JP7167938B2 - Oral biofilm formation inhibitor and oral composition - Google Patents
Oral biofilm formation inhibitor and oral composition Download PDFInfo
- Publication number
- JP7167938B2 JP7167938B2 JP2019557225A JP2019557225A JP7167938B2 JP 7167938 B2 JP7167938 B2 JP 7167938B2 JP 2019557225 A JP2019557225 A JP 2019557225A JP 2019557225 A JP2019557225 A JP 2019557225A JP 7167938 B2 JP7167938 B2 JP 7167938B2
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- Prior art keywords
- oral
- biofilm formation
- component
- polyacrylate
- molecular weight
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 45
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Classifications
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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
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
-
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
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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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- 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
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
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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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- 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
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/28—Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants
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)
- Oral & Maxillofacial Surgery (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
Description
本発明は、口腔バイオフィルム形成抑制剤及びこれを含有する口腔用組成物に関する。 TECHNICAL FIELD The present invention relates to an oral biofilm formation inhibitor and an oral composition containing the same.
口腔疾患は病原菌が原因で発症するが、この病原菌は歯面にプラーク(歯垢)を形成することで口腔内に定着し病原性を発揮する。そこで、口腔疾患の予防には、プラークコントロールが非常に重要である。プラークコントロールの手段としては、プラークの形成抑制や除去、殺菌などが挙げられ、中でもプラークの除去が重要とされている。
しかし、プラーク除去の基本であるブラッシング等の物理的な除去方法では、歯間や歯周ポケット等、ブラシが届きにくい箇所があるために除去効果には限界があることもあり、プラークが形成されるのを予め防止する技術が注目され、プラーク形成を抑制する技術の確立が期待されている。
近年、プラークは、単なる細菌の汚れという認識から、細菌凝集体と細菌外代謝物などからなるバイオフィルムであると考えられるようになり、このバイオフィルムは強固に構築されているため、殺菌剤等に対する抵抗性や、歯面から剥がれ難いといった物理的な抵抗性を有することも知られている。このような現状から、耐性の高いバイオフィルムを形成させないような抑制技術が望まれている。Oral diseases are caused by pathogenic bacteria, which colonize the oral cavity by forming plaque (dental plaque) on the tooth surface and exhibit pathogenicity. Therefore, plaque control is very important for prevention of oral diseases. Means for plaque control include suppression of plaque formation, removal, and sterilization, and among them, removal of plaque is considered to be important.
However, physical removal methods such as brushing, which is the basis of plaque removal, are limited in removal effect because there are places where it is difficult for the brush to reach, such as between teeth and periodontal pockets, and plaque is not formed. Techniques for preventing plaque formation are attracting attention, and the establishment of techniques for suppressing plaque formation is expected.
In recent years, plaque has been considered to be a biofilm consisting of bacterial aggregates and extracellular metabolites, etc., from the recognition that plaque is simply a stain of bacteria. It is also known to have physical resistance such as resistance to abrasion and resistance to peeling from the tooth surface. Under such circumstances, there is a demand for a control technique that prevents the formation of highly resistant biofilms.
歯垢に対する形成抑制技術として、抗菌剤であるトリクロサンの滞留性向上技術(特許文献1;特開平4-139118号公報)が提案されているが、抗菌剤を用いた効果であるため、バイオフィルムに対する効果は十分とは言い難い。また、特殊なアクリル酸コポリマーによる歯垢の付着抑制技術も提案されている(特許文献2;特開平3-14512号公報)が、歯垢の初期付着を抑制する技術であり、付着後の強固なバリア形成を抑制する効果ではなく、十分な効果とは言えない。 As a technology for suppressing the formation of dental plaque, a technology for improving the retention of triclosan, an antibacterial agent (Patent Document 1; Japanese Patent Application Laid-Open No. 4-139118), has been proposed. It is hard to say that the effect on In addition, a technique for suppressing plaque adhesion using a special acrylic acid copolymer has also been proposed (Patent Document 2; JP-A-3-14512). It is not an effect of suppressing the formation of a strong barrier, and cannot be said to be a sufficient effect.
本発明は、上記事情に鑑みなされたもので、新たな口腔バイオフィルム形成抑制剤及びこれを含有する口腔用組成物を提供することを目的とする。 The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a novel oral biofilm formation inhibitor and an oral composition containing the same.
本発明者らは、上記目的を達成するため鋭意検討を行った結果、重量平均分子量が特定値以下のポリアクリル酸塩が、口腔バイオフィルムの形成を抑制する作用を有し、優れたバイオフィルム形成抑制効果を奏すること、更に、非イオン性殺菌剤を併用すると、前記ポリアクリル酸塩による作用が増強し、バイオフィルム形成抑制効果が格段に向上することを知見した。そして、これにより、前記ポリアクリル酸塩、好ましくはこのポリアクリル酸塩と非イオン性殺菌剤との併用系を口腔用組成物に配合することで、優れたバイオフィルム形成抑制効果を付与し、また、良好な使用感を与えることができることを見出し、本発明をなすに至った。 The present inventors have made intensive studies to achieve the above objects, and found that a polyacrylate having a weight average molecular weight of a specific value or less has the effect of suppressing the formation of oral biofilms, and excellent biofilms. It has been found that the effect of inhibiting biofilm formation is exhibited, and when a nonionic fungicide is used in combination, the action of the polyacrylate is enhanced, and the effect of inhibiting biofilm formation is remarkably improved. And, thereby, the polyacrylate, preferably by blending the combination system of the polyacrylate and the nonionic disinfectant into the oral composition, imparts an excellent biofilm formation inhibitory effect, In addition, the present inventors have found that they can provide a good feel during use, and have completed the present invention.
口腔用組成物用の粘結剤としてポリアクリル酸又はその塩は公知であるが、一般的に重量平均分子量10万以上、通常は30万程度の架橋型のポリアクリル酸又はその塩が用いられている。これに対して、本発明では、(a)重量平均分子量20,000以下である特定分子量のポリアクリル酸塩、特に直鎖状のポリアクリル酸塩に、口腔内でバイオフィルムが形成されるのを抑制するという、今まで知られていなかった作用効果があることが判明し、これにより、重量平均分子量が20,000を超えるポリアクリル酸塩、あるいは重量平均分子量が20,000以下でも塩の形態ではないポリアクリル酸を使用した場合には達成し得ない、格別顕著な作用効果が得られた。
後述の表1、表3中の比較例に示すように、重量平均分子量300,000のポリアクリル酸ナトリウム、あるいは重量平均分子量6,000のポリアクリル酸によるバイオフィルム形成抑制効果はいずれも×であったが、表1~3中の実施例に示すように、(a)成分によるバイオフィルム形成抑制効果はいずれも○又は◎以上であり、優れるものであった。
また、非イオン性殺菌剤は、バイオフィルム浸透殺菌作用があることが知られているが、バイオフィルム形成の抑制作用は認識されておらず、実際、後述の表3中の比較例3に示すように、イソプロピルメチルフェノールによるバイオフィルム形成抑制効果は低いものであった。しかし、本発明では、(a)成分と(b)非イオン性殺菌剤とを併用すると両者が相乗的に作用し、(a)成分による不快な臭いを抑制しつつバイオフィルム形成抑制効果が格段に増強した(後述の表1~3中の実施例参照)。
なお、本発明におけるバイオフィルム形成抑制の作用機序の詳細は明らかではないが、(a)成分に特有の化学的作用によって、(a)成分がバイオフィルム自体に作用し、特に、バイオフィルムが歯面で成長する際の強固なバリア形成が阻害されることで、新たなバイオフィルムの形成が防止されると推測される。Polyacrylic acid or a salt thereof is known as a binder for oral compositions, but generally a crosslinked polyacrylic acid having a weight average molecular weight of 100,000 or more, usually about 300,000, or a salt thereof is used. ing. On the other hand, in the present invention, (a) a polyacrylate with a specific molecular weight having a weight average molecular weight of 20,000 or less, particularly a linear polyacrylate, does not form a biofilm in the oral cavity. It has been found that there is a hitherto unknown action and effect of suppressing the A particularly pronounced effect was obtained that could not be achieved when using non-morphic polyacrylic acid.
As shown in Comparative Examples in Tables 1 and 3 below, the effect of suppressing biofilm formation by sodium polyacrylate with a weight average molecular weight of 300,000 or polyacrylic acid with a weight average molecular weight of 6,000 is x. However, as shown in Examples in Tables 1 to 3, the effect of suppressing biofilm formation by the component (a) was all excellent, being ◯ or ⊚ or better.
In addition, nonionic fungicides are known to have a biofilm penetration sterilization effect, but an inhibitory effect on biofilm formation has not been recognized, and in fact, shown in Comparative Example 3 in Table 3 below. Thus, the biofilm formation inhibitory effect of isopropylmethylphenol was low. However, in the present invention, when the component (a) and the nonionic fungicide (b) are used in combination, both act synergistically, and the biofilm formation inhibitory effect is remarkable while suppressing the unpleasant odor caused by the component (a). (see Examples in Tables 1-3 below).
Although the details of the mechanism of action for suppressing biofilm formation in the present invention are not clear, due to the chemical action peculiar to the component (a), the component (a) acts on the biofilm itself, particularly the biofilm. It is speculated that the formation of a new biofilm is prevented by inhibiting the formation of a strong barrier during growth on the tooth surface.
特許文献3(特公平7-29907号公報)では、抗歯石剤として重量平均分子量が約3,500~7,500であるポリアクリル酸重合体又はポリアクリル酸共重合体が約2.5%以上の量で口腔用組成物に配合されることを提案している。特許文献4(特開2000-247851号公報)は、特定のアニオン性高分子化合物および/またはその塩として分子量2万以上のポリアクリル酸重合体等を含む歯牙の着色抑制コーティング剤を提案するが、これはコーティングによる着色抑制であり、コーティング後の歯牙表面が親水化することでステインドペリクルの容易な除去及び蓄積防止が達成されるものである。これらに対して、本発明は、(a)特定分子量のポリアクリル酸塩による口腔バイオフィルム形成抑制であり、かかる作用効果は、塩形態ではないポリアクリル酸では劣り、一方で、口腔用組成物中の(a)成分量が2質量%以下でも優れるものである。 In Patent Document 3 (Japanese Patent Publication No. 7-29907), about 2.5% of a polyacrylic acid polymer or polyacrylic acid copolymer having a weight average molecular weight of about 3,500 to 7,500 is used as an anticalculus agent. It is proposed to be blended in the oral composition in the above amounts. Patent Document 4 (Japanese Unexamined Patent Application Publication No. 2000-247851) proposes a tooth discoloration-inhibiting coating agent containing a specific anionic polymer compound and/or a polyacrylic acid polymer having a molecular weight of 20,000 or more as a salt thereof. This is the suppression of discoloration by coating, and the hydrophilicity of the tooth surface after coating makes it possible to easily remove the stained pellicle and prevent its accumulation. On the other hand, the present invention is (a) suppression of oral biofilm formation by a polyacrylic acid salt with a specific molecular weight, and such an effect is inferior to polyacrylic acid that is not in the form of a salt. It is excellent even if the amount of component (a) in it is 2% by mass or less.
従って、本発明は、下記の口腔バイオフィルム形成抑制剤及び口腔用組成物を提供する。
〔1〕
(a)重量平均分子量が1,000以上20,000以下のポリアクリル酸塩を含有する口腔バイオフィルム形成抑制剤。
〔2〕
(a)重量平均分子量が1,000以上20,000以下のポリアクリル酸塩、及び
(b)非イオン性殺菌剤
を含有する口腔バイオフィルム形成抑制剤。
〔3〕
(b)成分が、イソプロピルメチルフェノール、トリクロサン及びチモールから選ばれる1種以上の非イオン性殺菌剤である〔2〕に記載の口腔バイオフィルム形成抑制剤。
〔4〕
(a)/(b)が質量比として0.01~200である〔2〕又は〔3〕に記載の口腔バイオフィルム形成抑制剤。
〔5〕
ポリアクリル酸塩の重量平均分子量が1,000以上10,000以下である〔1〕~〔4〕のいずれかに記載の口腔バイオフィルム形成抑制剤。
〔6〕
(a)重量平均分子量が1,000以上20,000以下のポリアクリル酸塩、及び
(b)非イオン性殺菌剤
を含有する口腔用組成物。
〔7〕
ポリアクリル酸塩の重量平均分子量が1,000以上10,000以下である〔6〕に記載の口腔用組成物。
〔8〕
(b)成分が、イソプロピルメチルフェノール、トリクロサン及びチモールから選ばれる1種以上の非イオン性殺菌剤である〔6〕又は〔7〕に記載の口腔用組成物。
〔9〕
(a)/(b)が質量比として0.01~200である〔6〕~〔8〕のいずれかに記載の口腔用組成物。
〔10〕
(a)成分を0.01~2質量%、(b)成分を0.01~1質量%含有する〔6〕~〔9〕のいずれかに記載の口腔用組成物。
〔11〕
口腔バイオフィルム抑制用である〔6〕~〔10〕のいずれかに記載の口腔用組成物。
〔12〕
歯磨剤組成物である〔6〕~〔11〕のいずれかに記載の口腔用組成物。Accordingly, the present invention provides the following oral biofilm formation inhibitor and oral composition.
[1]
(a) An oral biofilm formation inhibitor containing a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less.
[2]
(a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and (b) an oral biofilm formation inhibitor containing a nonionic bactericide.
[3]
(b) The oral biofilm formation inhibitor according to [2], wherein the component is one or more nonionic fungicides selected from isopropylmethylphenol, triclosan and thymol.
[4]
The oral biofilm formation inhibitor according to [2] or [3], wherein (a)/(b) is 0.01 to 200 as a mass ratio.
[5]
The oral biofilm formation inhibitor according to any one of [1] to [4], wherein the polyacrylate has a weight average molecular weight of 1,000 or more and 10,000 or less.
[6]
An oral composition containing (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and (b) a nonionic bactericide.
[7]
The oral cavity composition according to [6], wherein the polyacrylate has a weight average molecular weight of 1,000 or more and 10,000 or less.
[8]
(b) The oral composition according to [6] or [7], wherein the component is one or more nonionic disinfectants selected from isopropylmethylphenol, triclosan and thymol.
[9]
The oral cavity composition according to any one of [6] to [8], wherein (a)/(b) is 0.01 to 200 as a mass ratio.
[10]
The oral composition according to any one of [6] to [9], containing 0.01 to 2% by mass of component (a) and 0.01 to 1% by mass of component (b).
[11]
The oral composition according to any one of [6] to [10], which is for oral biofilm suppression.
[12]
The oral composition according to any one of [6] to [11], which is a dentifrice composition.
本発明によれば、口腔バイオフィルムの形成を抑制する作用効果が優れる口腔バイオフィルム形成抑制剤及びこれを含有する口腔用組成物を提供できる。本発明の口腔用組成物は、バイオフィルム形成抑制効果が高く、使用感もよいことから、効果的にバイオフィルムを抑制することができるため、歯周病等の口腔疾患の予防又は抑制に好適である。 INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an oral biofilm formation inhibitor having an excellent effect of suppressing oral biofilm formation and an oral composition containing the same. Since the oral composition of the present invention has a high biofilm formation inhibitory effect and a good feeling when used, it can effectively inhibit biofilms, so it is suitable for preventing or inhibiting oral diseases such as periodontal disease. is.
以下、本発明につき更に詳述する。本発明の口腔バイオフィルム形成抑制剤は、(a)重量平均分子量が1,000以上20,000以下のポリアクリル酸塩であり、上記(a)成分を有効成分として含有する。
(a)成分のポリアクリル酸塩は、重量平均分子量(Mw)が1,000以上20,000以下である。この場合、バイオフィルム形成抑制効果の点から、重量平均分子量は1,000以上であり、また、20,000以下であり、好ましくは10,000以下、より好ましくは8,000以下である。重量平均分子量が1,000未満であると、バイオフィルム形成抑制効果が劣る。20,000を超えると、バイオフィルム形成抑制効果が低下し、十分な効果が得られない。The present invention will be described in further detail below. The oral biofilm formation inhibitor of the present invention is (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and contains the above component (a) as an active ingredient.
The polyacrylate of component (a) has a weight average molecular weight (Mw) of 1,000 or more and 20,000 or less. In this case, the weight average molecular weight is 1,000 or more and 20,000 or less, preferably 10,000 or less, and more preferably 8,000 or less, from the viewpoint of biofilm formation suppression effect. When the weight average molecular weight is less than 1,000, the biofilm formation inhibitory effect is poor. If it exceeds 20,000, the effect of suppressing biofilm formation is reduced, and a sufficient effect cannot be obtained.
上記重量平均分子量の測定は、GPC(ゲルパーミェーションクロマトグラフィー法)により、特許第5740859号公報に記載された方法及び測定条件で行った。具体的には下記に示す(以下同様)。
重量平均分子量の測定方法;
重量平均分子量は、ゲル浸透クロマトグラフ/多角度レーザー光散乱検出器(GPC-MALLS)を用いて測定された値であり、条件は以下の通りである。
移動相:0.3M NaClO4
NaN3水溶液カラム:TSKgelα-M 2本
プレカラム:TSKguardcolumn α
標準物質:ポリエチレングリコールThe weight average molecular weight was measured by GPC (gel permeation chromatography) under the method and measurement conditions described in Japanese Patent No. 5740859. Specifically, it is shown below (same below).
Method for measuring weight average molecular weight;
The weight average molecular weight is a value measured using a gel permeation chromatograph/multi-angle laser light scattering detector (GPC-MALLS) under the following conditions.
Mobile phase: 0.3M NaClO4
NaN 3 aqueous solution column: TSKgelα-M 2 pre-column: TSKguardcolumn α
Standard substance: Polyethylene glycol
(a)成分のポリアクリル酸塩は、バイオフィルム形成抑制効果の点から直鎖状のポリアクリル酸塩が好ましい。
塩としては、一価塩が好ましく、アルカリ金属塩又はアンモニウム塩がより好ましく、更に好ましくはアルカリ金属塩であり、ナトリウム塩が特に好ましい。
このようなポリアクリル酸塩としては、ポリサイエンス社や東亞合成(株)から販売されている市販品を使用し得る。
具体的な市販品として、ポリアクリル酸ナトリウム(Mw:1,000);直鎖状,ポリサイエンス社製、ポリアクリル酸ナトリウム(Mw:6,000);直鎖状,東亞合成(株)製,AC-10NP,AC-10NPD,アロンT-50、ポリアクリル酸ナトリウム(Mw:8,000);直鎖状,ポリサイエンス社製、ポリアクリル酸ナトリウム(Mw:20,000);直鎖状,東亞合成(株)製,アロンA-20UN等を使用することができる。(a) The polyacrylate of the component is preferably a linear polyacrylate from the viewpoint of the effect of suppressing biofilm formation.
The salt is preferably a monovalent salt, more preferably an alkali metal salt or an ammonium salt, still more preferably an alkali metal salt, and particularly preferably a sodium salt.
As such polyacrylic acid salts, commercial products sold by Polyscience Co., Ltd. or Toagosei Co., Ltd. can be used.
Specific commercial products include sodium polyacrylate (Mw: 1,000); linear, manufactured by Polyscience, sodium polyacrylate (Mw: 6,000); linear, manufactured by Toagosei Co., Ltd. , AC-10NP, AC-10NPD, Aron T-50, sodium polyacrylate (Mw: 8,000); linear, manufactured by Polyscience, sodium polyacrylate (Mw: 20,000); linear , Toagosei Co., Ltd., Aron A-20UN, etc. can be used.
なお、(a)成分のポリアクリル酸塩は、通常、歯磨剤に使用される粘結剤の架橋型のポリアクリル酸塩よりも重量平均分子量が低く、粘結剤として公知のポリアクリル酸塩とは異なるものである。
(a)成分に代えて、(a)成分以外のポリアクリル酸塩を使用した場合、あるいは塩の形態ではないポリアクリル酸を使用した場合は、バイオフィルム形成抑制効果が劣り、更に(b)成分を併用しても効果が劣り、また、不快な臭いが抑えられなくなって使用感が悪くなることもあり、本発明の目的は達成されない。The polyacrylate of component (a) has a lower weight average molecular weight than the crosslinked polyacrylate of the binder usually used in dentifrices, and is known as a binder. is different from
In place of the component (a), when a polyacrylate other than the component (a) is used, or when polyacrylic acid that is not in the form of a salt is used, the effect of suppressing biofilm formation is inferior, and further (b) Even if the ingredients are used in combination, the effect is inferior, and the unpleasant odor cannot be suppressed, resulting in a poor feeling of use, and the object of the present invention is not achieved.
本発明の口腔バイオフィルム形成抑制剤では、有効成分として(a)成分に加えて(b)非イオン性殺菌剤を併用することが好ましい。(a)及び(b)成分を併用すると、バイオフィルム形成抑制効果がより向上する。
非イオン性殺菌剤には、バイオフィルム浸透殺菌作用を有するものがあることは知られており、また、わずかではあるがバイオフィルム形成抑制作用があると認識されるもののその作用は十分ではなかった。これに対して、(b)成分を(a)成分に併用すると、バイオフィルム形成抑制作用が増強して発現し、予想外の格別な作用効果が得られる。なお、殺菌剤であってもカチオン性殺菌剤を(a)成分と併用した場合はバイオフィルム形成抑制作用の増強は認められず、(b)成分特有の効果である。In the oral biofilm formation inhibitor of the present invention, it is preferable to use (b) a nonionic bactericide in addition to the (a) component as an active ingredient. When the (a) and (b) components are used together, the biofilm formation inhibitory effect is further improved.
Some nonionic fungicides are known to have a biofilm penetration sterilization effect, and although it is recognized that it has a slight biofilm formation inhibitory effect, its effect was not sufficient. . On the other hand, when the component (b) is used in combination with the component (a), the biofilm formation inhibitory action is enhanced and manifested, and an unexpected and exceptional effect can be obtained. In addition, even if it is a fungicide, when a cationic fungicide is used together with the component (a), no enhancement of the biofilm formation inhibitory action is observed, which is an effect peculiar to the component (b).
(b)非イオン性殺菌剤としては、イソプロピルメチルフェノール、トリクロサン、チモールを使用し得る。これらは、1種単独でも2種を組み合わせてもよい。なお、イソプロピルメチルフェノールは、4-イソプロピル-3-メチルフェノール(ビオゾール(登録商標))である。チモールは、2-イソプロピル-5-メチルフェノールである。中でも、イソプロピルメチルフェノール(4-イソプロピル-3-メチルフェノール)が、口腔用組成物として使用した際の味の点で好ましい。これらは、市販品を使用できる。 (b) As nonionic fungicides, isopropylmethylphenol, triclosan, thymol can be used. These may be used alone or in combination of two. Isopropylmethylphenol is 4-isopropyl-3-methylphenol (Biosol (registered trademark)). Thymol is 2-isopropyl-5-methylphenol. Among them, isopropylmethylphenol (4-isopropyl-3-methylphenol) is preferable from the viewpoint of taste when used as an oral composition. These can use a commercial item.
更に、(a)成分と(b)成分との量比を示す(a)/(b)は、質量比として0.01~200が好ましく、より好ましくは0.01~100、更に好ましくは0.03~100、最も好ましくは0.03~80である。この範囲内であると、バイオフィルム形成抑制効果がより優れる。 Furthermore, (a)/(b), which indicates the quantitative ratio between component (a) and component (b), is preferably 0.01 to 200, more preferably 0.01 to 100, and still more preferably 0 as a mass ratio. 0.03 to 100, most preferably 0.03 to 80. Within this range, the biofilm formation inhibitory effect is more excellent.
本発明の口腔バイオフィルム形成抑制剤は、有効成分として(a)成分を単独で、好ましくは更に(b)成分を併用し、前記成分を配合することで得ることができる。また更に、必要に応じて、その他の口腔用として公知の成分を含んでいてもよく、この場合、公知成分は本発明の効果を妨げない範囲で配合し得る。 The oral biofilm formation inhibitor of the present invention can be obtained by using component (a) alone as an active ingredient, preferably using component (b) in combination, and blending the above components. Furthermore, if necessary, other ingredients known for oral use may be included, and in this case, the known ingredients can be blended within a range that does not impair the effects of the present invention.
本発明の口腔用組成物は、(a)成分、更には(b)成分を含有するものである。口腔用組成物としては、具体的には、ペースト状、ジェル状又は液状の歯磨剤(練歯磨、ジェル状歯磨、液状歯磨、液体歯磨等)、洗口剤、マウススプレー、塗布剤、貼付剤等に好適に配合できる。中でも歯磨剤組成物、とりわけ練歯磨剤組成物として好適である。また、優れたバイオフィルム抑制効果を有するため、口腔バイオフィルム抑制用口腔用組成物として好適である。 The oral composition of the present invention contains component (a) and component (b). Specific examples of oral compositions include paste-like, gel-like, or liquid dentifrices (toothpaste, gel-like dentifrice, liquid dentifrice, liquid dentifrice, etc.), mouthwashes, mouth sprays, coating agents, and patches. etc. can be suitably blended. Among them, it is suitable as a dentifrice composition, especially a toothpaste composition. Moreover, since it has an excellent biofilm inhibitory effect, it is suitable as an oral cavity composition for inhibiting oral biofilms.
この場合、本発明において、口腔バイオフィルム形成抑制剤として(a)及び(b)成分を併用する場合は、前記特定の比率で規定することができる。また更に、本発明において、(a)成分、更には(b)成分の配合量は、バイオフィルム形成抑制効果及び使用感の点から、それぞれ後述の範囲が好ましく、前記成分はこれらを満たす濃度で使用することが好ましい。 In this case, in the present invention, when the components (a) and (b) are used together as an oral biofilm formation inhibitor, the specific ratio can be defined. Furthermore, in the present invention, the blending amounts of the component (a) and further the component (b) are preferably in the ranges described below from the viewpoint of the effect of suppressing biofilm formation and the feeling of use. It is preferred to use
(a)成分の配合量は、組成物全体の0.01~2%(質量%、以下同様)が好ましく、より好ましくは0.01~1%、更に好ましくは0.03~1%、最も好ましくは0.08~0.8%である。0.01%以上であると、十分なバイオフィルム形成抑制効果が得られる。2%以下であると、(a)成分由来の不快な臭いを十分に抑制することができる。 The amount of component (a) is preferably 0.01 to 2% (% by mass, the same applies hereinafter), more preferably 0.01 to 1%, still more preferably 0.03 to 1%, and most preferably 0.01 to 1% of the total composition. Preferably it is 0.08 to 0.8%. Sufficient biofilm formation inhibitory effect is obtained as it is 0.01% or more. When it is 2% or less, the unpleasant odor derived from the component (a) can be sufficiently suppressed.
(b)成分の配合量は、組成物全体の0.01~1%が好ましく、より好ましくは0.03~0.5%である。0.01%以上であると、十分なバイオフィルム形成抑制効果が得られ、また、(a)成分による不快な臭いを十分に抑制できる。1%以下であると、それ自身による異味を抑え、(a)及び(b)成分の併用によって生じる苦味を十分に抑えることができる。 The content of component (b) is preferably 0.01 to 1%, more preferably 0.03 to 0.5% of the total composition. When it is 0.01% or more, a sufficient biofilm formation inhibitory effect can be obtained, and an unpleasant odor due to the component (a) can be sufficiently suppressed. If it is 1% or less, the offensive taste due to itself can be suppressed, and the bitter taste caused by the combined use of the components (a) and (b) can be sufficiently suppressed.
本発明の口腔用組成物には、更に任意成分として、剤型等に応じた公知成分を必要に応じて配合できる。任意成分は、本発明の効果を妨げない範囲で添加することが好ましい。具体的に歯磨剤には、研磨剤、粘結剤、粘稠剤、界面活性剤、更には甘味剤、防腐剤、着色剤、香料、有効成分等を配合でき、これら成分と水とを混合し、製造できる。 The composition for oral cavity of the present invention can further contain, as optional components, known components according to the dosage form and the like, if necessary. Optional components are preferably added within a range that does not impair the effects of the present invention. Specifically, dentifrices can contain abrasives, binders, thickening agents, surfactants, sweeteners, preservatives, coloring agents, fragrances, active ingredients, etc. These ingredients and water can be mixed. and can be manufactured.
研磨剤は、例えば、無水ケイ酸、結晶性シリカ、非晶性シリカ、シリカゲル、アルミノシリケート等のシリカ系研磨剤、第3リン酸カルシウム、第4リン酸カルシウム、リン酸水素カルシウム無水和物、リン酸水素カルシウム2水和物等のリン酸カルシウム系研磨剤、ゼオライト、ピロリン酸カルシウム、炭酸カルシウム、炭酸水素ナトリウム、水酸化アルミニウム、アルミナ、炭酸マグネシウム、第3リン酸マグネシウム、ケイ酸ジルコニウム、ハイドロキシアパタイト、合成樹脂系研磨剤が挙げられる。これらは1種単独で又は2種以上を組み合わせて使用し得るが、中でも、使用性の観点から、無機研磨剤である無水ケイ酸等のシリカ系研磨剤、リン酸カルシウム系研磨剤、とりわけ無水ケイ酸が好ましい(研磨剤の配合量は、通常、5~60%、練歯磨の場合には10~55%)。 Examples of abrasives include silica-based abrasives such as silicic anhydride, crystalline silica, amorphous silica, silica gel and aluminosilicate; tribasic calcium phosphate; quaternary calcium phosphate; calcium hydrogen phosphate anhydrate; and calcium hydrogen phosphate. Calcium phosphate abrasive such as dihydrate, zeolite, calcium pyrophosphate, calcium carbonate, sodium hydrogen carbonate, aluminum hydroxide, alumina, magnesium carbonate, magnesium tertiary phosphate, zirconium silicate, hydroxyapatite, synthetic resin abrasive is mentioned. These may be used alone or in combination of two or more. Among them, from the viewpoint of usability, silica-based abrasives such as silicic anhydride, which are inorganic abrasives, calcium phosphate-based abrasives, especially silicic anhydride. is preferred (the amount of abrasive compounded is usually 5 to 60%, and 10 to 55% in the case of toothpaste).
また、特に練歯磨等のペースト状組成物の場合には、粘結剤として、アルギン酸ナトリウム、アルギン酸プロピレングリコールエステル等のアルギン酸誘導体、キサンタンガム、トラガカントガム、ジェランガム、カラヤガム、アラビアガム等のガム類、重量平均分子量20,000超の架橋型のポリアクリル酸塩、カラギーナン、更にはカルボキシメチルセルロースナトリウム、メチルセルロース、ヒドロキシエチルセルロース、カルボキシメチルヒドロキシエチルセルロースナトリウム等のセルロース誘導体、ポリビニルアルコール、カルボキシビニルポリマー、ポリビニルピロリドンといった有機粘結剤、シリカゲル、アルミニウムシリカゲル、ビーガム、ラポナイトといった無機粘結剤を配合できる(配合量は通常、0.3~10%)。 In particular, in the case of paste compositions such as toothpaste, as a binder, alginic acid derivatives such as sodium alginate and propylene glycol alginate, gums such as xanthan gum, tragacanth gum, gellan gum, karaya gum, gum arabic, etc. Crosslinked polyacrylates with a molecular weight of more than 20,000, carrageenan, cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose, organic binders such as polyvinyl alcohol, carboxyvinyl polymer, and polyvinylpyrrolidone. agent, silica gel, aluminum silica gel, veegum, laponite, and other inorganic binders (usually 0.3-10%).
更に、特にペースト状や液状の歯磨剤では、粘稠剤として、ソルビトール、マルチトール、ラクチトール、エリスリトール等の糖アルコール、プロピレングリコール等の多価アルコールを1種又は2種以上配合し得る(配合量は通常、5~70%)。 Furthermore, paste-like or liquid-like dentifrices in particular may contain one or more of sugar alcohols such as sorbitol, maltitol, lactitol, and erythritol, and polyhydric alcohols such as propylene glycol as thickeners (mixture amount is typically 5-70%).
界面活性剤は、アニオン性界面活性剤、ノニオン性界面活性剤、両性界面活性剤を配合し得る。これらは、1種又は2種以上を使用できる。
アニオン性界面活性剤としては、炭素数が12~14、特に12のアルキル基を有するアルキル硫酸塩、アシルアミノ酸塩、アシルタウリン塩等が挙げられる。アシルアミノ酸塩及びアシルタウリン塩のアシル基は、それぞれ炭素数12~14、特に12がよい。
具体的にアルキル硫酸塩としては、ラウリル硫酸塩、ミリスチル硫酸塩、アシルアミノ酸塩としては、ラウロイルグルタミン酸塩、ミリストイルグルタミン酸塩等のアシルグルタミン酸塩、ラウロイルサルコシン塩等のアシルサルコシン塩が挙げられ、アシルタウリン塩としては、ラウロイルメチルタウリン塩が挙げられる。塩は、ナトリウム塩、カリウム塩等のアルカリ金属塩がよい。特に、アルキル硫酸塩、アシルサルコシン塩、アシルタウリン塩が好ましい。中でも、炭素数12の炭化水素基(ラウリル基)を有するアニオン性界面活性剤が好ましく、特にアルキル硫酸塩(ナトリウム塩)が、他の界面活性剤よりも味の点で優れることから、より好ましい。
ノニオン性界面活性剤としては、例えば、ポリオキシエチレンアルキルエーテル、ポリオキシエチレン-ポリオキシプロピレンブロック共重合体、ポリオキシエチレン硬化ヒマシ油、グリセリンエステルのポリオキシエチレンエーテル、ショ糖脂肪酸エステル、アルキロールアミド、ソルビタン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、グリセリン脂肪酸エステルが挙げられる。これらのうち、汎用性の点で、ポリオキシエチレンアルキルエーテル、ポリオキシエチレン硬化ヒマシ油、アルキロールアミド、ソルビタン脂肪酸エステルが好適である。ポリオキシエチレンアルキルエーテルは、アルキル鎖の炭素数が14~30、エチレンオキサイド平均付加モル数(平均付加EO)が3~30が好ましい。ポリオキシエチレン硬化ヒマシ油は、平均付加EOが10~100が好ましい。アルキロールアミドは、アルキル鎖の炭素数が12~14が好ましい。ソルビタン脂肪酸エステルは、脂肪酸の炭素数が12~18が好ましい。ポリオキシエチレンソルビタン脂肪酸エステルは、脂肪酸の炭素数が16~18、平均付加EOが10~40が好ましい。
両性界面活性剤としては、炭素数12~14のアシル基を有するアシルアミノ酢酸ベタイン、脂肪酸アミドプロピルベタインが挙げられる。アシルアミノ酢酸ベタインとしては、ラウロイルジメチルアミノ酢酸ベタイン、脂肪酸アミドプロピルベタインとしては、ヤシ油脂肪酸アミドプロピルベタインが挙げられる。Surfactants can be blended with anionic surfactants, nonionic surfactants, and amphoteric surfactants. These can use 1 type(s) or 2 or more types.
Examples of anionic surfactants include alkyl sulfates having 12 to 14 carbon atoms, particularly 12 alkyl groups, acyl amino acid salts, acyl taurine salts, and the like. The acyl group of the acylamino acid salt and acyl taurine salt preferably has 12 to 14 carbon atoms, preferably 12 carbon atoms.
Specific examples of alkyl sulfates include lauryl sulfate and myristyl sulfate, and examples of acyl amino acid salts include acyl glutamates such as lauroyl glutamate and myristoyl glutamate, acyl sarcosinates such as lauroyl sarcosinate, and acyl taurine. Salts include lauroyl methyl taurine salts. Salts are preferably alkali metal salts such as sodium salts and potassium salts. Alkyl sulfates, acyl sarcosine salts, and acyl taurine salts are particularly preferred. Among them, anionic surfactants having a hydrocarbon group of 12 carbon atoms (lauryl group) are preferred, and alkyl sulfates (sodium salts) are particularly preferred because they are superior in taste to other surfactants. .
Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene hydrogenated castor oil, polyoxyethylene ethers of glycerin esters, sucrose fatty acid esters, alkylols. amides, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and glycerin fatty acid esters. Among these, polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oils, alkylolamides, and sorbitan fatty acid esters are preferred in terms of versatility. The polyoxyethylene alkyl ether preferably has an alkyl chain with 14 to 30 carbon atoms and an average added mole number of ethylene oxide (average added EO) of 3 to 30. Polyoxyethylene hydrogenated castor oil preferably has an average added EO of 10-100. The alkylolamide preferably has 12 to 14 carbon atoms in the alkyl chain. The sorbitan fatty acid ester preferably has 12 to 18 carbon atoms. The polyoxyethylene sorbitan fatty acid ester preferably has 16 to 18 carbon atoms in the fatty acid and 10 to 40 average added EO.
Amphoteric surfactants include acylaminoacetic acid betaine and fatty acid amidopropyl betaine having an acyl group of 12 to 14 carbon atoms. Acylaminoacetic acid betaine includes lauroyldimethylaminoacetic acid betaine, and fatty acid amidopropyl betaine includes coconut oil fatty acid amidopropyl betaine.
界面活性剤の配合量は、通常、0.01~15%、特に0.01~10%である。
なお、アニオン性界面活性剤の配合量は0.1~3%、特に0.5~2%がよく、ノニオン性界面活性剤の配合量は0.01~10%がよい。The content of the surfactant is usually 0.01-15%, especially 0.01-10%.
The blending amount of the anionic surfactant is preferably 0.1 to 3%, particularly 0.5 to 2%, and the blending amount of the nonionic surfactant is preferably 0.01 to 10%.
本発明において、(a)成分に、ノニオン性界面活性剤、特にポリオキシエチレン硬化ヒマシ油を併用すると、その添加量によって臭いや味が悪くなり使用感が低下することがあるが、アルキル硫酸塩等のアニオン性界面活性剤と共に上記ノニオン性界面活性剤を添加すると、このような臭いや味の悪化が防止され、使用感が低下することなくバイオフィルム形成抑制効果がより向上する。 In the present invention, if a nonionic surfactant, especially polyoxyethylene hydrogenated castor oil, is used in combination with component (a), the smell and taste may deteriorate depending on the amount added, and the feeling of use may decrease. Addition of the above nonionic surfactant together with an anionic surfactant such as the above prevents deterioration of such odor and taste, and further improves the effect of suppressing biofilm formation without reducing the feeling of use.
甘味剤は、サッカリンナトリウム、ステビオサイド、グリチルリチン酸ジカリウム、ペリラルチン、ソーマチン、ネオヘスペリジルジヒドロカルコン、アスパラチルフェニルアラニンメチルエステルが挙げられる。防腐剤は、パラオキシ安息香酸エステル、安息香酸ナトリウムが挙げられる。
着色剤は、青色1号、黄色4号、二酸化チタンが挙げられる。Sweetening agents include saccharin sodium, stevioside, dipotassium glycyrrhizinate, perillartine, thaumatin, neohesperidyl dihydrochalcone, aspartylphenylalanine methyl ester. Preservatives include paraoxybenzoic acid esters and sodium benzoate.
Colorants include Blue No. 1, Yellow No. 4, and titanium dioxide.
香料は、ペパーミント油、スペアミント油、アニス油、ユーカリ油、ウィンターグリーン油、カシア油、クローブ油、タイム油、セージ油、レモン油、オレンジ油、ハッカ油、カルダモン油、コリアンダー油、マンダリン油、ライム油、ラベンダー油、ローズマリー油、ローレル油、カモミル油、キャラウェイ油、マジョラム油、ベイ油、レモングラス油、オリガナム油、パインニードル油、ネロリ油、ローズ油、ジャスミン油、イリスコンクリート、アブソリュートペパーミント、アブソリュートローズ、オレンジフラワー等の天然香料、及び、これら天然香料の加工処理(前溜部カット、後溜部カット、分留、液液抽出、エッセンス化、粉末香料化等)した香料、及び、メントール、カルボン、アネトール、サリチル酸メチル、シンナミックアルデヒド、3-l-メントキシプロパン-1,2-ジオール、リナロール、リナリールアセテート、リモネン、メントン、メンチルアセテート、N-置換-パラメンタン-3-カルボキサミド、ピネン、オクチルアルデヒド、シトラール、プレゴン、カルビールアセテート、アニスアルデヒド、エチルアセテート、エチルブチレート、アリルシクロヘキサンプロピオネート、メチルアンスラニレート、エチルメチルフェニルグリシデート、バニリン、ウンデカラクトン、ヘキサナール、イソアミルアルコール、ヘキセノール、ジメチルサルファイド、シクロテン、フルフラール、トリメチルピラジン、エチルラクテート、エチルチオアセテート等の単品香料、更に、ストロベリーフレーバー、アップルフレーバー、バナナフレーバー、パイナップルフレーバー、グレープフレーバー、マンゴーフレーバー、バターフレーバー、ミルクフレーバー、フルーツミックスフレーバー、トロピカルフルーツフレーバー等の調合香料等、口腔用組成物に用いられる公知の香料素材を使用することができ、実施例の香料に限定されない。
また、上記の香料素材は、組成物全体の0.000001~1%使用するのが好ましい。上記香料素材を使用した賦香用香料としては、組成物中に0.001~2.0%使用するのが好ましい。Peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime. Oil, Lavender Oil, Rosemary Oil, Laurel Oil, Chamomile Oil, Caraway Oil, Marjoram Oil, Bay Oil, Lemongrass Oil, Origanum Oil, Pine Needle Oil, Neroli Oil, Rose Oil, Jasmine Oil, Iris Concrete, Absolute Peppermint , natural fragrances such as absolute rose, orange flower, and fragrances obtained by processing these natural fragrances (pre-reservoir cut, rear-reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder perfume, etc.), and menthol, carvone, anethole, methyl salicylate, cinnamic aldehyde, 3-l-menthoxypropane-1,2-diol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-paramenthane-3-carboxamide, Pinene, Octylaldehyde, Citral, Pulegone, Carbyl Acetate, Anisaldehyde, Ethyl Acetate, Ethyl Butyrate, Allylcyclohexane Propionate, Methyl Anthranilate, Ethyl Methyl Phenyl Glycidate, Vanillin, Undecalactone, Hexanal, Isoamyl Alcohol , hexenol, dimethyl sulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate, ethyl thioacetate, etc., strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, Known flavoring materials used in oral compositions, such as blended flavorings such as mixed fruit flavors and tropical fruit flavors, can be used, and are not limited to the flavorings in the examples.
Moreover, it is preferable to use 0.000001 to 1% of the entire composition of the perfume material. It is preferable to use 0.001 to 2.0% in the composition as a perfume for perfuming using the above perfume material.
任意の有効成分は、例えば、デキストラナーゼ、ムタナーゼ、リゾチーム、アミラーゼ、プロテアーゼ、溶菌酵素、SOD(スーパーオキシドディスムターゼ)等の酵素;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アルカリ金属モノフルオロフォスフェート;フッ化ナトリウム、フッ化第一錫等のフッ化物;トラネキサム酸、イプシロンアミノカプロン酸、アラントイン、アラントインクロルヒドロキシアルミニウム、ジヒドロコレステロール、グリチルリチン酸、グリチルレチン酸等の抗炎症剤;硝酸カリウム、乳酸アルミニウム等の知覚過敏改善剤;グリセロフォスフェート、クロロフィル、塩化ナトリウムや、塩化亜鉛、酸化亜鉛、クエン酸亜鉛等の亜鉛化合物;グルコン酸銅、硫酸銅等の銅化合物;ポリリン酸ナトリウム等の水溶性無機リン酸化物;ビタミンA、ビタミンB群、ビタミンC、ビタミンE等のビタミン類;オウバクやチャ等の生薬が挙げられる。これら有効成分は、1種又は2種以上で使用でき、また、本発明の効果を妨げない範囲で有効量配合することができる。 Enzymes such as dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, and SOD (superoxide dismutase); alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate; Phosphate; Fluorides such as sodium fluoride and stannous fluoride; Anti-inflammatory agents such as tranexamic acid, epsilon aminocaproic acid, allantoin, allantoin chlorohydroxyaluminum, dihydrocholesterol, glycyrrhizic acid, glycyrrhetinic acid; potassium nitrate, aluminum lactate, etc. hypersensitivity improvers; zinc compounds such as glycerophosphate, chlorophyll, sodium chloride, zinc chloride, zinc oxide and zinc citrate; copper compounds such as copper gluconate and copper sulfate; water-soluble inorganic phosphorus such as sodium polyphosphate oxides; vitamins such as vitamin A, vitamin B group, vitamin C and vitamin E; crude drugs such as Phellodendron bark and tea. These active ingredients can be used singly or in combination of two or more, and can be blended in an effective amount within a range that does not interfere with the effects of the present invention.
口腔用組成物のpH(25℃)は、通常範囲でよく、pH5~9、特に6~8がよい。なお、公知のpH調整剤を添加してpH調整してもよく、例えば塩酸や、水酸化ナトリウム等のアルカリ金属の水酸化物を使用できる。 The pH (25° C.) of the oral composition may be within a normal range, preferably pH 5-9, particularly pH 6-8. A known pH adjuster may be added to adjust the pH, for example, hydrochloric acid or an alkali metal hydroxide such as sodium hydroxide can be used.
以下、実施例及び比較例を示し、本発明を具体的に説明するが、本発明は下記の実施例に制限されるものではない。なお、下記の例において%は特に断らない限りいずれも質量%を示す。
また、重量平均分子量(Mw)は、GPC(ゲルパーミェーションクロマトグラフィー法)によって上記と同様の方法及び測定条件で測定した。EXAMPLES Hereinafter, the present invention will be specifically described by showing examples and comparative examples, but the present invention is not limited to the following examples. In the following examples, % indicates % by mass unless otherwise specified.
Also, the weight average molecular weight (Mw) was measured by GPC (gel permeation chromatography) under the same method and measurement conditions as above.
[実施例、比較例]
表1に示す種類及び量のポリアクリル酸塩、更には(b)成分を配合した口腔用製剤を調製し、下記方法でバイオフィルム形成抑制効果を評価した。結果を表1に併記した。
また、表2、3に示す組成の歯磨剤組成物(練歯磨)を常法で調製し、アルミニウムラミネートチューブ容器に充填した。下記方法でバイオフィルム形成抑制効果及び使用感(臭い)を評価した。結果を表2、3に併記した。[Examples, Comparative Examples]
The types and amounts of polyacrylates shown in Table 1, and oral preparations containing the component (b) were prepared, and the biofilm formation inhibitory effect was evaluated by the following method. The results are also shown in Table 1.
Also, a dentifrice composition (toothpaste) having the composition shown in Tables 2 and 3 was prepared by a conventional method and filled in an aluminum laminate tube container. The effect of suppressing biofilm formation and the feeling of use (smell) were evaluated by the following methods. The results are shown in Tables 2 and 3 together.
(1)バイオフィルム形成抑制効果の評価方法
モデルバイオフィルムを作製するために使用した菌は、下記4種類である。
(i)アクチノマイセス ヴィスコサス(Actinomyces viscosus)ATCC43146
(ii)フゾバクテリウム ヌクレアタム(Fusobacterium nucleatum)ATCC10953
(iii)ポルフィロモナス ジンジバリス(Porphyromonas gingivalis)ATCC33277
(iv)ベイヨネラ パルビュラ(Veillonella parvula)ATCC17745
(i)、(ii)、(iii)の菌は、5mg/Lのヘミン(Sigma社製)及び1mg/LのビタミンK(和光純薬工業(株)製)を含むトッドへヴィットブロス(Becton and Dickinson社製)培養液により培養した。(iv)の菌は、1.26%乳酸ナトリウム(Sigma社製)を含むトッドへヴィットブロス(Becton and Dickinson社製)培養液により培養した。なお、培養は37℃で一晩嫌気培養(80vol%窒素、10vol%二酸化炭素、10vol%水素)した。
前記培養した4菌種を、予めベイサルメディウムムチン培養液(BMM)*1を3,000mL入れたRotating Disk Reactor(培養槽)に、それぞれ1×107cfu/mLになるように接種した。前記培養槽内に、0.45μmのフィルターでろ過したヒト無刺激唾液で4時間処理したハイドロキシアパタイト板(HOYA(株)製、直径φ7.0mm×厚さ3.5mm、以下、HA板と略記する)をモデルバイオフィルム形成の担体として設置した。この状態で、嫌気条件下(95vol%窒素、5vol%二酸化炭素)で24時間培養を行った。
次に、嫌気条件下(95vol%窒素、5vol%二酸化炭素)で、BMMを置換率5vol%/時間の流量で、別の流路から試験溶液(口腔用製剤の場合は人工唾液3倍希釈液、対照試験の場合はBMM)を置換率5vol%/時間の流量で、各々連続的に供給しながら、10日間連続培養した。
前記連続培養処理後のHA板を取り出し、24穴マルチプレート(住友ベークライト(株)製)に移し、リン酸緩衝生理食塩水*2(Phosphate Buffered Saline、以下、PBSと略記する)1mLで7回洗浄し、0.1%クリスタルバイオレット溶液に15分間浸漬して、HA板表面に形成されたバイオフィルムを染色した。クリスタルバイオレット溶液を除去し、1mLのPBSで5回洗浄した後、30%酢酸水溶液2mLで色素を抽出し、550nmの吸光度を測定し、吸光度の強さをバイオフィルム形成量とした。
対照試験を行った場合のバイオフィルム形成量を100として、それに対する各試験溶液を添加した際のバイオフィルム形成量率(%)を算出し、バイオフィルム形成抑制効果を評価した。(1) Method for evaluating biofilm formation inhibitory effect The following four types of bacteria were used to prepare model biofilms.
(i) Actinomyces viscosus ATCC43146
(ii) Fusobacterium nucleatum ATCC10953
(iii) Porphyromonas gingivalis ATCC33277
(iv) Veillonella parvula ATCC 17745
The bacteria (i), (ii), and (iii) are Toddhevit broth (Becton and Dickinson) culture medium. The bacteria of (iv) were cultured in a Toddhewitt broth (manufactured by Becton and Dickinson) containing 1.26% sodium lactate (manufactured by Sigma). The culture was carried out at 37° C. overnight anaerobic culture (80 vol % nitrogen, 10 vol % carbon dioxide, 10 vol % hydrogen).
The above-mentioned four strains of bacteria were inoculated into a Rotating Disk Reactor (fermenter) in which 3,000 mL of basal medium mucin culture medium (BMM) *1 had been placed in advance so as to obtain 1×10 7 cfu/mL. In the culture tank, a hydroxyapatite plate (manufactured by HOYA Corporation, diameter φ7.0 mm × thickness 3.5 mm, abbreviated as HA plate) was treated for 4 hours with unstimulated human saliva filtered through a 0.45 μm filter. ) was set up as a carrier for model biofilm formation. In this state, culture was performed for 24 hours under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide).
Next, under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide), the BMM is replaced at a flow rate of 5 vol% / hour, and the test solution (in the case of oral preparations, artificial saliva 3-fold dilution , and BMM in the case of the control test) were continuously supplied at a flow rate of 5 vol%/hour for 10 days of continuous culture.
After the continuous culture treatment, the HA plate was removed, transferred to a 24-well multiplate (manufactured by Sumitomo Bakelite Co., Ltd.), and treated with 1 mL of phosphate buffered saline *2 (hereinafter abbreviated as PBS) 7 times. It was washed and immersed in a 0.1% crystal violet solution for 15 minutes to stain the biofilm formed on the HA plate surface. After removing the crystal violet solution and washing 5 times with 1 mL of PBS, the pigment was extracted with 2 mL of 30% acetic acid aqueous solution, the absorbance at 550 nm was measured, and the strength of the absorbance was taken as the amount of biofilm formation.
Taking the biofilm formation amount in the control test as 100, the biofilm formation amount ratio (%) when each test solution was added to it was calculated, and the biofilm formation inhibitory effect was evaluated.
評価基準
◎◎:30%未満
◎ :30%以上50%未満
○ :50%以上70%未満
△ :70%以上90%未満
× :90%以上Evaluation criteria ◎◎: less than 30% ◎: 30% or more and less than 50% ○: 50% or more and less than 70% △: 70% or more and less than 90% ×: 90% or more
*1;BMMの組成(1リットル中の質量で表す。)
プロテオースペプトン(Becton and Dickinson社製):
4g/L
トリプトン(Becton and Dickinson社製): 2g/L
イーストエキス(Becton and Dickinson社製):
2g/L
ムチン(Sigma社製): 5g/L
ヘミン(Sigma社製): 2.5mg/L
ビタミンK(和光純薬工業(株)製): 0.5mg/L
KCl(和光純薬工業(株)製): 1g/L
システイン(和光純薬工業(株)製): 0.2g/L
蒸留水: 残
(全量が1Lになるようにメスアップし、120℃で20分間オートクレー
ブした。) *1 ; Composition of BMM (indicated by mass in 1 liter)
Proteose peptone (manufactured by Becton and Dickinson):
4g/L
Tryptone (manufactured by Becton and Dickinson): 2 g / L
Yeast extract (manufactured by Becton and Dickinson):
2g/L
Mucin (manufactured by Sigma): 5 g / L
Hemin (manufactured by Sigma): 2.5 mg/L
Vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.): 0.5 mg / L
KCl (manufactured by Wako Pure Chemical Industries, Ltd.): 1 g / L
Cysteine (manufactured by Wako Pure Chemical Industries, Ltd.): 0.2 g / L
Distilled water: Remainder (filled up to 1 L and autoclaved at 120°C for 20 minutes)
*2;PBSの組成(1リットル中の質量で表す。)
NaCl(和光純薬工業(株)製): 8.0g
KCl(和光純薬工業(株)製): 0.2g
Na2HPO4・12H2O(和光純薬工業(株)製): 3.63g
KH2PO4(和光純薬工業(株)製): 0.24g
蒸留水: 残
(1N HClによりpH7.4に調整し、全量が1Lになるようにメスア
ップした。) *2 ;Composition of PBS (indicated by mass in 1 liter)
NaCl (manufactured by Wako Pure Chemical Industries, Ltd.): 8.0 g
KCl (manufactured by Wako Pure Chemical Industries, Ltd.): 0.2 g
Na 2 HPO 4 .12H 2 O (manufactured by Wako Pure Chemical Industries, Ltd.): 3.63 g
KH 2 PO 4 (manufactured by Wako Pure Chemical Industries, Ltd.): 0.24 g
Distilled water: remainder (adjusted to pH 7.4 with 1N HCl and diluted to 1 L)
(2)使用感の評価方法
10名の被験者モニターが、歯磨剤組成物1gを歯ブラシにのせ、3分間ブラッシングして口腔内を洗浄した際の使用感(臭い)を下記の評点基準により評価した。10名の評価点の平均を算出し、下記の評価基準により判定した。
使用感(臭い)の評点基準
4点:口腔内で不快な臭いを感じない
3点:口腔内で不快な臭いをやや感じるが問題ないレベルである
2点:口腔内で不快な臭いを感じる
1点:口腔内で不快な臭いを強く感じる
使用感(臭いのなさ)の評価基準
◎:平均点3.5点以上
○:平均点3.0点以上3.5点未満
△:平均点2.0点以上3.0点未満
×:平均点2.0点未満(2) Evaluation method of feeling of use Ten subject monitors placed 1 g of the dentifrice composition on a toothbrush and brushed for 3 minutes to wash the oral cavity, and evaluated the feeling of use (smell) according to the following rating criteria. . The average of 10 evaluation points was calculated and judged according to the following evaluation criteria.
Scoring criteria for feeling of use (smell) 4 points: no unpleasant odor in the oral cavity 3 points: slightly unpleasant odor in the oral cavity, but no problem level 2 points: unpleasant odor in the oral cavity 1 Point: Strong sense of unpleasant odor in the oral cavity Evaluation criteria for feeling of use (absence of odor) ◎: Average score of 3.5 points or more ○: Average score of 3.0 or more and less than 3.5 points △: Average score of 2. 0 points or more and less than 3.0 points ×: Average score less than 2.0 points
使用原料の詳細を下記に示す。
(a)ポリアクリル酸ナトリウム(Mw:1,000)
直鎖状、ポリサイエンス社製
(a)ポリアクリル酸ナトリウム(Mw:6,000)
直鎖状、東亞合成(株)製、AC-10NP
(a)ポリアクリル酸ナトリウム(Mw:8,000)
直鎖状、ポリサイエンス社製
(a)ポリアクリル酸ナトリウム(Mw:20,000)
直鎖状、東亞合成(株)製、アロンA-20UN
ポリアクリル酸ナトリウム(Mw:300,000、比較品)
架橋型、ポリサイエンス社製
ポリアクリル酸(Mw:6,000、比較品)
直鎖状、東亞合成(株)製、アロンA-10SL
(b)イソプロピルメチルフェノール
4-イソプロピル-3-メチルフェノール(ビオゾール)、
大阪化成(株)製
(b)チモール
2-イソプロピル-5-メチルフェノール、大阪化成(株)製
(b)トリクロサン
BASF(株)製Details of raw materials used are shown below.
(a) sodium polyacrylate (Mw: 1,000)
Linear, manufactured by Polyscience (a) sodium polyacrylate (Mw: 6,000)
Linear, manufactured by Toagosei Co., Ltd., AC-10NP
(a) sodium polyacrylate (Mw: 8,000)
Linear, manufactured by Polyscience (a) sodium polyacrylate (Mw: 20,000)
Linear, manufactured by Toagosei Co., Ltd., Aron A-20UN
Sodium polyacrylate (Mw: 300,000, comparative product)
Crosslinked type, polyacrylic acid manufactured by Polyscience (Mw: 6,000, comparative product)
Linear, manufactured by Toagosei Co., Ltd., Aron A-10SL
(b) isopropylmethylphenol 4-isopropyl-3-methylphenol (Biozol),
Osaka Kasei Co., Ltd. (b) Thymol 2-isopropyl-5-methylphenol, Osaka Kasei Co., Ltd. (b) Triclosan BASF Co., Ltd.
Claims (10)
(b)イソプロピルメチルフェノール及びチモールから選ばれる1種以上の非イオン性殺菌剤
を含有する口腔バイオフィルム形成抑制剤(但し、次亜塩素酸塩を含有するものを除く)。 (a) polyacrylate having a weight average molecular weight of 1,000 or more and 8,000 or less, and (b) oral biofilm formation suppression containing one or more nonionic disinfectants selected from isopropylmethylphenol and thymol agents (excluding those containing hypochlorite) .
(b)イソプロピルメチルフェノール及びチモールから選ばれる1種以上の非イオン性殺菌剤
を含有する口腔用組成物(但し、次亜塩素酸塩を含有する口腔用組成物を除く)。 (a) a polyacrylate having a weight average molecular weight of 1,000 or more and 8,000 or less, and (b) an oral composition containing one or more nonionic disinfectants selected from isopropylmethylphenol and thymol ( However, oral compositions containing hypochlorite are excluded) .
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KR20230046772A (en) | 2021-09-30 | 2023-04-06 | 주식회사 테코자임 | Composition for preventing biofilm formation comprising extract of trigonellae semen |
KR20230046727A (en) | 2021-09-30 | 2023-04-06 | 주식회사 테코자임 | Composition for preventing biofilm formation comprising zinc salt |
KR20230046651A (en) | 2021-09-30 | 2023-04-06 | 주식회사 테코자임 | COMPOSITION FOR PREVENTING BIOFILM FORMATION COMPRISING EXTRACT OF Pharbitis nil |
KR20230046760A (en) | 2021-09-30 | 2023-04-06 | 주식회사 테코자임 | Composition for preventing biofilm formation comprising extract of vitidis viniferae caulis |
KR20230046792A (en) | 2021-09-30 | 2023-04-06 | 주식회사 테코자임 | COMPOSITION FOR PREVENTING BIOFILM FORMATION COMPRISING EXTRACT OF Piperis Nigri Fructus |
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JP2000247851A (en) | 1999-02-26 | 2000-09-12 | Lion Corp | Coating agent for controlling coloration |
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JP5573111B2 (en) * | 2009-11-06 | 2014-08-20 | ライオン株式会社 | Isopropylmethylphenol-containing liquid oral composition |
MY162054A (en) * | 2010-11-30 | 2017-05-31 | Lion Corp | Inhibitor of attachment of periodontal disease-inducing bacterium onto surfaces of teeth, oral biofilm formation inhibitor, and composition for oral applications |
JP5834881B2 (en) * | 2011-12-20 | 2015-12-24 | ライオン株式会社 | Dentifrice composition |
JP6673852B2 (en) * | 2014-12-26 | 2020-03-25 | 花王株式会社 | Liquid oral cavity composition in foam discharge container |
JP6413815B2 (en) * | 2015-02-06 | 2018-10-31 | ライオン株式会社 | Liquid oral composition |
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