CN116370333A - Compositions containing beta-glycyrrhetinic acid - Google Patents

Abstract

Compositions containing beta-glycyrrhetinic acid. [Problem] To provide a composition that inhibits the activity of neutrophil collagenase. [Solution] An oral composition comprising β-glycyrrhetinic acid and ethylenediaminetetraacetic acid and/or a salt thereof, ethylenediaminetetraacetic acid and/or 1 part by mass of β-glycyrrhetinic acid The total content of the salt is 0.15-5 parts by mass.

Description

Compositions containing beta-glycyrrhetinic acid

technical field

The present disclosure relates to a composition and the like containing β-glycyrrhetinic acid, preferably a composition and the like further containing ethylenediaminetetraacetic acid and/or a salt thereof. In addition, it relates to uses and the like of the composition.

Background technique

Matrix metalloproteinase (MMP, Matrix metalloproteinase) is a generic term for extracellular matrix-degrading enzymes that retain zinc (II) ions in their active sites. Its main substrates are biological macromolecules such as collagen, laminin, gelatin, and fibronectin.

MMPs are considered to play a role in maintaining homeostasis by controlling angiogenesis and building new tissues by degrading unnecessary extracellular matrix in the process of tissue remodeling and wound healing in vivo. However, if the activity of MMP is too high, tissue destruction progresses, and periodontal disease, rheumatoid arthritis, tumor infiltration, and its metastasis phenomenon are involved, so components that can control its activity have been searched for.

prior art literature

patent documents

Patent Document 1: Japanese Patent No. 5339708

non-patent literature

Non-Patent Document 1: Journal of the Periodic Dental Period 59(4): 185-190, 2017

Non-Patent Document 2: J Clin Periodontol. 2021 Aug; 48(8): 1051-1065.

Contents of the invention

The problem to be solved by the invention

MMP-8 is called neutrophil collagenase because it is a collagenase that produces neutrophils. It is known that it mainly degrades extracellular matrix such as collagen, and accounts for about ten percent of the MMP in the gingival crevicular leaching fluid. eight. It is believed that neutrophils respond to inflammation in the periodontal pocket and accumulate in the gingival sulcus leachate to produce neutrophil collagenase (MMP-8), thereby destroying the attached epithelium in the periodontal pocket and producing Periodontal pocket deepens, periodontal disease progresses (Non-Patent Document 1). Therefore, for the prevention of the progression of periodontal disease, it is desired to search for a component that can control the activity of neutrophil collagenase (Patent Document 1).

The object of the present disclosure is to provide a composition for inhibiting neutrophil collagenase activity.

solutions to problems

The inventors of the present invention found that β-glycyrrhetinic acid has inhibitory activity against neutrophil collagenase. Furthermore, it was found that the use of β-glycyrrhetinic acid and ethylenediaminetetraacetic acid in a specific ratio exhibits excellent inhibitory activity against neutrophil collagenase. Based on these findings, further improvements were repeated.

This disclosure includes, for example, the subjects described in the following items.

Item 1. An oral composition comprising β-glycyrrhetinic acid, and ethylenediaminetetraacetic acid and/or a salt thereof,

The total content of ethylenediaminetetraacetic acid and/or its salt is 0.15-5 mass parts with respect to 1 mass part of (beta)-glycyrrhetinic acid.

Item 2.

The composition according to item 1, wherein the content of β-glycyrrhetinic acid in the composition is 0.002% by mass or more.

Item 3.

The composition according to item 1 or 2, wherein the total content of ethylenediaminetetraacetic acid and/or salts thereof in the composition is 0.001% by mass or more.

Item 4.

Use of the composition for the manufacture of an oral composition for preventing the progression of periodontal disease, the composition containing β-glycyrrhetinic acid, and ethylenediaminetetraacetic acid and/or its salt, relative to β-glycyrrhetinic acid 1 The total content of ethylenediaminetetraacetic acid and/or its salt is 0.15-5 parts by mass.

Item 5.

Application of the composition in the manufacture of an oral composition for inhibiting the activity of neutrophil collagenase in the oral cavity, the composition contains β-glycyrrhetinic acid and ethylenediaminetetraacetic acid and/or its salt, relatively The total content of ethylenediaminetetraacetic acid and/or its salt is 0.15-5 mass parts with respect to 1 mass part of (beta)-glycyrrhetinic acid.

Item 6.

Use of β-glycyrrhetinic acid for producing an oral composition for inhibiting neutrophil collagenase activity in the oral cavity.

Item 7.

Use of β-glycyrrhetinic acid in the manufacture of an oral composition for inhibiting the degradation of gingival collagen.

Item 8.

Use of β-glycyrrhetinic acid for the manufacture of an oral composition for suppressing gingival recession, suppressing gingival destruction, suppressing gingiva descent, or suppressing attachment loss.

Item 9.

The use according to any one of Items 6 to 8, wherein the composition for oral cavity is a composition for oral cavity containing 0.005% by mass or more of β-glycyrrhetinic acid.

The effect of the invention

Can inhibit neutrophil collagenase activity. In addition, an effective composition for preventing progress of periodontal disease can be provided.

Description of drawings

Fig. 1 shows the measurement results of neutrophil collagenase activity when β-glycyrrhetinic acid was added.

Fig. 2 shows the measurement results of neutrophil collagenase (MMP-8) activity when each raw material was added.

Fig. 3 shows the measurement results of neutrophil collagenase activity when β-glycyrrhetinic acid and ethylenediaminetetraacetic acid 3 sodium salt were added.

Detailed ways

Each of the embodiments included in the present disclosure will be described in more detail below.

Compositions encompassed by the present disclosure contain β-glycyrrhetinic acid, preferably also ethylenediaminetetraacetic acid and/or salts thereof. In this specification, this composition may be described as "the composition of this disclosure."

β-glycyrrhetinic acid has the following formula:

Compounds shown. The β-glycyrrhetinic acid used in the composition of the present disclosure may be a synthetic product, or may be obtained by hydrolyzing glycyrrhizic acid extracted from natural products (such as licorice).

The content of β-glycyrrhetinic acid in the composition of the present disclosure is not particularly limited as long as it is within the range in which the effect is exhibited. For example, in the composition of the present disclosure, the content of β-glycyrrhetinic acid may be 0.002% by mass or more. Although the upper limit is not specifically limited, For example, 0.5 mass % is mentioned. The upper or lower limit of this range (0.002 to 0.5% by mass) can be, for example, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.015, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, or 0.4% by mass. For example, it may be 0.002 to 0.4 mass %, or may be 0.02 to 0.2 mass %.

Although not particularly limited, the content of β-glycyrrhetinic acid is preferably 0.005% by mass or more from the viewpoint of more strongly exerting the inhibitory activity of neutrophil collagenase activity by β-glycyrrhetinic acid. More preferably, it is 0.02 mass % or more.

Examples of salts of ethylenediaminetetraacetic acid include sodium salts, potassium salts, calcium salts, and magnesium salts. Among them, sodium salt is preferable. Examples of the sodium salt of EDTA include EDTA2 sodium, EDTA3 sodium, EDTA4 sodium, and the like.

The total content of ethylenediaminetetraacetic acid and/or its salt in the composition of this disclosure will not be specifically limited as long as it exists in the range which exhibits an effect. For example, in the composition of the present disclosure, the total content of ethylenediaminetetraacetic acid and/or its salt may be 0.001% by mass or more. The upper or lower limit of the range can be, for example, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 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 , or 0.5% by mass. For example, it may be 0.001 to 0.5% by mass, or may be 0.02 to 0.3% by mass.

It is preferable that the total content of ethylenediaminetetraacetic acid and/or its salt is 0.15-5 mass parts with respect to 1 mass part of (beta)-glycyrrhetinic acid in the composition of this disclosure. The upper limit or lower limit of this range can be 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, or 4 parts by mass, for example. For example, it may be 0.2-4 mass parts, and may be 0.25-2.5 mass parts.

Neutrophil collagenase (EC 3.4.24.34) refers to the collagenase produced by neutrophils, known as MMP-8.

Inhibition of neutrophil collagenase activity refers to inhibition of degradation of neutrophil collagenase-based substrates (such as type I collagen, type II collagen, type III collagen, etc.).

The composition of the present disclosure can inhibit the degradation of tissues (such as attachment epithelium, gingival sulcus epithelium, alveolar periosteum, etc.) Destruction, degradation of gingival collagen (collagen fibers that make up the gums), etc. In addition, because the composition of the present disclosure has an inhibitory effect on neutrophil collagenase activity, it can inhibit the activity of already produced neutrophil collagenase.

Therefore, the composition of the present disclosure is suitable as an oral composition. More specifically, the composition of the present disclosure can be used for, for example, inhibition of the progress of periodontal disease, inhibition of neutrophil collagenase activity, inhibition of gingival recession, inhibition of periodontal pocket formation, inhibition of periodontal pocket deepening, and periodontal tissue destruction. It is used for the prevention of the progress of periodontal diseases such as inhibition of gingival descent, inhibition of gingival collagen degradation, inhibition of attachment loss, protection of periodontal tissue collagen, and inhibition of destruction of periodontal tissue accompanied by chronic inflammation, and/or for the protection of dentin collagen Wait and use. In the present specification, "inhibition of periodontal pocket formation" means inhibition of the formation of periodontal pockets (sulcus between teeth and gums (gums)). In this specification, "inhibition of periodontal pocket deepening" refers to inhibiting deepening of periodontal pocket (sulcus between teeth and gums (gums)). In the present specification, "attachment loss inhibition" refers to inhibiting the detachment of the attachment epithelium of the gingiva from the tooth surface and the transfer of the attachment site between the gingiva and the tooth to the root side. In the present specification, "suppression of gingival recession" refers to suppression of movement of the entire gingiva to the root side. In the present specification, "suppressing gumline descent" refers to suppressing the exposure of the tooth root accompanying the movement of the entire gingiva toward the root side.

The subject to which the composition of the present disclosure is applied is preferably, for example, a subject with increased neutrophil collagenase activity. More specifically, for example, a person meeting level 1, 2, 3, or 4, or a person meeting level C in the diagnostic criteria for periodontal disease (Non-Patent Document 2). The diagnostic criteria for periodontal disease are the diagnostic criteria established by the joint research meeting of the American Society of Periodontology and the European Federation of Periodontology, and can be found on the website of the Japanese Society of Periodontology (https://www.perio.jp/ file/news/info_191220.pdf) confirmed. As a person who meets level 1 in the diagnostic criteria of periodontal disease, for example, the maximum clinical attachment level of the interdental space (the distance from the cementum enamel boundary to the gingival sulcus epithelium (measured in 1 mm unit)) 1 ~ 2mm or so people. Examples of persons meeting level 2 in the diagnostic criteria for periodontal disease include persons whose maximum clinical attachment level of interdental spaces is about 3 to 4 mm. Examples of persons meeting level 3 or 4 in the diagnostic criteria for periodontal disease include persons whose maximum clinical attachment level of interdental spaces is 5 mm or more. Among them, as a person who meets level 3 in the diagnostic criteria of periodontal disease, for example, a person who has lost 1 to 4 teeth due to periodontal disease, and the like. In addition, examples of persons meeting level 4 in the diagnostic criteria for periodontal disease include persons who have lost five or more teeth due to periodontal disease. Examples of persons who meet level C in the diagnostic criteria for periodontal disease include persons whose annual change in the clinical attachment level is 2 mm or more within 5 years, and the like. In addition, mammals including humans (such as dogs, cats, mice, rats, sheep, horses, cows, monkeys, etc.) etc. can be exemplified as application targets of the composition of the present disclosure. Among them, human is preferable.

Compositions of the present disclosure can be, for example, solid compositions, liquid compositions, and the like. In addition, the compositions of the present disclosure (particularly oral compositions) can be formed into ointments, pastes, skin pastes, gels, liquid preparations, sprays, mouthwash liquid preparations, liquid dentifrices, for example, according to conventional methods. , toothpaste, chewing gum, tablet, jelly beans and other forms (dosage forms). Among them, mouthwash liquid preparations, liquid dentifrice preparations, toothpaste preparations, ointments, paste preparations, liquid preparations, and gel preparations are preferable.

The composition of the present disclosure may further contain, for example, single or two or more optional components that can be blended in an oral composition within a range that does not impair the effect.

For example, as a surfactant, a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant can be blended. 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; polyoxyethylene alkyl ethers with a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group with 13 to 15 carbon atoms; a polyoxyethylene addition coefficient of 10 to 18 , polyoxyethylene alkylphenyl ether with 9 carbon atoms in the alkyl group; diethyl sebacate; polyoxyethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan ester, etc. Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate; sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate Sulfosuccinates such as sulfosuccinates; acyl amino acid salts such as sodium cocoyl sarcosinate and sodium lauroyl methylalanine; sodium cocoyl methyl taurate, etc. As the zwitterionic surfactant, acetic acid betaine type active agents such as lauryl dimethyl aminoacetic acid betaine, coconut oil fatty acid amidopropyl dimethyl aminoacetic acid betaine, etc.; N-cocoyl-N-carboxyl Imidazoline active agents such as sodium methyl-N-hydroxyethylethylenediamine, etc. These surfactants can be compounded individually or in combination of 2 or more types. The compounding quantity is 0.1-5 mass % normally with respect to a composition whole quantity.

In addition, as flavoring agents, for example, menthol, carvone, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, Esters, Citronellyl Acetate, Methyl Eugenol, Cineole, Linalool, Ethyl Linalool, Thymol, Spearmint Oil, Peppermint Oil, Lemon Oil, Orange Oil, Clary Sage Oil, Macaron Rosemary oil, cinnamon oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, allspice oil, d-camphor, d-borneol, anise oil, cinnamon oil, cinnamaldehyde, peppermint oil, vanillin and other spices . These can be compounded individually or in combination of 2 or more types, for example, 0.001-1.5 mass % with respect to the composition whole quantity.

In addition, as a sweetener, for example, sodium saccharin, acesulfame potassium, stevioside, neohesperidin dihydrochalcone, perillotine, thaumatin, aspartame, p-methoxycinnamaldehyde, etc. These can be compounded, for example, in an amount of 0.01 to 1 mass % with respect to the total amount of the composition.

Furthermore, as a wetting agent, sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, and lactitol can be compounded singly or in combination of two or more. , polyoxyethylene glycol, etc.

Examples of the binder include sodium carboxymethylcellulose, carboxymethylethylcellulose salt, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethyl Base cellulose, crystalline cellulose, cellulose derivatives such as crystalline cellulose and sodium carboxymethyl cellulose, polymers produced by microorganisms such as xanthan gum, tragacanth gum, locust gum, acacia gum, carrageenan, dextrin , agar, pectin, pullulan, gellan gum, locust bean gum, sodium alginate and other natural polymers or natural rubber, polyvinyl alcohol, polyvinylpyrrolidone, carboxy vinyl polymer, polyvinyl methyl ether , sodium polyacrylate and other synthetic polymers, thickening silica, inorganic binders such as magnesium aluminum silicate (Veegum), chloride O-[2-hydroxy-3-(trimethylammonium) propyl] Cationic binders such as hydroxyethyl cellulose. These binders can be used individually or in combination of 2 or more types.

As a preservative, paraben esters such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, alkyldiamino hydrochloride, etc. Ethylglycine, etc.

As a colorant, legal pigments such as Light Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral pigments such as ultramarine blue, enhanced ultramarine blue, and Prussian blue, and titanium oxide can be blended.

As a pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or these chemically realizable salts, sodium hydroxide, etc. can be compounded. These can be compounded individually or in combination of 2 or more types so that pH of a composition may exist in the range of 4-8, Preferably it is 5-7. The compounding quantity of a pH adjuster can be 0.01-2 weight%, for example.

It should be noted that, in the oral composition of the present disclosure, dl-α-tocopheryl acetate, tocopheryl succinate, or nicotinic acid may be compounded alone or in combination of two or more kinds as active ingredients. Vitamin E such as tocopheryl esters, amphoteric fungicides such as lauryl diaminoethylglycine, nonionic fungicides such as triclosan and isopropylmethylphenol, anionic fungicides such as sodium lauroyl sarcosinate , cetylpyridinium chloride, chlorhexidine hydrochloride, benzalkonium chloride, benzethonium chloride and other cationic fungicides, dextranase, amylase, protease, non-water-soluble dextranase, lysozyme, Enzymes such as lysozyme, alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, εaminocaproic acid, aluminum chlorohydroxy Allantoin, Dihydrocholesterol, Hebophenol, Glycyrrhizic Acid, Sodium Copperchlorophyllin, Glycerophosphoric Acid, Chlorophyll, Sodium Chloride, Carotide (Japanese: カロペプタイド), Allantoin, Carbaclochlor, Potassium Nitrate , Palatinitol, etc.

In addition, as a base, a composite ointment base (Plastibase) of alcohols, silicon, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, liquid paraffin, and polyethylene can also be added.

It should be noted that in this specification, "comprising" also includes "consisting essentially of" and "consisting of" (The term "comprising" includes "consisting essentially of" and "consisting of."). In addition, this disclosure includes all arbitrary combinations of the constituent requirements described in this specification.

In addition, any combination of the various characteristics (properties, structures, functions, etc.) described in the above-mentioned embodiments of the present disclosure may be used to identify the subject matter contained in the present disclosure. That is, the present disclosure includes all the subject matters including all combinations of combinable characteristics described in this specification.

[Example]

The contents of the present disclosure will be specifically described using the following experimental examples. However, the present disclosure is not limited by them in any way. In the following, the experiments were carried out under the conditions of atmospheric pressure and normal temperature, except for the cases specifically mentioned. In addition, "%" means "(weight/volume)%" except for the cases mentioned specifically. However, since the concentration of each component is sufficiently dilute and the solvent is also an aqueous system, this % does not substantially change from the value of mass %, and it can be interpreted as mass %.

Inhibition of neutrophil collagenase activity

[Study A]

1a. Dissolve each raw material (β-glycyrrhetinic acid (β-GR), dipotassium glycyrrhetinate (GK2), nicotinic acid dl-α - Tocopheryl ester (VEN), DL-alpha-tocopheryl acetate (VEA), L-ascorbic acid (VC), allantoin (AL), tranexamic acid (TXA), ε-aminocaproic acid (εACA) ).

2a. Neutrophil collagenase activity was evaluated using MMP-8 fluorometric drug discovery kit (EnzoLife Sciences, Inc., BML-AK415-0001). That is, 20 μl of each raw material solution prepared in 1a above, 20 μl of MMP-8 diluted to 200 times, and 50 μl of buffer provided with the kit were mixed and reacted at 37° C. for 60 minutes. At this time, as a positive control, prepare a sample in which a buffer is added in an equal amount without adding the raw material, or a sample in which a buffer is added in an equal amount without adding MMP-8 in order to measure only the background of the substrate.

3a. Dissolve the fluorescent substrate (BML-P126-9090) and dilute it 10 times with buffer (concentration: 40 μM). After adding 10 μl of the diluted fluorescent substrate and reacting at 37° C. for 20 minutes, the fluorescence intensity of excitation light: 328 nm and emitted light: 420 nm was measured. The value (NC) obtained by subtracting the fluorescence intensity of the substrate alone as the background from the fluorescence intensity of the positive control sample was taken as 100%, and the fluorescence intensity of the sample added to each raw material solution was calculated by subtracting the fluorescence of the substrate alone as the background The ratio of the values obtained for the intensity was taken as the enzyme activity.

The measurement results of neutrophil collagenase activity of β-glycyrrhetinic acid are shown in FIG. 1 . The horizontal axis shows the concentration of β-glycyrrhetinic acid in the reaction system of 3a above.

As shown in FIG. 1 , it was confirmed that β-glycyrrhetinic acid has inhibitory activity against neutrophil collagenase. Among them, it can be seen that when the concentration of β-glycyrrhetinic acid is 0.005% or more, it shows a neutrophil collagenase inhibitory effect of 40% or more, and when it is 0.03% or more, it shows a neutrophil collagenase inhibitory effect of 80% or more. Granulocyte collagenase inhibitory effect.

The measurement results of neutrophil collagenase (MMP-8) activity of each raw material are shown in FIG. 2 . The horizontal axis shows the concentration of each raw material in the reaction system of 3a above.

As shown in FIG. 2 , for raw materials other than β-glycyrrhetinic acid, no or slight inhibitory activity against neutrophil collagenase was found.

[Study B]

1b. Use β-glycyrrhetinic acid (β-GR) and ethylenediaminetetraacetic acid 3 sodium salt (EDTA-3Na) (buffer solution + 5% DMSO attached to the kit) at a concentration twice the target concentration way to dissolve. Equivalent amounts of β-GR and EDTA-3Na of each concentration were mixed to prepare a mixed solution of the target concentration.

2b. Neutrophil collagenase activity was evaluated using MMP-8 fluorometric drug discovery kit (EnzoLife Sciences, Inc., BML-AK415-0001). That is, 20 μl of each raw material solution prepared in 1a above, 20 μl of MMP-8 diluted to 200 times, and 50 μl of buffer provided with the kit were mixed and reacted at 37° C. for 60 minutes. At this time, as a positive control, prepare a sample in which a buffer is added in an equal amount without adding the raw material, or a sample in which a buffer is added in an equal amount without adding MMP-8 in order to measure only the background of the substrate.

3b. Dissolve the fluorescent substrate (BML-P126-9090) and dilute it 10 times with buffer (concentration 40 μM). After adding 10 μl of the diluted fluorescent substrate and reacting at 37° C. for 20 minutes, the fluorescence intensity of excitation light: 328 nm and emitted light: 420 nm was measured. The value (NC) obtained by subtracting the fluorescence intensity of the substrate alone as the background from the fluorescence intensity of the positive control sample was taken as 100%, and the fluorescence intensity of the sample added to each raw material solution was calculated by subtracting the fluorescence of the substrate alone as the background The ratio of the values obtained for the intensity was taken as the enzyme activity.

In order to evaluate the effect achieved by combining β-glycyrrhetinic acid (β-GR) and EDTA 3-sodium salt, the CI (Combination Index) value was calculated 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: β-GR addition concentration

(D) 2: Adding concentration of ethylenediaminetetraacetic acid 3 sodium salt

(Dx)1: Concentration at which β-GR alone inhibits 85% of neutrophil collagenase activity (IC85 value)

(Dx)2: The concentration (IC85 value) that inhibits 85% of neutrophil collagenase activity when EDTA 3 sodium salt alone

In the case of judging CI<1, there is a synergistic effect, in the case of CI=1, there is an additive effect, and in the case of CI>1, there is an antagonistic effect. The results are shown in Table 1. It should be noted that the concentrations in Table 1 represent the concentrations in the reaction system of 3b above. In addition, "EDTA" in Table 1 means ethylenediaminetetraacetic acid trisodium salt.

[Table 1]

As shown in Table 1, in the case of ethylenediaminetetraacetic acid trisodium salt:β-GR in the range of 3.2:1 to 0.2:1, it was confirmed that a synergistic effect was obtained with respect to the neutrophil collagenase inhibitory activity. In addition, in the combination (3.2:1, 1.6:1, 0.8:1, 0.4:1, 0.2:1, 0.1:1) in which the synergistic effect was confirmed, it was confirmed that the neutrophil collagenase activity was respectively reduced To around 13, 14, 12, 13, 14%. Some of the results are shown in Figure 3. In addition, the concentration in FIG. 3 represents the concentration in the reaction system of 3 mentioned above. In addition, "EDTA" in FIG. 3 represents ethylenediaminetetraacetic acid trisodium salt.

Claims (9)

1. An oral composition comprising β-glycyrrhetinic acid and ethylenediaminetetraacetic acid and/or a salt thereof, ethylenediaminetetraacetic acid and/or a salt thereof relative to 1 part by mass of β-glycyrrhetinic acid The total content is 0.15 to 5 parts by mass. 2. The composition according to claim 1, wherein the content of β-glycyrrhetinic acid in the composition is 0.002% by mass or more. 3. The composition according to claim 1 or 2, wherein the total content of ethylenediaminetetraacetic acid and/or salts thereof in the composition is 0.001% by mass or more. 4. Use of the composition in the manufacture of an oral composition for preventing the progression of periodontal disease, the composition containing β-glycyrrhetinic acid, and ethylenediaminetetraacetic acid and/or its salt, relative to β-glycyrrhetinic acid The total content of 1 mass part of ethylenediaminetetraacetic acid and/or its salt is 0.15-5 mass parts. 5. Use of the composition in the manufacture of an oral composition for inhibiting the activity of neutrophil collagenase in the oral cavity, the composition containing β-glycyrrhetinic acid, and ethylenediaminetetraacetic acid and/or a salt thereof , The total content of ethylenediaminetetraacetic acid and/or its salt is 0.15-5 mass parts with respect to 1 mass part of (beta)-glycyrrhetinic acid. 6. Use of β-glycyrrhetinic acid for the production of an oral composition for inhibiting neutrophil collagenase activity in the oral cavity. 7. Use of β-glycyrrhetinic acid in the manufacture of an oral composition for inhibiting the degradation of gingival collagen. 8. Use of β-glycyrrhetinic acid for the production of an oral composition for suppressing gingival recession, suppressing gingival destruction, suppressing gingiva descent, or suppressing attachment loss. 9. The use according to claim 6 or 7, wherein the composition for oral cavity is a composition for oral cavity containing 0.005% by mass or more of β-glycyrrhetinic acid.

Images