Oral care food

The oral care food addresses the inadequacies of conventional compositions by using specific compounds to inhibit Candida growth and improve microbial balance, achieving effective Candida suppression and bacterial flora improvement.

WO2025197729A1PCT designated stage Publication Date: 2025-09-25SANYO CHEM IND LTD +1
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Patent Information

Application Number
PCT/JP2025/009397
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-10-04
Filing Date
2025-03-12
Publication Date
2025-09-25

AI Technical Summary

Technical Problem

Conventional oral care compositions fail to sufficiently suppress the growth and hyphae formation of Candida fungi, leading to issues like bad breath and mycosis, and do not effectively balance the microbial flora in the oral cavity.

Method used

An oral care food containing specific compounds with a defined mass ratio of hydroxy groups, oxo acid groups, and other functional groups, along with a pH of 6 to 8 and a solid state at 25°C, which inhibits Candida proliferation and hyphae formation while improving the bacterial flora.

Benefits of technology

The oral care food effectively suppresses Candida growth and mycelium formation, maintains a balanced microbial flora, and selectively inhibits pathogenic bacteria while preserving non-pathogenic bacteria.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention addresses the problem of providing an oral care food which can sufficiently suppress the proliferation and hyphal formation of Candida and has a bacterial flora-improving effect. The present invention relates to an oral care food which contains a substance (X) that comprises at least one substance selected from the group consisting of a compound (X1) having two or more hydroxy groups contained in an oxo acid group and salts of the compound (X1), wherein the proportion of the sum of the mass of the oxo acid group in the compound (X1), the mass of hydroxy groups that are not contained in the oxo acid group, the mass of carbonyl groups that are not contained in the oxo acid group, the mass of carbon atoms that are contained in an imidazole skeleton and a pyridine skeleton, and the mass of nitrogen atoms that are contained in the imidazole skeleton and the pyridine skeleton is 45 mass% or more with respect to the molecular weight of the compound (X1), the molecular weight of the substance (X) is 550 or less, the pH of an aqueous solution containing the oral care food in an amount of 1 wt% is 6-8, and the oral care food has a solid form at 25°C.
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Description

Oral care foods

[0001] The present invention relates to an oral care food product.

[0002] The oral cavity contains both non-pathogenic resident bacteria and pathogenic bacteria. Normally, a balance is maintained between these resident bacteria and pathogenic bacteria, but poor oral hygiene can cause this balance to be disrupted. In such cases, pathogenic bacteria can increase, leading to disease.

[0003] Known examples of compositions that prevent the growth of pathogenic bacteria in the oral cavity include the composition described in Patent Document 1. Patent Document 1 proposes a technique for removing biofilms derived from Candida fungi using a composition containing a sugar alcohol such as erythritol and a cationic bactericide.

[0004] JP 2008-303188 A

[0005] Candida albicans, a type of Candida fungus, is a dimorphic fungus. When pathogenic, it changes form from yeast to hyphal, colonizes and grows in living tissue, and damages the target tissue [see, for example, Medical Testing Vol. 63, No. 5, 2014, pp. 545-549 (https: / / www.jstage.jst.go.jp / article / jamt / 63 / 5 / 63_13-104 / _pdf / -char / ja)].

[0006] Conventional technologies, including the technology described in Patent Document 1, exert a bactericidal effect on Candida fungi but do not sufficiently suppress mycelium formation and proliferation. Insufficient suppression of mycelium formation and proliferation can lead to the formation of tongue coating, which can cause bad breath, and the onset of mycosis, so improvements are needed. In addition, there is a need for an effect of improving the balance between non-pathogenic resident bacteria and pathogenic bacteria in the oral cavity (microbial flora improvement effect).

[0007] An object of the present invention is to provide an oral care food that sufficiently inhibits the growth and hyphae formation of Candida and has the effect of improving the bacterial flora.

[0008] The present inventors conducted extensive research to solve the above-mentioned problems and arrived at the present invention. Specifically, the present invention relates to an oral care food containing at least one substance (X) selected from the group consisting of compounds (X1) having two or more hydroxy groups contained in oxo acid groups and salts thereof, wherein the total mass of the oxo acid groups contained in compound (X1), the mass of hydroxy groups not contained in oxo acid groups, the mass of carbonyl groups not contained in oxo acid groups, the mass of carbon atoms contained in the imidazole skeleton and the pyridine skeleton, and the mass of nitrogen atoms contained in the imidazole skeleton and the pyridine skeleton of compound (X1) is 45% by mass or more based on the molecular weight of compound (X1), the molecular weight of substance (X) is 550 or less, an aqueous solution containing 1% by weight of the oral care food has a pH of 6 to 8, and the oral care food is solid at 25°C.

[0009] According to the present invention, an oral care food can be provided which sufficiently inhibits the proliferation and hyphae formation of Candida and has the effect of improving the bacterial flora.

[0010] The oral care food of the present invention is a food containing at least one substance (X) selected from the group consisting of compounds (X1) having two or more hydroxy groups in oxo acid groups and salts thereof. The total mass of the oxo acid groups in compound (X1), the mass of hydroxy groups not contained in oxo acid groups, the mass of carbonyl groups not contained in oxo acid groups, the mass of carbon atoms contained in the imidazole skeleton and pyridine skeleton, and the mass of nitrogen atoms contained in the imidazole skeleton and pyridine skeleton is 45% by mass or more based on the molecular weight of compound (X1), and the molecular weight of substance (X) is 550 or less. The pH of an aqueous solution containing 1% by weight of the oral care food is 6 to 8. The oral care food is solid at 25°C.

[0011] [Substance (X)] The oral care food of the present invention contains substance (X). Substance (X) is at least one selected from the group consisting of compounds (X1) having two or more hydroxy groups contained in an oxo acid group and salts thereof. Compound (X1) may have two or more oxo acid groups. In the present application, "oxo acid group" refers to a group having a structure in which a hydroxy group (-OH) and an oxo group (=O) are bonded to a single central atom (carbon atom, phosphorus atom, sulfur atom, tungsten atom, etc.). Two or more hydroxy groups and two or more oxo groups may be contained in one oxo acid group. For example, triphosphate The oxo acid groups of the molecule are -P(=O)(OH) 2 and the central -P(=O)(OH)-, and the oxo acid groups at both ends contain two hydroxy groups.

[0012] From the viewpoint of the Candida growth inhibitory effect, the total ratio of the mass of the oxo acid group contained in compound (X1), the mass of the hydroxy group not contained in the oxo acid group, the mass of the carbonyl group (C=O) not contained in the oxo acid group, the mass of the carbon atoms contained in the imidazole skeleton and the pyridine skeleton, and the mass of the nitrogen atom contained in the imidazole skeleton and the pyridine skeleton is 45% by mass or more, preferably 55% by mass or more, based on the molecular weight of compound (X1). When compound (X1) is a salt, the above ratio is calculated using the mass and molecular weight of each compound converted into a free compound. When an oral care food contains multiple compounds as compound (X1), each compound satisfies this condition. In the present application, the mass of the oxo acid group is the total mass of the central atom, the oxo group, and the hydroxy group. For example, malic acid having a molecular weight of 134.1 In the case of citrate, since free citric acid has two carboxy groups (formula weight 45.0) that are oxo acid groups and one hydroxy group (formula weight 17.0) that is not included in the oxo acid groups, the proportion of the total mass of these groups based on the molecular weight of malic acid is [(45.0 x 2 + 17.0 x 1) / 134.1] x 100 = 80 (mass%). Also, in the case of citrate, since free citric acid has three carboxy groups (formula weight 45.0) that are oxo acid groups and one hydroxy group (formula weight 17.0) that is not included in the oxo acid groups, the proportion of the total mass of these groups based on the molecular weight of citric acid (192.1) is [(45.0 x 3 + 17.0 x 1) / 192.1] x 100 = 79 (mass%). The compound (X1) has an oxo acid group as an essential group, but optionally has a hydroxy group not contained in an oxo acid group, a carbonyl group not contained in an oxo acid group, an imidazole skeleton, and a pyridine skeleton, which are not essential.

[0013] In the present application, the term "imidazole skeleton" refers to (R is a hydrogen atom or a group capable of bonding to imidazole). These structures may be contained in a condensed ring.

[0014] From the viewpoint of the Candida growth inhibitory effect, the total mass of the oxo acid groups, the hydroxy groups not contained in the oxo acid groups, and the carbonyl groups not contained in the oxo acid groups contained in the compound (X1) is preferably 45 mass% or more based on the molecular weight of the compound (X1).

[0015] Examples of the compound (X1) include polyphosphates (pyrophosphate, triphosphate, tetrapolyphosphate, etc.), tungstic acid (H 2 WO 4 Examples of the tungstic acid include organic acids (ethylenediaminetetraacetic acid, iminodiacetic acid, malic acid, citric acid, tartaric acid, adenosine triphosphate, guanosine triphosphate, etc.), and amino acids (glutamic acid, etc.). In the present application, tungstic acid is considered to be a compound containing two hydroxy groups and two oxo groups in one oxo acid group, as shown in the following chemical formula (1), and is included in compound (X1).

[0016]

[0017] From the viewpoint of the Candida growth inhibitory effect, the compound (X1) is 2 It is preferred that the aryl group does not have a " group.

[0018] When compound (X1) is a hydroxycarboxylic acid, the ratio of the number of moles of hydroxy groups to the number of moles of carboxy groups (—COOH) in the hydroxycarboxylic acid (number of moles of —OH / number of moles of —COOH) is preferably 1 / 3 or more, and more preferably 1 / 2 or more, from the viewpoint of the Candida growth inhibitory effect.

[0019] The salt of compound (X1) is not particularly limited, and examples thereof include inorganic acid salts such as hydrochloride, sulfate, nitrate, and phosphate; organic acid salts such as acetate, citrate, maleate, malate, oxalate, lactate, succinate, fumarate, and propionate; alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; ammonium salt; salts with organic bases such as triethylamine, triethanolamine, and pyridine; and amino acid salts with basic or acidic amino acids such as arginine and glutamic acid. Among these, sodium salts and potassium salts are preferred.

[0020] As compound (X1), polyphosphoric acid and salts thereof, organic acids and salts thereof, and amino acids are preferred. From the viewpoint of safety, polyphosphoric acid (the number of repeating phosphate units is preferably 2 to 5, and more preferably 3 to 5) and salts thereof are more preferred, and pentasodium triphosphate is even more preferred.

[0021] From the viewpoint of the Candida growth inhibitory effect, the molecular weight of the compound (X1) is not more than 550. When the oral care food contains a plurality of compounds as the compound (X1), the molecular weight of each molecule is not more than 550.

[0022] It is preferable that the amount of magnesium captured by compound (X1) is 1 g or more per 100 g of compound (X1) when measured by an ion-selective electrode method. When compound (X1) is a hydrate, this means per 100 g of weight excluding water of hydration. The measurement by the ion-selective electrode method is carried out at 20°C using 1 mM MgCl at pH 7. 2 The aqueous solution is carried out using 2 mM of compound (X1).

[0023] [Cellulose derivative (Y)] The oral care food of the present invention may contain a cellulose derivative (Y) in addition to the substance (X). Note that the compound (X1) does not fall under the category of components contained in the cellulose derivative (Y). In this specification, the "cellulose derivative (Y)" is also referred to as the "(Y) component."

[0024] Specific examples of the cellulose derivative (Y) include carboxyalkyl cellulose and salts thereof (carboxymethyl ethyl cellulose, sodium carboxymethyl cellulose, etc.), alkyl cellulose and salts thereof (methyl cellulose (methyl cellulose 4000, etc.)), hydroxyalkyl methyl cellulose (hydroxypropyl methyl cellulose, etc.), etc. The cellulose derivative (Y) is preferably at least one selected from the group consisting of sodium carboxymethyl cellulose, methyl cellulose, and hydroxyalkyl methyl cellulose.

[0025] The viscosity of a 2% aqueous solution of the component (Y) at 20° C. is preferably 100 to 100,000 mPa·s, and more preferably 1,000 to 10,000 mPa·s. The component (Y) may be used alone or in combination of two or more types.

[0026] [Other Components] The oral care food of the present invention may contain a component (Z) other than the above substances (X) and (Y).

[0027] Examples of the component (Z) include antioxidants, preservatives, fragrances, solvents (water, etc.), and the like.

[0028] [Oral Care Food] The content (weight percentage) of substance (X) is preferably 0.01 to 5 wt %, more preferably 0.05 to 5 wt %, and even more preferably 0.1 to 3.5 wt %, based on the weight of the oral care food. From the viewpoint of more suitably imparting the Candida growth inhibitory effect, the content (weight percentage) of substance (X) is preferably a lower limit of 0.01 wt %, more preferably 0.05 wt %, based on the weight of the oral care food of the present invention. Furthermore, from the viewpoint of suitably maintaining non-pathogenic resident flora, the content of substance (X) is preferably an upper limit of 5 wt %, more preferably 3 wt %, based on the weight of the oral care food of the present invention. By containing substance (X) in the above range, it is possible to suitably impart the effects of having a high Candida growth inhibitory effect while maintaining non-pathogenic resident flora, and maintaining the above performance for a long period of time.

[0029] When the oral care food contains component (Y), the content (weight percentage) of component (Y) is preferably 0.1 to 5 wt %, and more preferably 1 to 2 wt %, based on the weight of the oral care food. From the viewpoint of more suitably imparting the Candida growth inhibitory effect, the content (weight percentage) of component (Y) is preferably a lower limit of 0.1 wt %, and more preferably 1 wt %, based on the weight of the oral care food of the present invention. Furthermore, from the viewpoint of suitably maintaining non-pathogenic resident bacteria, the content of component (Y) is preferably an upper limit of 5 wt %, and more preferably 2 wt %, based on the weight of the oral care food of the present invention.

[0030] The oral care food of the present invention has a pH of 6 to 8 in an aqueous solution containing 1% by weight of the oral care food. An aqueous solution containing 1% by weight of the oral care food can be obtained by diluting the oral care food with water (e.g., ion-exchanged water) so that the concentration of the oral care food becomes 1% by weight. By having a pH of 6 to 8 in a 1% by weight aqueous solution, an excellent effect of inhibiting the growth of Candida fungi can be obtained. The pH of the aqueous solution is preferably 6.1 to 7.9.

[0031] The pH can be measured using a pH meter at 25° C. The pH may be adjusted by the type and blending ratio of the compound (X1), or by adding a component other than the compound (X1).

[0032] The oral care food is solid at 25°C. "Solid at 25°C" means that it has no fluidity at 25°C.

[0033] The oral care food may contain a component that serves as a base material for the food. The base material can be selected appropriately depending on the form of the oral care food. For example, if the oral care food is a candy, it may contain starch syrup or the like as a base material. Examples of the form of the oral care food include candy, gummies, chewing gum, chocolate, tablet sweets (such as chewing soft candy), and jelly (solid at 25°C).

[0034] The oral care food of the present invention can be produced by blending the components and mixing them uniformly at room temperature or, if necessary, by heating (for example, 30 to 70° C.) The order and method of blending the components are not particularly limited.

[0035] The effects of the oral care food of the present invention will be explained. When the oral care food is contained in the oral cavity, substance (X) is eluted from the food and acts on Candida fungi contained in the oral cavity, suppressing their growth and mycelium formation. Furthermore, substance (X) selectively suppresses the growth of pathogenic bacteria, thereby balancing the oral flora. As a result, according to the present invention, an oral care food can be provided that sufficiently suppresses the growth and mycelium formation of Candida fungi and has the effect of improving the oral flora.

[0036] In this specification, examples of pathogenic bacteria include Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Candida albicans, etc. Examples of non-pathogenic bacteria include Streptococcus salivarius, etc.

[0037] The present specification discloses the following items [1] to [4]. [1] An oral care food containing at least one substance (X) selected from the group consisting of a compound (X1) having two or more hydroxy groups in an oxo acid group and a salt thereof, wherein the total mass of the oxo acid groups in the compound (X1), the mass of the hydroxy groups not contained in the oxo acid group, the mass of the carbonyl groups not contained in the oxo acid group, the mass of the carbon atoms contained in the imidazole skeleton and the pyridine skeleton, and the mass of the nitrogen atoms contained in the imidazole skeleton and the pyridine skeleton is 45% by mass or more based on the molecular weight of the compound (X1), the molecular weight of the substance (X) is 550 or less, an aqueous solution containing 1% by weight of the oral care food has a pH of 6 to 8, and the oral care food is solid at 25°C. [2] The oral care food according to [1], further containing a cellulose derivative (Y). [3] The oral care food according to [2], wherein the cellulose derivative (Y) is at least one selected from the group consisting of sodium carboxymethylcellulose, methylcellulose, and hydroxyalkylmethylcellulose. [4] The oral care food according to any one of [1] to [3], wherein the weight proportion of the substance (X) is 0.01 to 5 wt % based on the weight of the oral care food.

[0038] The present invention will be further described below with reference to examples and comparative examples, but the present invention is not limited thereto. Unless otherwise specified, parts mean parts by weight and % means % by weight.

[0039] Examples 1 to 15 and Comparative Examples 1 to 5: Production of Oral Care Foods Reduced maltose starch syrup (manufactured by Marumi Co., Ltd.) was heated in a microwave oven to 140-150°C. After cooling to 120°C, substance (X) or (X') and, if necessary, component (Y) were added and mixed at room temperature to achieve the concentration (wt%) shown in Table 1-1 or Table 1-2. After dissolution, the mixture was allowed to cool and solidify at room temperature to produce candy (food) weighing approximately 3 g per piece. Aqueous solutions containing 1 wt% of each candy were prepared, and the pH was measured. The results are shown in Tables 1-1 and 1-2.

[0040] <Explanation of Each Component> The raw materials corresponding to each component used in the examples and comparative examples are as follows. [Substance (X)] (X-1): pentasodium triphosphate [manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd., molecular weight: 367.86, ratio of the total mass of oxo acid groups to the molecular weight of triphosphate: 88% by mass] (X-2): malic acid [manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd., molecular weight: 134.09, ratio of the total mass of oxo acid groups and hydroxy groups not contained in oxo acid groups to the molecular weight of malic acid: 80% by mass] (X-3): glutamic acid [manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd., molecular weight: 147.13, ratio of the total mass of oxo acid groups to the molecular weight of glutamic acid: 61% by mass] (X-4): citric acid monohydrate [manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd., molecular weight: 210.14, ratio of the total mass of oxo acid groups and hydroxy groups not contained in oxo acid groups to the molecular weight of citric acid: 79% by mass] (X-5): Sodium citrate [manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd., molecular weight: 258.06, ratio of the total mass of oxo acid groups and hydroxy groups not contained in oxo acid groups to the molecular weight of citric acid: 79% by mass] (X-6): Sodium pyrophosphate (tetrasodium phosphate) (molecular weight: 265.90, ratio of the total mass of oxo acid groups to the molecular weight of diphosphate: 91% by mass) (X-7): Sodium tetrapolyphosphate (molecular weight: 469.83, ratio of the total mass of oxo acid groups to the molecular weight of tetrapolyphosphate: 86% by mass) [Substance (X'): Substance used in place of substance (X)] (X'-1): Cetylpyridinium chloride [manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.] (X'-2): Sodium lauroyl glutamate (molecular weight: 329.43, ratio of the total mass of oxo acid groups and carbonyl groups not contained in oxo acid groups to the molecular weight of lauroyl glutamic acid: 36% by mass) [Component (Y)] (Y-1): Methylcellulose [manufactured by Shin-Etsu Chemical Co., Ltd., degree of methoxy group substitution: 1.8, viscosity of a 2% aqueous solution at 20°C: 4,000 mPa·s] (Y-2): Hydroxypropyl methylcellulose 60SH [manufactured by Shin-Etsu Chemical Co., Ltd., degree of methoxy group substitution: 1.9, number of moles of hydroxypropyl group substitution: 0.25, viscosity of a 2% aqueous solution at 20°C: 4,000 mPa s] (Y-3): Hydroxypropyl methylcellulose 65SH [Shin-Etsu Chemical Co., Ltd., degree of methoxy group substitution 1.8, number of moles of hydroxypropyl group substitution 0.15 moles, viscosity of a 2% aqueous solution at 20 ° C. 4,000 mPa s] (Y-4): Hydroxypropyl methylcellulose 90SH [Shin-Etsu Chemical Co., Ltd., degree of methoxy group substitution 1.4, number of moles of hydroxypropyl group substitution 0.2 moles, viscosity of a 2% aqueous solution at 20 ° C. 4,000 mPa s] (Y-5): Carboxymethylcellulose sodium [Fujifilm Wako Pure Chemical Industries, Ltd., viscosity of a 1% aqueous solution at 25 ° C. 1,500 mPa s],

[0041] <Evaluation Test 1: In Vitro Mycelium Formation Inhibition Test of Candida Fungi> (1) Candida albicans was used as the Candida fungus. RPMI 1640 medium (Fujifilm Wako Pure Chemical Industries, Ltd.) supplemented with 2.5% fetal bovine serum (Biosera) was used as the medium. Each candy prepared according to the composition listed in Table 1-1 or Table 1-2 was added to 1 mL of the medium and stirred at 500 rpm using a stirrer at 37°C for 1 minute. The resulting supernatant was used as the sample solution for the test. Strains cultured overnight at 37°C were diluted with each sample solution to an absorbance of 0.15 at 600 nm, dispensed in 200 μL aliquots into 96-well plates, and then statically cultured at 37°C under aerobic conditions. After 48 hours, the plates were collected, and mycelium was stained using the following method.

[0042] (2) Mycelial staining of Candida albicans The inhibitory activity against the mycelial growth of Candida albicans was evaluated by the crystal staining method. This method involves staining Candida albicans grown in mycelial form with an aqueous solution of crystal violet (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and measuring the amount of staining relative to the number of grown colonies or [H 3Based on the correlation between the amount of α-glucose uptake into cells and the amount of staining, the amount of staining is used as an indicator of the degree of mycelial growth of Candida albicans. After culturing, the supernatant culture medium was removed from the plate recovered, and 200 μL of 70 vol% aqueous ethanol was added, followed by washing twice with 200 μL of ultrapure water. After removing the supernatant, 200 μL of 0.01% aqueous crystal violet was added and stained for 20 minutes. After staining, the plate was washed twice with 200 μL of ultrapure water, the supernatant was removed, and the plate was allowed to dry at room temperature for 10 minutes. 150 μL of 0.04 N-HCl-containing isopropyl alcohol and 50 μL of 0.25% aqueous sodium dodecyl sulfate were added, stirred for 5 minutes, and the amount of mycelial formation of Candida albicans was evaluated by measuring the absorbance at 620 nm. The inhibitory effect on mycelium formation was expressed as a relative value when the absorbance of a mixture of the same weight of component (Y) and reduced maltose syrup only (composition obtained by removing substance (X) or (X') from each candy) (Comparative Example 1) was set at 100. The results are shown in Table 1-1 and Table 1-2.

[0043] <Evaluation Test 2: In Vitro Growth Inhibition Test of Candida> Candida albicans was used as the Candida fungus. YM medium (Sigma) was used as the medium. 1 mL of each candy prepared with the composition listed in Table 1-1 or Table 1-2 was added to the medium and stirred at 500 rpm using a stirrer for 1 minute at 37°C. The supernatant was used as the sample solution for the test. Strains cultured overnight at 30°C were diluted with each sample solution so that the absorbance at 600 nm was 0.00015, and 200 μL of each solution was dispensed into a 96-well plate and statically cultured at 24°C under aerobic conditions. After 48 hours, the plates were recovered, and the growth of each fungus was evaluated by measuring the absorbance at 600 nm. The growth inhibitory effect was expressed as a relative value when the absorbance of a mixture of the same weight of component (Y) and reduced maltose syrup only (composition obtained by removing substance (X) or (X') from each candy) (Comparative Example 1) was used instead of each candy, was set at 100. The results are shown in Table 1-1 and Table 1-2.

[0044] <Evaluation Test 3: Evaluation of Oral Hygiene Improvement Effect in Volunteer Test> (1) Measurement of Tongue Coating Amount and Candida albicans Viable Bacterial Count Five volunteers (Subjects 1-5) ingested each candy prepared with the composition shown in Table 1-1 or Table 1-2 for four days. On the morning of the first day of the test (Day 1), immediately after waking, the subject scrubbed their tongue three times with a commercially available tongue brush and collected in a tube containing physiological saline. The collected samples were transported refrigerated and centrifuged. The precipitate was collected and weighed, and this was used as the tongue coating amount. The precipitate was thoroughly dispersed and resuspended in RPMI 1640 medium, applied to a Candida selective medium, and cultured at 37°C for 48 hours to measure the viable Candida albicans count. On the morning of Day 5, tongue coating was collected and transported in the same manner, and the tongue coating amount and viable Candida albicans count were measured. Starting on the fifth day, the volunteers ingested approximately 3 g (1 piece) of candy three times a day after each meal for four days. On the morning of the ninth day after the start of the study, the tongue coating score was evaluated as described below. The tongue coating mass and viable Candida albicans count were then measured using the same method. The tongue coating mass and viable Candida albicans count on the morning of the ninth day were expressed as relative values, with the tongue coating mass and viable Candida albicans count on the tongue coating collected on the morning of the fifth day set at 100, respectively. The results are shown in Tables 1-1 and 1-2. For Comparative Examples 2 and 3, the pH of the 1 wt% aqueous solution of the candy was greater than 8 or less than 6, making it unsuitable for long-term human testing from a safety perspective. Therefore, this test was not performed. For Comparative Example 4, the substance (X'-2) was not edible, so this test was not performed. (2) Evaluation of Tongue Coating Index (TCI) On the morning of the ninth day after the start of the test, the degree of tongue coating was evaluated using the Tongue Coating Index (TCI) method of Shimizu et al. The tongue surface was divided into nine sections, and the state of tongue coating in each section was visually evaluated using a three-level score (0: no tongue coating observed, 1: thin tongue coating with visible papillae, 2: thick tongue coating with no visible papillae), and the TCI was calculated using the following formula. The results are shown in Tables 1-1 and 1-2. A lower TCI is preferable. TCI (%) = (total scores of nine sections / 18) x 100

[0045] <Evaluation Test 4: Test to Confirm Selective Bacterial Growth Inhibition> In the test, Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia were used as pathogenic bacteria, and Streptococcus salivarius was used as non-pathogenic bacteria. Modified GAM bouillon "Nissui" (manufactured by Shimadzu Diagnostics Co., Ltd.) was used as the medium for culturing each bacterium. Each candy prepared with the composition shown in Table 1-1 or Table 1-2 was added to 1 mL of modified GAM medium and stirred at 500 rpm using a stirrer at 37 ° C for 1 minute. The supernatant was used as the sample solution for the test. Each strain was cultured overnight at 37°C and diluted with each sample solution to an absorbance of 0.15 at 600 nm. 200 μL of each solution was dispensed into a 96-well plate, and then statically cultured at 37°C under anaerobic conditions using Anaeropack Kenki 10% (Mitsubishi Gas Chemical Co., Inc.). After 48 hours, the plates were collected and the absorbance at 600 nm was measured to evaluate the growth of each strain. The growth inhibitory effect was expressed as a relative value, with the absorbance of the mixture (composition obtained by removing substance (X) or (X') from each candy) (Comparative Example 1) set at 100. The results are shown in Tables 1-1 and 1-2.

[0046] When the oral care food of the present invention is applied to the oral cavity, if the growth of Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia is inhibited compared to Comparative Example 1, and the change in the growth of Streptococcus salivarius is small compared to Comparative Example 1, then the growth of the bacteria is selectively inhibited. For example, an embodiment in which the above relative values ​​are in the following ranges can be mentioned: an embodiment in which the test results for Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia are all 0 to 30, and the test result for Streptococcus salivarius is 50 to 100.

[0047]

[0048]

[0049] As shown in Tables 1-1 and 1-2, it was confirmed that the foods of Examples 1 to 15 containing substance (X) had superior inhibitory effects on Candida mycelium formation and proliferation compared to the food of Comparative Example 1. On the other hand, it was confirmed that the foods of Comparative Examples 2 to 5 had inferior inhibitory effects on mycelium formation compared to Examples 1 to 15. Furthermore, it was found that the foods of Examples 1 to 15 containing substance (X) selectively inhibited the proliferation of pathogenic bacteria with little effect on non-pathogenic bacteria, and therefore had a bacterial flora-improving effect. These results demonstrate that the present invention can provide an oral care food that sufficiently inhibits the proliferation and mycelium formation of Candida and has a bacterial flora-improving effect.

Claims

1. An oral care food containing at least one substance (X) selected from the group consisting of compounds (X1) having two or more hydroxy groups contained in oxo acid groups and salts thereof, wherein the total mass of the oxo acid groups contained in said compound (X1), the mass of hydroxy groups not contained in oxo acid groups, the mass of carbonyl groups not contained in oxo acid groups, the mass of carbon atoms contained in the imidazole skeleton and pyridine skeleton, and the mass of nitrogen atoms contained in the imidazole skeleton and pyridine skeleton is 45 mass% or more based on the molecular weight of compound (X1), the molecular weight of said substance (X) is 550 or less, the pH of an aqueous solution containing 1% by weight of said oral care food is 6 to 8, and said oral care food is solid at 25°C.

2. The oral care food according to claim 1, further comprising a cellulose derivative (Y).

3. The oral care food according to claim 2, wherein the cellulose derivative (Y) is at least one selected from the group consisting of sodium carboxymethylcellulose, methylcellulose, and hydroxyalkylmethylcellulose.

4. An oral care food according to any one of claims 1 to 3, wherein the weight proportion of the substance (X) is 0.01 to 5% by weight based on the weight of the oral care food.

Citation Information

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