CN102470113A - 包含糖醇的牙周病原菌增殖抑制抗菌剂 - Google Patents
包含糖醇的牙周病原菌增殖抑制抗菌剂 Download PDFInfo
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Abstract
本发明提供一种在牙周病和龋齿的改善及预防中发挥效果的抗菌剂,其特征在于,具有基于糖醇的牙周病原菌和龋齿病原菌的增殖抑制作用。该牙周病原菌增殖抑制抗菌剂以糖醇、特别是乳糖醇或麦芽糖醇作为有效成分。
Description
技术领域
本发明涉及包含糖醇、特别是包含乳糖醇、麦芽糖醇的抗菌剂。
背景技术
糖醇的卡路里低,不具有龋齿性,从预防龋齿和预防生活习惯病等角度考虑,糖醇被广泛应用于食品、化妆品、医药品、保健食品等产品。众所周知糖醇在口腔内对龋齿的病原菌具有增殖抑制作用,但对于其它的实用性大多不明。
本发明特别关注于与作为牙周病原因的牙周病原菌有关的糖醇的新实用性,进行了糖醇的抗菌性和牙病病原菌增殖抑制的评价。
关于糖醇的抗菌作用等,以往有各种现有技术文献。
非专利文献1中报道了木糖醇对牙龈卟啉单胞菌(P.gingivalis)的增殖抑制效果。但是,对于木糖醇以外的糖醇,关于龋齿病原菌和念珠菌的去除、对牙周病原菌的抗菌或增殖抑制完全没有报道。
专利文献1中揭示了一种牙周病的预防或治疗剂。该文献中,通过将乳酸菌与牙龈卟啉单胞菌混合接种在含有这些细菌能同化的糖类的培养基中,与单独的培养基相比牙龈卟啉单胞菌的增殖得到抑制。还有,未进行含糖类的培养基和不含糖类的培养基之间的增殖比较。实施例中,作为糖类仅使用了葡萄糖、乳糖、蔗糖,作为试验菌株仅使用了牙龈卟啉单胞菌。在权利要求2中,作为糖类还另外记载了木糖醇、赤藓醇、麦芽糖醇,在发明的实施方式中,作为驱除对象牙周病原菌还另外记载了中间普雷沃氏菌(Prevotella intermedia)、伴放线放线杆菌(Actinobacillusactinomycetemcomitans)、念珠菌、变形链球菌。但是,并没有单独的糖醇对牙周病原菌的抗菌作用的报道。
专利文献2中揭示了一种口腔内疾病的预防和/或治疗用组合物。通过在含乳酸菌培养滤液的培养基中添加木糖醇,与单独的培养滤液的条件相比,牙龈卟啉单胞菌、具核梭杆菌(F.nucleatum)、中间普雷沃氏菌(P.intermedia)、伴放线放线杆菌的增殖得到抑制。还有,即使单独将木糖醇添加至培养基,对这些细菌的增殖也几乎没有影响。此外,对于牙龈卟啉单胞菌,通过添加赤藓醇、麦芽糖醇,增殖也得到抑制。但是,并没有单独的糖醇对牙周病原菌的抗菌作用的报道。
专利文献3中揭示了一种以乳酸菌作为有效成分的活菌制剂和含有乳酸菌的食品。按照终浓度为5%的条件在基本培养基中添加赤藓醇,培养变形链球菌(Streptococcus mutans)24小时后,与未添加赤藓醇的条件相比,活菌数被抑制了75%,不溶性葡聚糖形成量被抑制了60%。此外,同时培养乳酸菌时,抑制程度进一步增大。权利要求11中,作为糖醇,组合物中仅含有赤藓醇。但是,并没有单独的糖醇对牙周病原菌的抗菌作用的报道。
如上所述,现有技术文献中虽然揭示了将糖醇添加至乳酸菌的培养基中以起到牙周病原菌的增殖抑制作用,但完全没有关于龋齿病原菌、金黄色葡萄球菌、念珠菌的去除以及单独存在糖醇的条件下对牙周病原菌的增殖的作用的报道。
现有技术文献
专利文献
专利文献1:日本专利特开2003-171292号公报
专利文献2:日本专利特表02/080946
专利文献3:日本专利特表03/082027
非专利文献
非专利文献1:Clin Diagn Lab Immunol.2005Nov;12(11):1285-91
发明的揭示
发明所要解决的技术问题
本发明的目的在于提供一种在牙周病和龋齿的改善及预防中发挥效果的抗菌剂,其特征在于,具有基于乳糖醇和麦芽糖醇的牙周病原菌和龋齿病原菌的增殖抑制作用。
解决技术问题所采用的技术方案
糖醇被广泛应用于食品、化妆品、医药品、保健食品等产品,众所周知糖醇在口腔内对龋齿病原菌具有增殖抑制作用,但对于其它的实用性大多不明。将牙周病原菌在含有乳糖醇或麦芽糖醇的培养基中培养,结果确认,与不含乳糖醇或麦芽糖醇的培养基相比,增殖得到显著抑制。此外,该效果并非杀菌性的,暗示可能是抑菌性的作用。
发明效果
本发明对于牙周病原菌具有抗菌作用,因此可以作为漱口剂、牙膏、吸入剂、含片剂等制剂以及口香糖、糖果、压片糖、软糖、饼干、巧克力等点心、雪糕、饮料等食品在日常生活中应用、摄取,对于牙周病和龋齿的改善及预防极为有效。
附图的简单说明
图1A是表示糖醇(木糖醇)对具核梭杆菌的增殖造成的影响的图。
图1B是表示糖醇(赤藓醇)对具核梭杆菌的增殖造成的影响的图。
图1C是表示糖醇(乳糖醇)对具核梭杆菌的增殖造成的影响的图。
图1D是表示糖醇(麦芽糖醇)对具核梭杆菌的增殖造成的影响的图。
图2A是表示糖醇(木糖醇)对牙龈卟啉单胞菌的增殖造成的影响的图。
图2B是表示糖醇(赤藓醇)对牙龈卟啉单胞菌的增殖造成的影响的图。
图2C是表示糖醇(乳糖醇)对牙龈卟啉单胞菌的增殖造成的影响的图。
图2D是表示糖醇(麦芽糖醇)对牙龈卟啉单胞菌的增殖造成的影响的图。
实施发明的最佳方式
本发明的一种实施方式是以糖醇作为有效成分的牙周病原菌增殖抑制抗菌剂。
本发明的另一种实施方式是以乳糖醇或麦芽糖醇作为有效成分的牙周病原菌增殖抑制抗菌剂。
本发明的又一种实施方式是由以乳糖醇或麦芽糖醇作为有效成分的牙周病原菌增殖抑制抗菌剂制成的漱口剂、牙膏、吸入剂和含片剂。
本发明的又另一种实施方式是含有以乳糖醇或麦芽糖醇作为有效成分的牙周病原菌增殖抑制抗菌剂的口香糖、糖果、压片糖、软糖、饼干、巧克力等点心、雪糕、饮料等食品。
以下,通过具体的实施例对本发明进行更详细的说明,但本发明不局限于这些实施例。
实施例
(实施例1)
糖醇的抗菌性试验如下所述进行。
1-1.受试试样的制备方法
使用2%乙醇,将木糖醇、赤藓醇、乳糖醇、麦芽糖醇调整至最终培养基浓度达到8%,将百里酚调整至最终培养基浓度达到800ppm,将氯化锌调整至最终培养基浓度达到200ppm,用2%乙醇制作2倍梯度稀释。
1-2.供试菌株
作为牙周病原菌,使用牙龈卟啉单胞菌(Porphyromonas gingivalis)ATCC33277株(以下简称为P.gingivalis)、具核梭杆菌(Fuusobacteriumnucleatum)ATCC25586株(以下简称为F.nucleatum)、中间普雷沃氏菌(Prevotella intermedia)ATCC25611株(以下简称为P.intermedia)、变黑普雷沃氏菌(Prevotella nigrescens)JCM6322株(以下简称为P.nigrescens)、齿垢密螺旋体(Treponema denticola)ATCC35405株(以下简称为T.denticola)、福赛斯坦纳菌(Tannerella forsythia)JCM10827株(以下简称为T.forsythia)。此外,舌苔细菌中,作为舌苔中的比例较高的口腔内细菌,使用产黑素普雷沃氏菌(Prevotella melaninogenica)JCM6325株(以下简称为P.melaninogenica)、小韦荣氏球菌(Veillonellaparvula)JCM12972株(以下简称为V.parvula)、殊异韦荣氏球菌(Veillonella dispar)ATCC17748株(以下简称为V.dispar)。
1-3.培养基
对于牙龈卟啉单胞菌、具核梭杆菌、中间普雷沃氏菌、变黑普雷沃氏菌、产黑素普雷沃氏菌,使用添加有酵母提取物(Yeast extract)(3.0g/l)、氯高铁血红素(Hemin)(5.0mg/l)、甲萘醌(Menadione)(0.5mg/l)的胰蛋白胨大豆肉汤(Trypticase soy broth),在37℃的厌氧条件下(10%CO2、10%H2、80%N2)培养。对于小韦荣氏球菌、殊异韦荣氏球菌,将添加有胰蛋白胨(5.0g/l)、酵母提取物(3.0g/l)、乳酸钠(Sodium lactate)(9.0g/l)、巯基乙酸钠(Sodium thioglycollate)(0.75g/l)、吐温80(1.0g/l)、葡萄糖(1.0g/l)的培养基用K2CO2调整至pH7.5,在相同条件下培养。对于福赛斯坦纳菌,将添加有酵母提取物(5.0g/l)、氯高铁血红素(5.0mg/l)、甲萘醌(0.5mg/l)的脑心浸出液肉汤(Brain heart infusion broth)进行120℃、15分钟的灭菌处理后,添加L-半胱氨酸(1.0g/l)、N-乙酰基神经氨酸(10.0mg/l)、胎牛血清(Fetal Bovine Serum)(50ml/l),使用所得培养基在相同条件下培养。齿垢密螺旋体用TYGVS培养基在相同条件下培养。
1-4.抗菌性的判定
抗菌性试验采用以2倍梯度稀释进行稀释的液体稀释法。即,将进行了2倍梯度稀释的受试试样液加入96孔板(每孔的液量为100μl),将在上述1-3的培养基中培养的菌液在同一培养基中稀释、混合至5%以下的浓度,将100μl该菌液添加于96孔板上。另外,将不含菌液而仅添加了100μl培养基的样品作为对照,进行24~48小时的厌氧培养(10%CO2、10%H2、80%N2),用分光光度计测定OD660值。将与对照相比OD660值大致相同、且用肉眼无法观察到细菌的发育的浓度记作最小抑菌浓度(以下简称为MIC)。
1-5.结果
为了确认各种糖醇对口臭病原菌的抗菌活性,进行了抗菌试验。
各试验菌株的MIC示于表1。对于变黑普雷沃氏菌、产黑素普雷沃氏菌、小韦荣氏球菌、福赛斯坦纳菌,所有受试试样在8%以下(百里酚为800ppm以下)的浓度下均未显示出抗菌性。对于齿垢密螺旋体,虽然百里酚未获得抗菌性,但试验所用的所有4种糖醇均确认具有8%的MIC。反之,对于殊异韦荣氏球菌,虽然百里酚显示出400ppm的MIC,但糖醇未观察到抗菌性。此外,对于牙龈卟啉单胞菌,虽然与25ppm锌、200ppm百里酚相比活性较弱,但所有的糖醇均确认具有弱抗菌性。弱抗菌性是指如下状态:虽然未完全抑制细菌的增殖,但显示出其它浓度的一半左右的OD660值,用肉眼能观察到一定程度的细菌的发育。关于氯化锌,仅针对牙龈卟啉单胞菌进行了抗菌试验。对于具核梭杆菌,虽然与200ppm百里酚相比活性较弱,但木糖醇、赤藓醇显示出8%的MIC。对于中间普雷沃氏菌,虽然未确认百里酚具有抗菌性,但赤藓醇显示出8%的MIC。
由以上结果可知,糖醇显示出细菌特异性抗菌性。牙龈卟啉单胞菌、具核梭杆菌、中间普雷沃氏菌、齿垢密螺旋体均为牙周病的主要病原菌,与牙周病的发病和恶化相关。糖醇对这些病原菌显示出抗菌性,但另一方面,对舌苔细菌中的舌苔中的比例较高的口腔内细菌(产黑素普雷沃氏菌、小韦荣氏球菌、殊异韦荣氏球菌)未显示出抗菌性。有报道称,韦荣氏球菌属在青年健康人的牙菌斑中的检出量高于牙周病患者。作为健康人的口腔内正常细菌,糖醇对于这些菌株未显示出抗菌性,这可以认为是作为食品添加物质的理想结果。对于牙龈卟啉单胞菌,起到细菌代谢抑制作用的氯化锌显示出极低的MIC,因此可以认为由代谢抑制导致的细菌增殖抑制是一大原因。
[表1]
表1对牙周病原菌及舌苔细菌的抗菌活性(MIC)
△:弱抗菌性、×:在所有浓度下均未确认具有抗菌性,
ND:无数据(No Data)
糖醇浓度:0.0078%~8%
百里酚浓度:0.78ppm~800ppm
氯化锌浓度:0.195ppm~200ppm
(实施例2)
糖醇的增殖抑制试验如下所述进行。
2-1.受试试样的制备方法
将木糖醇、赤藓醇、乳糖醇、麦芽糖醇调整至最终培养基浓度达到5%或10%。
2-2.供试菌株
作为菌株,使用实施例1的供试菌株中记载的具核梭杆菌和牙龈卟啉单胞菌。
2-3.培养基
对于牙龈卟啉单胞菌、具核梭杆菌,均使用添加有酵母提取物(3.0g/l)、氯高铁血红素(5.0mg/l)、甲萘醌(0.5mg/l)的胰蛋白胨大豆肉汤(Trypticase soy broth),在37℃的厌氧条件下(10%CO2、10%H2、80%N2)培养。增殖曲线测定时使用如下所得的培养基:按照终浓度为5%或10%的条件在上述培养基中添加糖醇,溶解后进行120℃、15分钟的灭菌处理。
2-4.增殖曲线的测定
将在上述2-3的培养基中培养至对数增殖期的菌液100μl添加至含5%或10%的各糖醇的培养基20ml。另外,将菌液100μl添加至不含糖醇的普通培养基20ml,将其作为对照。进行40~47小时的厌氧培养(10%CO2、10%H2、80%N2),其间用分光光度计适时地测定OD660值。
2-5.结果
在抗菌试验中,对牙龈卟啉单胞菌、具核梭杆菌等4种菌株确认到具有抗菌活性,因此,暗示对于这些菌株,糖醇可能可抑制增殖。为了确认该可能性,进行了含有糖醇的培养基中的牙龈卟啉单胞菌、具核梭杆菌的增殖曲线的测定。具核梭杆菌的增殖曲线示于图1A、1B、1C及1D,牙龈卟啉单胞菌的增殖曲线示于图2A、2B、2C及2D。对于各糖醇以n=2(图中记作1、2)进行试验,对照表示未添加糖醇的培养基。
对于具核梭杆菌,木糖醇、赤藓醇显示出特别强的增殖抑制。该结果与针对具核梭杆菌的抗菌试验的结果具有相关性。两种糖醇在5%、10%的浓度下,在经过44小时的培养后显示出比对照更低的OD660值。此外,对于乳糖醇、麦芽糖醇,虽然在5%浓度下显示出与对照同样的增殖,但在10%浓度下,在经过44小时的培养后显示出比对照更低的OD660值。
对于牙龈卟啉单胞菌,乳糖醇、麦芽糖醇显示出特别强的增殖抑制。
两种糖醇在5%、10%的浓度下,在经过40小时的培养后仍未观察到增殖,即使通过目测确认,培养液也为透明。此外,虽然木糖醇、赤藓醇的效果存在偏差,但显示出较弱的增殖抑制。两种糖醇在培养20小时左右时观察到细菌的增殖,经过46小时后显示出与对照相同程度的OD660值。对于乳糖醇、麦芽糖醇,认为细菌有因水分活性的影响而被杀灭的可能性,因此将经过40小时培养后的10%乳糖醇、10%麦芽糖醇培养液100μl分别涂布于血液平板培养基,在37℃的厌氧条件下(10%CO2、10%H2、80%N2)进行10天的培养。其结果是,在10%乳糖醇条件下确认到83个菌落,在10%麦芽糖醇条件下确认到308个菌落,两种糖醇均不是杀菌性的,暗示可能是抑菌性的作用。
对于10%木糖醇,观察到了偏差,需要确认重现性,但可以认为木糖醇、赤藓醇具有使进入对数增殖期的时间延后的效果。
接着,通过常规方法制造含有本发明的包含糖醇的牙周病原菌增殖抑制抗菌剂的漱口剂、牙膏、口臭用喷雾、含片、口香糖、糖果、压片糖、软糖、饮料。以下所示为它们的配方。本发明的产品不受到这些配方的限制。
(实施例3)
按照下述配方制造漱口剂。
(实施例4)
按照下述配方制造牙膏。
(实施例5)
按照下述配方制造口臭用喷雾。
(实施例6)
按照下述配方制造含片。
(实施例7)
按照下述配方制造口香糖。
(实施例8)
按照下述配方制造糖果。
(实施例9)
按照下述配方制造压片糖。
(实施例10)
按照下述配方制造软糖。
(实施例11)
按照下述配方制造饮料。
产业上利用的可能性
本发明的糖醇是广泛使用的原材料,可用于使用糖醇的各种产品、特别是牙周病预防特定保健用食品等。
本申请主张基于2009年7月14日提出申请的日本专利申请号2009-165554的优先权,引用其内容作为本申请的一部分。
Claims (7)
1.牙周病原菌增殖抑制抗菌剂,其以糖醇作为有效成分。
2.如权利要求1所述的抗菌剂,其中,所述糖醇是乳糖醇或麦芽糖醇。
3.漱口剂,其中包含权利要求1或2所述的抗菌剂。
4.牙膏,其中包含权利要求1或2所述的抗菌剂。
5.吸入剂,其中包含权利要求1或2所述的抗菌剂。
6.含片剂,其中包含权利要求1或2所述的抗菌剂。
7.食品,其中含有权利要求1或2所述的抗菌剂。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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JP2009165554A JP5710111B2 (ja) | 2009-07-14 | 2009-07-14 | ラクチトール、マルチトールからなる抗菌剤 |
JP2009-165554 | 2009-07-14 | ||
PCT/JP2010/004530 WO2011007551A1 (ja) | 2009-07-14 | 2010-07-13 | 糖アルコールを含む歯周病原菌増殖抑制抗菌剤 |
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JP (1) | JP5710111B2 (zh) |
KR (1) | KR20120042968A (zh) |
CN (1) | CN102470113A (zh) |
TW (1) | TW201117804A (zh) |
WO (1) | WO2011007551A1 (zh) |
Cited By (1)
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CN106061485A (zh) * | 2013-12-27 | 2016-10-26 | 高露洁-棕榄公司 | 使用糖类的益生性口腔护理方法 |
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WO2015084314A1 (en) * | 2013-12-02 | 2015-06-11 | Colgate-Palmolive Company | Oral care zinc compositions |
WO2023199057A1 (en) * | 2022-04-13 | 2023-10-19 | Brunel University London | Compositions for preventing and treating infection comprising an artificial sweetener |
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WO1999055342A1 (de) * | 1998-04-28 | 1999-11-04 | Südzucker Aktiengesellschaft | Isomalt als wirkstoff enthaltendes erkältungsmittel |
JP2008148614A (ja) * | 2006-12-17 | 2008-07-03 | Shuhei Higashimatsu | プリン様食品 |
JP2008283964A (ja) * | 2007-04-19 | 2008-11-27 | Lion Corp | 糖衣チューインガム組成物及び糖衣チューインガムの製造方法 |
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JPS5697215A (en) * | 1979-12-29 | 1981-08-05 | Lion Corp | Composition for oral cavity application |
JPS56118012A (en) * | 1980-02-23 | 1981-09-16 | Lion Corp | Composition for oral cavity |
JP3763075B2 (ja) * | 1998-04-24 | 2006-04-05 | サンスター株式会社 | 歯周病の予防又は治療用の食品組成物、口腔用組成物及び医薬組成物 |
JP4873805B2 (ja) * | 2001-09-07 | 2012-02-08 | 小林製薬株式会社 | 抗歯周病剤 |
JP4528472B2 (ja) * | 2001-11-29 | 2010-08-18 | ビオフェルミン製薬株式会社 | 歯周病の予防または治療剤 |
JP2006282562A (ja) * | 2005-03-31 | 2006-10-19 | Kobayashi Pharmaceut Co Ltd | セイヨウトチノキの抽出成分を配合した歯周病用剤 |
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2009
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2010
- 2010-07-13 WO PCT/JP2010/004530 patent/WO2011007551A1/ja active Application Filing
- 2010-07-13 KR KR1020127003725A patent/KR20120042968A/ko not_active Application Discontinuation
- 2010-07-13 CN CN2010800297408A patent/CN102470113A/zh active Pending
- 2010-07-14 TW TW099123129A patent/TW201117804A/zh unknown
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WO1999055342A1 (de) * | 1998-04-28 | 1999-11-04 | Südzucker Aktiengesellschaft | Isomalt als wirkstoff enthaltendes erkältungsmittel |
JP2008148614A (ja) * | 2006-12-17 | 2008-07-03 | Shuhei Higashimatsu | プリン様食品 |
JP2008283964A (ja) * | 2007-04-19 | 2008-11-27 | Lion Corp | 糖衣チューインガム組成物及び糖衣チューインガムの製造方法 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106061485A (zh) * | 2013-12-27 | 2016-10-26 | 高露洁-棕榄公司 | 使用糖类的益生性口腔护理方法 |
CN106061485B (zh) * | 2013-12-27 | 2019-07-23 | 高露洁-棕榄公司 | 使用糖类的益生性口腔护理方法 |
Also Published As
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WO2011007551A1 (ja) | 2011-01-20 |
JP5710111B2 (ja) | 2015-04-30 |
JP2011020935A (ja) | 2011-02-03 |
KR20120042968A (ko) | 2012-05-03 |
TW201117804A (en) | 2011-06-01 |
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