CN107073061B - 含有作为活性成分的桑白皮提取物与卫矛提取物的龋齿预防及治疗用口腔组合物 - Google Patents
含有作为活性成分的桑白皮提取物与卫矛提取物的龋齿预防及治疗用口腔组合物 Download PDFInfo
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- CN107073061B CN107073061B CN201680000798.7A CN201680000798A CN107073061B CN 107073061 B CN107073061 B CN 107073061B CN 201680000798 A CN201680000798 A CN 201680000798A CN 107073061 B CN107073061 B CN 107073061B
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- dental caries
- cortex mori
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Abstract
本发明涉及一种含有作为活性成分的桑白皮提取物与卫矛提取物的龋齿预防及治疗用口腔组合物，更具体地说，本发明涉及一种包含具有卓越的龋齿预防、改善及治疗效果的作为活性成分的桑白皮提取物与卫矛提取物的口腔组合物。凭借本发明，提供了具有卓越的龋齿预防、改善及治疗效果的口腔组合物或健康功能食品。
Description
技术领域
本发明涉及一种含有作为活性成分的桑白皮提取物与卫矛提取物的龋齿预防及治疗用口腔组合物，更具体地说，本发明涉及一种包含具有卓越的龋齿预防、改善及治疗效果的作为活性成分的桑白皮提取物与卫矛提取物的口腔组合物。
背景技术
人的口腔内栖息着各种微生物，引起口腔疾病的口腔微生物大部分栖息在形成于牙齿与牙龈之间的细菌膜的菌斑上。
上述口腔微生物在菌斑生成毒素而这些微生物所生产的毒素则侵入牙周组织内引起牙龈的炎症、牙槽骨的破坏及感染而成为牙周病，这些细菌生成酸时则成为蛀齿原因。
如前所述，分布在口腔内的微生物能够引起臼齿、龋齿及牙周病之类的疾病，这些微生物中的一部分还可以作为条件致病菌而导致各种疾病。
常驻于口腔内并且引起龋齿与牙周炎的病原性微生物有很多种，其中，变形链球菌(Streptococcus mutans)与牙龈卟啉单胞菌(Porphyromonas gingivalis)被视为引起龋齿与牙周炎的主病原体。
口腔内病原性微生物从菌体外或表面分泌出称为葡萄糖基转移酶(Glucosyltransferase，GTase)的酶并且以食物内的蔗糖(sucrose)为基质生成葡萄糖(glucose)与果糖(fructose)，与此同时，在齿面上形成葡萄糖聚合物不溶性葡聚糖(insoluble glucan)。所形成的葡聚糖让其它微生物附接在齿面而形成齿面细菌膜，亦即，形成齿斑(dental plaque)。乳酸菌则在该齿斑内增殖并且以果糖为碳源生成乳酸，乳酸被捕集浓缩在附接性葡聚糖，这样浓缩后的高浓度酸则让构成牙齿的磷酸钙中的Ca2+融化而把作为牙齿外膜的珐琅质(enamel)加以溶解并且因此导致龋齿。
因此，人们开发了能够有效抑制口腔微生物的很多种药物并且开发了应用该药物的各种口腔卫生品。
与此相关的先前技术可以举例大韩民国公开专利第10-2012-0022423号“含有作为活性成分的海燕窝提取物的口腔卫生增进用组合物”和大韩民国公开专利第10-2008-0113504号“含有作为活性成分的人参果实提取物的口腔细菌抑制用组合物”。
桑白皮是桑树(Morus alba L.)或同属植物的根皮，其在很久以前就作为消炎性利尿剂、缓和剂及镇咳祛痰剂应用于中医药剂。
近来，这些桑白皮所含各种成分逐渐被人们发现并且探明了其药理效果，尤其是，其降血压、降血糖及镇痛作用被广泛认知。
卫矛(winged spindle)是无患子目卫矛科的落叶灌木并且分布在韩国、日本、库页岛、中国地区。其嫩叶作为山菜食用，而其树枝上的翼则称为鬼箭羽。叶子含有表木栓醇(epifriedelanol)、木栓酮(friedelin)、槲皮素(quercetin)、卫矛醇(dulcitol)。其种子油则含有饱和脂肪酸(20%)、油酸、亚油酸、亚麻酸、羊蜡酸及安息香酸等。在在中医药上用于止血、驱淤血及生理痛。 为此，本发明人为了开发出对龋齿致病菌具有卓越抗菌效果的药物而使用具备前述效能的桑白皮与卫矛并且确认其效能而完成了本发明。
发明内容
技术问题
本发明的目的是提供一种含有作为活性成分的桑白皮提取物与卫矛提取物的龋齿预防及治疗用口腔组合物。
本发明需要解决的技术问题不限于前述问题，本领域所属领域中具备通常知识者可以在下面的记载中明确地了解到前面没有提到的其它问题。
用于解决问题的手段
为了达到上述目的，本发明的龋齿预防及治疗用口腔组合物或龋齿预防及改善用健康功能食品的特征在于，含有作为活性成分的桑白皮提取物与卫矛提取物，并且呈现出对于龋齿病原菌的生长抑制活性。
*上述龋齿病原菌是变形链球菌(Streptococcus mutans)。
上述桑白皮提取物与卫矛提取物以1:1重量比组成。
上述桑白皮提取物或卫矛提取物是以乙醇(Ethanol)提取的。
上述口腔组合物具有选自牙膏类、口香糖、口腔清净剂、口腔清洗剂及口腔喷雾剂的一个以上的剂型。
上述健康功能食品具有选自粉末、颗粒、片剂、胶囊或饮料的一个以上的剂型。
发明效果
凭借本发明，能够提供一种含有作为活性成分的桑白皮提取物与卫矛提取物并且具有卓越的龋齿预防、改善及治疗效果的口腔组合物或健康功能食品。凭此，相比于现有的一般牙膏，本发明能够提高口腔用药效成分的稳定性并且发挥出预防及治疗龋齿疾病的效果。
附图说明
图1是示出桑白皮提取物的抗菌活性的曲线图。
图2是示出卫矛提取物的抗菌活性的曲线图。
图3及4是示出由桑白皮提取物+卫矛提取物构成的混合提取物的抗菌活性的曲线图。
具体实施方式
下面将详细说明本发明，下面将省略可能会非必要地混淆本发明主旨的公知结构或功能的详细说明。
本发明提供一种含有作为活性成分的桑白皮提取物与卫矛提取物的龋齿预防及治疗用口腔组合物。
此时，关于上述桑白皮提取物或卫矛提取物的提取，先让桑白皮或卫矛各自干燥再以各重量(g)的5～15倍溶剂提取，优选地，可溶于选自水、C1到C4低碳醇或其混合溶剂的溶剂的提取物，优选地，利用乙醇在10到50℃下(在20到30℃下更佳)于1到150小时期间(在3到36小时期间更佳)反复提取1到10次(反复提取3到5次更佳)后得到提取物。
本发明人得知，把如前所述地制备的上述桑白皮提取物与卫矛提取物各自作为活性成分使用时，在提取物上以100到1000ppm以上的高浓度包含才能对龋齿病原菌呈现出抗菌活性。为此，为了制造出即使在低浓度提取物也能呈现出本发明所追求的针对龋齿病原菌的抗菌活性地制造出可产品化的组合物，把上述桑白皮提取物与上述卫矛提取物混合使用较佳，相比于现有的一般牙膏，本发明不仅能够提高口腔用药效成分的稳定性，还能发挥出龋齿疾病的预防及治疗效果。
此时，为了得到本发明所追求的对于龋齿病原菌的最佳生长抑制活性，需要把上述桑白皮提取物与上述卫矛提取物以1:1重量比混合后作为龋齿预防及治疗用口腔组合物的活性成分使用较佳，本发明尤其对龋齿病原菌中的变形链球菌(Streptococcus mutans)呈现出抗菌活性。
如前所述，含有本发明的提取物的口腔组合物可以制成牙膏类、口香糖、口腔清净剂、口腔清洗剂及口腔喷雾剂之类的剂型后使用，但并不限定于此。
本发明的牙膏类包含选自研磨剂、黏结剂、保湿剂、活性成分、发泡剂、甜味料、调味剂的组合物。
关于研磨剂，可以把氢氧化铝、二氧化硅、硅酸铝、磷酸二钙、第二氢氧化物及酸酐、磷酸三钙、碳酸钙、焦磷酸钙、不溶性偏磷酸鈉、磷酸三镁、碳酸镁、硫酸钙、聚甲基丙烯酸甲酯、其它合成树脂等的1种或2种以上以整体组合物的约20-90%的量配合后使用(如果是膏状牙膏，则为20-60%)。关于黏结剂，可以把角菜胶、各种增粘用纤维素衍生物、黄原胶、龙须胶(Tragacanth gum)之类的胶类、聚乙烯醇、聚丙烯酸钠、聚丙烯酸/马来酸共聚物、羧乙烯基聚合物之类的合成高分子衍生物等有机黏结剂和二氧化硅、锂藻土之类的无机黏结剂的1种或2种以上以整体组合物的约0.3-5%的量配合后使用。
关于牙膏类，在膏态与液态口腔用组合物方面可以在制造时把山梨醇、甘油、乙二醇、丙二醇、聚醚多元醇、聚丙二醇等的1种或2种以上作为保湿剂以整体组合物的约10-70%的量配合后使用。
另一方面，关于含有本发明的提取物的口腔组合物，可以把薄荷醇(Mentol)、茴香脑(Anetol)、丁香油酚(Eugenol)、柠檬油精(Limonene)、罗勒烯(Ocimene)、n-十二醇(n-Dodecy Alcohol)、香茅醇(Citronenol)、α-松油醇(a-Terpineol)、甲基水杨酸辛酯(Methyl salycilate)、乙酸甲酯(Methyl Acetate)、乙酸香草酯(Citronelyl Acetate)、桉油酚(Cineol)、芳樟醇(Linalool)、乙基芳樟醇(Ethyl Linalool)、香草醛(Vanillin)、麝香草酚(Thymol)、荷兰薄荷(Speamint)油、鼠尾草(Sage)油、迷迭香(Rosemary)油、桂皮(Cinamon)油之类的香料以单独或组合方式以整体组合物的0.1-10%，优选地，以0.5-5%的量配合后使用。
而且，把糖精钠、甜菊苷、阿斯巴甜、D-木糖(D-Xylose)之类的甜味剂等以整体组合物的0-1%，优选地，以0.01-0.5%的量配合后使用。
而且，关于本发明的口腔组合物，可以把二氯苯氧氯酚、双氯苯双胍己烷、苄索氯铵、苯扎氯铵、氯化十六烷吡啶之类的阳离子性杀菌剂；单氟磷酸钠与单氟磷酸钙之类的碱金属单氟磷酸鹽；氟化钠、氟化亚锡之类的氟化物；氨甲环酸、ε-氨基已酸、铝克洛沙、二氢胆甾醇、甘草酸类、甘油磷酸、氯化钠、水溶性无机磷酸化合物、抗坏血酸(纳)、醋酸dl-a-生育酚、木糖醇、盐酸吡哆辛、聚乙烯吡咯烷酮之类的各种效能成分的1种或2种以上加以选择并配合后使用。
而且，在本发明的口腔组合物中作为泡沫成分使用的表面活性剂方面，可以使用阴离子表面活性剂、非离子表面活性剂及/或阳离子表面活性剂。在此，阴离子表面活性剂可以使用十二烷基硫酸钠、十四烷基硫酸钠之类的硫酸烷基钠；月桂酰肌氨酸钠(SodiumN-Lauroyl sarcosinate)、N-十四烷基肌氨酸钠(Sodium N-miristyl sarcosinate)之类的N-酰基肌氨酸钠(Sodium N-acyl sarcosinate)等，非离子表面活性剂可以使用糖脂肪酸酯、麦芽糖脂肪酸酯、乳糖脂肪酸酯等源于糖的脂肪酸酯；聚氧乙烯氢化蓖麻油、高碳醇聚氧乙烯醚, 聚氧乙烯聚氧丙烯共聚物、聚氧乙烯 聚丙烯脂肪酸酯等。阳离子表面活性剂可以使用N-十二烷基二氨基乙基甘氨酸(N-LAURYL DIAMINOETHYLGLYCINE), N-十四烷基二氨基乙基甘氨酸之类的N-烷基二氨基乙基甘氨酸、N-烷基-N-羧甲基铵甜菜碱(N-ALKYLCARBOXYMETHYL AMMONIUM BETAINE)、N-烷基-1-羟乙基咪唑啉甜菜碱钠等。此时，泡沫成分主要使用阴离子表面活性剂，其中具有代表性者以十二烷基硫酸钠之类的烷基硫酸钠最广泛地使用。而且，这些表面活性剂可以单独使用1种或者把2种以上混合后使用，配合量通常以整体组合物的0.01-0.5%，更优选地，以0.05-0.3%使用。
而且，本发明还揭示了含有作为活性成分的上述提取物的龋齿预防及改善用健康功能食品。
含有本发明的提取物的健康功能食品可以多样化地应用于预防及改善龋齿的药剂、食品及饮料等处。可添加本发明的提取物的食品可以举例各种食品类、饮料、口香糖、茶维生素复合剂、健康辅助食品类等，能以粉末、颗粒、片剂、胶囊或饮料形态使用。
本发明的提取物本身几乎没有毒性及副作用，因此即使为了预防而长时间服用也能够放心使用。
为此，本发明的上述提取物可以为了预防及改善龋齿而添加到食品或饮料。此时，关于食品或饮料中的上述提取物的量，本发明的健康食品组合物通常可以添加整体食品重量的0.01到15重量%，健康饮料组合物则能以100㎖为基准添加0.02到10g，优选地，能以0.3到1g的比率添加。
本发明的健康饮料组合物作为必要成分必须以所设定的比率含有上述提取物或化合物，除此之外，本发明对液体成分没有特别限制，和一般饮料一样地能把各种调味剂或天然碳水化合物等作为辅助性成分包含在内。前述天然碳水化合物可以举例诸如葡萄糖、果糖之类的单糖；诸如麦芽糖、蔗糖之类的二糖；诸如糊精、环糊精之类的多糖及木糖醇、山梨糖醇、赤藓醇之类的糖醇。上述成分之外的调味剂可以使用天然调味剂(甜味蛋白、甜叶菊提取物(例如莱苞迪甙A、甘草皂苷等)及合成调味剂(糖精、阿斯巴甜等)。本发明的组合物100㎖中上述天然碳水化合物的比率通常是大约1到20g，优选地，大约5到12g。
除此之外，本发明的组合物还可以包含各种营养剂、维生素、矿物(电解质)、合成风味剂及天然风味剂之类的风味剂、着色剂及增味剂(乳酪、巧克力等)、果胶酸及其盐、藻酸及其盐、有机酸、保护性胶体增粘剂、pH调节剂、稳定剂、防腐剂、甘油、乙醇、碳酸饮料所用碳酸化剂等。除此之外，本发明的健康功能食品可以包含用来制作天然果汁、果汁饮料及蔬菜饮料的果肉。该成分可以独立使用或组合后使用。该添加剂的比率不是很重要，但通常以本发明的组合物100重量份为基准选择0到约20重量份。
下面将结合实施例及实验例进一步说明本发明，但这些实施例及实验例的目的仅仅在于说明本发明，其并不能限制本发明的请求范围。
<实施例1> 制备由桑白皮提取物+卫矛提取物构成的混合提取物
甲．制备桑白皮提取物
利用精制水清洗桑白皮后，在常温下自然干燥了7天。
在上述干燥处理后以粉碎机予以粉末化，然后把该桑白皮粉末1kg放入70%乙醇10ℓ并且在常温下回流提取3小时，反复进行3次后制成了提取物。
过滤上述提取物并且只回收余液，然后减压蒸馏得到液态桑白皮提取物(受领浓度: 10000ppm)。
此时，利用灭菌蒸馏水以10倍为单位依次稀释上述制成的桑白皮提取物后制成了各个浓度(0.1、1、10、100、1000、10000ppm)。
乙．制备卫矛提取物
利用精制水清洗卫矛树枝后，在常温下自然干燥了7天。
在上述干燥处理后以粉碎机予以粉末化，然后把该卫矛粉末1kg放入70%乙醇10ℓ并且在常温下回流提取3小时，反复进行3次后制成了提取物。
过滤上述提取物并且只回收余液，然后减压蒸馏得到液态卫矛提取物(受领浓度:10000ppm)。
此时，利用灭菌蒸馏水以10倍为单位依次稀释上述制成的卫矛提取物后制成了各个浓度(0.1、1、10、100、1000、10000ppm)。
丙．制备混合提取物
按照各相同浓度备妥上述步骤甲中制成的桑白皮提取物与上述步骤乙中制成的卫矛提取物后，制成了以1:1重量比混合的混合提取物。
<实验例 1>确认抗菌活性
为了确认桑白皮提取物与卫矛提取物及它们的混合提取物对龋齿菌的抗菌活性，进行了MIC(mininal inhibitory concentration)测试。
1. 试验对象菌株
所用的菌株是由韩国生命工程研究院模式培养物集存库(Korea Collection forType Cultures, KCTC)分配的、作为龋齿病原菌的变形链球菌(Streptococcus mutans)KCTC 3065菌株。
2. 试验方法
1)菌株培养条件
把上述获得分配的、作为龋齿病原菌的变形链球菌(Streptococcus mutans)KCTC 3065菌株接种到Brain heart infusion broth培养基后，在37℃进行了静止培养。
2)提取物的处理
①让最终混合液成为5㎖地把灭菌的液体培养基4.45㎖、提取物0.5㎖(10%, V/V)、106cfu/㎖浓度的细菌培养液0.05㎖混合到试验管后制成了混合液。
②关于提取物，对利用原液与灭菌蒸馏水以10倍为单位依次稀释的稀释液进行了处理。
③桑白皮提取物与卫矛提取物的混合处理组则把各提取物以0.25㎖放入，不处理提取物时则处理0.5㎖的灭菌蒸馏水。
3)培养方法
在37℃下培养试验管30小时，该试验管则装入了包含细菌培养液、提取物、灭菌后的液体培养基的上述①的混合液。
关于抗菌活性的判定，每培养3小时就取出各处理组的混合液0.1㎖后利用96wellpalte在600nm测量了细菌增殖所导致的吸光度变化。
2. 实验结果
1)桑白皮提取物的抗菌活性
图1以Streptococcus mutans KCTC 3065菌株为对象对桑白皮提取物的抗菌活性进行了试验，通过该试验得知，在低浓度的10ppm几乎没有抗菌活性，在50ppm下也只是呈现出较弱的抗菌活性。
2)卫矛提取物的抗菌活性
图2以Streptococcus mutans KCTC 3065菌株为对象对卫矛提取物的抗菌活性进行了试验，通过该试验得知，在低浓度的10ppm、50ppm下几乎没有抗菌活性。
3)由桑白皮提取物+卫矛提取物组成的混合提取物的抗菌活性
图3及图4以Streptococcus mutans KCTC 3065菌株为对象对桑白皮提取物+卫矛提取物所构成的混合提取物的抗菌活性进行了试验，对混合提取物以10～100ppm处理时呈现出抗菌活性。
具体比较说明的话，如图3所示，单独处理低浓度的卫矛提取物5ppm时(-▲-)几乎没有呈现出活性。而且，单独处理桑白皮提取物5ppm时(-■-)也几乎没有呈现出活性，与此相反，作为本发明的活性成分的1:1混合提取液(实施例1)的抗菌活性则相比于各自投入的情形相对较高(-◆-)。
尤其是，如图4所示，单独处理卫矛提取物50ppm(-▲-)及单独处理桑白皮提取物50ppm时(-■-)也没有达到本发明所追求的抗菌活性，与此相反，作为本发明的活性成分的1:1混合提取液(实施例1)则对作为龋齿病原菌的变形链球菌(Streptococcus mutans)呈现出100%的抑制活性，相比于单独处理的提取物，作为本发明的活性成分的1:1混合提取液(实施例1)被判定为对抗菌活性具备了相乘效应(-◆-)。
因此，利用根据本发明制备的牙周病预防及治疗用组合物时能够对引起牙周病的菌株发挥出优异的抗菌活性而能够发挥出预防及治疗牙周病的效果，凭此，其可以作为健康食品、医药品之类的材料使用而得以提高其附加价值。
<制剂例1: 牙膏的制备>
以70到75℃的温度把属于下述表1的a的成分投入制造单元后搅拌20分钟让粉体完全溶解，然后冷却到常温。
接着是保湿剂、甜味料及有益成分的溶解工序，把含有上述实施例1所制载体的属于b的成分以25到30℃投入制造单元后搅拌混合15分钟地予以溶解。
接着是粉体及粘性剂混合工序，把属于c的成分在25到35℃混合后按阶段投入。下一个工序是起泡剂混合及第一阶段除沫工序，添加属于d的成分并且在25到35℃下历时40分钟的工序期间完成了第一阶段除沫。最后一个工序是香混合工序，添加属于e的成分并且在25到35℃下进行第二阶段除沫后制成牙膏。
其组合物则遵守下列表1的内容。
[表1]
前文以优选实施例为主说明了前述本发明，本发明所属领域中具有通常知识者可以在本发明的本质性技术范围内实现不同于上述发明内容的其它形态的实施例。在此，本发明的本质性技术范围呈现在权利要求书中，与其处于同等范围内的一切差异均应阐释为属于本发明。
Claims (5)
1.一种龋齿预防及治疗用口腔组合物，其特征在于，
以1:1重量比含有作为活性成分的桑白皮的70％(v/v)乙醇水溶液提取物与卫矛的70％(v/v)乙醇水溶液提取物，并且呈现出对于作为龋齿病原菌的变形链球菌(Streptococcus mutans)的生长抑制活性。
2.根据权利要求1所述的龋齿预防及治疗用口腔组合物，其特征在于，
上述口腔组合物为口腔清净剂的剂型。
3.根据权利要求1所述的龋齿预防及治疗用口腔组合物，其特征在于，上述口腔组合物具有选自牙膏、口香糖、口腔清洗剂及口腔喷雾剂的一个以上的剂型。
4.一种龋齿改善用健康功能食品，其特征在于，
以1:1重量比含有作为活性成分的桑白皮的70％(v/v)乙醇水溶液提取物与卫矛的70％(v/v)乙醇水溶液提取物，并且呈现出对于作为龋齿病原菌的变形链球菌(Streptococcus mutans)的生长抑制活性。
5.根据权利要求4所述的龋齿改善用健康功能食品，其特征在于，
上述健康功能食品具有选自粉末、颗粒、片剂、胶囊或饮料的一个以上的剂型。
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- 2016-04-27 CN CN201680000798.7A patent/CN107073061B/zh not_active Expired - Fee Related
- 2016-04-27 WO PCT/KR2016/004410 patent/WO2016186335A2/ko active Application Filing
Non-Patent Citations (1)
| Title |
|---|
| Inhibition of Major Virulence Pathways of Streptococcus mutans by Quercitrin and Deoxynojirimycin: ASynergistic Approach of Infection Control;Sadaf Hasan等;《Plos one》;20140331;第9卷(第3期);第1-12页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107073061A (zh) | 2017-08-18 |
| KR101641215B1 (ko) | 2016-07-20 |
| WO2016186335A2 (ko) | 2016-11-24 |
| WO2016186335A3 (ko) | 2017-01-12 |
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