JP2008063282A - Composition for oral cavity - Google Patents

Composition for oral cavity Download PDF

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JP2008063282A
JP2008063282A JP2006243519A JP2006243519A JP2008063282A JP 2008063282 A JP2008063282 A JP 2008063282A JP 2006243519 A JP2006243519 A JP 2006243519A JP 2006243519 A JP2006243519 A JP 2006243519A JP 2008063282 A JP2008063282 A JP 2008063282A
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composition
oral cavity
sodium
hyaluronic acid
oral
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Seiko Nagao
清香 長尾
Yoshihiro Sakaguchi
由洋 坂口
Shuji Kariya
周司 苅谷
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GC Corp
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GC Corp
GC Dental Industiral Corp
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for oral cavity, consisting of an aqueous solution of platinum nano colloid and without agglomerating the platinum nano colloid during its preservation. <P>SOLUTION: This composition for oral cavity contains the platinum nano colloid having 1 to 5 nm mean particle diameter, a hyaluronic acid salt and water. The composition can be used as a liquid dental paste material, mouth wash, tooth surface-applying agent, etc. These compositions can be blended with, for example a thickening agent, a surfactant, a sweetener, a preservative, various active ingredients, a coloring matter, an aromatizing agent or the like as necessary. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

本発明は抗酸化能を有する口腔用組成物に関する。   The present invention relates to an oral composition having antioxidant ability.

歯の表面には主に細菌と細菌が作り出す多糖とからなる歯垢が付いており、その内部に蓄えられた酸が歯質のエナメル質を脱灰して齲蝕を発生させ、更に特定の菌により産生された毒素が歯肉炎,歯周炎,歯槽膿漏をもたらすといわれている。   The surface of the tooth has plaque mainly consisting of bacteria and polysaccharides produced by the bacteria, and the acid stored in the tooth decalcifies the enamel of the tooth to generate caries, and then a specific bacteria It is said that the toxin produced by this causes gingivitis, periodontitis, and alveolar pyorrhea.

一方生体は、これらの細菌の感染及び侵襲に対して血球成分の一つである多形核白血球やマクロファージ等の生体防御反応を誘導する因子を動員して細菌の排除を行う免疫機構を持つ。免疫機構が働くと生体防衛反応として免疫細胞から活性酸素が放出され細菌等を死滅させるが、一方で活性酸素は周辺組織細胞をも破滅してしまうことが知られている。高濃度の活性酸素は粘膜組織を傷害するだけでなく疼痛,外科処置後の治癒不全,歯周病による歯周組織破壊、義歯性褥瘡の痛みや治癒の遅延,更には細胞DNAをも傷害するため口腔癌の高いリスクファクターの可能性が指摘されている。   On the other hand, the living body has an immune mechanism that mobilizes factors that induce biological defense reactions such as polymorphonuclear leukocytes and macrophages that are one of blood cell components against infection and invasion of these bacteria to eliminate bacteria. It is known that when the immune mechanism works, active oxygen is released from immune cells as a biological defense reaction and kills bacteria and the like, while active oxygen also destroys surrounding tissue cells. High concentrations of active oxygen not only damage mucosal tissue but also pain, healing failure after surgery, periodontal tissue destruction due to periodontal disease, pain and delayed healing of denture pressure ulcers, and even cellular DNA Therefore, the possibility of a high risk factor for oral cancer has been pointed out.

口腔内の活性酸素を除去するための組成物として、ヒアルロン酸の塩と抗酸化物質とを含む口腔用組成物があるが(特許文献1参照。)、アスコルビン酸,酢酸トコフェノール,カロテノイド等のビタミン類や,カテキン,ポリフェノール等の抗酸化物質は体内に存在しているとされる11種類の活性酸素の中で、それぞれがその中の1種類あるいは2〜3種類を除去することしかできない。例えば、アスコルビン酸はスーパーオキシドのみを除去して自身は抗酸化作用を持たないデヒドロアスコルビン酸へと変化してしまう。このように従来の抗酸化物質とヒアルロン酸の塩との組み合わせでは、特定の活性酸素は除去できるものの除去後に抗酸化作用を持たない物質へと変化してしまうのでその効果が限定的という問題があった。   As a composition for removing active oxygen in the oral cavity, there is an oral composition containing a salt of hyaluronic acid and an antioxidant (see Patent Document 1), but ascorbic acid, tocophenol acetate, carotenoids, etc. Antioxidants such as vitamins, catechins, and polyphenols can only remove one or two or three of them among the 11 types of active oxygen that are supposed to exist in the body. For example, ascorbic acid removes only superoxide and changes itself to dehydroascorbic acid which does not have an antioxidant action. As described above, in the combination of the conventional antioxidant and the salt of hyaluronic acid, although the specific active oxygen can be removed, it changes to a substance having no antioxidant action after the removal, so that the effect is limited. there were.

一方、従来から白金ナノコロイドに活性酸素を除去する能力があることが知られている(例えば、特許文献2参照)。白金ナノコロイドは白金の保有する触媒作用を利用して活性酸素を除去するため、それ自身が存在する限り何度でも活性酸素を除去することができる長所がある。また白金ナノコロイドは、スーパーオキシドアニオン,スーパーオキシドアニオンラジカル,過酸化水素,ヒドロキシラジカル,一重項酸素,過酸化脂質ラジカル,過酸化アルコールラジカル,一酸化窒素等様々な種類の活性酸素を除去する能力を有している。しかしながら従来の白金ナノコロイドを水溶液として用いると当該組成物においてその保存期間中に白金ナノコロイドが凝集してしまい活性酸素除去の効果が低下するという問題があった。
特開平10−182390号公報 国際公開第2005/023467号公報
On the other hand, it is conventionally known that platinum nanocolloids have the ability to remove active oxygen (see, for example, Patent Document 2). Since platinum nanocolloid removes active oxygen using the catalytic action of platinum, it has an advantage that it can remove active oxygen as many times as it exists. Platinum nanocolloid has the ability to remove various types of active oxygen such as superoxide anion, superoxide anion radical, hydrogen peroxide, hydroxy radical, singlet oxygen, lipid peroxide radical, alcohol peroxide radical, and nitric oxide. have. However, when a conventional platinum nanocolloid is used as an aqueous solution, there is a problem in that the platinum nanocolloid aggregates during the storage period in the composition and the effect of removing active oxygen is reduced.
Japanese Patent Laid-Open No. 10-182390 International Publication No. 2005/023467

本発明は、白金ナノコロイドの水溶液から成る口腔用組成物において、白金ナノコロイドが保存期間中に凝集することがない保存安定性の高い口腔用組成物を提供することを課題とする。   An object of the present invention is to provide an oral composition comprising a platinum nanocolloid aqueous solution and having a high storage stability in which the platinum nanocolloid does not aggregate during the storage period.

本発明者等は前記課題を解決すべく鋭意研究を重ねた結果、白金ナノコロイドの水溶液である口腔用組成物に所定量のヒアルロン酸の塩を配合すると前記課題を解決できることを見出して本発明を完成した。   As a result of intensive studies to solve the above problems, the present inventors have found that the above problems can be solved by adding a predetermined amount of hyaluronic acid salt to an oral composition which is an aqueous solution of platinum nanocolloid. Was completed.

即ち本発明は、1〜5nmの平均粒子径を有する白金ナノコロイドと所定量のヒアルロン酸の塩と水とを含む口腔用組成物である。   That is, the present invention is an oral composition containing platinum nanocolloid having an average particle diameter of 1 to 5 nm, a predetermined amount of a salt of hyaluronic acid, and water.

本発明に係る口腔用組成物は、白金ナノコロイドが保存期間中に凝集することがない保存安定性の高い優れた口腔用組成物である。   The composition for oral cavity according to the present invention is an excellent composition for oral cavity with high storage stability in which platinum nanocolloids do not aggregate during the storage period.

本発明に係る白金ナノコロイドは、一重項酸素除去能を有する物質として従来から知られているものであって水溶液として存在していれば良い。例えば国際公開第2005/023467号公報に記載されているものが使用できる。組成物中の白金ナノコロイド濃度は0.1〜10μmol/Lであることが好ましい。0.1μmol/L未満では活性酸素除去の効果が低く、10μmol/Lを超えると製造コストがかかり過ぎる問題がある。   The platinum nanocolloid according to the present invention is conventionally known as a substance having a singlet oxygen removing ability and may be present as an aqueous solution. For example, what is described in International Publication No. 2005/023467 can be used. The platinum nanocolloid concentration in the composition is preferably 0.1 to 10 μmol / L. If it is less than 0.1 μmol / L, the effect of removing active oxygen is low, and if it exceeds 10 μmol / L, there is a problem that the production cost is too high.

本発明に係る口腔用組成物に用いるヒアルロン酸の塩は、白金ナノコロイドが水溶液中で保存期間中に凝集するのを防ぐ効果がある。塩としては、ナトリウム、カリウム等の一価の金属塩が利用可能であり、生体に安全である物質から適宜選択できる。ヒアルロン酸の塩の配合量は組成物全体の0.1〜2重量%が好ましく、0.1重量%未満では効果を得難く、2重量%を超えて配合しても効果は向上しない。   The hyaluronic acid salt used in the oral composition according to the present invention has an effect of preventing the platinum nanocolloid from aggregating in an aqueous solution during storage. As the salt, a monovalent metal salt such as sodium or potassium can be used, and can be appropriately selected from substances that are safe for living bodies. The blending amount of the hyaluronic acid salt is preferably 0.1 to 2% by weight of the total composition, and if it is less than 0.1% by weight, it is difficult to obtain the effect, and even if it exceeds 2% by weight, the effect is not improved.

本発明に係る口腔用組成物は、歯磨剤、洗口剤,歯面塗布剤,人工唾液等に応用可能である。これらの応用製品群には必要に応じて例えば粘稠剤,界面活性剤,甘味剤,防腐剤,各種有効成分,色素,香料等が配合できる。   The composition for oral cavity according to the present invention can be applied to dentifrices, mouthwashes, tooth surface coating agents, artificial saliva and the like. These applied product groups can contain, for example, thickeners, surfactants, sweeteners, preservatives, various active ingredients, pigments, fragrances and the like as necessary.

粘稠剤としては、グリセリン,ソルビット,プロピレングリコール,ポリエチレングリコール,カルボキシメチルセルロースナトリウム,ヒドロキシエチルセルロース,カラギーナン,アルギン酸ナトリウム,キサンタンガム,カーボポール,グアーガム,モンモリロナイト,ゼラチン、あるいはヒュームドシリカ等が挙げられる。粘調剤は口腔用組成物中に0.05〜15重量%配合されることが好ましい。   Examples of the thickener include glycerin, sorbit, propylene glycol, polyethylene glycol, sodium carboxymethyl cellulose, hydroxyethyl cellulose, carrageenan, sodium alginate, xanthan gum, carbopol, guar gum, montmorillonite, gelatin, and fumed silica. It is preferable that 0.05 to 15% by weight of the viscous agent is blended in the composition for oral cavity.

界面活性剤としては、アニオン界面活性剤,カチオン界面活性剤,非イオン性界面活性剤を配合し、具体的にはラウリル硫酸ナトリウム,α−オレフィンスルホン酸ナトリウム,N−アシルサルコシネート,N−アシルグルタメート,2−アルキル−N−カルボキシメチル−N−ヒドロキシエチルイミダゾリニウムベタイン,N−アシルタウレート,ショ糖脂肪酸エステル,アルキロールアマイド,ポリオキシエチレンソルビタンモノステアレート,プルロニックが例示できる。これらの界面活性剤は口腔用組成物中に0.1〜5重量%配合されることが好ましい。   As the surfactant, an anionic surfactant, a cationic surfactant, and a nonionic surfactant are blended. Specifically, sodium lauryl sulfate, sodium α-olefin sulfonate, N-acyl sarcosinate, N- Examples thereof include acyl glutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, N-acyl taurate, sucrose fatty acid ester, alkylol amide, polyoxyethylene sorbitan monostearate, and pluronic. These surfactants are preferably blended in the oral composition in an amount of 0.1 to 5% by weight.

甘味剤としては、キシリトール,サッカリンナトリウム,ステビオサイド,パラメトキシシンナミックアルデヒド,ネオヘスペリジルジヒドロカルコン,ペリラルチン,キシリット,マルチット,ラクチット等の従来から一般的な口腔用組成物に用いられているものが使用でき、甘味料は口腔用組成物中に0.1〜20重量%配合されることが好ましい。   As sweeteners, those conventionally used in general oral compositions such as xylitol, sodium saccharin, stevioside, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perilartine, xylit, maltite, lactit can be used. The sweetener is preferably blended in the oral composition in an amount of 0.1 to 20% by weight.

防腐剤としては、パラオキシ安息香酸ブチル,パラオキシ安息香酸メチル,パラオキシ安息香酸エチル等の安息香酸エステル,安息香酸ナトリウム,安息香酸,ソルビン酸カリウム,デヒドロ酸ナトリウム,サリチル酸等が使用でき、口腔用組成物中に0.01〜5重量%配合されることが好ましい。   As preservatives, benzoic acid esters such as butyl paraoxybenzoate, methyl paraoxybenzoate, ethyl paraoxybenzoate, sodium benzoate, benzoic acid, potassium sorbate, sodium dehydroate, salicylic acid, etc. can be used, and oral compositions It is preferable that 0.01 to 5 weight% is mix | blended in.

各種有効成分も従来の口腔用組成物で用いられていたものが特に制限無く使用できる。例えば、齲蝕予防の有効成分として、フッ化ナトリウム,フッ化カリウム,フッ化アンモニウム,フッ化第一スズ,モノフルオロリン酸ナトリウム,モノフルオロリン酸カリウム等のフッ化物。歯石沈着防止の有効成分として、正リン酸のカリウム塩,ナトリウム塩等の水溶性リン酸化合物やピロリン酸ナトリウム,ポリリン酸ナトリウム,ゼオライト,デキストラナーゼ。歯周病予防や口臭予防の有効成分として、アラントインクロルヒドロキシアルミニウム,ヒノキチオール,塩化リゾチーム,グリチルリチン酸及びその塩類,塩化ナトリウム,ε-アミノカプロン酸,イソプロピルメチルフェノール,クロルヘキシジン塩類,塩化セチルピリジニウム,アズレンスルホン酸ナトリウム,銅クロロフィリンナトリウム,塩化ベンゼトニウム,酢酸dl-α-トコフェノール,トリクロサン。その他の有効成分として、塩化カルシウム,塩化ナトリウム,リン酸カリウム,塩化ストロンチウム,硝酸カリウム,シュウ酸カリウム,乳酸アルミニウム,ヒドロキサム酸及びその誘導体,ポリビニルピロリドン,グルコン酸銅等の銅化合物,ムタナーゼ,アミラーゼ,ジヒドロコレステロール,エピジヒドロコレステリン,トリクロロカルバニリド,ベルベリン,α−ビサボロール,トウキ軟エキス,オウバクエキス,チョウジ,ローズマリー,オウゴン,ベニバナなどの抽出物等がある。更に香料としては、l−メントール,カルボン,アネトール,リモネンのテルペン類又はその誘導体、着色剤としては、青色1号,黄色4号,二酸化チタン等が例示される。各種有効成分は本発明に係る口腔用組成物中に0.01〜10重量%配合されることが好ましい。   Various active ingredients that have been used in conventional oral compositions can be used without particular limitation. For example, fluoride such as sodium fluoride, potassium fluoride, ammonium fluoride, stannous fluoride, sodium monofluorophosphate, potassium monofluorophosphate as an active ingredient for preventing caries. Water-soluble phosphate compounds such as orthophosphate potassium and sodium salts, sodium pyrophosphate, sodium polyphosphate, zeolite, and dextranase as active ingredients for preventing calculus deposition. As an active ingredient for preventing periodontal disease and bad breath, allantochlorohydroxyaluminum, hinokitiol, lysozyme chloride, glycyrrhizic acid and its salts, sodium chloride, ε-aminocaproic acid, isopropylmethylphenol, chlorhexidine salts, cetylpyridinium chloride, azulenesulfonic acid Sodium, copper chlorophyllin sodium, benzethonium chloride, dl-α-tocophenol acetate, triclosan. Other active ingredients include calcium chloride, sodium chloride, potassium phosphate, strontium chloride, potassium nitrate, potassium oxalate, aluminum lactate, hydroxamic acid and its derivatives, polyvinyl pyrrolidone, copper compounds such as copper gluconate, mutanase, amylase, dihydro There are extracts such as cholesterol, epidihydrocholesterin, trichlorocarbanilide, berberine, α-bisabolol, soft sugar beet extract, buckwheat extract, clove, rosemary, ugone, safflower. Furthermore, examples of the fragrance include l-menthol, carvone, anethole, limonene terpenes or derivatives thereof, and examples of the colorant include blue No. 1, yellow No. 4, titanium dioxide and the like. It is preferable that 0.01 to 10% by weight of various active ingredients is blended in the oral composition according to the present invention.

<実施例>
「実施例1,2、比較例1,2」
表1に示した配合量に従い、白金ナノコロイド水溶液(白金ナノコロイド:シーテック社製 濃度 1mmol/L)にヒアルロン酸の塩を加えた実施例1,2及びヒアルロン酸の塩を加えない比較例1、ヒアルロン酸の塩を加えずにクエン酸ナトリウムを加えた比較例2の各口腔用組成物(フッ素供給用の口腔用洗浄液)を作製した。下記の評価方法により白金ナノコロイドの凝集の有無と活性酸素の除去能力を評価した。結果を表1に示す。
<Example>
"Examples 1 and 2, Comparative Examples 1 and 2"
According to the blending amounts shown in Table 1, Examples 1 and 2 in which a hyaluronic acid salt was added to a platinum nanocolloid aqueous solution (platinum nanocolloid: Concentration 1 mmol / L, manufactured by Seatec Co.) and Comparative Example 1 in which no hyaluronic acid salt was added Each oral composition of Comparative Example 2 in which sodium citrate was added without adding the hyaluronic acid salt (oral cleaning solution for supplying fluorine) was prepared. The presence or absence of aggregation of platinum nanocolloids and the ability to remove active oxygen were evaluated by the following evaluation methods. The results are shown in Table 1.

<表1> (重量部)

Figure 2008063282
<Table 1> (parts by weight)
Figure 2008063282

「実施例3,4、比較例3,4」
表2に示した配合量に従い、白金ナノコロイド水溶液にヒアルロン酸の塩を加えた実施例3,4及びヒアルロン酸の塩を加えない比較例3,ヒアルロン酸の塩を加えずにクエン酸ナトリウムを加えた比較例4の各口腔用組成物(口腔内洗浄液)を作製した。
"Examples 3 and 4, Comparative Examples 3 and 4"
Examples 3 and 4 in which a salt of hyaluronic acid was added to a platinum nanocolloid aqueous solution according to the blending amount shown in Table 2, and Comparative Example 3 in which a salt of hyaluronic acid was not added. Sodium citrate was added without adding a salt of hyaluronic acid. Each composition for oral cavity of Comparative Example 4 (oral cleaning solution) was prepared.

<表2> (重量部)

Figure 2008063282
<Table 2> (parts by weight)
Figure 2008063282

表3に示した配合量に従い、各口腔用組成物(人工唾液)を調製した。下記評価方法により白金ナノコロイドの凝集の有無を評価した。結果を表3に示す。   Each oral composition (artificial saliva) was prepared according to the blending amount shown in Table 3. The presence or absence of aggregation of platinum nanocolloid was evaluated by the following evaluation method. The results are shown in Table 3.

<表3> (重量部)

Figure 2008063282
<Table 3> (Parts by weight)
Figure 2008063282

<凝集の評価方法>
作製した口腔用組成物を60℃の条件下で7日間保存し、液面を上から目視にて確認した。微少な白金ナノコロイドの凝集体である黒点が1個以上確認された場合を「有り」、1つも確認できなかった場合を「無し」として評価した。
<Aggregation evaluation method>
The prepared oral composition was stored for 7 days under the condition of 60 ° C., and the liquid level was visually confirmed from above. The case where one or more black spots, which are agglomerates of minute platinum nanocolloids, were confirmed was evaluated as “present” and the case where none was confirmed as “absent”.

<活性酸素の除去能力>
体内に存在すると言われている活性酸素の中で、比較的安定で体内に多く存在している過酸化水素を指標として活性酸素の除去能力を評価した。500mmol/Lの過酸化水素100μL毎に各実施例及び比較例の口腔用組成物を200μL混合し37℃で24時間静置しサンプルとした。蒸留水により1000倍希釈した各サンプル150μLとシュウ酸ジエステル(TDPO)とピレン混合溶液50μLを混合攪拌し、混合から40秒間の発光量をルミネッセンサーPSN(ATTO社)で測定し積算値を算出した(a)。また、コントロールとして、各実施例及び比較例の口腔用組成物の代わりに蒸留水を加えたサンプルの1000倍希釈液150μLにTDPO/ピレン混合溶液50μLを混合攪拌し、混合から40秒間の発光量を積算値を算出した結果(b)を用い、以下の計算式に従い活性酸素の除去能力を評価した。なお、TDPOと過酸化水素が反応し1,2−ジオキセタンジオンとなり、これがピレンと反応して発光するため、測定対象中に過酸化酸素の残量が多いほど発光量が多い。

活性酸素の除去能力(%) = (1−a/b) × 100
<Removability of active oxygen>
Among the active oxygens that are said to be present in the body, the ability to remove active oxygen was evaluated using hydrogen peroxide, which is relatively stable and present in the body, as an index. Each 100 μL of 500 mmol / L of hydrogen peroxide was mixed with 200 μL of the oral composition of each example and comparative example and allowed to stand at 37 ° C. for 24 hours to prepare a sample. 150 μL of each sample diluted 1000 times with distilled water, 50 μL of oxalic acid diester (TDPO) and pyrene mixed solution are mixed and stirred, and the amount of luminescence for 40 seconds after mixing is measured with a luminescence sensor PSN (ATTO) to calculate the integrated value. (A). In addition, as a control, 50 μL of a TDPO / pyrene mixed solution was mixed and stirred in 150 μL of a 1000-fold diluted sample of distilled water added instead of the oral composition of each Example and Comparative Example, and the amount of light emitted for 40 seconds after mixing. Using the result (b) of calculating the integrated value, the ability to remove active oxygen was evaluated according to the following calculation formula. Since TDPO and hydrogen peroxide react to form 1,2-dioxetanedione, which reacts with pyrene to emit light, the more the amount of oxygen peroxide remaining in the measurement target, the greater the amount of light emitted.

Removal capacity of active oxygen (%) = (1-a / b) × 100

Claims (1)

1〜5nmの平均粒子径を有する白金ナノコロイドと、ヒアルロン酸の塩と、水とを含む口腔用組成物。   An oral composition comprising platinum nanocolloid having an average particle diameter of 1 to 5 nm, a hyaluronic acid salt, and water.
JP2006243519A 2006-09-08 2006-09-08 Composition for oral cavity Pending JP2008063282A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014034538A (en) * 2012-08-08 2014-02-24 Ibio Epoch:Kk Tooth paste and its production method, and dental rinse
JP2021028308A (en) * 2019-08-09 2021-02-25 株式会社日本触媒 Aqueous dispersion for cosmetics, dispersion protective agent, and manufacturing method of cosmetics
RU2788728C1 (en) * 2022-01-17 2023-01-24 Георгий Александрович Фролов Composition with long-lasting biocidal effect and the composition mouthwash

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014034538A (en) * 2012-08-08 2014-02-24 Ibio Epoch:Kk Tooth paste and its production method, and dental rinse
JP2021028308A (en) * 2019-08-09 2021-02-25 株式会社日本触媒 Aqueous dispersion for cosmetics, dispersion protective agent, and manufacturing method of cosmetics
RU2788728C1 (en) * 2022-01-17 2023-01-24 Георгий Александрович Фролов Composition with long-lasting biocidal effect and the composition mouthwash

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