CN111479553B - Oral composition - Google Patents

Abstract

The present invention addresses the problem of providing an oral composition which can effectively inhibit the decomposition of a collagen layer located on the inner side of dentin when the collagen layer is exposed, and the use thereof, and the present invention provides an oral composition containing a component (A): glycerophosphoric acid and/or a salt thereof, and (B) component: pyrrolidone carboxylic acid and/or inorganic base salts thereof, and their use.

Description

Oral composition

Technical Field

The present invention relates to oral compositions.

Background

In the oral cavity, the dentin of a tooth is usually protected by enamel. However, when the gum is atrophic with the onset of periodontal disease, the root portion previously covered with the gum is exposed in the oral cavity. In the root portion, dentin exists in a state of not being covered with enamel. Since this dentin has numerous tubule structures and contains many organic layers mainly composed of collagen, the mineral density is as low as about 50%, and it is physically and chemically weak as compared with enamel having a mineral density of about 97%. Therefore, caries tends to occur in the root portion exposed in the oral cavity. Here, "caries" refers to substantial tooth loss caused by demineralization (elution of mineral components) of enamel and dentin by acid produced by metabolism of sugar by bacteria in the oral cavity. In caries, the dentinal caries occurring at the root of a tooth is called "root-surface caries".

The pathogenesis of root-facet caries is as follows. First, plaque adheres to dentinal surfaces exposed in the mouth, and bacteria in the plaque cause sugar metabolism to produce acid. The generated acid then demineralizes the crystalline layer of dentin, exposing the collagen layer present inside the dentin. Thus, the exposed collagen layer is physically/chemically destroyed. As a result, substantial defects in the root surface are caused. On the other hand, it has been pointed out that: when the collagen layer remains, it becomes a point of remineralization, and crystals of calcium ions and phosphate ions derived from saliva may precipitate on the collagen.

Therefore, it can be said that inhibition of the decomposition of the exposed collagen layer is effective for the prevention of root caries.

With the progress to an aging society, there is a tendency that root-surface caries increases with the onset of periodontal disease. Therefore, it is now sought to establish an efficient technique for preventing root caries.

Here, as a technique for preventing caries, there are known: fluoride slow release techniques such as a technique of using calcium phosphate cement and fluoride in combination (patent document 1), a technique of using an adhesive in which a metal fluoride is mixed (patent document 2), and the like; fluoride retention techniques such as a technique of using a water-soluble calcium salt, other 2-valent metal, a water-soluble phosphate and a water-soluble fluoride together (patent document 3).

Patent document 4 describes: lactam compounds such as pyrrolidone carboxylic acid alone or specific combinations containing the same have a collagen degradation inhibitory effect.

[ Prior art documents ]

[ patent literature ] A

[ patent document 1] Japanese patent application laid-open No. 5-23386

[ patent document 2] Japanese patent laid-open No. 2001-322908

[ patent document 3] Japanese Kohyo publication Hei 10-511104

[ patent document 4] WO2013/047826

Disclosure of Invention

[ problem to be solved by the invention ]

However, although the techniques using fluoride as disclosed in patent documents 1 to 3 can exert a certain effect on dental enamel caries, collagen exposed from root caries cannot be protected by fluoride, and thus decomposition of collagen cannot be suppressed. Therefore, these techniques cannot be expected to exert effects on dental caries.

Patent document 4 discloses that pyrrolidone carboxylic acid or a salt thereof alone or a specific combination containing pyrrolidone carboxylic acid or a salt thereof exerts a collagen degradation-inhibiting effect, and does not provide any motivation for combining pyrrolidone carboxylic acid or a salt thereof with another compound.

The present invention addresses the problem of providing an oral composition which can effectively inhibit the decomposition of a collagen layer located on the inner side of dentin when the collagen layer is exposed, and the use thereof.

[ means for solving the problems ] to solve the problems

The present inventors have found that by using the (a) component in combination: glycerophosphoric acid and/or a salt thereof and (B) component: pyrrolidone carboxylic acid and/or an inorganic alkali salt thereof can solve the above problems and effectively suppress the decomposition of an exposed collagen layer, thereby completing the present invention.

That is, the present invention provides the following [ 1] to [ 8 ].

[ 1] an oral composition comprising the following components (A): glycerophosphoric acid and/or a salt thereof and (B) component: pyrrolidone carboxylic acid and/or inorganic base salts thereof.

[ 2] the oral composition according to [ 1], wherein the content of the component (A) in the oral composition is from 0.005 to 1% by mass.

[ 3] the oral composition according to [ 1] or [ 2], wherein the content of the component (B) in the oral composition is 0.1 to 20% by mass.

[ 4] the oral composition according to any one of [ 1] to [ 3], wherein the ratio (A/B) of the mass of the component (A) to the mass of the component (B) is 0.001 to 6.

[ 5] the oral composition according to any one of [ 1] to [ 4], wherein the oral composition further comprises 1 or more selected from citric acid and salts thereof and phosphoric acid and salts thereof.

[ 6] the oral composition according to any one of [ 1] to [ 5], wherein the oral composition is a liquid.

[ 7] the oral composition according to any one of [ 1] to [ 6], wherein the oral composition is a liquid dentifrice or mouthwash.

[ 8 ] the oral composition according to any one of [ 1] to [ 7], wherein the oral composition is for inhibiting decomposition of oral collagen.

[ Effect of the invention ]

The present invention can provide: an oral composition which can remarkably suppress the decomposition of an exposed collagen layer and effectively suppress the decomposition of a collagen layer located inside dental caries, and use thereof.

Detailed Description

The present invention will be described in detail below with reference to preferred embodiments thereof. In the present specification, the content of each component is a value based on the amount of each component added in the preparation of the composition.

[1. Composition for oral cavity ]

The oral composition of the present invention contains component (a) and component (B). Further, the oral composition of the present invention may contain any ingredient.

< ingredient (A) >

The component (A) is glycerophosphoric acid and/or a salt thereof.

The glycerophosphoric acid includes alpha-glycerophosphoric acid and beta-glycerophosphoric acid, preferably alpha-glycerophosphoric acid.

Examples of the salt of glycerophosphoric acid include inorganic alkali salts such as alkali metal salts (e.g., sodium salt and potassium salt), alkaline earth metal salts (e.g., calcium salt and magnesium salt), copper salts, zinc salts, aluminum salts, and ammonium salts; organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt and diisopropylammonium salt. Among these salts, alkali metal salts and alkaline earth metal salts are preferable, sodium salts, potassium salts and calcium salts are more preferable, and calcium salts are even more preferable.

Component (a) may be glycerophosphoric acid alone or a salt of glycerophosphoric acid alone, or a combination of glycerophosphoric acid and a salt of glycerophosphoric acid, or a combination of 2 or more salts of glycerophosphoric acid.

Glycerophosphoric acid and/or its salt may be a commercially available product. Examples of commercially available products of α -glycerocalcium phosphate include "Ca glycerophosphate (trade name)" manufactured by nippon pharmaceutical corporation.

The content of the component (a) in the oral composition of the present invention is not particularly limited, and is usually 0.005 mass% or more, preferably 0.01 mass% or more, relative to the total amount of the oral composition. This effectively suppresses the degradation of the collagen layer located inside the dentin when exposed (collagen degradation-suppressing effect). The upper limit of the content is usually 1% by mass or less, preferably 0.5% by mass or less. This can provide excellent feeling in use and can suppress the irritating feeling and the unpleasant odor derived from the component (A). In a preferred embodiment, the content of the component (A) is usually 0.005 to 1% by mass, preferably 0.01 to 0.5% by mass.

< ingredient (B) >

(B) The component (B) is pyrrolidone carboxylic acid and/or inorganic alkali salt thereof. The pyrrolidone carboxylic acid is a compound represented by the following formula (1).

[ CHEM 1]

The method for producing pyrrolidone carboxylic acid and inorganic base salts thereof is not particularly limited. Examples of the production method include: a method of dehydrating glutamic acid extracted from a living body such as seaweed or sugarcane or a processed product such as wheat flour to obtain pyrrolidone carboxylic acid, and bonding a metal ion (for example, sodium ion) to the pyrrolidone carboxylic acid, thereby producing a pyrrolidone carboxylic acid metal salt.

Examples of the inorganic alkali salt of pyrrolidone carboxylic acid include inorganic alkali salts of metals having 1 to 3 valences. Examples of the 1 to 3-valent metal inorganic base salt include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salts and magnesium salts; copper salt, zinc salt, aluminum salt, and ammonium salt, and alkali metal salt (sodium salt and potassium salt) is preferable. Sodium salt of pyrrolidone carboxylic acid (sodium PCA) is more preferable because it has good stability (e.g., oxidation stability) and is highly safe as a constituent of NMF (natural moisturizing factor) which is a substance for retaining moisture in the stratum corneum of the skin.

(B) The component (A) may be 1 kind selected from pyrrolidone carboxylic acid and its inorganic base salt, or a combination of 2 or more kinds.

The content of the component (B) in the oral composition of the present invention is not particularly limited, and is usually 0.1 mass% or more, preferably 0.3 mass% or more, and more preferably 0.5 mass% or more, based on the total amount of the oral composition. This can exert a collagen degradation-inhibiting effect. The upper limit of the content is usually 20% by mass or less, preferably 10% by mass or less, and more preferably 5% by mass or less. This makes it possible to provide a user with an excellent feeling of use. Further, the odor derived from the component (B) can be suppressed. In a preferred embodiment, the content of the component (B) is usually 0.1 to 20% by mass, preferably 0.1 to 15% by mass, more preferably 0.3 to 10% by mass, and still more preferably 0.5 to 5% by mass.

<A/B>

In the oral composition of the present invention, the ratio (a/B) of the mass of component (a) to the mass of component (B) is usually 0.001 or more, preferably 0.005 or more, and more preferably 0.01 or more. This can more effectively exhibit the collagen degradation-inhibiting effect. The upper limit of the mass ratio is usually 6 or less, preferably 5 or less, more preferably 2 or less, and particularly preferably 1 or less. This makes it possible to provide a user with an excellent feeling of use. Especially, the odor can be suppressed. In a preferred embodiment, the value of A/B is usually 0.001 to 6, preferably 0.001 to 5, more preferably 0.005 to 2, and particularly preferably 0.01 to 1.

< dosage forms >

The dosage form of the oral composition is not limited, and is preferably liquid at normal temperature and pressure (e.g., 25 ℃ and 101.325 kPa) from the viewpoint of increasing the possibility of contacting the collagen layer exposed in the oral cavity. The liquid oral composition can be formulated into liquid preparations suitable for use as gargles (e.g., gargles, rinses), liquid dentifrices, mouth fresheners, and the like. The liquid may be concentrated. The oral composition can be any of medicinal products, quasi-medicinal products, cosmetics and foods.

< optional Components >

In addition to the above-mentioned ingredients, any ingredients may be mixed in the oral composition of the present invention as necessary. Any component can be selected as appropriate depending on the use and the dosage form of the oral composition. For example, when the oral composition is a liquid, as optional ingredients, a surfactant, a thickener, a sweetener, a preservative, a flavor, a pharmaceutical ingredient, a thickener, a humectant other than the component (a), a pH adjuster, a buffer, and a solvent can be exemplified. In addition, when the oral composition is in a form other than a liquid, examples of the components other than the optional components described above include a binder and an abrasive. The content of any component is not particularly limited, and may be set to an amount used in a usual oral composition within a range not impairing the effects of the present invention.

Examples of the surfactant include anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants.

Examples of the anionic surfactant include N-acyl amino acid salts, α -olefin sulfonates, N-acyl sulfonates, alkyl sulfates, and sulfates of glycerin fatty acid esters.

Examples of the N-acylamino acid salt include acylamino acids having a saturated or unsaturated hydrocarbon group (e.g., having 8 to 18, preferably 12 to 16 carbon atoms; and may be either a straight chain or a branched chain), acyl taurines, and salts thereof, and specifically include methyltaurates such as lauroyl methyltaurate, coconut fatty acid methyltaurate, and myristoyl methyltaurate; methyl alanine salts such as lauroyl methyl alanine salt; glutamates such as lauroyl glutamate and myristoyl glutamate.

As the α -olefin sulfonate, for example, sodium α -olefin sulfonate can be cited. The number of carbon atoms of the alkyl group of the α -olefin sulfonic acid is, for example, 10 to 16. As the α -olefin sulfonate, tetradecene sulfonate is preferable, and sodium tetradecene sulfonate is more preferable.

Examples of the alkyl sulfate include sodium lauryl sulfate and sodium myristyl sulfate. The alkyl sulfate preferably has 12 to 14 carbon atoms in the alkyl group.

Examples of the other anionic surfactants include sodium acyl sarcosinates such as sodium N-lauroyl sarcosinate and sodium N-myristoyl sarcosinate; sodium N-methyl-N-acylalanine, sodium dodecyl benzene sulfonate, sodium monoglyceride monosulfate of hydrogenated coconut oil fatty acid, sodium lauroyl sulfoacetate, sodium N-palmitoyl glutamate, etc. Examples of the anionic surfactant having good foamability and/or hard water resistance include sodium acyl sarcosinate (e.g., sodium lauroyl sarcosinate), sodium α -olefin sulfonate, and alkyl sulfate (e.g., sodium lauryl sulfate), which are preferable.

Examples of the nonionic surfactant include polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene hydrogenated castor oils, polyoxyethylene ethers of glycerides, sucrose fatty acid esters, alkanolamides, sorbitan fatty acid esters, and polyglycerol fatty acid esters. Specific examples thereof include: polyoxyethylene alkyl ether having an alkyl chain with a carbon chain length (number of carbon atoms) of 14 to 18 and an average number of moles of ethylene oxide added of 15 to 30; polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 5 to 100, preferably 50 to 100, more preferably 60 to 100; alkanolamides having an alkyl chain with a carbon chain length (number of carbon atoms) of 12 to 14; sorbitan fatty acid esters having 12 to 18 carbon atoms in the fatty acid; a polyoxyethylene sorbitan fatty acid ester having 16 to 18 carbon atoms in the fatty acid and 10 to 40 moles of ethylene oxide added on the average.

Examples of the cationic surfactant include quaternary ammonium compounds. Examples of the quaternary ammonium compound include alkylammonium compounds and alkylbenzyl ammonium compounds. Examples of the alkylammonium compound include cetylpyridinium chloride, and examples of the alkylbenzylammonium compound include benzethonium chloride and benzalkonium chloride.

Examples of the amphoteric surfactant include alkylamide betaine amphoteric surfactants; acetic acid betaine amphoteric surfactants such as alkyldimethylaminoacetic acid betaine and fatty acid amide propyldimethylaminoacetic acid betaine; imidazoline type amphoteric surfactants such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine salt.

Examples of the thickener include propylene glycol, butylene glycol, glycerin, sorbitol, polyethylene glycol, alcohols (e.g., ethanol, modified ethanol), and sugar alcohol-reduced starch saccharides. When the oral composition contains a thickener, the content of the thickener is usually 0.3 to 50% by mass based on the total amount of the oral composition.

Examples of the sweetener include xylitol, saccharin sodium, stevioside, neohesperidin dihydrochalcone, glycyrrhizin, perillatin, p-methoxycinnamaldehyde, thaumatin (thaumatin), maltitol, aspartame, erythritol, and the like. The sweetener can also be used as spice.

Examples of the preservatives include parabens such as methyl paraben and ethyl paraben; sodium benzoate; parabens such as butyl paraben, methyl paraben and ethyl paraben; ethylene diamine tetraacetic acid salt; benzalkonium chloride.

The perfume is not particularly limited, and examples thereof include natural perfumes, synthetic perfumes (individual perfumes), and blend perfumes (oil perfumes (oily perfumes), powdery perfumes, and the like). As the perfume, for example, 1 or more selected from the following perfumes are suitable: natural essential oils such as peppermint oil (peppermint oil), spearmint oil, eucalyptus oil, wintergreen oil, clove oil, thyme oil, cardamom oil, coriander oil, marjoram oil, nutmeg oil, lavender oil, jambu (para stress) oil, peppermint oil, and the like; extracts such as Capsici fructus extract, rhizoma Zingiberis recens extract, fructus Piperis extract, and fructus Zanthoxyli extract; fruit-based essences such as lemon and strawberry; l-menthol, carvone (l-carvone), cinnamaldehyde, p-methoxycinnamaldehyde, methyl salicylate, eugenol, anethole, linalool oxide, limonene, ocimene, 1,8-cineole, N-decanol, benzyl alcohol, phenethyl alcohol, citronellol, vanillin (vanillin), alpha-terpineol, methyl salicylate, thymol, menthone, menthyl acetate, citral, camphor, borneol, pinene, spilanthol, ethyl acetate, ethyl butyrate, ethyl 2-methylbutyrate, isoamyl acetate, hexyl acetate, linalyl acetate, allyl caproate, hexanal, hexenal, cis-3-hexenal, trans-2-hexenal, decanal, isovaleryl alcohol, isovaleryl acetate, linalyl caproaldehyde, hexenal, and linalyl methyl anthranilate, ethyl methylphenylglycidate, phenylethyl glycidate, benzaldehyde, vanillin, ethyl vanillin, vanillyl butyl ether, furanone, maltol, ethyl maltol, γ/δ decalactone, γ/δ undecanolactone, N-ethyl-p-menthane-3-carboxamide, N-ethyl-2-isopropyl-5-methylcyclohexanecarboxamide, N- [ (ethoxycarbonyl) methyl ] -p-menthane-3-carboxamide, N-p-phenylacetonitrile menthanecarboxamide, N- (2- (pyridin-2-yl) ethyl) -3-p-menthanecarboxamide, menthyl lactate, ethylene glycol-l-menthyl carbonate, methyl heptynecarboxylate, menthofuran (methofuran), 3-l-menthoxypropane-1,2-diol, menthyl glycerol ether, spilanthol, menthyl succinate, isopulegol, ethyl cyclopentenolone, 4,5-dimethyl-3-hydroxy-2 (5H) -furanone, methyl cyclopentenolone (cyclotene), 2-methylbutanoic acid, acetic acid, propionic acid, octanol, methyl cinnamate, ionone, ethyl beta-methylthiopropionate, cis-6-nonenol, 7-methyl-2H-1,5-benzodioxapin-3 (4H) -one (7-methyl-2H-1,5-benzoxadiol epine-3 (4H) -one), methyl jasmonate; a perfume raw material such as rosemary oil, sage oil, perilla oil, lemon oil, orange oil, lime oil, mandarin oil, grapefruit oil, fennel oil, cinnamon oil, bay oil, caraway oil, basil oil, mastic oil (mastic oil), neroli oil (neroli oil) (orange flower oil)), lemongrass oil, jasmine oil, rose oil, iris oil, and the like; apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, pumpkin, coffee, brandy, yogurt, vanilla, and other flavoring essences.

Examples of the pharmaceutical agent include the following: anticaries agents such as fluoride (e.g., sodium fluoride, sodium monofluorophosphate, stannous fluoride); quaternary ammonium compounds such as chlorhexidine, zinc gluconate, zinc citrate, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, dequalinium chloride, and the like; biguanide compounds such as chlorhexidine gluconate and chlorhexidine hydrochloride; bactericides or antibacterial agents such as alkyldiaminoethylglycine hydrochloride and isopropylmethylphenol; dental calculus preventives such as condensed phosphates and ethane hydroxy diphosphonates; tranexamic acid, glycyrrhizin 2 potassium salt, epsilon-aminocaproic acid, and cortex Phellodendri extract; coating agents such as hydroxyethyl cellulose dimethyldiallylammonium chloride; allantoin, allantoin chlorohydroxy aluminium, vitamin C, lysozyme chloride, glycyrrhetinic acid and its salts, sodium chloride, and other astringents or vitamins; sensory hypersensitivity inhibitors such as strontium chloride, potassium nitrate and aluminum lactate; a copper compound; and a plant extract. The medicinal components may be 1 kind alone or a combination of 2 or more kinds.

When the oral composition contains a medicinal ingredient, the content of each medicinal ingredient can be appropriately set within a pharmaceutically acceptable range.

Examples of the thickener include xanthan gum, carrageenan, hydroxyethyl cellulose, sodium alginate, polyvinyl alcohol, and carboxymethyl cellulose. When a thickener is mixed, the content of the thickener is usually 0.01 to 10% by mass based on the total amount of the oral composition.

Examples of the humectant include sugar alcohols such as sorbitol, maltitol, and lactitol; polyols such as glycerol, ethylene glycol, polyethylene glycol, and propylene glycol.

Examples of the pH adjuster and the buffer include citric acid, tartaric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, phosphoric acid, carbonic acid, and potassium salts, sodium salts, and ammonium salts thereof; ribonucleic acids and salts thereof, and lactic acid; hydrochloric acid; acetic acid; nitric acid; sodium hydroxide; potassium hydroxide, and the like. Wherein the oral composition can be stably maintained at a pH of 5 to 8.5 at 25 ℃ by using 1 or more selected from citric acid and salts thereof, and phosphoric acid and salts thereof. This can suppress demineralization of enamel of the tooth. Sodium citrate is an example of a salt of citric acid. Examples of the salt of phosphoric acid include disodium hydrogenphosphate and sodium dihydrogenphosphate. pH adjusters, buffers may be used in amounts to achieve the target pH of the liquid oral composition.

When the oral composition is a liquid or when the oral composition is a liquid preparation, the pH (25 ℃) is usually 4.5 to 9, preferably 5 to 8.5, for example 6 to 8 or 6 to 7.5. This can suppress demineralization of enamel of the tooth, and can maintain effectiveness and stability. Immediately after the preparation of the liquid oral composition, the pH was measured at 25 ℃ for 3 minutes using a pH meter (model Hm-30S) manufactured by Toyo electric wave industries, ltd. The oral composition may contain a pH adjusting agent as needed for pH adjustment. When the oral composition contains a pH adjuster, the content thereof may be appropriately determined as needed (for example, within a range not impairing the effects of the present invention).

When the oral composition is a liquid, it preferably contains a solvent. Examples of the solvent include water, alcohols (e.g., lower monohydric alcohols such as ethanol), and propylene glycol. The solvent is preferably a mixed solvent, and more preferably, the ratio of ethanol: 0 to 30 percent of mixed solvent, 70 to 95 percent of water and 0 to 10 percent of propylene glycol. Propylene glycol may also function as a thickener. When the liquid oral composition contains water, the content of water is usually 60% by mass or more based on the total amount of the liquid oral composition. When the liquid oral composition contains a lower monohydric alcohol, the content thereof is usually 30% by mass or less, preferably 20% by mass or less, based on the total amount of the liquid oral composition.

The method of using the oral composition of the present invention is not particularly limited. In the case of mouth wash and mouth refresher, for example, a method of rinsing the mouth with an appropriate amount of the mouth for 10 to 30 seconds, particularly preferably about 20 seconds, is exemplified. In addition, in the case of liquid dentifrices, teeth are usually brushed after rinsing.

< use >

The oral composition of the present invention is useful for inhibiting collagen degradation. The collagen is not particularly limited, and the collagen in the oral cavity is usually collagen containing type I collagen. In dentin caries, a collagen layer of dentin is exposed, and when decomposed by collagenase, a substantial defect is generated in the root of a tooth. By applying the oral composition to teeth, collagen degradation can be suppressed or improved, and dental caries can be prevented.

The subject to be ingested with the oral composition of the present invention is not particularly limited. Examples thereof include: in a subject who has developed and wants to improve symptoms caused by collagen degradation (for example, development of dentinal caries, periodontal tissue problems (gingival atrophy, alveolar bone resorption, etc.)), a subject who wants to prevent these symptoms, though not developing the symptoms, and the like.

[2. Method for producing oral composition ]

The oral composition of the present invention can be produced by mixing the above components. The order of mixing the components is not particularly limited, and a uniform mixing order is preferable. In the production, a solvent may be used as a dispersion medium. In the production of the liquid oral composition, it is preferable to stably maintain the pH of the liquid oral composition at 25 ℃ in the range of 5 to 7 by using citric acid. It is also preferable to stably maintain the pH of the liquid oral composition at 25 ℃ in the range of 6 to 8 by using phosphoric acid instead of citric acid or in combination with phosphoric acid and citric acid.

[ examples ] A method for producing a compound

The present invention will be described in more detail below with reference to examples. The following examples are intended to appropriately illustrate the present invention and are not intended to limit the present invention. In addition, "%" indicates "% by mass" unless otherwise specified. The blending amounts of the respective components shown in tables 1 and 2 are values (AI) converted into pure components. The amount of water (the balance) includes the amount of water contained in each component.

Examples 1 to 14 and comparative examples 1 to 3

The mouth rinses of examples 1 to 14 and comparative examples 1 to 3 were prepared by uniformly mixing all the components according to the compositions shown in tables 1 and 2 (unit of content of each component in tables 1 and 2: mass%). Specifically, the raw materials were sequentially added to purified water, stirred, and uniformly dissolved using a Three-in-One stirrer (BL 1200, manufactured by HEIDON corporation) to prepare a mouth wash. The pH (25 ℃) of the resulting mouthwash was 6.2.

The details of each component are as follows.

< ingredient (A) >

Calcium glycerophosphate: alpha-Glycerol calcium phosphate (product of Yangcheng pharmaceutical Co., ltd. "Glycerol calcium phosphate Ca (trade name)")

< ingredient (B) >

Sodium pyrrolidone carboxylate: ajiew (registered trademark) N-50, manufactured by Ajiew K.K.) "

< optional Components >

(surfactant) polyoxyethylene hydrogenated castor oil: "Polyoxyethylene (60) hydrogenated castor oil" (addition mol number of ethylene oxide: 60) manufactured by Nikkiso K.K.)

(thickening agent) propylene glycol (manufactured by Asahi glass Co., ltd.)

(thickening agent) Glycerol (85% purity, manufactured by saka pharmaceutical industries, ltd.)

(sweetener) xylitol (manufactured by Roguette FREES Co., ltd.)

(pH adjuster) citric acid (manufactured by Hibiscus chemical Co., ltd.)

(pH adjuster) sodium citrate (manufactured by Hibiscus chemical Co., ltd.)

(pH adjuster) disodium hydrogenphosphate (manufactured by Taiping chemical industry Co., ltd.)

(pH adjuster) sodium dihydrogen phosphate (manufactured by Taiping chemical industry Co., ltd.)

(pH adjuster) sodium hydroxide (manufactured by Kanto chemical Co., ltd.)

(sweetener) saccharin sodium salt (manufactured by Dadong chemical Co., ltd.)

(fragrance) fragrance compositions A to P (high-purity mixtures of lion Wang Zhushi, manufactured by Shi 5363 Zxft 5363) shown in tables 3 and 4 to 10

(solvent) Water: purified water for sale (external standard 2006 of medical ministry)

The respective mouthwashes of tables 1 and 2 were evaluated for collagen degradation inhibitory effect and feeling of use according to the following methods and criteria. The results are shown in tables 1 and 2.

< method for evaluating collagen degradation inhibitory Effect >

(1) Method for preparing root and surface caries sample

After grinding the bovine root surface to remove cementum at a width of about 2mm as a demineralization window, a slice having a thickness of 250 μm was cut out using a micro cutter. In the cementum-removed part, about 1.5mm × 250 μm was used as a demineralization window, and the other part was covered with nail polish. After the nail polish was dried at room temperature, it was immersed in a 0.1mol/L aqueous acetic acid solution (pH 4.5 (25 ℃ C.)) for 6 hours to expose the collagen in the demineralization window, thereby producing a root-facet caries sample.

(2) Experimental procedure for collagen degradation inhibition test

The root caries samples obtained in the above (1) were immersed in the examples and ratios shown in tables 1 and 2 at room temperatureThe mouth rinse of the comparative example was rinsed with distilled water for 5 minutes (mouth rinse treatment), and then immersed in artificial saliva (CaCl) containing collagenase at 37 ℃ ₂ ：2.2mmol/L，KH ₂ PO ₄ :2.2mmol/L, acetic acid: 0.1mol/L, and collagenase (Type 1A, manufactured by Sigma) from Clostridium histolyticum (Clostridium histolyticum); 1.0 unit/mL, pH6.5 (25 ℃)). The treatment with the mouth rinse was performed 3 times a day in the morning, noon, and evening, and the mouth rinse was immersed in artificial saliva containing collagenase for the remaining time periods, which were repeated for 4 days in total. In parallel, the same experiment was also performed on a control group treated with purified water instead of the mouth rinse of example/comparative example.

(3) Calculation of collagen degradation inhibition Rate and evaluation of dentin caries prevention Effect

After the experiment, the root caries samples were observed with a microscope, and the decomposition depth of collagen exposed at 3 spots was measured for each sample and averaged. That is, n =3 was measured, and the average value was calculated. Here, the "depth of dissolution" refers to the depth of erosion based on the surface height at which the demineralization window in the root caries sample is formed.

Next, the dentin collagen degradation inhibition rate (%) was calculated by the following formula, and the calculated dentin collagen degradation inhibition rate was used to evaluate the collagen degradation inhibition rate on a 4-step basis according to the following criteria. The results are shown in tables 1 and 2.

[ formula ]

Dentin collagen degradation inhibition rate (%) = { (depth of degradation in control group-depth of degradation in example group/comparative example group)/(depth of degradation in control group) } × 100

(evaluation criteria)

A: the collagen protein decomposition inhibition rate is more than 80 percent

B: the collagen protein decomposition inhibition rate is more than 70% and less than 80%

C: the collagen protein decomposition inhibition rate is more than 50% and less than 70%

D: the collagen protein decomposition inhibition rate is less than 50%

< method for evaluating feeling of use (presence or absence of odor and presence or absence of stimulus >

For each of the rinses in tables 1 and 2,5 judges judged the flavor (feeling of use) after rinsing. In the determination, 10mL of each mouth wash was first contained in the mouth of each of the panelists, and the mouth wash was circulated in the oral cavity for 30 seconds and then discharged. Next, each of the judges rated the feeling of use of the mouth rinse in 4 grades according to the following rating standards from the viewpoint of the presence or absence of the offensive odor and the presence or absence of the irritating feeling. As a standard of the mouth rinse without unpleasant odor and irritation, a mouth rinse containing neither the component (a) nor the component (B) was used, that is, a mouth rinse containing no component (a) added to the mouth rinse of comparative example 1. The average of the obtained scores was obtained, and the feeling of use of each mouthwash was evaluated according to the following evaluation criteria. The results are shown in tables 1 and 2.

(1) Presence or absence of odor

(evaluation Standard for the Presence or absence of offensive odor after gargling)

And 4, dividing: has no peculiar smell

And 3, dividing: almost no peculiar smell

And 2, dividing: slightly off-flavor

1 minute: has peculiar smell

(evaluation criteria for the presence or absence of unpleasant odor after gargling)

A: an average score of 3.5 to 4.0

B: an average score of 3.0 to less than 3.5

C: an average score of 2.0 to less than 3.0

D: average score is less than 2.0

(2) Presence or absence of irritation

(evaluation criteria for stimulating after gargling)

And 4, dividing: has no irritation

And 3, dividing: has little irritation

And 2, dividing: slightly irritate

1 minute: with stimulation

(evaluation criteria for the Presence or absence of irritation after gargling)

A: an average score of 3.5 to 4.0

B: an average score of 3.0 to less than 3.5

C: an average score of 2.0 to less than 3.0

D: the average score is less than 2.0

[ TABLE 2]

[ Table 2: comparative examples 1 to 3

[ discussion ]

As shown in tables 1 and 2, the evaluation results of the collagen degradation inhibition effect in comparative examples 1 to 3 were "D", whereas the evaluation results of the collagen degradation inhibition effect in examples 1 to 14 were "a" or "B". Therefore, it was found that the mouth washes of examples 1 to 14 can effectively suppress the decomposition of collagen present inside dentin by containing the components (a) and (B). On the other hand, the mouth rinses of comparative examples 1 to 3 are considered to have a lower collagen degradation inhibitory effect than the mouth rinses of examples 1 to 14 because they contain one and not the other of the component (a) and the component (B). When the component (a) is contained and the component (B) is replaced with a long-chain organic salt (comparative example 2), the effect of inhibiting collagen degradation is inferior to those of the mouth rinses of examples 1 to 14.

As shown in tables 1 and 2, the evaluation results of the feeling of use were poor in comparative examples 1 to 3, while the evaluation results of the feeling of use were excellent in all of examples 1 to 14. Therefore, it was found that the mouth rinses of examples 1 to 14 had a good feeling of use when they contained the component (a) and the component (B).

In addition, 0.2 mass% of each of the fragrance compositions B to P shown in tables 3 and 4 to 10 (the unit of the content of each component in table 3: mass%, which represents the unit of the composition of each component in tables 4 to 10: parts by mass) was added to the mouth wash instead of adding 0.2 mass% of the fragrance composition a to the mouth wash in examples 2, 3, 5, 6, 8, 13 and 14 to prepare a mouth wash, and the same evaluation was performed. As a result, the same evaluation results as in examples 2, 3, 5, 6, 8, 13 and 14 in which 0.2 mass% of the fragrance composition a was added were obtained in the mouth wash to which either of the fragrance compositions was added.

[ TABLE 3]

[ TABLE 4]

[ Table 4: flavor essence 1

Linalool	1
		Mint furans	1
Anethole	1
		Menthones	1
Menthyl acetate	1
		Is totaled	5 portions of

[ TABLE 5]

[ Table 5: flavor essence 2)

Orange oil	1
		Lemon oil	1
Lime oil	1
		Orange oil	1
Grapefruit oil	1
		Citral	1
Decanal	1
		Total up to	7 portions of

[ TABLE 6]

[ Table 6: flavor essence 3

Fennel oil	1
		Eucalyptus oil	1
Cinnamon oil	1
		Clove oil	1
Thyme oil	1
		Sage oil	1
Cardamom oil	1
		Coriander oil	1
Rosemary oil	1
		Laurel oil	1
Artemisia oil	1
		Basil oil	1
Total up to	12 portions of

[ TABLE 7]

[ Table 7: flavor essence 4)

Wintergreen oil	1
		Mastic oil (mastic oil)	1
Lavender oil	1
		Neroli oil (neroli oil; orange flower oil)	1
Lemongrass oil	1
		Jasmine oil	1
Rose oil	1
		Iris oil	1
Vanilla oil	1
		Total up to	9 portions of

[ TABLE 8 ]

[ Table 8: flavor essence 5

Menthyl lactate	1
		N-ethyl-2-isopropyl-5-methylcyclohexanecarboxamide	1
N- [ (ethoxycarbonyl) methyl group]-p-menthane-3-carboxamide	1
		N-p-phenylacetonitrile menthane carboxamide	1
N- (2- (pyridin-2-yl) ethyl) -3-p-menthanecarboxamide	1
		3-l-menthoxypropane-1,2-diol	1
Menthyl glyceryl ether	1
		Spilanthol	1
Succinic acid menthyl ester	1
		Linalool oxide	1
Vanillyl butyl ether	1
		Isopulegol	1
Capsicum extract	1
		Ginger extract	1
Pepper extract	1
		Zanthoxylum piperitum extract	1
Total up to	16 portions of

[ TABLE 9 ]

[ Table 9: flavor essence 6

Maltol	1
		Ethyl maltol	1
Vanillin	1
		Ethyl vanillin	1
Furaneol (4-hydroxy-2,5-dimethyl-3 (2H) furanone)	1
		Ethyl cyclopentenolone	1
4,5-dimethyl-3-hydroxy-2 (5H) -furanone	1
		Methylcyclopentadienyl alcohol ketone (cyclotene)	1
2-methyl butyric acid	1
		Acetic acid	1
Propionic acid	1
		Total up to	11 portions of

[ TABLE 10 ]

[ Table 10: flavor essence 7)

P-methoxy cinnamic aldehyde	1
		Cis-3-hexenal	1
Trans-2-hexenal	1
		Undecalactones	1
Decanolide	1
		Butyric acid ethyl ester	1
Acetic acid isoamyl ester	1
		Benzaldehyde	1
Acetic acid hexyl ester	1
		2-Methylbutanoic acid ethyl ester	1
Benzyl alcohol	1
		Alpha-terpineol	1
Linalyl acetate	1
		Phenylethyl glycidic acid ester	1
Phenylethanolic acid	1
		Allyl caproate	1
Octanol (I)	1
		Cinnamic acid methyl ester	1
Heptynecarboxylic acid methyl ester	1
		Ionones	1
Beta-methylthiopropionic acid ethyl ester	1
		Cis-6-nonenol	1
7-methyl-2H-1,5-benzodioxapin-3 (4H) -one	1
		Jasmonic acid methyl ester	1
Total up to	24 portions of

Claims (10)

1. An oral composition comprising:

(A) The components: glycerophosphoric acid and/or a salt thereof, and

(B) The components: pyrrolidone carboxylic acid and/or inorganic base salts thereof;

the salt of the component (A) is selected from alkali metal salts and alkaline earth metal salts, the salt of the component (B) is selected from alkali metal salts,

the content of the component (A) is 0.01 to 0.5 mass%, and the content of the component (B) is 0.3 to 10 mass%;

the oral composition has a pH of 5 to 8.5 at 25 ℃.

2. The oral composition of claim 1, wherein the glycerophosphate is a-glycerophosphate.

3. The oral composition according to claim 1 or 2, wherein the content of the component (B) in the oral composition is 0.5% by mass or more and 5% by mass or less.

4. The oral composition according to claim 1 or 2, wherein the value of a/B, which is the ratio of the mass of the component (a) to the mass of the component (B), is 0.001 to 6.

5. The oral composition of claim 1 or 2, wherein the salt of ingredient (a) is a calcium salt.

6. The oral composition according to claim 1 or 2, wherein the salt of the component (B) is a sodium salt,

the content of the component (B) is 0.5 to 10 mass%.

7. The oral composition according to claim 1 or 2, further comprising 1 or more selected from citric acid and salts thereof and phosphoric acid and salts thereof.

8. The oral composition of claim 1 or 2, wherein the oral composition is a liquid.

9. The oral composition of claim 1 or 2, wherein the oral composition is a liquid dentifrice or mouthwash.

10. The oral composition according to claim 1 or 2, wherein the oral composition is for inhibiting decomposition of oral collagen.