Composition containing monoammonium glycyrrhizinate

Abstract

To develop methods to further enhance the anti-inflammatory effects of monoammonium glycyrrhizinate. [Solution] An oral composition containing (A) monoammonium glycyrrhizinate and (B) a compound having an ethylene oxide polymerization structure, wherein the mass ratio of (A) to (B) is 1:1 to 12 or 1:38 to 50.

Description

Technical Field

[0005]

[0001] The present disclosure relates to a composition containing monoammonium glycyrrhizinate and the like. More specifically, the present disclosure relates to an oral composition containing monoammonium glycyrrhizinate and the like.

Background Art

[0002] Monoammonium glycyrrhizinate (hereinafter also referred to as "MAG") is an ammonium salt of glycyrrhizic acid, a component derived from licorice. This component has an anti-inflammatory effect and is added, for example, to oral compositions to impart an anti-inflammatory effect and is used in various oral preparations. Since suppressing inflammation is important for preventing and suppressing the progression of periodontal disease, the development of preparations having a higher anti-inflammatory effect is required.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] The present inventors conducted studies for the purpose of developing a means to further enhance the anti-inflammatory effect of monoammonium glycyrrhizinate. [[ID=4之0]]

Means for Solving the Problems

[0005] The present inventors found that when monoammonium glycyrrhizinate is used in combination with a compound having an ethylene oxide polymerization structure, the anti-inflammatory effect of monoammonium glycyrrhizinate can be enhanced, and further improvements were made. The present disclosure includes, for example, the subject matter described in the following items. Item 1. (A) Monoammonium glycyrrhizinate, and (B) Compounds having an ethylene oxide polymerization structure It contains, The mass ratio of (A) to (B) contained is 1:1 to 12, or 1:38 to 50. Oral composition. Section 2. (A) 0.01~0.2 mass%, (B) 0.1-2% by mass, Contains, The oral composition described in item 1. Section 3. (A) 0.01 to 0.1 mass%, (B) 0.1-2% by mass, The oral composition described in item 1 contains. Section 4. (B) is polyoxyethylene hydrogenated castor oil. The oral composition according to any one of claims 1 to 3. Section 5. The oral composition according to item 4, wherein (B) is polyoxyethylene hydrogenated castor oil having an ethylene oxide addition mole number of 10 to 100. Section 6. (A) contains 0.01 to 0.05% by mass, (B) is polyoxyethylene hydrogenated castor oil (HCO3). Oral compositions as described in item 3 or 5. [Effects of the Invention]

[0006] A composition (particularly an oral composition) is provided in which the anti-inflammatory effect of monoammonium glycyrrhizinate is efficiently enhanced. More specifically, a composition (particularly an oral composition) is provided that exhibits excellent anti-inflammatory effects even with a relatively low monoammonium glycyrrhizinate content. [Brief explanation of the drawing]

[0007] [Figure 1]The anti-inflammatory effects of monoammonium glycyrrhizinate (MAG) and dipotassium glycyrrhizinate (GK2) against inflammation caused by LPS derived from Porphyromonas gingivalis (Pg bacteria) are shown by the percentage increase or decrease in the inflammatory cytokine TNF-α. [Figure 2] The anti-inflammatory effects of monoammonium glycyrrhizinate (MAG), polyoxyethylene hydrogenated castor oil (HCO-60), and combinations thereof against inflammation caused by LPS derived from P. gingivalis are shown by the percentage increase or decrease in the inflammatory cytokine TNF-α. [Figure 3] The anti-inflammatory effects of a combination of monoammonium glycyrrhizinate (MAG) and polyoxyethylene hydrogenated castor oil (HCO-60) against inflammation caused by LPS derived from P. gingivalis are shown as the percentage increase or decrease in the inflammatory cytokine TNF-α. [Figure 4] The anti-inflammatory effects of a combination of monoammonium glycyrrhizinate (MAG) and polyoxyethylene hydrogenated castor oil (HCO-10, HCO-60, or HCO-100) against inflammation caused by LPS derived from P. gingivalis are shown as the percentage increase or decrease in the inflammatory cytokine TNF-α. [Modes for carrying out the invention]

[0008] The embodiments included in this disclosure will be described in more detail below. This disclosure preferably includes, but is not limited to, compositions (particularly oral compositions) containing (A) monoammonium glycyrrhizinate (MAG) and (B) compounds having an ethylene oxide polymerization structure, and includes everything disclosed herein and recognizable to those skilled in the art. Monoammonium glycyrrhizinate may be referred to as component (A), and compounds having an ethylene oxide polymerization structure as component (B). Furthermore, compositions containing the aforementioned components (A) and (B) included in this disclosure may hereinafter be referred to as the compositions of this disclosure.

[0009] Component (B) is a compound having an ethylene oxide polymerization structure. Examples of such compounds include polyoxyethylene hydrogenated castor oil (HCO), polyethylene glycol (PEG), polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, and the like.

[0010] Also, in component (B), the number of moles of ethylene oxide added in the ethylene oxide polymerization structure is preferably 10 to 100. The upper or lower limit of this range may be, for example, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95. For example, this range may be 20 to 80, or 30 to 70.

[0011] Although not particularly limited, polyoxyethylene hydrogenated castor oil is preferred as component (B), and particularly preferred is polyoxyethylene hydrogenated castor oil having an ethylene oxide addition mole number of 10 to 100 (more preferably 20 to 80, even more preferably 30 to 70). Component (B) can be used alone or in combination of two or more.

[0012] Components (A) and (B) are contained in a mass ratio ((A) component : (B) component) of 1:1 to 12, or 1:38 to 50.

[0013] The upper or lower limit of the mass ratio range (1 to 12) of the former component (B) may be, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, �.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8, 8.ı, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 11, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, or 11.9. For example, the range may be 1.1 to 11 or 1.2 to 10.

[0014] It should be noted that there seems to be a character "�" in the original text which might be a typo in the Chinese part. I've translated it as it is in the English version for the purpose of following the rules. If it's incorrect, please provide the correct text.Furthermore, the upper or lower limits of the mass ratio range (38-50) of the latter component (B) are, for example, 38.1, 38.2, 38.3, 38.4, 38.5, 38.6, 38.7, 38.8, 38.9, 39, 39.1, 39.2, 39.3, 39.4, 39.5, 39.6, 39.7, 39.8, 39.9, 40, 40.1, 40.2, 40.3, 40.4, 40 0.5, 40.6, 40.7, 40.8, 40.9, 41, 41.1, 41.2, 41.3, 41.4, 41.5, 41.6, 41.7, 41.8, 41.9, 42, 42.1, 42.2, 42.3, 42.4, 42.5, 42.6, 42.7, 42.8, 42.9, 43, 43.1, 43.2, 43.3, 43.4, 43.5, 43.6, 43. 7, 43.8, 43.9, 44, 44.1, 44.2, 44.3, 44.4, 44.5, 44.6, 44.7, 44.8, 44.9, 45, 45.1, 45.2, 45.3, 45.4, 45.5, 45.6, 45.7, 45.8, 45.9, 46, 46.1, 46.2, 46.3, 46.4, 46.5, 46.6, 46.7, 46.8, 46. The range may also be 9, 47, 47.1, 47.2, 47.3, 47.4, 47.5, 47.6, 47.7, 47.8, 47.9, 48, 48.1, 48.2, 48.3, 48.4, 48.5, 48.6, 48.7, 48.8, 48.9, 49, 49.1, 49.2, 49.3, 49.4, 49.5, 49.6, 49.7, 49.8, or 49.9. For example, the range may be 39-49 or 40-48.

[0015] Furthermore, in the compositions of this disclosure, component (A) is preferably contained in an amount of 0.01 to 0.2% by mass. The upper or lower limit of this range may be, for example, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, or 0.19% by mass. This range may also be, for example, 0.01 to 0.15% by mass, 0.01 to 0.1% by mass, or 0.01 to 0.05% by mass, or 0.02 to 0.15% by mass, or 0.02 to 0.1% by mass.

[0016] Furthermore, in the compositions of this disclosure, component (B) is preferably contained in an amount of 0.1 to 2% by mass. The upper or lower limit of this range may be, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, or 1.9% by mass. This range may be, for example, 0.1 to 1% by mass, or for example, 0.2 to 2% by mass or 0.2 to 1% by mass.

[0017] The above-mentioned range of content (mass%) of component (A) and the range of content (mass%) of component (B) can be combined in any way to preferably form the composition of this disclosure, but for example, satisfying the above-mentioned mass ratio of component (A) to component (B), and having component (A) at 0.01 to 0.2 mass%, It is preferable to contain 0.1 to 2% by mass of component (B), and more preferably to contain 0.01 to 0.1% by mass of component (A) and 0.1 to 2% by mass of component (B).

[0018] The compositions of this disclosure are not particularly limited, but can be preferably used, for example, as oral compositions and topical compositions. These may be referred to as the oral compositions and topical compositions of this disclosure, respectively.

[0019] The oral composition of this disclosure may be, for example, a solid composition or a liquid composition, and is preferably a solid composition. The oral composition can be used, for example, as a pharmaceutical or quasi-drug. The form of the oral composition of this disclosure is not particularly limited, but can be made into, for example, an ointment, paste, paste, gel, liquid, spray, mouthwash, liquid toothpaste, toothpaste, gum, lozenge, candy, etc., according to conventional methods. Among these, it is preferably a mouthwash, liquid toothpaste, toothpaste, ointment, paste, liquid, or gel, and more preferably a toothpaste, ointment, paste, or gel.

[0020] Furthermore, the oral composition of this disclosure, by containing component (A) and component (B) in the above-mentioned specific mass ratio, can exert an anti-inflammatory effect more efficiently (specifically, even at relatively low concentrations), and is therefore preferably used, for example, for the improvement and prevention of periodontal disease.

[0021] The oral compositions of this disclosure may contain, alone or in addition to two or more optional components that can be incorporated into oral compositions, as long as they do not impair the effects.

[0022] For example, cationic surfactants, nonionic surfactants, anionic surfactants, or amphoteric surfactants can be incorporated as surfactants. Specifically, examples of cationic surfactants include ammonium salts with alkyl groups such as dodecylpyridinium chloride, and cationic amino acid-based surfactants such as N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate. 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; sorbitan fatty acid esters; glycerin fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers with a polyoxyethylene addition coefficient of 8 to 10 and 13 to 15 carbon atoms in the alkyl group; polyoxyethylene alkylphenyl ethers with a polyoxyethylene addition coefficient of 10 to 18 and 9 carbon atoms in the alkyl group; 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 sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; 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 activators such as lauryl dimethylaminoacetic acid betaine and coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine; imidazoline-type activators such as sodium N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine; and amino acid-type activators such as N-lauryldiaminoethylglycine. 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.

[0023] Furthermore, as flavoring agents, for example, menthol, carboxylic acid, 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.

[0024] 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 in amounts of, for example, 0.01 to 1% by mass relative to the total amount of the composition.

[0025] 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.

[0026] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride may be included.

[0027] As coloring agents, 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 added.

[0028] 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.

[0029] The oral compositions disclosed herein further include, as pharmaceutically active ingredients, vitamin E derivatives such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate; vitamin C derivatives such as ascorbic acid, sodium ascorbate, or magnesium ascorbate phosphate; vitamin B6 derivatives such as pyridoxine hydrochloride; vitamin B5 derivatives such as pantothenic acid and panthenol; amphoteric bactericides such as dodecyldiaminoethylglycine; nonionic bactericides such as triclosan, isopropylmethylphenol, and hinokitiol; anionic bactericides such as sodium lauroyl sarcosinate; and cationic bactericides such as cetylpyridinium chloride, chlorhexidine hydrochloride, and benzethonium chloride. The following can be formulated individually or in combination of two or more: an agent, enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and lytic enzymes (Litec enzyme); 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, sodium copper chlorophyllin, glycerophosphate, chlorophyll, sodium chloride, caropeptide, allantoin, carbazochrome, potassium nitrate, and palatinite.

[0030] Furthermore, it is possible to add alcohols, silicones, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, Plastibase, etc., as base materials.

[0031] Furthermore, the topical compositions of the present invention are particularly preferably used as compositions applied to the skin. Examples of topical compositions include pharmaceutical compositions, quasi-drug compositions, and cosmetic compositions. The dosage form is not particularly limited, but examples include face packs, pastes, ointments, creams, gels, lotions, emulsions, serums, toners, and sprays. Furthermore, the topical composition disclosed herein can exert an anti-inflammatory effect more efficiently (specifically, even at relatively low concentrations) by containing component (A) and component (B) in the above-mentioned specific mass ratio. Therefore, it can be preferably used, for example, as an anti-inflammatory topical agent (particularly an anti-dermatological agent or atopic agent for the neck). The topical composition disclosed herein may further contain other components that can be incorporated into the topical composition, either alone or in combination with two or more other components, as long as the effect is not impaired.

[0032] Other components that can be included include, for example, polymers, proteins and their hydrolysates, and mucopolysaccharides. Examples of polymers include, but are not limited to, carboxyvinyl polymer, xanthan gum, and sodium alginate. Carboxyvinyl polymer and xanthan gum are preferred, and carboxyvinyl polymer is particularly preferred. These polymers can be used individually or in combination of two or more. The amount of polymer included is not particularly limited, but is 0.001 to 20%, preferably 0.005 to 10%, and particularly preferably 0.01 to 5%. Examples of proteins and their hydrolysates include collagen, elastin, keratin, casein, their hydrolysates, salts of hydrolysates, esters of hydrolysates, or enzymatically treated proteins, but collagen is particularly preferred. The amount of protein and its hydrolysates included is not particularly limited, but is 0.001 to 5%, preferably 0.01 to 1%. Examples of mucopolysaccharides include chondroitin sulfate, hyaluronic acid, dermatan sulfate, heparan sulfate, mucoitin sulfate, heparin and its derivatives, and their salts, but chondroitin sulfate, hyaluronic acid, and their sodium salts are particularly preferred. The amount of mucopolysaccharide is not particularly limited, but is 0.0005 to 5%, preferably 0.001 to 1%.

[0033] In addition, known components commonly used in topical compositions may also be incorporated, as long as they do not impair the effects of the present invention. Examples of such components include humectants, water-soluble polymers, oil components, colorants, antioxidants, chelating agents, preservatives, pH adjusters, cooling agents, fragrances, UV absorbers / scatterers, antioxidants, and pharmacoactive ingredients. The compositions of this disclosure (e.g., the oral and topical 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 components (A) and (B) and, if necessary, other components.

[0034] Furthermore, the subjects to whom the compositions of this disclosure (for example, the oral and topical compositions of this disclosure) can be applied are not particularly limited, but humans and non-human mammals are preferred. Preferred non-human mammals include livestock and pets, more specifically dogs, cats, mice, rats, horses, cattle, sheep, monkeys, etc. The oral compositions of this disclosure exhibit excellent anti-inflammatory effects against oral inflammation caused by Porphyromonas gingivalis (Pg bacteria), a causative agent of periodontitis, etc. (particularly oral inflammation caused by Pg bacteria LPS), and are therefore preferably used for subjects (particularly humans) who have Pg bacteria in their oral cavity.

[0035] In this specification, the term "comprising" includes both "consisting essentially of" and "consisting of." Furthermore, this disclosure encompasses all any combination 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 embodiments of this disclosure will be described in more detail below with examples, but the embodiments of this disclosure are not limited to the examples below. The test substances used were monoammonium glycyrrhizinate (MAG), dipotassium glycyrrhizinate (GK2), and polyoxyethylene hydrogenated castor oil (HCO2). The number following HCO2, separated by a hyphen, represents the number of moles of ethylene oxide added to the HCO2. For example, HCO2-60 indicates polyoxyethylene hydrogenated castor oil with 60 moles of ethylene oxide added. In addition, one or two of each test substance were dissolved in 1 vol% DMSO (dimethyl sulfoxide) to prepare the test substance solution.

[0038] Furthermore, human monocyte-derived THP-1 cells were purchased from the cell bank of the Japan Biomedical Innovation, Health and Nutrition (JCRB) and used. The culture medium used was RPMI-1640 medium (Sigma-Aldrich) supplemented with 10% FBS (biowest). For LPS (Lipopolysaccharide) derived from Porphyromonas gingivalis (Pg bacteria), LPS-PG Standard (Invitrogen) dissolved in water was used.

[0039] Human monocyte-derived THP-1 cells were treated with PMA (phorbol myristate acetate) and differentiated into macrophage-like cells (MΦ). Various concentrations of test substance solutions and Pg bacteria-derived LPS were simultaneously added to these macrophage-like cells, and the culture supernatant was collected after 2 hours. Control experiments were also performed with only Pg bacteria-derived LPS added (LPS(+)) or with no addition (LPS(-)). The inhibitory effect on inflammatory cytokine TNF-α production was evaluated using ELISA with the collected culture supernatant. Specifically, TNF-α concentration was measured using the AuthenhiKine TNF-alpha ELISA Kit (proteintech), and the TNF-α increase / decrease rate (%) was calculated using the following formula. Note that when only Pg bacteria-derived LPS was added (LPS(+)), the TNF-α increase / decrease rate (%) was 100%. TNF-α increase / decrease rate (%) = (TNF-α concentration with LPS added and each test substance added) / (TNF-α concentration with LPS added and no test substances added) × 100

[0040] Figure 1 shows the percentage increase or decrease in TNF-α when using a 0.05% by mass test solution of MAG and a 0.05% by mass test solution of GK2. It was found that MAG has a higher anti-inflammatory effect compared to GK2 on inflammation caused by P. gynecocytes.

[0041] Furthermore, Figure 2 shows the percentage increase or decrease in TNF-α when using the HCO-60 0.2% by mass test solution, the MAG 0.04% by mass test solution, and the HCO-60 0.2% by mass and MAG 0.04% by mass test solutions. It was found that HCO did not show an anti-inflammatory effect on inflammation caused by P. gingivalis, while it significantly enhanced the anti-inflammatory effect of MAG. Therefore, we investigated test substance solutions containing MAG and HCO-60 at various concentrations and calculated the percentage increase or decrease in TNF-α. Then, to evaluate the effect of using MAG and HCO-60 in combination, we calculated the Combination Index (CI) value according to the following formula (TING-CHAO CHOU, et al. Trends Pharmacol Sci. 1983;4:450-454, C Patrick Reynolds, et al. Methods Mol Med. 2005;110:173-83). CI = (D)1 / (Dx)1 + (D)2 / (Dx)2 (D)1:MAG concentration (mass%) (D)2:HCO-60 concentration (mass%) (Dx)1: The concentration (IC90 value) that inhibits the TNF-α increase / decrease rate (%) by 90% when using MAG alone. (Dx)2: The concentration (IC90 value) at which HCO-60 alone inhibits 90% of the TNF-α increase / decrease rate.

[0042] Furthermore, inhibiting the TNF-α increase / decrease rate (%) by 90% also means that the TNF-α increase / decrease rate (%) becomes 10% or less.

[0043] A synergistic effect was determined when CI ≤ 0.9. The results are shown in the table below. [Table 1]

[0044] Furthermore, Figure 3 shows the percentage increase or decrease in TNF-α when using test solutions with MAG:HCO-60 (concentration ratio) of 1:40, 1:10, and 1:2.5, as shown in the table.

[0045] Furthermore, in the table, the percentage increase or decrease in TNF-α when using the test solution for which a synergistic effect was judged as "yes" was 10% or less (= 90% or more inhibition). In addition, in the table, although the synergistic effect was judged as "no" when using the test solutions with MAG:HCO-60 (concentration ratio) of 1:15 and 1:30, the percentage increase or decrease in TNF-α for the former was approximately 15% (= approximately 85% inhibition), and for the latter it was approximately 30% (= approximately 70% inhibition), which still shows a significant improvement in effect compared to MAG alone.

[0046] These results show that even at relatively low concentrations of MAG (for example, 0.2% by mass or less, preferably 0.1% by mass or less), sufficient anti-inflammatory effects can be obtained when used in combination with HCO3.

[0047] Furthermore, the percentage increase or decrease in TNF-α when HCO-10 with different amounts of added ethylene oxide was used in combination with MAG was investigated. Figure 4 shows the percentage increase or decrease in TNF-α when using the following test solutions: MAG 0.04% by mass, MAG 0.04% by mass and HCO-10 0.3% by mass, MAG 0.04% by mass and HCO-60 0.3% by mass, and MAG 0.04% by mass and HCO-100 0.3% by mass.

[0048] The following are examples of prescriptions. [Table 2A] [Table 2B] [Table 2C] [Table 2D] [Table 2E]

Claims

1. (A) Monoammonium glycyrrhizinate, and (B) Compounds having an ethylene oxide polymerization structure It contains, The mass ratio of (A) to (B) contained is 1:1 to 12, or 1:38 to 50. Oral composition.

2. (A) 0.01 to 0.2 mass%, (B) 0.1 to 2% by mass, Contains, The oral composition according to claim 1.

3. (A) 0.01 to 0.1 mass%, (B) 0.1 to 2% by mass, An oral composition according to claim 1, comprising the following:

4. (B) is polyoxyethylene hydrogenated castor oil. An oral composition according to any one of claims 1 to 3.

5. The oral composition according to claim 4, wherein (B) is polyoxyethylene hydrogenated castor oil having an ethylene oxide addition mole number of 10 to 100.

6. (A) contains 0.01 to 0.05% by mass, (B) is polyoxyethylene hydrogenated castor oil (HCO). The oral composition according to claim 3.

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