JP2018020995A - Gingiva care agent and gingiva care oral composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide methods which enhance the gingiva by strengthening intercellular adhesion to inhibit gingival regression or form a periodontal pocket.SOLUTION: A composition containing ε-aminocaproic acid or a pharmaceutically acceptable salt thereof is used as a gingiva care agent (intercellular adhesion factor expression enhancer, gingival recession inhibitor, periodontal pocket formation inhibitor, gingiva enhancer), or as a gingiva care oral composition.SELECTED DRAWING: None

Description

  The present invention relates to a gingival care agent that acts on the gingiva and exhibits the desired effect, and a gingival care oral composition containing the same. Specifically, the present invention reinforces a gingival care agent (an intercellular adhesion factor expression enhancer) used for enhancing the expression of an intercellular adhesion factor involved in adhesion between gingival cells, or strengthens the gingiva. The present invention relates to a gingival care agent (gingival strengthening agent) used for the purpose, and an oral composition for gingival care containing the same.

  When gingiva is exposed to physical stimuli (mechanical stress) such as strong brushing or pressure from dentures, and chemical stimuli such as endotoxin of periodontal pathogens, tissue destruction proceeds by inflammatory mediators and inflammatory cytokines. It is known that the inter-barrier function is reduced and diseases such as gingival retraction, denture stomatitis, or alveolar pyorrhea occur (see, for example, Non-Patent Documents 1 to 5). In particular, the onset of periodontal disease is thought to start by weakening of cell-cell adhesion of the gingival epithelium. E-cadherin is expressed in the gingival epithelium as an intercellular adhesion factor, and is thought to be deeply involved in maintaining the function of the gingival epithelium (function to firmly adhere cells to cells). Is said to be caused by decreased expression of the intercellular adhesion factor (protein) and decreased function of the intercellular adhesion device. The formation of periodontal pockets, which are closely related to the development of periodontal disease, does not start with the removal of the gingival epithelium from the tooth surface, but instead of the formation of gaps between cells of the gingival epithelium due to cell-cell adhesion failure. Invasion occurs, and further, tissue destruction occurs due to enzymes secreted by inflammatory cells, and the disease progresses to periodontal disease (Non-patent Document 5).

  Conventionally, as a method of reducing physical irritation to the gingiva, a toothbrush (Patent Document 1) in which the shape of the hair tip is devised to reduce gingival damage, and soft elasticity is developed to reduce the burden on the gums. An effective denture stabilizer (Patent Document 2) has been proposed. In recent research, it is said that it is important to make gingiva strong against physical and chemical stimulation, and in order to keep the intercellular adhesion device (desmosome, tight junction) that is the physical barrier of gingiva normal. As a method for this, it has been proposed to use irsogladine maleic acid, which is a gastric mucosa protective component (Non-patent Document 5).

  By the way, it is known that anti-plasmin agents such as ε-aminocaproic acid and tranexamic acid can suppress inflammation and bleeding in the oral cavity by antagonizing plasmin that inhibits blood coagulation, and anti-plasmin agent was added. Oral compositions have also been reported (Patent Document 3).

  However, it is not known that these components have an action of enhancing gene expression of intercellular adhesion factor of gingival epithelium and strengthening cell-cell adhesion.

JP 2001-353026 A JP 2011-63538 A JP 2002-20250 A

Asahi Tominaga et al., "Analysis of inflammatory mediators expressed in gingival epithelial cells with mechanical stress", Journal of Japan Prosthodontic Society 52 (3): 439-439, 2008 Akihiro Tominaga et al., “Inflammatory response in gingival epithelial cells loaded with mechanical stress”, Journal of Oral Biosciences 50 (suppl): 126-126, 2008 Asahi Tominaga et al., "Inhibition of inflammation by hyaluronic acid in gingival epithelial cells loaded with mechanical stress", Kyushu Dental Society Journal 63 (5/6): 292, 2010 Mitsunobu Sumita, "Inflammation of the submucosal mucosa", Journal of Japanese Prosthodontic Society 5 (2): 189-192, 1961 Tsuyoshi Fujita, Journal of Japanese Periodontal 55 (4): 287-293, 2013

  An object of the present invention is to provide a method of strengthening gingiva by strengthening cell-cell adhesion, suppressing gingival retraction, and suppressing formation of periodontal pockets. More specifically, it is intended to provide a gingival care agent, specifically, an intercellular adhesion factor expression enhancer and a gingival strengthening agent for making the gingiva resistant to stimulation by enhancing the expression level of the intercellular adhesion factor. Is an issue.

  As a result of intensive studies to solve the above problems, the present inventors have found that ε-aminocaproic acid or a pharmaceutically acceptable salt thereof enhances the gene expression level of the intercellular adhesion factor of gingiva. From these findings, according to these components, the gingiva can be made strong against physical or chemical stimulation, and gingival retraction can be suppressed and the formation of periodontal pockets can be suppressed.

The present invention has been completed based on this finding, and includes the following embodiments.
(I) Gingival care agent (I-1) A gingival care agent comprising ε-aminocaproic acid or a pharmaceutically acceptable salt thereof.
(I-2) The gingival care agent according to (I-1), wherein the gingival care agent is an intercellular adhesion factor expression enhancer.
(I-3) The gingival care agent described in (I-1), wherein the gingival care agent is a gingival strengthening agent.
(I-4) The gingival care agent described in (I-3), wherein the gingival strengthening effect of the gingival care agent is due to an effect of enhancing gene expression of an intercellular adhesion factor.
(I-5) The gingival care agent described in (I-2) or (I-4), wherein the intercellular adhesion factor is E-cadherin.

(II) Oral composition for gingival care comprising the gingival care agent described in any one of (II-1) (I-1) to (I-5).

(III) Gingival care method (III-1 ) A gingival care method comprising a step of treating the oral cavity of a subject using an oral composition containing ε-aminocaproic acid or a pharmaceutically acceptable salt thereof.
(III-2) The method described in (III-1), wherein the gingival care method is a gingival strengthening method for a subject's gingiva.
(III-3) The method according to (III-1), wherein the gingival care method is a gingival retraction suppression method or periodontal pocket formation suppression method for a subject's gingiva.

  The oral cavity composition for gingival care containing the gingival care agent of the present invention can enhance the gene expression of the intercellular adhesion factor of the gingival epithelium by treating the oral cavity, and as a result, cell indirect of the gingival epithelium. By strengthening the wear, the gums can be strengthened, and gingival retraction can be suppressed, and the formation of periodontal pockets can be suppressed.

(I) Gingival care agent The gingival care agent of the present invention comprises ε-aminocaproic acid or a pharmaceutically acceptable salt thereof.

Hereinafter, the component contained in the gingival care agent of this invention and a gingival care agent are demonstrated.
(A) ε-aminocaproic acid or a pharmaceutically acceptable salt thereof ε-aminocaproic acid or a pharmaceutically acceptable salt thereof has an antiplasmin effect, a hemostatic effect, and an anti-inflammatory effect, and is useful for cosmetics and pharmaceuticals. Widely used. The pharmaceutically acceptable salt of ε-aminocaproic acid is not particularly limited as long as it is pharmaceutically acceptable. Specifically, alkali metal salts such as sodium salt and potassium salt; calcium salt, magnesium salt and the like Alkaline earth metal salts; inorganic acid salts such as hydrochlorides and sulfates. These salts of ε-aminocaproic acid may be used alone or in combination of two or more.

  In the gingival care agent of the present invention, either one of ε-aminocaproic acid or a salt thereof may be used alone, or a combination thereof may be used. Ε-aminocaproic acid is preferred. These ε-aminocaproic acid or a pharmaceutically acceptable salt thereof can be obtained commercially as a cosmetic or pharmaceutical raw material. It can be obtained. The compounding quantity of the said (epsilon) -aminocaproic acid or its pharmaceutically acceptable salt in the gingival care agent of this invention can mention the range of 0.001-1 mass% in 100 mass% of gingival care agents. Preferably it is 0.005-0.5 mass%, More preferably, it is 0.01-0.2 mass%.

(B) Other component and its form The gingival care agent of this invention is mix | blended and used as an active ingredient which has a pharmacological action (gingival care action) in the composition for oral cavity so that it may mention later. The gingival care agent of the present invention may be composed of the above-mentioned ε-aminocaproic acid or a pharmaceutically acceptable salt thereof. It may contain other components. Such other ingredients include one or more additives well known in the art (eg, excipients, diluents, thickeners, buffers, preservatives, surfactants, surfactants). , Binders, dispersants, disintegrants, solvents). In addition, antioxidants, stabilizers, emulsifiers, preservatives, coloring agents, sweetening agents, and flavoring agents can be blended.

  The gingival care agent of this invention can mix | blend the component for preparing it according to the formulation form in the said technical field. Examples of the gingival care agent include liquid, gel, cream (paste), powder (powder), granule, tablet, film, sheet and the like without limitation.

(C) Effect and Use of Gingival Care Agent The gingival care agent of the present invention has the effect of enhancing the gene expression of E-cadherin, which is an intercellular adhesion factor of gingival epithelium, as shown in the experimental examples described later.

  Therefore, the gingival care agent of the present invention can be effectively used as a preparation for enhancing the expression of intercellular adhesion factor of gingival epithelium (intercellular adhesion factor expression enhancer). Moreover, the gingival care agent of this invention can be used effectively as a formulation (cell adhesion enhancer) for strengthening the cell adhesion of the gingival epithelium by the cell adhesion factor expression enhancer.

  In addition, the gingival care agent of the present invention can be effectively used to suppress gingival retraction (gum thinning) caused by cell-cell adhesion failure by enhancing intercellular adhesion and strengthening gingiva.

  Furthermore, the gingival care agent of this invention can be effectively used in order to suppress the formation of the periodontal pocket which arises by cell-cell adhesion failure by strengthening cell adhesion and strengthening gingiva.

  That is, the gingival care agent of the present invention can be used effectively as a gingival strengthening agent because it can comprehensively strengthen the gingiva by enhancing cell-cell adhesion.

  These various gingival care agents (intercellular adhesion factor expression enhancer, gingival regression inhibitor, periodontal pocket formation inhibitor, gingival strengthening agent) are added to the oral composition to form an oral composition for gingival care. The effect can be exhibited by applying it in the oral cavity. For this reason, the gingival care agent of the present invention is used by being added to various oral compositions.

  Such oral compositions include dentifrices (including powder, liquid, cream, and paste preparations), mouthwashes (including liquid and foam preparations), ointments, pasta, gingiva Examples include creams, gingival gels, denture stabilizers, lozenges, chewing agents (including chewing gums, gummies, etc.), patches (films, packs) and the like. These oral compositions can be blended with various components used in the field according to each form, and are not limited as long as the effects of the present invention are not hindered. For example, in the case of dentifrices, abrasives, wetting agents, binders, foaming agents, surfactants, sweeteners, preservatives, fragrances, colorants, pH adjusters, etc. The medicinal component can be blended.

  As a blending ratio of the gingival care agent of the present invention when used by adding to and blended with these oral compositions, if the oral composition is 100% by mass, ε which is an active ingredient of the gingival care agent of the present invention -The proportion of aminocaproic acid or a pharmaceutically acceptable salt thereof is 0.001-1% by mass, preferably 0.005-0.5% by mass, more preferably 0.01-0.2% by mass. .

  Moreover, as a density | concentration of (epsilon) -aminocaproic acid or its pharmaceutically acceptable salt mix | blended with an oral composition, 75-75000micromol, Preferably it is 375-37500micromol, More preferably, 750-15000micromol can be mentioned.

(II) Oral composition for gingival care The present invention comprises the gingival care agent (intercellular adhesion factor expression enhancer, gingival regression inhibitor, periodontal pocket formation inhibitor, gingival enhancer) as an active ingredient. It is an oral composition for care. The oral composition can be effectively used for gingival care. Specifically, it can be used to suppress gingival retraction (gum thinness), to suppress periodontal pocket formation, or to strengthen the gingiva.

  As described above, the blending ratio of the gingival care agent to be added to the gingival care oral composition of the present invention is an active ingredient of the gingival care agent when the gingival care oral composition is 100% by mass. In terms of the proportion of ε-aminocaproic acid or a pharmaceutically acceptable salt thereof, it is usually 0.001 to 1% by mass, preferably 0.005 to 0.5% by mass, more preferably 0.01 to 0.2%. % By mass. The concentration of ε-aminocaproic acid or a pharmaceutically acceptable salt thereof contained in the oral cavity composition for gingival care of the present invention is 75 to 75000 μM, preferably 375 to 37500 μM, more preferably 750 to 15000 μM. Can do.

  The oral cavity composition for gingival care of the present invention includes a dentifrice (including powder, liquid, cream and paste preparations), a mouthwash (including liquid and foam preparations), and an ointment. , Pasta preparations, gingival creams, gingival gels, denture stabilizers, lozenges, chewing agents (including chewing gum, gummi, etc.), patches (films, packs) and the like. These oral cavity compositions for gingival care can be blended with various components used in the field according to each form, and are not limited as long as the effects of the present invention are not hindered. For example, in the case of a dentifrice, an abrasive, a wetting agent, a binder, a foaming agent, a thickener, a surfactant, a sweetener, a fragrance, a coloring agent, an antiseptic, and the like, as long as the effects of the present invention are not hindered. The medicinal component (for example, anti-inflammatory agent, etc.) can be blended.

  [Abrasive] Silica-based abrasives such as precipitated silica, silica gel, aluminosilicate, zirconosilicate, phosphorous such as dentifrice calcium hydrogen phosphate, dicalcium phosphate dihydrate, dicalcium phosphate dihydrate, calcium pyrophosphate Acid-based abrasives, aluminum hydroxide, alumina, titanium dioxide, crystalline zirconium silicate, polymethyl methacrylate, insoluble calcium metaphosphate, light calcium carbonate, heavy calcium carbonate, magnesium carbonate, tribasic magnesium phosphate, zeolite, silicic acid Zirconium, hydroxyapatite, fluoroapatite, calcium deficient apatite, tricalcium phosphate, quaternary calcium phosphate, eighth calcium phosphate, synthetic resin abrasive.

  [Humectant] Polyhydric alcohols such as glycerin, concentrated glycerin, diglycerin, sorbitol, maltitol, dipropylene glycol, propylene glycol, 1,3-butylene glycol and xylitol.

  [Binder] Cellulose binders such as sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxymethyl ethyl cellulose, methyl cellulose, xanthan gum, carrageenan, guar gum, sodium alginate, cationized cellulose, montmorillonite, gelatin, Sodium polyacrylate, etc.

  [Foaming agent] Sodium lauryl sulfate, sodium lauroyl sarcosine, sodium alkylsulfosuccinate, sodium coconut oil fatty acid monoglycerol sulfonate, sodium α-olefin sulfonate, N-acyl glutamate, N-acyl amino acid salts, 2-alkyl-N -Carboxymethyl-N-hydroxyethylimidazolinium betaine, maltitol fatty acid ester, sucrose fatty acid ester, polyglycerin fatty acid ester, fatty acid diethanolamide, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, polyoxyethylene Fatty acid esters, alkyl glycosides, etc.

  [Thickening agent] Glycerin, sorbit, propylene glycol, polyethylene glycol having a molecular weight of 200 to 6000, ethylene glycol, 1,3-butylene glycol, reduced starch saccharified product, and the like.

  [Surfactant] Anionic surfactants, nonionic surfactants, amphoteric surfactants, cationic surfactants and the like can be blended. Anionic surfactants include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosine such as sodium N-lauroyl sarcosine, sodium N-myristoyl sarcosine, sodium dodecylbenzenesulfonate, hydrogenated coconut fatty acid N-acyl glutamate such as sodium monoglyceride monosulfate, sodium lauryl sulfoacetate, sodium N-palmitoyl glutamate, sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acylalanine, sodium α-olefin sulfonate Is mentioned. Nonionic surfactants include, for example, polyoxyethylene hydrogenated castor oil, sucrose fatty acid ester, alkylol amide, polyoxyethylene sorbitan monostearate, polyoxyethylene polyoxypropylene glycol, alkyl glucoside, decaglyceryl laurate, etc. Used. Examples of amphoteric surfactants include lauryl dimethylaminoacetic acid betaine, N-coconut oil fatty acid acyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine, and coconut oil fatty acid amidopropyl. Betaine etc.

  [Sweeting agents] Sodium saccharin, aspartame, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perilartin, sucralose, xylitol, reduced palatinose, erythritol, maltitol and the like.

  [Perfume] Peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime Oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, absolute peppermint , Absolute rose, orange flower, and other natural fragrances, and fragrances and menthols processed by these natural fragrances (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder fragrance, etc.) , Carvone, anethole, cineol, methyl salicylate, Namic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-paramentane-3-carboxamide, pinene, octylaldehyde, Citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, propyl alcohol, butanol, isoamyl alcohol , Hexenol, dimethyl sulfide, cycloten, furfural, trimethylpyrazine, ethyl lactate, methyl lactate, ethylthioacetate Separately perfume, further, strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavors, blended fragrance such as tropical fruit flavors.

  [Colorant] Blue No. 1, Yellow No. 4, Green No. 3, etc.

  [Preservatives] Parabens such as methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate, phenoxyethanol, alkyldiaminoethylglycine hydrochloride and the like.

  [Medical ingredients] Fluorine compounds such as sodium fluoride, sodium monofluorophosphate and tin fluoride, water-soluble phosphate compounds such as potassium salt and sodium salt of orthophosphoric acid, sodium polyphosphate, tranexamic acid, allantoin, allantoinchlor Hydroxyaluminum, hinokitiol, ascorbic acid, dl-α-tocopherol acetate, dl-α-tocopherol nicotinate, pyridoxine hydrochloride, dihydrocholesterol, α-bisabolol, chlorhexidine salts, sodium azulene sulfonate, giazulene sulfonic acid, glycyrrhizic acid, Copper compounds such as dipotassium glycyrrhizinate, glycyrrhetin, glycyrrhetinic acid, copper gluconate, copper chlorophyllin sodium, aluminum lactate, strontium chloride, potassium nitrate, bell Phosphorus, hydroxamic acid and its derivatives, zeolite, methoxyethylene maleic anhydride copolymer, polyvinylpyrrolidone, polyethylene glycol, epidihydrocholesterin, cetylpyridinium chloride, benzethonium chloride, isopropylmethylphenol, sodium lauroylsarcosine, dihydrocholesterol, triclosan , Trichlorocarbanilide, zinc citrate, sugar beet extract, buckwheat extract, chamomile, clove, rosemary, hornon, safflower extract, lysozyme chloride, sodium chloride and the like.

  In addition, the compounding quantity of these arbitrary components can be made into the normal quantity used in this industry in the range which does not prevent the effect of this invention.

(III) Gingival Care Method The present invention relates to a method for caring for the gingiva of a subject. Here, gingival care is at least one of suppressing intercellular adhesion failure of the gingival epithelium of a subject, suppressing gingival retraction, suppressing periodontal pocket formation, or strengthening gingiva. It means to do one.

  This method can be performed by treating the oral cavity of a subject with an oral composition containing ε-aminocaproic acid or a pharmaceutically acceptable salt thereof.

  The oral composition used here is the above-described oral care composition for gingival care of the present invention, and the oral cavity of the subject can be treated by normal use according to the use of each oral composition. it can. For example, when the oral cavity composition for gingival care is a dentifrice, the gingival care method of the present invention can be carried out by brushing the subject's teeth using the oral cavity composition for gingival care. Moreover, when the oral cavity composition for gingival care is a mouthwash, the gingival care method of this invention can be implemented by wash | cleaning (rinsing) a test subject's oral cavity using the said oral cavity composition for gingival care. it can.

  The number of times of gingival care is not particularly limited, and can be carried out once to several times a day, preferably after meals and / or before and after going to bed.

  Hereinafter, the present invention will be described using experimental examples and examples. However, the present invention is not limited to these experimental examples.

Experimental Example 1 E-cadherin gene expression evaluation test (1) Test method A human gingival epithelial cell line OBA9 was cultured in HuMedia-KG2 medium (KURABO). Cells were seeded at a density of 3 × 10 ⁵ cells / well in a 6-well plate and cultured in an incubator at 37 ° C. and 5% CO ₂ until they became confluent. Thereafter, HuMedia-KG2 medium (excluding bovine pituitary extract BPE) (control), or HuMedia-KG2 medium (excluding bovine pituitary extract BPE) to which various test substances were added at the concentrations shown in Table 1. ) And cultured for 24 hours under the same conditions. As a control, an “no addition group” in which no test substance was added was used. The highest concentration that has been confirmed to be safe for each substance was adopted as the evaluation concentration.

  Total RNA was extracted from the cells using RNeasy mini kit (QIAGEN) according to the attached manual. The RNA concentration was calculated using BioPhotometer plus (Eppendorf).

  Using 500 ng of total RNA, reverse transcription reaction was performed using Super Script VILO Master Mix kit (Invitrogen) according to the attached manual.

  Real-time PCR was performed using StepOneplus real-time PCR System (Applied Biosystems). Specifically, using the Universal SYBR Select master mix (Life Technologies ABI) and the various primers shown in Table 2 (100 nM, Sigma-Aldrich), gene expression comparison by the Comparative CT (△△ CT) method with reference to the control Carried out. The expression level of GAPDH as an internal standard gene was quantified and standardized. From the obtained value, the E-cadherin gene expression enhancement rate (%) was calculated by the following formula.

  The results are shown in Table 3.

  As shown in Table 3, ε-aminocaproic acid can significantly enhance gene expression of intercellular adhesion factor (E-cadherin) compared to other compounds known to have anti-inflammatory and antibacterial effects. found. Irsogladine maleic acid (Non-Patent Document 5), which is considered to be useful for maintaining a normal cell-cell adhesion device (desmosome, tight junction) that is a physical barrier of gingiva, There was no effect of enhancing gene expression.

Formulation example
Formulation Example 1: Paste dentifrice The following ingredients are mixed, and a paste dentifrice is prepared according to a conventional method.

Formulation Example 2: Paste dentifrice The following ingredients are mixed, and a paste dentifrice is prepared according to a conventional method.

Formulation Example 3: Paste Dentifrice The following ingredients are mixed, and a paste dentifrice is prepared according to a conventional method.

Formulation Example 4: Liquid dentifrice The following ingredients are mixed, and a liquid dentifrice is prepared according to a conventional method.

Formulation Example 5: Mouthwash The following ingredients are mixed and a mouthwash is prepared according to a conventional method.

  SEQ ID NO: 1 is the base sequence of the sense strand of the primer used for the detection of the E cadherin gene, SEQ ID NO: 2 is the base sequence of the antisense strand of the primer used for the detection of the E cadherin gene, and SEQ ID NO: 3 is the detection of the GAPDH gene The base sequence of the sense strand of the primer used, SEQ ID NO: 4 shows the base sequence of the antisense strand of the primer used for detection of the GAPDH gene.

Claims (7)

  A gingival care agent comprising ε-aminocaproic acid or a pharmaceutically acceptable salt thereof.   The gingival care agent according to claim 1, wherein the gingival care agent is an agent for enhancing expression of an intercellular adhesion factor in the gingival epithelium.   The gingival care agent according to claim 1, wherein the gingival care agent is a gingival strengthening agent.   The gingival care agent according to claim 3, wherein the gingival strengthening effect of the gingival care agent is due to an effect of enhancing the expression of an intercellular adhesion factor in the gingival epithelium.   The gingival care agent according to claim 2 or 4, wherein the intercellular adhesion factor is E-cadherin.   The oral cavity composition for gingival care containing the gingival care agent in any one of Claims 1 thru | or 5.   A gingival care method comprising a step of treating the oral cavity of a subject using an oral composition containing ε-aminocaproic acid or a pharmaceutically acceptable salt thereof.