JP6375349B2 - Oral composition - Google Patents

Description

  The present invention relates to an oral composition.

  The gingiva in the oral cavity is easily retracted with periodontal disease or aging of the living body. When the gingiva is retracted, the root of the tooth (root) that has not been exposed is exposed. At the root of the tooth, the dentin is not covered with enamel. Dentin has countless tubule structures and contains many organic layers mainly of collagen, so the mineral density is as low as about 50%, compared to enamel with a mineral density of about 97%, It is chemically vulnerable. Therefore, when the root portion is exposed in the oral cavity due to gingival retraction, caries (dentin caries) is easily generated. Such dentin caries at the root of the tooth starting from the exposure of the root is called root caries.

  As for the onset mechanism of dentin caries (root caries), first, plaque adheres to the dentin surface exposed in the oral cavity, and metabolism of sugar is caused by bacteria in the plaque and acid is produced. Dentin mineral components are eluted (decalcified) by the acid, and the organic (collagen) layer is exposed. Furthermore, the collagen layer is physically and chemically destroyed, and the root of the tooth is substantially lost.

  Conventionally, several techniques for preventing demineralization and techniques for promoting remineralization have been proposed as methods for preventing dentin caries (see Patent Documents 1 to 4).

  Patent Document 1 discloses dentin mineral elution using an oral composition having hydrolyzed silk and light calcium carbonate having an average primary particle size of 0.04 to 0.5 μm as components. Inhibiting is described.

  Patent Document 2 discloses a tooth remineralization accelerator comprising (a) a monomer having a hydroxyl group and (b) a monomer having a phosphorus atom-containing acidic group with a blending amount of 5 to 200% by weight based on the component (a). Is used to promote remineralization.

  Patent Document 3 uses an oral composition having (A) a zinc compound and (B) at least one selected from the group consisting of an aldehyde-based compound, a phenol-based compound, and a tea-extracted polyphenol compound. It describes the prevention of quality caries, especially root caries.

  Patent Document 4 discloses that collagen decomposition and decalcification are suppressed using a root caries preventive agent comprising flavanones and / or glycosides thereof.

  In dentin caries (root caries), even if the collagen layer is exposed, it becomes a scaffold for remineralization, and it consumes calcium ions and phosphate ions in saliva and crystals are exposed in the exposed collagen layer. The possibility of deposition is pointed out. Therefore, it can be said that the inhibition of degradation of the exposed collagen layer is essential for prevention of dentin caries.

  As a conventional caries prevention technique, fluoride is mainly used, and fluoride sustained release / retention techniques such as a combined use technique with metal ions such as calcium (Patent Documents 5 to 7) are disclosed. These may have a certain effect on enamel caries, but fluoride cannot sufficiently protect the exposed collagen layer during dentin caries (root caries). Collagen breaks down.

  On the other hand, as a coating technique, a tooth surface coating technique using phosphoric acid ester or polymer (Patent Documents 8 and 9), a tooth protection technique using aluminum, fluoride, and calcium (Patent Document 10) are disclosed. The coating effect of the collagen layer was insufficient.

  Polyphenols can be coated onto the exposed collagen layer. Polyphenol also has a function of reducing collagenase enzyme activity, and as a result, it is known as a substance that is expected to have an effect of inhibiting degradation of the exposed collagen layer. For example, acid strengthening technology for tooth substance blended with tea polyphenol, fluoride and aluminum salt (Patent Document 11), and a combination of longan seed extract, fluoride and sugar alcohol (Patent Document 12) or Hesperidin (Patent Document) The technique for imparting acid resistance to root surfaces according to 13) is disclosed. However, polyphenols have the disadvantage of easily causing discoloration and turbidity due to oxidation, pH change, complex formation, etc., so it is difficult to maintain stability in dosage forms such as dentifrices and mouthwashes. . In addition to polyphenols, there were problems such as reduced efficacy after storage of the preparation and unnecessary coloring of the exposed collagen layer after application of the preparation. Therefore, the development of an active ingredient that can suppress the degradation of collagen exposed to dentin even after storage of the preparation, prevents coloring of the exposed collagen layer, and exhibits high preparation stability when prepared as a preparation. Is desired.

[Dentine hypersensitivity]
When the root is exposed and dentin is exposed as described above, thermal, chemical, and mechanical external stimuli are applied to the dentin, which is known as transient dentin hypersensitivity. Causes very unpleasant pain in sex.

  The cause of dentin hypersensitivity is thought to be because nerves are stimulated through dentinal tubules.

  To prevent and improve (relieve) dentin hypersensitivity with oral hygiene products such as dentifrices, methods such as blocking dentinal tubules with aluminum lactate, etc., and reducing pain by blunting nerves with potassium nitrate, etc. Can be mentioned.

  Aluminum lactate is known to have an action of closing the opening of the dentinal tubule and improving the sensitivity of the dentinal perception (Patent Document 14). However, it takes time until the effect of aluminum lactate is obtained, and there is a drawback that it lacks immediate effect. The expression of the peculiarity of aluminum lactate and the appearance of metallic taste has also been a problem.

  On the other hand, many potassium nitrates have been adopted as a nerve blunt component (Patent Document 15), but although it has immediate effect, its effect is hardly sustained. In other words, the effect of potassium nitrate is limited. Potassium nitrate has a strong bitter taste and may be uncomfortable to use.

[Stain removal]
Teeth colored stains are called stains or stained pellicles, and are colored by coloring polyphenols (tannin, chlorogenic acid, etc.), metal ions, tobacco tar, etc. derived from food and drink on pellicles where saliva proteins are adsorbed on the tooth surface. It is considered. Of these, the most frequently observed stain is called brown stain, which is said to involve polyphenol compounds in food and drink such as tannin and chlorogenic acid.

  Conventionally, a technique based on the mechanical action of an abrasive compounded in an oral composition such as a dentifrice is mainly used to remove stains adhering to the tooth surface. On the other hand, stain removal technology by chemical action such as a dentifrice composition blended with pyrophosphate (Patent Document 16) and an oral composition for inhibiting stain formation blended with a sulfosuccinic surfactant (Patent Document 17) Further, toothpaste containing papain (Patent Document 18), (A) lytic enzyme and / or (B) stain removal containing one or more enzymes of lipase, dextranase, glucosidase, 1,3-glucanase and mutanase Techniques for removing stains by enzymatic action such as oral compositions (Patent Document 19) have been proposed.

  On the other hand, techniques for suppressing the formation of dental stains have been proposed. For example, a liquid oral composition containing polyphosphoric acid or a salt thereof and an acyl taurine salt and exhibiting a predetermined pH (Patent Document 20), (A) polyphosphoric acid or a salt thereof, (B) a specific disaccharide, and (C) It has been proposed that a liquid oral composition (patent document 21) containing malic acid, tartaric acid and salts thereof has an effect of preventing tooth coloring.

  However, if the stain is to be removed by the mechanical action of the abrasive, there are concerns about tooth damage due to excessive brushing, stain remaining at a site where the brush tip does not reach, and the like.

  On the other hand, in the removal of the stain by a chemical action, the bad taste derived from a removal component and the fall of a feeling of use are problems. In the removal of stain by enzymatic action, when papain is used, there is a problem that papain may act on soft tissues in the oral cavity. Even when other enzymes are used, there is a problem that the stain component does not necessarily correspond to the enzyme degradation substrate.

  None of the above-mentioned stain formation suppression techniques has been overcome by the fact that it contains polyphosphoric acid such as sodium tripolyphosphate. It wasn't technical.

  In the above-described conventional techniques, no technique has been found that exhibits both the stain formation suppressing effect and the stain removal effect sufficiently, further exhibits the gloss effect, and is excellent in the feeling of using the preparation.

  As described above, suppression of dentin caries (root caries), suppression and improvement of dentin hypersensitivity, and suppression and removal of stains have been studied by various conventional methods. Accordingly, the present situation is that it is desired to provide new means capable of appropriately suppressing and improving dentin caries (root caries) and dentin hypersensitivity, and suppressing and removing stains. In particular, dentin caries (root caries) and dentine hypersensitivity continue to increase with the aging of the population, and their suppression and improvement are urgent.

  Conventionally, pyrrolidone carboxylic acid and / or a salt thereof is known as a component of a gelled topical composition that is applied to the skin, scalp, hair, nails and / or mucous membrane for cosmetic treatment (Patent Document 22). However, its use as a component of oral compositions has not been known.

JP 2007-176862 A JP 2006-8596 A Japanese Patent Laid-Open No. 11-228368 JP 2009-256341 A Japanese National Patent Publication No. 10-511104 JP-A-11-106322 Japanese Patent Application Laid-Open No. 2005-112841 JP-A-5-320032 JP 2005-200345 A JP-A-5-155746 JP-A-6-298632 JP 2011-168510 A JP 2009-256341 A JP 2010-222325 A Japanese Patent Application Laid-Open No. 08-175943 Japanese Patent Laid-Open No. 10-182389 Japanese Patent Laid-Open No. 10-17443 JP-T-1-503142 JP 2001-181163 A JP 2009-051734 A JP 2005-343794 A JP-A-9-202708

  An object of the present invention is to provide an agent that exhibits various functions such as suppression of dentin caries, suppression or improvement of dentin hypersensitivity, suppression or removal of stain formation, or an oral composition. In detail, the following five are mentioned as the object of the present invention.

  The first object of the present invention is to provide an oral composition having a dentin caries inhibitory effect, a dentin hypersensitivity inhibitory or improving effect, and a stain inhibiting or removing effect.

  The second object of the present invention is to provide an oral composition that remarkably suppresses degradation and coloring of an exposed collagen layer and exhibits high formulation stability when it is prepared.

  The third object of the present invention is to provide a composition for oral cavity that remarkably reduces pain due to hypersensitivity and has a good feeling of use (taste). For example, the opening of dentinal tubules can be sealed early (early dentinal tubule sealing effect), and the pain felt by the patient can be reduced (pain reducing effect). It is to provide an oral composition having no or almost no expression (good feeling of use (taste)).

  The fourth object of the present invention is to provide a composition for oral cavity useful for tooth whitening, which has both a stain removal effect and a stain formation inhibitory effect, has a gloss effect, and is excellent in preparation feeling. That is.

  The fifth object of the present invention is to provide an oral composition that can suppress collagen coloring.

The present invention provides the following [1] to [24].
[1] Component (A): An oral composition containing a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group.
[2] The composition for oral cavity according to the above [1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
[3] The composition for oral cavity according to the above [1] or [2], wherein the content of the component (A) is 0.3 to 10% by mass.
[4] Component (1-B): The composition for oral cavity according to [1] or [2], further containing a fluorine compound.
[5] The oral composition according to the above [4], wherein the (1-B) component is at least one selected from sodium fluoride and sodium monofluorophosphate.
[6] The composition for oral cavity according to the above [4] or [5], wherein the mass ratio of the component (A) to the amount of fluorine in the composition for oral cavity is 1 to 250.
[7] Component (1-C): The oral cavity according to any one of [4] to [6] above, further containing a protein containing 1.0 to 6.0% by mass of a sulfur-containing amino acid residue Composition.
[8] The composition for oral cavity according to the above [7], wherein the (1-C) component is casein.
[9] Component (2-B): The oral composition according to the above [1] or [2], further containing one or more polyphenol compounds selected from the group consisting of longan seed extract, proanthocyanidins, catechins and hesperidins .
[10] Component (3-B): The composition for oral cavity according to the above [1] or [2], further containing aluminum lactate.
[11] (3-C) component: The composition for oral cavity according to the above [10], further containing a monofluorophosphate.
[12] Component (3-D): The composition for oral cavity according to the above [10] or [11], further containing an inorganic water-soluble potassium salt.
[13] Component (4-B): The composition for oral cavity according to [1] or [2], further containing an inorganic water-soluble potassium salt.
[14] Component (4-C): The composition for oral cavity according to [13], further containing a water-soluble fluorine compound.
[15] Component (5-B): The composition for oral cavity according to the above [1] or [2], further containing cationized cellulose.
[16] The composition for oral cavity according to the above [15], wherein the component (5-B) is hydroxyethyl cellulose dimethyl diallylammonium chloride.
[17] Component (6-B): The composition for oral cavity according to the above [1] or [2], further containing a polyphenol compound.
[18] Component (A): A collagen coloring inhibitor comprising a lactam compound having an acid group and having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton.
[19] Component (A): A collagen degradation inhibitor having as an active ingredient a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group.
[20] Component (A): A dentinal tubule blocking agent containing a lactam compound having an acid group and having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, or an ε-lactam skeleton.
[21] Component (A): Dentin hypersensitivity comprising as an active ingredient a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton, and having an acidic group. Inhibitor or improver.
[22] Component (A): A stain remover having as an active ingredient a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group.
[23] The agent according to any one of [18] to [22], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
[24] The composition for oral cavity according to any one of [1], [2] and [9] to [14], which is for a person with hypersensitivity to dentin.

[Oral composition]
In order to obtain a composition for oral cavity, which is superior in suppression of collagen degradation, suppression of collagen coloring, suppression or improvement of dentin hypersensitivity, and stain removal effect as compared with conventional oral compositions. In earnest investigation. As a result, “a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group” represented by pyrrolidonecarboxylic acid and / or a salt thereof. It has been found that the composition for oral cavity contains excellent effects of inhibiting collagen degradation, inhibiting collagen coloring, inhibiting or improving dentin hypersensitivity, and removing stains.

The present invention provides the following oral compositions [0-1] to [0-4].
[0-1] Component (A): An oral composition containing a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group.
[0-2] The composition for oral cavity according to [0-1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
[0-3] The composition for oral cavity according to the above [0-1] or [0-2], wherein the content of the component (A) is 0.3 to 10% by mass.
[0-4] The composition for oral cavity according to any one of the above [0-1] to [0-3], which is for a person with hypersensitivity to dentin.

[Composition for oral cavity (1)]
The inventors of the present invention have made extensive studies in order to obtain an oral composition superior in dentin caries prevention effect as compared with conventional oral compositions. In the examination, “a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group” represented by pyrrolidonecarboxylic acid and / or a salt thereof. And a fluorine compound were simultaneously used as ingredients to prepare an oral composition. This oral composition was used for a carious sample, and its dentin caries inhibitory effect was evaluated by applying Transverse Microradiography (hereinafter abbreviated as TMR method).

  The TMR method is a technique for measuring the demineralization depth and the amount of mineral loss by obtaining a tooth mineral amount profile by luminance equivalent conversion according to the aluminum thickness using a microradiograph of the tooth flake cross section, As a method for measuring the degree of caries, this is a method for which reliability is officially recognized.

  As a result of evaluation by the evaluation method of dentin caries inhibitory effect applying the above TMR method, it was found that “having any lactam skeleton of γ-lactam skeleton, δ-lactam skeleton and ε-lactam skeleton, and having an acidic group It came to discover that the composition for oral cavity (1) having the “lactam compound having” and the “fluorine compound” as components at the same time exhibits a dentine caries inhibitory effect that exceeds that of the conventional oral composition.

The present invention provides the following oral composition (1).
[1-1] Component (A): a lactam compound having an acidic group and one or more lactam skeletons selected from the group consisting of a γ-lactam skeleton, a δ-lactam skeleton, or an ε-lactam skeleton, or a salt thereof And (1-B) component: The composition for oral cavity characterized by containing a fluorine compound.
[1-2] The composition for oral cavity according to the above [1-1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
[1-3] The composition for oral cavity according to [1-1] or [1-2], wherein the (1-B) component is at least one selected from sodium fluoride and sodium monofluorophosphate.
[1-4] The oral cavity according to any one of [1-1] to [1-3] above, wherein the mass ratio of the component (A) to the amount of fluorine in the oral composition is 1 to 250. Composition.
[1-5] (1-C) component: any one of [1-1] to [1-4] above, further containing a protein containing 1.0 to 6.0% sulfur-containing amino acid residues The composition for oral cavity according to 2.
[1-6] The composition for oral cavity according to the above [1-5], wherein the (1-C) component is casein.

[Composition for oral cavity (2)]
As a result of intensive studies to achieve the above object, the present inventor has found that the combination of a predetermined polyphenol compound and a predetermined lactam compound suppresses the degradation of the exposed collagen layer as compared with the case where each is used alone (dentin) It was found that the effect of inhibiting collagen degradation) and the effect persisted after storage of the preparation (inhibition effect of dentin collagen degradation after storage). The lactam compound suppresses the discoloration of the preparation itself after storage of the preparation with the polyphenol compound, has no problem with the shape retention (preparation stability), and suppresses coloring of the dentin with polyphenol for a long period of time ( The effect of inhibiting dentin collagen coloring after storage was also found. In this way, the present invention has been made.

The present invention provides the following oral composition (2).
[2-1] Component (A): a compound having at least one lactam skeleton selected from the group consisting of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton, and having an acidic group, or a salt thereof; (2-B) Component: An oral composition containing one or more polyphenol compounds selected from the group consisting of longan seed extract, proanthocyanidins, catechins and hesperidins.
[2-2] The composition for oral cavity according to the above [2-1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.

[Composition for oral cavity (3)]
The present invention provides the following oral composition (3).
[3-1] Component (A): a compound having at least one lactam skeleton selected from the group consisting of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton, and having an acidic group, or a salt thereof; (3-B) Component: Composition for oral cavity containing aluminum lactate.
[3-2] The composition for oral cavity according to the above [3-1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
[3-3] (3-C) component: The composition for oral cavity according to the above [3-1] or [3-2], which further contains a monofluorophosphate.
[3-4] (3-D) component: The composition for oral cavity according to any one of [3-1] to [3-3], further containing an inorganic water-soluble potassium salt.
[3-5] The composition for oral cavity according to any one of the above [3-1] to [3-4], which is for a person with hypersensitivity to dentin.

[Composition for oral cavity (4)]
The present inventors have found that oral compositions containing a combination of a specific lactam compound having an acidic group or a salt thereof and an inorganic water-soluble potassium salt significantly reduce pain due to hypersensitivity, and have good use. It has been found that it has a feeling (taste).

The present invention provides the following oral composition (4).
[4-1] Component (A): a lactam compound having at least one lactam skeleton selected from the group consisting of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton, and having an acidic group, or a salt thereof (4-B) component: oral cavity composition containing inorganic water-soluble potassium salt.
[4-2] The component (A) is selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, and salts thereof The composition for oral cavity according to the above [4-1], which is the above compound.
[4-3] The composition for oral cavity according to the above [4-1] or [4-2], further comprising (4-C) a water-soluble fluorine compound.
[4-4] The composition for oral cavity according to any one of the above [4-1] to [4-3], which is for a person with hypersensitivity to dentin.

[Composition for oral cavity (5)]
The present invention provides the following oral composition (5).
[5-1] Component (A): a compound having at least one lactam skeleton selected from the group consisting of a γ-lactam skeleton, a δ-lactam skeleton and an ε-lactam skeleton, and having an acidic group, or a salt thereof; (5-B) Component: An oral composition containing cationized cellulose.
[5-2] The composition for oral cavity according to the above [5-1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
[5-3] The composition for oral cavity according to the above [5-1] or [5-2], wherein the component (5-B) is hydroxyethyl cellulose dimethyl diallylammonium chloride.

[Oral composition (6)]
The present invention provides the following oral composition (6).
[6-1] Component (A): a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group, and (6-B) component : Oral composition containing polyphenol compound.

[Agent]
The present invention provides the following various agents.
[7-1] Component (A): Collagen coloring suppression containing a lactam compound having an acid group and having a lactam skeleton of any of a γ-lactam skeleton, a δ-lactam skeleton, or an ε-lactam skeleton. Agent.
[7-2] Component (A): Inhibition of collagen degradation containing a lactam compound having an acid group and having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, or an ε-lactam skeleton. Agent.
[7-3] Component (A): A dentinal tubule blockade containing a lactam compound having an acid group and having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, or an ε-lactam skeleton. Agent.
[7-4] Component (A): Dentin perception comprising as an active ingredient a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group An agent for preventing or improving hypersensitivity.
[7-5] Component (A): Stain remover having as an active ingredient a lactam compound having a lactam skeleton of any one of a γ-lactam skeleton, a δ-lactam skeleton, and an ε-lactam skeleton and having an acidic group .
[7-6] The agent according to any one of [7-1] to [7-5] above, wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.

  ADVANTAGE OF THE INVENTION According to this invention, the composition and agent for oral cavity useful for suppression of a dentin caries, suppression or improvement of a dentine hypersensitivity, suppression of formation of a stain, or a removal etc. are provided.

  ADVANTAGE OF THE INVENTION According to this invention, the composition for oral cavity (1) which is excellent in the dentine caries inhibitory effect and excellent in formulation stability is provided. The composition for oral cavity (1) is composed of components that can be absorbed into the body. Therefore, the oral composition (1) provides an excellent dentine caries prevention effect in simple forms such as quasi-drugs such as dentifrices and mouthwashes, and foods such as gums, candy and tablet confections. can do.

  ADVANTAGE OF THE INVENTION According to this invention, the composition for oral cavity (2) which can suppress significantly decomposition | disassembly of an exposed collagen layer is provided. The effect can be maintained after storage of the formulation. The composition for oral cavity (2) can also suppress coloring to exposed collagen and discoloration and turbidity in the preparation caused by the polyphenol compound after storage of the preparation.

  According to the present invention, there are provided oral compositions (3) and (4) that remarkably reduce pain due to hypersensitivity and have a good feeling of use (taste). The composition for oral cavity (3) is further excellent in dentinal tubule sealing effect. The oral compositions (3) and (4) are useful for suppressing or improving (relaxing) dentin hypersensitivity.

  ADVANTAGE OF THE INVENTION According to this invention, the composition for oral cavity (5) which can exhibit the stain removal effect, the stain formation inhibitory effect, the gloss effect, and the outstanding usability of a formulation is provided.

  According to this invention, the composition for oral cavity (6) which exhibits a collagen coloring inhibitory effect is provided.

  According to the present invention, there are provided a collagen coloring inhibitor, a collagen degradation inhibitor, a dentinal tubule blocking agent, a hypersensitivity inhibitor or ameliorating agent, and a stain remover, which comprise the component (A) as an active ingredient.

  Hereinafter, the present invention will be described in detail. In the following description, “%” indicates “% by mass” unless otherwise specified.

[(A) component]
The component (A) in the present invention is a compound having at least one lactam skeleton selected from the group consisting of a γ-lactam skeleton, a δ-lactam skeleton and an ε-lactam skeleton, and having an acidic group (hereinafter referred to as a lactam compound). And / or a salt thereof.

  The lactam compound or a salt thereof is not particularly limited as long as the lactam compound or a salt thereof has any one of the above-mentioned three specific lactam skeletons and has an acidic group. The molecule may have two or more lactam skeletons, may have two or more acidic groups, or have two or more lactam skeletons and two or more acidic groups. May be. In a preferred embodiment, the lactam skeleton is a γ-lactam skeleton.

  As an acidic group which a lactam compound or its salt has, a phenolic hydroxyl group, a carboxyl group, a sulfonic acid group, etc. are mentioned, for example. Of these, a carboxyl group is preferred as the acidic group.

  Examples of the lactam compound having a γ-lactam skeleton and an acidic group include pyrrolidone carboxylic acid, 4- (3-hydroxyphenyl) -4-Aza-tricyclo (5.2.1.0 (2, 6 )) Dec-8-ene-3,5-dione, 2- (3,5-dioxo-4-Aza-tricyclo (5.2.1.0 (2,6)) Dec-8-ene-4- yl) benzoic acid, and salts thereof, pyrrolidone carboxylic acid and salts thereof are preferred.

  Examples of the lactam compound having a δ-lactam skeleton and an acidic group include 6-oxo-2-piperidinecarboxylic acid, 4- (2-oxo-1-piperidinyl) butanoic acid, 1-ethyl-6- Examples include oxo-3-piperidinecarboxylic acid and salts thereof, and 6-oxo-2-piperidinecarboxylic acid is preferable.

  Examples of lactam compounds having an ε-lactam skeleton and an acidic group include 3- (2-oxo-1-azepanyl) propanoic acid and 3- (2-bromo-5-hydroxyphenyl) -1-methyl. Examples include 2-azepanone and salts thereof, and 3- (2-oxo-1-azepanyl) propanoic acid is preferable.

  The lactam compound salt is not particularly limited as long as it is a pharmacologically acceptable salt. Examples of pharmacologically acceptable salts include acid addition salts, base addition salts, and amino acid salts. Specific examples thereof include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, hydroiodide, nitrate, phosphate; citrate, oxalate, acetate, formate, propion Acid salt, benzoate salt, trifluoroacetate salt, maleate salt, tartrate salt, methanesulfonate salt, benzenesulfonate salt, paratoluenesulfonate salt, etc .; sodium salt, potassium salt, calcium salt, magnesium Inorganic base salts such as salts and ammonium salts; organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt and diisopropylammonium salt; and amino acid salts such as arginine salt, aspartate and glutamate.

  The lactam compound is preferably pyrrolidone carboxylic acid, 6-oxo-2-piperidine carboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, more preferably pyrrolidone carboxylic acid or a salt thereof.

  The lactam compound and its salt can be synthesized according to a known scheme. Commercial products may be used for the lactam compound and its salt.

  As a commercial item of the lactam compound (for example, pyrrolidone carboxylic acid) which has (gamma) -lactam frame | skeleton, "AJIDEW A-100 (trademark)" put on the market from Ajinomoto Co., Inc. is mentioned, for example.

  As a commercial product of a lactam compound having a δ-lactam skeleton (for example, 6-oxo-2-piperidinecarboxylic acid), for example, “(S) -6-Oxo-2-” sold by Sigma Aldrich Japan Co., Ltd. is available. piperidine carboxylic acid (trade name) ”.

  As a commercially available product of a lactam compound having an ε-lactam skeleton (for example, 3- (2-oxo-1-azepanyl) propanoic acid), for example, “3- (2-Oxozepan” sold by Sigma Aldrich Japan Co., Ltd. -1-yl) propanoic acid (trade name) ”.

  The kind of the lactam compound as the component (A) in the composition of the present invention may be a single kind or a combination of two or more kinds.

[(1-B) component]
The (1-B) component in the present invention is a fluorine compound. Examples of the fluorine compound include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, potassium monofluorophosphate, sodium silicon fluoride, and calcium calcium fluoride. It is done. Preferred fluorine compounds are sodium fluoride and sodium monofluorophosphate.

  A commercial item may be used for a fluorine compound. As an example of a commercial product of sodium fluoride, “sodium fluoride” marketed by Stella Chemifa Corporation can be mentioned. As an example of a commercial product of sodium monofluorophosphate, “sodium monofluorophosphate” marketed by Rhodia Nikka Co., Ltd. can be mentioned.

[(1-C) component]
The (1-C) component in the present invention is a protein containing 1.0 to 6.0% by mass of sulfur-containing amino acid residues.

  The sulfur-containing amino acid residue means a residue obtained by removing one or more hydrogen from a sulfur-containing amino acid. The sulfur-containing amino acid is an amino acid containing sulfur, and examples thereof include methionine and cysteine.

  The (1-C) component preferably contains a phosphate group.

  In the component (1-C), the number average molecular weight of the protein is preferably 1,000 to 100,000, more preferably 10,000 to 100,000. When the number average molecular weight is 1000 or more, affinity with dentin can be maintained, it is difficult to be washed away by saliva, and sufficient dentin caries inhibitory effect can be exhibited. On the other hand, when the number average molecular weight is 100,000 or less, the adsorptivity to the teeth can be maintained, and the effect of suppressing dentine caries can be sufficiently obtained.

  In the (1-C) component, the method for measuring the number average molecular weight of the protein is as follows.

  Examples of the method for calculating the number average molecular weight generally include a method of calculating using gel filtration chromatography (GPC) and a method of calculating by analysis nitrogen value calculation. The latter method is often used to calculate the number average molecular weight of proteins and polypeptide compounds. The number average molecular weight of the protein of (1-C) component can also be measured by the latter method.

  The number average molecular weight of the (1-C) component can be calculated by, for example, the following formula (1-1) based on the total nitrogen amount in the molecule, the amino nitrogen amount, and the average molecular weight of the constituent amino acids.

  In Formula (1-1), the average molecular weight of the constituent amino acids is calculated by multiplying the abundance ratio (%) of the constituent amino acids determined by ordinary amino acid analysis and the molecular weight of each amino acid. The total nitrogen amount can be measured by the first nitrogen determination method of the cosmetic raw material standard general test method or by gas chromatography (GC). The amount of amino nitrogen can be measured by a formol titration method.

  Examples of the “protein having an average molecular weight of 1000 to 100,000 containing 1.0 to 6.0% by mass of a sulfur-containing amino acid residue” include lactoferrin, collagen degradation products, and casein.

  Lactoferrin is an iron-binding glycoprotein having a molecular weight of about 80,000 that is widely distributed in the animal body. The origin and production method of lactoferrin are not limited. For example, colostrum, transitional milk, regular milk, end milk, etc. of mammals (eg, humans, cows, sheep, goats, horses, etc.) or processed products of these milks (eg, skim milk, whey, etc.) For example, lactoferrin separated by ion exchange chromatography or the like. Lactoferrin prepared by a known method may be used. As lactoferrin, bovine-derived lactoferrin is preferably used.

  A commercially available product may be used as lactoferrin. Examples of commercial products of bovine-derived lactoferrin include “Lactoferrin (derived from milk) (trade name)” sold by Wako Pure Chemical Industries, Ltd., “MLF-1” “ MLF-EX ”and“ Lactoferrin ”sold by Nippon Shinyaku Co., Ltd. can be mentioned. As the (1-C) component, one type of lactoferrin may be used, or two or more types of lactoferrin having different origins or separation conditions may be used in combination.

  Examples of collagen degradation products include collagen degradation products produced from pork skin and collagen degradation products produced from fish scales. Among these, collagen degradation products produced from fish scales are preferred. In the component (1-C), one type of collagen degradation product may be used, or a combination of two or more types of collagen degradation products having different raw materials may be used. A commercially available product may be used as the collagen degradation product. As an example of the commercial item of the collagen degradation product manufactured from a fish scale, the brand name "HACP-U2" currently sold from ZERAYS Co., Ltd. is mentioned.

  Casein is contained in dairy products such as milk and cheese, and accounts for about 80% by mass of milk protein contained in milk. Casein is a protein containing a phosphate group, that is, a type of phosphoprotein (phosphorylated protein). Phosphoric acid is bound to many serine residues constituting casein. In the component (1-C), one type of collagen degradation product may be used, or a combination of two or more types of collagen degradation products having different raw materials may be used. A commercially available product may be used as casein. As an example of a commercial product of casein derived from milk, trade name “casein (derived from milk)” sold by Wako Pure Chemical Industries, Ltd. may be mentioned.

  The content of the sulfur-containing amino acid residue of the protein in the (1-C) component is 1.0 to 6.0% by mass per mass of the protein. When the content of the sulfur-containing amino acid residue is 1.0% or more, the affinity with dentin can be improved and the effect of inhibiting dentin caries can be sufficiently obtained. On the other hand, when the content of the sulfur-containing amino acid residue is 6% or less, the (1-C) component does not become so bulky as to cause a steric hindrance with other components, and the dentin is obtained. (1-C) component or other components can be effectively prevented from lowering the adsorptive properties, and the effect of inhibiting dentin caries can be sufficiently obtained.

[(2-B) component]
The component (2-B) is one or more polyphenol compounds selected from the group consisting of longan seed extract, proanthocyanidins, catechins and hesperidins.

  Longan (Euphoria longana) is a plant belonging to the family Mucaceae cultivated in tropical America and Southeast Asia. Longan pulp is used as a traditional Chinese medicine for tonic and sedation. Longan is sometimes called Longan.

  Longan seed extract is an extract extracted from longan seeds. Longan seed extract contains polyphenol (Japanese Patent Application Laid-Open No. 2003-327596, The effects of Longan seeded polyphenols on colorogenic carcinoma cells. Eur J Clin Invest. (2010, 40 (8), p7131f). and quantification of polyphenolic compounds in Longan (Euphoria longana Lam.) fruit. J Agric Food Chem. (2005, 53 (5), p1387-1392)).

  The extraction method of longan seed extract from longan seeds is not particularly limited. Examples of the extraction method include a method of crushing longan seeds and solvent extraction using a known extraction method. As the solvent, water, monohydric alcohol, polyhydric alcohol, a mixture thereof and the like can be usually used. Examples of the solvent include water, lower monohydric alcohols such as methanol, ethanol and isopropanol, ethylene glycol, and polyethylene. Examples thereof include polyhydric alcohols such as glycol, propylene glycol, polypropylene glycol, and 1,3-butylene glycol. These can be used alone or in combination of two or more.

  As longan seed extract, a solvent extract may be used as it is, or a concentrate obtained by distilling off the solvent and concentrating may be used. You may use the powder obtained by removing a solvent by drying (example: freeze-drying etc.) a solvent extract or a concentrate. Further, an excipient or the like may be added. A powder obtained by re-dissolving a solvent extract such as a lyophilized product in a solvent and adjusting the concentration appropriately may be used. In addition, the yield at the time of extracting longan seed extract is not specifically limited.

  A commercially available product may be used as the longan seed extract. Examples of commercially available products include Agetect manufactured by Katakura Chikkarin Co., Ltd. and Longan Seed Extract Powder SD manufactured by the same company. Agetect is extracted from longan seed ground, freeze-dried after concentration, and dissolved in 1,3-butylene glycol and water so that the extract concentration is 1.0%. (Longan seed extract concentration in Agetect is 1.0%). Longan seed extract powder SD is a powdery extract prepared by adding dextrin as an excipient to powder obtained by extraction and freeze-drying in the same manner as above (in Longan seed extract powder SD) Longan seed extract concentration of 83%).

  Proanthocyanidins are a kind of polyphenol having a structure in which a plurality of catechin skeletons are bonded. The origin of proanthocyanidins is not particularly limited, and may be derived from plants (for example, fruits, wheat, beans, etc.), or may be artificial synthetic products. Among these, proanthocyanidins derived from plants are preferable, and proanthocyanidins derived from grape seeds are preferable. This is because grape seeds are rich in proanthocyanidins.

  In the case of proanthocyanidins derived from grape seeds, the method for extracting proanthocyanidins from grape seeds is not particularly limited. Examples of the extraction method include a method of crushing grape seeds and solvent extraction using a known extraction method. Examples of the solvent usually include water, monohydric alcohol, polyhydric alcohol, or a mixture thereof. For example, water, lower monohydric alcohol such as methanol, ethanol, isopropanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene And polyhydric alcohols such as glycol and 1,3-butylene glycol. These can be used alone or in combination of two or more.

  As proanthocyanidins, a solvent extract can be used as it is, but a concentrate obtained by distilling off the solvent and concentrating may be used. Powder obtained by removing the solvent by drying (eg, freeze-drying, etc.) the solvent extract or concentrate may be used, and an excipient or the like may be further added. And you may use what re-dissolved powder, such as a lyophilized product, in the solvent, and adjusted it to the density | concentration suitably. In addition, the yield at the time of extracting proanthocyanidins is not specifically limited.

  A commercially available product may be used as proanthocyanidins. For example, Gravinol-SL manufactured by Kikkoman Corp., Gravinol-N manufactured by the same company, or the like can be used. Gravinol-SL is a grape seed extract and purified product, and is a brown powder whose main component is proanthocyanidins (the concentration of proanthocyanidins in Gravinol-SL is 82%). Similarly, Gravinol-N is a purified and extracted product of grape seeds and is a light brown powder (the concentration of proanthocyanidins in Gravinol-N is 38%).

Catechin is a general term for a kind of flavonoid (C ₁₅ H ₁₄ O ₆ ) and its derivatives. Examples of catechin include catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, gallocatechin gallate, epigallocatechin gallate and the like. In the component (2-B), catechin may be one of these, or two or more. The origin of catechin is not particularly limited, and may be derived from a plant (for example, tea) or an artificial synthetic product. Among these, catechins derived from plants are preferable, catechins derived from tea are more preferable, and catechins derived from tea leaves are more preferable. This is because tea leaves are rich in catechins.

  In the case of catechins derived from tea leaves, the method for extracting catechins from tea leaves is not particularly limited. For example, it is possible to use a tea leaf prepared by crushing and solvent extraction by a known extraction method. Examples of the solvent usually include water, monohydric alcohol, polyhydric alcohol, or a mixture thereof. For example, water, lower monohydric alcohol such as methanol, ethanol, isopropanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene Examples thereof include polyhydric alcohols such as glycol and 1,3-butylene glycol, and these can be used alone or in combination of two or more.

  As the catechin, a solvent extract can be used as it is, but a concentrate obtained by distilling off the solvent and concentrating may be used. Powder obtained by removing the solvent by drying (eg, freeze-drying, etc.) the solvent extract or concentrate may be used, and an excipient or the like may be further added. And what lyophilized | freeze-dried powder etc. redissolved in the solvent and adjusted to the density | concentration suitably may be used. In addition, the yield at the time of extracting catechin is not specifically limited.

  As catechin, you may use a commercial item. For example, Sanphenon EGCG, Sunphenon 90S manufactured by Taiyo Kagaku Co., Ltd. can be used. Sanphenon EGCG is an extraction product of green tea and is a white to light gray powder containing epigallocatechin gallate in high purity (the epigallocatechin gallate concentration in sunphenone EGCG is 95%). Sanphenon 90S is also a green tea extraction and refined product, and is a pale yellow to reddish brown powder (the concentration of catechin in sunphenone 90S (total concentration of various catechins) is 70%).

  Hesperidin is a polyphenol also called vitamin P. The origin of hesperidin is not particularly limited, and it may be derived from a plant (for example, citrus fruits such as Wenzhou mandarin orange or Hassaku) or an artificial synthetic product. Among them, hesperidin derived from plants is preferable, hesperidin derived from citrus is preferable, and hesperidin derived from citrus peel is more preferable. This is because citrus peels are rich in hesperidin.

  In the case of hesperidin derived from the skin, the method for extracting hesperidin from the skin is not particularly limited. For example, what prepared by crushing a fruit skin and carrying out solvent extraction by a well-known extraction method can be used. Examples of the solvent usually include water, monohydric alcohol, polyhydric alcohol, or a mixture thereof. For example, water, lower monohydric alcohol such as methanol, ethanol, isopropanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene Examples thereof include polyhydric alcohols such as glycol and 1,3-butylene glycol, and these can be used alone or in combination of two or more.

  As hesperidin, it is possible to use the solvent extract as it is in the form of a solution, but it is also possible to use a solvent obtained by distilling off the solvent and concentrating to an appropriate concentration. These may be freeze-dried or the like, and may be used in the form of a powder obtained by removing the solvent, or may be used as it is or after adding an excipient or the like. A powdery product such as a freeze-dried product may be used by re-dissolving in a solvent and adjusting the concentration appropriately. The yield when extracting hesperidin is not particularly limited.

  As hesperidin, a commercially available product may be used. For example, hesperidin manufactured by Wako Pure Chemical Industries, Ltd., methyl hesperidin manufactured by Tokyo Chemical Industry, etc. can be used. Hesperidin is extracted and purified from the crushed peel and is a yellow powder (hesperidin concentration is 92%). Methyl hesperidin is obtained by methylating hesperidin with dimethyl sulfate and making it soluble in water, and is a light yellow to red yellow powder (methyl hesperidin concentration is 90%).

  As the component (2-B), one or more longan seed extracts, one or more proanthocyanidins, one or more catechins, or one or more hesperidins may be used, or a plurality of these may be used in combination. As the component (2-B), longan seed extract and / or proanthocyanidins are preferably used, and more preferably longan seed extract is used.

[(3-B) component]
The (3-B) component in the present invention is aluminum lactate.

  A commercially available product may be used as the component (3-B). For example, as a commercial product of aluminum lactate, trade name “aluminum lactate” manufactured by Wako Pure Chemical Industries, Ltd. may be mentioned.

  When aluminum lactate is used in the oral cavity, it may feel puffy and / or metallic, but in the oral composition (3), the component (A) is blended with the component (3-B). Ogumi and metallic taste are prevented from being generated, and the feeling of use (taste) can be improved.

[(3-C) component]
The (3-C) component is a monofluorophosphate.

  As the monofluorophosphate, it is sufficient if monofluorophosphate ions can be supplied, and water-soluble monofluorophosphate is preferable. Examples of the monofluorophosphate include alkali metal salts of monofluorophosphoric acid, alkaline earth metal salts of monofluorophosphoric acid, ammonium salts of monofluorophosphoric acid, etc. Among them, sodium monofluorophosphate, monofluorophosphate, etc. Potassium phosphate, ammonium monofluorophosphate and the like are preferable, and sodium monofluorophosphate is more preferable.

  A commercially available product may be used as the (3-C) component. For example, as a commercial product of monofluorophosphate, “sodium monofluorophosphate” marketed by Rhodia Nikka Co., Ltd. may be mentioned.

  The component (3-C) may be a single monofluorophosphate or a combination of two or more monofluorophosphates.

  The monofluorophosphate which is the (3-C) component is mainly responsible for fluorine in the component. The total amount of fluorine contained in the oral composition (3) is preferably 0.01% by mass (100 ppm) or more, and 0.02% by mass (200 ppm) with respect to the total amount of the oral composition (3). More preferably. The upper limit is preferably 1% by mass (10000 ppm) or less, and more preferably 0.5% by mass (5000 ppm) or less. 0.01-1 mass% (100-10000 ppm) is preferable and, as for the amount of fluorine contained in the composition for oral cavity (3) of this invention, 0.02-0.5 mass% (200-5000 ppm) is more preferable.

[(3-D) component and (4-B) component]
(3-D) component and (4-B) component are inorganic water-soluble potassium salts.

  In the present invention, the “inorganic water-soluble potassium salt” refers to an inorganic potassium salt that can be dissolved in 2 g or more in 100 g of water at 20 ° C.

  Examples of the inorganic water-soluble potassium salt include potassium nitrate, potassium chloride, potassium dihydrogen phosphate, potassium sulfate, potassium carbonate, potassium hydrogen carbonate, and alum. Among these, potassium nitrate and potassium chloride are preferable from the viewpoint of a remarkable alleviating effect on pain due to hypersensitivity and a feeling of use (taste). These inorganic water-soluble potassium salts may use commercially available reagents (available from suppliers such as Wako Pure Chemical Industries, Ltd.).

  Each of the (3-D) component and the (4-B) component may be a single type or a combination of two or more types.

  The component (4-B) has a problem that the effect of reducing the pain due to hypersensitivity is limited, and causes a bitter taste and a poor feeling of use (taste). Among the components (4-B), potassium nitrate has a certain effect in reducing pain due to hypersensitivity, but has a strong bitterness and a poor feeling of use (taste). In the composition for oral cavity (4), by using the component (A) in combination with the component (4-B), the effect of reducing pain due to hypersensitivity of the component (4-B) is significantly improved, 4-B) The bitterness derived from the component is suppressed, and even when potassium nitrate is used, a good feeling of use (taste) has been achieved.

[(4-C) component]
In the present invention, the (4-C) component is a water-soluble fluorine compound. The “water-soluble fluorine compound” refers to a fluorine compound that can be dissolved in 2 g or more in 100 g of water at 20 ° C.

  The water-soluble fluorine compound is a well-known component that has been conventionally used in oral compositions as a source of fluoride ions having tooth remineralization action. It has been found that a functional fluorine compound can further enhance the effect of the component (A) (that is, the remarkable improvement in the effect of reducing the component (B) against pain due to hypersensitivity).

  Examples of the water-soluble fluorine compound that can be suitably used as the (4-C) component include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, and monofluorolin. Examples include potassium acid, sodium silicon fluoride, and calcium calcium fluoride. Especially, from a viewpoint of improving the effect of (A) component, as a water-soluble fluorine compound, sodium fluoride and sodium monofluorophosphate are preferable. For these water-soluble fluorine compounds, commercially available reagents (for example, available from suppliers such as Stella Chemifa and Rhodia Nikka) may be used.

[(5-B) component]
The component (5-B) is cationized cellulose.

  Examples of the cationized cellulose include cellulose derivatives to which a cationic group is added. Examples of the cationic group include dimethyldiallylammonium and 2-hydroxy-3 (trimethylammonio) propyl. Examples of the cellulose derivative to which a cationic group is added include hydroxyethylcellulose dimethyl diallylammonium chloride, O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose, and derivatives thereof. The cationized cellulose preferably has a nitrogen content of 0.1 to 3% by mass.

  The component (5-B) may be one type or a combination of two or more types.

  As the component (5-B), hydroxyethyl cellulose dimethyl diallylammonium chloride can be suitably used because it is excellent in the effect of inhibiting the formation of dental stains and the gloss effect.

[(6-B) component]
The component (6-B) is a polyphenol compound. Examples of the polyphenol compound include flavonoids, phenylcarboxylic acid, chlorogenic acid, lignan, curcumin, and examples of the above (2-B) component.

[Composition or agent of the present invention]
The composition or agent of this invention contains the lactam compound and / or its salt which are (A) components. A lactam compound and / or a salt thereof is contained as an active ingredient.

  The content of the component (A) in the composition or agent of the present invention is not particularly limited.

  When the active component of the composition of the present invention is the component (A) alone, the content of the component (A) is preferably 0.3% by mass or more, more preferably 0.5%, based on the total amount of the composition. It is at least mass%. Thereby, the effect by mix | blending a lactam compound can fully be acquired. In the case where the component (A) is a lactam compound having a γ-lactam skeleton and / or an ε-lactam skeleton, the blending amount is more preferably 1% by mass or more.

  When the active ingredient of the composition of the present invention is the component (A) alone, the amount of the component (A) is preferably 10% by mass or less, and preferably 5% by mass or less with respect to the total amount of the composition. Is more preferable. This is because the contribution to improving each effect is limited even if blended in a large amount.

  It is preferable that the compounding quantity of (A) component in the agent of this invention is 0.3-10 mass% with respect to the whole quantity of a composition, More preferably, it is 0.5-5 mass%.

  Hereinafter, the preferable aspect in case the composition of this invention is a composition for oral cavity is demonstrated.

[Composition for oral cavity (1)]
The composition for oral cavity of the present invention may contain a component (A) and a component (1-B). Hereinafter, the composition for oral cavity containing (A) component and (1-B) component is called oral composition (1).

[Content of Component (A) in Oral Composition (1)]
The content of the component (A) in the oral composition (1) is not particularly limited, but is preferably 0.1% by mass or more, more preferably 0.8%, based on the total amount of the oral composition (1). It is 5 mass% or more, More preferably, it is 1 mass% or more. When the content of the component (A) is 0.1% by mass or more, a dentine caries inhibitory effect can be sufficiently obtained.

  The upper limit of the content of the component (A) in the oral composition (1) is preferably 10% by mass or less, and more preferably 5% by mass or less. Thereby, the gelling ability of the thickener in the composition for oral cavity (1) can be maintained, precipitation of the component (A) over time can be prevented, and good formulation stability can be maintained. it can. Accordingly, the effect of suppressing dentin caries can be maintained.

  As for content of (A) component, 0.1-10 mass% of composition for oral cavity (1) whole quantity is preferable, More preferably, it is 0.5-5 mass%. When the component (A) is a lactam compound having a δ-lactam skeleton and / or an ε-lactam skeleton, the content of the component (A) is more preferably 1 to 5% by mass.

[Content of (1-B) Component in Oral Composition (1)]
In the composition for oral cavity (1) of the present invention, the actions of both the (1-B) component that is a source of fluoride ions in the oral cavity and the component (A) are additively and synergistically combined. Thus, an excellent anti-dental caries prevention effect is exhibited.

  The effect of the (1-B) component used in the present invention is borne by the fluorine in the (1-B) component, so the blending amount of the (1-B) component is the amount in the oral composition (1). It is more useful to define in terms of fluorine content. Therefore, in the following description, the content of the component (1-B) in the oral composition (1) is indicated by the fluorine content in the oral composition (1).

  The content of the component (1-B) in the oral composition (1) is preferably 0.01% by mass (100 ppm) or more in terms of fluorine content relative to the total amount of the oral composition (1). 02 mass% (200 ppm) or more is more preferable. Thereby, sufficient dentine caries inhibitory effect can be acquired.

  On the other hand, the upper limit of the content of the component (1-B) in the oral composition (1) is preferably 1% by mass (10000 ppm) or less in terms of the fluorine content relative to the total amount of the oral composition (1). 0.5 mass% (5000 ppm) or less is more preferable. When the amount of fluorine is 1% by mass (10000 ppm) or less, formulation stability can be maintained. Examples of maintaining the stability of the preparation include prevention of reduction in gelling ability of the thickener in the oral composition (1). As another example, when oral composition (1) is a liquid formulation, prevention of generation | occurrence | production of an orientation is mentioned.

  The content of the component (1-B) in the oral composition (1) of the present invention is 0.01 to 1% by mass (100 to 100%) in terms of the fluorine content relative to the total amount of the oral composition (1). 10,000 ppm) is preferable, and 0.02 to 0.5 mass% (200 to 5000 ppm) is more preferable.

[(A) Component / (1-B) Component in Oral Composition (1)]
In this invention, there exists a preferable range in the compounding ratio of (A) component and (1-B) component. The mass ratio of the (A) component to the (1-B) component in the oral composition (1) can be expressed by the mass ratio of the (A) component to the fluorine content [(A) component / fluorine content]. it can. [(A) component / fluorine content] is preferably 1 or more, and more preferably 2 or more. Thereby, since the quantity of the fluoride ion with respect to (A) component is moderate, precipitation of the fluoride ion on the dentin surface is prevented, and sufficient dentine caries inhibitory effect can be acquired.

  The upper limit of the mass ratio of the component (A) to the fluorine content in the oral composition (1) is preferably 250 or less, and more preferably 100 or less. Thereby, since the quantity of fluoride ion is an appropriate range with respect to (A) component, the remarkable dentine caries inhibitory effect can be acquired.

  The mass ratio of the component (A) to the fluorine content in the oral composition (1) is preferably 1 to 250, and more preferably 2 to 100.

  The composition for oral cavity (1) of the present invention may further contain a (1-C) component. This is preferable because the effect of preventing dentin caries of the oral composition (1) is further increased.

[Content of (1-C) Component in Oral Composition (1)]
When the composition for oral cavity (1) contains the component (1-C), the content of the component (1-C) is not particularly limited, but is preferably 0.1 with respect to the total amount of the composition for oral cavity (1). It is 10 mass%, More preferably, it is 0.1-5 mass%. A dentine caries inhibitory effect can fully be acquired because content is 0.1 mass% or more. On the other hand, discoloration can be prevented by being 10 mass% or less, and the usability | use_condition fall by generation | occurrence | production of the base odor derived from a (1-C) component can be prevented.

[(1-C) Component / (1-B) Component in Oral Composition (1)]
When the composition for oral cavity (1) contains the (1-C) component, the mass ratio of the (1-C) component to the (1-B) component is (the fluorine content in the oral composition (1) ( It can be represented by the mass ratio of the 1-C) component, that is, the mass of the (1-C) component / the fluorine content.

  The mass ratio of the (1-C) component to the amount of fluorine in the oral composition (1) [(1-C) component / fluorine content] is preferably 0.3 to 800, preferably 0.5 to 80 is more preferable. When the mass ratio is 0.3 or more, the amount of fluoride ions with respect to the (1-C) component is appropriate, so that precipitation of fluoride ions on the dentin surface is prevented and sufficient dentin caries inhibition is achieved. An effect can be obtained. On the other hand, when the mass ratio is 800 or less, since the amount of fluoride ions is within an appropriate range with respect to the (1-C) component, a synergistic effect can be obtained with respect to the effect of inhibiting dentine caries.

[Composition for oral cavity (2)]
The composition for oral cavity of the present invention may contain a component (A) and a component (2-B). Hereinafter, the composition for oral cavity containing (A) component and (2-B) component is called oral composition (2).

[Content of Component (A) in Oral Composition (2)]
The content of the component (A) in the oral composition (2) is not particularly limited, but is preferably 0.5% or more, more preferably 1 with respect to the total amount of the oral composition (2) of the present invention. % Or more. Thereby, by using together with (2-B) component, the dentin collagen degradation inhibitory effect after a preservation | save and the dentin collagen coloring inhibitory effect after a preservation | save can fully be exhibited. The upper limit of the content of the component (A) in the oral composition (2) is preferably 10% or less, and more preferably 5% or less. Thereby, formulation stability can fully be exhibited and the dentine collagen degradation inhibitory effect after a preservation | save can also be fully exhibited in connection with it. The content of the component (A) is preferably 0.5 to 10%, and more preferably 1 to 5%.

[Content of (2-B) Component in Oral Composition (2)]
The content of the component (2-B) in the oral composition (2) is not particularly limited, but is preferably 0.001% or more based on the total amount of the oral composition (2), 0.01% More preferably. When the content is 0.001% or more, both the dentin collagen degradation inhibitory effect and the dentin collagen degradation inhibitory effect after storage can be sufficiently exhibited by the combined use with the component (A). The upper limit of the content of the (2-B) component is preferably 0.5% or less, and more preferably 0.2% or less. Thereby, the coloring inhibitory effect and formulation stability to dentin collagen after a preservation | save can fully be exhibited. The content of the component (2-B) is preferably 0.001 to 0.5%, and more preferably 0.01 to 0.2%.

[Component (A) / Component (2-B) in Oral Composition (2)]
In the composition for oral cavity (2), the mass ratio ((A) / (2-B)) of the component (A) to the component (2-B) is not particularly limited, but is usually 5 or more, preferably 10 That's it. Thereby, the dentin collagen coloring inhibitory effect after a preservation | save and formulation stability can fully be exhibited. The upper limit of the mass ratio of the component (A) to the component (2-B) is usually 3000 or less, preferably 300 or less. Thereby, the dentin collagen degradation inhibitory effect can be sufficiently exerted even after storage. The mass ratio ((A) / (2-B)) of the component (A) to the component (2-B) in the oral cavity composition (2) is preferably 5 to 3000, and preferably 10 to 300. Is more preferable.

[Composition for oral cavity (3)]
The composition for oral cavity of the present invention may contain a component (A) and a component (3-B). Hereinafter, the composition for oral cavity containing (A) component and (3-B) component is called oral composition (3).

[Content of Component (A) in Oral Composition (3)]
The content of the component (A) in the oral composition (3) is not particularly limited, but is preferably 0.1% by mass or more, more preferably based on the total amount of the oral composition (3) of the present invention. It is 0.5 mass% or more. Thereby, the dentinal tubule early blockage effect and the pain reduction effect can be sufficiently obtained. When the component (A) is a compound having a γ-lactam skeleton and having an acidic group and / or a compound having an ε-lactam skeleton and having an acidic group, the content is more preferably 1% by mass or more. The upper limit of the content of component (A) is preferably 10% by mass or less, and more preferably 5% by mass or less. This is because even if it exceeds 10% by mass, there is a possibility that the improvement of the early occlusion effect of dentinal tubules cannot be obtained.

  The content of the component (A) is preferably 0.1 to 10% by mass, and more preferably 0.5 to 5% by mass. When the component (A) is a compound having a γ-lactam skeleton and having an acidic group and / or a compound having an ε-lactam skeleton and having an acidic group, the content of the component (A) is from 1 to More preferably, it is 5 mass%.

[Content of (3-B) Component in Oral Composition (3)]
The content of the component (3-B) in the oral composition (3) is not particularly limited, but is preferably 0.01% by mass or more based on the total amount of the oral composition (3) of the present invention, and more. Preferably it is 0.1 mass% or more. Thereby, the dentinal tubule early blockage effect and the pain reduction effect can be sufficiently obtained. The upper limit of the content of the (3-B) component is preferably 10% by mass or less, and more preferably 5% by mass or less. Thereby, a feeling of use (taste) can be kept favorable, and generation | occurrence | production of a gummy, metal taste, etc. can be prevented. The content of the (3-B) component is preferably 0.01 to 10% by mass, more preferably 0.1 to 5% by mass.

[Component (A) / Component (3-B) in Oral Composition (3)]
In the composition for oral cavity (3), the mass ratio [(A) / (3-B)] of the component (A) to the component (3-B) is preferably 0.1 or more, and 0.5 or more. It is more preferable that Thereby, the use feeling (taste) improving effect can be more fully exhibited. The upper limit is preferably 500 or less, and more preferably 45 or less. Thereby, the dentinal tubule sealing effect of (3-B) component is fully exhibited, and the synergistic effect of (A) component and (3-B) component can be expressed notably. The mass ratio of the component (A) to the component (3-B) is preferably 0.1 to 500, and more preferably 0.5 to 45.

[Content of (3-C) Component in Oral Composition (3)]
The composition for oral cavity (3) may further contain a component (3-C).

  When the composition for oral cavity (3) contains the component (3-C), the content of the component (C) in the composition for oral cavity (3) is the total fluorine content contained in the composition for oral cavity (3). However, 0.01-1 mass% (100-10000 ppm) is preferable and, as for the amount of fluorine contained in the composition for oral cavity of this invention, 0.02-0.5 mass% (200-5000 ppm) is more preferable.

  In the case of sodium monofluorophosphate, the content of the (3-C) component in the oral composition (3) is preferably 0.076% by mass or more, and more preferably 0.15% by mass or more. preferable. Thereby, the dentinal tubule early blockage effect and the pain reduction effect can be sufficiently obtained. The upper limit of the content of the (3-C) component in the oral cavity composition (3) is preferably 7.6% by mass or less, and more preferably 3.8% by mass or less. Thereby, a feeling of use (taste) can be kept favorable. The content of the (3-C) component is preferably 0.076 to 7.6% by mass, and more preferably 0.15 to 3.8% by mass.

[Content of (3-D) Component in Oral Composition (3)]
The composition for oral cavity (3) may further contain a component (3-D).

  The content of the (3-D) component in the oral composition (3) is not particularly limited, but is preferably 0.005% by mass or more based on the total amount of the oral composition (3) of the present invention. More preferably, it is 1% by mass or more. Thereby, the pain reduction effect can be sufficiently obtained. The upper limit is preferably 10% by mass, and more preferably 7% by mass or less. Thereby, a feeling of use (taste) can be kept favorable. The content of the (3-D) component is preferably 0.005 to 10% by mass, and more preferably 0.1 to 7% by mass.

[Composition for oral cavity (4)]
The composition of the present invention may contain a component (A) and a component (4-B). Hereinafter, the composition for oral cavity containing (A) component and (4-B) component is called oral composition (4).

[Content of Component (A) in Oral Composition (4)]
The content of the component (A) in the composition for oral cavity (4) is preferably 0.1% by mass or more from the viewpoint of a remarkable alleviating effect on pain due to hypersensitivity and an effect of improving the feeling of use (taste). More preferably, the content is 0.5% by mass or more. When the δ-lactam compound having an acidic group, the ε-lactam compound having an acidic group, or a salt thereof is used as the component (A), the content of the component (A) in the oral composition is a pain due to hypersensitivity. From the viewpoint of a remarkable reduction effect on the content, it is particularly preferably 1% by mass or more.

  The upper limit of the content of the component (A) in the oral composition (4) is not particularly limited. However, even if it is a large amount, the contribution to a remarkable reduction effect on pain due to hypersensitivity is limited. % Or less is preferable and 5 mass% or less is more preferable.

  In one embodiment, the content of the component (A) in the oral composition (4) is preferably 0.1 to 10% by mass, and 0.5 to 5% by mass with respect to the total amount of the oral composition (4). % Is particularly preferred. When the δ-lactam compound having an acidic group or the ε-lactam compound having an acidic group is used as the component (A), the content of the component (A) in the oral composition is particularly preferably 1 to 5% by mass.

[Content of (4-B) Component in Oral Composition (4)]
The content of the component (4-B) in the composition for oral cavity (4) is preferably 0.1% by mass or more, more preferably 1.0% by mass or more, from the viewpoint of a remarkable alleviating effect on pain due to hypersensitivity. .

  In light of usability (taste), the content of the component (4-B) in the oral cavity composition (4) is preferably 10% by mass or less, and more preferably 7% by mass or less.

  In one embodiment, the content of the (4-B) component in the oral cavity composition (4) is preferably 0.1 to 10% by mass, and particularly preferably 1.0 to 7% by mass.

[Component (A) / Component (4-B) in Oral Composition (4)]
In the composition for oral cavity (4), the mass ratio of the component (A) to the component (4-B) in order to achieve both a remarkable alleviating effect on pain caused by hypersensitivity and an improvement effect on the feeling of use (taste). Has a preferred range. That is, in the composition for oral cavity (4), the mass ratio of the component (A) to the component (4-B) [(A) component / (4-B) component] is preferably 0.02 to 80. 0.1 to 10 is more preferable, and 0.1 to 5 is still more preferable.

[Content of (4-C) Component in Oral Composition (4)]
The composition for oral cavity (4) may further contain a (4-C) component.

  Since the effect of the water-soluble fluorine compound used in the present invention is attributed to fluorine in the (4-C) component, the content of the (4-C) component is the fluorine content in the oral composition (4). It is more useful to prescribe it in terms of quantity. Therefore, in the following description, the content of the (4-C) component is shown as a substitute for the fluorine content in the oral composition (4).

  The content of the component (4-C) in the oral composition (4) further enhances the effect of the component (A), and further reduces the pain due to hypersensitivity of the oral composition (4). From the viewpoint of increasing, it is preferably 0.01% by mass (100 ppm) or more, more preferably 0.02% by mass (200 ppm) or more in terms of fluorine content relative to the total amount of the oral composition (4).

  From the viewpoint of feeling of use (taste), the content of the (4-C) component in the oral composition of the present invention is a fluorine amount, and is 1% by mass (10,000 ppm) with respect to the total amount of the oral composition (4). The following is preferable, and 0.5 mass% (5000 ppm) or less is more preferable.

  In one embodiment, the content of the component (4-C) in the oral composition of the present invention is 0.01 to 1% by mass (in terms of fluorine content) with respect to the total amount of the oral composition (4). 100 to 10000 ppm) is preferable, and 0.02 to 0.5 mass% (200 to 5000 ppm) is more preferable.

[(4-C) Component / (A) Component in Oral Composition (4)]
In further increasing the effect of the component (A) and further enhancing the remarkable alleviating effect on pain due to hypersensitivity of the oral composition (4), the mass ratio of the component (A) to the component (4-C) is: There is a preferred range. That is, in the composition for oral cavity (4), the mass ratio of the (4-C) component to the (A) component [(4-C) component / (A) component] is preferably 0.002 to 5. 0.005 to 0.5 is more preferable (however, the mass of the component (C) is a fluorine content conversion value).

[Composition for oral cavity (5)]
The composition of the present invention may contain a component (A) and a component (5-B). Hereinafter, the composition for oral cavity containing (A) component and (5-B) component is called oral composition (5).

[Content of Component (A) in Oral Composition (5)]
The content of the component (A) in the oral composition (5) is not particularly limited, but is preferably 0.1% by mass or more based on the total amount of the oral composition (5) of the present invention. Thereby, a stain removal effect and a stain formation inhibitory effect are sufficiently obtained. The content of the component (A) in the oral composition (5) is preferably 10% by mass or less based on the total amount of the oral composition (5) of the present invention. As a result, good solubility and appearance can be obtained, and a sense of incongruity can be suppressed and the usability can be improved. The content of the component (A) in the oral composition (5) is preferably 0.1 to 10% by mass, and 0.5 to 5% by mass with respect to the total amount of the oral composition (5) of the present invention. % Is more preferable.

[Content of (5-B) Component in Oral Composition (5)]
The content of the component (5-B) in the oral composition (5) is preferably 0.005% by mass or more based on the total amount of the oral composition (5). Thereby, the stain formation suppressing effect and the gloss effect can be sufficiently exhibited. The content of the component (5-B) in the oral composition (5) is preferably 0.1% by mass or less with respect to the total amount of the oral composition (5). Thereby, the discomfort derived from a cationized cellulose can be suppressed and a favorable usability | use_condition can be hold | maintained. The content of the component (5-B) in the oral composition (5) is preferably 0.005 to 0.1% by mass relative to the total amount of the oral composition (5) of the present invention. It is more preferable that it is 0.01-0.05 mass% at the point of a stain formation inhibitory effect and a gloss effect.

[Component (A) / Component (5-B) in Oral Composition (5)]
In the composition for oral cavity (5), the mass ratio ((A) / (5-B)) of the component (A) to the component (5-B) is not particularly limited, but is usually 3 or more, preferably 15 That's it. The mass ratio of the component (A) to the component (5-B) is usually 600 or less, preferably 300 or less. When the ratio is 3 or more, the stain formation suppressing effect and the stain removing effect can be sufficiently exhibited. By being 600 or less, the stain formation suppressing effect and the gloss effect can be sufficiently exhibited, and a good usability can be maintained. The ratio of the component (A) to the component (5-B) is preferably 3 to 600, and more preferably 15 to 300.

[Effect of composition for oral cavity (5)]
In the oral cavity composition (5), the (A) component and the (5-B) component are presumed to exhibit a stain formation inhibitory effect, a stain removal effect, a gloss effect, and an excellent feeling in use of the preparation by the following actions. .

  The component (5-B) effectively suppresses the adhesion of stain to the enamel surface and imparts gloss to the teeth. On the other hand, the component (A) has an action of softening and dissolving the calcified substance after adsorption to the stain adhering to the enamel surface or further calcified after adhesion, and an action of suppressing the lamination of the stain. Have

  The combination of the component (A) and the component (5-B) makes it possible to strongly suppress the adhesion and lamination of the stain on the tooth surface, whereby the composition for oral cavity (5) is a dental stain. It can have both removal effect, stain formation suppression effect and gloss effect. Since both the component (A) and the component (5-B) have no discomfort or taste problems with the oral mucosa of the conventional condensed phosphoric acid, enzyme, and surfactant, The composition (5) can also exhibit an excellent feeling of use of the preparation.

[Oral composition (6)]
The composition of the present invention may contain a component (A) and a component (6-B). Hereinafter, the composition for oral cavity containing (A) component and (6-B) component is called oral composition (6). In addition, (6-B) component: Since the polyphenol compound contains each compound of (2-B) component, the composition for oral cavity (6) can also be said to be a superordinate concept of the composition for oral cavity (2). However, they are different in effect.

[Content of Component (A) in Oral Composition (6)]
The content of the component (A) in the oral composition (6) is not particularly limited, but is preferably 0.3% by mass or more based on the total amount of the oral composition (6) of the present invention. Thereby, the collagen coloring suppression effect by (6-B) component is fully acquired. The content of the component (A) in the oral composition (6) is preferably 10% by mass or less based on the total amount of the oral composition (6) of the present invention. As a result, good solubility and appearance can be obtained, and a sense of incongruity can be suppressed and the usability can be improved. The content of the component (A) in the oral composition (6) is preferably 0.3 to 10% by mass, and 0.5 to 5% by mass with respect to the total amount of the oral composition (6) of the present invention. % Is more preferable.

[Content of (6-B) Component in Oral Composition (6)]
The content of the component (6-B) in the oral composition (6) is preferably 0.001% by mass or more based on the total amount of the oral composition (6). Thereby, (6-B) component becomes a cause of collagen coloring, and the collagen coloring inhibitory effect by combined use of (A) component and (6-B) component can be expected. The content of the component (6-B) in the oral composition (6) is preferably 5% by mass or less based on the total amount of the oral composition (6). Thereby, the collagen coloring inhibitory effect by (A) component can fully be exhibited. The content of the component (6-B) in the oral composition (6) is preferably 0.001 to 5% by mass relative to the total amount of the oral composition (6) of the present invention, and is 0.01 to More preferably, it is 1 mass%.

[Component (A) / Component (6-B) in Oral Composition (6)]
In the composition for oral cavity (6), the mass ratio ((A) / (6-B)) of the component (A) and the component (6-B) is not particularly limited, but is usually 0.5 or more, preferably Is 3 or more. The mass ratio of the component (A) and the component (6-B) is usually 1000 or less, preferably 200 or less. By being in this range, the collagen coloring suppression effect by the component (A) can be sufficiently exerted. The ratio of the component (A) to the component (6-B) is preferably 0.5 to 200, and more preferably 3 to 1000.

  In addition, in this invention, content of each component in a composition is based on the preparation amount of each component at the time of manufacturing a composition.

  The dosage form of the composition of the present invention is not particularly limited. For example, oral administration (eg, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.) and the like can be mentioned. Among these, a less invasive dosage form is preferable, and oral administration is more preferable.

  The dosage form of the composition of the present invention can be appropriately determined according to the dosage form and the like, and is not particularly limited. Examples of dosage forms for oral administration include liquid (liquid), syrup (syrup), tablets (tablets, tablets), capsules (capsules), powders (granules, fine granules), soft capsules (Soft capsule), solid, semi-solid (gummy etc.), film, semi-liquid, cream, paste, chewing gum and the like. Of these, granular, capsule, powder, soft capsule, and solid are preferable, and granular (tablet) is more preferable. Examples of dosage forms for transdermal administration include aerosols, creams, lotions, sprays, sticks, and the like.

  When the composition of the present invention is an oral composition, the dosage form is preferably liquid (liquid, liquid, paste) or solid (solid, solid, semi-solid, film).

[Pharmacologically acceptable carrier (optional component)]
In addition to the above components, the oral composition of the present invention may contain a pharmacologically acceptable carrier (optional component) as necessary. Examples of optional components include surfactants, binders, thickeners, sweeteners, preservatives, fragrances, acidulants, lubricants, abrasives, coloring agents, preservatives, brighteners, fluidizing agents, A binder, a disintegrant, a medicinal component, a solvent (solvent) such as water, and an excipient can be blended within a range that does not impair the stability and the decalcification inhibiting effect. Although the specific example of an arbitrary component is shown below, the component which can be mix | blended with the composition of this invention is not restrict | limited to these.

  Examples of the abrasive include silica-based abrasives such as silicic anhydride, crystalline silica, amorphous silica, silica gel, aluminosilicate, zeolite, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, Examples thereof include calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tribasic magnesium phosphate, zirconium silicate, tertiary calcium phosphate, hydroxyapatite, tetracalcium phosphate, and a synthetic resin abrasive.

  An abrasive | polishing agent can be used individually by 1 type or in combination of 2 or more types. When mix | blending an abrasive | polishing agent, it is preferable that the compounding quantity is 2 to 40% of the whole composition in a dentifrice, and it is more preferable that it is 5 to 20%. In a mouthwash, it is preferable that it is 0 to 10% of the whole composition, and it is more preferable that it is 0 to 5%.

  Examples of the binder include thickening silica, pullulan, gelatin, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, carrageenan, sodium alginate, xanthan gum, sodium polyacrylate, gum arabic, guar gum, locust bean gum, Polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, etc. are mentioned. A binder can be used individually by 1 type or in combination of 2 or more types. The amount of the binder used is usually 0.01 to 3% with respect to the total amount of the composition.

  Examples of the thickening agent (wetting agent) include sorbitol, propylene glycol, butylene glycol, glycerin, polyethylene glycol and the like. A thickener can be used individually by 1 type or in combination of 2 or more types. When using a viscous agent, the content can be defined in the range which does not prevent the effect of this invention, and is 1 to 60% normally with respect to the whole quantity of a composition.

  Examples of the surfactant include an anionic surfactant and a nonionic surfactant.

  Examples of anionic surfactants include N-acyl amino acid salts, α-olefin sulfonates, N-acyl sulfonates, alkyl sulfates, sulfates of glycerin fatty acid esters, POE alkyl sulfosuccinates, POE alkyl ether sulfates. Examples thereof include salts and POE alkyl ether phosphates. Of these, N-acylamino acid salts, α-olefin sulfonates, alkyl sulfates and the like are preferable from the viewpoint of versatility, and lauroyl sarcosine sodium, alkyl chain carbon chain length from the viewpoint of foamability and hard water resistance. More preferred are sodium α-olefin sulfonates having 10 to 16 carbon atoms, sodium lauryl sulfate, and the like.

  Nonionic surfactants include, for example, polyoxyethylene alkyl ether, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene hydrogenated castor oil, glycerin ester polyoxyethylene ether, sucrose fatty acid ester, alkylolamide And glycerin fatty acid ester. Of these, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, alkylolamide, sorbitan fatty acid ester and the like are preferably used from the viewpoint of versatility. The polyoxyethylene alkyl ether preferably has a carbon chain length of 14 to 18 carbon atoms. The polyoxyethylene alkyl ether preferably has an average ethylene oxide addition mole number of 15 to 30. The polyoxyethylene hydrogenated castor oil preferably has an ethylene oxide average addition mole number (average addition EO) of 20 to 100. The alkylolamide preferably has an alkyl chain with a carbon chain length of 12 to 14 carbon atoms. The sorbitan fatty acid ester preferably has 12 to 18 carbon atoms in the fatty acid. The polyoxyethylene sorbitan fatty acid ester preferably has 16 to 18 carbon atoms in the fatty acid. The polyoxyethylene sorbitan fatty acid ester preferably has an ethylene oxide average added mole number of 10 to 40.

  Surfactant can be used individually by 1 type or in combination of 2 or more types. Content in the case of using surfactant is 0-10% normally with respect to the whole quantity of a composition, and it is preferable that it is 0.01-5%.

  Examples of the sweetening agent include saccharin sodium, stevioside, neohesperidin hydrochalcone, glycyrrhizin, perilartin, p-methoxycinnamic aldehyde, thaumatin, palatinose, maltitol, xylitol, arabitol and the like. A sweetener can be used individually by 1 type or in combination of 2 or more types. When using a sweetener, content can be suitably determined in the range which does not impair the effect of this invention.

  Examples of the preservative include paraoxybenzoic acid esters such as sodium benzoate, methylparaben, ethylparaben, and butylparaben, ethylenediaminetetraacetate, benzalkonium chloride, and the like. A preservative can be used individually by 1 type or in combination of 2 or more types. When using a preservative, the content can be appropriately determined within a range not impairing the effects of the present invention.

  Examples of the fragrances include natural fragrances, synthetic fragrances (single fragrances), and blended fragrances (oil and fat fragrances (oil-based fragrances), powder fragrances, and the like). A fragrance | flavor can be used individually by 1 type or in combination of 2 or more types.

  Natural flavors include, for example, mastic oil, parsley oil, anise oil, eucalyptus oil, winter green oil, cassia oil, menthol oil, spearmint oil, peppermint oil, lemon oil, coriander oil, orange oil, mandarin oil, lime oil , Lavender oil, laurel oil, chamomile oil, cardamom oil, caraway oil, bay oil, lemongrass oil, pine needle oil, neroli oil, rose oil, jasmine oil, Iris concrete, absolute peppermint, absolute rose, orange flower, citrus Oil, mixed fruit oil, strawberry oil, cinnamon oil, clove oil, grape oil, thyme oil, sage oil, mint oil, rosemary oil, marjoram oil, origanum oil, grapefruit oil, sweetie oil, straw oil, perilla oil, etc. Cited That.

  As a single item fragrance, for example, carvone, anethole, methyl salicylate, cinnamic aldehyde, linalool, linalyl acetate, limonene, menthone, menthyl acetate, pinene, octyl aldehyde, citral, pregon, carbyl acetate, anisaldehyde, ethyl acetate, Ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl anthranilate, vanillin, undecalactone, hexanal, ethinone alcohol, propyl alcohol, butanol, isoamyl alcohol, hexenol, dimethylsulfide, cycloten, furfural , Trimethylpyrazine, ethyl lactate, ethylthioacetate, cineol, eugenol, ocimene, n-decyla Call, citronellol, alpha-terpineol, and the like.

  A blended flavor is a flavor made by blending a single flavor and / or a natural flavor. Examples include menthol micron, strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, tropical fruit flavor, butter flavor, milk flavor, yogurt flavor, fruit mix flavor, herbal mint flavor and the like.

  The form of the fragrance is not limited, and any of essential oil, extract, solid, and powder obtained by spray-drying any of these may be used. It is preferable to use 0.000001-1% of said fragrance | flavor raw material in a formulation composition. It is preferable to use 0.1-2.0% of the fragrance | flavor for fragrance | flavor which uses the said fragrance | flavor raw material in a formulation composition.

  Medicinal components include, for example, the following components: anticalculus agents such as condensed phosphates and ethane hydroxydiphosphonates; astringents such as sodium chloride; suppression of hypersensitivity such as strontium chloride, strontium acetate and zinc chloride Agents. Content in the case of using a medicinal component can be suitably set within a pharmaceutically acceptable range for each medicinal component.

  Examples of the colorant include natural pigments such as safflower red pigment, gardenia yellow pigment, gardenia blue pigment, perilla pigment, red potato pigment, red cabbage pigment, carrot pigment, hibiscus pigment, cacao pigment, spirulina pigment, tamarind pigment, and the like. Red 3, No. 104, Red No. 105, Red No. 106, Yellow No. 4, Yellow No. 5, Green No. 3, Blue No. 1 and other legal dyes, riboflavin, copper chlorophyllin sodium, titanium dioxide and the like. When it contains a coloring agent, it is preferable that the content is 0.00001 to 3% with respect to the whole quantity of a composition.

  Examples of the brightener include waxes such as shellac, carnauba wax, and candelilla wax, and calcium stearate. When it contains a brightener, its content is preferably 0.01 to 5% with respect to the total amount of the composition.

  PH (20 degreeC) in case the composition of this invention is a composition for oral cavity is 6-10 normally, Preferably it is 7-9. Examples of the pH adjuster include acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, Examples include acids and alkalis such as sodium citrate, sodium hydrogen citrate, sodium phosphate, and sodium dihydrogen phosphate, and buffers. When it contains a pH adjuster, its content can be appropriately determined within a range not impairing the effects of the present invention.

  Examples of the solvent include water and lower alcohols having 3 or less carbon atoms such as ethanol and propanol. The solvent is usually contained in a liquid oral composition. When water is contained as a solvent, the content is preferably 20 to 95% with respect to the total amount of the composition. When a lower alcohol is contained as a solvent, the content is preferably 1 to 20% with respect to the total amount of the composition.

  Examples of excipients include syrup, glucose, fructose, invert sugar, dextrin, oligosaccharide and the like. When the oral composition is a food preparation, an excipient is usually contained. In the case of containing an excipient, the content can be appropriately determined within a range not impairing the effects of the present invention.

  PH (20 degreeC) of the composition for oral cavity of this invention is 5-10 normally, Preferably it is 6-10, More preferably, it is 6-9, More preferably, 6-8 or 7-9 It is. Examples of the pH adjuster include acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, Examples include acids such as sodium citrate, sodium hydrogen citrate, sodium phosphate, and sodium dihydrogen phosphate, alkalis, and buffers. When it contains a pH adjuster, its content can be appropriately determined within a range not impairing the effects of the present invention.

[Dosage Form of Oral Composition of the Present Invention]
The shape and dosage form of the composition for oral cavity of the present invention are not particularly limited. For example, it can be prepared in various shapes such as a liquid system (liquid, liquid, paste) and a solid system (solid, solid). Examples of dosage forms include toothpaste compositions such as toothpaste, liquid dentifrice, liquid dentifrice, powder dentifrice, mouthwash composition, coating composition, oral pasta, mouth freshener composition, food form (for example, Chewing gum, tablet confectionery, candy, gummi, film, troche, etc.). In the form of food, tablet candy, candy, chewing gum, gummi and film are preferred from the viewpoint of convenience and portability that can be used regardless of time and place.

  Examples of the candy include soft candy such as caramel and nougat, hard candy such as drop and toffee, and the like. Although not particularly limited, a hard candy is preferable in terms of imparting a high functional feeling. The hard candy can be produced by a conventional method, and is not particularly limited. For example, water is added to raw materials other than the functional ingredient and the fragrance, and the mixture is boiled at a high temperature (eg, 140 to 200 ° C.) and then cooled (eg, 70 ˜130 ° C.), adding functional components and fragrance, and further cooling and molding. In order to mix stably while maintaining the activity of the functional ingredient, water is added to raw materials other than the functional ingredient and the fragrance, and after boiling at a high temperature (140 to 200 ° C.), cooling (for example, from 70 ° C. to 100 ° C.) However, it is more preferable to manufacture by a method of adding a functional ingredient and a fragrance, further cooling and molding.

  Chewing gum is a food with chewing elasticity that uses a gum base and a sugar as main ingredients, and may have a sugar coating. Chewing gum can be produced by a conventional method and is not particularly limited. For example, in the case of plate-like chewing gum, it can be produced by mixing and molding each component containing the active ingredient in the present invention such as the component (A). In the case of sugar-coated chewing gum, the active ingredient in the present invention such as the component (A) may be contained in either or both of sugar-coated and gum base, but is preferably contained in sugar-coated. Thereby, the storage stability of sugar-coated chewing gum can be improved. Such sugar-coated chewing gum can be manufactured, for example, by mixing and molding each raw material mainly composed of chewing gum and then coating with sugar coating containing the active ingredient in the present invention such as the component (A). The content of the active ingredient in the present invention such as the component (A) in the sugar coating layer in the case of sugar-coating chewing gum is preferably mass% of each of the above-mentioned components with respect to the total amount of sugar coating.

  As a gum base blended mainly in chewing gum, those usually used for chewing gum can be used. The gum base is, for example, a polyvinyl acetate resin (average polymerization degree of about 100 to about 1000), natural resins (ticule, gelton, solver, etc.), resins for gum base such as polyisobutylene, polybutene, ester gum (base agent), Emulsifier, calcium carbonate, calcium phosphate, filler (such as talc), lanolin, stearic acid, sodium stearate, potassium stearate, glyceryl triacetate, plasticizer or softener such as glycerin, natural wax, petroleum wax, paraffin, etc. The thing which mix | blended the component is mentioned. A commercially available product can be used as the gum base. Specifically, a gum base manufactured by Natural Base Co., Ltd. and a gum base manufactured by Youth Co., Ltd. are suitable. In addition, the said gum base may contain coloring agents, such as natural pigment | dyes, such as gardenia, safflower, and abalone, and titanium dioxide.

  The gum base content is preferably 10 to 50%, more preferably 15 to 30%, based on the total amount of the composition.

  The tablet confectionery is a saccharide used as a main raw material and compression-molded with a device such as a tableting machine, and may have a sugar coating. Tablet confectionery can be produced by a conventional method, and is not particularly limited. For example, it is produced by mixing each component and compressing it with a device such as a tableting machine (for example, under a pressure condition of 5 to 20 kN). Can do.

  When the example of the application amount to the human of the composition for oral cavity of this invention is given, when applying 3 times per day, the usage-amount of 1 time is 0.5-2g, Preferably it is about 0.5-1g. The amount can be adjusted as appropriate.

  Although the use of the composition of this invention is not specifically limited, From the viewpoint of an application site | part, the composition for oral cavity (a food-drinks composition is also included) is mentioned, for example. Examples of oral compositions include dentifrice compositions such as toothpaste, liquid dentifrice, liquid dentifrice, and powder dentifrice, mouthwash compositions, mouth freshener compositions, and food and beverage compositions.

  Other examples of the composition of the present invention include a collagen coloring inhibitory composition, a collagen degradation inhibitory composition, a dentin caries inhibitory composition, a dentinal tubule sealing composition, a composition for reducing pain due to hypersensitivity, and a stain formation inhibitory composition. Or a stain removal composition, a tooth surface gloss imparting composition, etc. are mentioned.

  The application target of the composition of the present invention is not particularly limited. For example, a person with dentinal hypersensitivity, a patient with dentinal caries, dentinal hypersensitivity and dentinal caries, but not confirmed whether or not, For example, those who want to prevent dental caries.

  The composition of the present invention may be any of pharmaceuticals, quasi drugs, cosmetics, and foods and drinks.

[Collagen coloring inhibitor]
Since the lactam compound or salt thereof as the component (A) has an effect of suppressing coloring to collagen, it is useful as an active ingredient of a collagen coloring inhibitor.

  Collagen is present in animal tissues. Human collagen is classified into several tens of types, and the main collagen is type I. The collagen targeted by the collagen coloring inhibitor of the present invention is not particularly limited, but is preferably collagen containing type I collagen.

  Collagen coloring means a change from the original color of collagen to another color. Collagen coloring targeted by the collagen coloring inhibitor is preferably collagen coloring generated in the living body, and more preferably coloring of the dentin collagen layer. Examples of collagen coloring include coloring of dentin collagen layers by drugs, food and drink, and oral bacteria. When suffering from dentine caries, the dentin may be colored by oral bacteria, or the dentin collagen layer may be colored by applying a drug in the treatment of dentine caries. Moreover, the same coloring may arise by ingestion of food and drink. By applying the collagen degradation inhibitor of the present invention, the above coloration can be suppressed. The main example of a drug that causes collagen coloring is polyphenol. Examples of the polyphenol include flavonoids, phenylcarboxylic acid, chlorogenic acid, lignan, curcumin, and examples of the above (2-B) component. In addition, foods and drinks containing a large amount of the above polyphenol (for example, black tea or green tea containing catechin, coffee containing chlorogenic acid, etc.) can also cause coloring.

  The administration form of the collagen coloring inhibitor of the present invention is not particularly limited. For example, oral administration (eg, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.) and the like can be mentioned. Among these, a less invasive dosage form is preferable, and oral administration or transdermal administration is more preferable.

  Examples of subjects who take the collagen coloring inhibitor of the present invention include subjects who have already developed collagen coloring and want to improve, subjects who have not developed collagen coloring but want to prevent, etc. . The administration time of the agent of the present invention is not particularly limited.

[Collagen degradation inhibitor]
Since the lactam compound or salt thereof as the component (A) has a collagen degradation inhibitory effect, it is useful as an active ingredient of a collagen degradation inhibitor.

  The collagen targeted by the collagen degradation inhibitor of the present invention is not particularly limited, but is preferably collagen containing type I collagen.

  When the dentin collagen layer is exposed and destroyed by collagenase in dentin caries, the root of the tooth is substantially lost. By applying the collagen degradation inhibitor of the present invention to teeth, collagen degradation can be suppressed or improved, and dentine caries can be prevented.

  Periodontal collagen degradation causes periodontal tissue troubles such as gingival retraction and alveolar bone resorption. Collagen degradation can be suppressed by the collagen degradation inhibitor of the present invention, so that troubles in periodontal tissue can be prevented.

  The dosage form of the collagen degradation inhibitor of the present invention is not particularly limited. Examples of dosage forms and preferred examples are the same as the examples and preferred examples given in the description of the collagen coloring inhibitor.

  The subject of intake of the collagen degradation inhibitor or ameliorating agent of the present invention has already developed symptoms due to collagen degradation (eg, progression of dentin caries, periodontal tissue trouble (gingival recession, alveolar bone resorption, etc.)) And subjects who want to improve and those who do not develop these symptoms but want to prevent. The administration time of the agent of the present invention is not particularly limited.

[Ivory tubule sealant]
The lactam compound and / or salt thereof as the component (A) is useful as a dentinal tubule sealing agent because it has an early dentinal tubule blocking effect.

  The administration form of the dentinal tubule blocking agent of the present invention is not particularly limited. Examples of dosage forms and preferred examples are the same as the examples and preferred examples given in the description of the collagen degradation inhibitor.

  The subject who ingested the dentinal tubule-blocking agent of the present invention has already developed dentinal hypersensitivity, and the subject who wants to block the dentinal tubule, whether the symptom has not developed or has developed Although it is not, there are subjects who want to prevent it. The administration time of the agent of the present invention is not particularly limited.

[Inhibitor or ameliorator of dentin hypersensitivity]
The lactam compound and / or salt thereof as the component (A) is useful as an agent for suppressing or improving dentinal hypersensitivity because it has an effect of early blocking of dentinal tubules and a pain reducing effect.

  The administration form of the agent for suppressing or improving dentin hypersensitivity of the present invention is not particularly limited. Examples of dosage forms and preferred examples are the same as the examples and preferred examples given in the description of the collagen degradation inhibitor.

  The subject of ingestion of the dentin hypersensitivity inhibitor or ameliorating agent of the present invention is a subject who has already developed dentine hypersensitivity and wants to improve the symptom. The target person is considered. The administration time of the agent of the present invention is not particularly limited.

[Stain remover]
The lactam compound or a salt thereof as the component (A) is useful as an active ingredient of a stain remover because it has an effect of removing stains that are tooth stains.

  The subject who takes the stain remover of the present invention includes a subject who wants to remove stains due to stains on the teeth. The administration time and administration form of the agent of the present invention are not particularly limited, but may be the same as the administration form of the composition described above.

  Hereinafter, the present invention will be described in detail with reference to examples. Each of the following examples is for explaining the present invention suitably, and does not limit the present invention. In the following examples,% indicates a mass percentage.

Examples 1-1 to 1-30 and Comparative Examples 1-1 to 1-4
[Main ingredients used]
[(A) component]
(1) Pyrrolidone carboxylic acid (γ-lactam compound):
Product name “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc.
(2) 6-Oxo-2-piperidinecarboxylic acid (δ-lactam compound):
Product name “(S) -6-Oxo-2-piperidine carboxylic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
(3) 3- (2-Oxo-1-azepanyl) propanoic acid (ε-lactam compound):
Product name “3- (2-Oxozepan-1-yl) propanoic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
[Comparative product of component (A)]
(4) Polyvinylpyrrolidone (lactam compound having no acidic group):
Product name “Polyvinylpyrrolidone K25” manufactured by Wako Pure Chemical Industries, Ltd.
(5) Proline (cyclic amino acid):
Wako Pure Chemical Industries, Ltd., trade name "DL-proline"
[(1-B) component]
(6) Sodium fluoride:
Product name "Sodium fluoride" manufactured by Stella Chemifa
(7) Sodium monofluorophosphate:
Product name "Sodium monofluorophosphate" manufactured by Rhodia Nikka Co., Ltd.
[(1-C) component]
(8) Casein:
Wako Pure Chemical Industries, Ltd., trade name "casein (derived from milk)"
Sulfur-containing amino acid content (%): 3.0
Average molecular weight: 88000
Phosphate group: Existence (9) Lactoferrin:
Wako Pure Chemical Industries, Ltd., trade name "Lactoferrin (derived from milk)"
Sulfur-containing amino acid content (%): 5.4
Average molecular weight: 86000
Phosphate group: None (10) Hydrolyzed collagen:
Product name “HACP-U2” manufactured by Zerais
Sulfur-containing amino acid content (%): 1.5
Average molecular weight: 1500
Phosphoric acid group: None (11) Other additive components other than the above active ingredients:
Sodium hydroxide (pH adjuster), citric acid (pH adjuster), sorbite solution (viscous agent), sodium saccharin (sweetener), propylene glycol (viscous agent), sodium polyacrylate (binding agent), carboxy Sodium methylcellulose (binding agent), silicic anhydride (abrasive), sodium lauryl sulfate (anionic surfactant), fragrance

[Preparation of dentifrice]
Using the above-mentioned active ingredients, 1.0 kg (100 parts by mass) of a dentifrice was prepared by the following conventional method for preparing a dentifrice according to the mass ratio (parts by mass) shown in Tables 1 to 9 below.

(Method for preparing dentifrice)
The following “(i) A phase active ingredient” and “(ii) A phase additive” were mixed and dissolved at room temperature in purified water to prepare A phase. On the other hand, the following “(iii) B phase additive component” was dissolved or dispersed in propylene glycol at room temperature to prepare B phase. Next, B phase was added and mixed in A phase under stirring, and C phase was prepared. Finally, the following “(iv) Additive component for C phase” is mixed in C phase at room temperature using a 1.5 L kneader (manufactured by Ishiyama Kogakusho), depressurized to 4 kPa, defoamed, and dentifrice 1.0 kg (100 parts by mass) was obtained. The content of each component was as shown in Tables 1-9.

(Active ingredients and additive ingredients blended in Phase A, Phase B and Phase C)
(I) Active ingredients for phase A: pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, sodium fluoride, sodium monofluorophosphate, casein, Additives for lactoferrin, hydrolyzed collagen (ii) A phase: sorbite solution, sodium saccharin, citric acid, sodium hydroxide (iii) Additives for phase B: propylene glycol, sodium polyacrylate, sodium carboxymethylcellulose (iv) Additives for Phase C: Silicic anhydride, sodium lauryl sulfate, fragrance

  Using each dentifrice obtained as described above, dentin caries inhibitory effect and formulation stability were evaluated as follows.

(Evaluation of dentin caries inhibitory effect)
(1) A dentin block having a window formed on the surface from a bovine tooth root was prepared and immersed in a decalcification solution of acetic acid 100 mmol / L and pH 4.8 at 37 ° C. for 6 hours to obtain a carious tooth sample.

  (2) Assuming that the dentifrice is diluted with saliva at the time of use, each dentifrice was diluted 3 times with distilled water to obtain each dentifrice treatment solution. The carious tooth sample was immersed in each dentifrice treatment solution for 3 minutes at room temperature, and then the dentifrice treatment solution was lightly removed.

(3) Collagenase derived from Clostridium histolyticum (Type 1A) of CaCl ₂ : 1.5 mmol / L, KH ₂ PO ₄ : 5.0 mmol / L, acetic acid: 100 mmol / L, NaCl: 100 mmol / L, 1.0 unit / mL A remineralization solution having a pH of 6.5 containing Sigma) was prepared. Each carious tooth sample after the treatment of (2) was immersed in a remineralization solution at 37 ° C. for 18 hours.

  (4) Each carious tooth sample after the treatment of (3) was immersed again in each dentifrice treatment solution for 3 minutes at room temperature, and the dentifrice treatment solution was lightly removed. It was immersed in a decalcification solution of acetic acid 100 mmol / L and pH 4.8 at 37 ° C. for 6 hours, and the decalcification solution was lightly removed.

  (5) The processes (2) to (4) were repeated once a day for a total of 3 days.

  (6) After the treatment for 3 days, each carious tooth sample was rinsed well with distilled water and perpendicular to the sample window with a microcutter (Malto Co., Ltd., “MC-201 (trade name)”). Then, a section having a thickness of about 200 μm was carefully cut out under running water.

  (7) A sample slice cut out in a wet state is placed on a soft X-ray film (“SO-343 (trade name)” manufactured by Kodak Co., Ltd.), and a soft X-ray generator (Softex Corporation) ), “CMRII (trade name)”) was irradiated with soft X-rays (2.8 mA, 18 kVp) for 60 minutes to obtain a TMR (Transverse Micro Radiography) image of each flake sample.

(8) Finally, the degree of decalcification of each flake sample was confirmed as follows. From the TMR images of 15 aluminum step wedges photographed with the flake sample, the mineral profile of the TMR image of each flake sample was obtained using an image analyzer (Pierce Co., Ltd., “PIAS-V (trade name)”). Created. A mineral loss amount ΔZ (decalcification amount) was calculated from each obtained mineral profile.
The decalcification amount of the sample not subjected to the treatment with the dentifrice treatment liquid (untreated group) was also calculated in the same manner.

  (9) The series of experimental operations described above was performed with N = 3 for each group (Example, Comparative Example, and untreated group). For each group, an average value (average ΔZ) of each individual constituting the group was obtained and set as “average ΔZ of untreated group”, “average ΔZ of Examples”, and “average ΔZ of Comparative Examples”. The “average ΔZ of the untreated group” was defined as the reference decalcification amount, and the dentin caries inhibition rate was determined by the following formula (1-2) from “average ΔZ of Examples” or “average ΔZ of Comparative Examples”.

  The dentin caries prevention effect of each Example and Comparative Example was evaluated based on the following five-step criteria. If the following evaluation score is 3 or more, it may be considered that there is a good dentine caries prevention effect.

〔Evaluation criteria〕
5 points: Dentin caries inhibition rate is 70% or more 4 points: Dentine caries inhibition rate is 50% or more and less than 70% 3 points: Dentin caries inhibition rate is 30% or more and less than 50% 2 points: Dentine Caries inhibition rate is 10% or more and less than 30% 1 point: Dentin caries inhibition rate is less than 10%

(Stability evaluation of drug product)
The appearance immediately after the manufacture of the dentifrices of each Example and Comparative Example was visually evaluated. The sensory evaluation of the flavor immediately after manufacture of the dentifrice of each Example and a comparative example was carried out. Thereafter, samples stored for 1 month in a 50 ° C. environment were similarly evaluated.

  Evaluation was performed according to the following criteria.

〔Evaluation criteria〕
A: No precipitation / precipitation, no discoloration, no liquid separation / layer separation. There is no deterioration of flavor.
B: Although any or all of precipitation / precipitation, discoloration, liquid separation, and flavor deterioration are slightly observed, the level is not problematic.
C: Although there is no problem immediately after production, there is a problem that at least one of precipitation / precipitation, discoloration, liquid separation, and flavor is remarkably deteriorated after storage for 1 month in a 50 ° C. environment.
D: At least one of precipitation / precipitation, discoloration, liquid separation, and flavor is remarkably worse immediately after production.

  The dentine caries inhibitory effect and formulation stability of each Example and Comparative Example evaluated according to the above evaluation methods and evaluation criteria are shown in Tables 1 to 9 below.

  In Examples 1-1 to 1-5 shown in Table 1 above, (1-C) component which is an arbitrary active component is not added, pyrrolidone carboxylic acid is used as component (A), and (1-B) Sodium fluoride is used as a component.

  Evaluation of the dentine caries inhibitory effect of Examples 1-1 to 1-5 is 3 or more, which is favorable.

  It is well known that fluorine compounds are effective in suppressing caries. However, as shown in Comparative Example 1-1 to be described later, the evaluation of the dentine caries inhibitory effect by the fluorine compound alone is 2, which is insufficient in practice.

  On the other hand, evaluation of the dentine caries inhibitory effect of the composition for oral cavity of the Example which uses (A) component and (1-B) component simultaneously as an active ingredient is 3 or more, and an Example in particular 1-1 to 1-3 have an evaluation of 4. Therefore, by using the component (A) and the component (1-B) as active components at the same time, an effect more than the additive of the component (A) and the component (1-B), that is, a synergistic effect can be obtained. I understand that

  In Examples 1-6 and 1-7 shown in Table 2, the (1-C) component is not added, and sodium fluoride is used as the (1-B) component. In Example 1-6, 6-oxo-2-piperidinecarboxylic acid was used as the (A) component, and in Example 1-7, 3- (2-oxo-1-azepanyl) propanoic acid was used as the (A) component. Yes.

  Evaluation of the dentine caries inhibitory effect of Examples 1-6 and 1-7 is 3, which is good.

  In Examples 1-8 to 1-11 shown in Table 3 above, as in Examples 1-1 to 1-5 of Table 1, (1-C) component was not added, and pyrrolidone was used as component (A). Carboxylic acid is used, and sodium fluoride is used as the (1-B) component.

  Evaluation of the dentine caries inhibitory effect of Examples 1-8 to 1-11 is 3 or more, which is good. Among them, the evaluation of Examples 1-8 and 1-9 is 4. This shows that the synergistic effect of (A) component and (1-B) component is acquired.

  In Examples 1-12 to 1-15 shown in Table 4, the (1-C) component was not added, and pyrrolidone carboxylic acid was used as the (A) component. In Examples 1-12 and 1-13, sodium monofluorophosphate was used as the (1-B) component, and in Examples 1-14 and 1-15, sodium fluoride was used.

  Evaluation of the dentine caries inhibitory effect of Examples 1-12 to 1-15 is 3 or more, which is good. Among them, Examples 1-12 and 1-13 have a rating of 4. This shows that the synergistic effect of the component (A) and the component (1-B) is obtained.

  Examples 1-16 to 1-19 shown in Table 5 use casein as the (1-C) component, use pyrrolidone carboxylic acid as the (A) component, and use sodium fluoride as the (1-B) component. ing.

  Evaluation of the dentine caries inhibitory effect of Examples 1-16 to 1-19 is 5. From this, it can be seen that by adding the (1-C) component to the (A) component and the (1-B) component, a high dentin caries inhibitory effect can be obtained.

  In Examples 1-20 and 1-21 shown in Table 6, the (1-C) component is added. In Example 1-20, lactoferrin is used as the (1-C) component, and in Example 1-21, hydrolyzed collagen is used as the (1-C) component. In each example, pyrrolidone carboxylic acid is used as the component (A), and sodium fluoride is used as the component (1-B).

  Evaluation of the dentine caries inhibitory effect of Examples 1-20 and 1-21 is 5, and by adding (1-C) component to (A) component and (1-B) component, high dentin It can be seen that a caries suppression effect is obtained.

  In Examples 1-22 to 1-26 shown in Table 7, a plurality of types of compounds are used in combination as active ingredients.

  In Example 1-22, pyrrolidonecarboxylic acid (γ-lactam compound) and 6-oxo-2-piperidinecarboxylic acid (δ-lactam compound) are used in combination as component (A).

  In Example 1-23, as component (A), pyrrolidonecarboxylic acid (γ-lactam compound) and 3- (2-oxo-1-azepanyl) propanoic acid (ε-lactam compound) are used in combination.

  In Example 1-24, 6-oxo-2-piperidinecarboxylic acid (δ-lactam compound) and 3- (2-oxo-1-azepanyl) propanoic acid (ε-lactam compound) were used as the component (A). Used together.

  In Example 1-25, as component (A), pyrrolidonecarboxylic acid (γ-lactam compound), 6-oxo-2-piperidinecarboxylic acid (δ-lactam compound), and 3- (2-oxo-1- Azepanyl) propanoic acid (ε-lactam compound).

  In Example 1-26, pyrrolidone carboxylic acid (γ-lactam compound) is used as the component (A), and sodium fluoride and sodium monofluorophosphate are used in combination as the component (1-B).

  In Examples 1-27 to 1-30 shown in Table 8, a plurality of types of compounds are used in combination as active ingredients.

  In Example 1-27, casein and lactoferrin are used in combination as the (1-C) component.

  In Example 1-28, casein and hydrolyzed collagen are used in combination as the (1-C) component.

  In Example 1-29, lactoferrin and hydrolyzed collagen are used in combination as the (1-C) component.

  In Example 1-30, casein, lactoferrin, and hydrolyzed collagen are used in combination as the (1-C) component.

  Comparative Example 1-1 uses sodium fluoride as the (1-B) component without using the (A) component.

  In Comparative Examples 1-2 and 1-3, lactam compounds and analogs of lactam compounds are used as comparative products of the component (A). In Comparative Example 1-2, polyvinylpyrrolidone is used as a comparative product of the component (A). Polyvinylpyrrolidone is a lactam compound having no acidic group. In Comparative Example 1-3, proline is used instead as a comparative product of component (A). Proline is a cyclic amino acid.

  Comparative Example 1-4 uses pyrrolidone carboxylic acid as the component (A) without using the component (1-B).

  Comparative Example 1-1 uses sodium fluoride as the (1-B) component without using the (A) component. It is well known that fluorine compounds are effective in suppressing caries. However, evaluation of the dentine caries inhibitory effect by this fluorine compound alone is 2, which is insufficient in practical use.

  Moreover, in Comparative Example 1-4, although evaluation of formulation stability was (circle), evaluation of the dentine caries inhibitory effect was 1.

  As is clear from the evaluation results of the comparative examples 1-1 and 1-4 and the evaluation results of the above-described examples, the components (A) and (1-B) are used as active ingredients at the same time. More than the additive effect can be obtained.

  Below, two types of prescription examples of the composition for oral cavity which concerns on this invention are shown. Also in this prescription example, the dentine caries prevention effect similar to the composition for oral cavity of the above-mentioned Example can be acquired.

Examples 2-1 to 2-36 and Comparative Examples 2-1 to 2-6
[Main ingredients used]
[(A) component]
(1) Pyrrolidone carboxylic acid (γ-lactam compound):
Product name “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc.
(2) 6-Oxo-2-piperidinecarboxylic acid (δ-lactam compound):
Product name “(S) -6-Oxo-2-piperidine carboxylic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
(3) 3- (2-Oxo-1-azepanyl) propanoic acid (ε-lactam compound):
Product name “3- (2-Oxozepan-1-yl) propanoic acid” manufactured by Sigma Aldrich Japan Co., Ltd.

[Comparative product of component (A)]
(4) Polyvinylpyrrolidone:
Product name “Polyvinylpyrrolidone K25” manufactured by Wako Pure Chemical Industries, Ltd.
[(2-B) component]
(5) Longan seed extract (used in Examples and Comparative Examples other than Examples 2-12 and 2-13):
Product name “Agetect” manufactured by Katakura Chikkarin Co., Ltd.
Longan seed extract content: 1%;
(6) Longan seed extract (used in Examples 12 and 13):
Product name “Longan Seed Extract Powder SD” manufactured by Katakura Chikkarin Co., Ltd.
Longan seed extract content: 83%;
(7) Proanthocyanidins:
Product name "Gravinol-SL" manufactured by Kikkoman Corporation
Proanthocyanidin content: 82%
(8) Catechin:
Product name "Sunphenon EGCg" manufactured by Taiyo Chemical Co., Ltd.
Catechin content: 95%
(9) Hesperidin:
Product name “Methylhesperidin”, manufactured by Tokyo Chemical Industry Co., Ltd.
Hesperidin content: 90%

[Comparison product of component (2-B)]
(10) Rosemary extract:
Product name “RKC-87” manufactured by Maruzen Pharmaceutical Co., Ltd.
Rosemary extract content: 1.5%

  The blending ratio of each polyphenol compound shown in Tables 12 to 16 is the blending ratio of the polyphenol contained in each commercially available product in the raw material of each composition.

Experimental Example 2-1 Evaluation of Dentin Collagen Degradation Inhibitory Effect [Preparation of Dentifrice]
Each composition for oral cavity of the composition shown to Tables 12-16 was prepared. The preparation method is as follows. A phase in which water-soluble raw materials (lactam compound, polyphenol compound, disodium hydrogen phosphate, sodium saccharin) were mixed in purified water containing 70% sorbite, and B phase in which sodium alginate, carrageenan, and methylparaben were added to propylene glycol were mixed. . In the resulting mixture, silicic anhydride, a fragrance, and sodium lauryl sulfate were mixed at room temperature in a 1.5 L kneader (manufactured by Ishiyama Works). Thereafter, the pressure was reduced to 4 kPa to perform defoaming, and further mixing was continued to obtain a composition. The obtained composition was used within 1 week at room temperature for the following evaluation.

[Collagen degradation inhibition evaluation]
The surface of the bovine tooth root was polished with a width of about 2 mm for a demineralization window to remove cementum, and then a slice having a thickness of 250 μm was cut out with a microcutter. About 1.5 mm × 250 μm of the part from which the cementum was removed was used for the decalcification window, and the other part was coated with nail polish. After drying the nail polish at room temperature, a root caries sample was prepared by dipping in a 0.1 mol / L acetic acid aqueous solution (pH 4.5) for 50 hours to expose the collagen in the window portion. This sample was immersed in a 3-fold water dilution of the composition of each Example and Comparative Example for 5 minutes at room temperature, washed with distilled water, and then artificial saliva (CaCl ₂ : 2.2 mmol / L, KH _{2 at} 37 ° C. It was immersed in PO ₄ : 2.2 mmol / L, acetic acid: 0.1 mol / L, collagenase derived from Clostridium histolyticum (Type 1A, manufactured by Sigma): 1.0 unit / mL, pH 6.5). The composition treatment was performed 3 times / day in the morning, noon, and night, and was immersed in artificial saliva containing collagenase at other times and repeated for a total of 4 days. After the experiment was completed, the root caries sample was observed with a microscope, and the depth of exposed collagen was measured at three locations per sample and averaged. The measurement was performed at n = 3, and the average value was calculated. The collagen degradation inhibition rate was calculated by the following formula and evaluated according to the following criteria. In the following formulae, the example or comparative group represents a group treated with the composition shown in the example or comparative example, and the control group represents a group not treated with the composition shown in the example or comparative example. Indicates. Each example and comparative example were similarly evaluated with n = 3. These results are shown in Tables 12-16.

[Evaluation criteria for dentin collagen degradation inhibitory effect]
A: Dentin collagen degradation inhibition rate is 70% or more and less than 90% B: Dentin collagen degradation inhibition rate is 50% or more and less than 70% C: Dentin collagen degradation inhibition rate is 20% or more and less than 50% D: Dentin collagen Decomposition rate is 0% or more and less than 20%

Experimental example 2-2 Evaluation of dentin collagen degradation inhibitory effect after storage (after storage at 50 ° C. for 1 month)
[Preparation of composition]
The composition for oral cavity of the composition shown to Tables 12-16 similar to Experimental example 2-1 was prepared, and it was stored and used for 1 month in a 50 degreeC high temperature tank.

[Evaluation of inhibitory effect on dentin collagen degradation after storage]
The composition of the preserved product was used, and dentin collagen degradation inhibition evaluation after the preservation was performed. The evaluation method, the method for calculating the dentin collagen degradation inhibition rate, and the evaluation criteria were all the same as in Experimental Example 2-1.

Experimental Example 2-3 Evaluation of Dentin Collagen Coloring Inhibition Effect after Storage (After Storage at 50 ° C. for 1 Month)
[Preparation of dentifrice]
The composition for oral cavity of the composition shown to Tables 12-16 similar to Experimental example 2-1 was prepared, and it was stored and used for 1 month in a 50 degreeC high temperature tank.

[Evaluation of inhibition of dentin collagen coloring after storage]
The bovine tooth root was cut on a block, and the cementum was removed by surface polishing. About 3.5 mm × 3.5 mm of the part from which the cementum was removed was used for the decalcification window, and the other part was coated with nail polish. After drying the nail polish at room temperature, a root caries sample was prepared by dipping in a 0.1 mol / L acetic acid aqueous solution (pH 4.5) for 72 hours to expose the collagen in the window portion. First, color differences (L ^* 0, a ^* 0, b ^* 0) were measured as initial values. Next, this sample was immersed in a 3-fold water dilution of the composition of each Example and Comparative Example for 5 minutes at room temperature, washed with distilled water, and then at 37 ° C. artificial saliva (CaCl ₂ : 2.2 mmol / L). KH ₂ PO ₄ : 2.2 mmol / L, acetic acid: 0.1 mol / L, collagenase derived from Clostridium histolyticum (Type 1A, manufactured by Sigma): 0.1 unit / mL, pH 6.5). The composition treatment was performed 3 times / day in the morning, noon, and night, and was immersed in artificial saliva containing collagenase at other times and repeated for a total of 4 days. After the experiment was completed, color difference (L ^* 1, a ^* 1, b ^* 1) measurement was performed at n = 3, and an average value was calculated. The color difference is measured using a spectrocolorimeter (manufactured by Konica Minolta Co., Ltd., CM-2022), and the coloring suppression effect is evaluated based on the following evaluation criteria from the ΔE value calculated from the following formula (2-2). did. These results are shown in Tables 12-16.
ΔE value = ((L ^* 1-L ^* 0) ² + (a ^* 1-a ^* 0) ² + (b ^* 1-b ^* 0) ² ) ^1/2

[Evaluation criteria]
A: 0 ≦ ΔE <2.0
B: 2.0 ≦ ΔE <4.0
C: 4.0 ≦ ΔE <6.0
D: 6.0 ≦ ΔE <8.0

Experimental Example 2-4 Evaluation of formulation stability (after storage at 50 ° C for 1 month)
Similarly to Experimental Example 2-1, dentifrices having the compositions shown in Tables 12 to 16 were prepared and stored in a high-temperature bath at 50 ° C. for 1 month. The appearance after storage was visually confirmed, and the preparation stability (discoloration and shape retention) was evaluated based on the following evaluation criteria.

[Evaluation criteria]
A: Discoloration of the composition extracted from the tube is not recognized, and there is no problem in shape retention.
B: There is almost no problem in discoloration and shape retention of the composition extracted from the tube.
C: There is a slight problem in discoloration and / or shape retention of the composition extracted from the tube.
D: The composition extracted from the tube has a considerable problem in discoloration and / or shape retention.

  The result of Experimental Example 2-1 to 2-4 about the composition for oral cavity of each Example and a comparative example was shown to Tables 12-16.

  The following can be understood from Tables 12-16. The preparation of the composition for oral cavity (Examples 2-34 to 2-36) using the component (A) maintains an excellent dentin collagen degradation inhibitory effect equivalent to that before storage even after storage at 50 ° C. for 1 hour. Was. Moreover, the dentin collagen degradation inhibitory effect of the formulation of an oral composition (Examples 2-34 to 2-36) was superior to the oral composition (Comparative Example 2-5) using polyvinylpyrrolidone. The composition for oral cavity (Example) in which the component (A) and the component (2-B) are blended, each of the component (A) component and the component (2-B) is used alone, or the component (A) and the component (2). -B) Compared with the composition for oral cavity using each comparative product of components (Comparative Example), the dentin collagen degradation inhibitory rate is remarkably high, and the dentin is high even after the preparation is stored at 50 ° C. for 1 month. It was confirmed that the collagen degradation inhibitory effect was sustained. Moreover, the composition for oral cavity (Example) which mix | blended (A) component or mix | blended (A) component and (2-B) component is suppressed remarkably to the dentin collagen by a polyphenol component. In addition, discoloration after storage of the preparation was significantly suppressed. These results show that the oral composition of the present invention has a well-balanced balance between dentin collagen degradation inhibitory effect, dentin collagen degradation inhibitory effect after storage, dentin collagen coloration inhibitory effect after storage, and formulation stability. It is shown to be demonstrated. These results show that the oral composition (2) is remarkable in any of the dentin collagen degradation inhibitory effect, the dentin collagen degradation inhibitory effect after storage, the dentin collagen coloration inhibitory effect after storage, and the formulation stability. It also shows that it is excellent.

  Further formulation examples are shown below. Also in this prescription example, the same effect as the above-mentioned Example can be acquired.

Examples 3-1 to 3-26 and comparative examples 3-1 to 3-3
[Main ingredients used]
[(A) component]
(1) Pyrrolidone carboxylic acid (γ-lactam compound):
Product name “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc.
(2) 6-Oxo-2-piperidinecarboxylic acid (δ-lactam compound):
Product name “(S) -6-Oxo-2-piperidine carboxylic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
(3) 3- (2-Oxo-1-azepanyl) propanoic acid (ε-lactam compound):
Product name “3- (2-Oxozepan-1-yl) propanoic acid” manufactured by Sigma Aldrich Japan Co., Ltd.

[Comparative product of component (A)]
(4) Polyvinylpyrrolidone:
Wako Pure Chemical Industries, Ltd., trade name “Polyvinylpyrrolidone K25”, Wako Pure Chemical Industries, Ltd. (5) Proline:
Wako Pure Chemical Industries, Ltd., trade name "DL-proline"

[(3-B) component]
(6) Aluminum lactate:
Wako Pure Chemical Industries, Ltd., trade name “Aluminum lactate”

[(3-C) component]
(7) Sodium monofluorophosphate:
Purchased from Rhodia Nikkasha, trade name “Sodium Monofluorophosphate”

[(3-D) component]
(8) Potassium nitrate:
Wako Pure Chemical Industries, Ltd., trade name "Potassium nitrate"

  The following “(i) A phase active ingredient” and “(ii) A phase additive” were mixed and dissolved at room temperature in purified water to prepare A phase. On the other hand, the following “(iii) B phase additive component” was dissolved or dispersed in propylene glycol at room temperature to prepare B phase. Next, B phase was added and mixed in A phase under stirring, and C phase was prepared. Finally, the following “(iv) Additive component for C phase” is mixed in C phase at room temperature using a 1.5 L kneader (manufactured by Ishiyama Kogakusho), depressurized to 4 kPa, defoamed, and dentifrice 1.0 kg (100 parts by mass) was obtained. The amount of each component was as shown in Tables 25-29.

(Active ingredients blended in Phase A, Phase B, Phase C and other additive ingredients)
(I) Active ingredients for phase A: pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, aluminum lactate, sodium monofluorophosphate, potassium nitrate (ii ) Additives for phase A: 70% by weight sorbitol, sodium saccharin, sodium hydroxide (iii) Additives for phase B: propylene glycol, xanthan gum, sodium carboxymethylcellulose, methylparaben (iv) Additives for phase C: anhydrous silica Acid, sodium lauryl sulfate, fragrance

  Each dentifrice obtained as described above was evaluated according to the following Experimental Examples 3-1 to 3-3 for the dentinal tubule early blocking effect, the pain reducing effect, and the feeling of use (taste).

(Experimental example 3-1) Evaluation of dentinal tubule early blockage effect
Using the dentifrice prepared as described above, the permeability of dentinal tubule fluid was measured by a modification of the method of Pashley et al. (J. Dent. Res. 57, 187-193, 1978). Capillary early blockage effect was evaluated.

A 3 mm thick dentin disc was cut out from the crown of a human molar, polished with water-resistant abrasive paper # 2000, etched with a 37% aqueous phosphoric acid solution, and opened with dentinal tubules as samples. PH 7 containing 10 g of each dentifrice, 1.5 mM equivalent of CaCl ₂ , 2.5 mM equivalent of KH ₂ PO ₄ , 0.1 M equivalent of NaCl, 0.1 M equivalent of acetic acid and 1.0 unit / mL acid phosphatase. 0 g of artificial saliva was mixed to give a 3-fold diluted solution, which was used as a treatment solution. The reason for the 3-fold dilution is that it is assumed that the dentifrice is diluted 3-fold with saliva during tooth brushing. The sample was immersed in this treatment solution for 3 minutes, rinsed lightly with distilled water to remove excess treatment solution, and immersed in the artificial saliva at 37 ° C. for 15 hours. Rinse the sample thoroughly with distilled water, drain the water, fix it to the device, run distilled water under constant pressure for 5 minutes, measure the amount of distilled water per unit time (5 minutes) passing through the sample, before treatment The passability suppression rate of each of the examples and the comparative examples was calculated with respect to the passage amount of (Equation (3-1)). In each of the examples and comparative examples, the evaluation was performed at N = 5, and the average value of the permeability control rate of the samples constituting each example was calculated. When the average value was 60% or more, the example or comparative example Evaluated that dentinal tubules had an early sealing effect.

Footnote (*) in formula (3-1)
The passing amount means the amount of distilled water (μL) passing through for 5 minutes.

(Experimental Example 3-2) Evaluation of Pain Relieving Effect Three subjects with hypersensitivity having teeth that felt transient pain during water rinsing after brushing were used as subjects. The subject brushed his teeth twice a day using a dentifrice prepared in the same manner as in Experimental Example 3-1. The degree of pain at the time of rinsing with water just after brushing after 2 days was scored based on the following rating criteria (1 to 5 points), and the pain reduction effect was evaluated from the average value of the scores of the three people. In addition, the pain level before the start of the test was one point of the following rating criteria for all subjects.

[Score for pain level]
5 points: no pain 4 points: almost no pain 3 points: slightly painful but no problem 2 points: somewhat painful 1 point: quite painful

[Evaluation criteria for pain relief]
A: Average value 5 points B: Average value 4 points or more and less than 5 points C: Average value 3 points or more and less than 4 points D: Average value 2 points or more and less than 3 points E: Average value 2 points or less

(Experimental example 3-3) Evaluation of feeling of use (taste) When the pain-reducing effect was evaluated for the three subjects in Experimental example 3-2, the toothpastes of each dentifrice, metallic taste, taste, etc. We asked for a questionnaire about the feeling of use (taste). In the questionnaire, the score was given based on the following criteria (1-4 points). The feeling of use (taste) of each dentifrice was evaluated from the average value of the scores of three subjects.

[Scoring criteria for feeling of use (taste)]
4 points: good 3 points: somewhat good 2 points: somewhat bad 1 point: bad

[Evaluation criteria for feeling of use (taste)]
A: Average value of 3.5 points or more B: Average value of 3.0 points or more and less than 3.5 points C: Average value of 2.0 points or more and less than 3.0 points D: Average value of less than 2.0 points

  The following can be understood from the results of Experimental Examples 3-1 to 3-3 shown in Tables 25 to 29. (A) Dentin tubule early blockage effect, pain relief effect, feeling of use (taste) of dentifrice (Example 3-26) using component (A) alone, (3-B) component used individually, or (A ) It was superior to dentifrices (Comparative Examples 1 to 3) using comparative products (polyvinylpyrrolidone or proline). (A) Component and (3-B) Dentifrice (Examples 3-1 to 3-25) containing dentinal tubules early blocking effect, pain-reducing effect, and feeling of use (taste) include (A) component and Compared to the dentifrice (Example 3-26, Comparative Examples 3-1 to 3-3) using each component (3-B) alone or using a comparative product (polyvinylpyrrolidone or proline) of component (A). It was remarkably superior. In the dentifrice (Examples 3-16 to 3-19) containing the component (3-C) in addition to the component (A) and the component (3-B), the dentinal tubule early blocking effect was very excellent. Moreover, the dentifrice (Examples 3-24 and 3-25) containing the (3-D) component was very excellent in pain reduction effect. Furthermore, in the dentifrice (Examples 3-20 to 3-23) which mix | blended (3-C) component and (3-D) component, the dentinal tubule early blockade effect and the pain reduction effect were very excellent.

  These results indicate that the composition for oral cavity of the present invention is excellent in the effect of early blocking of dentinal tubules, the pain-reducing effect, and the feeling of use (taste). These results also show that the composition for oral cavity (3) of the present invention is remarkably excellent in dentinal tubule early-sealing effect, pain-reducing effect, and feeling of use (taste).

  Further formulation examples are shown below. Also in this prescription example, the same effect as the above-mentioned Example can be acquired.

Examples 4-1 to 4-22 and Comparative Example 4-1
[Main ingredients used]
[(A) component]
(A-1): Pyrrolidone carboxylic acid “AJIDE A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc.
(A-2): 6-oxo-2-piperidinecarboxylic acid Sigma Aldrich Japan Co., Ltd., trade name "(S) -6-Oxo-2-piperidine carboxylic acid"
(A-3): 3- (2-oxo-1-azepanyl) propanoic acid Sigma-Aldrich Japan Co., Ltd., trade name “3- (2-Oxozepan-1-yl) propanoic acid”

[Component (B)]
(B-1): Potassium nitrate Wako Pure Chemical Industries, reagent grade

[Component (C)]
(C-1): Sodium fluoride, manufactured by Stella Chemifa, trade name “sodium fluoride”
(C-2): Sodium monofluorophosphate, manufactured by Rhodia Nikka Co., Ltd., trade name “sodium monofluorophosphate”

[Other additive components]
Silicic anhydride (abrasive), sodium lauryl sulfate (anionic surfactant), propylene glycol (viscous agent), 70% by weight sorbitol (viscous agent), sodium carboxymethylcellulose (binder), sodium hydroxide (pH) Adjuster), sodium saccharin (sweetener), flavor, methylparaben (preservative), purified water (solvent)

  Using the above-mentioned components, 1.0 kg (100 parts by mass) of a dentifrice was prepared by the conventional method for preparing a dentifrice according to the blending ratio (parts by mass) shown in Tables 33 to 35.

(Method for preparing dentifrice)
The following “(i) active ingredient for phase I” and “(ii) additive component for phase I” were mixed and dissolved at room temperature in purified water to prepare phase I. On the other hand, the following “(iii) Additive component for phase II” was dissolved or dispersed at room temperature in propylene glycol to prepare phase II. Next, the phase II was added and mixed into the stirring phase I to prepare the phase III. Finally, in Phase III, the following “(iv) Additive component for Phase III” is mixed at room temperature using a 1.5 L kneader (manufactured by Ishiyama Works), defoamed to 4 kPa, and dentifrice. 1.0 kg (100 parts by mass) was obtained. The amount of each component was as shown in Tables 33-35.

(Active ingredients blended in Phase I, Phase II, Phase III and other additive ingredients)
(I) Active ingredients for phase I: pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, potassium nitrate, sodium fluoride (ii) for phase I Additive components: 70 mass% sorbitol, sodium saccharin, sodium hydroxide (iii) Additive components for phase II: propylene glycol, sodium carboxymethylcellulose, methylparaben (iv) Phase III additive components: anhydrous silicic acid, sodium lauryl sulfate, fragrance

  About each dentifrice obtained as mentioned above, the reduction effect with respect to the pain by hypersensitivity and the usability (taste) were evaluated as follows.

(Evaluation of reduction effect on pain caused by hypersensitivity)
Of the 23 types of dentifrices prepared as described above, 3 patients with hypersensitivity who had teeth that felt transient pain during tooth rinsing after toothbrushing consisted of 8 groups, 24 subjects in total. Eight types (the dentifrices of “Example 4-1” to “Example 4-8”) were assigned to each group, and brushing twice a day was performed for 3 days. From day 4 onward, all groups were similarly brushed twice a day using a placebo dentifrice prepared by removing the active ingredient from Phase I. After switching to a placebo dentifrice, give a score (1-5 points) based on the following score criteria for the degree of pain when rinsing with water just after brushing one week later. Calculated.

  After an interval of about 3 weeks, each of the 8 groups in total 24 subjects was given another 8 kinds of dentifrices (the dentifrices of “Example 4-9” to “Example 4-16”). The same evaluation test was conducted by assigning to groups.

  After an interval of 3 weeks again, among the above subjects, a total of 21 people in 7 groups received 7 other dentifrices ("Example 4-17" to "Example 4-22", "Comparative Example 4"). -1 "dentifrice) was assigned to each group, and the same evaluation test was conducted.

  Based on the average score calculated for each dentifrice, the effect of reducing pain due to hypersensitivity was evaluated based on the following evaluation criteria. The degree of pain before the start of each evaluation test was 1 point on the following score criteria for all subjects.

[Scoring criteria for pain level]
5 points: no pain 4 points: almost no pain 3 points: slightly painful but no problem 2 points: somewhat painful 1 point: quite painful

[Evaluation Criteria for Mitigating Pain Caused by Hypersensitivity]
A: Average value 4.5 points or more and 5.0 points or less B: Average value 4.0 points or more and less than 4.5 points C: Average value 3 points or more and less than 4 points D: Average value 2 points or more and less than 3 points E: Average value less than 2 points

(Evaluation of feeling of use (taste))
At the time of the evaluation test on the alleviation of pain due to hypersensitivity, we conducted a questionnaire on the feeling of use (taste) of the dentifrice, metal taste, taste, etc. Based on the score (1-4 points), the average value was calculated. The feeling of use (taste) was evaluated from the average value of the calculated scores based on the following evaluation criteria.

[Usage (Taste) Score Criteria]
4 points: good 3 points: somewhat good 2 points: somewhat bad 1 point: bad

[Evaluation criteria for feeling of use (taste)]
A: Average value of 3.5 points or more B: Average value of 3.0 points or more and less than 3.5 points C: Average value of 2.0 points or more and less than 3.0 points D: Average value of less than 2.0 points

  Tables 33 to 35 show the alleviation effect and feeling of use (taste) on pain caused by hypersensitivity in each Example and Comparative Example evaluated according to the above evaluation methods and evaluation criteria.

  The dentifrice of Comparative Example 4-1 containing no component (A) and no component (4-B) is pain due to hypersensitivity at the time of water rinsing immediately after brushing one week after switching to a placebo dentifrice. Almost no reduction effect was observed, and the feeling of use (taste) was poor (Table 35).

  The toothpaste of Example 4-22 containing no (4-B) component and containing the component (A) is one week after switching to a placebo dentifrice compared to the dentifrice of Comparative Example 4-1. In the case of rinsing with water immediately after brushing the teeth, the effect of reducing the pain due to hypersensitivity and the feeling of use (taste) were excellent (Table 35).

  On the other hand, the dentifrices of Examples 4-1 to 4-21 containing the component (A) in combination with the component (4-B) were rinsed with water immediately after brushing one week after switching to a placebo dentifrice. In addition, the pain due to hypersensitivity was effectively reduced, and it was confirmed that the pain due to hypersensitivity was significantly reduced (Tables 33 and 34). It was also confirmed that the dentifrices of Examples 4-1 to 4-21 had a good feeling of use (taste).

  The dentifrice of Examples 4-16 to 4-21 containing the component (4-C) in addition to the component (A) and the component (4-B) is immediately after brushing one week after switching to a placebo dentifrice. Even when rinsing with water, the pain due to hypersensitivity is hardly felt or not felt at all, and by containing the component (4-C), the effect of the component (A) is further enhanced. It was confirmed that the remarkable alleviation effect on pain due to hypersensitivity was further increased (contrast between Example 4-11 and Examples 4-16 to 4-19, and Examples 4-2 and 4-20, 4). (Contrast with -21).

  Below, the three types of formulation examples of the composition for oral cavity which concern on this invention are shown. Also in such a prescription example, the remarkable relief effect with respect to the pain by the hypersensitivity similar to the composition for oral cavity of the above-mentioned Example and a favorable usability (taste) are obtained.

Examples 5-1 to 5-14 and comparative examples 5-1 to 5-5 (dentifrice)
Dentifrices having the compositions shown in Tables 39 to 41 were prepared. That is, A phase was prepared by mixing and dissolving water-soluble components (component (A), component (5-B), sodium fluoride, sodium saccharin, sorbitol, etc.) in purified water at room temperature. On the other hand, a B phase was prepared by dissolving or dispersing an oil-soluble component such as methylparaben, sodium polyacrylate, sodium alginate and the like in propylene glycol at room temperature. Next, B phase was added and mixed in A phase under stirring, and C phase was prepared. In the C phase, fragrance, anhydrous silicic acid and other components (sodium lauryl sulfate, etc.) were mixed at room temperature using a 1.5 L kneader, depressurized to 4 kPa and defoamed to prepare each composition. In addition, the unit of the compounding quantity of each component in Tables 39-41 is mass%.

[Main ingredients used]
[(A) component]
(1) Pyrrolidone carboxylic acid:
Product name “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc.
(2) 6-oxo-2-piperidinecarboxylic acid:
Product name “(S) -6-Oxo-2-piperidine carboxylic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
(3) 3- (2-Oxo-1-azepanyl) propanoic acid (ε-lactam compound):
Product name “3- (2-Oxozepan-1-yl) propanoic acid” manufactured by Sigma Aldrich Japan Co., Ltd.

[Comparative product of component (A)]
(4) Polyvinylpyrrolidone:
Product name “Polyvinylpyrrolidone K25” manufactured by Wako Pure Chemical Industries, Ltd.
(5) Proline:
Wako Pure Chemical Industries, Ltd., trade name "DL-proline"

[(5-B) component]
(6) Hydroxyethylcellulose dimethyl diallylammonium chloride:
Product name “Selcoat L-200”, manufactured by Nippon NSC Co., Ltd.
(7) O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose chloride:
Product name “Leoguard GP” (low viscosity product), manufactured by Lion Corporation
(8) O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose chloride:
Product name “Poise C-150L” (high viscosity product), manufactured by Kao Chemical Co., Ltd.

[Comparison of (5-B) component]
(9) Cationized guar gum:
Product name "JAGUAR C-13S" manufactured by Rhodia

[Other ingredients]
(10) Sodium fluoride:
Product name "Sodium fluoride" manufactured by Stella Chemifa

  The dentifrice of each Example and the comparative example was used for the following Experimental examples 5-1 to 5-4.

Experimental Example 5-1. 1. Evaluation of stain formation inhibitory effect Preparation of green tea extract The green tea extract was prepared by the extraction method described in Food ingredient analysis. That is, a tea pack containing 3 g of green tea leaves (a farmer's own tea 980, manufactured by ITO EN) was added to 100 mL of tap water at about 90 ° C., and extracted for 2 minutes.

2. Evaluation of Stain Formation Inhibition Effect Using Hydroxyapatite (HA) Disc The spectroscopic measurement of the initial HA color difference of a HA disc (APP-735; manufactured by Pentax Co., Ltd.) whose surface to be tested was polished with # 1,500 sandpaper It was measured with a color meter (CM2022, manufactured by Konica Minolta, Inc.). Next, 6 HA disks were attached to the mouthpiece and fixed to the lower lingual side of 11 volunteers. The fixing time was 1 hour, and after stirring and washing in distilled water, it was immersed in the green tea extract for 5 minutes. After repeating this intraoral fixation and dipping in green tea extract three times, the dentifrice of each example was diluted 3 times with distilled water, and the centrifugal supernatant (room temperature, 20 minutes, 10,000 rotations) was diluted. These HA discs were immersed for 5 minutes. Thereafter, it was rinsed lightly with distilled water, and excess water was blotted with a filter paper. The reason why the three-fold diluted solution is used is that it is assumed that the dentifrice is diluted with saliva during brushing. The reason for rinsing with distilled water is that a mouthwash after using the dentifrice was assumed. This intraoral fixation, immersion in a green tea extract, and immersion in a treatment solution were performed twice a day, and were immersed in physiological saline for other times. This operation was repeated for 14 days, the color difference of HA was measured with a spectrocolorimeter, and the degree of coloring was evaluated based on the b ^* value of the L ^* a ^* b ^* color system. The Δb ^* value was calculated by the following equation (5-0).

Formula (5-0):
(Δb ^* value) = b ^* value after treatment for 14 days−initial b ^* value

[Evaluation criteria for stain formation inhibitory effect]
A series of experimental operations were performed at N = 3 for each example and comparative example, the average value of each Δb ^* value was calculated, and the stain formation inhibitory effect was evaluated according to the following evaluation criteria.
A: Δb ^* value is less than 0.5 B: Δb ^* value is 0.5 or more and less than 3.0 C: Δb ^* value is 3.0 or more and less than 6.0 D: Δb ^* value is less than 6.0

Experimental example 5-2. Evaluation of stain removal effect Preparation of Concentrated Black Tea Extract Liquid tea tea bags (Nitto Tea Daily Club, manufactured by Mitsui Norin Co., Ltd.) were poured into boiling 200 mL distilled water and extracted for 10 minutes. Thereafter, the extract was filtered with a filter paper (No. 5C, manufactured by Advantech Toyo Co., Ltd.) to obtain a concentrated black tea extract.

2. Preparation of model stain After the surface of HA (Hydroxyapatite) disk (APP-735; manufactured by HOYA Co., Ltd.) was roughed by sandblasting, the HA disk was added to a 0.5% by weight albumin solution for 20 minutes. A model stain was prepared by repeating 20 times in the prepared concentrated black tea extract for 20 minutes and 20 minutes in a 0.3 mass% ferric chloride solution for 20 minutes in total.

3. Model stain removal test First, as a reference value, the chromaticity of the HA disk before model stain formation was measured with a spectrocolorimeter (CM2022, manufactured by Konica Minolta Co., Ltd.), and the L ^* a ^* b ^* table as in Experiment 1 was used. The L ^* value of the color system was measured and set to L ^* 0. Next, the chromaticity of the model stain prepared as described above was measured as chromaticity before cleaning (L ^* 1).

For this HA disk on which model stain is formed, 1 mL of a solution obtained by diluting the dentifrice of each example with distilled water three times is soaked in the head of a toothbrush (4 rows of Clinica brushes, manufactured by Lion Corporation) for 3 minutes. Swept. After wiping, the HA disk was lightly rinsed with distilled water, and excess water was blotted with a filter paper. After drying the HA disk, the chromaticity (L ^* 2) after the cleaning was measured. From these measured values, the stain removal rate was determined by the following equation (5-1).

[Evaluation criteria for stain removal effect]
A series of experimental operations were performed at N = 3 for each example and comparative example, the average value of the stain removal rates was calculated, and the stain removal effect was evaluated according to the following evaluation criteria.
A: Stain removal rate is 80% or more B: Stain removal rate is 60% or more and less than 80% C: Stain removal rate is 30% or more and less than 60% D: Stain removal rate is less than 30%

Experimental Example 5-3. Evaluation of Glossy Effect The toothpaste of each example was diluted 3 times with distilled water on a HA disk (APP-735; manufactured by Pentax Co., Ltd.) whose surface to be tested was polished with # 3,500 sandpaper, and its supernatant was centrifuged. These HA disks were immersed in the liquid (room temperature, 20 minutes, 10,000 rotations) for 5 minutes. Thereafter, it was rinsed lightly with distilled water, and excess water was blotted with a filter paper. Next, it was immersed at 37 ° C. in artificial saliva (CaCl ₂ : 1.0 mmol / L, KH ₂ PO ₄ : 3.0 mmol / L, acetic acid: 100 mmol / L, NaCl: 100 mmol / L, pH 6.5). This operation was performed 3 times a day for a total of 3 days.

[Evaluation criteria for gloss effect]
Three days later, the HA disk was taken out, rinsed well with distilled water, and then naturally dried, and the gloss effect was evaluated by five persons based on the following criteria of the evaluator. The experiment was performed with N = 3 in each of the examples and comparative examples. Finally, the average value of the evaluator's score was calculated, and the gloss effect was evaluated based on the following average value standard.
(Evaluator's score standard)
3: The entire surface is glossy 2: Part is glossy 1: Part is glossy 0: No gloss (no change)

(Evaluator's average score standard)
A: 2.5 points or more B: 1.6 points or more and less than 2.5 points C: 0.5 points or more and less than 1.6 points D: Less than 0.5 points

Experimental Example 5-4. Evaluation of the feeling of use of the preparations The treatment liquid obtained by diluting each dentifrice 3 times with distilled water was included in the mouth by five panelists for 30 seconds.

[Evaluation criteria for drug use feeling]
The use feeling of the preparation after using the treatment liquid was evaluated based on the following criteria. Finally, the average value of five people was calculated, and the usability of the preparation was evaluated based on the following average value criteria.

(Evaluator's score standard)
3: It is a good feeling of use. 2: Feels slightly bitter and unpleasant 1: Feels bitter and unpleasant 0: Feels strong bitter and unpleasant

A: 2.5 points or more B: 1.6 points or more and less than 2.5 points C: 0.5 points or more and less than 1.6 points D: Less than 0.5 points

  The composition of Example 5-14 containing the component (A) was excellent in the stain removal effect and the feeling of use of the preparation (Table 41). The compositions of Examples 5-1 to 5-13 containing the component (A) and the component (5-B) were excellent in balance with respect to the stain formation suppressing effect, the stain removing effect, the gloss effect, and the feeling of use of the preparation (Table). 39 and 40). On the other hand, none of the compositions of Comparative Examples lacking the component (B) satisfied all the four effects (Table 41). As a result, the composition for oral cavity of the present invention contains a component (A) and a component (5-B), and is excellent in a stain formation suppressing effect, a stain removing effect, a gloss effect and a feeling of use of the preparation. It is shown that.

Examples 5-15 to 5-17 (mouth wash)
Examples of mouthwash are shown below.

  A specified amount of purified water is put into a stainless steel container equipped with a three-one motor and a stirrer having rotating blades, and water components such as (A) component, (5-B) component, and sorbitol among the blended components of each example. The sex component was added and dissolved while stirring. On the other hand, in a separate stainless steel container equipped with a three-one motor and a stirrer with rotating blades, a specified amount of organic solvent such as ethanol is added and oil-soluble components such as fragrance and methylparaben are added while stirring. , Dissolved. Further, the oil-soluble component was added to the container in which the water-soluble component was dissolved, and the mixture was stirred for 30 minutes to prepare a mouthwash as a uniform solution.

Examples 6-1 to 6-14 and Comparative Examples 6-1 to 6-2
A dentifrice was prepared in the same manner as in Example 5-1, except that the composition was changed to the compositions shown in Tables 45 and 46. Dentin collagen coloring inhibition evaluation of each dentifrice was performed under the following conditions.

[Evaluation of inhibition of dentin collagen coloration]
The bovine tooth root was cut into blocks and the cementum was removed by surface polishing. About 3.5 mm × 3.5 mm of the part from which the cementum was removed was used for the decalcification window, and the other part was coated with nail polish. After drying the nail polish at room temperature, a root caries sample was prepared by dipping in a 0.1 mol / L acetic acid aqueous solution (pH 4.5) for 72 hours to expose the collagen in the window portion. First, color differences (L ^* 0, a ^* 0, b ^* 0) were measured as initial values. Next, this sample was immersed in a 3-fold water dilution of the composition of each Example and Comparative Example for 3 minutes at room temperature, washed with distilled water, and then at 37 ° C. artificial saliva (CaCl ₂ : 2.2 mmol / L). KH ₂ PO ₄ : 2.2 mmol / L, acetic acid: 0.1 mol / L, collagenase derived from Clostridium histolyticum (Type 1A, manufactured by Sigma): 0.2 unit / mL, pH 6.5) was immersed for 5 hours. . Thereafter, the immersion for 20 minutes in 0.2% bovine serum albumin at 37 ° C. and the immersion for 20 minutes in the coloring liquid (1) or (2) at 37 ° C. were repeated five times. After the experiment was completed, color difference (L ^* 1, a ^* 1, b ^* 1) measurement was performed at n = 3, and an average value was calculated. The color difference is measured using a spectrocolorimeter (manufactured by Konica Minolta Co., Ltd., CM-2022), and the coloring suppression effect is evaluated based on the following evaluation criteria from the ΔE value calculated from the following formula (6-1). did. These results are shown in Tables 45-46.

Formula (6-1):
ΔE value = ((L ^* 1-L ^* 0) ₂ + (a ^* 1-a ^* 0) ₂ + (b ^* 1-b ^* 0) ² ) ^1/2

[Coloring liquid]
Colored liquid (1): 0.3% instant black tea (Kroger (registered trademark) Instant Tea) aqueous solution Colored liquid (2): 1.5% instant coffee (NESCAFE Excella: Nestle Japan Co., Ltd.) aqueous solution

[Evaluation criteria]
A: 0 ≦ ΔE <2.0
B: 2.0 ≦ ΔE <4.0
C: 4.0 ≦ ΔE <6.0
D: 6.0 ≦ ΔE <8.0

  In the compositions of Comparative Examples 6-1 to 6-2 not containing the component (A), the dentin collagen coloring effect was not seen, whereas in the examples 6-1 to 6-14 containing the component (A) The composition was excellent in dentin collagen coloring suppression effect. This result has shown that (A) component is useful as an active ingredient of a dentin collagen coloring inhibitor. Moreover, this result has suggested that the composition for oral cavity (6) can exhibit a collagen coloring inhibitory effect.

Claims (12)

Component (A): at least one lactam compound selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid and salts thereof, and (2-B) component: An oral composition containing at least one polyphenol compound selected from the group consisting of longan seed extract, proanthocyanidins, catechins and hesperidins. The composition for oral cavity according to claim 1 , wherein the content of the component (A) is 0.5 to 10% by mass. The composition for oral cavity according to claim 1 or 2 , wherein the content of the component (2-B) is 0.001 to 0.5% by mass. The composition for oral cavity according to any one of claims 1 to 3 , wherein the mass ratio ((A) / (2-B)) of the component (A) to the component (2-B) is 5 to 3000. (A) Component is pyrrolidone carboxylic acid and / or its salt, The composition for oral cavity of any one of Claims 1-4 . (1-B) component: The composition for oral cavity of any one of Claims 1-5 which further contains a fluorine compound. The composition for oral cavity according to claim 6 , wherein the component (1-B) is sodium fluoride. The composition for oral cavity according to any one of claims 1 to 7 , comprising 20 to 95% by mass of water and / or 1 to 20% by mass of a lower alcohol. The composition for oral cavity according to any one of claims 1 to 8 , wherein the dosage form is a dentifrice, a mouthwash, an oral application agent, an oral pasta, or a food form.   (A) Component: Effective at least one lactam compound selected from the group consisting of pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid and salts thereof Dentin collagen coloring inhibitor as an ingredient. Component (A): at least one lactam compound selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid and salts thereof, and (2 -B) ingredients: longan seed extract, proanthocyanidins, catechin, and dentin collagen degradation inhibitor comprising as an active ingredient, at least one polyphenol compound selected from Hesuperiji down or Ranaru group. The agent according to claim 10 or 11 , wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.