JP7333751B2 - human antimicrobial peptide production promoter - Google Patents

Description

TECHNICAL FIELD The present invention relates to human antimicrobial peptide production promoters.

Various bacteria coexist in the human body and form bacterial communities. Pathogenic bacteria and opportunistic infectious bacteria exist in the bacterial flora in addition to resident bacteria, and are known to induce various diseases. On the other hand, it is a common practice to control disease by suppressing pathogenic bacteria and opportunistic bacteria by treatment with fungicides and antibiotics, but in recent years, the wrong use of fungicides and antibiotics is a factor in the emergence of drug-resistant bacteria. This has become a social problem.

Human antimicrobial peptides are one of the innate host defense mechanisms to protect the host from infection by pathogenic microorganisms. The activity of antimicrobial peptides is known to exhibit a wide antimicrobial spectrum against microorganisms such as bacteria and fungi. Unlike enzymes and proteins, antimicrobial peptides act on bacterial cell membranes, which are less likely to mutate. Therefore, antimicrobial peptides are attracting attention because they are thought to be more difficult for bacteria to acquire resistance than antibiotics. Furthermore, some human antibacterial peptides have cytokine-like actions, immune system activation actions, etc., and in addition to the role of the primary defense mechanism against microorganisms, elimination of microorganisms at the site of infection, suppression of inflammation The role of secondary, tertiary, and subsequent biological defense mechanisms, such as, is also expected. From the above viewpoints, it is suggested that increasing and maintaining the expression level of human antimicrobial peptides to an optimal state is important from the viewpoint of various disease prevention.

Bacterial infection and stimulation of inflammatory cytokines such as IL-1 are known as representative methods for promoting the expression of human antimicrobial peptides, but these methods are not realistic. In addition, it is known that the expression of antimicrobial peptides is induced by active vitamin D and all-trans-type retinoic acid, but these are very expensive and unstable, so there is a problem in terms of commercial use. . Under these circumstances, there is a strong demand for the development of a method for promoting and controlling the expression of antimicrobial peptides useful for maintaining and promoting the epithelial barrier in everyday life. For example, yeast-derived inactive fractions, yeast-derived mannan-containing components, combinations of epigallocatechin gallate and vitamin C, quercetins, butcher bloom extracts, and lactic acid bacteria materials have been reported to promote the expression of human antimicrobial peptides. (See Patent Documents 1 to 5).

α-Lipoic acid is a vitamin-like substance found in liver and yeast, and is present in mitochondria in cells. Synthesized by intestinal bacteria, it is usually not deficient, but is said to decrease with age. It has been reported that α-lipoic acid has a very strong antioxidative action and other actions such as an anti-glycemic action and an energy metabolism action. Therefore, α-lipoic acid is also used as functional foods and pharmaceuticals (see Patent Document 6). In addition, α-lipoic acid has been found to have the ability of fibroblasts to produce collagen, and skin external preparations, oral compositions, and foods that have the effect of preventing and improving skin aging symptoms and periodontal disease have been proposed (Patent Documents 7).

JP-A-2003-262 JP 2006-241023 A JP 2013-151442 A JP 2018-104364 A WO2015/087919 JP 2007-246541 A JP 2009-242309 A

However, the agents described in Patent Documents 1 to 5 have a problem that their human antibacterial peptide production promoting activity is insufficient. Moreover, Patent Documents 6 and 7 do not describe that α-lipoic acid has human antibacterial peptide production promoting activity.

An object of the present invention is to provide an agent that can be used as foods, pharmaceuticals, quasi-drugs, especially oral preparations, which has a human antimicrobial peptide production-promoting action.

The present invention provides the following [1] to [8].
[1] A human antimicrobial peptide production promoter containing α-lipoic acid or a derivative thereof.
[2] The human of [1], wherein the human antibacterial peptide has antibacterial activity against one or more bacteria selected from the group consisting of periodontal disease-causing bacteria, halitosis-causing bacteria, cariogenic bacteria and Candida. Antibacterial peptide production accelerator.
[3] Human antimicrobial peptide production according to [1] or [2], wherein the human antimicrobial peptide is at least one selected from the group consisting of cathelicidin, human β-defensin 2, human β-defensin 3, and calprotectin accelerator.
[4] The human antimicrobial peptide production promoter according to any one of [1] to [3], which promotes the production of human antimicrobial peptides in at least one site selected from the group consisting of mucosa, oral mucosa and gingiva. .
[5] An oral composition for promoting human antimicrobial peptide production, containing α-lipoic acid or a derivative thereof as an active ingredient.
[6] A food and drink composition for promoting human antimicrobial peptide production, containing α-lipoic acid or a derivative thereof as a functional ingredient.
[7] A pharmaceutical or quasi-drug composition for promoting human antimicrobial peptide production, containing α-lipoic acid or a derivative thereof as an active ingredient.
[8] An agent for preventing or alleviating at least one symptom selected from periodontal disease, bad breath, dental caries and Candida infection by promoting human antimicrobial peptide production, containing α-lipoic acid or a derivative thereof.

INDUSTRIAL APPLICABILITY According to the present invention, there is provided an agent that has a human antibacterial peptide production-enhancing action and that can be used as a food or drink product, a pharmaceutical product, or a quasi-drug, especially for preparations applied to the oral cavity.

The present invention will be described below.

<α-Lipoic acid and derivatives thereof>
The agent of the present invention contains α-lipoic acid and its derivatives. As a result, it is possible to exert the action of promoting the production of human antimicrobial peptides. The agent of the present invention may contain at least one selected from the group consisting of α-lipoic acid and derivatives thereof, and may contain two or more.

α-Lipoic acid is an analogue of octanoic acid, and has a structure in which the carbons at the 6th and 8th positions are linked by a disulfide bond in a ring. Since the 6-position carbon is an asymmetric carbon atom, there are two types, (R)-α-lipoic acid and (S)-α-lipoic acid, but either one is acceptable.

Examples of α-lipoic acid derivatives include salts of α-lipoic acid (e.g., alkali metal salts (sodium salts, potassium salts, etc.), amine salts, ammonium salts), esters of α-lipoic acid (e.g., alkyl and alkenyl esters, amides of α-lipoic acid (e.g., lipoamide and lipoyllysine), other examples include dihydrolipoic acid, which is a reductant of α-lipoic acid, and esters of dihydrolipoic acid (e.g., alkyl and alkenyl esters). ), and amides of dihydrolipoic acid, such as lipoamide and lipoyl lysine.The α-lipoic acid derivative is preferably thioctic acid amide, methyl thioctic acid, more preferably thioctic acid amide.

α-Lipoic acid and its derivatives may be powdered or liquid. In the case of a powder product, it may be in the form of an α-lipoic acid clathrate with a solubilizing agent (eg, cyclodextrin).

<Content of α-lipoic acid and its derivatives>
The content of α-lipoic acid and derivatives thereof in the agent of the present invention (when two or more selected from α-lipoic acid and derivatives thereof are included, the total content thereof) is not particularly limited, but α-lipoic acid The amount of is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more. This makes it possible to obtain a favorable effect of promoting the production of antimicrobial peptides. Although the upper limit is not particularly limited, it is preferably 1% by mass or less, more preferably 0.1% by mass or less. As a result, it is possible to suppress a decrease in the production-promoting action due to cell damage. Therefore, it is usually 0.00001 to 1% by mass, preferably 0.0001 to 0.1% by mass.

<Solubilizer>
The agent of the present invention may further contain a solubilizing agent. This can increase the solubility of α-lipoic acid and its derivatives in various applications. Examples of solubilizing agents include ethanol and cyclodextrin. When a solubilizing agent is included, the content of α-lipoic acid and its derivatives is preferably 0.0001% by mass or more, more preferably 0.0001% by mass or more, based on the total amount of α-lipoic acid or its derivatives and the solubilizing agent. 001% by mass or more. Although the upper limit is not particularly limited, it is preferably 15% by mass or less, more preferably 1.5% by mass or less.

<Human antimicrobial peptide production promotion effect>
The agent of the present invention has a human antimicrobial peptide production-promoting effect. As used herein, a human antimicrobial peptide is an antimicrobial peptide produced in the human body, specifically, for example, a human mucous membrane, preferably a human oral tissue-derived antimicrobial peptide. The agent of the present invention is a causative bacterium for oral diseases, for example, periodontal disease-causing bacteria (e.g., Porphyromonas spp. (Porphyromonas gingivalis, etc.), Aggregatibacter spp. (Aggregatibacter actinomyces cerevisiae). Temcomitans, etc.)), bad breath-causing bacteria (e.g., Fusobauterium spp. (Fusobauterium nucleatum, etc.)), caries-causing bacteria (e.g., Streptococcus spp. (Streptococcus mutans, etc.)) and Candida fungi It has the effect of promoting the production of human antimicrobial peptides. Therefore, according to the present invention, oral compositions, foods and drinks, pharmaceuticals, and quasi-drugs intended to prevent or improve oral diseases such as periodontal disease, bad breath, dental caries, and Candida infections due to an increase in human antimicrobial peptides Application to products can be expected.

Antimicrobial peptides derived from human oral tissue include, for example, cathelicidin, the defensin family, calprotectin. More preferred representative examples are cathelicidin (LL-37), human β-defensin 2 (hBD-2), human β-defensin 3 (hBD-3), and calprotectin. LL-37 and hBD-3 are known to have high bactericidal activity against bacterial species closely related to the onset of periodontal disease, such as Porphyromonas gingivalis and Aggregatebacter actinomycetemcomitans. there is In addition, LL-37 and hBD-2, 3 are known to have high bactericidal activity against Fusobauterium nucleatum, which has been reported to be associated with bad breath (Journal of Antimicrobial Chemotherapy (2005) 55, 888-896 ). LL-37 and hBD-3 are known to have high bactericidal activity against Streptococcus mutans, which has been reported to be highly associated with dental caries. Calprotectin is known to reduce the adherence of P. gingivalis to epithelial cells (Nihon Periodonshi 40(1): 13-19, 2007). The agent of the present invention more effectively prevents or improves oral diseases such as periodontal disease, halitosis, dental caries, and Candida-derived diseases by having the growth-promoting action of each peptide exemplified as the preferred human antimicrobial peptides described above. It can be expected to be applied to oral compositions, food and drink, pharmaceuticals, and quasi-drugs intended for

As used herein, promoting human antimicrobial peptide production means that the amount of human antimicrobial peptide produced is improved compared to a control sample having the same composition except that it does not contain α-lipoic acid and its derivatives.

<Dosage form/dosage form/application>
Although the shape of the agent of the present invention is not particularly limited, it is preferably a shape that can be easily applied to mucous membranes (preferably oral mucosa) and gums. tablets, solid formulations, etc.).

The dosage form of the agent of the present invention is preferably a topical dosage form that allows the agent to contact mucous membranes (preferably oral mucosa) and/or gums. Therefore, the agent itself may be used as a food or drink (preferably a functional food), an oral composition, or a pharmaceutical that contacts the oral mucosa. You may utilize it as an active ingredient and a functional ingredient.

(food and drink)
Examples of food and drink include beverages (e.g., soft drinks, carbonated drinks, nutritional drinks, powdered drinks, fruit drinks, milk drinks, jelly drinks), foods (e.g., gums, candies, tablets, gummies, films, lozenges, cookies, jelly). Functional foods (health foods) include, for example, foods for promoting human antibacterial peptide production, foods for preventing or improving periodontal disease, foods for preventing or improving bad breath, foods for preventing or improving dental caries, and preventing or improving Candida-derived diseases. food for When the agent of the present invention is used as a food or drink (preferably a functional food), auxiliary raw materials or additives may be blended as necessary.

Auxiliary raw materials or additives are not particularly limited and can be appropriately selected according to the purpose. For example, fructose, granulated sugar, sucrose, sugar, glucose, maltose, sorbitol, maltitol, dextrin, xylitol, gum base, stevioside, rubusoside, corn syrup, lactose, starch syrup, reduced starch syrup, corn starch, starch hydrolyzate, citric acid, Tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, l-menthol, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid Ester, polyvinylpyrrolidone, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, vitamin C, nicotinamide, calcium pantothenate, amino acids, calcium salts, crystalline cellulose, gum base, flavor, pigment, fragrance, Preservatives, fruit juice, fine silicon dioxide and the like can be mentioned.

(Composition for oral cavity)
Examples of oral compositions include dentifrices, mouthwashes, oral pastas, mouth sprays, liniments, sheets and the like. When the agent of the present invention is used as an oral composition, optional ingredients may be added as necessary. Optional ingredients include abrasives, surfactants, binders, wetting agents, sweeteners, preservatives, flavors, colorants, pH adjusters, solvents, solvents, excipients, various medicinal ingredients, and selected from these. A combination of two or more is mentioned.

Examples of abrasives include silicic anhydride (hereinafter, silicic anhydride as an abrasive is also referred to as "abrasive silica" or "silicic anhydride (abrasive)"), crystalline silica, amorphous silica, silica gel, alumino Silica-based abrasives such as silicate, zeolite, calcium hydrogen phosphate anhydrate, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tri-magnesium phosphate, silicic acid Zirconium, tribasic calcium phosphate, hydroxyapatite, quaternary calcium phosphate, synthetic resin abrasives, and the like. When the oral composition contains an abrasive, its content is preferably 2 to 40% by mass, more preferably 5 to 20% by mass of the total composition in the case of a dentifrice.
In addition, an abrasive can be used individually by 1 type or in combination of 2 or more types.

As surfactants, anionic surfactants, nonionic surfactants, amphoteric surfactants and the like can be used.

Examples of anionic surfactants include N-acyl amino acid salts, α-olefin sulfonates, N-acyl sulfonates, alkyl sulfates, sulfates of glycerin fatty acid esters, and the like. Among these, N-acyl amino acid salts, α-olefin sulfonates, alkyl sulfates, etc. are preferable from the viewpoint of versatility, and sodium lauroyl sarcosinate, carbon chain length of the alkyl chain are preferable from the viewpoint of foamability and hard water resistance. α-olefin sodium sulfonate having 10 to 16 carbon atoms, sodium lauryl sulfate and the like are more preferable. Examples of N-acyl amino acid salts include N-acyl taurine salts, lauroylmethyl having a linear or branched saturated or unsaturated hydrocarbon group having 8 to 18 carbon atoms, preferably 12 to 16 carbon atoms. Methyl taurate salts such as taurine salts, coconut oil fatty acid methyl taurate salts, and myristoyl methyl taurate salts; methylalanine salts such as lauroyl methylalanine salts; and glutamate salts such as lauroyl glutamate and myristoyl glutamate may also be used.

Nonionic surfactants include polyoxyethylene alkyl ether, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene hydrogenated castor oil, polyoxyethylene ether of glycerin ester, sucrose fatty acid ester, alkylolamide, glycerin. Fatty acid ester etc. are mentioned. Among these, polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oils, alkylolamides, sorbitan fatty acid esters, and the like are preferably used in terms of versatility. The polyoxyethylene alkyl ether preferably has an alkyl chain with a carbon chain length of 14 to 18 carbon atoms. The polyoxyethylene alkyl ether preferably has an ethylene oxide average addition mole number of 15-30. The polyoxyethylene hydrogenated castor oil preferably has an average added mole number of ethylene oxide (average added EO) of 20-100. The alkylolamide preferably has an alkyl chain with a carbon chain length of 12 to 14 carbon atoms. The sorbitan fatty acid ester preferably has 12 to 18 carbon atoms in the fatty acid. The polyoxyethylene sorbitan fatty acid ester preferably has 16 to 18 carbon atoms in the fatty acid. Moreover, the polyoxyethylene sorbitan fatty acid ester preferably has an average number of moles of ethylene oxide added of 10 to 40.

Amphoteric surfactants include alkyl betaine surfactants, amine oxide surfactants, imidazolinium betaine surfactants, and the like. Examples of amphoteric surfactants include coconut oil fatty acid amidoalkyl betaine and the like, and coconut oil fatty acid amidopropyl betaine is preferred.

When the oral composition contains a surfactant, the content thereof is usually 10% by mass or less, preferably 0.01 to 5% by mass, based on the total oral composition. Surfactants may be used alone or in combination of two or more.

Examples of binders include organic binders and inorganic binders. When the oral composition contains an organic binder, the content is usually 0.01 to 3.5% by mass based on the total oral composition. When the oral composition contains an inorganic binder, the content thereof is preferably 1 to 10% by mass, more preferably 1 to 7% by mass, and 2 to 6% by mass, based on the total oral composition. % is more preferred. A caking agent can be used individually by 1 type or in combination of 2 or more types.

Organic binders include sodium polyacrylate, carrageenan, carboxymethylcellulose, sodium alginate, xanthan gum, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, propylene glycol alginate, pullulan, gelatin, gum arabic, guar gum, locust bean gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer and the like. Examples of inorganic binders include silicic anhydride (hereinafter, silicic anhydride as a binder is also referred to as "thickening silica" or "silicic anhydride (thickening)"), bentonite, and the like. Among them, silicic anhydride (thickening property) is preferable. Each of the organic binder and the inorganic binder may be used alone, or two or more of them may be used in combination. The binder may be a combination of organic and inorganic binders.

Excipients include, for example, cellulose such as hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, crystalline cellulose, ethylcellulose, low-substituted hydroxypropylcellulose, and pharmacologically acceptable derivatives thereof: polyvinylpyrrolidone, partially saponified polyvinyl alcohol. , Synthetic polymers such as starch decomposition products; gelatin, gum arabic powder, pullulan, agar, alginic acid, sodium alginate, polysaccharides such as xanthan gum; ethanol, isobutyl alcohol, isopropyl alcohol, butanol, propanol, 2-pentanol, 2- Lower alcohols such as methylbutanol, 3-methyl-2-butanol, 3-methyl-2-butenol, 1-penten-3-ol; hydrogenated rapeseed oil alcohol, lauryl alcohol, stearyl alcohol, cetyl alcohol, cetostearyl alcohol , lanolin alcohol, octyldodecanol, and other higher aliphatic alcohols; maize starch, potato starch, carboxymethylcellulose, carboxymethylcellulose calcium, sodium carboxymethylstarch, hydroxypropyl starch, partially pregelatinized starch, pregelatinized starch , Starch such as dextrin and pharmacologically acceptable derivatives thereof; Sugars and sugar alcohols such as maltitol and lactitol; Polyhydric alcohols such as propylene glycol and glycerin; mentioned.

Wetting agents include propylene glycol, butylene glycol; sugar alcohols such as glycerin, sorbitol (sorbitol), xylitol, erythritol and maltitol; polyethylene glycol and the like. When the oral composition contains a humectant, its content is usually 5 to 70% by mass based on the total oral composition.

Sweeteners include saccharin sodium, stevioside, neohesperidin hydrochalcone, glycyrrhizin, perillartine, p-methoxycinnamic aldehyde, thaumatin, palatinose, maltitol, xylitol, arabitol and the like. When the composition for oral cavity contains a sweetener, its content can be appropriately determined within a range that does not impair the effects of the present invention. A sweetener can be used individually by 1 type or in combination of 2 or more types.

Examples of the antiseptic include sodium benzoate, paraoxybenzoic acid esters such as methylparaben, ethylparaben and butylparaben, ethylenediaminetetraacetate, benzalkonium chloride and the like. When the oral cavity composition contains a preservative, its content can be appropriately determined within a range that does not impair the effects of the present invention. Preservatives may be used singly or in combination of two or more.

Examples of fragrances include natural fragrances, synthetic fragrances (single fragrances), compounded fragrances (fat fragrances (oily fragrances), powder fragrances, etc.), and the like. These fragrances may be used singly or in combination of two or more.

Natural flavors include mastic oil, parsley oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, menthol oil, spearmint oil, peppermint oil, lemon oil, coriander oil, orange oil, mandarin oil, lime oil, lavender. Oil, Laurel Oil, Chamomile Oil, Cardamom Oil, Caraway Oil, Bay Oil, Lemongrass Oil, Pine Needle Oil, Neroli Oil, Rose Oil, Jasmine Oil, Iris Concrete, Peppermint Absolute, Rose Absolute, Orange Flower, Citrus Oil, Mixed fruit oil, strawberry oil, cinnamon oil, clove oil, grape oil, thyme oil, sage oil, mint oil, rosemary oil, perilla oil, marjoram oil, origanum oil, grapefruit oil, sweetie oil, yuzu oil, mango absolute, orange flower absolute, capsicum extract, ginger oleoresin, pepper oleoresin, capsicum oleoresin and the like.

Single fragrances include 1-menthol, carvone, eugenol, anethole, methyl salicylate, thymol, cinnamaldehyde, linalool, linalyl acetate, limonene, ocimene, n-decyl alcohol, citronellol, vanillin, menthone, menthyl acetate, pinene, and octylaldehyde. , citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl anthranilate, vanillin, undecalactone (γ-undecalactone, δ- undecalactone, etc.), hexanal (trans-2-hexenal, etc.), ethynon alcohol, propyl alcohol, butanol, isoamyl alcohol, hexenol (cis-3-hexenol, etc.), dimethylsulfide, cyclotene, furfural, trimethylpyrazine, ethyl Lactate, ethyl lioacetate, cineol (1,8-cineole, etc.), menthofuran, linalool oxide, vanillyl butyl ether, isopulegol, furaneol, ethylcyclopentenolone, 2-methylbutyric acid, propionic acid, decalactone (γ- decalactone, δ-decalactone, etc.), nonalactone (γ-nonalactone, δ-nonalactone, etc.), hexalactone (γ-hexalactone, δ-hexalactone, etc.), isoamyl acetate, benzaldehyde, hexyl acetate, ethyl-2-methylbutyrate , benzyl alcohol, α-terpineol, phenylethylglycidate, phenylethyl alcohol, allylhexanoate, methylcinnamate, ethyl β-methylthiopropionate, cis-6-nonenol, caron, methyljasmonate and the like. .

The single perfume may be a cooling agent. Cooling agents include menthol, N-ethyl-p-menthane-3-carboxamide, N-(ethoxycarbonylmethyl)-3-p-menthanecarboxamide, and N,2,3-trimethyl-2-isopropylbutanamide. , 3-(L-methoxy)propane-1,2-diol, menthyl lactate (menthyl lactate), monomenthyl succinate, menthone glycerin acetal, 3-l-menthoxypropane-1,2-diol, menthone glycerin ether, spiranthol , monomenthyl succinate, and the like.

Mixed perfumes are perfumes made by mixing single perfumes and/or natural perfumes. Menthol micron, strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, tropical fruit flavor, butter flavor, milk flavor, yogurt flavor, mixed fruit flavor, herb mint flavor and the like.

Flavors include essential oils such as peppermint, spearmint, rosemary oil, sage oil, perilla oil, lemon oil, and orange oil, fruit essences such as lemon and strawberry, 1-menthol, carvone, eugenol, anethole, linalool, and limonene. , ocimene, cineol, n-decyl alcohol, citronellol, vanillin, α-terpineol, methyl salicylate, and thymol.

The form of the fragrance is not limited, and may be essential oil, extract, solid matter, or powder obtained by spray-drying any of these. When the composition for oral cavity contains a fragrance material, the content thereof is preferably 0.000001 to 1.5% by mass based on the total composition for oral cavity. In addition, when a fragrance for flavoring using the above fragrance material is contained, the content thereof is preferably 0.1 to 2.0% by mass with respect to the entire oral composition.

Coloring agents include natural pigments such as safflower red pigment, gardenia yellow pigment, gardenia blue pigment, perilla pigment, monascus pigment, red cabbage pigment, carrot pigment, hibiscus pigment, cacao pigment, spirulina blue pigment, tamarind pigment, and red. Legal dyes such as No. 3, Red No. 104, Red No. 105, Red No. 106, Yellow No. 4, Yellow No. 5, Green No. 3 and Blue No. 1, riboflavin, sodium copper chlorophyllin, titanium dioxide and the like. When the oral composition contains a coloring agent, the content thereof is preferably 0.00001 to 3% by mass based on the total oral composition.

pH adjusters include phosphoric acid or its salts (sodium phosphate, sodium dihydrogen phosphate, etc.), citric acid or its salts (sodium citrate, etc.), malic acid or its salts, gluconic acid or its salts, maleic acid or salts thereof, succinic acid or salts thereof, glutamic acid or salts thereof, lactic acid, hydrochloric acid, acetic acid, nitric acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate and the like. When the composition for oral cavity contains a pH adjuster, the content can be appropriately determined within a range that does not impair the effects of the present invention.

Examples of solvents include water, monohydric lower alcohols such as ethanol and propanol, propylene glycol and polyethylene glycol.

Medicinal ingredients include bactericidal or antibacterial agents such as chlorhexidine, triclosan, isopropylmethylphenol, cetylpyridinium chloride, zinc gluconate, and zinc citrate; anticalculus agents such as condensed phosphate and ethanehydroxydiphosphonate; Anti-inflammatory agents such as tranexamic acid, dipotassium glycyrrhizin, ε-aminocaproic acid, Phellodendron bark extract; coating agents such as hydroxyethylcellulose dimethyldiallylammonium chloride; allantoin chlorohydroxyaluminum, vitamin C, lysozyme chloride, glycyrrhetinic acid and its salts, sodium chloride , astringents such as allantoin; hypersensitivity inhibitors such as strontium chloride; stain removers such as sodium polyphosphate and sodium metaphosphate; enzyme agents such as dextranase and mutanase; and combinations of two or more thereof. . When the oral composition contains medicinal ingredients, the content of each medicinal ingredient may be adjusted within a pharmaceutically acceptable range.

(medicine)
Pharmaceuticals include, for example, orally disintegrating tablets, orally dissolving tablets, troches, mouthwashes, ointments, etc., and external preparations are preferred. When the agent of the present invention is used as a drug, optional ingredients may be added as necessary. As the optional component, one that conforms to pharmaceutical standards such as the Japanese Pharmacopoeia may be appropriately selected and used from among those exemplified as the optional component of the oral cavity composition.

EXAMPLES The present invention will be described in detail below with reference to examples. The following examples are intended to better illustrate the present invention and are not intended to limit the present invention. Unless otherwise specified, the method for measuring physical properties is the method described above.

EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples. In the following examples, % indicates % by mass unless otherwise specified.

Examples 1 to 9 and Comparative Example 1: Evaluation of antimicrobial peptide production promoting effect (Journal of Pediatric Dentistry 52 (4): 509-517 2014 509)
Human gingival epithelial cells were seeded in a 48-well plate at 0.5×10 ⁵ cells/well and cultured in a basal medium Humedia-KG2 (manufactured by Kurabo Industries, Ltd.) until confluent. Thereafter, the cells were cultured for 2 days in a medium supplemented with each evaluation substance in the amount (concentration in medium, mass %) shown in Tables 1 and 2. Two days after the addition, the culture supernatant was collected and an ELISA kit was used to detect cathelicidin in the supernatant (Examples 1 to 6), defensin 2 (Example 7), defensin 3 (Example 8), calprotectin (Example 9) Concentration was measured. Concentration % after culture when the concentration of cathelicidin, human β-defensin 2, human β-defensin 3, and calprotectin in the supernatant when cultured in a basal medium alone (control) to which no evaluation substance is added is 100% It was calculated as the production acceleration rate of each antimicrobial peptide and evaluated according to the following scores.

(Rating of production promotion rate of antimicrobial peptide)
+++: Antimicrobial peptide production promotion rate of 130% or more ++: Antimicrobial peptide production promotion rate of 110% or more and less than 130% +: Antimicrobial peptide production promotion rate of 105% or more and less than 110% -: Antimicrobial peptide production promotion rate of less than 105%

(footnote to table)
α-lipoic acid: α-lipoic acid-WSP7 (manufactured by Oryza Petrochemical Co., Ltd.)
α-lipoic acid amide: 5-(1,2-dithiolan-3-yl)pentanamide (manufactured by Sigma-Aldrich)

As is clear from Tables 1 and 2, in Examples 1 to 9, a good antimicrobial peptide production promotion rate was observed. This result indicates that the agent of the present invention has an effect of promoting antimicrobial peptide production.

The formulation examples of human antimicrobial peptide production promoters are shown below.
Formulation example 1: chewing gum sugar 50.0%
gum base 20.0%
Starch syrup 15.0%
Glucose 14.0%
α-lipoic acid 0.5%
Perfume 0.5%
Total 100.0%

Formulation example 2: Gummy reduced starch syrup 40.0%
Granulated sugar 20.0%
Glucose 20.0%
Gelatin 5.0%
Perfume 0.5%
α-lipoic acid 0.1%
Pigment 0.02%
water balance
Total 100.0%

Formulation Example 3: candy sugar 50.0%
Starch syrup 33.0%
Organic acid 2.0%
α-lipoic acid 1.0%
Perfume 0.5%
water balance
Total 100.0%

Prescription Example 4: Tablet candy (tablet)
Sugar 76.0%
Glucose 20.0%
Sucrose fatty acid ester 0.2%
α-lipoic acid 0.001%
water balance
Total 100.0%

Formulation Example 5: Tablet lactose 55.0%
Crystalline cellulose 25.0%
Starch hydrolyzate 10.0%
Glycerin fatty acid ester 5.0%
α-lipoic acid 0.002%
water balance
Total 100.0%

Formulation Example 6: Toothpaste Sorbit (AI = 100) 30.0%
Silicic anhydride 20.0%
Propylene glycol 3.0%
Sodium lauryl sulfate 1.0%
Xanthan gum 1.0%
Perfume 1.0%
Saccharin Na 0.1%
α-lipoic acid 0.005%
water balance
Total 100.0%

Formulation Example 7: Mouthwash ethanol 8.0%
Glycerin (AI=100) 5.0%
Xylitol 3.0%
Propylene glycol 3.0%
POE (60) hydrogenated castor oil 0.5%
Na citrate 0.3%
Perfume 0.2%
Citric acid 0.1%
α-lipoic acid 0.0001%
water balance
Total 100.0%

Formulation Example 8: Oral Pasta Sorbit (70% aqueous solution) 40.0%
Hydroxyethyl cellulose 3.0%
Sucrose palmitate monoester 2.0%
Carrageenan 1.0%
Sodium tartrate 1.0%
α-lipoic acid 1.0%
Perfume 1.0%
Aluminum lactate 0.8%
Sodium lauroyl sarcosinate 0.3%
Saccharin sodium 0.1%
Hydrochloric acid or sodium hydroxide appropriate amount
water balance
Total 100.0%

Claims (7)

A human antimicrobial peptide production promoter containing α-lipoic acid or a derivative thereof ,
The agent, wherein the human antimicrobial peptide is at least one selected from the group consisting of cathelicidin, defensin family, and calprotectin . The human antimicrobial peptide production promoter according to claim 1 , wherein the human antimicrobial peptide is at least one selected from the group consisting of cathelicidin, human β-defensin 2, human β-defensin 3, and calprotectin. The human antimicrobial peptide production promoter according to claim 1 or 2 , which promotes the production of human antimicrobial peptides in at least one site selected from the group consisting of mucosa, oral mucosa and gingiva. An oral composition for promoting human antimicrobial peptide production containing α-lipoic acid or a derivative thereof as an active ingredient ,
The composition, wherein the human antimicrobial peptide is at least one selected from the group consisting of cathelicidin, defensin family, and calprotectin . A food and drink composition for promoting human antimicrobial peptide production containing α-lipoic acid or a derivative thereof as a functional ingredient ,
The composition, wherein the human antimicrobial peptide is at least one selected from the group consisting of cathelicidin, defensin family, and calprotectin . A pharmaceutical or quasi-drug composition for promoting human antimicrobial peptide production containing α-lipoic acid or a derivative thereof as an active ingredient ,
The composition, wherein the human antimicrobial peptide is at least one selected from the group consisting of cathelicidin, defensin family, and calprotectin . An agent for preventing or alleviating at least one symptom selected from periodontal disease, bad breath, dental caries and Candida infection containing α-lipoic acid or a derivative thereof by promoting human antimicrobial peptide production ,
The agent, wherein the human antimicrobial peptide is at least one selected from the group consisting of cathelicidin, defensin family, and calprotectin .