JP2022103980A - Composition for oral cavity - Google Patents

Abstract

To increase concentration of Streptococcus oralis inside an oral cavity.SOLUTION: A composition for oral cavity contains specific amino acid, and specific saccharide with the polymerization degree of 1 or more and 10 or less. The specific amino acid is at least one kind selected from aspartic acid, aspartate, glutamic acid, glutamate, alanine, proline, serine, valine, and glycine.SELECTED DRAWING: None

Description

The present invention relates to an oral composition.

Many bacteria in the oral cavity are either floating in the oral cavity or present in bacterial aggregates called biofilms. Because biofilms are resistant to both physical and chemical action, removing biofilms is more difficult than removing floating bacteria.

The mechanism by which bacteria floating in the oral cavity adhere to the surface of teeth and oral mucosa has been studied for a long time and various findings have been obtained. In order to effectively inhibit the formation of biofilm, it is important to prevent the early colonization bacteria, which are bacteria that adhere to clean tooth surfaces in a short time and form initial plaque, to adhere to the tooth surface. It is considered. Early colonization bacteria have receptors that bind to salivary proteins and are known to promote attachment when bound to specific salivary proteins. This salivary protein is roughly classified into high proline protein and high proline glycoprotein. Streptococcus mutans, Streptococcus gordonii, Porphyromonas gingivalis, etc. are known as typical bacteria having the former receptor, and Staphylococcus aureus, Fusobacterium nucleatum, Streptococcus oralis, etc. are known as typical bacteria having the latter receptor. Has been done. Therefore, it is necessary to develop a technique having an effective adhesion prevention effect against these two bacterial groups. For example, Patent Document 1 prevents bacteria such as Streptococcus mutans and Staphylococcus aureus from adhering to and proliferating in oral tissues by using a composition containing liposomes containing hydrogenated phospholipids as an essential component. The technology to be used is disclosed.

Japanese Unexamined Patent Publication No. 2018-115179

As a result of diligent research by the present inventors, it is said that those who have no history of caries have a higher concentration of Streptococcus oralis (hereinafter referred to as S. olaris) in the oral cavity than those who have a history of caries. Findings were obtained. From this finding, from the viewpoint of ensuring a healthy oral environment, S. It is suggested that it is important to increase the concentration of Oralis.

The present invention has been made based on the above findings, and an object thereof is S. cerevisiae in the oral cavity. The purpose is to increase the concentration of Oralis.

The oral composition that solves the above-mentioned problems is an oral composition containing an amino acid and a sugar having a degree of polymerization of 1 or more and 10 or less, and the amino acid is aspartic acid, aspartate, glutamic acid, glutamic acid. , Alanine, proline, serine, valine, and glycine.

In the oral composition, the amino acid is preferably at least one selected from aspartic acid, aspartate, glutamic acid, glutamic acid, alanine, and glycine.

In the oral composition, the sugar is preferably at least one selected from lactose, galactose, raffinose, galactooligosaccharides, and hydrates thereof.

According to the present invention, S. in the oral cavity. The concentration of Oralis can be increased.

Hereinafter, an embodiment of the present invention will be described.
The oral composition of the present embodiment contains a specific amino acid and a specific sugar.
(Specific amino acid)
The particular amino acid contained in the oral composition is at least one selected from aspartic acid, aspartate, glutamic acid, glutamic acid, alanine, proline, serine, valine, and glycine. Specific examples of asparagate and glutamate include alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as magnesium salt and calcium salt.

The oral composition may contain only one of the above-mentioned specific amino acids alone, or may contain two or more of them in combination. It is particularly preferable that the oral composition contains at least one selected from aspartic acid, aspartate, glutamic acid, glutamic acid, alanine, and glycine as a specific amino acid.

The content of the specific amino acid in the oral composition is, for example, 0.5 to 4% by mass, preferably 1.5 to 3% by mass, and more preferably 1.5 to 2% by mass.
(Specific sugar)
The specific sugar contained in the oral composition is a sugar having a degree of polymerization of 1 or more and 10 or less. Specific sugar types include, for example, monosaccharides, disaccharides, oligosaccharides of trisaccharides or higher, and sugar alcohols.

Examples of monosaccharides include galactose, mannose, arabinose, and hydrates thereof.
Examples of the disaccharide include maltose, sucrose, lactose, and hydrates thereof.

Examples of oligosaccharides include raffinose, galactooligosaccharides, soybean oligosaccharides, milk fruit oligosaccharides, xylooligosaccharides, gentiooligosaccharides, maltooligosaccharides, cyclic oligosaccharides, milk oligosaccharides, and hydrates thereof.

Examples of the sugar alcohol include those obtained by industrially reducing the above-mentioned monosaccharides, disaccharides, or oligosaccharides, and examples thereof include sorbitol, lactitol, and reduced isomaltitol (Palatinit (registered trademark)). , Traitol, pentaerythritol, dipentaerythritol, tripentaerythritol, arabitol, ribitol, mannitol, thraitol, gritol, taritol, gaaritol, altritor, dolsitol, iditol, inositol, maltitol, isomartitol, lactitol, turanitol. Will be.

The oral composition may contain only one of the above-mentioned specific sugars alone, or may contain two or more of them in combination. In addition, it is particularly preferable that the oral composition contains at least one selected from lactose, galactose, raffinose, galactooligosaccharide, and hydrates thereof as a specific sugar.

The content of the specific sugar in the oral composition is, for example, 0.5 to 4% by mass, preferably 1.5 to 3% by mass, and more preferably 1.5 to 2% by mass. The mass ratio of a specific sugar to a specific amino acid (specific sugar / specific amino acid) in the oral composition is, for example, 0.5 to 4, preferably 0.5 to 2, more preferably. Is 1-2.

(Combination of specific amino acids and specific sugars)
The oral composition contains at least one selected from aspartic acid and aspartate as a specific amino acid, and at least one selected from lactose, galactose, raffinose, and galactooligosaccharide as a specific sugar. Is preferable. Further, the oral composition preferably contains at least one selected from glutamic acid and glutamic acid salt as a specific amino acid, and preferably contains galactooligosaccharide as a specific sugar.

(Applicable form, application, and dosage form)
The application form of the oral composition is not particularly limited, and can be used as, for example, a pharmaceutical product, a quasi-drug, or a cosmetic product. As the use of the oral composition, known ones can be appropriately adopted, for example, a denture polish, a mouthwash, a moisturizer, a liquid dentifrice, a biofilm dispersant, a mouth odor preventive agent, and a gum massage agent. , Oral moisturizer, tongue moss remover, oral coating agent, oral sterilizer, throat sterilizer, oral throat agent, periodontal disease treatment agent, denture mounting agent, denture coating agent, denture stabilizer, denture preservative , Denture cleaning agents, implant care agents.

The dosage form of the oral composition is not particularly limited, and for example, by containing a solvent such as water or alcohol, an ointment, a paste, a pasta, a spray, a gel, a liquid, a suspension / emulsifier, etc. It can be applied to gum agents and the like.

The type of water used as the solvent is not particularly limited, and for example, distilled water, pure water, ultrapure water, purified water, tap water and the like can be used. The type of alcohol used as the solvent is not particularly limited, and for example, ethanol can be used. Water and alcohol can be mixed and used.

When the oral composition is composed of a liquid, the content of the solvent such as water is preferably, for example, 60 to 99.8% by mass, more preferably 70 to 90% by mass.

(Other ingredients)
The oral composition may contain other components other than the above-mentioned components depending on the purpose of application, form, use and the like. Other ingredients include, for example, antibacterial agents, anti-inflammatory agents, fragrances, wetting agents, surfactants, abrasives, alcohols, thickeners, sweetening ingredients, medicinal ingredients, colorants, stabilizers, and pH adjusters. Can be mentioned. As the other components, known ones to be blended in the oral composition can be used. The oral composition may contain only one kind of each of the above other components alone, or may contain two or more kinds in combination.

Examples of the antibacterial agent include cetylpyridinium chloride, paraben, sodium benzoate, triclosan, chlorhexidine hydrochloride, isopropylmethylphenol, benzalkonium chloride, benzethonium chloride, and hinokithiol.

Examples of the anti-inflammatory agent include glycyrrhizate, tranexamic acid, ε-aminocaproic acid, and Phellodendron amur extract.
Examples of the fragrance include anethole, eugenol, carboxylic, winter green, methyl salicylate, timol, clove oil, sage oil, ossimen oil, and citronellol.

Examples of the surfactant include nonionic surfactants, anionic surfactants, and amphoteric surfactants.
Examples of the nonionic surfactant include sucrose fatty acid ester, sugar fatty acid ester such as maltose fatty acid ester, sugar alcohol fatty acid ester such as maltitol fatty acid ester, sorbitan fatty acid ester such as monolauric acid sorbitan, and polyoxyethylene sorbitan mono. Polyoxyethylene sorbitan fatty acid esters such as laurate and polyoxyethylene sorbitan monostearate, fatty acid alkanolamides such as lauric acid diethanolamide, polyoxyethylene alkyl ethers such as polyoxyethylene stearyl ether and polyoxyethylene oleyl ether, and monoolein. Polyethylene glycol fatty acid esters such as polyethylene glycol acid and polyethylene glycol monolaurate, alkyl glucosides such as lauryl glucoside and decyl glucoside, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene fatty acid ester, alkyl glucosides, polyoxyethylene Examples include cured castor oil, glycerin fatty acid ester, and polyoxyethylene propylene block copolymer.

Examples of the anionic surfactant include sulfate ester salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate, sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate, cocoyl sarcosine sodium and lauroyl. Examples thereof include acyl amino acid salts such as sodium methylalanine and sodium cocoylmethyltaurine.

Examples of the amphoteric surfactant include amino acid type amphoteric surfactants such as N-lauryldiaminoethylglycine and N-myristyldiethylglycine, alkyldimethylaminoacetate betaine, and N-alkyl-N'-carboxymethyl-N'-hydroxy. Examples thereof include betaine-based amphoteric surfactants such as ethylethylenediamine salt and 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine.

Examples of the polishing agent include calcium carbonate, magnesium carbonate, dicalcium phosphate, calcium triphosphate, magnesium phosphate, silica, zeolite, sodium metaphosphate, aluminum hydroxide, magnesium hydroxide, calcium pyrophosphate, red iron oxide, calcium sulfate, and anhydrous. Calcium can be mentioned.

Examples of alcohols include ethyl alcohol, lauryl alcohol, myristyl alcohol and the like.
Examples of the thickener include sodium polyacrylate, carrageenan, sodium carboxymethyl cellulose, sodium alginate, xanthan gum, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, and propylene glycol alginate.

Examples of the medicinal component include fluorides such as sodium monofluorophosphate, sodium fluoride, stannous fluoride and strontium fluoride, condensed phosphates such as sodium pyrophosphate and sodium polyphosphate, and sodium monohydrogen phosphate. , Phosphates such as trisodium phosphate, ascorbic acid, sodium ascorbate, pyridoxin hydrochloride, tocopherol acetate and other vitamins, dextranase, glucanase enzymes such as mutanase, proteases, degrading enzymes such as lysoteam, zinc chloride, Examples thereof include inorganic salts such as zinc citrate, strontium chloride and potassium nitrate, chelating compounds such as chlorophyll and glycerophosphate, polyethylene glycol which dissolves fat, sodium chloride, aluminum lactate and strontium chloride.

Examples of the colorant include legal dyes such as Green No. 1, Blue No. 1, and Yellow No. 4, titanium oxide, and the like.
Examples of the stabilizer include sodium edetate, sodium thiosulfate, sodium sulfite, calcium lactate, lanolin, triacetin, castor oil, magnesium sulfate and the like.

Examples of the pH adjuster include citric acid, malic acid, lactic acid, tartrate acid, acetic acid, phosphoric acid, pyrophosphate, glycerophosphate, various salts such as potassium salt, sodium salt and ammonium salt, sodium hydroxide and the like. Can be mentioned. The oral composition is preferably adjusted so that the pH is in the range of 4 to 9, particularly 5 to 7, by adding a pH adjuster.

Next, the operation of this embodiment will be described.
Although the details are omitted, the S.I. When the olaris concentration was compared, the subject group with no history of caries was found to be S. The results showed that the concentration of Oralis was significantly high. From this result, from the viewpoint of ensuring a healthy oral environment, S. It is considered important to increase the concentration of Oralis. The mechanism can be inferred as follows.

Early colonization bacteria are bacteria that attach to the tooth surface to form early plaques and mediate the attachment of biofilm-forming pathogens to the tooth surface. Among the early colonization bacteria, S. Oralis has weak adhesion to biofilm-forming pathogens and has S. cerevisiae on the tooth surface. The part where the alaris has settled becomes a part where the pathogen is less likely to adhere as compared with the part where the other early colonizing bacteria have adhered.

Therefore, in the oral cavity, S. When the concentration of Oralis increased, when the early colonizing bacteria were established on the tooth surface, S.I. The proportion of the part where Oralis has settled increases. In other words, S. in the oral cavity. The increase in the concentration of Oralis competitively inhibits the colonization of other early colonization bacteria to which pathogens are likely to adhere to the tooth surface. As a result of suppressing the colonization of other early colonization bacteria to which pathogens tend to adhere to the tooth surface, the formation of biofilm is suppressed, and a healthy oral environment can be easily obtained.

The oral composition of the present embodiment is S.I. Oralis can be grown in the oral cavity. The oral composition of the present embodiment is S.I. An effect of suppressing the formation of biofilm can be expected based on the effect of growing Oralis in the oral cavity.

Next, the effect of this embodiment will be described.
(1) The oral composition contains a specific amino acid and a specific sugar having a degree of polymerization of 1 or more and 10 or less. The particular amino acid is at least one selected from aspartic acid, aspartate, glutamic acid, glutamic acid, alanine, proline, serine, valine, and glycine. According to the above configuration, S. Oralis can be grown in the oral cavity.

(2) The specific amino acid is at least one selected from aspartic acid, aspartate, glutamic acid, glutamic acid, alanine, and glycine. In this case, S. The effect of growing Oralis in the oral cavity is more remarkable.

(3) The specific sugar is at least one selected from lactose, galactose, raffinose, galactooligosaccharides, and hydrates thereof. In this case, S. The effect of growing Oralis in the oral cavity is more remarkable.

(4) The specific amino acid is at least one selected from aspartic acid and aspartate. The particular sugar is at least one selected from galactose, raffinose, and galactooligosaccharides. In this case, S. The effect of growing Oralis in the oral cavity is more remarkable.

(5) The specific amino acid is at least one selected from glutamic acid and glutamic acid salt. The specific sugar is a galactooligosaccharide. In this case, S. The effect of growing Oralis in the oral cavity is more remarkable.

The oral composition of the present invention will be described in more detail based on the following examples and comparative examples. The present invention is not limited to the configuration of the following examples.
<Test 1>
(S. Oralis culture test)
In BHI medium (Brain Heart Infusion broth (manufactured by BD)), S. Oralis was cultured. After measuring the turbidity of the culture solution at a wavelength of 660 nm, the culture solution was diluted with BHI medium so that the measured turbidity became 0.1, and this was used as a bacterial solution. S. Streptococcus oralis spp. Denisani, tigurinus was used as the olaris.

Sample solutions of Examples 1 to 7 and Comparative Examples 1 to 6 in which amino acids and sugars were dissolved in BHI medium were prepared. The types of amino acids and sugars used in each sample solution are as shown in Table 1. The amino acid concentrations in each sample solution are as shown in Table 1. The concentration of sugar in each sample solution was 20 mg / ml.

100 μl of the bacterial solution and 100 μl of the sample solution were added to the wells of the 96-well plate, and the cells were cultured at 37 ° C. under anaerobic conditions for 24 hours. After culturing, the supernatant was removed, 110 μl of Alamar Blue solution (manufactured by Invitrogen) diluted 11-fold with phosphate buffered saline (PBS) was added, and the fluorescence intensity was measured at an excitation wavelength of 545 nm and a fluorescence wavelength of 590 nm. The relative value of the control to which the sample solution was not added with respect to the fluorescence intensity was set to S.I. It was calculated as the degree of growth of Oralis, and the calculated degree of growth was evaluated according to the following evaluation criteria. The results are shown in Table 1.

⊚: 10 or more ○: 5 or more and less than 10 ×: less than 5

表１に示すように、アミノ酸として、アスパラギン酸ナトリウム、グルタミン酸ナトリウム、アラニン、プロリン、セリン、バリン、又はグリシンを用いるとともに、糖として、ラクトース一水和物を用いた実施例１～７を添加した場合には、Ｓ．オラリスの増殖が促進された。Ｓ．オラリスの増殖を促進する効果は、アミノ酸として、アスパラギン酸ナトリウム、グルタミン酸ナトリウム、アラニン、及びグリシンを用いた場合に顕著であった。一方、アミノ酸を含有しない比較例１、及びアミノ酸として、メチオニン、システイン、イソロイシン、トリプトファン、又はフェニルアラニンを用いた比較例２～６を添加した場合には、Ｓ．オラリスの増殖を促進させる効果は得られなかった。

As shown in Table 1, Examples 1 to 7 using sodium aspartate, monosodium glutamate, alanine, proline, serine, valine, or glycine as amino acids and lactose monohydrate as sugar were added. In some cases, S. The growth of Oralis was promoted. S. The effect of promoting the growth of Oralis was remarkable when sodium aspartate, monosodium glutamate, alanine, and glycine were used as amino acids. On the other hand, when Comparative Example 1 containing no amino acid and Comparative Examples 2 to 6 using methionine, cysteine, isoleucine, tryptophan, or phenylalanine as amino acids were added, S. No effect was obtained to promote the growth of Oralis.

<Test 2>
Next, when sodium aspartate and monosodium glutamate, which showed a remarkable growth promoting effect in Test 1, were used as amino acids, the type of sugar was changed. The degree of growth of Oralis was measured. The test method is the same as in Test 1 except that the combination of amino acids and sugars used in each sample solution is changed and the concentrations of amino acids in each sample solution are all 20 mg / ml. Table 2 shows the types of amino acids and sugars used in each sample solution and the measurement results of the degree of growth.

表２に示すように、アミノ酸として、アスパラギン酸ナトリウム、又はグルタミン酸ナトリウムを用い、糖の種類を異ならせた実施例８～実施例２０を添加した場合には、いずれもＳ．オラリスの増殖が促進された。Ｓ．オラリスの増殖を促進する効果は、糖として、ラクトース一水和物、ガラクトース、ラフィノース、又はガラクトオリゴ糖を用いた場合に顕著であった。特に、アスパラギン酸ナトリウムと、ガラクトース、ラフィノース、又はガラクトオリゴ糖とを組み合わせた場合、及びグルタミン酸ナトリウムとガラクトオリゴ糖とを組み合わせた場合には、育成度が２００以上になり、Ｓ．オラリスの増殖が一層、顕著に促進された。試験１及び試験２の結果から、Ｓ．オラリスの増殖を促進させる効果は、特定のアミノ酸と任意の糖とを組み合わせた場合に限定的に得られる効果であることが分かる。

As shown in Table 2, when sodium aspartate or monosodium glutamate was used as the amino acid and Examples 8 to 20 having different types of sugars were added, S.A. The growth of Oralis was promoted. S. The effect of promoting the growth of Oralis was remarkable when lactose monohydrate, galactose, raffinose, or galactooligosaccharide was used as the sugar. In particular, when sodium aspartate is combined with galactose, raffinose, or galactooligosaccharide, or when monosodium glutamate and galactooligosaccharide are combined, the degree of growth becomes 200 or more, and S.I. The proliferation of Oralis was further significantly promoted. From the results of Test 1 and Test 2, S. It can be seen that the effect of promoting the growth of Oralis is a limited effect obtained when a specific amino acid is combined with an arbitrary sugar.

Next, the technical idea that can be grasped from the above embodiment is described below.
(A) The oral composition in which the amino acid is at least one selected from aspartic acid and aspartate, and the sugar is at least one selected from lactose, galactose, raffinose, and galactooligosaccharide.

(B) The oral composition in which the amino acid is at least one selected from glutamic acid and glutamic acid salt, and the sugar is a galactooligosaccharide.
(C) The oral composition having a mass ratio (sugar / amino acid) of the sugar to the amino acid of 0.5 to 3.

(D) A composition for promoting bacterial growth that promotes the growth of Streptococcus oralis, which contains an amino acid and a sugar having a degree of polymerization of 1 or more and 10 or less, and the amino acids are aspartic acid, aspartate, glutamic acid, and the like. A composition for promoting bacterial growth, which is at least one selected from glutamic acid, alanine, proline, serine, valine, and glycine.

(E) A method for promoting bacterial growth that promotes the growth of Streptococcus oralis in saliva, which comprises adding the composition for promoting bacterial growth to saliva.

Claims (3)

An oral composition containing an amino acid and a sugar having a degree of polymerization of 1 or more and 10 or less.
The oral composition is characterized in that the amino acid is at least one selected from aspartic acid, aspartate, glutamic acid, glutamic acid, alanine, proline, serine, valine, and glycine. The oral composition according to claim 1, wherein the amino acid is at least one selected from aspartic acid, aspartate, glutamic acid, glutamic acid, alanine, and glycine. The oral composition according to claim 1 or 2, wherein the sugar is at least one selected from lactose, galactose, raffinose, galactooligosaccharides, and hydrates thereof.