CN117956976A - 非水系口腔用组合物 - Google Patents
非水系口腔用组合物 Download PDFInfo
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- CN117956976A CN117956976A CN202280062561.7A CN202280062561A CN117956976A CN 117956976 A CN117956976 A CN 117956976A CN 202280062561 A CN202280062561 A CN 202280062561A CN 117956976 A CN117956976 A CN 117956976A
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- oral composition
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- nonaqueous
- carboxamide
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Abstract
本发明的技术问题在于,在包含酶的非水系口腔用组合物中,抑制或缓和使用时的发涩感的产生。本发明提供一种非水系口腔用组合物,其包含:(A)成分:酶,和(B)成分:选自由N‑乙基‑对薄荷烷‑3‑甲酰胺、3‑L‑薄荷氧基‑1,2‑丙二醇、N‑(4‑氰基甲基苯基)‑对薄荷烷甲酰胺、(1R,2S,5R)‑5‑甲基‑2‑丙烷‑2‑基‑N‑(2‑吡啶‑2‑基乙基)环己烷‑1‑甲酰胺、3‑(对薄荷烷‑3‑甲酰胺)乙酸乙酯、2‑异丙基‑N,2,3‑三甲基丁酰胺、乳酸薄荷酯、琥珀酸单薄荷酯、异胡薄荷醇以及薄荷酮甘油缩酮组成的组中的至少一种冷感剂。
Description
技术领域
本发明涉及一种非水系口腔用组合物。
背景技术
作为洁齿剂的溶剂,通过使用非水溶剂代替水,能够对洁齿剂赋予溶剂的水合热引起的温感实感。在这样的非水系洁齿剂中进行配合具有牙垢的分解和去除功能的酶(例如专利文献1和2)。
在此,若在非水系洁齿剂中配合酶,则由于非水系特有的分散性差,有时在刷牙初期感觉到发涩感,有时使用感降低。为了消除这样的不利,配合有冷感剂。专利文献3中记载了通过在包含酶、阴离子表面活性剂的洁齿剂组合物中配合羟乙基纤维素二甲基二烯丙基铵盐和特定的香料组合物,能够改善酶的口腔内滞留性,抑制液体分离。专利文献4中记载了含有具有特定的数均分子量的聚乙烯吡咯烷酮、特定的二醇类以及酶的非水系牙膏。专利文献4中记载了可以包含葡萄糖氧化酶等酶、以及胡椒薄荷油、留兰香油等矫味矫臭剂。
现有技术文献
专利文献
专利文献1:日本专利第4723068号公报
专利文献2:日本专利第4803889号公报
专利文献3:日本特开2002-187829号公报
专利文献4:日本特表2013-512897号公报
发明内容
发明要解决的技术问题
然而,在专利文献3及4那样的现有技术中,难以充分抑制在配合酶时产生的发涩感。本发明的目的在于,在包含酶的非水系口腔用组合物中,实现抑制或缓和使用时的发涩感的产生。
用于解决技术问题的技术方案
本发明人等提供下述的〔1〕~〔8〕。
〔1〕一种非水系口腔用组合物,其含有:
(A)成分:酶,以及
(B)成分:选自由N-乙基-对薄荷烷-3-甲酰胺、3-L-薄荷氧基-1,2-丙二醇、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、(1R,2S,5R)-5-甲基-2-丙烷-2-基-N-(2-吡啶-2-基乙基)环己烷-1-甲酰胺、3-(对薄荷烷-3甲酰胺)乙酸乙酯、2-异丙基-N,2,3-三甲基丁酰胺、乳酸薄荷酯、琥珀酸单薄荷酯、异胡薄荷醇以及薄荷酮甘油缩酮组成的组中的至少一种冷感剂。
〔2〕根据〔1〕所述的非水系口腔用组合物,其中,非水系口腔用组合物还含有(C)成分:甘油脂肪酸酯。
〔3〕根据〔1〕或〔2〕所述的非水系口腔用组合物,其中,(B)成分的含量为0.0001质量%~0.3质量%。
〔4〕根据〔1〕~〔3〕中任一项所述的非水系口腔用组合物,其中,(A)成分包含选自由葡聚糖酶(glucanase)、加氧酶以及蛋白酶组成的组中的至少一种。
〔5〕根据〔4〕所述的非水系口腔用组合物,其中,非水系口腔用组合物至少满足以下条件中的至少任一项:
葡聚糖酶为α-1,6-葡聚糖酶(dextranase)或变聚糖酶(mutanase);
加氧酶为漆酶、乳过氧化物酶或葡萄糖氧化酶;以及
蛋白酶为木瓜蛋白酶、猕猴桃蛋白酶、菠萝蛋白酶或纳豆激酶。
〔6〕根据〔1〕~〔5〕中任一项所述的非水系口腔用组合物,其中,还含有(D)成分:选自由聚乙二醇、甘油、二甘油、丙二醇以及聚丙二醇组成的组中的至少一种多元醇。
〔7〕根据〔1〕~〔6〕中任一项所述的非水系口腔用组合物,其中,(A)成分的酶的酶效价相对于(B)成分的含量的比率(A/B比)为6000单位/g~200000000单位/g。
〔8〕根据〔1〕~〔7〕中任一项所述的非水系口腔用组合物,其中,所述非水系口腔用组合物为洁齿剂、漱口剂、口腔喷雾、口腔用保湿凝胶、乳膏或乳膏口腔喷雾。
发明效果
根据本发明,提供一种非水系口腔用组合物,其尽管含有酶,也能够抑制或缓和使用时的发涩感的产生。
具体实施方式
〔1.口腔用组合物〕
组合物包含下述的(A)以及(B)成分,优选还包含(C)成分。
〔(A)成分:酶〕
(A)成分为酶。
酶通常为水解酶(hydrolase)、氧化还原酶(加氧酶oxygenase),其中,优选为与在口腔内进行抑制、预防龋齿相关的酶(例如,牙垢的分解、导致口臭的成分分解、色斑的去除)相关的酶。作为这样的水解酶,例如可举出葡聚糖酶以及蛋白酶。
-葡聚糖酶-
葡聚糖酶是催化葡聚糖的糖苷键的水解的酶。作为葡聚糖酶的底物的葡聚糖是具有D-葡萄糖通过糖苷键(例如,α-1,3键、α-1,4键、α-1,6键、β-1,3键、β-1,4键、β-1,6键)连接的结构的聚合物(二糖类以上的多糖类)。作为葡聚糖,例如可举出:α-葡聚糖(例如,葡聚糖、变聚糖、普鲁兰多糖、支链淀粉、糖原、直链淀粉)、β-葡聚糖(例如,纤维素、昆布多糖、凝胶多糖、愈创葡聚糖)。葡聚糖酶优选为分解α-1,3键、α-1,6键或者α-1,3键以及α-1,6键的葡聚糖酶,更优选为α-1,6-葡聚糖酶、变聚糖酶。由此,能够分解变形链球菌(Streptococcus mutans)生成的葡聚糖,实现口腔内牙垢的分解及去除。葡聚糖酶的来源没有特别限定,可以是微生物、植物、动物等天然来源,也可以是基因重组、化学合成等人工制备的物质。在葡聚糖酶为α-1,6-葡聚糖酶的情况下,也可以是来自于具有生成α-1,6-葡聚糖酶的能力的细菌(例如,毛壳菌属、青霉属、曲霉属、穗霉(Spicaria)属、乳酸杆菌属、纤维弧菌属细菌)的α-1,6-葡聚糖酶。葡聚糖酶可以单独使用一种或组合使用两种以上。
-蛋白酶-
蛋白酶是催化蛋白质的肽键水解的酶。蛋白酶可以为肽链内切酶以及肽链端解酶(氨肽酶、羧肽酶)中的任一种,优选为肽链内切酶。作为内切蛋白酶,例如可举出:木瓜蛋白酶、菠萝蛋白酶、猕猴桃蛋白酶等半胱氨酸蛋白酶,纳豆激酶等丝氨酸蛋白酶;优选为半胱氨酸蛋白酶,更优选为木瓜蛋白酶。木瓜蛋白酶的每单位质量的活性高,能够以较少的量发挥口腔生物膜去除效果。蛋白酶的来源没有特别限定,可以是微生物、植物、动物等天然来源,也可以是基因重组、化学合成等人工制备的物质。在为天然来源的情况下,纯度没有特别限定,可以包含蛋白酶以外的成分(例如,植物提取物)。在蛋白酶为半胱氨酸蛋白酶的情况下,优选来自于番木瓜、菠萝、猕猴桃等植物,但并不限定于这些,也可以来自于曲霉属(Aspergillus属)、芽孢杆菌属(Bacillus属)等微生物。蛋白酶可以单独使用一种或组合使用两种以上。
-氧化还原酶(加氧酶oxygenase)-
加氧酶是催化氧化还原的酶。作为加氧酶,例如可举出多酚氧化酶、葡萄糖氧化酶、乳过氧化物酶,优选为多酚氧化酶。多酚氧化酶是将邻苯二酚、酪氨酸、绿原酸、多巴、邻苯三酚等酚系化合物氧化的氧化酶。作为多酚氧化酶,例如可举出漆酶、儿茶酚氧化酶、单酚氧化酶,优选为漆酶。加氧酶的来源没有特别限定,可以是微生物、植物、动物等天然来源,也可以是基因重组、化学合成等人工制备的物质。在为天然来源的情况下,纯度没有特别限定,可以包含加氧酶以外的成分(例如,植物提取物)。在加氧酶为多酚氧化酶的情况下,优选来自于白腐菌(例如,栓菌属(Trametes)细菌)。加氧酶可以单独使用一种或组合使用两种以上。
-(A)成分的酶效价-
(A)成分的酶效价(在为两种以上的酶的组合的情况下,各种酶的酶效价)优选为2单位/g以上,更优选为10单位/g以上。由此,能够更有效率地分解和去除牙垢。上限优选为200单位/g以下,更优选为50单位/g以下。由此,能够抑制使用时的发涩感的产生。因此,优选为2单位/g~200单位/g,更优选为10单位/g~50单位/g。
在酶效价中,1单位是指,基于1964年国际生物化学联合会的“国际单位”的定义,“在最佳条件下,在1L试样中,温度30℃下1分钟能够使1μmol的底物变化的酶量”(参照https://www.jslm.org/committees/standard/standard_Q&A.pdf)。
〔(B)成分:冷感剂〕
(B)成分是冷感剂。(B)成分例如为N-乙基-对薄荷烷-3-甲酰胺、乳酸薄荷酯、琥珀酸单薄荷酯、异胡薄荷醇、薄荷酮甘油缩酮、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、3-L-薄荷氧基-1,2-丙二醇、5-甲基-2-丙烷-2-基-N-(2-吡啶-2-基乙基)环己烷-1-甲酰胺、3-(对薄荷烷-3-甲酰胺)乙酸乙酯、2-异丙基-N,2,3-三甲基丁酰胺、选自它们中的两种以上的组合。其中,优选为N-乙基-对薄荷烷-3-甲酰胺、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、3-L-薄荷氧基-1,2-丙二醇、5-甲基-2-丙烷-2-基-N-(2-吡啶-2-基乙基)环己烷-1-甲酰胺以及3-(对薄荷烷-3-甲酰胺)乙酸乙酯。
-(B)成分的含量-
相对于组合物总量,(B)成分的含量优选为0.0001质量%以上,更优选为0.001质量%以上,进一步优选为0.01质量%以上。由此,能够抑制使用时的发涩感的产生,能够实现良好的使用感。上限优选为0.3质量%以下,更优选为0.2质量%以下。由此,能够抑制苦味,实现良好的使用感。因此,(B)成分的含量优选为0.0001质量%~0.3质量%,更优选为0.001质量%~0.3质量%,进一步优选为0.01质量%~0.2质量%。
〔A/B比〕
(A)及(B)成分的含量的比率(A/B比)能够用(A)成分的酶效价相对于(B)成分的含量的比率(单位/g)表示,优选为6000单位/g以上,更优选为10000单位/g以上,上限优选为200000000单位/g以下,更优选为500000单位/g以下。因此,A/B比优选为6000单位/g~200000000单位/g,更优选为10000单位/g~500000单位/g。由此,能够适当地调整(A)成分的含量,能够改善使用时的发涩感。
〔(C)成分:甘油脂肪酸酯〕
(C)成分为甘油脂肪酸酯。甘油脂肪酸酯可以是单酯、二酯以及三酯中的任一种,优选为甘油脂肪酸三酯(脂肪酸甘油三酯)。来自于脂肪酸的部分的碳原子数优选为4~22,更优选为6~16,进一步优选为6~12,更进一步优选为8~10。脂肪酸可以为不饱和以及饱和脂肪酸中的任一种,可以为支链脂肪酸、直链脂肪酸,例如可举出己酸、辛酸、癸酸、月桂酸、肉豆蔻酸、棕榈酸、油酸、亚油酸。构成甘油脂肪酸二酯及三酯的脂肪酸成分可以各自不同,也可以三种通用。甘油脂肪酸酯可以以单体添加到制剂中,也可以作为香料中的成分存在。(C)成分可以为单独一种或两种以上的组合。
-(C)成分的含量-
相对于组合物总量,(C)成分的含量优选为0.001质量%以上,更优选为0.01质量%以上。由此,能够抑制使用时发涩感的产生。上限优选为3%以下,更优选为2%以下。由此,能够抑制变色等品质降低。因此,(C)成分的含量优选为0.001质量%~3质量%,更优选为0.01质量%~2质量%。
〔(D)成分:多元醇〕
(D)成分为多元醇。(D)成分为非水系口腔用组合物中的溶剂的定位。多元醇通常为在与水接触时产生水合热的25℃下为液体的多元醇。作为这样的多元醇,例如为聚乙二醇、甘油、二甘油、丙二醇、聚丙二醇、它们的两种以上的组合,优选为聚乙二醇、甘油、二甘油、丙二醇,更优选为甘油、聚乙二醇、丁二醇。由此,能够使温感实感的提升变好,提高口腔内的脱脂感。
-甘油-
多元醇通常具有苦味,但甘油的苦味较少。因此,通过(D)成分至少包含甘油,能够抑制组合物的苦味。相对于(D)成分整体,甘油的含量优选为20质量%以上,更优选为50质量%以上。由此,组合物的外观变得良好,能够调整为适度的粘度。上限为100质量%以下即可,优选为85质量%以下,更优选为80质量%以下。由此,能够抑制来自于(D)成分的苦味。因此,相对于(D)成分整体,甘油的含量优选为20质量%~100质量%,更优选为50质量%~85质量%,进一步优选为50质量%~80质量%。
-聚乙二醇的平均分子量-
聚乙二醇的平均分子量(准医药品原料规格2006记载的平均分子量,以下同样)优选为190~630。由于上述平均分子量的聚乙二醇较强地有助于温感实感,因此能够提高温感实感的强度。作为这样的聚乙二醇,例如可举出聚乙二醇200(平均分子量190~210)、聚乙二醇400(平均分子量380~420)、聚乙二醇600(平均分子量570~630)。
-聚乙二醇的含量-
相对于组合物总量,聚乙二醇(优选为平均分子量190~630的聚乙二醇)的含量优选为10质量%以上,更优选为15质量%以上。由此,能够抑制由来自于聚乙二醇的苦味导致的对使用感的影响。上限优选为30质量%以下。因此,优选为10质量%以上,更优选为15质量%~30质量%。
-(D)成分的优选方式-
作为(D)成分的优选方式,可举出以下方式:
(1)甘油及平均分子量190~630的聚乙二醇的并用体系;以及
(2)甘油、平均分子量190~630的聚乙二醇及丁二醇的并用体系。
其中,优选为(1),更优选为(1)中甘油的含量为成分(D)总量的50%以上、优选为50%~85%的方式。
-(D)成分的含量-
相对于组合物总量,(D)成分的含量通常为20质量%以上,优选为40质量%以上。由此,能够抑制组合物的外观的劣化。相对于组合物的总量,上限通常为90质量%以下,优选为85质量%以下,更优选为80质量%以下。由此,能够抑制粘度的过度降低,保持良好的使用感。因此,(D)成分的含量通常为20质量%~90质量%,优选为20质量%~85质量%,更优选为40质量%~80质量%。
〔非水系〕
组合物为非水系口腔用组合物。本说明书中,非水系是指实质上不含水分,在口腔用组合物的制造工序中,优选为不有意地加入水、仅包含原料中的水。非水系口腔用组合物中的水分量通常为2质量%以下,优选为1质量%以下,更优选为0.5质量%以下。口腔用组合物的水分量能够以配合前的原料中所包含的水分量的合计相对于全部原料的比例(质量%)的形式、或者以口腔用组合物的干燥后重量与干燥前重量之差相对于干燥前重量的比例(质量%)的形式算出。
〔粘度〕
组合物的粘度(25℃)优选为20Pa·s~100Pa·s,更优选为30Pa·s~90Pa·s,进一步优选为35Pa·s~80Pa·s,进一步更优选为35Pa·s~70Pa·s,尤其优选为40Pa·s~60Pa·s。粘度是使用东机产业株式会社株式会社(型号:VISCOMETER TVB-10)、转子No.6或7,在转速20rpm、测定时间3分钟、25℃的条件下测定时的测定值。
〔任意成分〕
在不损害本发明的效果的范围内,组合物可以含有(A)~(D)成分以外的其他成分。作为其他成分,例如可举出:表面活性剂、甜味剂、香料、湿润剂、粘结剂、研磨剂、pH调节剂、防腐剂、药用成分、油性成分、着色剂(色素)等能够配合于口腔用组合物的成分,但不限定于这些。
-表面活性剂-
作为表面活性剂,例如可举出阴离子表面活性剂、两性表面活性剂、非离子表面活性剂,为了能够进一步改善温感的提升,优选为阴离子表面活性剂、两性表面活性剂,更优选为阴离子表面活性剂。
作为阴离子表面活性剂,例如可举出烷基硫酸盐、酰基氨基酸盐、酰基牛磺酸盐、α-烯烃磺酸盐、氢化椰油脂肪酸单甘油酯单硫酸盐、月桂基磺基乙酸盐。烷基、酰基可以是直链以及支链中的任一种,可以是饱和以及不饱和中的任一种,其碳原子数通常为10~20,优选为12~18,更优选为14~16。盐能够从药理学上允许的盐中选择。作为药理学上允许的盐,例如可举出碱加成盐和氨基酸盐。作为其具体例,可举出钠盐、钾盐、钙盐、镁盐、铵盐等无机碱盐;三乙基铵盐、三乙醇铵盐、吡啶鎓盐、二异丙基铵盐等有机碱盐;精氨酸盐等碱性氨基酸盐。其中,优选无机碱盐,更优选碱金属盐(例如,钠盐、钾盐)或铵盐,进一步优选钠盐。
作为烷基硫酸盐,例如可举出月桂基硫酸盐、肉豆蔻酰基硫酸盐。作为酰基氨基酸盐,例如可举出:月桂酰基肌氨酸盐、肉豆蔻酰基肌氨酸盐等酰基肌氨酸盐;月桂酰基谷氨酸盐、肉豆蔻酰基谷氨酸盐、棕榈酰基谷氨酸盐等酰基谷氨酸盐;N-月桂酰基-N-甲基甘氨酸盐、椰油酰基甘氨酸盐等酰基甘氨酸盐;N-月桂酰基-β-丙氨酸盐、N-肉豆蔻酰基-β-丙氨酸盐、N-椰油酰基-β-丙氨酸盐、N-月桂酰基-N-甲基-β-丙氨酸盐、N-肉豆蔻酰基-N-甲基-β-丙氨酸盐、N-甲基-N-酰基丙氨酸盐等酰基丙氨酸盐;月桂酰基天冬氨酸盐等酰基天冬氨酸盐。作为酰基牛磺酸盐,例如可举出:月桂酰甲基牛磺酸盐、N-甲基-N-酰基牛磺酸盐、N-椰油酰甲基牛磺酸盐。作为α-烯烃磺酸盐,可举出C14~16烯基磺酸盐(碳原子数14~16的α-烯烃磺酸)(日文:テトラデセンスルホン酸塩)等碳原子数12~18的α-烯烃磺酸盐。作为阴离子表面活性剂的其他例子,可举出氢化椰油脂肪酸单甘油酯单硫酸钠、月桂醇磺基乙酸酯钠。
作为阴离子表面活性剂,优选为α-烯烃磺酸盐,更优选为C14~16烯基磺酸盐(碳原子数14~16的α-烯烃磺酸)。阴离子表面活性剂可以是一种,也可以是两种以上的组合。
包含阴离子表面活性剂情况下的含量优选为组合物整体的0.1质量%以上,更优选为0.5质量%以上。由此,使用时制剂在口腔内的分散性得到改善,温感实感的提升变得良好。上限优选为3质量%以下,更优选为2质量%以下。由此,能够降低使用后的口腔内的脱脂感。因此,优选为组合物整体的0.1质量%~3质量%,更优选为0.5质量%~2质量%。
作为两性表面活性剂,例如可举出甜菜碱型、氨基酸型,优选为甜菜碱型。作为甜菜碱型两性表面活性剂,例如可举出:脂肪酸酰胺丙基甜菜碱(例如,椰油脂肪酸酰胺丙基甜菜碱)、烷基乙酸甜菜碱(例如,月桂基二甲基氨基乙酸甜菜碱等烷基氨基乙酸甜菜碱)、烷基咪唑啉甜菜碱(例如,烷基羧甲基羟乙基咪唑啉甜菜碱),优选为脂肪酸酰胺丙基甜菜碱、烷基乙酸甜菜碱,更优选为椰油脂肪酸酰胺丙基甜菜碱。在两性表面活性剂具有烷基、酰基的情况下,它们可以是直链以及支链的任一种,可以是饱和以及不饱和的任一种,其碳原子数通常为10~20,优选为12~18,更优选为14~16。两性表面活性剂优选为纯组分(甜菜碱纯组分)65%以上的溶液或粉末。由此,组合物的水分的调整变得容易。
作为两性表面活性剂,优选为脂肪酸酰胺烷基甜菜碱,更优选为椰油脂肪酸酰胺丙基甜菜碱等脂肪酸酰胺丙基甜菜碱。两性表面活性剂可以是一种,也可以是两种以上的组合。
包含两性表面活性剂情况下的含量优选为组合物整体的0.1质量%以上,更优选为0.3质量%以上。由此,口腔内的脱脂感充分改善,并且提高温感实感的提升。上限优选为3质量%以下,更优选为2质量%以下。由此,苦味得到抑制,能够充分维持味道的好的使用感。因此,优选为0.1质量%~3质量%,更优选为0.3质量%~2质量%。
作为非离子表面活性剂,例如可举出:聚氧乙烯烷基醚、聚氧乙烯氢化蓖麻油、山梨糖醇酐脂肪酸酯、聚氧乙烯山梨糖醇酐脂肪酸酯(例如,聚氧乙烯山梨糖醇酐单硬脂酸酯)、烷醇酰胺、聚氧乙烯脂肪酸酯、聚氧乙烯烯基醚、甘油脂肪酸酯、蔗糖脂肪酸酯(例如,麦芽糖脂肪酸酯)、糖醇脂肪酸酯(例如,麦芽糖醇脂肪酸酯、乳糖醇脂肪酸酯)、脂肪酸二乙醇酰胺(例如,月桂酸单或二乙醇酰胺)、聚氧乙烯聚氧丙烯共聚物、聚氧乙烯聚氧丙烯脂肪酸酯、聚氧乙烯聚氧丙烯(EOPO)共聚物、烷基葡糖苷、脂肪酸聚甘油酯。聚氧乙烯烷基醚的烷基的碳原子数通常为12~18,优选为14~18(例如,月桂基、硬脂基),环氧乙烷平均加成摩尔数通常为5摩尔~30摩尔,优选为15摩尔~30摩尔。聚氧乙烯氢化蓖麻油的环氧乙烷平均加成摩尔数通常为5摩尔~100摩尔,优选为20摩尔~100摩尔,更优选为20摩尔~60摩尔。山梨糖醇酐脂肪酸酯的脂肪酸的碳原子数通常为12~18。聚氧乙烯山梨糖醇酐脂肪酸酯的脂肪酸的碳原子数通常为16~18,环氧乙烷平均加成摩尔数通常为10摩尔~40摩尔。烷醇酰胺的烷基链的碳原子数通常为12~14。聚氧乙烯聚氧丙烯(EOPO)共聚物优选为环氧乙烷的平均加成摩尔数为20~210、环氧丙烷的平均加成摩尔数为15~60,可以为嵌段共聚物也可以为无规共聚物。
包含非离子表面活性剂情况下的含量优选为组合物整体的0.05质量%以上,更优选为0.5质量%以上。由此,改善口腔内的脱脂感变得良好。上限优选为2质量%以下,更优选为1质量%以下。由此,能够抑制苦味,能够充分维持味道的好的使用感。因此,优选为0.05质量%~2质量%,更优选为0.5质量%~1质量%。
-甜味剂-
作为甜味剂,例如可举出木糖醇、赤藓糖醇、麦芽糖醇、糖精、糖精钠、阿斯巴甜、甜菊糖、甜叶菊提取物、对甲氧基肉桂醛、新橙皮苷二氢查耳酮、紫苏葶、甘草酸苷(glycyrrhizin)、奇异果甜蛋白、天冬氨酰苯基丙氨酸甲酯、对甲氧基肉桂醛。甜味剂可以单独使用一种,也可以组合使用两种以上。
-香料-
香料例如可举出:胡椒薄荷油(peppermint oil)、留兰香油、茴香油、桉树油、冬青油、肉桂油、丁香油、百里香油、鼠尾草油、柠檬油、橙油、亚洲薄荷油、小豆蔻油、芫荽油、柑橘油,酸橙油、薰衣草油、迷迭香油、月桂油、洋甘菊油、葛缕子油、马郁兰油、月桂叶油、柠檬草油、牛至油、松针油、橙花油、玫瑰油、茉莉油、鸢尾油,薄荷纯油、玫瑰纯油、橙花油等天然香料、以及将这些天然香料加工处理(例如,预蒸馏部切割、后蒸馏部切割、分馏、液液萃取、精馏化、香料粉末化等)而得到的香料,以及薄荷醇,香芹酮、茴香脑、桉树脑、水杨酸甲酯、肉桂醛、丁子香酚、麝香草酚、芳樟醇、乙酸芳樟酯、柠檬烯、薄荷酮、乳酸薄荷酯、N-取代-对薄荷烷-3-甲酰胺、蒎烯、辛醛、柠檬醛、长叶薄荷酮(pulegone)、乙酸香芹酯、茴香醛、乙酸乙酯、丁酸乙酯、环己烷丙酸烯丙酯、邻氨基苯甲酸甲酯、甲基苯基缩水甘油酸乙酯,香草醛、十一烷酸内酯、己醛、丙醇、丁醇、异戊醇、己烯醇、二甲基硫醚、环甘素、糠醛、三甲基吡嗪、乳酸乙酯、乳酸甲酯,硫代乙酸乙酯等单品香料、还有草莓香精、苹果香精、香蕉香精、菠萝香精、葡萄香精、芒果香精、黄油香精、牛奶香精,水果混合香精、热带水果香精等调和香料等,能够使用用于口腔用组合物的公知的香料原材料。香料可以单独使用一种,也可以组合使用两种以上。
上述香料原材料在组合物中优选使用0.000001质量%~1质量%,使用了上述香料原材料的赋香用香料在组合物中可以使用0.1质量%~2.0质量%。
-湿润剂-
作为湿润剂,优选为作为(D)成分而例示的多元醇以外的多元醇,例如可举出:山梨糖醇(山梨醇)等糖醇;乙二醇等二元醇;还原淀粉糖化物。湿润剂可以为一种,也可以为两种以上的组合。平均分子量是准医药品原料规格2006记载的平均分子量。
湿润剂的含量通常为0质量%~20质量%,优选为1质量%~10质量%。
-粘结剂-
粘结剂例如可使用水溶性高分子等有机粘结剂、无机粘结剂。作为有机粘结剂,例如可举出纤维素系粘结剂(例如,羧甲基纤维素(CMC)、其钠盐、羟乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、甲基纤维素、阳离子化纤维素)、其他多糖系粘结剂(例如,黄原胶、瓜尔胶、结冷胶、黄蓍胶、刺梧桐胶、阿拉伯胶、刺槐豆胶、卡拉胶、海藻酸钠)、合成水溶性高分子(例如,(交联型)聚丙烯酸钠、羧基乙烯基聚合物、聚乙烯醇、海藻酸丙二醇酯)。关于无机粘结剂,例如可举出:沉降性二氧化硅、火成性二氧化硅、凝胶性二氧化硅、凝胶性铝二氧化硅等增稠性二氧化硅、蜂胶、蒙脱土、膨润土等粘土矿物,优选为有机粘结剂,更优选为纤维素系粘结剂、其他多糖系粘结剂、合成水溶性高分子,进一步优选为羧甲基纤维素钠、卡拉胶、羧基乙烯基聚合物。粘结剂可以是一种,也可以是两种以上的组合。
粘结剂的含量优选为组合物整体的0.1质量%~3质量%,更优选为0.1质量%~2质量%。
-研磨剂-
作为研磨剂,例如可以是无机研磨剂以及有机研磨剂中的任一种。作为无机研磨剂,例如可举出:硅酸铝、硅酸锆、结晶性硅酸锆、钛结合性二氧化硅等研磨性二氧化硅;磷酸氢钙·2水合盐或非水合物、磷酸二氢钙、磷酸三钙、焦磷酸钙等磷酸钙系化合物;碳酸钙等碳酸钙系研磨剂;氢氧化钙、硫酸钙等碳酸/磷酸以外的钙系研磨剂;氧化铝(aluminiumoxide)、氢氧化铝、氧化铝(alumina)等铝系材料;无水硅酸、沸石、硅酸锆等硅酸系材料;碳酸镁、磷酸三镁等镁系材料;羟基磷灰石、氟磷灰石、钙缺损磷灰石等磷灰石系材料;二氧化钛、云母钛、氧化钛等钛系材料;膨润土等矿物。作为有机研磨剂,例如可举出聚甲基丙烯酸甲酯、合成树脂系研磨剂。其中,优选为研磨性二氧化硅、磷酸钙系化合物,更优选为研磨性二氧化硅。研磨剂可以是一种,也可以是两种以上的组合。
研磨剂的配合量通常为组合物整体的0质量%~70质量%,优选为2质量%~30质量%。
-pH调节剂-
作为pH调节剂,例如可举出:邻苯二甲酸、柠檬酸、琥珀酸、乙酸、富马酸、苹果酸、乳酸等有机酸或它们的盐;磷酸(正磷酸)等无机酸或它们的盐(例如,钾盐、钠盐及铵盐);氢氧化钠、氢氧化钾等氢氧化物。作为无机酸盐,例如可举出磷酸氢二钠、磷酸二氢钠。pH调节剂的含量通常为使添加后的组合物的pH成为5~9的量、优选为成为6~8.5的量。本说明书中,pH值通常是从测定开始起25℃、3分钟后的值,可以使用东亚电波工业公司制造的pH计(型号Hm-30S)进行测定。
-防腐剂-
作为防腐剂,例如可举出:对羟基苯甲酸酯(例如,对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯)、苯甲酸钠。防腐剂可以单独使用一种,也可以组合使用两种以上。
-药用成分-
作为药用成分,例如可举出:非离子型杀菌剂(例如,异丙基甲基苯酚)、阳离子型杀菌剂(例如,氯化十六烷基吡啶、苄索氯铵、苯扎氯铵)、葡萄糖酸锌、柠檬酸锌、三氯生、扁柏酚、氯化溶菌酶、氯己定盐类、三氯二苯脲等杀菌或抗菌剂;氟化钠、单氟磷酸钠、氟化锡等氟化物;ε-氨基己酸、尿囊素类(例如,尿囊素、尿囊素碱式氯化铝)、氨甲环酸、薁、二氢胆固醇、α-红没药醇、甘草酸苷、甘草次酸、小檗碱、表二氢胆甾醇(Epidihydrocholesterin)等抗炎症剂;锌、铜盐、锡盐等金属盐;正磷酸的钾盐、钠盐等水溶性磷酸化合物;磷酸甘油等螯合性磷酸化合物;缩合磷酸盐、乙烷羟基二磷酸酯等牙结石预防剂、维生素E(例如,DL-α-生育酚乙酸酯等生育酚乙酸酯)等血流促进剂;硝酸钾、乳酸铝、氯化锶等知觉过敏抑制剂;羟乙基纤维素二甲基二烯丙基氯化铵等涂布剂;维生素C(例如,抗坏血酸或其盐)、氯化钠等收敛剂;叶绿素铜、葡萄糖酸铜等铜化合物;牙结石预防剂、丙氨酸、甘氨酸、脯氨酸等氨基酸类;当归软提取物、黄柏提取物,洋甘菊、丁香、迷迭香、黄芩、红花、百里香、黄芩、丁香、北美金缕梅等植物提取物;海狗肽(Caropeptide)、聚乙烯吡咯烷酮、羟肟酸及其衍生物、三聚磷酸盐、甲氧基乙烯马来酸酐共聚物、氯化钠、叶绿素、血根碱提取物、小檗碱、羟肟酸及其衍生物、焦磷酸盐、沸石、表二氢胆甾醇、三氯二苯脲、柠檬酸锌。药用成分可以单独使用一种,也可以组合使用两种以上。上述药用成分的含量可以在不妨碍本发明的效果的范围内按照常规方法适当设定有效量。
-油性成分-
作为油性成分,例如可举出:角鲨烷、液体石蜡、凡士林、微晶蜡、巴西棕榈蜡、米糠蜡、松香等烃类;高级醇(例如,月桂醇、鲸蜡醇、鲸蜡硬脂醇(Cetostearyl alcohol)、油醇、异硬脂醇等碳原子数8~22的醇);高级脂肪酸(例如,月桂酸、肉豆蔻酸、油酸、异硬脂酸等碳原子数8~22的脂肪酸)、橄榄油、蓖麻油、椰油等植物油;肉豆蔻酸异丙酯等脂肪酸酯。
-着色剂-
作为着色剂,例如可举出:红花红色素、栀子黄色素、栀子蓝色素、紫苏色素、红曲色素、红甘蓝色素、胡萝卜色素、木槿(Hibiscus)色素、可可色素、螺旋藻蓝色素、罗望子色素等天然色素,红色2号、红色3号、红色104号、红色105号、红色106号、红色227号、黄色4号、黄色5号、绿色3号、蓝色1号、蓝色4号等法定色素,核黄素,叶绿素铜钠。
非水系口腔用组合物包含着色剂时,相对于非水系口腔用组合物的整体,其含量优选为0.00001质量%~3质量%。
组合物可以用作牙膏,凝胶状洁齿剂、液状洁齿剂、液体洁齿剂、粉洁齿剂等洁齿剂,口腔用保湿凝胶、口腔用乳膏等口腔用涂布剂,口腔喷雾,漱口剂;优选为牙膏。
组合物的剂型能够根据利用方式适当选择,没有特别限定。作为剂型,例如可举出凝胶状、糊状、液状。
〔2.组合物的制造方法〕
组合物的制造方法没有特别限定,能够根据剂型通过各种通常的方法制备得到。例如在用作牙膏的情况下,可举出如下方法:在制备溶解于溶剂的成分后,混合除此以外的不溶性成分,根据需要进行脱泡(例如,减压)。所得到的牙膏可以容纳于容器中而制成产品。容器的形状和材质没有特别限制,能够使用通常的牙膏组合物中使用的容器,例如可举出聚乙烯、聚丙烯、聚对苯二甲酸乙二醇酯、尼龙等塑料容器。
实施例
以下,示出实施例及比较例对本发明进行具体说明,但本发明并不限于下述实施例。需要说明的是,表中的%只要没有特别说明则表示质量%。
[实施例及比较例中使用的主要原料]
(A-1)α-1,6-葡聚糖酶:第一三共PROPHARMA公司制造,13000单位(unit)/g
(A-2)漆酶:天野酶公司制造,“Laccase DAIWA”(来自于白腐菌(Trametes sp.))
(A-3)木瓜蛋白酶:三菱化学食品公司制造,“精制木瓜蛋白酶”
(A-4)变聚糖酶:天野酶株式会社株式会社制造,“变聚糖酶”
(A-5)乳过氧化物酶:Sigma-Aldrich公司制造,“乳过氧化物酶来自于牛奶”
(A-6)葡萄糖氧化酶:Sigma-Aldrich公司制造,“葡萄糖氧化酶来自于黑曲霉”
(A-7)猕猴桃蛋白酶:BHN株式会社制造,“Zyactinase(注册商标)”
(A-8)菠萝蛋白酶:联合酒精株式会社制造,“菠萝蛋白酶”
(A-9)纳豆激酶:株式会社日本生物科学研究所制造,“纳豆菌培养提取物NSK-SD”
(B-1)N-乙基-对薄荷烷-3-甲酰胺:Givaudan公司制造,“WS-3”
(B-2)N-(4-氰基甲基苯基)-对薄荷烷甲酰胺:Givaudan公司制造,“EVERCOOL(注册商标)G-180”
(B-3)3-L-薄荷氧基-1,2-丙二醇:高砂香料工业株式会社制造,“CA-10”
(C)脂肪酸甘油三酯:不二制油株式会社,“中链脂肪酸甘油三酯”
(D-1)浓甘油:阪本药品工业株式会社制造,“化妆品用浓甘油(99.5%)”
(D-2)聚乙二醇400:三洋化成工业株式会社制造,“聚乙二醇400”
CMC(羧甲基纤维素钠):Daicel Fine Chem株式会社制造,“CMC1260”
SDS(十二烷基硫酸钠):富士胶片和光纯药株式会社制造,“十二烷基硫酸钠”
二氧化硅:Solvay公司制造,“Tixosil(注册商标)73”
关于其他成分,使用符合准医药品原料规格2006的成分。
实施例1~35以及比较例1~2(牙膏)
根据下述制备方法制备牙膏。各例的配合组成示于表1~6。以配合前的原料中所包含的水分量的合计相对于全部原料的比例(质量%)的形式算出组合物的水分量,其结果均为2质量%以下。需要说明的是,各组成中的酶制剂的使用量为100g。
[洁齿剂组合物的制备方法]
通过常规方法配合原料,使用1.5L捏和机(石山工作所公司制造)在常温下混合,进行基于减压(压力4kPa)的脱泡,得到洁齿剂组合物。
按照下述步骤评价所得到的洁齿剂组合物。
[评价方法]
-刷牙初期的发涩感的评价-
将洁齿剂组合物1g放置于牙刷(Clinica Advantage牙刷,4排紧凑普通,狮王公司制造)上,并按照通常的方法进行刷洗时,根据下述所示的评分基准,以4个等级评价刷牙初期的发涩感。算出7名试验者的平均分,根据以下的评价基准,以+++、++、+、-、--示于表中。
(评分基准)
4分:完全感觉不到刷牙初期的发涩感
3分:稍微感觉到刷牙初期的发涩感
2分:感觉到刷牙初期的发涩感
1分:强烈地感觉到刷牙初期的发涩感
(评价基准)
+++:平均3.5分以上
++:平均3.0分以上且小于3.5分
+:平均2.5分以上且小于3.0分
-:平均2.0分以上且小于2.5分
--:平均小于2.0分
[表1]
[表2]
[表3]
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[表4]
[表5]
[表6]
在包含(A)成分但不包含(B)成分的比较例1及2中,在刷牙初期感觉到发涩感,在包含(A)及(B)成分的实施例1~35中,刷牙初期的发涩感得到抑制。关于除了包含(A)及(B)成分以外还包含(C)成分的实施例10~25、27、29~35,刷牙初期的发涩感不明显程度良好。
以下,示出配方例。
配方例1:漱口剂
配方例2:漱口剂
配方例3:漱口剂
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配方例4:漱口剂
配方例5:口腔喷雾
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Claims (8)
1.一种非水系口腔用组合物,其特征在于,含有:
(A)成分:酶;以及
(B)成分:选自由N-乙基-对薄荷烷-3-甲酰胺、3-L-薄荷氧基-1,2-丙二醇、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、(1R,2S,5R)-5-甲基-2-丙烷-2-基-N-(2-吡啶-2-基乙基)环己烷-1-甲酰胺、3-(对薄荷烷-3-甲酰胺)乙酸乙酯、2-异丙基-N,2,3-三甲基丁酰胺、乳酸薄荷酯、琥珀酸单薄荷酯、异胡薄荷醇以及薄荷酮甘油缩酮组成的组中的至少一种冷感剂。
2.根据权利要求1所述的非水系口腔用组合物,其中,所述非水系口腔用组合物还含有(C)成分:甘油脂肪酸酯。
3.根据权利要求1或2所述的非水系口腔用组合物,其中,(B)成分的含量为0.0001质量%~0.3质量%。
4.根据权利要求1~3中任一项所述的非水系口腔用组合物,其中,(A)成分包含选自由葡聚糖酶、加氧酶以及蛋白酶组成的组中的至少一种。
5.根据权利要求4中所述的非水系口腔用组合物,其中,所述非水系口腔用组合物满足以下条件中的至少任一项:
葡聚糖酶为α-1,6-葡聚糖酶或变聚糖酶;
加氧酶为漆酶、乳过氧化物酶或葡萄糖氧化酶;以及
蛋白酶为木瓜蛋白酶、猕猴桃蛋白酶、菠萝蛋白酶或纳豆激酶。
6.根据权利要求1~5中任一项所述的非水系口腔用组合物,其中,所述非水系口腔用组合物还含有(D)成分:选自由聚乙二醇、甘油、二甘油、丙二醇以及聚丙二醇组成的组中的至少一种多元醇。
7.根据权利要求1~6中任一项所述的非水系口腔用组合物,其中,作为(A)成分的酶的酶效价相对于(B)成分的含量的比率、即A/B比为6000单位/g~200000000单位/g。
8.根据权利要求1~7中任一项所述的非水系口腔用组合物,其中,所述非水系口腔用组合物为洁齿剂、漱口剂、口腔喷雾、口腔用保湿凝胶、或乳膏。
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