CN116669693A - 口腔用组合物 - Google Patents
口腔用组合物 Download PDFInfo
- Publication number
- CN116669693A CN116669693A CN202180086970.6A CN202180086970A CN116669693A CN 116669693 A CN116669693 A CN 116669693A CN 202180086970 A CN202180086970 A CN 202180086970A CN 116669693 A CN116669693 A CN 116669693A
- Authority
- CN
- China
- Prior art keywords
- streptococcus
- amino acid
- oral composition
- stomatitis
- oral
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Abstract
口腔用组合物含有氨基酸和特定的糖。特定的糖为选自乳糖、2’‑岩藻糖基乳糖、半乳糖、棉子糖、以及低聚半乳糖中的至少一种。
Description
技术领域
本发明涉及口腔用组合物。
背景技术
口腔内的大量细菌悬浮在口腔内、或者存在于被称为生物膜的细菌的聚集体中。生物膜对物理作用和化学作用均具有抗性,因此除去生物膜比除去悬浮的细菌更加困难。
关于悬浮在口腔内的细菌附着于牙齿或口腔粘膜表面的机理,很久以来进行了研究,得到了各种见解。为了有效地实施生物膜的形成抑制,防止早期固定细菌(其是在短时间内附着于清洁的齿面而形成初期菌斑的细菌)在口腔内组织等中的附着被认为是重要的。已知早期固定细菌具有与唾液蛋白结合的受体,该受体与特定的唾液蛋白结合时,可促进附着。该唾液蛋白大致分为高脯氨酸蛋白和高脯氨酸糖蛋白。作为具有与前者的唾液蛋白结合的受体的代表性细菌,已知有变形链球菌(Streptococcus mutans)、格氏链球菌(Streptococcus gordonii)、牙龈卟啉单胞菌(Porphyromonas gingivalis)等,作为具有与后者的唾液蛋白结合的受体的代表性细菌,已知有金黄色葡萄球菌(Staphylococcusaureus)、核梭杆菌(Fusobacterium nucleatum)、口腔链球菌(Streptococcus oralis)等。因此,有必要开发出对于这两个菌组具有有效的防止附着效果的技术。例如,专利文献1中公开了通过使用含有以进行了氢化处理的磷脂作为必要成分的脂质体的组合物而防止变形链球菌(Streptococcus mutans)、金黄色葡萄球菌(Staphylococcus aureus)等细菌在口腔内组织中的附着和增殖的技术。
现有技术文献
专利文献
专利文献1:日本特开2018-115179号公报
发明内容
发明所要解决的课题
本发明人进行了深入研究,结果得到了下述见解:与具有龋齿史的人相比,不具有龋齿史的人口腔内的口腔链球菌(Streptococcus oralis)(也记载为S.Oralis)的浓度高。由该见解暗示出,从确保健康的口腔环境的观点出发,提高口腔内的口腔链球菌(S.Oralis)浓度是重要的。
本发明是基于上述见解而完成的,其目的在于提高口腔内的口腔链球菌(S.Oralis)浓度。
用于解决课题的手段
解决上述课题的口腔用组合物是含有氨基酸和糖的口腔用组合物,其中,上述糖为选自乳糖、2’-岩藻糖基乳糖、半乳糖、棉子糖以及低聚半乳糖中的至少一种。
上述口腔用组合物中,上述氨基酸可以为选自酸性氨基酸以及酸性氨基酸盐中的至少一种。
具体实施方式
以下对本发明的一个实施方式进行。
本实施方式的口腔用组合物含有特定的糖、以及氨基酸。
(特定的糖)
口腔用组合物中含有的特定的糖为选自乳糖、2’-岩藻糖基乳糖、半乳糖、棉子糖、低聚半乳糖以及它们的水合物中的至少一种。口腔用组合物可以单独含有上述特定糖中的仅一种,也可以组合含有两种以上。
口腔用组合物中的特定的糖的含量例如为0.5~4质量%、优选为1~3质量%、更优选为1~2质量%。
(氨基酸)
口腔用组合物中含有的氨基酸没有特别限定。作为上述氨基酸,例如可以举出丙氨酸、脯氨酸、苏氨酸、丝氨酸、缬氨酸、甘氨酸、瓜氨酸等中性氨基酸;天冬氨酸、谷氨酸等酸性氨基酸以及酸性氨基酸盐;赖氨酸、精氨酸、组氨酸等碱性氨基酸以及碱性氨基酸盐。作为酸性氨基酸盐的具体例,可以举出钠盐、钾盐等碱金属盐;镁盐、钙盐等碱土金属盐。作为碱性氨基酸盐的具体例,可以举出盐酸盐、硫酸盐。
口腔用组合物可以单独含有上述氨基酸中的仅一种,也可以组合含有两种以上。另外,口腔用组合物中,作为氨基酸,特别优选含有选自酸性氨基酸以及酸性氨基酸盐中的至少一种。
口腔用组合物中的氨基酸的含量例如为0.5~4质量%、优选为1~3质量%、更优选为1.5~3质量%。另外,口腔用组合物中的氨基酸相对于特定的糖的质量比(氨基酸/特定的糖)例如为0.25~4、优选为0.5~3、更优选为1~2。
(特定的糖与特定的氨基酸的组合)
优选在口腔用组合物中含有选自乳糖、半乳糖、棉子糖以及低聚半乳糖中的至少一种作为特定的糖,并且含有选自天冬氨酸以及天冬氨酸盐中的至少一种作为特定的氨基酸。另外,优选在口腔用组合物中含有选自棉子糖以及低聚半乳糖中的至少一种作为特定的糖,并且含有选自谷氨酸以及谷氨酸盐中的至少一种作为特定的氨基酸。另外,优选在口腔用组合物中含有半乳糖作为特定的糖,并且含有瓜氨酸作为特定的氨基酸。另外,优选在口腔用组合物中含有2’-岩藻糖基乳糖作为特定的糖,并且含有精氨酸作为特定的氨基酸。
(应用形态、用途、以及剂型)
口腔用组合物的应用形态没有特别限定,例如可以作为医药品、准药品、化妆品使用。作为口腔用组合物的用途,可以适宜地采用公知的形态,例如可以举出牙膏、洗口剂、含漱剂、液体洁牙剂、生物膜分散剂、口臭预防剂、牙龈按摩剂、口腔用湿润赋予剂、舌苔除去剂、口腔内涂布剂、口腔杀菌剂、咽喉杀菌剂、口腔咽喉剂、牙周病治疗剂、义齿安装剂、义齿涂布剂、义齿稳定化剂、义齿保存剂、义齿清洗剂、种植体护理剂。
口腔用组合物的剂型没有特别限定,例如通过含有水、醇等溶剂,可应用于软膏剂、糊剂、膏剂、喷雾剂、胶冻剂、液剂、悬浮-乳化剂、口香糖剂等。
作为溶剂使用的水的种类没有特别限定,例如可以使用蒸馏水、纯水、超纯水、纯净水、自来水等。作为溶剂使用的醇的种类没有特别限定,例如可以使用乙醇。也可以将水和醇混合使用。
将口腔用组合物构成为液态的情况下,水等溶剂的含量优选为60~99.8质量%、更优选为70~90质量%。
口腔用组合物可以作为用于促进口腔内的口腔链球菌(S.Oralis)的增殖的细菌增殖促进用组合物使用。作为细菌增殖促进用组合物,例如可以举出饮食品以及上述的医药品、准药品、化妆品。
应用于饮食品的口腔用组合物可以作为各种食品材料、或者通过添加到饮料品材料中而使用。作为饮食品的形态没有特别限定,可以为液态、粉末状、凝胶状、固体状等中的任一者。作为具体例,可以举出咀嚼剂、含剂、片剂、颗粒、粉末、饮料用粉末、饮料、口内崩解性膜、口腔用喷雾、以及口香糖、糖果、软糖、果冻等点心类。饮食品的用途没有特别限定,可以作为所谓常规食品、健康食品、功能性食品、营养辅助食品、补品、特定保健用食品、具有功能性声明的食品、病人用食品。
(其他成分)
口腔用组合物可以根据应用目的、形态、用途等含有上述成分以外的其他成分。作为其他成分,例如可以举出抗菌剂、抗炎剂、香料、润湿剂、表面活性剂、研磨剂、醇类、增稠剂、甜味成分、药用成分、着色剂、稳定化剂、pH调节剂。其他成分可以使用混配在口腔用组合物中的公知的成分。口腔用组合物中,上述其他成分分别可以单独含有仅一种,也可以组合含有两种以上。
作为抗菌剂,例如可以举出氯化十六烷基吡啶鎓、对羟基苯甲酸酯、苯甲酸钠、三氯生、盐酸洗必泰、异丙基甲基苯酚、苯扎氯铵、苄索氯铵、扁柏酚。
作为抗炎剂,例如可以举出甘草酸盐、传明酸、ε-氨基己酸、黄柏提取物。
作为香料,例如可以举出茴香脑、丁子香酚、香芹酮、冬青、水杨酸甲酯、百里酚、丁香油、药用鼠尾草油、罗勒烯油、香茅醇。
作为表面活性剂,例如可以举出非离子型表面活性剂、阴离子表面活性剂、两性表面活性剂。
作为非离子型表面活性剂,例如可以举出蔗糖脂肪酸酯、麦芽糖脂肪酸酯等糖脂肪酸酯、麦芽糖醇脂肪酸酯等糖醇脂肪酸酯、单月桂酸山梨糖醇酐等山梨聚糖脂肪酸酯、聚氧乙烯山梨糖醇酐单月桂酸酯、聚氧乙烯山梨糖醇酐单硬脂酸酯等聚氧乙烯山梨聚糖脂肪酸酯、月桂酸二乙醇酰胺等脂肪酸烷醇酰胺、聚氧乙烯硬脂基醚、聚氧乙烯油基醚等聚氧乙烯烷基醚、单油酸聚乙二醇酯、单月桂酸聚乙二醇酯等聚乙二醇脂肪酸酯、月桂基葡糖苷、癸基葡糖苷等烷基葡糖苷、聚甘油脂肪酸酯、聚氧乙烯甘油脂肪酸酯、聚氧乙烯脂肪酸酯、烷基葡糖苷类、聚氧乙烯氢化蓖麻油、甘油脂肪酸酯、聚氧乙烯丙烯嵌段共聚物。
作为阴离子表面活性剂,例如可以举出月桂基硫酸钠、聚氧乙烯月桂基醚硫酸钠等硫酸酯盐、月桂基磺化琥珀酸钠、聚氧乙烯月桂基醚磺化琥珀酸钠等磺化琥珀酸盐、椰油酰基肌氨酸钠、月桂酰甲基丙氨酸钠等酰基氨基酸盐、椰油酰基甲基牛磺酸钠。
作为两性表面活性剂,例如可以举出N-月桂基二氨基乙基甘氨酸、N-肉豆蔻基二乙基甘氨酸等氨基酸型两性表面活性剂、烷基二甲氨基乙酸甜菜碱、N-烷基-N’-羧甲基-N’-羟基乙基乙二胺盐、以及2-烷基-N-羧甲基-N-羟基乙基咪唑啉鎓甜菜碱等甜菜碱系两性表面活性剂。
作为研磨剂,例如可以举出碳酸钙、碳酸镁、磷酸氢二钙、磷酸三钙、磷酸镁、二氧化硅、沸石、偏磷酸钠、氢氧化铝、氢氧化镁、焦磷酸钙、氧化铁红、硫酸钙、硅酸酐。
作为醇类,例如可以举出乙醇、月桂醇、肉豆蔻醇等。
作为增稠剂,例如可以举出聚丙烯酸钠、卡拉胶、羧甲基纤维素钠、藻酸钠、黄原胶、羟基乙基纤维素、羟丙基甲基纤维素、甲基纤维素、藻酸丙二醇酯。
作为药用成分,例如可以举出单氟磷酸钠、氟化钠、氟化亚锡、氟化锶等氟化物、焦磷酸钠、多聚磷酸钠等缩合磷酸盐、磷酸氢二钠、磷酸三钠等磷酸盐、抗坏血酸、抗坏血酸钠、盐酸吡哆醇、生育酚乙酸酯等维生素剂、葡聚糖酶、变聚糖酶等葡聚糖水解酶、蛋白酶、溶菌酶等分解酶、氯化锌、柠檬酸锌、氯化锶、硝酸钾等无机盐类、叶绿素、甘油磷酸等螯合性化合物、溶解脂的聚乙二醇等、氯化钠、乳酸铝、氯化锶。
作为着色剂,例如可以举出绿色1号、蓝色1号、黄色4号等法定色素、氧化钛等。
作为稳定化剂,例如可以举出依地酸钠、硫代硫酸钠、亚硫酸钠、乳酸钙、羊毛脂、甘油三乙酸酯、蓖麻油、硫酸镁等。
作为pH调节剂,例如可以举出柠檬酸、苹果酸、乳酸、酒石酸、乙酸、磷酸、焦磷酸、甘油磷酸、以及它们的钾盐、钠盐和铵盐等各种盐、氢氧化钠等。口腔用组合物优选通过混配pH调节剂而将pH调整为4~9、特别为5~7的范围。
接着对本实施方式的作用进行记载。
尽管省略详细内容,但在具有龋齿史的对象组与不具有龋齿史的对象组之间对唾液中的口腔链球菌(S.Oralis)浓度进行比较时,在不具有龋齿史的对象组中,口腔链球菌浓度得到了明显更高的结果。根据该结果可认为,从确保健康的口腔环境的观点出发,提高口腔内的口腔链球菌浓度是重要的。其机理可推测如下。
早期固定细菌是附着于齿面而形成初期菌斑的细菌,其介导形成生物膜的病原菌在齿面的附着。早期固定细菌中,口腔链球菌对于形成生物膜的病原菌的附着性弱,齿面的口腔链球菌所固定的部分与其他的早期固定细菌所附着的部分相比成为病原菌不容易附着的部位。
因此,若口腔内的口腔链球菌浓度上升,则在早期固定细菌固定于齿面的部分,口腔链球菌所固定的部分的比例增加。换言之,通过使口腔内的口腔链球菌浓度上升,可竞争性抑制容易附着病原菌的其他早期固定细菌在齿面上的固定。由于抑制容易附着病原菌的其他早期固定细菌在齿面上的固定,因此可抑制生物膜的形成,容易得到健康的口腔环境。
本实施方式的口腔用组合物可以使口腔链球菌在口腔内增殖。本实施方式的口腔用组合物中,基于口腔链球菌在口腔内增殖的效果,可期待抑制生物膜的形成的效果。
接着记载本实施方式的效果。
(1)口腔用组合物含有氨基酸和特定的糖。特定的糖为选自乳糖、2’-岩藻糖基乳糖、半乳糖、棉子糖以及低聚半乳糖中的至少一种。根据上述构成,能够使口腔链球菌在口腔内增殖。
(2)氨基酸为选自酸性氨基酸以及酸性氨基酸盐中的至少一种。这种情况下,可更显著地得到使口腔链球菌在口腔内增殖的效果。
(3)特定的糖为选自乳糖、半乳糖、棉子糖以及低聚半乳糖中的至少一种。氨基酸为选自天冬氨酸以及天冬氨酸盐中的至少一种。这种情况下,可更显著地得到使口腔链球菌在口腔内增殖的效果。
(4)特定的糖为选自棉子糖以及低聚半乳糖中的至少一种。氨基酸为选自谷氨酸以及谷氨酸盐中的至少一种。这种情况下,可更显著地得到使口腔链球菌在口腔内增殖的效果。
实施例
基于下述实施例和比较例对本发明的口腔用组合物更详细地进行说明。另外,本发明并不限定于以下实施例的构成。
<试验1>
(口腔链球菌的培养试验)
利用BHI培养基(脑心浸液肉汤培养基,Brain Heart Infusion broth(BD公司制造))培养口腔链球菌。对于培养液在波长660nm下的浊度进行测定后,按照所测定的浊度为0.1的方式将培养液用BHI培养基稀释,将其作为菌液。作为口腔链球菌,使用口腔链球菌苏黎世亚种(Streptococcus oralis spp.Tigurinus)。
制备将氨基酸和糖溶解在BHI培养基中而成的实施例和比较例的样品溶液。各样品溶液中使用的氨基酸和糖的种类如表1所示。各样品溶液中的氨基酸的浓度为0mg/ml或15mg/ml,糖的浓度为20mg/ml。
在96孔板的孔中添加菌液100μl和样品溶液100μl,在37℃、厌氧条件下培养24小时。培养后,去除上清,添加用磷酸缓冲盐水(PBS)稀释了11倍的阿尔玛蓝(Alamar Blue)溶液(Invitrogen公司制造)110μl,在激发波长545nm、荧光波长590nm下测定荧光强度。计算出相对于未添加样品溶液的对照的荧光强度的相对值,将其作为口腔链球菌的生长度,并且按以下的评价基准对计算出的生长度进行评价。将它们的结果示于表1。
A:10以上
B:5以上且小于10
C:小于5
[表1]
如表1所示,在添加了作为糖使用乳糖一水合物、半乳糖、棉子糖或低聚半乳糖、并且作为氨基酸使用了精氨酸的实施例1~4的情况下,促进了口腔链球菌的增殖。另一方面,在添加了不含有糖的比较例1、以及作为糖使用异麦芽低聚糖、低聚果糖、菊粉、木糖醇、赤藓醇、甘油的比较例2~7的情况下,未得到促进口腔链球菌的增殖的效果。
<试验2>
接着,作为糖,使用在试验1中显示出增殖促进效果的乳糖一水合物、半乳糖、棉子糖以及低聚半乳糖,变更氨基酸的种类,对这种情况下的口腔链球菌的生长度进行测定。试验方法与试验1相同。将各样品溶液中使用的氨基酸和糖的种类、以及生长度的测定结果示于表2。另外,在试验2中,关于各样品溶液中的氨基酸的浓度,仅在使用精氨酸的实施例5中为15mg/ml,在其他实施例中为20mg/ml。
[表2]
如表2所示,在添加了氨基酸的种类不同的实施例5~实施例23的情况下,均促进了口腔链球菌的增殖。在作为氨基酸使用属于酸性氨基酸盐的天冬氨酸钠或者谷氨酸钠的情况下,促进口腔链球菌的增殖的效果特别显著。特别是在半乳糖与天冬氨酸钠组合的情况下、棉子糖与天冬氨酸钠或谷氨酸钠组合的情况下、以及低聚半乳糖与天冬氨酸钠或谷氨酸钠组合的情况下,生长度为200以上,进一步显著促进了口腔链球菌的增殖。由试验1和试验2的结果可知,促进口腔链球菌的增殖的效果是在将特定的糖与任意的氨基酸组合时限定性地得到的效果。
<试验3>
接着对于作为糖使用半乳糖、并且作为氨基酸使用瓜氨酸的情况下的口腔链球菌的生长度进行测定。试验方法与试验1相同。将各样品溶液中的半乳糖以及瓜氨酸的各浓度、以及生长度的测定结果示于表3。另外,试验3中,各样品溶液中的半乳糖的浓度为0mg/ml或2mg/ml,瓜氨酸的浓度为0.5~3.0mg/ml。
[表3]
如表3所示,比较例8是在半乳糖和瓜氨酸中仅含有瓜氨酸、改变瓜氨酸的浓度的示例。在添加了比较例8的各样品溶液的情况下,促进了口腔链球菌的增殖,但随着瓜氨酸的浓度增加,促进增殖的效果降低。
另一方面,实施例24是含有半乳糖和瓜氨酸这两者、半乳糖的浓度固定、改变瓜氨酸的浓度的示例。在添加了实施例24的各样品溶液的情况下,随着瓜氨酸的浓度增加,促进增殖的效果增加。另外,在对瓜氨酸的浓度为相同浓度的示例相互比较的情况下,在任一示例中均是实施例24的生长度比比较例8的生长度高的结果。
由上述结果可知,通过将瓜氨酸与半乳糖合用,瓜氨酸对口腔链球菌的增殖带来的影响发生变化。具体地说,在瓜氨酸单独使用时,具有口腔链球菌的增殖促进以瓜氨酸浓度依赖性的方式降低的倾向。瓜氨酸单独使用时的倾向通过与半乳糖的合用而变化成口腔链球菌的增殖促进以瓜氨酸浓度依赖性的方式增加的倾向。该结果显示出,瓜氨酸与半乳糖不是单独地对口腔链球菌的增殖产生影响,而是共同对其产生影响。
<试验4>
接着对于作为糖使用2’-岩藻糖基乳糖、并且作为氨基酸使用精氨酸的情况下的口腔链球菌的生长度进行测定。试验方法与试验1相同。将各样品溶液中的2’-岩藻糖基乳糖和精氨酸的各浓度、以及生长度的测定结果示于表4。另外,在试验4中,各样品溶液中的2’-岩藻糖基乳糖的浓度为1~4mg/ml,瓜氨酸的浓度为0mg/ml或1.5mg/ml。
[表4]
如表4所示,比较例9是仅含有2’-岩藻糖基乳糖和精氨酸中的2’-岩藻糖基乳糖、改变精氨酸的浓度的示例。在添加了比较例9的各样品溶液的情况下,几乎不能确认到促进口腔链球菌的增殖的效果。
另一方面,实施例25是含有2’-岩藻糖基乳糖和精氨酸这两者、精氨酸的浓度固定、改变2’-岩藻糖基乳糖的浓度的示例。在添加了实施例25的各样品溶液的情况下,确认到了促进口腔链球菌的增殖的效果。并且,促进口腔链球菌的增殖的效果与2’-岩藻糖基乳糖的浓度相应地发生变化。该结果显示出,并非仅精氨酸单独地对口腔链球菌的增殖产生影响,而是2’-岩藻糖基乳糖和精氨酸共同对其产生影响。
接着,以下记载能够由上述实施方式掌握的技术思想。
(a)如上述的口腔用组合物,其中,上述糖为选自半乳糖、棉子糖以及低聚半乳糖中的至少一种,上述氨基酸为选自天冬氨酸以及天冬氨酸盐中的至少一种。
(b)如上述的口腔用组合物,其中,上述糖为选自棉子糖以及低聚半乳糖中的至少一种,上述氨基酸为选自谷氨酸以及谷氨酸盐中的至少一种。
(c)如上述的口腔用组合物,其中,上述氨基酸相对于上述糖的质量比(氨基酸/糖)为0.5~4。
(d)一种细菌增殖促进用组合物,其是促进口腔链球菌(Streptococcus oralis)的增殖的细菌增殖促进用组合物,其特征在于,其含有氨基酸和糖,上述糖为选自乳糖、半乳糖、棉子糖以及低聚半乳糖中的至少一种。
(e)一种细菌增殖促进方法,其是促进唾液中的口腔链球菌(Streptococcusoralis)的增殖的细菌增殖促进方法,其特征在于,将上述细菌增殖促进用组合物添加到唾液中。
Claims (2)
1.一种口腔用组合物,其是含有氨基酸和糖的口腔用组合物,其特征在于,所述糖为选自乳糖、2’-岩藻糖基乳糖、半乳糖、棉子糖以及低聚半乳糖中的至少一种。
2.根据权利要求1所述的口腔用组合物,其中,所述氨基酸为选自酸性氨基酸以及酸性氨基酸盐中的至少一种。
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JPH1112168A (ja) * | 1997-06-20 | 1999-01-19 | Lion Corp | 抗内毒素剤及び口腔用組成物 |
US6592908B1 (en) * | 2002-09-23 | 2003-07-15 | Albert Crum | Nutritional or therapeutic compositions |
US9795579B1 (en) * | 2017-04-24 | 2017-10-24 | Knoze Jr. Corporation | Oral microbiota promoting method |
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