的皮肤外用剂 - Google Patents
用于改善皱纹的皮肤外用剂 Download PDFInfo
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- CN113693965A CN113693965A CN202111020188.2A CN202111020188A CN113693965A CN 113693965 A CN113693965 A CN 113693965A CN 202111020188 A CN202111020188 A CN 202111020188A CN 113693965 A CN113693965 A CN 113693965A
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- skin
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- oil
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Abstract
本发明提供一种提高对皮肤的老化的预防或改善有效的化合物的皮肤贮存性的方法。本发明的含有1)由下述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐、和2)部分交联型甲基聚硅氧烷的油胶剂型的皮肤外用剂使制剂中的所述1)的有效成分易于浸润皮肤并且增强皮肤吸收性,进而提高皮肤内贮存性。[式中,R1表示被羧基取代的碳数1~4的直链或支链的烷基或被具有碳数1~4的烷基链的羧酸酯基取代的碳数1~4的直链或支链的烷基,R2及R3各自独立地表示碳数1~4的直链或支链的烷基]。
Description
本申请是国际申请日为2017年6月21日、进入中国国家阶段日期为2018年12月6日、国家申请号为201780035325.5、发明名称为“用于改善皱纹的皮肤外用剂”的PCT进入中国国家阶段申请的分案申请。
技术领域
本发明涉及一种适合作为化妆品(包括医药部外品(quasi-drug))的皮肤外用剂,更详细而言,涉及一种特征在于含有1)由下述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐、和2)部分交联型甲基聚硅氧烷的油胶剂型的皮肤外用剂。
【化学式1】
[式中、R1表示被羧基取代的碳数1~4的直链或支链的烷基、或者被具有碳数1~4的烷基链的羧酸酯基取代的碳数1~4的直链或支链的烷基,R2及R3各自独立地表示碳数1~4的直链或支链的烷基]。
背景技术
作为因年轻增加而导致的皮肤老化现象的代表性症状,可列举出皱纹形成。皱纹可大致分类为,通过保湿可改善的在皮肤表面上形成的浅皱纹、和因暴露于紫外线、积聚物理刺激而产生的深皱纹,后者的深皱纹形成的预防或改善是非常困难的。此外,迄今为止,已经开发了各种各样的皱纹改善剂(例如、参照非专利文献1)。作为这种皱纹改善剂,众所周知的是以视黄酸作为有效成分的。虽然在美国视黄酸作为用于治疗皱纹、粉刺的医药品已得到认可,但是由于在皮肤刺激等安全性方面有问题,因此在日本并未得到认可。此外,作为其他的皱纹改善剂,已经报道了胶原产生促进剂(例如、参照专利文献1)、透明质酸产生促进剂(例如、参照专利文献2)等。然而,上述皱纹改善剂不能说是均可获得足够的效果,而且并没有实现有效手段的确立。此外,作为其原因之一,可列举出在皱纹改善剂以及皮肤外用剂的稳定性、而且在皮肤透过性或贮存性等方面有问题的皱纹改善剂的存在。
具有不同于上述皱纹改善剂的作用机制的皱纹改善剂中含有弹性蛋白酶抑制剂。作为存在于皮肤组织内的结构蛋白之一的弹性蛋白通过构建交联结构来维持组织的弹性。已知暴露于紫外线等皮肤刺激通过使弹性蛋白降解酶的弹性蛋白酶过度表达和活化而使弹性蛋白改性和破坏,从而引起皮肤的紧致及弹性的降低,进而促进皱纹形成。弹性蛋白酶抑制剂通过抑制前述的弹性蛋白降解酶来发挥对皱纹形成的预防或改善效果。另一方面,虽然进行了弹性蛋白降解酶及底物的结构解析、结构活性相关研究,但难以通过有机低分子实现高酵素抑制活性以及选择性,作为具有高酵素抑制作用的成分中存在许多肽及其衍生物(例如、参照专利文献3)。作为这种肽衍生物的弹性蛋白酶抑制剂,已知WS7622A单硫酸酯或者二硫酸酯等肽衍生物(例如、参照专利文献4),通过所涉及的药理作用来实现对缺血性疾病的应用。此外,已知由所述化学式(1)表示的化合物与WS7622A同样存在白细胞弹性蛋白酶抑制作用,并已报道了皮肤的老化预防或治疗作用(例如、参照专利文献5)。然而,上述肽及其衍生物的分子尺寸也比较大,存在相对于具有多个酰胺键等到达真皮的到达性而并不优选的化学结构上的特性,因此会担心有效量会达不到达皱纹形成部位。实际上,在对肽及其衍生物进行经皮给药的情况下,有效成分以及皮肤外用剂的稳定性、而且皮肤透过性或贮存性等方面存在较多问题,而且无法获得所期待的效果并不少见。
通常,在化妆品等皮肤外用剂含有皱纹改善剂的情况下,作为所选择的剂型,可选择乳液剂型、精华剂型、乳霜剂型等水性剂型。前述的弹性蛋白酶抑制剂、尤其是期待有高弹性蛋白酶抑制活性的肽及其衍生物具有相对大的分子量、且具有亲油性部分含有小的亲水性部分的化学结构,因此在选择水系剂型并含有皱纹改善剂的情况下,皱纹改善剂不易从皮肤表面浸润真皮,而是倾向于通过汗等方式在短时间内从皮肤上脱落。因此,大多数情况下,生物利用度会变得极低,并且不会发挥出所期待的对皱纹形成的预防或改善作用。另一方面,通过蜡等将液体油脂固化后的常规油胶制剂具有能够抑制前述的因汗等造成的皱纹改善剂的脱落,或者抑制对水不稳定的皱纹改善剂的变质等优点,相反,大多数情况下,不能说浸润、浸透真皮是非常好。此外,在油胶制剂中还存在黏腻等使用性的问题。因此,为了提高作为油胶制剂的化妆品的使用性,已经报道过混合了硅油的油胶剂型的皮肤外用剂(例如、参照专利文献6、专利文献7)。而且,已知油胶剂型中混合了硅油的化妆品,香气的性质不易随时间发生变化(例如、参照专利文献8)。
此外,已知一种如下的技术,以改善细纹等皮肤整体上的容貌,即,在使化妆组合物中含有交联的硅氧烷弹性体(silicone elastomer,部分交联型甲基聚硅氧烷)并且将该组合物涂覆在皮肤的情况下会形成顺滑的薄膜来抚平细纹及皱纹,或者还含有球形粒子来赋予作为使细纹及皱纹上产生光学散射的光学扩散器的功能而使皮肤的表面检验发生变化的技术(例如、参照专利文献9)。
在先技术文献
专利文献
专利文献1:日本特开2002-255847号公报
专利文献2:日本特开2004-123637号公报
专利文献3:国际公开第2001/40263号
专利文献4:国际公开第1998/27998号
专利文献5:国际公开第1999/43352号
专利文献6:日本专利第3242874号公报
专利文献7:日本专利第3492483号公报
专利文献8:日本特开2003-300851号公报
专利文献9:日本特开2001-294510号公报
非专利文献
非专利文献1:防老化·美白·保湿化妆品的开发技术、CMC出版、铃木正人监修、第2章防老化抗皱纹)功能性化妆品
发明内容
发明所要解决的课题
如上所述,作为化妆品的剂型而采用油胶剂型本身是已知的技术,但以应用于皮肤为目的而含有有效成分的油胶剂型的皮肤外用剂中,该有效成分会对经皮吸收性造成怎样的影响,尚不明确。因此,未尝试过使这种油胶制剂含有由所述化学式(1)表示的化合物。
本发明是在这样的状况下所完成的发明,其课题在于提供一种提高由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐的皮肤贮存性的方法。
用于解决课题的手段
鉴于这种状况,本发明人寻求提高由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐的皮肤贮存性的方法,经过反复研究,其结果为,本发明人发现通过使作为结构基体的含有交联型甲基聚硅氧烷的油胶剂型的皮肤外用剂中含有由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐,从而会改善皮肤外用剂中的该化合物的存在容易度和浸润皮肤的平衡性,进而会提高皮肤贮存性。
而且还发现加入了球状粉体的油胶剂型的皮肤外用剂使皮肤外用剂的粘度降低且流动性增加,从而可改善使用感并且易于使皮肤外用剂向皮肤的铺展,进而会关系到经皮吸收性的提高。基于该见解,本发明人发现油胶剂型的皮肤外用剂会提高皮肤外用剂中的由所述化学式(1)表示的化合物等的皮肤贮存性,从而完成了本发明。即,本发明如下所示。
<1>、一种油胶剂型的皮肤外用剂,其特征在于,含有:1)由下述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐、和2)部分交联型甲基聚硅氧烷。
【化学式2】
[式中、R1表示被羧基取代的碳数1~4的直链或支链的烷基、或被具有碳数1~4的烷基链的羧酸酯基取代的碳数1~4的直链或支链的烷基,R2及R3各自独立地表示碳数1~4的直链或支链的烷基]
<2>、<1>所述的油胶剂型的皮肤外用剂,其特征在于,由所述化学式(1)表示的化合物为,由下述化学式(2)表示的化合物、其异构体及/或其药理学上可容许的盐。
【化学式3】
[式中、R4表示被羧基取代的碳数1~4的直链或支链的烷基,R5及R6各自独立地表示碳数1~4的直链或支链的烷基。]
<3>、<2>所述的油胶剂型的皮肤外用剂,其特征在于,所述化学式(2)表示的化合物为,由下述式(3)表示的3(RS)-[[4-(羧基甲基氨基羰基)苯基羰基]-L-缬氨酰-L-脯氨酰]氨基-1,1,1-三氟-4-甲基-2-氧代戊烷、其异构体及/或其药理学上可容许的盐。
【化学式4】
<4>、<1>~<3>中任一项所述的油胶剂型的皮肤外用剂,其特征在于,还含有球状粉体。
<5>、<4>所述的油胶剂型的皮肤外用剂,其特征在于,所述球状粉体为,有机球状粉体。
<6>、<4>或<5>所述的油胶剂型的皮肤外用剂,其特征在于,所述球状粉体为,聚甲基丙烯酸甲酯。
<7>、<4>~<6>中任一项所述的油胶剂型的皮肤外用剂,其特征在于,所述球状粉体相对于皮肤外用剂总量而含有12~50质量%。
发明效果
若使用本发明的油胶剂型的皮肤外用剂,则使由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐到达真皮、使该化合物的皮肤贮存性得到提高,从而能够解决对于皱纹形成的预防或改善等美容上的问题。
具体实施方式
<本发明的由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐>
本发明的油胶剂型的皮肤外用剂的特征在于,含有1)由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐、和2)部分交联型甲基聚硅氧烷。此外,本发明的油胶剂型的皮肤外用剂会提高由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐的皮肤贮存性,从而发挥出优异的对于皱纹形成的预防或改善效果。本发明的由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐,例如,可通过日本特开平04-297446号公报所述的方法来制造。本发明的由所述化学式(1)表示的化合物具有人体白细胞弹性蛋白酶抑制活性,从而可期待对脑梗死等脑缺血性疾病的治疗效果。此外,例如WO1999/43352号公报所述,具有皮肤老化的预防或治疗效果。本发明的由所述化学式(1)表示的化合物具有真皮乳头部的弹性纤维的新生、表皮正下方的真皮部位的微细的胶原原纤维的新生、表皮厚的增加等作用,并且通过所涉及的作用来发挥对皱纹形成的预防或改善效果。此外,由于本发明的由所述化学式(1)表示的化合物在其分子结构中具有多个不对称碳原子的光学活性化合物,因此作为其异构体而存在对映体、非对映异构体。而且,作为本发明的由所述化学式(1)表示的化合物,存在外消旋体、对映体、非对映异构体,还存在所述异构体以任意的比率混合的化合物。
关于本发明的由所述化学式(1)表示的化合物,式中、R1表示被羧基取代的碳数1~4的直链或支链的烷基或者被具有碳数1~4的烷基链的羧酸酯基取代的碳数1~4的直链或支链的烷基,R2及R3各自独立地表示碳数1~4的直链或支链的烷基。
若具体地例示所述R1优选的基团,可优选例示出羧基甲基、羧基乙基、羧基丙基、羧基丁基、甲氧基羰基甲基、甲氧基羰基乙基、甲氧基羰基丙基、甲氧基羰基丁基、乙氧基羰基甲基、乙氧基羰基乙基、乙氧基羰基丙基、乙氧基羰基丁基、丙氧基羰基甲基、丙氧基羰基乙基、丙氧基羰基丙基、丙氧基羰基丁基、丁氧基羰基甲基、丁氧基羰基乙基、丁氧基羰基丙基、丁氧基羰基丁基等,更优选例示出羧基甲基。
若具体地例示所述R2及R3各自独立优选的基团,可优选例示出甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基等,更优选例示出异丙基。
作为由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐之中优选的示例,可优选例示出由所述化学式(2)表示的化合物、其异构体及/或其药理学上可容许的盐,作为更优选的化合物,可优选例示出3-[[4-(羧基甲基氨基羰基)苯基羰基]-缬氨酰-脯氨酰]氨基-1,1,1-三氟-4-甲基-2-氧代戊烷、其异构体及/或其药理学上可容许的盐,作为进一步优选的化合物,可优选例示出3(RS)-[[4-(羧基甲基氨基羰基)苯基羰基]-L-缬氨酰-L-脯氨酰]氨基-1,1,1-三氟-4-甲基-2-氧代戊烷或其钠盐(以下、有时将该钠盐简称为KSK32)。
通过使本发明的由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐与部分交联型甲基聚硅氧烷一起含在油胶剂型的皮肤外用剂中,从而提高皮肤贮存性,进而提高对皱纹形成的预防或改善效果。
关于本发明的由所述化学式(2)表示的化合物,式中、R4表示被羧基取代的碳数1~4的直链或支链的烷基,R5及R6各自独立地表示碳数1~4的直链或支链的烷基。所述R4表示被羧基取代的碳数1~4的直链或支链的烷基,若具体地例示所述R4优选的基团,可优选例示出羧基甲基、1-羧基乙基、2-羧基乙基、1-羧基丙基、2-羧基丙基、3-羧基丙基、1-羧基丁基、2-羧基丁基、3-羧基丁基、4-羧基丁基等,作为进一步优选的基团,可优选例示出羧基甲基。
所述R5及R6各自独立地表示碳数1~4的直链或支链的烷基,若具体地例示所述R5及R6优选的基团,可优选例示出甲基、乙基、n-丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基等,作为进一步优选的基团,可优选例示出异丙基。而且,若具体地例示由所述化学式(2)表示的化合物的优选的化合物,可优选例示出N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基乙基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丙基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丁基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基乙基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丙基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丁基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基乙基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丙基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丁基)氨基]羰基]苯甲酰]-L-丙氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基乙基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丙基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丁基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基乙基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丙基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丁基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺(3(RS)-N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺)、N-[4-[[(羧基乙基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丙基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、N-[4-[[(羧基丁基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、其异构体及/或其药理学上可容许的盐,作为进一步优选的化合物,可优选例示出由化学式(3)表示的N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[(RS)-3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺、其异构体及/或其药理学上可容许的盐。另外,由化学式(3)表示的化合物如上所述,也可以表达成3(RS)-[[4-(羧基甲基氨基羰基)苯基羰基]-L-缬氨酰-L-脯氨酰]氨基-1,1,1-三氟-4-甲基-2-氧代戊烷。
另外,以下有时将N-[4-[[(羧基甲基)氨基]羰基]苯甲酰]-L-缬氨酰-N-[(RS)-3,3,3-三氟-1-(1-甲基乙基)-2-氧代丙基]-L-脯氨酰胺的钠盐简称为KSK32。另外,上述的KSK32是指,仅命名不同的同一化合物。
通过使本发明的由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐与部分交联型甲基聚硅氧烷一起含在油胶剂型的皮肤外用剂中,从而提高皮肤贮存性,并抑制皱纹形成,使皱纹的新形成与消失的平衡倾向于消失的一方,从而提高对于皱纹形成的预防或改善效果。
此外,虽然本发明的由所述化学式(1)表示的化合物也可以以原有的状态含在油胶剂型的皮肤外用剂中,但是也可以与药理学上可容许的酸或碱一起进行处理并转化成盐的形式并用作盐。例如,可列举出盐酸盐、硫酸盐、硝酸盐、磷酸盐、碳酸盐等无机酸盐;马来酸盐、富马酸盐、草酸盐、柠檬酸盐、乳酸盐、酒石酸盐、甲磺酸盐、对甲苯磺酸盐、苯磺酸盐等有机酸盐;钠盐、钾盐等的碱金属盐、钙盐、镁盐等的碱土类金属盐;三乙胺盐、三乙醇胺盐、铵盐、单乙醇胺盐、哌啶盐等的有机胺盐、赖氨酸盐、精氨酸盐等的碱性氨基酸盐;等等。本发明的油胶剂型的皮肤外用剂中可含有选自由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐中的1种或2种以上。
为了使本发明的由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐含在油胶剂型的皮肤外用剂中来发挥前述的效果,优选为相对于皮肤外用剂总量而含有0.01质量%~10质量%,更优选为含有0.1质量%~5质量%。这是因为,当含在油胶剂型的皮肤外用剂中的由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐的量过少时,存在所述效果下降的倾向,即使过多,也会存在所述效果达到顶峰的倾向。
<本发明的部分交联型甲基聚硅氧烷>
本发明的皮肤外用剂为,特征在于含有1)由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐、和2)部分交联型甲基聚硅氧烷的油胶剂型的皮肤外用剂。被分类为部分交联型有机聚硅氧烷聚合物的部分交联型甲基聚硅氧烷为,具有通过硅氧烷键而形成的直链状聚合物部分交联了的结构的硅油。另外,本发明中提到的“部分交联型”是指,通过以表示交联的程度的交联率成为20~30%程度的方式进行交联而制造出的物质。
此外,从稳定性、使用感的观点出发,优选为使用本发明中所使用的部分交联型甲基聚硅氧烷在25℃下的稠度为100~500的物质。
另外,部分交联型甲基聚硅氧烷在25℃下的稠度可根据JIS K2220来进行测定。
上述那样的部分交联型甲基聚硅氧烷中有作为化妆品的通用原料而在市面上出售的商品。本发明的部分交联型甲基聚硅氧烷可购入这种市售品来使用。
作为市售品,既可以使用除了部分交联型甲基聚硅氧烷以外,还含有十甲基环五硅氧烷、甲基聚硅氧烷、八甲基环四硅氧烷、甲基苯基聚硅氧烷等其他硅油的商品,也可以使用仅含有部分交联型甲基聚硅氧烷的商品。
作为市面上出售的部分交联型甲基聚硅氧烷之中优选的商品,可列举出信越化学工业株式会社制的KSG-15(部分交联型甲基聚硅氧烷约5质量份以及十甲基环五硅氧烷约95质量份的混合物)、KSG-16(部分交联型甲基聚硅氧烷约20~30质量份以及甲基聚硅氧烷约70~80质量份的混合物)、KSG-17(部分交联型甲基聚硅氧烷约5质量份以及八甲基环四硅氧烷约95质量份的混合物)、KSG-18(部分交联型甲基聚硅氧烷约10~20质量份以及甲基苯基聚硅氧烷约80~90质量份的混合物)等,尤其优选为KSG-16。
本发明的油胶剂型的皮肤外用剂中既可以含有选自所述的部分交联型甲基聚硅氧烷的市售品中的1种或2种以上,也可以在单独含有部分交联型甲基聚硅氧烷的市售品中含有其他硅油。所涉及的部分交联型甲基聚硅氧烷在本发明的皮肤外用剂中作为凝胶形成剂来发挥作用,并赋予维持皮肤外用剂的油胶结构的作用。为了发挥出这样的作用,所涉及的部分交联型甲基聚硅氧烷的含量相对于油胶剂型的皮肤外用剂总量,优选为采用5~25质量%,更优选为10~20质量%。这是因为,当过少时,存在难以维持结构的倾向,当过多时,存在制剂化的自由度受损的倾向。
<本发明的皮肤外用剂>
本发明的油胶剂型的皮肤外用剂的特征在于,含有1)由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐、和2)部分交联型甲基聚硅氧烷。本发明的油胶剂型的皮肤外用剂通过促进从所述化学式(1)表示的化合物的制剂中的释放、提高皮肤贮存性等来使真皮中的有效成分的浓度上升,从而有效地提高抗老化、对于皱纹形成的预防或改善作用。
虽然本发明的油胶剂型的皮肤外用剂通过使用前述的部分交联型甲基聚硅氧烷来形成油胶剂型,但是除了交联型甲基聚硅氧烷以外,还可以含有除前述的硅油之外的成分。前述的市售品中所含有的硅油在油胶剂型之中作为被凝胶化的油性成分来发挥作用,作为这样的油性成分,尤其可优选例示出1个气压下的沸点为200℃以下的挥发性硅油。作为这样的挥发性硅油,可优选例示出25℃下1mPa·s以下的甲基聚硅氧烷、前述的十甲基环五硅氧烷、甲基聚硅氧烷、八甲基环四硅氧烷等。
所述挥发性硅油优选为,相对于油胶剂型的皮肤外用剂总量而含有30~60质量%。本发明的油胶剂型的皮肤外用剂通过部分交联型甲基聚硅氧烷而使所述油性成分凝胶化并进行油胶剂型化,从而能够提高由所述化学式(1)表示的化合物的皮肤贮存性。此外,通过由所述化学式(1)表示的化合物的皮肤贮存的提高,从而提高对于皱纹形成的预防或改善效果。
作为本发明的油胶剂型的皮肤外用剂,例如,优选为含有良好地实现皮肤外用剂的铺展等的增强脂溶性的球状粉体。另外,本发明中的“球状”是指,除了正球体形状以外,还包括在表面上具有凹凸部分的大致球状的形状。
这样的球状粉体的平均粒子径优选为,5~20μm。这是因为会存在如下情况,即,当小于5μm时,在涂覆时会强烈地感受到发涩感,另一方面,当超过20μm时,涂覆时会强烈地感受到因球状粉体而造成的凹凸感。
此外,在本说明书中,对于球状粉体的粒子径的测量,可使用麦奇克(Microtrac)法(激光衍射、散射法),例如,使用日机装株式会社制的Microtrac MT3000II系列来进行测量。
作为本发明的油胶剂型的皮肤外用剂中所含有的球状粉体,可优选例示出球状二氧化硅、球状碳酸钙、球状碳酸镁、球状硅酸钙、球状硅酸镁等球状硅酸盐等球状无机粉体、聚酰胺粉末、聚甲基丙烯酸甲酯、聚酯粉末等有机球状粉体,其中,更优选为使用有机球状粉体,尤其优选为使用聚甲基丙烯酸甲酯。
这是因为,在有机球状粉体中,除了所述的使用性的提高作用以外,还具有显著地增强由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐的皮肤贮存性的作用。
本发明的有机球状粉体的聚甲基丙烯酸甲酯可使用市面上出售的商品,作为市面上出售的商品,可优选例示出由松本油脂制药株式会社销售的微球M330。而且,为了实现前述的作用,所述的球状粉体相对于油胶剂型的皮肤外用剂总量,优选为,在总量中含有12~50质量%,更优选为含有15~45质量%,尤其优选为含有20~30质量%。这是因为,当过少时存在所述效果降低的倾向,当过多时存在处方自由度受损的情况。此外,本发明的油胶剂型的皮肤外用剂中可含有选自所述球状粉体的1种或2种以上。
本发明的油胶剂型的皮肤外用剂中,除了所涉及的成分以外,还可含有通常皮肤外用剂中所使用的任意成分。作为这种任意成分,例如,可优选例示出澳洲坚果油、鳄梨油、玉米油、橄榄油、菜籽油、芝麻油、蓖麻油、红花油、棉籽油、霍霍巴油、椰子油、棕榈油、液状羊毛脂、硬化椰子油、硬化油、木蜡、硬化蓖麻油、蜂蜡、小烛树蜡、巴西棕榈蜡、虫蜡、羊毛脂、氢化羊毛脂、硬质羊毛脂、霍霍巴蜡等油、蜡类;液态石蜡、角鲨烷、姥鲛烷、地蜡(ozokerite)、石蜡、赛洛辛(ceresin)、矿脂、微晶蜡等烃类;油酸、异硬脂酸、月桂酸、肉豆蔻酸、棕榈酸、硬脂酸磷酸、山嵛酸、十一碳烯酸等高级脂肪酸类;鲸蜡醇、硬脂醇、异硬脂醇、山嵛醇、辛基十二烷醇、肉豆蔻醇、棕榈醇等高级醇等;异辛酸十六烷基酯、肉豆蔻酸异丙酯、己基癸醇异硬脂酸酯、己二酸二异丙酯、癸二酸二辛酯、鲸蜡醇乳酸酯、二异硬脂醇苹果酸酯、二-2-乙基己酸乙二醇酯(ethylene glycol di-2-ethylhexanoate)、新戊二醇二癸酸酯、二-2-庚基十一烷酸甘油酯(glycerin di-2-heptylundecanoate)、三-2-乙基己酸甘油酯(glycerin tri-2-ethylhexanoate)、三羟甲基丙烷三-2-乙基己酸酯、三羟甲基丙烷三异硬脂酸酯、;季戊四醇四-2-乙基己酸酯等合成酯油类;氨基改性聚硅氧烷、聚醚改性聚硅氧烷、烷基改性聚硅氧烷、氟改性聚硅氧烷等改性聚硅氧烷等未被分类在上述硅氧烷中的硅油等油剂类;月桂酸钠、棕榈酸钠等脂肪酸皂、十二烷基硫酸钾、烷基硫酸三乙醇胺醚等阴离子表面活性剂类;硬脂基三甲基氯化铵、苯扎氯铵、十二烷基氧化胺等阳离子表面活性剂类;2-椰油基-2-氢氧化咪唑啉-1-羧基乙氧基二钠盐(2-cocoyl-2-imidazoliniumhydroxide-1-carboxyethyloxy disodium salt)等咪唑啉系两性表面活性剂、烷基甜菜碱、酰胺甜菜碱、磺基甜菜碱等甜菜碱系表面活性剂、酰基甲基牛磺酸盐(acylmethyltaurine)等两性表面活性剂类;山梨醇单硬脂酸酯、山梨坦倍半油酸酯等山梨醇脂肪酸酯类、单硬脂酸甘油酯等甘油脂肪酸类、单硬脂酸丙二醇酯等丙二醇脂肪酸酯类、硬化蓖麻油衍生物、甘油烷基醚、POE山梨醇油酸酯(POE sorbitan monooleate)、聚氧乙烯山梨醇单硬脂酸酯等POE山梨醇脂肪酸酯类、POE-山梨醇单月桂酸酯等POE山梨醇脂肪酸酯类、POE-甘油单异硬脂酸酯等POE甘油脂肪酸酯类、聚乙二醇单油酸酯、POE二硬脂酸酯等POE脂肪酸酯类、POE2-辛基十二烷基醚等POE烷基醚类、POE壬基苯基醚等POE烷基苯基醚类、普朗尼克(Pluronic)型类、POE·POP2-癸基十四烷基醚等POE·POP烷基醚类、Tetronic类、POE蓖麻油、POE硬化蓖麻油等POE蓖麻油·硬化蓖麻油衍生物、蔗糖脂肪酸酯、烷基糖苷等非离子表面活性剂类;聚乙二醇、甘油、1,3-丁二醇、赤藓醇、山梨醇、木糖醇、麦芽糖醇、丙二醇、二丙二醇、二甘油、异戊二醇、1,2-戊二醇、2,4-己二醇、1,2-己二醇、1,2-辛二醇等多元醇类;吡咯烷酮羧酸钠、乳酸、乳酸钠等保湿成分类;可被表面处理的绢云母、云母、滑石、高岭土、合成云母、硫酸钡等粉体类;可被表面处理的氧化铁红、氧化铁黄、氧化铁黑、氧化钴、群青蓝、铁蓝(iron blue)、氧化钛、氧化锌等无机颜料类;可被表面处理的云母钛、鱼鳞箔(pearl essence)、氯氧化铋等珠光剂类;可被色淀化的红色202号、红色228号、红色226号、黄色4号、青色404号、黄色5号、红色505号、红色230号、红色223号、橙色201号、红色213号、黄色204号、黄色203号、青色1号、绿色201号、紫色201号、红色204号等有机色素类;聚乙烯粉末、聚甲基丙烯酸甲酯、尼龙粉末;对氨基苯甲酸系紫外线吸收剂;邻氨基苯甲酸系紫外线吸收剂;水杨酸系紫外线吸收剂;桂皮酸系紫外线吸收剂;二苯甲酮系紫外线吸收剂;糖系紫外线吸收剂;2-(2’-羟基-5’-t-辛基苯基)苯并三唑、4-甲氧基-4’-叔丁基二苯甲酰甲烷等紫外线吸收剂类;乙醇、异丙醇等低级醇类;维生素A或其衍生物、维生素B6盐酸盐、维生素B6三棕榈酸酯、维生素B6二辛酸酯、维生素B2或其衍生物、维生素B12、维生素B15或其衍生物等维生素B类;α-生育酚、β-生育酚、γ-生育酚、维生素E乙酸酯等维生素E类、维生素D类、维生素H、泛酸、泛硫乙胺、吡咯喹啉醌等维生素类等;苯氧基乙醇等抗菌剂等。
本发明的油胶剂型的皮肤外用剂可通过依照常规方法对所述必须成分、优选成分、任意成分等进行处理来制造出,例如,优选为,依照如下所述的顺序来进行制造。如此制造出的本发明的油胶剂型的皮肤外用剂可应用于包括医药部外品在内的化妆品、皮肤外用医药组合物、皮肤外用杂货等,但尤其优选为应用于化妆品。
除了硅油那样的油性成分以外,还可以使用球磨机、灰浆机等湿式粉碎手段并通过湿式粉碎方式来使由所述化学式(1)表示的化合物、其异构体及/或其药理学上可容许的盐均匀分散。可通过揉合该分散液以及部分交联型甲基聚硅氧烷(“KSG-16”(信越化学工业株式会社制))来制备出油胶剂型的皮肤外用剂。
此外,通过向其中添加具有相溶性的环甲硅脂(例如、“DC345”(道康宁东丽株式会社制)等,从而能够稀释均匀,并对硬度进行调节。在含有该环甲硅脂的情况下,优选为,相对于皮肤外用剂总量而含有20~60质量%。
并且在该情况下,部分交联型甲基聚硅氧烷的含量过少时结构变得过于松弛,因此,为了维持处方的稳定性,优选为,相对于由所述化学式(1)表示的化合物的油胶剂型的皮肤外用剂的含量0.01~10质量%而将部分交联型甲基聚硅氧烷的含量调节为5~25质量%。
实施例
以下,列举实施例来对本发明进行更详细地说明,当然,本发明并仅局限于所涉及的实施例。
<制造例1:本发明的比较用皮肤外用剂(乳化剂型)的制造方法>
依照下述的表1中所示的处方来制造乳化剂型的皮肤外用剂。即,分别将(A)、(B)的成分加热至70℃,在(B)中搅拌(A)的同时逐渐加入。搅拌至40℃的同时进行冷却,之后,逐渐添加(C)的成分并搅拌均匀。30℃下停止冷却、搅拌,从而获得乳化剂型的皮肤外用剂(乳化处方1)。
【表1】
表1
[实施例1]
<制造例2:本发明的油胶剂型的皮肤外用剂的制造方法1>
称取“有机硅KSG-16(信越化学工业株式会社)”60.0(g)以及“三异辛酸甘油酯(Glyceryl Triisooctanate)(Nomcort TIO)(日清奥利友株式会社)”5.0(g),并揉匀。向“KSK32”1.0(g)中加入“三异辛酸甘油酯”9.0(g),来制备通过粉碎机而粉碎了的KSK32分散液。向其中加入“聚甲基丙烯酸甲酯球状粉体(微球M330)(松本油脂制药株式会社)”20.0(g)、“绢云母(绢云母FSE、三信矿工株式会社)”5.0(g)并进行揉合,从而制造出油胶剂型处方。如此,便可获得油胶剂型的处方的皮肤外用剂(化妆品1)。
<比较制造例:本发明的皮肤外用剂(光泽制剂)的制造方法>
称取Rheopearl KL2(千叶制粉株式会社)10(g)、三异辛酸甘油酯(日清奥利友集团株式会社)40(g)以及Lusplan(日本精化株式会社)45(g),并在85℃下进行加热溶解。向“KSK32”0.5(g)中加入“三异辛酸甘油酯(日清奥利友集团株式会社)”4.5(g),并添加通过粉碎机而粉碎了的KSK32分散液,在搅拌混合的同时恢复至常温,从而获得光泽剂型的皮肤外用剂(比较例1)。
<试验例1:本发明的油胶剂型的皮肤外用剂的皮肤贮存性评价1>
关于按照所述的方法所制造出的比较用皮肤外用剂(乳化处方1)、油胶剂型的皮肤外用剂(化妆品1)以及比较例1(光泽制剂),对KSK32的皮肤贮存性进行评价。在弗兰茨(Franz)型扩散池中安放摘出人体皮肤(高加索人、50岁男性、背部皮肤),并用PBS填满接收侧。向供给侧添加根据上述内容所制备出的处方,并在37℃下放置24小时后,擦拭附着在皮肤表面上的残留处方后,用甲醇进行清洗。使用胶带将清洗后的皮肤上角层除去后,从用甲醇处理后的皮肤(除了角层以外的表皮以及真皮部分)提取KSK32,并利用HPLC(柱:反相系柱(3.0×100mm)、柱温:室温、流动相:阴离子系磺酸型表面活性剂水溶液/THF25%、pH;3、流速;0.4mL/min.、检测;240nm)来对皮肤内的贮存量进行计算。结果示于表2。在使用乳化处方1的情况下,未检测出KSK32。此外,在比较例1的光泽制剂中,可确认出KSK32的少许的贮存。另一方面,可确认出在油胶剂型的皮肤外用剂(化妆品1)中KSK32的皮肤内贮存,从而了解通过油胶剂型处方会提高皮肤贮存性。
【表2】
表2
[实施例2]
<制造例3:本发明的油胶剂型的皮肤外用剂的制造方法2>
称量“有机硅KSG-16(信越化学工业株式会社制)”65.0(g)以及“Nomcort TIO(日清奥利友株式会社)”15.0(g),并揉匀。向“KSK32”0.5(g)中加入“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中加入KSK32分散液、“微球M330(松本油脂制药株式会社)”15.0(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品2)。
[实施例3]
<制造例4:本发明的油胶剂型的皮肤外用剂的制造方法3>
称取“有机硅KSG-16(信越化学工业株式会社)”65.0(g)以及“Nomcort TIO(日清奥利友株式会社)”15.0(g)、“有机硅KF96-6(信越有机硅株式会社)”5.0(g),并揉匀。向“KSK32”0.5(g)中加入“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中加入KSK32分散液、“微球M330(松本油脂制药株式会社)”10.0(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品3)。
[实施例4]
<制造例5:本发明的油胶剂型的皮肤外用剂的制造方法4>
称取“有机硅KSG-16(信越化学工业株式会社)”65.0(g)以及“Nomcort TIO(日清奥利友株式会社)”15.0(g)、“有机硅KF96-6(信越化学工业株式会社制)”7.5(g),并揉匀。向“KSK32”0.5(g)中加入“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中加入KSK32分散液、“微球M330(松本油脂制药株式会社)”7.5(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品4)。
[实施例5]
<试验例2:本发明的油胶剂型的皮肤外用剂的皮肤贮存性评价2>
依照试验例1所述的方法来评价根据实施例3~5所述的方法所制造出的混入浓度不同的混入微球处方(化妆品2~化妆品4)的皮肤内贮存性。结果示于表3。
【表3】
表3
启示出增加油胶剂型的皮肤外用剂(化妆品2~4)处方中的微球M330含量,会提高KSK32的皮肤贮存性。
[实施例6]
<制造例6:本发明的油胶剂型的皮肤外用剂的制造方法5>
称取“有机硅KSG-16(信越化学工业株式会社)”75.0(g)以及“Nomcort TIO(日清奥利友(nisshin-oillio)株式会社)”5.0(g),并揉匀。向“KSK32”0.5(g)中加入“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中加入KSK32分散液、“微球M330(松本油脂制药株式会社)”15.0(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品5)。
[实施例7]
<制造例7:本发明的油胶剂型的皮肤外用剂的制造方法6>
称取“有机硅KSG-16(信越化学工业株式会社)”65.0(g)以及“Nomcort TIO(日清奥利友株式会社)”5.0(g),并揉匀。向“KSK32”0.5(g)中加入“DC345”(道康宁东丽株式会社)4.5(g),从而制备通过粉碎机而粉碎了的KSK32分散液。向“KSG-16以及Nomcort TIO”组合物中加入KSK32分散液、“微球M330(松本油脂制药株式会社)”25.0(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品6)。
[实施例8]
<试验例3:本发明的油胶剂型的皮肤外用剂的皮肤贮存性评价3>
按照试验例1所述的方法来评价依照实施例6以及7所述的方法所制造出的混入浓度不同的混入微球处方(化妆品5以及化妆品6)的皮肤内贮存性。结果示于表4。
【表4】
表4
根据表3以及表4的结果可知,作为球状粉体的含量,在15质量%附近存在阈值,作为球状粉体的含量,优选为12质量%以上,更优选为15质量%以上,进一步优选为20质量%以上,另一方面,优选为50质量%以下,更优选为45质量%以下,进一步优选为30质量%以下。
<制造例8:本发明的油胶剂型的皮肤外用剂的制造方法7>
对“有机硅KSG-16(信越化学株式会社)”71.0(g)以及“聚醚改性有机硅(有机硅KF-6017、信越化学株式会社)”2.4(g)、“DC345(道康宁东丽株式会社)”18.3(g)、“苯氧基乙醇(四日市合成株式会社)”0.4(g)、“乙醇(和光纯药工业株式会社)”5.9(g)、“KSK32”2(g)进行揉合,从而制造出未混入粉体油胶剂型的皮肤外用剂(未混入粉体的皮肤外用剂)。
[实施例9]
<制造例9:本发明的油胶剂型的皮肤外用剂的制造方法8>
对“有机硅KSG-16(信越有机硅株式会社制)”60.0(g)、“微球M330(松本油脂制药株式会社)”15.0(g)进行揉合。对“聚醚改性有机硅(有机硅KF-6017、信越化学株式会社)”2.0(g)、“DC345(道康宁东丽株式会社)”15.7(g)、“苯氧基乙醇(四日市合成株式会社)”0.3(g)、“乙醇(和光纯药工业株式会社)”5.0(g)、“KSK32”2.0(g)进行揉合,从而制造出含有“聚甲基丙烯酸甲酯球状粉体(微球M330、松本油脂制药株式会社)”的油胶剂型的皮肤外用剂(化妆品7)。
[实施例10]
<制造例10:本发明的油胶剂型的皮肤外用剂的制造方法9>
对“有机硅KSG-16(信越化学工业株式会社)”60.0(g)、“球状聚酰胺树脂(尼龙SP500、东邦株式会社)”15.0(g)进行揉合。对“有机硅KF-6017(信越化学株式会社)”2.0(g)、“DC345(道康宁东丽株式会社)”15.7(g)、“苯氧基乙醇(四日市合成株式会社)”0.3(g)、“乙醇(和光纯药工业株式会社)”5.0(g)、“KSK32”2.0(g)进行揉合,从而制造出含有球状聚酰胺树脂粉体的油胶剂型的皮肤外用剂(化妆品8)。
[实施例11]
<试验例4:本发明的油胶剂型的皮肤外用剂的皮肤贮存性评价4>
按照试验例1所述的方法来评价本发明的油胶剂型的皮肤外用剂(化妆品7以及化妆品8)的皮肤贮存性。结果示于表5。
【表5】
表5
任一有机球状粉体与未混入球状粉体进行比较,会显示出高皮肤内贮存。尤其表示微球M330高的皮肤贮存性。
<制造例11:本发明的油胶剂型的皮肤外用剂的制造方法10>
称取“有机硅KSG-16(信越化学工业株式会社)”80.0(g)以及“Nomcort TIO(日清奥利友株式会社)”15.0(g)并揉均。向“KSK32”0.5(g)中添加“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中添加KSK32分散液并进行揉合,从而制造出油胶剂型的皮肤外用剂(未混入粉体的皮肤外用剂)。
[实施例12]
<制造例12:本发明的油胶剂型的皮肤外用剂的制造方法11>
称取“有机硅KSG-16(信越化学工业株式会社)”65.0(g)以及“Nomcort TIO(日清奥利友株式会社)”15.0(g),并揉匀。向“KSK32”0.5(g)中添加“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中加入KSK32分散液、“聚甲基丙烯酸甲酯球状粉体(微球M330、松本油脂制药株式会社)”15.0(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品9)。
[实施例13]
<制造例13:本发明的油胶剂型的皮肤外用剂的制造方法12>
称取“有机硅KSG-16(信越化学工业株式会社)”65.0(g)以及“Nomcort TIO(日清奥利友株式会社)”15.0(g)并揉匀。向“KSK32”0.5(g)中加入“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中加入KSK32分散液、“绢云母(绢云母FSE、三信矿工株式会社)”15.0(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品10)。
[实施例14]
<试验例5:本发明的油胶剂型的皮肤外用剂的皮肤贮存性评价5>
关于依照制造例11、实施例11以及实施例12所述的方法所制造出的本发明的油胶剂型的皮肤外用剂(未混入粉体的皮肤外用剂、化妆品9以及10),依照试验例1所述的方法来对皮肤贮存性进行评价。结果示于表6。
依据上述方法来对根据上述内容所制备出的未混入粉体处方、混入微球处方、绢云母(硅酸盐矿物)混入处方的皮肤内贮存性进行试验并进行比较。
【表6】
表6
作为球状粉体的微球含有处方的化妆品9对比板状粉体的含有“绢云母”处方的化妆品10而显示出高皮肤内贮存量。
[实施例15]
<制造例14:本发明的油胶剂型的皮肤外用剂的制造方法13>
称取“有机硅KSG-16(信越化学工业株式会社)”65.0(g)以及“Nomcort TIO(日清奥利友株式会社)”15.0(g),并揉匀。向“KSK32”0.5(g)中加入“DC345(道康宁东丽株式会社)”4.5(g),来制备通过粉碎机而粉碎了的KSK32分散液。向KSG-16以及Nomcort TIO组合物中加入KSK32分散液、球状无水硅酸(“二氧化碳微珠P1500(触媒化成工业株式会社)”15.0(g)并进行揉合,从而制造出油胶剂型的皮肤外用剂(化妆品11)。
[实施例16]
<试验例5:本发明的油胶剂型的皮肤外用剂的皮肤贮存性评价5>
关于化妆品9、依照实施例15所制造出的本发明的油胶剂型的皮肤外用剂(化妆品11),依照试验例1所述的方法来对皮肤贮存性进行评价。结果示于表7。
【表7】
表7
作为球状无机粉体的代表例,对二氧化碳微珠混入的油胶剂型的皮肤外用剂(化妆品11)的皮肤贮存性进行评价时,与有机球状粉体进行比较而显示出低皮肤贮存性。
【产业上的可利用性】
本发明可应用于化妆品等皮肤外用剂。
Claims (7)
4.根据权利要求1至3中任一项所述的油胶剂型的皮肤外用剂,其特征在于,
还含有球状粉体。
5.根据权利要求4所述的油胶剂型的皮肤外用剂,其特征在于,
所述球状粉体为有机球状粉体。
6.根据权利要求4所述的油胶剂型的皮肤外用剂,其特征在于,
所述球状粉体为聚甲基丙烯酸甲酯。
7.根据权利要求4所述的油胶剂型的皮肤外用剂,其特征在于,
所述球状粉体相对于皮肤外用剂总量而含有12~50质量%。
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