Hinokitiol-containing composition

Abstract

To provide a composition that inhibits neutrophil collagenase activity and also provide a composition for preventing the progress of periodontitis.SOLUTION: An oral composition contains (A) hinokitiol and (B) at least one selected from a group consisting of cysteine and salts thereof, zinc gluconate, alkyldiaminoethylglycine and salts thereof, and ethylenediaminetetraacetic acid and salts thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This disclosure relates to hinokitiol-containing compositions and their uses. [Background technology]

[0002] Matrix metalloproteinases (MMPs) are a general term for extracellular matrix-degrading enzymes that possess zinc(II) ions in their active site. Their main substrates are biomolecules such as collagen, laminin, gelatin, and fibronectin.

[0003] MMPs are thought to play a role in maintaining homeostasis during tissue remodeling and wound healing processes in the body by breaking down unnecessary extracellular matrix and controlling angiogenesis and the construction of new tissue. However, excessive MMP activity can lead to tissue destruction and is associated with periodontal disease, rheumatoid arthritis, tumor invasion, and metastasis. Therefore, researchers are searching for components that can control MMP activity. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] Patent No. 5339708 [Non-patent literature]

[0005] [Non-Patent Document 1] Japanese Journal of Periodontology 59(4):185-190, 2017 [Non-Patent Document 2] J Clin Periodontol.2021 Aug;48(8):1051-1065. [Overview of the project] [Problems that the invention aims to solve]

[0006] MMP-8, also known as neutrophil collagenase, is a collagenase produced by neutrophils. It is known to primarily degrade extracellular matrix components such as collagen and accounts for approximately 80% of MMPs in gingival crevicular exudate. It is believed that neutrophils accumulate in gingival crevicular exudate in response to inflammation in periodontal pockets and produce neutrophil collagenase (MMP-8), which destroys the attached epithelium within the periodontal pocket, leading to deepening of the periodontal pocket and progression of periodontal disease (Non-Patent Literature 1). Therefore, there is a need to search for components that can control the activity of neutrophil collagenase in order to prevent the progression of periodontal disease (Patent Literature 1).

[0007] This disclosure aims to provide a composition that inhibits neutrophil collagenase activity. Another objective is to provide a composition that prevents the progression of periodontal disease. [Means for solving the problem]

[0008] The inventors have discovered that combining hinokitiol with L-cysteine, zinc gluconate, alkyldiaminoethylglycine hydrochloride, or trisodium ethylenediaminetetraacetate exhibits inhibitory activity against neutrophil collagenase, and have further refined these findings.

[0009] This disclosure includes, for example, the following subjects: Section 1. (A) Hinokitiol, and (B) An oral composition containing at least one selected from the group consisting of cysteine ​​and its salts, zinc gluconate, alkyldiaminoethylglycine and its salts, and ethylenediaminetetraacetic acid and its salts. Section 2. The composition described in item 1 for preventing the progression of periodontal disease. Section 3. The composition according to item 1 or 2, which is used for at least one application selected from the group consisting of inhibition of periodontal tissue destruction, inhibition of gingival recession, inhibition of periodontal pocket formation, inhibition of periodontal pocket deepening, inhibition of attachment loss, inhibition of gingival collagen degradation, and inhibition of neutrophil collagenase activity. Item 4. The composition according to any one of items 1 to 3, wherein the content of hinokitiol in the composition is 0.005% by mass or more. Item 5. When the composition contains cysteine and / or its salt, the total content of cysteine and / or its salt is 0.005% by mass or more, When the composition contains zinc gluconate, the content of zinc gluconate is 0.01% by mass or more, When the composition contains alkyldiaminoethylglycine and / or its salt, the total content of alkyldiaminoethylglycine and / or its salt is 0.0005% by mass or more, The composition according to any one of items 1 to 4, when the composition contains ethylenediaminetetraacetic acid and / or its salt, the total content of ethylenediaminetetraacetic acid and / or its salt is 0.005% by mass or more.

Advantages of the Invention

[0010] It can inhibit neutrophil collagenase activity. Also, an effective composition for preventing the progression of periodontal disease can be provided.

Brief Description of the Drawings

[0011] [Figure 1] Shows the measurement results of neutrophil collagenase activity when hinokitiol and L-cysteine are added. [Figure 2] Shows the measurement results of neutrophil collagenase activity when hinokitiol and zinc gluconate are added. [Figure 3] Shows the measurement results of neutrophil collagenase activity when hinokitiol and alkyldiaminoethylglycine hydrochloride are added. [Figure 4]The measurement results of neutrophil collagenase activity when hinokitiol and trisodium ethylenediaminetetraacetate are added are shown.

BEST MODE FOR CARRYING OUT THE INVENTION

[0012] Hereinafter, each embodiment included in the present disclosure will be described in more detail. The composition included in the present disclosure contains (A) hinokitiol, and at least one selected from the group consisting of (B) cysteine and its salts, zinc gluconate, alkyldiaminoethylglycine and its salts, and ethylenediaminetetraacetic acid and its salts. In this specification, the composition may be referred to as "the composition of the present disclosure".

[0013] Hinokitiol has the following formula:

[0014]

Chemical formula

[0015] It is a compound represented by. The hinokitiol used in the composition of the present disclosure may be a synthetic product or may be extracted from a natural product (for example, Chamaecyparis obtusa).

[0016] The hinokitiol content in the composition of the present disclosure is not particularly limited as long as the effect is achieved. For example, in the composition of the present disclosure, the content of hinokitiol can be 0.005% by mass or more. The upper or lower limit of the range may be, for example, 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, or 0.3% by mass. For example, it may be 0.005 to 0.3% by mass, or 0.01 to 0.1% by mass. [[ID=​​ Examples of cysteine ​​salts include inorganic salts such as hydrochloride, nitrate, and acetate; alkali metal salts such as potassium and sodium salts; and alkaline earth metal salts such as calcium and magnesium salts. Among these, L-cysteine ​​is preferred.

[0018] The total content of cysteine ​​and / or its salts in the compositions of this disclosure is not particularly limited, as long as the effect is achieved. For example, the total content of cysteine ​​and / or its salts in the compositions of this disclosure may be 0.005% by mass or more. The upper or lower limits of this range may be, for example, 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 0.005 to 0.5% by mass, or 0.01 to 0.2% by mass.

[0019] The total content of cysteine ​​and / or its salts per 1 part by mass of hinokitiol in the compositions of this disclosure may be, for example, 0.5 to 20 parts by mass. The upper or lower limit of this range may be, for example, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19 parts by mass. For example, it may be 0.6 to 19 parts by mass, or 0.7 to 18 parts by mass.

[0020] The zinc gluconate content in the compositions of this disclosure is not particularly limited, as long as the effect is achieved. For example, the zinc gluconate content in the compositions of this disclosure may be 0.01% by mass or more. The upper or lower limits 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, 0.2, 0.3, 0.4, or 0.5% by mass. For example, it may be 0.01 to 0.5% by mass, or 0.02 to 0.2% by mass.

[0021] In the composition of the present disclosure, the content of zinc gluconate relative to 1 part by mass of hinokitiol can be, for example, 0.5 to 150 parts by mass. The upper or lower limit of this range can be, for example, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 50, 100, or 125 parts by mass. For example, it may be 0.6 to 125 parts by mass, or 0.7 to 25 parts by mass.

[0022] Alkyldiaminoethyl glycine is a compound represented by the following formula:

Chemical formula

[0023] In the formula, R is C8H 12 , <000…~C 16 H 33 and mainly C 12 H 25 and C 14 H 29 Among them, C 12 H 25 and C 14 H 29 The total amount of C8H1… and C10H2… is preferably 50, 60, 70, 80, or 90% or more of alkyldiaminoethyl glycine.

[0024] Examples of salts of alkyldiaminoethyl glycine include inorganic acid salts, organic acid salts, metal salts, etc. Examples of inorganic acid salts include hydrochloride, sulfate, etc. Examples of organic acid salts include tartrate, acetate, etc. Examples of metal salts include sodium salt, potassium salt, calcium salt, magnesium salt, etc. Among them, alkyldiaminoethyl glycine hydrochloride is preferred.

[0025] The total content of alkyldiaminoethylglycine and / or its salts in the compositions of this disclosure is not particularly limited, as long as the effect is achieved. For example, the total content of alkyldiaminoethylglycine and / or its salts in the compositions of this disclosure may be 0.0005% by mass or more. The upper or lower limits of this range may be, for example, 0.0006, 0.0007, 0.0008, 0.0009, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.06, 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 mass%, or 0.005 to 0.2 mass%.

[0026] The total content of alkyldiaminoethylglycine and / or its salt per 1 part by mass of hinokitiol in the compositions of this disclosure may be, for example, 0.01 to 5 parts 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, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, or 4 parts by mass. For example, it may be 0.02 to 4 parts by mass, or 0.03 to 3 parts by mass.

[0027] Examples of ethylenediaminetetraacetic acid salts include sodium salt, potassium salt, calcium salt, and magnesium salt. Among these, sodium salt is preferred. Examples of sodium salts of EDTA include EDTA2 sodium, EDTA3 sodium, and EDTA4 sodium.

[0028] The total content of ethylenediaminetetraacetic acid and / or its salts in the compositions of this disclosure is not particularly limited, as long as the effect is achieved. For example, the total content of ethylenediaminetetraacetic acid and / or its salts in the compositions of this disclosure may be 0.005% by mass or more. The upper or lower limit of this range may be, for example, 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 0.005 to 0.5% by mass, or 0.01 to 0.3% by mass.

[0029] The total content of ethylenediaminetetraacetic acid and / or its salt per 1 part by mass of hinokitiol in the compositions of this disclosure may be, for example, 0.1 to 25 parts 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, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 parts by mass. For example, it may be 0.2 to 24 parts by mass, or 0.3 to 23 parts by mass.

[0030] Neutrophil collagenase (EC 3.4.24.34) is a collagenase produced by neutrophils and is also known as MMP-8.

[0031] Neutrophil collagenase activity inhibition means inhibiting the breakdown of substrates (such as type I collagen, type II collagen, type III collagen, etc.) by neutrophil collagenase.

[0032] The compositions of this disclosure inhibit the degradation of substrates by neutrophil collagenase, thereby suppressing the destruction of tissues (e.g., attached epithelium, gingival sulcus epithelium, periodontal ligament, etc.) and the degradation of gingival collagen (collagen fibers that make up the gums) by neutrophil collagenase. Furthermore, since the compositions of this disclosure have neutrophil collagenase activity inhibitory effects, they can inhibit the activity of neutrophil collagenase that has already been produced.

[0033] For this reason, the compositions of the present disclosure are suitable as oral compositions. More specifically, the compositions of the present disclosure can be used, for example, to prevent the progression of periodontal disease, such as inhibiting the progression of periodontal disease, inhibiting neutrophil collagenase activity, inhibiting gingival recession, inhibiting periodontal pocket formation, inhibiting periodontal pocket deepening, inhibiting periodontal tissue destruction, inhibiting gum recession, inhibiting gingival collagen degradation, inhibiting attachment loss, protecting periodontal tissue collagen, and inhibiting the destruction of periodontal tissue associated with chronic inflammation, and / or for protecting dentin collagen, etc. In this specification, "inhibition of periodontal pocket formation" means inhibiting the formation of periodontal pockets (grooves between the tooth and the gums (gingiva)). In this specification, "inhibition of periodontal pocket deepening" means inhibiting the deepening of periodontal pockets (grooves between the tooth and the gums (gingiva)). In this specification, "inhibition of attachment loss" means inhibiting the separation of the gingival epithelium from the tooth surface and the shift of the attachment position between the gingiva and the tooth toward the tooth root. In this specification, "inhibition of gingival recession" means inhibiting the movement of the entire gingiva toward the tooth root. In this specification, "inhibition of gum recession" means inhibiting the exposure of the tooth root due to the movement of the entire gingiva toward the tooth root.

[0034] The composition disclosed herein is preferably applied to subjects with elevated neutrophil collagenase activity. More specifically, examples include individuals who meet the diagnostic criteria for periodontal disease at stages 1, 2, 3, or 4, or those who meet grade C (Non-Patent Literature 2). The diagnostic criteria for periodontal disease were developed at a workshop co-sponsored by the American Academy 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). Examples of individuals who meet the diagnostic criteria for stage 1 of periodontal disease include those whose largest interdental clinical attachment level (distance from the cementoenamel junction to the gingival sulcus epithelium (measured in 1mm units)) is approximately 1-2 mm. Examples of individuals who meet the diagnostic criteria for stage 2 of periodontal disease include those whose largest interdental clinical attachment level is approximately 3-4 mm. Individuals who meet the diagnostic criteria for periodontal disease at stage 3 or 4 include, for example, those whose largest interdental clinical attachment level is 5 mm or more. Specifically, those meeting the diagnostic criteria for stage 3 include, for example, those who have experienced tooth loss due to periodontal disease (1 to 4 teeth). Those meeting the diagnostic criteria for stage 4 include, for example, those who have experienced tooth loss due to periodontal disease (5 or more teeth). Individuals meeting the diagnostic criteria for grade C include, for example, those whose clinical attachment level changes over time by 2 mm or more in 5 years. Furthermore, examples of animals to which the disclosed composition can be applied include mammals, including humans (e.g., dogs, cats, mice, rats, sheep, horses, cattle, monkeys, etc.). Humans are particularly preferred.

[0035] The compositions disclosed herein may be, for example, solid compositions, liquid compositions, etc. Furthermore, the compositions disclosed herein (especially oral compositions) can be made into forms (dosage forms) such as ointments, pastes, pastes, gels, liquids, sprays, mouthwashes, liquid toothpastes, toothpastes, gums, tablets, drops, etc., according to conventional methods. Among these, mouthwashes, liquid toothpastes, toothpastes, ointments, pastes, liquids, and gels are preferred.

[0036] The compositions of this disclosure may contain, alone or in combination of two or more optional components that can be incorporated into, for example, oral compositions, as long as they do not impair the effects.

[0037] For example, nonionic surfactants, anionic surfactants, or amphoteric surfactants can be incorporated as surfactants. Specifically, examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; glycerin fatty acid esters; sorbitan fatty acid esters; fatty acid monoglycerides; 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 surfactants such as lauryldimethylaminoacetic acid betaine and coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine; and imidazoline-type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium. These surfactants can be used individually or in combination of two or more. The amount used is usually 0.1 to 5% by mass of the total composition.

[0038] Furthermore, as flavoring agents, for example, menthol, carvone, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole, linalool, ethyl linalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, fennel oil, cinnamon oil, cinnamaldehyde, peppermint oil, vanillin, and other fragrances can be used. These can be added individually or in combination of two or more in amounts of, for example, 0.001 to 1.5% by mass of the total composition.

[0039] 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.

[0040] 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.

[0041] Examples of binders include cellulose derivatives such as sodium carboxymethylcellulose, carboxymethyl ethylcellulose salt, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, crystalline cellulose, and crystalline cellulose-carmellose sodium; microbially produced polymers such as xanthan gum; natural polymers or natural rubbers such as tragacanth gum, karaya gum, arabic gum, carrageenan, dextrin, agar, pectin, pullulan, gellan gum, locust bean gum, and sodium alginate; synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, polyvinyl methyl ether, and sodium polyacrylate; inorganic binders such as thickening silica and bee gum; and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride. These binders can be used individually or in combination of two or more.

[0042] Parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, as well as sodium benzoate and phenoxyethanol, can be added as preservatives.

[0043] 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.

[0044] 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.

[0045] Furthermore, the oral composition disclosed herein may also contain, as pharmaceutically active ingredients, vitamin E derivatives such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate; amphoteric bactericides such as dodecyldiaminoethylglycine; nonionic bactericides such as triclosan and isopropylmethylphenol; anionic bactericides such as sodium lauroyl sarcosinate; cationic bactericides such as cetylpyridinium chloride, chlorhexidine hydrochloride, benzalkonium chloride, and benzethonium chloride; dextranase, amylase, protease, mutanase, lysozyme, and lytic enzymes (Litec Enzyme) Enzymes such as (M), alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon-aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, glycyrrhetinic acid, glycyrrhizic acid, copper chlorophyllin sodium, glycerophosphate, chlorophyll, sodium chloride, caropeptide, allantoin, carbazochrome, potassium nitrate, and palatinite can be formulated individually or in combination of two or more.

[0046] Furthermore, it is possible to add alcohols, silicones, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, Plastibase, etc., as base materials.

[0047] In this specification, the term "comprising" includes both "consisting essentially of" and "consisting of." Furthermore, this disclosure encompasses all combinations of the constituent elements described herein.

[0048] 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]

[0049] The contents of this disclosure will be specifically explained using the following experimental examples. However, this disclosure is not limited to these examples. Unless otherwise specified below, the experiments were conducted under atmospheric pressure and room temperature conditions. Unless otherwise specified, "%" means "(weight / volume)%".

[0050] Neutrophil collagenase activity inhibition Neutrophil collagenase activity inhibition 1. Each material (hinokitiol, zinc gluconate, ethylenediaminetetraacetic acid (EDTA) trisodium salt, alkyldiaminoethylglycine hydrochloride, and L-cysteine) was dissolved in a solvent (buffer included in the kit + 5% DMSO) to twice the desired concentration. Equal amounts of each concentration of hinokitiol, zinc gluconate, ethylenediaminetetraacetic acid trisodium salt, alkyldiaminoethylglycine hydrochloride, and L-cysteine ​​were mixed to prepare a mixed solution of the desired concentration. 2. Neutrophil collagenase activity was evaluated using the MMP-8 fluorimetric drug discovery kit (Enzo Life Sciences, Inc., BML-AK415-0001). Specifically, 20 μl of each material solution prepared in 1 above, 20 μl of MMP-8 diluted 200-fold, and 50 μl of the buffer provided with the kit were mixed and reacted at 37°C for 60 minutes. At this time, a sample with an equal volume of buffer added without the material was prepared as a positive control, and a sample with an equal volume of buffer added without MMP-8 was prepared to measure the background of the substrate only. 3. The fluorescent substrate (BML-P126-9090) was dissolved and diluted 10-fold with buffer (concentration 40 μM). 10 μl of the diluted fluorescent substrate was added and reacted at 37°C for 20 minutes. The fluorescence intensity was then measured at excitation light: 328 nm and emission light: 420 nm. The enzyme activity was calculated as the ratio of the fluorescence intensity of each material solution added to the fluorescence intensity of the sample with the substrate alone subtracted as background (NC), with the value obtained by subtracting the fluorescence intensity of the substrate alone as background (NC) from the fluorescence intensity of the positive control sample being set to 100%. The results are shown in Figures 1-4. Note that the concentrations in the figures represent the concentrations of each material during preparation as described in 1 above, and are 5 times higher than the concentrations in the reaction system described in 3 above. This is because, when using oral compositions such as toothpaste, they are diluted by saliva, etc., so the evaluation is conducted assuming the conditions under which they are actually used in the oral cavity.

[0051] As shown in Figures 1-4, it was confirmed that combining hinokitiol with zinc gluconate, trisodium ethylenediaminetetraacetate, alkyldiaminoethylglycine hydrochloride, or L-cysteine ​​improved inhibitory activity against neutrophil collagenase.

Claims

1. (A) Hinokitiol, and (B) An oral composition containing at least one selected from the group consisting of cysteine ​​and its salts, zinc gluconate, alkyldiaminoethylglycine and its salts, and ethylenediaminetetraacetic acid and its salts, It is used to inhibit neutrophil collagenase activity, If the composition contains cysteine ​​and / or a salt thereof, the total content of cysteine ​​and / or a salt thereof is 0.005 to 0.5% by mass. If the composition contains zinc gluconate, the zinc gluconate content is 0.01 to 0.5% by mass. If the composition contains alkyldiaminoethylglycine and / or a salt thereof, the total content of alkyldiaminoethylglycine and / or a salt thereof is 0.005 to 0.5% by mass. If the composition contains ethylenediaminetetraacetic acid and / or a salt thereof, the total content of ethylenediaminetetraacetic acid and / or a salt thereof is 0.05 to 0.5% by mass.

2. The composition according to claim 1, wherein the content of hinokitiol in the composition is 0.005% by mass or more.

Images