Oral components

Abstract

To provide a composition for oral use, the composition containing a dl-α-tocopherol 2-L-ascorbic acid phosphoric acid diester alkali metal salt.SOLUTION: The present invention provides compositions for oral use, containing a dl-α-tocopherol 2-L-ascorbic acid phosphoric acid diester alkali metal salt (where, the compositions for oral use do not include ones with at least one selected from the group consisting of polyoxyethylene alkyl phenyl ether, polyoxyethylene alkyl ether, and polyoxyethylene fatty acid ester).SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to oral compositions and the like, and more particularly to oral compositions and the like containing an alkali metal salt of dl-α-tocopherol 2-L-ascorbic acid phosphate diester.

Background Art

[0002] Dl-α-tocopherol 2-L-ascorbic acid phosphate diester (which may be referred to as "EPC" in this specification) is a compound in which ascorbic acid (vitamin C) and tocopherol (vitamin E) are ester-bonded via phosphate, and has antioxidant and moisturizing effects, and is used in cosmetics such as hair growth agents (Patent Document 1).

[0003] Although EPC is expected to be applied in the oral field, there has been no report yet on what effects it actually exhibits in the oral region.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

[0006] The object of this disclosure is to provide an oral composition comprising dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt. [Means for solving the problem]

[0007] The inventors have discovered that dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt suppresses the destruction of the oral mucosal epithelial barrier function and inhibits the activity of matrix metalloproteinases (MMPs), and have further improved upon this finding.

[0008] This disclosure includes, for example, the following subjects: Section 1. Oral compositions comprising dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt (excluding oral compositions comprising at least one selected from the group consisting of polyoxyethylene alkylphenyl ethers, polyoxyethylene alkyl ethers, and polyoxyethylene fatty acid esters). Section 2. The composition according to item 1, containing 0.001 to 1% by mass of dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt. Section 3. The composition according to claim 1 or 2, wherein the alkali metal salt of dl-α-tocopherol 2-L-ascorbic acid phosphate diester is dl-α-tocopherol 2-L-ascorbic acid phosphate diester potassium salt. Section 4. A composition according to any one of items 1 to 3, which is for the purpose of preventing periodontal disease, preventing oral mucositis, or preventing caries. Section 5. A composition according to any one of items 1 to 4, for enhancing the barrier function of the oral mucosal epithelium. Section 6. A composition according to any one of items 1 to 5, for inhibiting matrix metalloproteinase activity in the oral cavity. [Effects of the Invention]

[0009] The compositions of this disclosure include dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt, which can suppress the disruption of oral mucosal epithelial barrier function and / or inhibit the activity of MMPs. [Brief explanation of the drawing]

[0010] [Figure 1] The transmittance (%) is shown when EPC-K (dl-α-tocopherol 2-L-ascorbic acid phosphate diester potassium salt) is added. [Figure 2] This shows the transmittance (%) when EPC-K is added. [Figure 3]It shows the transmittance (%) when EPC-K, APM (magnesium ascorbate phosphate), VC (ascorbic acid), VEA (tocopherol acetate), and VEN (nicotinic acid tocopherol) are added. [Figure 4] It shows the measurement results of MMP-8 activity. [Figure 5] It shows the measurement results of MMP-1 activity. [Figure 6] It shows the cell viability (%) when sorbeth-60 tetraoleate, diethyl sebacate, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene (9) lauryl ether, and polyoxyethylene (20) stearyl ether are added. [Figure 7] It shows the cell viability (%) when polyoxyethylene (9) lauryl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (10) octyl phenyl ether, and polyoxyethylene glycol monolaurate are added.

Mode for Carrying Out the Invention

[0011] Hereinafter, each embodiment included in the present disclosure will be described in more detail. The oral composition included in the present disclosure contains dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt. In this specification, the composition may be referred to as "the oral composition of the present disclosure".

[0012] dl-α-tocopherol 2-L-ascorbic acid phosphate diester (EPC) is a compound in which ascorbic acid (vitamin C) and tocopherol (vitamin E) are ester-bonded via phosphoric acid, and is also referred to as (ascorbyl / tocopheryl) phosphate. The chemical formula is shown below.

[0013]

Chemical formula

[0014] Examples of alkali metal salts of dl-α-tocopherol 2-L-ascorbic acid phosphate diester include dl-α-tocopherol 2-L-ascorbic acid phosphate diester potassium salt, dl-α-tocopherol 2-L-ascorbic acid phosphate diester sodium salt, and dl-α-tocopherol 2-L-ascorbic acid phosphate diester lithium salt. Among these, dl-α-tocopherol 2-L-ascorbic acid phosphate diester potassium salt is preferred. Furthermore, the alkali metal salt of dl-α-tocopherol 2-L-ascorbic acid phosphate diester may be a monosalt or a disalt.

[0015] The content of dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt in the oral composition of this disclosure can be, for example, about 0.001 to 1% by mass. The upper or lower limit of this range may be, for example, about 0.002, 0.005, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, or 0.9% by mass. More specifically, it may be, for example, about 0.002 to 0.5% by mass, or about 0.005 to 0.3% by mass.

[0016] The oral composition of this disclosure contains dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt, which has the effect of suppressing the destruction of the oral mucosal epithelial barrier function. For this reason, the oral composition of this disclosure can be suitably used to enhance the barrier function of the oral mucosal epithelium. The oral mucosal epithelium is not particularly limited and includes epithelium constituting the masticatory mucosa (e.g., gingiva, etc.) (e.g., attached epithelium, gingival sulcus epithelium, etc.), epithelium constituting the covering mucosa (e.g., buccal mucosa), and epithelium constituting special mucosa (e.g., tongue mucosa).

[0017] Furthermore, the oral composition of this disclosure contains dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt, thereby exhibiting an effect of inhibiting the activity of MMPs. For this reason, the oral composition of this disclosure can be suitably used for inhibiting the activity of matrix metalloproteinases (MMPs) in the oral cavity. Moreover, because the oral composition of this disclosure exhibits an MMP activity inhibitory effect, it can inhibit the activity of neutrophil collagenase that has already been produced. Examples of matrices (MMPs) in the oral cavity include MMP-1, 2, 3, 8, 9, and 13. Among these, MMP-1 and 8 are preferred. MMP-1 (EC 3.4.24.7) is also called interstitial collagenase, and MMP-8 (EC 3.4.24.34) is also called neutrophil collagenase.

[0018] Furthermore, it has been reported that the gingival epithelium forms a barrier against invading microorganisms, protecting periodontal tissue from infection (Non-Patent Literature 1). It is also known that periodontal pathogens such as Porphyromonas gingivalis secrete bacterial proteases and destroy the gingival epithelium, thereby achieving invasion into periodontal tissue (Non-Patent Literature 2). As the invasion of periodontal pathogens into the tissue progresses, immune cells such as neutrophils accumulate to eliminate them, and it is known that the production of MMPs increases. MMPs are proteolytic enzymes that break down the extracellular matrix (e.g., collagen such as type I, type II, and type III collagen), which destroys periodontal tissue and causes periodontal disease to progress. In fact, increases in MMP-1, 2, 3, 8, 9, and 13 have been observed in the gingival crevicular fluid (GCF) of patients with periodontal disease (Non-Patent Literature 3). The oral composition disclosed herein contains dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt, which exerts the effect of suppressing the destruction of the oral mucosal epithelial barrier function and / or inhibiting the activity of MMPs, and is therefore suitably used for anti-periodontal disease purposes. In other words, the oral composition disclosed herein can prevent the progression of periodontal disease bacteria into periodontal tissue by enhancing the barrier function of the oral mucosal epithelium. Furthermore, the oral composition disclosed herein can prevent the destruction of periodontal tissue by inhibiting matrix metalloproteinase activity in the oral cavity. For this reason, it is expected to be applicable to all stages of periodontal disease, from the early stages to advanced stages. In this specification, "anti-periodontal disease" means the prevention of the onset of periodontal disease and / or the suppression of the progression of periodontal disease.

[0019] Furthermore, it has been reported that when ulcers form on the oral mucosa due to bites, burns, or side effects of chemotherapy or radiotherapy (oral mucositis), the epithelial barrier function is lost, leading to infection by oral bacteria (Non-Patent Literature 4). The oral composition of this disclosure contains dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt, which has the effect of suppressing the destruction of the oral mucosal epithelial barrier function, and is therefore suitably used as an anti-oral mucositis composition. In this specification, "anti-oral mucositis" means prevention of the onset of oral mucositis and / or suppression of the progression of oral mucositis.

[0020] Furthermore, dentin contains approximately 20% collagen, which is an organic substance, and the progression of dentin caries involves demineralization and collagen degradation. It is believed that MMPs in saliva penetrate the dentin and degrade collagen (Non-Patent Literature 5). The oral composition disclosed herein contains dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt, which inhibits the activity of MMPs, and is therefore suitable for use as an anti-cariogenic agent. In this specification, "anti-cariogenic" means prevention of the onset of caries and / or inhibition of the progression of caries.

[0021] Examples of animals to which the oral compositions of this disclosure can be applied include mammals, including humans (e.g., dogs, cats, mice, rats, sheep, horses, cattle, monkeys, etc.). Humans are particularly preferred. The people to whom the oral compositions of this disclosure are applicable are not limited to, for example, people with periodontal disease or suspected periodontal disease; people with oral mucositis or suspected oral mucositis; people with dental caries or suspected dental caries; people with weakened barrier function of oral mucosal epithelium; people with elevated matrix metalloproteinase activity in the oral cavity; etc., but may also include healthy individuals (for example, people who want to prevent the onset of periodontal disease, people who want to suppress the progression of periodontal disease, people who want to prevent the onset of oral mucositis, people who want to suppress the progression of oral mucositis, people who want to prevent the onset of dental caries, people who want to suppress the progression of dental caries, etc.).

[0022] The oral compositions of this disclosure may be, for example, solid compositions, liquid compositions, etc. Furthermore, the oral compositions of this disclosure can be made into forms (dosage forms) such as ointments, pastes, pasta preparations, gels, liquids, sprays, mouthwashes, liquid toothpastes, toothpastes, gums, tablets, drops, etc., according to conventional methods. Among these, mouthwashes, liquid toothpastes, toothpastes, ointments, pastes, liquids, and gels are preferred.

[0023] The oral composition of this disclosure may contain, in addition to dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt, one or more other optional components that can be incorporated into the oral composition.

[0024] For example, nonionic surfactants, anionic surfactants, or amphoteric surfactants can be incorporated as surfactants. Specifically, examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; glycerin fatty acid esters; sorbitan fatty acid esters; fatty acid monoglycerides; diethyl sebacate; polyoxyethylene hydrogenated castor oil; and fatty acid polyoxyethylene sorbitan. Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and polyoxyethylene lauryl ether sodium sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and polyoxyethylene lauryl ether sulfosuccinate sodium; acyl amino acid salts such as sodium cocoyl sarcosinate and sodium lauroyl methylalanine; and sodium cocoyl methyl taurate. Examples of amphoteric surfactants include betaine-type surfactants such as lauryldimethylaminoacetic acid betaine and coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine; and imidazoline-type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium. These surfactants can be used individually or in combination of two or more. The amount used is usually 0.1 to 5% by mass of the total composition. It is preferable that oral compositions of this disclosure exclude those containing, for example, at least one selected from the group consisting of polyoxyethylene alkylphenyl ethers, polyoxyethylene alkyl ethers, and polyoxyethylene fatty acid esters. Examples of polyoxyethylene alkylphenyl ethers include those having an average number of moles of ethylene oxide added of 1 to 40 and an alkyl group with 7 to 30 carbon atoms. Examples of polyoxyethylene alkyl ethers include those having an average number of moles of ethylene oxide added of 1 to 40 and an alkyl group with 1 to 18 carbon atoms. Examples of polyoxyethylene fatty acid esters include those having an average number of moles of ethylene oxide added of 1 to 40 and an alkyl group with 1 to 20 carbon atoms.

[0025] Furthermore, as flavoring agents, for example, menthol, carvone, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole, linalool, ethyl linalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, fennel oil, cinnamon oil, cinnamaldehyde, peppermint oil, vanillin, and other fragrances can be used. These can be added individually or in combination of two or more in amounts of, for example, 0.001 to 1.5% by mass of the total composition.

[0026] Furthermore, sweeteners such as sodium saccharin, potassium acesulfamethamate, stevioside, neohesperidyl dihydrochalcone, perillartin, thaumatin, aspartylphenylalanyl methyl ester, and p-methoxycinnamic aldehyde can be used. These can be added individually or in combination of two or more in amounts of, for example, 0.01 to 1% by mass of the total composition.

[0027] Furthermore, sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, etc., can be used as humectants, either individually or in combination of two or more.

[0028] Examples of binders include cellulose derivatives such as sodium carboxymethylcellulose, carboxymethyl ethylcellulose salt, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, crystalline cellulose, and crystalline cellulose-carmellose sodium; microbially produced polymers such as xanthan gum; natural polymers or natural rubbers such as tragacanth gum, karaya gum, arabic gum, carrageenan, dextrin, agar, pectin, pullulan, gellan gum, locust bean gum, and sodium alginate; synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, polyvinyl methyl ether, and sodium polyacrylate; inorganic binders such as thickening silica and bee gum; and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride. These binders can be used individually or in combination of two or more.

[0029] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride can be included. These can be used individually or in combination of two or more.

[0030] As colorants, legally approved pigments such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral pigments such as ultramarine, enhanced ultramarine, and navy blue, and titanium dioxide may be included. These can be used individually or in combination of two or more.

[0031] As pH adjusters, citric acid, phosphoric acid, malic acid, pyrophosphate, lactic acid, tartaric acid, glycerophosphate, acetic acid, nitric acid, or chemically possible salts thereof, or sodium hydroxide may be included. These can be included individually or in combination of two or more so that the pH of the composition is in the range of 4 to 8, preferably 5 to 7. The amount of pH adjuster may be, for example, 0.01 to 2% by weight.

[0032] Furthermore, the oral composition disclosed herein may also contain, as pharmaceutically active ingredients, vitamin E derivatives such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate; amphoteric bactericides such as dodecyldiaminoethylglycine; nonionic bactericides such as triclosan and isopropylmethylphenol; anionic bactericides such as sodium lauroyl sarcosinate; cationic bactericides such as cetylpyridinium chloride, chlorhexidine hydrochloride, benzalkonium chloride, and benzethonium chloride; dextranase, amylase, protease, mutanase, lysozyme, and lytic enzymes (Litec Enzyme) Enzymes such as (M), alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon-aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, glycyrrhetinic acid, glycyrrhizic acid, copper chlorophyllin sodium, glycerophosphate, chlorophyll, sodium chloride, caropeptide, allantoin, carbazochrome, potassium nitrate, and palatinite can be formulated individually or in combination of two or more.

[0033] Furthermore, it is possible to add alcohols, silicones, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, Plastibase, etc., as bases. These can be used individually or in combination of two or more.

[0034] The oral compositions of this disclosure can be prepared by known methods or by methods readily conceivable from known methods. For example, they can be prepared by appropriately mixing dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt and other components as needed.

[0035] In this specification, the term "comprising" includes both "consisting essentially of" and "consisting of." Furthermore, this disclosure encompasses all combinations of the constituent elements described herein.

[0036] Furthermore, the various characteristics (properties, structure, function, etc.) described in each embodiment of this disclosure above may be combined in any way to identify the subject matter covered by this disclosure. In other words, this disclosure covers all subject matter consisting of any combination of the combinable characteristics described herein. [Examples]

[0037] The contents of this disclosure will be specifically explained using the following experimental examples. However, this disclosure is not limited in any way to these examples. Unless otherwise specified below, the experiments were conducted under atmospheric pressure and room temperature conditions. Unless otherwise specified, "%" means "mass%". Also, unless otherwise specified, the composition values ​​of each component listed in each table are also in "mass%".

[0038] 1. Epithelial barrier function evaluation test cell regulation Epi4 gingival epithelial cells were cultured on Transwell until confluence. The Epi4 cells were cultured in a medium consisting of Epilife (Thermo Fisher) with 1 / 100th the volume of Supplemental S7 (Thermo Fisher) added. The Transwell is designed as a suspended device with the insert positioned in the middle of the well, allowing for evaluation of cell permeability.

[0039] bacterial regulation Porphyromonas gingivalis W83 was cultured in modified GAM medium (Nissui Pharmaceutical Co., Ltd.), and after culturing, it was recovered by centrifugation at 10,000 rpm. 600 The Pg bacteria concentration was adjusted in the cell culture medium to equal 1.0.

[0040] Material preparation Each evaluation material was prepared to its respective evaluation concentration in a cell culture medium containing 2.5% DMSO. The materials used were EPC-K (dl-α-tocopherol 2-L-ascorbic acid phosphate dipotassium salt), APM (magnesium ascorbic acid phosphate), VC (ascorbic acid), VEA (tocopherol acetate), and VEN (tocopherol nicotinate).

[0041] Barrier function evaluation The culture medium was removed from Epi4 cells cultured on a Transwell, and 300 μl of each prepared material-containing medium was added. The mixture was incubated at 37°C for 1 hour at a CO2 concentration of 5%. A control group was used for the medium treatment without the material. Next, 100 μl of the prepared Pg bacteria suspension was added and incubated for 2 hours at 37°C under a CO2 concentration of 5% by volume. For the control, two samples were prepared: one with Pg bacteria suspension added and incubated (Pg(+)), and another with only medium without Pg bacteria added and incubated (Pg(-)). After incubation, the culture medium was removed, washed with PBS, and FITC (Fluoresceinisothiocyanate)-dextran (4kDa) adjusted to 1 mg / ml was added. The mixture was incubated at 37°C for 1 hour. The FITC-dextran that passed through the Transwell was collected, and the fluorescence intensity (excitation light: 490 nm, emitted light: 520 nm) was measured using a fluorescence plate reader (Gemini XPS). The transmittance when processing materials at each concentration was calculated by converting the FITC transmittance when adding Pg bacteria solution to the control (no Pg(+) material) to 100% and the FITC transmittance when adding only Pg bacteria-free medium to the control (Pg(-)) to 0%. The results are shown in Figures 1-3. Note that the material concentration in the figures is the concentration at the time of preparation, and the final concentration (concentration after adding Pg bacteria) is 3 / 4 of that concentration value. Furthermore, a lower transmittance indicates a higher epithelial barrier function.

[0042] As shown in Figures 1-3, EPC-K was confirmed to suppress the destruction of the oral mucosal epithelial barrier by P. gingivalis. However, similar effects were not observed with ascorbic acid and its derivative APM, as well as with tocopherol derivatives VEA and VEN.

[0043] 2. MMP activity measurement test Material preparation Each evaluation material was adjusted to its respective evaluation concentration using a solvent (buffer included in the kit described below + 5% DMSO) to prepare the evaluation material solution. The materials used were EPC-K (dl-α-tocopherol 2-L-ascorbic acid phosphate dipotassium salt), VC (ascorbic acid), VEA (tocopherol acetate), and VEN (tocopherol nicotinate).

[0044] Enzyme activity measurement MMP-8 (neutrophil collagenase) activity was evaluated using the MMP-8 fluorimetric drug discovery kit (Enzo Life Sciences, Inc., BML-AK415-0001), and MMP-1 (fibroblast collagenase) activity was evaluated using the MMP-1 fluorimetric drug discovery kit (Enzo Life Sciences, Inc., BML-AK405-0001). To 20 μl of each prepared material solution, 0.1 μl of MMP-8 and 69.9 μl of the included buffer, or 0.2 μl of MMP-1 and 69.8 μl of the included buffer, were mixed and reacted at 37°C for 60 minutes. At this time, a sample with equal amounts of buffer added without the material was prepared as a positive control (Cont.), and a sample with equal amounts of buffer added without MMP-8 or MMP-1 was prepared to measure the background of the substrate only (NC). The fluorescent substrate included in the kit was diluted 10-fold with buffer, and 10 μl was added to the solution after 60 minutes of reaction. After addition, MMP-8 was reacted at 37°C for 20 minutes, and MMP-1 was reacted at 37°C for 60 minutes, after which the fluorescence intensity at excitation light: 328 nm and emitted light: 420 nm was measured. The fluorescence intensity of the positive control sample (Cont.) minus the fluorescence intensity of the substrate alone (NC) as background was set to 100%, and the ratio of the fluorescence intensity of each material solution added to the fluorescence intensity minus the fluorescence intensity of the substrate alone (NC) as background was calculated as the enzyme activity. Since MMP-8 was more reactive than MMP-1 with respect to the reaction substrates included in both kits, tests were conducted with different dilution ratios and reaction times for both MMP-8 and MMP-1 to examine their reactivity under similar conditions. The results are shown in Figures 4 and 5. Note that the material concentration shown in the figure is the concentration at the time of material preparation, and the final concentration (concentration at the time of fluorescence intensity measurement) will be 1 / 5 of that concentration value.

[0045] As shown in Figures 4 and 5, EPC-K was confirmed to inhibit MMP activity (MMP-8 and MMP-1) in a concentration-dependent manner. Similar effects were not observed with ascorbic acid, or with tocopherol derivatives VEA and VEN.

[0046] 3. Cytotoxicity evaluation test cell culture Oral epithelial cell lines (Ca9-22 cells) were cultured in 96-well plates until confluence was reached.

[0047] Material preparation A PBS solution containing 0.5% DMSO was prepared as the solvent so that the final concentration of each surfactant in the evaluation solution was 1%. The surfactants used were polyoxyethylene(9) lauryl ether, polyoxyethylene(20) cetyl ether, polyoxyethylene(20) stearyl ether, polyoxyethylene(10) octylphenyl ether, polyoxyethylene glycol monolaurate, sorbeth-60 tetraoleate, diethyl sebacate, and polyoxyethylene hydrogenated castor oil 10.

[0048] Cytotoxicity assessment 100 μl of the prepared evaluation solution was added to cultured Ca9-22 cells and allowed to stand at room temperature for 10 minutes. After 10 minutes, the cells were washed three times with 200 μl of PBS and reacted with WST-1 reagent (Takara Bio) for 30 minutes. After the reaction, the absorbance at 450 nm and 600 nm was measured, and the value obtained by subtracting the absorbance at 600 nm from the absorbance at 450 nm was calculated. Of the calculated values, the value for solvent-only treatment was set to 100% and the cell viability was calculated. The results are shown in Figures 6 and 7.

[0049] As shown in Figures 6 and 7, polyoxyethylene alkylphenyl ethers (polyoxyethylene(10) octylphenyl ether), polyoxyethylene alkyl ethers (polyoxyethylene(9) lauryl ether, polyoxyethylene(20) cetyl ether, polyoxyethylene(20) stearyl ether), and polyoxyethylene fatty acid esters (polyoxyethylene glycol monolaurate) were found to cause cytotoxicity in oral-derived cells. On the other hand, other surfactants such as tetraoleate sorbeth-60, diethyl sebacate, and polyoxyethylene hydrogenated castor oil 10 were found not to cause cytotoxicity in oral-derived cells.

Claims

1. Oral compositions comprising dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt (excluding oral compositions comprising at least one selected from the group consisting of polyoxyethylene alkylphenyl ethers, polyoxyethylene alkyl ethers, and polyoxyethylene fatty acid esters).

2. The composition according to claim 1, comprising 0.001 to 1% by mass of dl-α-tocopherol 2-L-ascorbic acid phosphate diester alkali metal salt.

3. The composition according to claim 1 or 2, wherein the alkali metal salt of dl-α-tocopherol 2-L-ascorbic acid phosphate diester is potassium salt of dl-α-tocopherol 2-L-ascorbic acid phosphate diester.

4. A composition according to any one of claims 1 to 3, which is for the purpose of preventing periodontal disease, preventing oral mucositis, or preventing dental caries.

5. A composition according to any one of claims 1 to 4, for enhancing the barrier function of the oral mucosal epithelium.

6. A composition according to any one of claims 1 to 5, for use in inhibiting matrix metalloproteinase activity in the oral cavity.

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