CN114585418A - 口腔护理组合物 - Google Patents
口腔护理组合物 Download PDFInfo
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- CN114585418A CN114585418A CN202080039349.XA CN202080039349A CN114585418A CN 114585418 A CN114585418 A CN 114585418A CN 202080039349 A CN202080039349 A CN 202080039349A CN 114585418 A CN114585418 A CN 114585418A
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- oral care
- silica
- care composition
- composition
- enzyme
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
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- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
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- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
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- 235000013772 propylene glycol Nutrition 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
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- 229940084560 sanguinarine Drugs 0.000 description 1
- YZRQUTZNTDAYPJ-UHFFFAOYSA-N sanguinarine pseudobase Natural products C1=C2OCOC2=CC2=C3N(C)C(O)C4=C(OCO5)C5=CC=C4C3=CC=C21 YZRQUTZNTDAYPJ-UHFFFAOYSA-N 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
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- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 description 1
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- YVDPOVXIRVBNAL-UHFFFAOYSA-J tetrapotassium;phosphonatooxy phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OOP([O-])([O-])=O YVDPOVXIRVBNAL-UHFFFAOYSA-J 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
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- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
- 229960000314 zinc acetate Drugs 0.000 description 1
- 235000013904 zinc acetate Nutrition 0.000 description 1
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- 239000011670 zinc gluconate Substances 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/25—Silicon; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/66—Enzymes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Cosmetics (AREA)
Abstract
一种包含酶和二氧化硅的组合物，其中至少50重量％的至少一种酶被吸附到二氧化硅上。
Description
技术领域
本发明涉及包含酶的组合物。更具体地，本发明涉及含有酶的口腔护理组合物。
背景技术
EP3192496、EP3192495及EP3192565和EP3192564中描述了含有酶的口腔护理组合物。然而，仍然需要配制具有增强的酶活性的组合物。
本申请涉及一种用于提高口腔护理产品中酶的活性的组合物和方法。
发明内容
本申请涉及一种包含表面活性剂、酶和二氧化硅的组合物，其中至少50重量％的至少一种酶被吸附到二氧化硅上。
本申请还涉及一种制备根据前述权利要求中任一项所述的组合物的方法，其中将所述酶加入到二氧化硅的预混合物中。
吸附是一种界面现象，其中颗粒或分子结合于材料的顶层。
为避免疑义，本发明的一个方面的任何特征可用于本发明的任何其他方面。任何描述为“优选的”特征应理解为与进一步优选的一个或多个特征组合是特别优选的。本文中，特定实施方案的任何特征可用于本发明的任何其他实施方案中。所有百分比为重量/重量百分比，除非表明另外的情况。
具体实施方式
本申请涉及包含酶的组合物，优选地组合物是个人护理组合物并且更优选地组合物是口腔护理组合物。本发明组合物的优选产品形式是适用于刷洗和/或冲洗口腔表面的那些。
本发明的组合物最优选为洁牙剂(dentifrice)的形式。术语“洁牙剂”表示用于清洁口腔表面的口腔组合物。这种组合物不是为了全身施用治疗剂的目的而有意吞咽，而是应用于口腔，用于处理口腔，然后吐出。通常这样的组合物与清洁工具如牙刷结合使用，通常通过将其施加到牙刷的刷毛然后刷洗口腔的可及表面。
优选地，洁牙剂/牙膏是可挤出的半固体形式，如乳膏、糊剂或凝胶(或其混合物)。
根据本发明的组合物包含酶。优选地，酶选自以下的组：
i)糖苷水解酶，更优选淀粉酶，最优选淀粉葡萄糖苷酶；
ii)作用于供体的OH基团的氧化还原酶(oxoreductase)，更优选以氧作为受体的氧化酶，最优选葡萄糖氧化酶；
iii)血红素过氧化物酶，更优选卤素过氧化物酶，最优选乳过氧化物酶。
优选地酶是上述两种的混合物，更优选上述三种的混合物，最优选淀粉葡萄糖苷酶、葡萄糖氧化酶和乳过氧化物酶的混合物。
在本发明的上下文中，单独的或作为酶混合物的部分的葡萄糖氧化酶是特别优选的。
优选地，酶的总含量为总组合物的0.01重量％至2重量％。更优选为总组合物的0.05重量％至1重量％。
优选地，组合物中糖苷水解酶的总含量为总组合物的0.05至1重量％。
优选地，作用于供体的OH基团的氧化还原酶的总含量为总组合物的0.05至1重量％。
优选地，血红素过氧化物酶的总含量为总组合物的0.0005至0.01重量％。
优选地，组合物中糖苷水解酶与其他酶的重量比大于1:1，更优选大于3:2。
本发明的组合物还可包含其他蛋白质如溶菌酶、乳铁蛋白和初乳。优选地，这些其他蛋白质以总组合物的0.001至0.5重量％，优选总组合物的0.005至0.1重量％的总含量存在。
根据本发明的组合物包含二氧化硅。本发明中使用的优选二氧化硅是具有低折射率的二氧化硅。它可用作唯一的磨料二氧化硅，或与低含量的其他磨料二氧化硅(例如，根据EP 236070的那些)结合使用。在本发明中用作磨料的低折射率二氧化硅优选地是表观折射率(apparent refractive index)(R.I.)在1.41-1.47，优选地1.43-1.45范围内，优选地具有5-15μm的重均粒径，介于10至150m2/g之间的BET(氮)表面积和约为70-150cm3/100g的吸油量的二氧化硅，但也可以使用表观折射率较低的磨料二氧化硅。合适的低折射率磨料二氧化硅(例如具有介于1.435和1.445之间的R.I.)的典型例子是来自Rhone Poulenc的Tixosil 63和73；来自Degussa的Sident 10；来自Zeofinn的Zeodent 113；来自Huber的Zeodent 124，来自Crosfield Chemicals的Sorbosil AC 77(具有约1.440的R.I.)。这些二氧化硅在组合物中的量范围一般为总组合物的5-60重量％，更优选地5-20重量％。
优选地酶吸附在增稠二氧化硅上。优选地，二氧化硅具有小于150cm3/100g、更优选地小于1cm3/100g的吸油量。优选地，二氧化硅是研磨二氧化硅。优选地，二氧化硅具有8至14微米，更优选10至12微米的平均粒径。特别优选的二氧化硅是Zeodent 165和Tixosil43，因为这种类型的二氧化硅由于增强了酶活性而是优选的。
优选地总二氧化硅与总酶的比率为150:1至5:1，更优选地100:1至10:1，最优选地60:1至20:1。
优选地酶吸附在二氧化硅上。优选地，吸附可以通过主物料法(main batchmethod)进行，其中酶紧接在二氧化硅分散体之后并在聚合物增稠剂/结构化剂和/或调味剂之前添加，或者通过使用侧锅(side pot)法进行，其中二氧化硅添加到酶预混合溶液，随后预混合物在聚合物增稠剂/结构化剂和/或调味剂之前加入到主物料(main batch)。
优选地口腔护理组合物含有组合物的0.2至7重量％的量的表面活性剂。优选的是非离子表面活性剂，例如聚乙氧基化脂肪酸脱水山梨糖醇酯、乙氧基化脂肪酸、聚乙二醇酯、脂肪酸单甘油酯和二甘油酯的乙氧基化物，以及环氧乙烷/环氧丙烷嵌段聚合物。特别优选的是脂肪醇的聚乙二醇醚，特别是每个单元具有20至40个环氧乙烷基团的聚乙二醇醚。这种合适的表面活性剂的例子包括被称为Steareth表面活性剂的一组表面活性剂，例如Steareth 30。优选地，非离子表面活性剂的含量为总组合物的0.5至7重量％，更优选地为总组合物的1至5重量％。
尽管可以存在其他表面活性剂，优选的是，它们的含量限于低于总组合物的0.5重量％，优选地低于总组合物的0.1重量％。
口腔护理组合物，尤其是在洁牙剂的情况下，还可含有结构化剂和例如粘合剂和增稠剂的试剂。基于组合物的总重量，这些结构化剂通常以0.1至1重量％的量存在。合适的粘合剂或增稠剂包括羧乙烯基聚合物(例如与聚烯丙基蔗糖或聚烯丙基季戊四醇交联的聚丙烯酸)、羟乙基纤维素、羟丙基纤维素、天然树胶(例如角叉菜胶、刺梧桐树胶、瓜尔胶、黄原胶、阿拉伯树胶和黄蓍胶)。基于天然树胶的增稠剂，特别是角叉菜胶，是特别优选的。
在优选产品形式中，基于组合物的总重量，水和/或多元醇的量以水和/或多元醇的总重量计通常为至少10％，优选至少30％，更优选至少50％。优选地，水和/或多元醇的含量低于总组合物的90重量％，更优选地低于85重量％。
根据本发明的洁牙剂组合物通常含有不同相对量的水和多元醇的混合物作为水性连续相，水的量通常为10至50重量％(基于洁牙剂的总重量)并且多元醇的量通常为20-60重量％(基于洁牙剂的总重量)。
用于口腔护理组合物，特别是根据本发明的洁牙剂组合物中的典型多元醇包括保湿剂，例如甘油、山梨糖醇、聚乙二醇、聚丙二醇、丙二醇、木糖醇(和其他可食用多元醇)、氢化部分水解多糖及其混合物。优选甘油和山梨糖醇，特别优选山梨糖醇。
口腔护理组合物，特别是洁牙剂组合物包含磨料。基于洁牙剂的总重量，磨料通常以0.5至75重量％，优选3至60重量％的量存在。合适的磨料清洁剂包括二氧化硅干凝胶、水凝胶和气凝胶以及沉淀的颗粒状二氧化硅；碳酸钙、磷酸二钙、磷酸三钙、煅烧氧化铝、偏磷酸钠和偏磷酸钾、焦磷酸钠和焦磷酸钾、三偏磷酸钠、六偏磷酸钠、颗粒状羟基磷灰石及其混合物。二氧化硅是特别优选的，因为它们可以执行双重功能，作为磨料和增强酶活性的手段。优选地，组合物，特别是牙膏，包含如上所述的基于二氧化硅的磨料。
组合物，特别是牙膏，优选地包含占总组合物重量的约0.10至约15％的比例的无机或天然或合成增稠剂或胶凝剂，取决于所选择的材料。本发明洁牙剂组合物中增稠剂的这些比例形成可挤出的、形状保持的产品，其可以从管中挤压到牙刷上并且不会落入牙刷的刷毛之间，而是在其上基本上保持其形状。可用于实施本发明的合适的增稠剂或胶凝剂包括细分的硅酸盐、锂蒙脱石、碳酸钙、胶态硅酸镁铝及其混合物，优选的是无机增稠二氧化硅，如可从Huber Corporation以商品名Zeodent 165获得的无定形二氧化硅，和/或树胶如爱尔兰苔藓(Irish moss)、iota-角叉菜胶、黄蓍胶和聚乙烯吡咯烷酮。
本发明的组合物可包含金属离子，如锡或锌。优选地，锌离子的来源是氯化锌、乙酸锌、葡萄糖酸锌、硫酸锌、氟化锌、柠檬酸锌、乳酸锌、氧化锌、单甘油酸锌、酒石酸锌、焦磷酸锌、马来酸锌及其混合物。
本发明的组合物可包含氟化物源如氟化钠、氟化亚锡、单氟磷酸钠、氟化锌铵、氟化锡铵、氟化钙、氟化钴铵及其混合物。
本发明的组合物还可包含本领域惯用的其他任选成分，例如抗菌剂，例如洗必泰、血根碱提取物、甲硝唑、季铵化合物，如西吡氯铵；双胍类，如二葡萄糖酸氯己定、海克替啶、奥替尼啶、阿来西丁；和卤化双酚化合物，如2,2'-亚甲基双-(4-氯-6-溴苯酚)；
抗炎药，如布洛芬、氟比洛芬、阿司匹林、消炎痛等；
防龋剂，如氟化钠和氟化亚锡、胺氟化物、单氟磷酸钠、三偏磷酸钠和酪蛋白；
菌斑缓冲剂，如尿素、乳酸钙、甘油磷酸钙和聚丙烯酸锶；
维生素，如维生素A、C和E；
植物提取物；
植物来源的抗氧化剂，如类黄酮、儿茶素、多酚和单宁化合物及其混合物；
脱敏剂，例如，柠檬酸钾、氯化钾、酒石酸钾、碳酸氢钾、草酸钾、硝酸钾和锶盐；
抗牙结石剂，例如，碱金属焦磷酸盐、含次磷酸盐的聚合物、有机磷酸盐和磷酸柠檬酸盐等；
生物分子，例如，细菌素、抗体、酶等；
风味剂，例如，薄荷和留兰香油；
蛋白质性材料如胶原蛋白；
防腐剂；
遮光剂；
氨基酸，如精氨酸；
着色剂；
pH调节剂；
甜味剂；
药学上可接受的载体，例如，淀粉、蔗糖、水或水/醇系统等；
表面活性剂，如阴离子表面活性剂、非离子表面活性剂、阳离子表面活性剂和两性离子表面活性剂或两性表面活性剂；
保湿剂，如甘油、山梨糖醇、丙二醇、木糖醇、乳糖醇等；
粘合剂和增稠剂，如
黄原胶、阿拉伯胶等，以及合成聚合物，如聚丙烯酸酯和羧乙烯基聚合物，如
还可以包括可以增强活性成分(如抗菌剂)递送的聚合物；
缓冲剂和盐以缓冲口腔护理组合物的pH值和离子强度；和
其他可能包含的任选成分是例如，漂白剂，如过氧化合物(例如过氧二磷酸钾)、泡腾系统(如碳酸氢钠/柠檬酸系统)、变色系统，等等。
现在将通过以下非限制性实施例说明本发明：
实施例
葡萄糖氧化酶预混合物的组成如表1所示：
表1
| 材料 | 量/g |
| 苯甲酸钠 | 0.2 |
| 硫氰酸钾 | 10.0 |
| 甘油 | 30.5 |
| 水 | 41.3 |
| Maxapal葡萄糖氧化酶4L | 68.0 |
按照表2中的量制备样品。使用磁力搅拌器在室温下分散粉末30分钟。Zeta电位是通过动态光散射测量的，其使用具有通用浸入池和173度反向散射角的Malvern ZetaSizerNanoSeries。之后使用水稀释样品以使浊度最小化。所有测量均重复3次。Zeta电位结果表明酶，葡萄糖氧化酶(GOx)，在二氧化硅上的显著吸附，如从颗粒表面电荷的大幅度下降指示的。
表2
葡萄糖氧化酶在37℃下与单个配方成分一起在0.05mM柠檬酸盐-磷酸盐缓冲液，pH 7中孵育。10分钟后，使用标准试剂盒和试剂测量葡萄糖氧化酶活性。
·
Red葡萄糖/葡萄糖检测试剂盒-来自Invitrogen-目录号A22189。
·
UltraRed试剂-来自Invitrogen-目录号A36006]。
表3
表3表明当酶吸附到二氧化硅上时，活性增加。与Tixosil 43相比，Zeodent 113具有增强的酶活性。
本发明的一个实施例如下：
表4
(组合物含有1450ppm的作为NaF的F)
*沉淀二氧化硅
**增稠二氧化硅
在该实施例中，在加入到牙膏混合物之前，将葡萄糖氧化酶加入增稠二氧化硅中。
Claims (15)
1.一种包含表面活性剂、酶和二氧化硅的口腔护理组合物，其中至少50重量％的至少一种酶被吸附到二氧化硅上。
2.如权利要求1所述的口腔护理组合物，其中所述二氧化硅具有8至14微米的平均粒径。
3.如权利要求2所述的口腔护理组合物，其中所述口腔护理组合物是洁牙剂。
4.如前述权利要求中任一项所述的口腔护理组合物，其中所述酶选自糖苷水解酶、作用于供体的OH基团的氧化还原酶、血红素过氧化物酶或其混合物。
5.如前述权利要求中任一项所述的口腔护理组合物，其中所述酶选自淀粉酶、以氧作为受体的氧化酶、卤素过氧化物酶或其混合物。
6.如前述权利要求中任一项所述的口腔护理组合物，其中所述酶选自淀粉葡萄糖苷酶、葡萄糖氧化酶、乳过氧化物酶或其混合物。
7.如前述权利要求中任一项所述的口腔护理组合物，其中所述酶或酶混合物包含葡萄糖氧化酶。
8.如前述权利要求中任一项所述的口腔护理组合物，其中所述组合物包含吸附在二氧化硅上的至少两种如前述权利要求中任一项所述的酶的混合物。
9.如前述权利要求中任一项所述的口腔护理组合物，其中所述组合物包含吸附在二氧化硅上的至少三种如前述权利要求中任一项所述的酶的混合物。
10.如前述权利要求中任一项所述的口腔护理组合物，其中所述二氧化硅的吸油量小于150cm3/100g。
11.如前述权利要求中任一项所述的口腔护理组合物，其中总二氧化硅与总酶的比率为100:1至10:1。
12.如前述权利要求中任一项所述的口腔护理组合物，其中所述组合物进一步包含非离子表面活性剂。
13.如权利要求12所述的口腔护理组合物，其中所述非离子表面活性剂是脂肪醇的聚乙二醇醚。
14.一种制备如前述权利要求中任一项所述的组合物的方法，其中将所述酶添加到二氧化硅的预混合物中。
15.如权利要求14所述的方法，其中添加所述组合物的组分使得所述二氧化硅紧接在添加所述酶之前添加到所述预混合物中。
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| CN102015028A (zh) * | 2008-04-22 | 2011-04-13 | 丹尼斯科美国公司 | 含有氧化酶的口腔护理组合物 |
| WO2014067933A1 (en) * | 2012-10-31 | 2014-05-08 | C-Lecta Gmbh | Bioactive carrier preparation for enhanced safety in care products and food |
| EP3192496A1 (en) * | 2016-01-12 | 2017-07-19 | Unilever PLC | Oral care compositions |
| EP3192565A1 (en) * | 2016-01-12 | 2017-07-19 | Unilever PLC | Oral care composition comprising a protein for balancing the bacterial flora of the mouth |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2020239627A1 (en) | 2020-12-03 |
| EP3976203A1 (en) | 2022-04-06 |
| BR112021021541A2 (pt) | 2021-12-28 |
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Application publication date: 20220603 |