JP7412869B2 - Gum care agent and oral composition for gum care containing the same - Google Patents

Description

The present invention is intended to suppress gingival troubles caused by insufficient adhesion between cells in the gingival epithelium, such as gingival recession (thinning of the gums) and formation of periodontal pockets caused by excessive brushing and inflammation such as periodontitis and gingivitis. The present invention relates to a gingival care agent and an oral composition for gingival care containing the same. More specifically, the present invention provides an intercellular adhesion factor expression reduction inhibitor that suppresses the reduction in the expression of intercellular adhesion factors caused by inflammatory cytokines, and a gingival epithelial cell adhesion inhibitor that suppresses gingival epithelial cell-to-cell adhesion failure caused by inflammatory cytokines. Gingival care agents such as adhesion failure inhibitors, gingival recession inhibitors that inhibit gingival recession, periodontal pocket formation inhibitors that inhibit periodontal pocket formation, or gingival strengthening agents that strengthen gingiva, and gingiva containing the same. The present invention relates to a care oral composition.

When the gingiva is exposed to physical stimuli (mechanical stress), such as forceful brushing or pressure from dentures, and chemical stimuli, such as endotoxins from periodontal pathogens, inflammatory mediators and inflammatory cytokines (e.g., TNF-α) are released into the gingiva. etc.), tissue destruction progresses and the intercellular barrier function deteriorates, which is known to cause diseases such as gingival recession, denture stomatitis, and alveolar pyorrhea (for example, see Non-Patent Documents 1 to 6). . In particular, the onset of periodontal disease is thought to begin with weakening of intercellular adhesion in 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 (the function of firmly adhering cells to each other); It is said that this is caused by a decrease in the expression of the intercellular adhesion factor (protein) and a decrease in the function of the intercellular adhesion apparatus. The formation of periodontal pockets, which are closely related to the onset of periodontal disease, begins not with the peeling of the gingival epithelium from the tooth surface, but with the formation of gaps between the cells of the gingival epithelium due to poor intercellular adhesion, and then the formation of inflammatory cells. Infiltration occurs, and tissue destruction occurs due to enzymes secreted by inflammatory cells, which progresses to periodontal disease (Non-Patent Document 5).

Conventionally, methods for reducing physical irritation to the gums include toothbrushes whose bristles are shaped to be less harmful to the gums (Patent Document 1), and toothbrushes that exhibit soft elasticity to reduce the burden on the gums. An effective denture stabilizer (Patent Document 2) has been proposed. Recent research has shown that it is important to make the gingiva resistant to physical and chemical stimuli, and to maintain normal intercellular adhesion devices (desmosomes and tight junctions), which are the physical barrier of the gingiva. As a method for this, it has been proposed to utilize irsogladine maleic acid, which is a gastric mucosal protective component (Non-Patent Documents 5 to 6).

By the way, oral compositions include an oral composition containing copper chlorophyllin sodium as a bactericidal component (Patent Document 3), and an oral composition that prevents periodontal disease through the anti-inflammatory action of glycyrrhizinate (Patent Documents 4 to 4). 6), a pharmaceutical composition containing triclosan that modulates Toll-like receptors for the prevention of oral tissue inflammation (Patent Document 7) is known. However, these ingredients have the effect of suppressing the defective intercellular adhesion in the gingival epithelium, specifically, suppressing the decrease in the expression of intercellular adhesion factors caused by inflammatory cytokines, and the effect of suppressing the defective cell adhesion. Some things are not known.

Japanese Patent Application Publication No. 2001-353026 Japanese Patent Application Publication No. 2011-63538 Japanese Patent Application Publication No. 2002-302429 Japanese Patent Application Publication No. 2009-107988 Japanese Patent Application Publication No. 2011-073997 Japanese Patent Application Publication No. 2011-126818 Special Publication No. 2009-523029

Asahiro Hisanaga et al., “Analysis of inflammatory mediators expressed in gingival epithelial cells subjected to mechanical stress,” Journal of the Japanese Society of Prosthodontics 52(3): 439-439, 2008 Asahiro Hisanaga et al., “Inflammatory response in gingival epithelial cells subjected to mechanical stress,” Journal of Oral Biosciences 50(suppl): 126-126, 2008 Asahiro Hisunaga et al., “Inflammation suppressing effect of hyaluronic acid on gingival epithelial cells subjected to mechanical stress,” Kyushu Dental Society Journal 63(5/6): 292-292, 2010 Mitsunobu Sumita et al., "Inflammation of the mucosa under the denture base", Journal of the Japanese Society of Prosthodontics 5(2): 189-192, 1961 Tsuyoshi Fujita, Japanese Journal of Periodontology 55(4): 287-293, 2013 Fujita T et al., Journal of Periodontal Research 47(1): 55-61, 2012

The present invention strengthens the gingiva by suppressing cell-to-cell adhesion failure due to decreased expression of cell-to-cell adhesion factors caused by inflammatory cytokines caused by physical and chemical stimulation, suppresses gingival recession, and prevents periodontal pockets. The objective is to provide a method for suppressing the formation of. More specifically, the present invention provides a gingival care agent for implementing the method, specifically an intercellular adhesion factor expression reduction inhibitor that suppresses the reduction in the expression of intercellular adhesion factors caused by inflammatory cytokines, and an inflammatory cytokine. A gingival epithelial cell-to-cell adhesion inhibitor that suppresses gingival epithelial cell-to-cell adhesion failure caused by gingival epithelium, a gingival recession inhibitor that suppresses gingival recession, a periodontal pocket formation inhibitor that suppresses periodontal pocket formation, or a gingival strengthening agent. An object of the present invention is to provide a gingival care agent such as a gingival strengthening agent, and an oral composition for gingival care containing the same.

The present inventors conducted intensive research to solve the above problem and found that glycyrrhizic acid or its salt, sodium copper chlorophyllin, and triclosan all normalize the intercellular adhesion apparatus of the gingival epithelium under the action of inflammatory cytokines. They found that this is due to suppressing the decrease in gene expression of intercellular adhesion factors in the gingival epithelium caused by inflammatory cytokines. Based on this knowledge, it is considered that each of these components can suppress the cell-to-cell adhesion failure in the gingival epithelium caused by the action of inflammatory cytokines, and suppress the recession of the gingiva and the formation of periodontal pockets. That is, according to each of the above-mentioned components, it is possible to strengthen the gums against physical or chemical stimulation (strengthening of the gums).

The present invention was completed based on these findings, and includes the following embodiments.

(I) Gum care agent (I-1) A gingival care agent containing at least one member selected from the group consisting of glycyrrhizic acid or a pharmaceutically acceptable salt thereof, sodium copper chlorophyllin, and triclosan.
(I-2) The gingival care agent according to (I-1), wherein the gingival care agent is an inhibitor of decrease in expression of intercellular adhesion factor.
(I-3) The gingival care agent is at least one selected from the group consisting of a gingival epithelial intercellular adhesion defect inhibitor, a gingival recession inhibitor, a periodontal pocket formation inhibitor, and a gingival strengthening agent (I -1) The gum care agent described in 1).
(I-4) The gingival care agent's effect of suppressing intercellular adhesion deficiency in the gingival epithelium, gingival recession suppressing effect, periodontal pocket formation suppressing effect, or gingival strengthening effect suppresses the decrease in the expression of intercellular adhesion factors in the gingival epithelium. The gingival care agent described in (I-3), which is due to the action.
(I-5) The gingival care agent according to (I-2) or (I-4), wherein the intercellular adhesion factor is E-cadherin.

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

(III) Gum care method (III-1) Using an oral composition containing at least one member selected from the group consisting of glycyrrhizic acid or its pharmaceutically acceptable salt, copper chlorophyllin sodium, and triclosan, A gum care method that includes a process of treating the inside of the oral cavity.
(III-2) The gingival care method is a method of suppressing intercellular adhesion failure of the gingival epithelium of the subject, a method of suppressing gingival recession, a method of suppressing periodontal pocket formation, or a method of strengthening the gingiva, The method described in (III-1).

By treating the oral cavity with an oral composition for gingival care containing the gingival care agent of the present invention, it is possible to suppress cell-to-cell adhesion failure caused by inflammatory cytokines caused by physical or chemical stimulation. As a result, it is possible to strengthen the gingiva, suppress gingival recession, and suppress the formation of periodontal pockets.

(I) Gum Care Agent The gingival care agent of the present invention is characterized by containing at least one member selected from the group consisting of glycyrrhizic acid or a pharmaceutically acceptable salt thereof, sodium copper chlorophyllin, and triclosan.

Hereinafter, the components contained in the gum care agent of the present invention and the gum care agent will be explained.

(A) Glycyrrhizic acid or its pharmaceutically acceptable salt Glycyrrhizic acid or its salt is a component extracted from plant materials such as licorice roots and stems of legumes, and has been traditionally used as an anti-inflammatory agent due to its anti-inflammatory properties. It is used as.

Pharmaceutically acceptable salts of glycyrrhizic acid include dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, monoammonium glycyrrhizinate, and diammonium glycyrrhizinate. Among these, it is preferable to use dipotassium glycyrrhizinate as an oral composition such as the gum care agent of the present invention. In addition, these glycyrrhizinic acid and its salt may be used individually by 1 type, and can also be used in arbitrary combinations of 2 or more types. Glycyrrhizic acid and its salts can be obtained commercially as raw materials for cosmetics or pharmaceuticals; for example, dipotassium glycyrrhizinate can be obtained from Alps Yakuhin Kogyo Co., Ltd., Maruzen Pharmaceutical Co., Ltd., etc.

The blending amount of the component (A) in the gum care agent of the present invention can range from 0.001 to 1% by mass based on 100% by mass of the gum care agent. It is preferably 0.01 to 0.5% by weight, more preferably 0.05 to 0.4% by weight.

(B) Copper chlorophyllin sodium Copper chlorophyllin sodium is a component widely used as a bactericidal agent in cosmetics and pharmaceuticals due to its bactericidal action. The component can be obtained commercially as a raw material for cosmetics or pharmaceuticals, for example, from Eisai Food Chemical Co., Ltd., Tama Biochemical Co., Ltd., etc.

The blending amount of the component (B) in the gum care agent of the present invention can range from 0.001 to 1% by mass based on 100% by mass of the gum care agent. It is preferably 0.005 to 0.5% by weight, more preferably 0.05 to 0.15% by weight.

(C) Triclosan Triclosan is a component widely used as a disinfectant in cosmetics and pharmaceuticals due to its bactericidal action. The component can be obtained commercially as a raw material for cosmetics or pharmaceuticals, for example from BASF Japan Co., Ltd. and the like.

The blending amount of the component (C) in the gingival care agent of the present invention can be in the range of 0.001 to 1% by mass based on 100% by mass of the gingival care agent. It is preferably 0.01 to 0.3% by weight, more preferably 0.02 to 0.1% by weight.

The gum care agent of the present invention may contain at least one of the above-mentioned components (A) to (C), or two or more of these components, as long as it exhibits the effects of the present invention. They can also be blended in any combination. Examples include combinations of components (A) and (B), combinations of components (A) and (C), combinations of components (B) and (C), and combinations of components (A) to (C). be able to.

(D) Other components and their forms The gingival care agent of the present invention is used by being blended into an oral composition as an active ingredient having pharmacological action (gingival care action), as described below. The gingival care agent of the present invention may be composed of at least one of the components (A) to (C), or may have the effects of the present invention in addition to the components (A) to (C). It may optionally contain other components as long as they do not interfere with the above. Such other ingredients may include one or more additives well known in the art, such as excipients, diluents, thickeners, buffers, preservatives, surfactants, surfactants, etc. , binders, dispersants, disintegrants, solvents) may be mentioned without limitation. In addition, antioxidants, stabilizers, emulsifiers, preservatives, colorants, sweeteners, and flavoring agents can also be blended.

The ingredients for preparing the gum care agent of the present invention can be blended according to the formulation form known in the art. Examples of the form of the gingival care agent include, without limitation, liquid, gel, cream (paste), powder (powder), granule, tablet, film, sheet, and the like.

(E) Effects and uses of the gingival care agent The gingival care agent of the present invention reduces gene expression of E-cadherin, an intercellular adhesion factor of the gingival epithelium, due to the action of inflammatory cytokines, as shown in the experimental examples described below. It has the effect of suppressing

Therefore, the gingival care agent of the present invention can be effectively used as a preparation for suppressing a decrease in intercellular adhesion factors in the gingival epithelium (an agent for suppressing decrease in intercellular adhesion factor expression). Furthermore, the gingival care agent of the present invention can be effectively used as a preparation (an agent for suppressing intercellular adhesion deficiency) for suppressing intercellular adhesion deficiency in the gingival epithelium caused by decreased expression of intercellular adhesion factors.

Furthermore, the gingival care agent of the present invention can prevent or suppress gingival recession caused by defective cell-to-cell adhesion due to the action of inflammatory cytokines by inhibiting defective cell-to-cell adhesion; therefore, it can be used as a gingival recession inhibitor. It can be used effectively.

Furthermore, the gingival care agent of the present invention can prevent or suppress the formation of periodontal pockets caused by defective cell-to-cell adhesion caused by inflammatory cytokines by suppressing the defective cell-to-cell adhesion, thereby inhibiting periodontal pocket formation. It can be effectively used as an agent.

Furthermore, the gingival care agent of the present invention can comprehensively strengthen the gingiva by suppressing cell-to-cell adhesion failure, and therefore can be effectively used as a gingival strengthening agent.

These various gingival care agents (intercellular adhesion factor expression reduction inhibitor, intercellular adhesion deficiency inhibitor, gingival recession inhibitor, periodontal pocket formation inhibitor, gingival strengthening agent) are added to the oral composition, The effect can be exerted by applying it to the oral cavity as an oral composition for gum care. Therefore, 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, paste preparations, and gingival preparations. Examples include creams, gum gels, denture stabilizers, troches, chewing agents (including chewing gum, gummies, etc.), patches (films, packs), and the like. These oral compositions can be blended with various ingredients used in the field, depending on the form, and are not limited thereto as long as they do not impede the effects of the present invention. For example, in the case of toothpaste, abrasives, wetting agents, binders, foaming agents, surfactants, sweeteners, preservatives, fragrances, colorants, pH adjusters, etc., as long as they do not impede the effects of the present invention. Medicinal ingredients can be blended.

Assuming that the oral composition is 100% by mass as the blending ratio of the gingival care agent of the present invention when added and used in these oral compositions, the active ingredient of the gingival care agent of the present invention is ( The proportion of A) to (C) is usually 0.001 to 1% by mass, preferably 0.01 to 0.5% by mass, more preferably 0.05 to 0.4% by mass for component (A). Component (B) is usually 0.001 to 1% by mass, preferably 0.005 to 0.5% by mass, more preferably 0.05 to 0.15% by mass, and component (C) is The amount is usually 0.001 to 1% by weight, preferably 0.01 to 0.3% by weight, and more preferably 0.02 to 0.1% by weight.

In addition, as for the concentration of each component added to the oral composition, component (A) is 10 to 10,000 μM, preferably 100 to 5,000 μM, more preferably 500 to 4,000 μM, and component (B) is 15 to 15,000 μM, preferably is 75 to 7500 μM, more preferably 750 to 2250 μM, and component (C) is 35 to 35000 μM, preferably 350 to 10500 μM, more preferably 700 to 3500 μM.

(II) Oral composition for gingival care The present invention provides the above-mentioned gingival care agents (inhibitor of decrease in expression of intercellular adhesion factor, inhibitor of intercellular adhesion deficiency, inhibitor of gingival recession, inhibitor of periodontal pocket formation, agent for strengthening gingiva) ) is an oral composition for gum care containing as an active ingredient. The oral composition can be effectively used for gingival care. Specifically, to suppress adhesion failure between cells in the gingival epithelium, to prevent or suppress gingival recession (thinning of the gums), to prevent or suppress periodontal pocket formation, or to strengthen the gingiva. It can be used for.

As mentioned above, the blending ratio of the gingival care agent added to the oral composition for gingival care of the present invention is as follows, assuming that the oral composition for gingival care is 100% by mass, the active ingredient of the gingival care agent. Component (A) is usually 0.001 to 1% by mass, preferably 0.01 to 0.5% by mass, more preferably 0.05 to 0.4% by mass, and component (B) is usually 0. .001 to 1% by mass, preferably 0.005 to 0.5% by mass, more preferably 0.05 to 0.15% by mass, and for component (C) usually 0.001 to 1% by mass, preferably is 0.01 to 0.3% by mass, more preferably 0.02 to 0.1% by mass. In addition, as for the concentration of each component contained in the oral composition for gum care of the present invention, component (A) is 10 to 10,000 μM, preferably 100 to 5,000 μM, more preferably 500 to 4,000 μM, and component (B) is , 15 to 15,000 μM, preferably 75 to 7,500 μM, more preferably 750 to 2,250 μM, and component (C) is 35 to 35,000 μM, preferably 350 to 10,500 μM, more preferably 700 to 3,500 μM.

The oral composition for gum care of the present invention includes dentifrices (including powder, liquid, cream, and paste preparations), mouthwashes (including liquid and foam preparations), and ointments. Examples include paste preparations, gum creams, gum gels, denture stabilizers, troches, chewing agents (including chewing gums, gummies, etc.), adhesive patches (films, packs), and the like. These oral compositions for gum care can be blended with various ingredients used in the field, depending on the form, and are not limited thereto as long as they do not impede the effects of the present invention. For example, in the case of toothpaste, abrasives, wetting agents, binders, foaming agents, thickeners, surfactants, sweeteners, fragrances, coloring agents, preservatives, etc. may be used as long as they do not impede the effects of the present invention. Medicinal ingredients (for example, anti-inflammatory agents, etc.) can be blended.

[Abrasives] Silica-based abrasives such as precipitated silica, silica gel, aluminosilicate, zirconosilicate, etc., phosphorus such as calcium hydrogen phosphate for tooth brushing, dicalcium phosphate dihydrate, dicalcium phosphate anhydrate, calcium pyrophosphate, etc. Acid-based abrasive, 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, octabasic calcium phosphate, synthetic resin abrasive.

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

[Binder] Cellulose binders such as sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylethylcellulose, methylcellulose, xanthan gum, carrageenan, guar gum, sodium alginate, cationized cellulose, montmorillonite, gelatin, Sodium polyacrylate etc.

[Foaming agent] Sodium lauryl sulfate, sodium lauroyl sarcosine, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglycerol sulfonate, sodium α-olefin sulfonate, N-acylamino acid salts such as N-acylglutamate, 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, sorbitol, propylene glycol, polyethylene glycol with a molecular weight of 200 to 6,000, ethylene glycol, 1,3-butylene glycol, reduced starch saccharide, etc.

[Surfactant] Anionic surfactants, nonionic surfactants, amphoteric surfactants, cationic surfactants, etc. can be blended. Examples of anionic surfactants include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosines such as sodium N-lauroyl sarcosine and sodium N-myristoyl sarcosine, sodium dodecylbenzenesulfonate, and hydrogenated coconut fatty acids. N-acylglutamates such as sodium monoglyceride monosulfate, sodium lauryl sulfoacetate, sodium N-palmitoylglutamate, sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acylalanine, sodium α-olefin sulfonate, etc. can be mentioned. Examples of nonionic surfactants include polyoxyethylene hydrogenated castor oil, sucrose fatty acid ester, alkylolamide, polyoxyethylene sorbitan monostearate, polyoxyethylene polyoxypropylene glycol, alkyl glucoside, decaglyceryl laurate, etc. used. Examples of amphoteric surfactants include lauryldimethylaminoacetic acid betaine, N-coconut oil fatty acid acyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine, and coconut oil fatty acid amidopropyl fatty acid. Betain et al.

[Sweeteners] Saccharin sodium, aspartame, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perillartine, sucralose, xylitol, reduced palatinose, erythritol, maltitol, etc.

[Fragrance] Peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime Oil, lavender oil, rosemary oil, laurel oil, chamomile oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, absolute peppermint. , absolute rose, orange flower, and other natural fragrances, as well as fragrances processed from these natural fragrances (cutting the front reservoir, cutting the rear reservoir, fractional distillation, liquid-liquid extraction, essence, powder fragrance, etc.), and menthol. , carvone, anethole, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linaryl acetate, limonene, menthone, menthyl acetate, N-substituted paramenthane -3-carboxamide, pinene, octylaldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone , hexanal, propyl alcohol, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cyclotene, furfural, trimethyl pyrazine, ethyl lactate, methyl lactate, ethyl thioacetate, etc., as well as strawberry flavor, apple flavor, banana flavor, pineapple flavor. , grape flavor, mango flavor, butter flavor, milk flavor, mixed fruit flavor, tropical fruit flavor, etc.

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

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

[Medicinal ingredients] Fluorine compounds such as sodium fluoride, sodium monofluorophosphate, and tin fluoride, water-soluble phosphoric acid compounds such as potassium salts and sodium salts of orthophosphoric acid, sodium polyphosphate, tranexamic acid, and epsilon-aminocaproic acid. , allantoin, allantoin chlorhydroxyaluminum, hinokitiol, ascorbic acid, dl-α-tocopherol acetate, dl-α-tocopherol nicotinate, pyridoxine hydrochloride, dihydrocholesterol, α-bisabolol, chlorhexidine salts, sodium azulene sulfonate, guaiazulene sulfone Acid, copper compounds such as glycyrrhetinic acid, glycyrrhetinic acid, copper gluconate, aluminum lactate, strontium chloride, potassium nitrate, berberine, hydroxamic acid and its derivatives, zeolite, methoxyethylene maleic anhydride copolymer, polyvinylpyrrolidone, polyethylene glycol, epidihydro Cholesterin, cetylpyridium chloride, benzethonium chloride, isopropyl methylphenol, sodium lauroyl sarcosine, dihydrocholesterol, trichlorocarbanilide, zinc citrate, soft extract of chili pepper, auricum extract, chamomile, clove, rosemary, scutellariae, safflower, etc. extracts, lysozyme chloride, sodium chloride, etc.

The amount of these optional components to be blended can be any amount commonly used in the art as long as the effects of the present invention are not impaired.
(III) Gum care method
The present invention relates to a method of caring for a subject's gums. Gingival care here refers to at least one of the following: suppressing adhesion failure between cells in the gingival epithelium of the test subject, suppressing gingival recession, suppressing periodontal pocket formation, or strengthening the gingiva. It means to do one thing.

The method includes treating the oral cavity of a subject using an oral composition containing at least one member selected from the group consisting of glycyrrhizic acid or a pharmaceutically acceptable salt thereof, sodium copper chlorophyllin, and triclosan. It can be implemented.

The oral composition used here is the above-mentioned oral composition for gum care of the present invention, and it is possible to treat the inside of the subject's oral cavity by using it normally depending on the intended use of each oral composition. can. For example, when the oral composition for gingival care is a dentifrice, the gingival care method of the present invention can be carried out by brushing the test subject's teeth using the oral composition for gingival care. In addition, when the oral composition for gum care is a mouthwash, the gum care method of the present invention can be carried out by washing (rinsing) the oral cavity of the subject using the oral composition for gum care. can.

The number of times the gum care is performed is not particularly limited, and can be performed once or multiple times a day, preferably after meals and/or before and after going to bed.

The present invention will be explained below 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 Human gingival epithelial cell line OBA9 was cultured in HuMedia-KG2 medium (KURABO). Cells were seeded at 3×10 ⁵ cells/well in a 6-well plate, and cultured in an incubator at 37° C. and 5% CO ₂ until confluent. Then, change to HuMedia-KG2 medium (excluding bovine pituitary extract BPE) or HuMedia-KG2 medium (excluding bovine pituitary extract BPE) containing various test substances at the concentrations listed in Table 1. The cells were then cultured for an additional hour under the same conditions. Next, for those to which the test substance was not added, the medium as it was (control: non-addition group) or human recombinant TNF-α (R&D Systems) was added to a final concentration of 100 ng/mL (TNF-α addition group). ) and cultured under the same conditions for 24 hours. In addition, for those to which the test substance had been added, human recombinant TNF-α was added to a final concentration of 100 ng/mL (TNF-α/test substance addition group), and cultured under the same conditions for 24 hours. In addition, the highest concentration for which safety has been confirmed for each substance was used as the evaluation concentration.

Total RNA was extracted from cells using the RNeasy mini kit (QIAGEN) according to the attached manual. 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 Universal SYBR Select master mix (Life Technologies ABI, Inc.) and various primers (100nM, Sigma-Aldrich) shown in Table 2, the TNF-α addition group and TNF The E-cadherin expression level was calculated for each of the -α and test substance addition groups, and the two were compared using the Comparative CT (ΔΔCT) method. The expression level of GAPDH was quantified and standardized as an internal standard gene.

From the obtained values, the E-cadherin gene expression reduction inhibition rate (%) was calculated using the following formula.

The results are shown in Table 3.

As shown in Table 3, salts of glycyrrhizic acid, triclosan, and sodium copper chlorophyllin all significantly suppressed the decrease in gene expression of intercellular adhesion factor (E-cadherin) caused by inflammatory cytokines (TNF-α). found. In particular, it was confirmed that the inhibitory effects of glycyrrhizic acid salts and copper chlorophyllin sodium on the decrease in expression were extremely high, and could almost be inhibited. On the other hand, even ingredients known to have anti-inflammatory and bactericidal effects (Table 3) could not suppress the decrease in gene expression of intercellular adhesion factor (E-cadherin).

Prescription example
Formulation Example 1: Paste Toothpaste The following ingredients are mixed to prepare a paste toothpaste according to a conventional method.

Formulation Example 2: Paste Toothpaste The following ingredients are mixed to prepare a paste toothpaste according to a conventional method.

Formulation Example 3: Paste Toothpaste The following ingredients are mixed to prepare a paste toothpaste according to a conventional method.

Formulation Example 4: Paste Toothpaste The following components are mixed to prepare a paste toothpaste according to a conventional method.

Formulation Example 5: Paste Toothpaste The following ingredients are mixed to prepare a paste toothpaste according to a conventional method.

Formulation Example 6: Paste Toothpaste The following ingredients are mixed to prepare a paste toothpaste according to a conventional method.

Formulation Example 7: Liquid dentifrice The following ingredients are mixed to prepare a liquid dentifrice according to a conventional method.

Formulation Example 8: Preparation of mouthwash A mouthwash can be prepared by mixing the following components and following a conventional method.

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

Claims (2)

Reducing the expression of E-cadherin, which comprises treating the oral cavity of a subject with an oral composition containing at least one member selected from the group consisting of glycyrrhizic acid or a pharmaceutically acceptable salt thereof, and triclosan. Gingival care methods (excluding treatment methods) to suppress adhesion defects between gingival epithelial cells caused by gingival epithelial cells. The gingival care method is a method of suppressing gingival recession and/or periodontal pocket formation by suppressing intercellular adhesion failure due to decreased expression of E-cadherin in the gingival epithelium of the subject. The gingival care method according to claim 1 .