Oral composition and prophylactic or treatment method for diseases of the oral cavity

Abstract

Provided is an oral composition that includes Lactobacillus plantarum cells or cell cultures or an extract of these. The Lactobacillus plantarum is ideally at least one type selected from NITE-BP-03198, NITE-BP-03199, NITE-BP-03200, NITE-BP-03201, and NITE-BP-03202. Also provided is a prophylactic or therapeutic method for oral cavity diseases, that includes the application of Lactobacillus plantarum cells or cell cultures or an extract of these to the oral cavity of animals.

Description

Oral composition and method for preventing or treating oral diseases

[0001] The present invention relates to an oral composition and a method for preventing or treating oral diseases.

[0002] Periodontal disease is an infectious disease caused by pathogenic microorganisms such as periodontal disease bacteria, and many people suffer from it.In order to suppress periodontal disease, the composition containing the component with antibacterial activity against pathogenic bacteria has been developed.WO 2011 / 007584 (Patent Document 1) discloses the preventive or therapeutic agent for oral diseases, which contains as active ingredient the bacterial cell or bacterial cell culture of one or more bacteria selected from Lactobacillus rhamnosus KO3 strain, Lactobacillus casei YU3 strain and Lactobacillus paracasei YU4 strain.WO 2012 / 108518 (Patent Document 2) discloses the preventive or therapeutic composition for oral diseases, which contains Kog1 or Kog3 produced by Lactobacillus rhamnosus KO1 strain and Lactobacillus rhamnosus KO3 strain.

[0003] Chinese Patent Publication No. 108685716 (Patent Document 3) discloses a toothpaste containing nisin. Chinese Patent Publication No. 105326656 (Patent Document 4) discloses an oral antibacterial composition containing nisin and polylysine. German Patent Publication No. 102011116325 (Patent Document 5) discloses an oral care composition containing bacterial cells or parts thereof belonging to Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus acidophilus.

[0004] International Publication No. WO 2011 / 007584 International Publication No. WO 2012 / 108518 Chinese Patent Application Publication No. 108685716 Chinese Patent Application Publication No. 105326656 German Patent Application Publication No. 102011116325

[0005] An object of the present invention is to provide a novel composition capable of suppressing oral diseases.

[0006] The present invention relates to the following exemplified items. [1] An oral composition comprising Lactobacillus plantarum cells or a cell culture, or an extract thereof. [2] The composition according to [1], which is a food product. [3] The composition according to [2], wherein the food product is a fermented food product. [4] The composition according to [1], which is a mouthwash or a dentifrice. [5] The composition according to [1] or [4], which further comprises a fluorine compound. [6] The composition according to any one of [1] to [5], wherein the Lactobacillus plantarum is at least one selected from NITE-BP-03198, NITE-BP-03199, NITE-BP-03200, NITE-BP-03201, and NITE-BP-03202. [7] The composition according to any one of [1] to [6], which is a composition for preventing or treating an oral disease. [8] The composition according to [7], wherein the oral disease is periodontal disease. [9] A method for preventing or treating oral diseases, comprising applying Lactobacillus plantarum cells or a cell culture, or an extract thereof, to the oral cavity of an animal.

[10] The method according to [9], wherein the oral disease is periodontal disease.

[11] A growth inhibitor or bactericide against periodontal disease-causing bacteria, comprising Lactobacillus plantarum cells or a cell culture, or an extract thereof.

[12] The growth inhibitor or bactericide according to

[11] , wherein the periodontal disease-causing bacteria comprises at least one selected from Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola.

[13] A method for inhibiting the growth or killing periodontal disease-causing bacteria, comprising contacting Lactobacillus plantarum cells or a cell culture, or an extract thereof, with periodontal disease-causing bacteria.

[0007] According to the present invention, a composition capable of suppressing oral diseases can be provided.

[0008] 1 shows (A) colony shape and (B) Gram staining results for NITE BP-03198 in Experiment 1. 2 shows (A) colony shape and (B) Gram staining results for NITE BP-03199 in Experiment 2. 3 shows (A) colony shape and (B) Gram staining results for NITE BP-03200 in Experiment 3. 4 shows (A) colony shape and (B) Gram staining results for NITE BP-03201 in Experiment 4. 5 shows (A) colony shape and (B) Gram staining results for NITE BP-03202 in Experiment 5. 6 shows diagrams illustrating antibacterial activity evaluation tests against bacteria in Experiments 6 to 8.

[0009] Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments. In this specification, an expression in the form of "A to B" means the upper and lower limits of a range (i.e., A or more and B or less), and when no unit is specified for A and a unit is specified only for B, the unit of A and the unit of B are the same.

[0010] [Oral Composition] An oral composition according to one embodiment of the present invention comprises Lactobacillus plantarum cells, a culture of Lactobacillus plantarum cells, or an extract thereof. The composition according to the present invention has antibacterial activity against periodontal disease bacteria.

[0011] The Lactobacillus plantarum is preferably at least one selected from NITE-BP-03198, NITE-BP-03199, NITE-BP-03200, NITE-BP-03201 and NITE-BP-03202. NITE-BP-03198, NITE-BP-03199, NITE-BP-03200, NITE-BP-03201, and NITE-BP-03202 are, respectively, accession numbers NITE BP-03198 (original deposit date: April 9, 2020), NITE BP-03199 (original deposit date: April 9, 2020), NITE BP-03200 (original deposit date: April 9, 2020), NITE BP-03201 (original deposit date: April 9, 2020), and NITE BP-03202. These bacteria have been internationally deposited under the Budapest Treaty at the National Institute of Technology and Evaluation (NPMD) Patent Microorganism Depositary (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, 292-0818) as BP-03202 (original deposit date: April 9, 2020). All of the above bacteria belong to Lactobacillus plantarum, a type of lactic acid bacteria. The bacteriological properties of the above bacteria are shown in Tables 1 to 10 and Figures 1 to 5, which will be described later.

[0012] NITE-BP-03198 is present in fermented foods, and NITE-BP-03199, NITE-BP-03200, NITE-BP-03201, and NITE-BP-03202 are present in the natural environment, and therefore are considered to be highly safe for humans. The lactic acid bacteria may be isolated bacteria.

[0013] An oral composition according to one embodiment of the present invention comprises bacterial cells or a bacterial cell culture of at least one type of bacteria selected from NITE-BP-03198, NITE-BP-03199, NITE-BP-03200, NITE-BP-03201, and NITE-BP-03202, or an extract thereof. The bacterial cells may be isolated from a fermented food or the environment, or may be cultured. The bacterial cells may be killed or live. The bacterial cells may be present in a culture medium, a buffer solution, or the like, or may be a concentrated form of these that has had the liquid removed, or a freeze-dried form thereof, or may be frozen stock.

[0014] The bacterial cell culture may contain bacterial secretions, metabolites, etc. The bacterial cell culture may contain peptides, proteins, sugars, enzymes, organic acids produced by the bacteria, and media (liquid media and solid media) containing these. The bacterial cell culture may also be the supernatant obtained after culturing the bacteria. The culture supernatant can be obtained, for example, by removing the bacteria from the liquid medium in which the bacteria have been cultured by centrifugation, filtration, etc.

[0015] NITE-BP-03198, NITE-BP-03199, NITE-BP-03200, NITE-BP-03201, and NITE-BP-03202 can be cultured according to a conventional culture method for lactic acid bacteria, typically using MRS (de Man, Rogosa, and Sharpe) liquid medium or MRS agar medium at 30°C.

[0016] Extracts of bacterial cells or bacterial cell cultures are prepared so as not to lose the antibacterial activity of the lactic acid bacteria cells or bacterial cell cultures against periodontal disease bacteria. Extracts can be obtained, for example, by subjecting bacterial cells or bacterial cell cultures to ultrasonic disruption, bead milling, freeze-thawing, chemical lysis, or other treatments. Extracts can also be obtained by subjecting bacterial cells or bacterial cell cultures to salting-out, ultrafiltration, ion exchange chromatography, or liquid-phase extraction using organic solvents. These treatments can be combined as appropriate. Extracts may contain bacterial cell fragments, nucleic acids, peptides, proteins, sugars, and enzymes. Herein, bacterial cells or bacterial cell cultures, or extracts thereof, are also referred to as "bacterial cell preparations."

[0017] The oral composition may be an oral composition that is ingested into the body through the oral cavity. The oral composition may be a food product, and may be a food or feed product for animals other than humans. The oral composition may be a composition that is used in the oral cavity and is discharged from the oral cavity after use. The oral composition may be a composition that is used outside the oral cavity. A composition that is used outside the oral cavity may be, for example, a denture cleanser. The oral composition may be, for example, an oral care product.

[0018] The oral composition, preferably the oral composition, can contain additives as long as they do not impair the effects of the present invention. Examples of additives suitable for oral ingestion include solvents such as water, carbohydrates, proteins, lipids, vitamins, minerals, biologically essential trace metals (manganese sulfate, zinc sulfate, magnesium chloride, potassium carbonate, etc.), flavorings, hygienically or pharmaceutically acceptable carriers, food additives, etc. One or a combination of two or more additives can be appropriately selected and added as needed.

[0019] Examples of carbohydrates include sugars, modified starches (dextrin, soluble starch, British starch, oxidized starch, starch esters, starch ethers, etc.), and dietary fibers.

[0020] Examples of proteins include animal and plant proteins such as whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, α-casein, β-casein, κ-casein, β-lactoglobulin, α-lactalbumin, lactoferrin, soy protein, chicken egg protein, and meat protein, as well as hydrolysates thereof, and various milk-derived components such as butter, milk minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipids, and lactose.

[0021] Examples of lipids include animal fats and oils such as lard, fish oil, fractionated oils thereof, hydrogenated oils thereof, and interesterified oils thereof, as well as vegetable fats and oils such as palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, hydrogenated oils thereof, and interesterified oils thereof.

[0022] Examples of vitamins include vitamin A, carotenes, B vitamins, vitamin C, D vitamins, vitamin E, K vitamins, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline, and folic acid.

[0023] Minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium.

[0024] Oral compositions (preferably oral compositions) may be in any form that can be orally ingested, such as solutions, suspensions, emulsions, powders, pastes, semi-solid compositions, or solid compositions. Examples of foods (including beverages) include milk, plant-based milk, dairy drinks, soft drinks, fermented milk, lactic acid bacteria drinks, dairy drinks, infant formula, liquid milk, liquid diets, foods for the sick, frozen foods, fermented foods, processed foods, confectioneries, seasonings, and other commercially available foods. More specific examples include yogurt, cheese, ice cream, frozen desserts, chocolate, tablets, gummies, candies, jellies, chewing gum, bread, biscuits, crackers, and pizza crust. Oral compositions may be supplements, health foods, functional foods, foods for special dietary uses, foods with health claims, foods with specified health uses, foods with nutrient functions, foods with functional claims, quasi-drugs, cosmetics, or tablets, capsules, powders, granules, jellies, or the like.

[0025] The oral composition, preferably the oral care product, can contain additives as long as they do not impair the effects of the present invention. Examples of additives include fluorine compounds, medicinal ingredients, abrasives, binders, thickeners, surfactants, flavoring agents, preservatives, fragrances, colorants, pH adjusters, solvents, solubilizers, bases, detergents, and adsorbents. The additives can be selected appropriately depending on the dosage form of the composition. One or a combination of two or more additives can be selected appropriately and blended as needed.

[0026] Examples of fluorine compounds include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluorides, sodium monofluorophosphate, potassium monofluorophosphate, sodium silicon fluoride, calcium silicon fluoride, etc., and sodium fluoride or sodium monofluorophosphate is preferred. Fluorine compounds can inhibit dental caries.

[0027] The fluorine compound is used in an amount such that the concentration in the composition is, for example, 1001 ppm to 3000 ppm, preferably 1001 ppm to 2000 ppm, more preferably 1001 ppm to 1500 ppm in terms of fluorine concentration.

[0028] The oral cavity composition may contain medicinal ingredients such as bactericides, anti-inflammatory agents, blood circulation promoters, tartar deposition inhibitors, stain removers, hypersensitivity inhibitors, vitamins, herbal extracts, plaque-decomposing enzymes, etc. These medicinal ingredients are not particularly limited as long as they can be used in pharmaceuticals, etc.

[0029] Examples of disinfectants include cationic disinfectants such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate; amphoteric disinfectants such as dodecyldiaminoethylglycine; nonionic disinfectants such as triclosan and isopropylmethylphenol; and hinokitiol.

[0030] Examples of anti-inflammatory agents include β-glycyrrhetinic acid, glycyrrhetinic acid, glycyrrhizinic acid, diammonium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, ε-aminocaproic acid, sodium azulene sulfonate hydrate, allantoin, allantoin chlorhydroxyaluminum, alcloxa, allantoin dihydroxyaluminum, aldioxa, epidihydrocholesterol, dihydrocholesterol, and lysozyme hydrochloride.

[0031] Examples of blood circulation promoters include sodium chloride.

[0032] Examples of tartar deposit inhibitors include zeolite, disodium hydrogen phosphate, disodium dihydrogen pyrophosphate, sodium pyrophosphate, anhydrous sodium pyrophosphate, tetrasodium pyrophosphate (anhydrous), disodium monohydrogen phosphate, sodium hydrogen phosphate hydrate, disodium hydrogen phosphate (crystalline), trisodium phosphate, and sodium polyphosphate.

[0033] Examples of stain removers include macrogol (Macrogol 200, Macrogol 300, Macrogol 400, Macrogol 600, Macrogol 1000, Macrogol 1500, Macrogol 1540, Macrogol 4000, Macrogol 6000, Macrogol 20000, etc.), sodium polyphosphate, polyvinylpyrrolidone, etc.

[0034] Examples of the desensitizing agent include potassium nitrate and aluminum lactate.

[0035] Examples of vitamin preparations include ascorbic acid, L-ascorbic acid, sodium ascorbate, L-sodium ascorbate, pyridoxine hydrochloride, DL-α-tocopherol acetate, tocopherol acetate, dl-α-tocopherol nicotinate, and tocopherol nicotinate.

[0036] Examples of abrasives include silica-based abrasives such as silicic acid anhydride, silica (crystalline silica or amorphous silica), silica gel, and aluminosilicate, zeolite, calcium hydrogen phosphate anhydrate, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, magnesium tertiary phosphate, zirconium silicate, calcium tertiary phosphate, hydroxyapatite, calcium quaternary phosphate, and synthetic resin-based abrasives.

[0037] Examples of binders include organic binders such as pullulan, gelatin, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, carrageenan, sodium alginate, xanthan gum, sodium polyacrylate, gum arabic, guar gum, locust bean gum, polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymers, as well as inorganic binders such as thickening anhydrous silicic acid and bentonite.

[0038] Examples of thickening agents include polyhydric alcohols (more specifically, sorbitol, glycerin, concentrated glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, propanediol (1,3-propanediol), polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, etc.), trehalose, sodium hyaluronate, and hydrolyzed collagen.

[0039] Examples of surfactants include anionic surfactants such as N-acylamino acid salts, α-olefin sulfonates, N-acylsulfonates, alkyl sulfates (e.g., sodium lauryl sulfate), and sulfates of glycerin fatty acid esters. Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene hydrogenated castor oil, polyoxyethylene ethers of glycerin esters, sucrose fatty acid esters, alkylolamides, glycerin fatty acid esters, and alkyl glycosides. Examples of amphoteric surfactants include alkyl betaine surfactants, amine oxide surfactants, and imidazolinium betaine surfactants. Specific examples of these include 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryl dimethylaminoacetic acid betaine, coconut oil alkyl betaine (coconut oil alkyl dimethylaminoacetic acid betaine), stearyl dimethylaminoacetic acid betaine, sodium stearyl dimethyl betaine, coconut oil fatty acid amido alkyl betaine, palm oil fatty acid amidopropyl betaine, lauric acid amidopropyl betaine, ricinoleic acid amidopropyl betaine, and stearyl dihydroxyethyl betaine.

[0040] Examples of flavoring agents include sodium L-glutamate, saccharin, saccharin sodium, disodium glycyrrhizinate, trisodium glycyrrhizinate, sucrose, glucose, fructose, lactose, honey, aspartame, stevia, sucralose, xylitol, inositol, D-sorbitol, D-mannitol, arabitol, raffinose, lactulose, lactitol, erythritol, reduced palatinose, palatinose, palatinit, acesulfame K, maltose, maltosyl trehalose, maltitol, neohesperidin dihydrochalcone, perillartine, p-methoxycinnamic aldehyde, and thaumatin.

[0041] Examples of preservatives include glycine, sodium benzoate, paraoxybenzoic acid esters such as methylparaben, ethylparaben, butylparaben, isopropylparaben, propylparaben, isobutylparaben, and benzylparaben, alcohols such as phenoxyethanol and ethanol, sorbic acid, benzoic acid, dehydroacetic acid, propionic acid and salts thereof, ethylenediaminetetraacetate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, and alkyldiaminoethylglycine hydrochloride.

[0042] Flavoring agents include, for example, L-menthol, peppermint, spearmint, fruit flavors, peppermint oil, etc. Flavoring agents also have the advantage of stimulating saliva secretion.

[0043] Examples of coloring agents include natural dyes such as safflower red dye, gardenia yellow dye, gardenia blue dye, perilla dye, red koji dye, red cabbage dye, carrot dye, hibiscus dye, cacao dye, spirulina blue dye, and coumarind dye; legal dyes such as Red 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; and titanium dioxide.

[0044] Examples of pH adjusters include acids, alkalis, and buffers such as formic acid, lactic acid, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, pyrophosphoric acid, tartaric acid, sodium hydroxide acetate, potassium hydroxide, sodium acetate, sodium carbonate, sodium citrate, sodium hydrogen citrate, phosphoric acid, sodium phosphate, sodium monohydrogen phosphate, and sodium dihydrogen potassium phosphate.

[0045] The solvent includes water and lower alcohols such as ethanol and propanol.

[0046] A solubilizer may be added to promote dissolution of the additive or active ingredient in water. Examples of such solubilizers include polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, and polyethylene glycol.

[0047] Examples of bases include sodium bicarbonate.

[0048] The detergent may include sodium polyphosphate.

[0049] The adsorbent may include β-cyclodextrin.

[0050] Examples of oral compositions include mouthwashes, dentifrices (toothpaste, liquid dentifrice, tooth powder, etc.), mouth fresheners, gums, lozenges, buccal tablets, gum-adherent tapes, oral gels, oral ointments, oral sprays, oral pastes, oral pastes, oral pills, oral tablets, oral powders, oral powders, oral liquids, oral suspensions, oral emulsions, oral granules, oral capsules, and denture cleaners. The oral composition is preferably a mouthwash or a dentifrice. The oral composition may also be a quasi-drug, hygiene product, or cosmetic.

[0051] The method for producing the oral composition is not particularly limited. The oral composition may be produced by any method for producing general oral compositions, oral care products, etc. The method for producing the oral composition may, for example, include a step of adding the lactic acid bacteria cell preparation in any step of the method for producing general oral compositions, oral care products, etc. The method for producing the oral composition may also include a step of adding the lactic acid bacteria cell preparation to the produced oral composition, oral care product, etc. The oral composition may be the lactic acid bacteria cell preparation itself. The oral composition may include a liquid, a spreader, etc. that facilitates adhesion, absorption, or mixing of the lactic acid bacteria cell preparation with the oral composition, oral care product, etc.

[0052] The amount of the lactic acid bacteria cell preparation contained in the oral composition is not particularly limited as long as it is sufficient to exhibit antibacterial activity against periodontal disease bacteria. The total amount of the lactic acid bacteria cell preparation in the oral composition is, for example, 1 × 10 ３ ~1 x 10 １２ cfu (colony forming units) / g, and 1 x 10 ４ ~1 x 10 １２ cfu / g, and may be 1 x 10 ５ ~1 x 10 １２ The colony forming units may be expressed as cfu / g. The colony forming units can be determined by the agar plate culture method. The total amount (content) of the lactic acid bacteria cell preparation in the oral composition may be 0.0001% to 30% by mass, preferably 0.001% to 10% by mass, relative to the weight of the oral composition. The total concentration of the lactic acid bacteria cell preparation in the oral composition may be 0.1 to 100,000 ppm, 1 to 100,000 ppm, or 10 to 100,000 ppm. The total amount can be measured using a balance or the like.

[0053] The oral composition may be applied to animals. The animals may be humans or non-human animals. The animals include mammals. The mammals may include Rodentia, Lagomorpha, Carnivora, Cetacea, Perissodactyla, and Primates. More specifically, the mammals include mice, rats, hamsters, guinea pigs, hedgehogs, ferrets, rabbits, dogs, cats, cows, pigs, goats, horses, sheep, monkeys, orangutans, chimpanzees, etc. The animals may be pets, livestock, or laboratory animals.

[0054] One embodiment of the present invention is the use of Lactobacillus plantarum cells or cell cultures, or extracts thereof, in the manufacture of an oral composition.

[0055] The oral composition of the present invention may be a composition for preventing or treating an oral disease. In this specification, "treatment" includes alleviation of symptoms, improvement of symptoms, and complete cure. The preventive or therapeutic composition may be a pharmaceutical or veterinary drug, a quasi-drug, a cosmetic, etc.

[0056] Lactobacillus plantarum shows antibacterial activity against the bacteria that cause oral diseases, so it can be used to prevent or treat oral diseases.The oral diseases include periodontal diseases such as gingivitis and periodontitis, dental caries, oral candidiasis, mucositis, glossitis, cheilitis, and angular cheilitis. Examples of bacteria that cause periodontal disease include Porphyromonas gingivalis (hereinafter also referred to as "P.g. bacteria"), Tannerella forsythia (hereinafter also referred to as "T.f. bacteria"), Treponema denticola (hereinafter also referred to as "T.d. bacteria"), Prevotella intermedia, Actinobacillus actinomycetemcomitans, and Fusobacterium nucleatum. Examples of bacteria that cause dental caries include Streptococcus mutans, Streptococcus sobrinus, etc. Examples of Candida fungi include Candida albicans, Candida glabrata, Candida tropicalis, etc.

[0057] Among the bacteria that cause periodontal disease, P.g., T.f., and T.d. are known to aggravate periodontal disease. Lactobacillus plantarum cells or cell cultures, or extracts thereof, have antibacterial activity against all three of the highly malignant periodontal disease bacteria. Therefore, a composition containing a Lactobacillus plantarum cell preparation is effective for preventing or treating oral diseases. A composition containing a Lactobacillus plantarum cell preparation has less effect on the normal oral bacteria than antibiotics (such as minocycline) and chemical disinfectants (such as cetylpyridinium chloride (CPC), isopropylmethylphenol (IPMP)). Therefore, a composition containing a Lactobacillus plantarum cell preparation is less likely to disrupt the balance of oral microflora. A Lactobacillus plantarum cell preparation can also inhibit the growth of bacteria that promote plaque formation. An example of bacteria that promotes dental plaque formation is Streptococcus gordonii (hereinafter also referred to as "Gordonii bacteria").

[0058] The preventive or therapeutic composition may or may not contain other antibacterial agents and antibiotics against the causative bacteria of oral diseases.The dosage form and manufacturing method of the preventive or therapeutic composition may be the same as the dosage form and manufacturing method of the above-mentioned composition.The content of the Lactobacillus plantarum bacterial cell preparation in the preventive or therapeutic composition is not particularly limited as long as it shows antibacterial activity against periodontal disease bacteria, and may be in the same range as the content in the above-mentioned oral composition.

[0059] One embodiment of the present invention is the use of Lactobacillus plantarum cells or a culture of cells, or an extract thereof, in the manufacture of a composition for preventing or treating oral diseases.

[0060] [Method for preventing or treating oral diseases] The method for preventing or treating oral diseases according to one embodiment of the present invention comprises applying Lactobacillus plantarum cells or cell culture or their extract to the oral cavity of animal.The animal can be human or non-human animal.The oral diseases include periodontal diseases such as gingivitis and periodontitis; dental caries; oral candidiasis; mucositis; glossitis; cheilitis; and angular cheilitis etc.The Lactobacillus plantarum cell preparation can be taken orally, or can be discharged outside the oral cavity after being used in the oral cavity.The Lactobacillus plantarum cell or cell culture or their extract can be provided as the oral composition.

[0061] One embodiment of the present invention is the use of Lactobacillus plantarum cells or a culture of cells, or an extract thereof, for the prevention or treatment of oral diseases.

[0062] [Growth inhibitor or bactericide for periodontal disease-causing bacteria, and method for inhibiting or sterilizing the growth of periodontal disease-causing bacteria] The growth inhibitor or bactericide for periodontal disease-causing bacteria according to one embodiment of the present invention comprises Lactobacillus plantarum cells or cell cultures, or extracts thereof. The periodontal disease-causing bacteria include, for example, at least one selected from Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Lactobacillus plantarum cells or cell cultures, or extracts thereof, can inhibit or sterilize the growth of periodontal disease-causing bacteria, and in particular, have antibacterial activity against all three of the above-mentioned causative bacteria. The growth inhibitor or bactericide may be in the same form as the oral composition. The growth inhibitor or bactericide may or may not contain other antibacterial agents and antibiotics against oral disease-causing bacteria.

[0063] The content of the lactic acid bacteria cell preparation contained in the growth inhibitor or disinfectant is not particularly limited, but may be, for example, 1 x 10 ３ ~1 x 10 １２ cfu / mL, and 1 x 10 ５ ~1 x 10 １２ cfu / mL, and 1 x 10 ７~1 x 10 １２ The colony forming units may be expressed as cfu / mL. The colony forming units can be determined by the agar plate culture method. The total concentration of the lactic acid bacteria cell preparation contained in the growth inhibitor or disinfectant is not particularly limited, and may be 0.1 to 100,000 ppm, 1 to 100,000 ppm, or 10 to 100,000 ppm. The total concentration can be measured using a balance or the like.

[0064] The method for inhibiting or sterilizing the growth of periodontal disease-causing bacteria according to one embodiment of the present invention comprises contacting Lactobacillus plantarum cells or cell culture or their extract with periodontal disease-causing bacteria.The method for contacting Lactobacillus plantarum cell preparation with periodontal disease-causing bacteria is not particularly limited, for example, can be added to the environment where periodontal disease-causing bacteria exist, can be immersed in the liquid that contains Lactobacillus plantarum cell preparation, or can be orally administered to the host that is infected with periodontal disease-causing bacteria the composition that contains Lactobacillus plantarum cell preparation.Lactobacillus plantarum cell preparation can also be provided in the form of the growth inhibitor or bactericide of periodontal disease-causing bacteria.

[0065] One embodiment of the present invention is the use of Lactobacillus plantarum cells, a cell culture, or an extract thereof in the manufacture of a growth inhibitor or bactericide for periodontal disease-causing bacteria.One embodiment of the present invention is the use of Lactobacillus plantarum cells, a cell culture, or an extract thereof for inhibiting the growth of or killing periodontal disease-causing bacteria.

[0066] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0067] [Experiment 1: Isolation and identification of NITE BP-03198] The source material (shiokara squid) was ground with sterilized water. The ground liquid was appropriately diluted and added to a 1 / 2 MRS liquid medium for enrichment culture. The enrichment culture was smeared on a calcium carbonate-containing MRS agar medium, and microorganisms that formed halos were isolated. Hereinafter, this isolate will be referred to as isolate A. When the culture liquid of isolate A was suspended in hydrogen peroxide, no bubbles were generated. Isolate A did not have catalase activity, and was therefore confirmed to be a lactic acid bacterium.

[0068] Isolate A was identified by 16S rRNA gene analysis, morphological observation, and physiological and biochemical property tests. (1) 16S rRNA gene analysis Genomic DNA was extracted from isolate A, and the resulting genomic DNA was used as a template for PCR amplification of the 16S rRNA gene using the forward cloning primer 9F and the reverse cloning primer 1510R (Yasuyoshi Nakagawa et al.: Genetic Analysis Method: 16S rRNA Gene Sequencing Method, edited by the Japanese Society for Actinomycetes, Classification and Identification of Actinomycetes, pp. 88-117, Japan Society Administration Center, 2001). PCR amplification was performed using Tks Gflex DNA polymerase (manufactured by Takara Bio Inc.), and the amplified product after PCR was purified.

[0069] Cycle sequencing reactions were performed using the purified PCR amplification products. Cycle sequencing reactions were performed using the BigDye Terminator v3.1 Cycle Sequencing Kit. The resulting reaction solution was purified, and the purified solution was subjected to DNA sequence analysis (3130xl DNA Analyzer) to determine the base sequence of the 16S rRNA gene of the template DNA extracted from isolate A. Primers used for sequence analysis were 9F, 515F, 1099F, 536R, 926R, and 1510R (Yasuyoshi Nakagawa et al.: Genetic Analysis Method: 16S rRNA Gene Base Sequencing Method, Edited by the Japanese Society of Actinomycetes, Classification and Identification of Actinomycetes, pp. 88-117, Japan Society Office, 2001).

[0070] The nucleotide sequence of the 16S rRNA gene of isolate A was subjected to a BLAST homology search against the microbial identification database DB-BA15.0 (Techno Suruga Lab) and the international nucleotide sequence database (DDBJ / ENA (EMBL) / GenBank) using the microbial identification system "ENKI" (Techno Suruga Lab). The nucleotide sequence of the 16S rRNA gene of isolate A had 99.87% identity with the 16S rRNA gene sequence of Lactobacillus pentosus (JCM1558) and 99.87% identity with Lactobacillus plantarum subsp. The 16S rRNA gene sequence of isolate A showed 99.87% identity to the 16S rRNA gene sequence of Lactobacillus plantarum (JCM1149) and 99.73% identity to the 16S rRNA gene sequence of Lactobacillus paraplantarum (DSM10667). However, there were no microorganisms with 16S rRNA genes that completely matched the 16S rRNA gene sequence of isolate A.

[0071] (2) Morphological observation and physiological / biochemical property tests Isolate A was spread on MRS agar medium and aerobically cultured at 30°C for 48 hours, and cell morphology, Gram staining, motility, and colony morphology were observed using the following methods. Cell morphology was observed using an optical microscope BX50F4 (Olympus Corporation). Gram staining was performed using Faber G "Nissui" (Nissui Pharmaceutical Co., Ltd.). Colony morphology was observed using a stereomicroscope SMZ800N (Nikon Corporation). Tests were performed on catalase reaction, oxidase reaction, acid / gas production from glucose, and glucose oxidation / fermentation (O / F) based on the method described by Barrow & Feltham (Cowan and Steel's Manual for the Identification of Medical Bacteria, 3rd ed. Cambridge: Cambridge University Press; 1993). Physiological and biochemical reactions of the bacteria were examined using an API50CHB kit (bioMérieux, France).

[0072] As shown in Figure 1 (A), isolate A formed circular colonies. As shown in Figure 1 (B), isolate A was Gram-stained positive. The results of physiological and biochemical property tests and fermentation tests for isolate A are shown in Tables 1 and 2. Isolate A is a non-motile, Gram-positive bacillus that does not form spores, has negative catalase and oxidase reactions, and ferments glucose. These properties are consistent with those of the genus Lactobacillus, which was indicated as a possible Lactobacillus species by 16S rDNA partial sequence analysis. Fermentation tests performed using an API kit showed that isolate A fermented galactose, fructose, melezitose, etc., but did not ferment glycerol, D-xylose, etc. Isolate A did not exhibit arginine dihydrolase activity and grew at 15°C. These properties are consistent with those of the Lactobacillus species, which was indicated as a possible Lactobacillus species by 16S rDNA partial sequence analysis. Compared to L. pentosus and L. plantarum, isolate A did not exhibit glycerol or D-xylose fermentation, which differed from L. pentosus, but its characteristics were consistent with those of L. plantarum. Therefore, isolate A was found to be a new isolate belonging to Lactobacillus plantarum. Isolate A was deposited internationally under NITE BP-03198.

[0073]

[0074]

[0075] [Experiment 2: Isolation and identification of NITE BP-03199] Isolate strain B was isolated by the same method as in Experiment 1, except that Waxberry was used as the isolation source. Isolate strain B was identified by the same method as in Experiment 1.

[0076] The base sequence of the 16S rRNA gene of isolate B was 100.0% identical to the base sequence of the 16S rRNA gene of Lactobacillus pentosus (JCM1558), 100.0% identical to the base sequence of the 16S rRNA gene of Lactobacillus plantarum subsp. plantarum (JCM1149), and 99.80% identical to the base sequence of the 16S rRNA gene of Lactobacillus paraplantarum (DSM10667).

[0077] As shown in Figure 2(A), isolate B formed circular colonies. As shown in Figure 2(B), isolate B was Gram-stain positive. The results of physiological and biochemical property tests and fermentation tests for isolate B are shown in Tables 3 and 4. Isolate B is a non-motile, Gram-positive bacillus that does not form spores, exhibits negative catalase and oxidase reactions, and ferments glucose. These properties are consistent with those of the genus Lactobacillus, which was indicated as a possible species by 16S rDNA partial sequence analysis. Fermentation tests performed using an API kit showed that isolate B fermented galactose, fructose, α-methyl-D-mannoside, melezitose, etc., but did not ferment glycerol, D-xylose, etc. Isolate B did not exhibit arginine dihydrolase activity and grew at 15°C. These properties were consistent with those of L. plantarum, whose assignment was suggested by partial 16S rDNA sequence analysis, except that it did not exhibit glycerol or D-xylose fermentation, unlike L. pentosus. Therefore, isolate B was found to be a new isolate belonging to Lactobacillus plantarum. Isolate B was deposited internationally under NITE BP-03199.

[0078]

[0079]

[0080] [Experiment 3: Isolation and identification of NITE BP-03200] Isolate strain C was isolated by the same method as in Experiment 1, except that Pandanus orbicularis was used as the isolation source. Isolate strain C was identified by the same method as in Experiment 1.

[0081] The base sequence of the 16S rRNA gene of isolate C was 99.87% identical to the base sequence of the 16S rRNA gene of Lactobacillus pentosus (JCM1558), 99.87% identical to the base sequence of the 16S rRNA gene of Lactobacillus plantarum subsp. plantarum (JCM1149), and 99.66% identical to the base sequence of the 16S rRNA gene of Lactobacillus paraplantarum (DSM10667). However, there were no microorganisms with a 16S rRNA gene that completely matched the base sequence of the 16S rRNA gene of isolate C.

[0082] As shown in Figure 3 (A), isolate C formed circular colonies. As shown in Figure 3 (B), isolate C was Gram-stain positive. The results of physiological and biochemical property tests and fermentation tests for isolate C are shown in Tables 5 and 6. Isolate C is a non-motile, Gram-positive bacillus that does not form spores, exhibits negative catalase and oxidase reactions, and ferments glucose. These properties are consistent with those of the genus Lactobacillus, which was indicated as a possible member of the genus Lactobacillus by partial 16S rDNA sequence analysis. Fermentation tests performed using an API kit showed that isolate C fermented galactose, fructose, α-methyl-D-mannoside, melezitose, etc., but did not ferment glycerol, D-xylose, etc. Isolate C did not exhibit arginine dihydrolase activity and grew at 15°C. These properties were consistent with those of L. plantarum, which was shown to be closely related to L. pentosus and L. plantarum as a result of 16S rDNA partial base sequence analysis, except that it did not exhibit glycerol or D-xylose fermentation, unlike L. pentosus. Therefore, isolate C was found to be a new isolate belonging to Lactobacillus plantarum. Isolate C was deposited internationally under NITE BP-03200.

[0083]

[0084]

[0085] [Experiment 4: Isolation and identification of NITE BP-03201] Isolate strain D was isolated by the same method as in Experiment 1, except that Giran's dogwood was used as the isolation source. Isolate strain D was identified by the same method as in Experiment 1.

[0086] The base sequence of the 16S rRNA gene of isolate D was 99.93% identical to the base sequence of the 16S rRNA gene of Lactobacillus pentosus (JCM1558), 99.93% identical to the base sequence of the 16S rRNA gene of Lactobacillus plantarum subsp. plantarum (JCM1149), and 99.73% identical to the base sequence of the 16S rRNA gene of Lactobacillus paraplantarum (DSM10667). However, there were no microorganisms with a 16S rRNA gene that completely matched the base sequence of the 16S rRNA gene of isolate D.

[0087] As shown in Figure 4 (A), isolate D formed circular colonies. As shown in Figure 4 (B), isolate D was Gram-stained positive. The results of physiological and biochemical property tests and fermentation tests for isolate D are shown in Tables 5 and 6. Isolate D is a non-motile, Gram-positive bacillus that does not form spores, exhibits negative catalase and oxidase reactions, and ferments glucose. These properties are consistent with those of the genus Lactobacillus, which was indicated as a possible Lactobacillus species based on 16S rDNA partial sequence analysis. Fermentation tests performed using an API kit showed that isolate D fermented galactose, fructose, melezitose, etc., but did not ferment glycerol, D-xylose, etc. Isolate D did not exhibit arginine dihydrolase activity and grew at 15°C. These properties are consistent with those of the Lactobacillus species, which was indicated as a possible Lactobacillus species based on 16S rDNA partial sequence analysis. Compared to L. pentosus and L. plantarum, isolate D did not exhibit glycerol or D-xylose fermentation, which differed from L. pentosus and matched the characteristics of L. plantarum. Therefore, isolate D was found to be a new isolate belonging to Lactobacillus plantarum. Isolate D was deposited internationally under NITE BP-03201.

[0088]

[0089]

[0090] [Experiment 5: Isolation and identification of NITE BP-03202] Isolate E was isolated by the same method as in Experiment 1, except that pine cones were used as the isolation source. Isolate E was identified by the same method as in Experiment 1.

[0091] The base sequence of the 16S rRNA gene of isolate E was 99.93% identical to the base sequence of the 16S rRNA gene of Lactobacillus pentosus (JCM1558), 99.93% identical to the base sequence of the 16S rRNA gene of Lactobacillus plantarum subsp. plantarum (JCM1149), and 99.73% identical to the base sequence of the 16S rRNA gene of Lactobacillus paraplantarum (DSM10667). However, there were no microorganisms with a 16S rRNA gene that completely matched the base sequence of the 16S rRNA gene of isolate E.

[0092] As shown in Figure 5(A), isolate E formed circular colonies. As shown in Figure 5(B), isolate E was Gram-stain positive. The results of physiological and biochemical property tests and fermentation tests for isolate E are shown in Tables 9 and 10. Isolate E is a non-motile, Gram-positive bacillus that does not form spores, exhibits negative catalase and oxidase reactions, and ferments glucose. These properties are consistent with those of the genus Lactobacillus, which was indicated as a possible species by 16S rDNA partial sequence analysis. Fermentation tests performed using an API kit showed that isolate E fermented galactose, fructose, α-methyl-D-mannoside, melezitose, etc., but did not ferment glycerol, D-xylose, etc. Isolate E did not exhibit arginine dihydrolase activity and grew at 15°C. These properties were consistent with those of L. plantarum, whose assignment was suggested by partial 16S rDNA sequence analysis, except that it did not exhibit glycerol or D-xylose fermentation, unlike L. pentosus. Therefore, isolate E was found to be a new isolate belonging to Lactobacillus plantarum. Isolate E was deposited internationally under NITE BP-03202.

[0093]

[0094]

[0095] [Experiment 6: Test to evaluate the antibacterial activity of Lactobacillus plantarum against bacteria causing periodontal disease] It was examined whether the bacterial cell preparations NITE BP-03198, NITE BP-03199, NITE BP-03200, NITE BP-03201, and NITE BP-03202 inhibit the growth of bacteria causing periodontal disease.

[0096] The experimental method will be described with reference to Figure 6. Periodontal disease-causing bacteria (P.g., T.f., and T.d.) were pre-cultured using the medium and culture conditions listed in Table 11. The periodontal disease-causing bacteria were suspended in GAM broth and incubated with McFarland No. 0.5 (approximately 1 x 10 ８ ~2 x 10 ８This was further diluted 10 times to prepare bacterial suspension 11 (approximately 1 × 10 ７ ~2 x 10 ７ cfu / mL). 100 μL of the periodontal disease bacteria solution 11 was dropped onto the measurement agar medium 12 and evenly spread with a cone-larger. Once the surface of the agar medium had dried, 10 μL of Lactobacillus plantarum cell preparation 13 was dropped onto the agar medium and cultured at 35°C in an anaerobic environment. P.g. bacteria were cultured for 5 days, T.f. bacteria for 7 days, and T.d. bacteria for 4 days. When the Lactobacillus plantarum cell preparation has antibacterial activity against periodontal disease-causing bacteria, a growth inhibition zone 14 is formed. The Lactobacillus plantarum cell preparation was prepared by culturing any of the lactic acid bacteria NITE BP-03198, NITE BP-03199, NITE BP-03200, NITE BP-03201, and NITE BP-03202 in MRS Broth at 30°C, and precipitating the cells by centrifugation to obtain a culture supernatant (cell culture). The results of the antibacterial activity against P.g., T.f., and T.d. are shown in Tables 12, 13, and 14, respectively. A medium for lactic acid bacteria (MRS Broth) was used as a negative control. As a positive control, SensiDisc "MEPM" (manufactured by Nippon Becton Dickinson) containing 10 μg / 6 mmφ of meropenem or SensiDisc "LVFX" (manufactured by Nippon Becton Dickinson) containing 10 μg / 6 mmφ of the quinolone antibacterial agent levofloxacin were used. ATCC-11454 is a lactic acid bacterium (Lactococcus subsp. lactis) that produces nisin A. The nisin A-producing strain was cultured in the same manner as Lactobacillus plantarum, and the culture supernatant was prepared.

[0097]

[0098]

[0099]

[0100]

[0101] All of the bacterial cell cultures of NITE BP-03198, NITE BP-03199, NITE BP-03200, NITE BP-03201, and NITE BP-03202 formed growth inhibition circles in all growth media for P.g., T.f., and T.d. bacteria. All of the Lactobacillus plantarum bacterial cell cultures were shown to be able to inhibit the growth of P.g., T.f., and T.d. bacteria. On the other hand, the culture supernatant of the nisin A-producing strain inhibited the growth of T.d. bacteria, but was unable to inhibit the growth of P.g. and T.f. bacteria.

[0102] [Experiment 7: Test to evaluate the antibacterial activity of Lactobacillus plantarum against bacteria that promote dental plaque formation] It was examined whether the bacterial cell preparations NITE BP-03198, NITE BP-03199, NITE BP-03200, NITE BP-03201, and NITE BP-03202 inhibit the growth of bacteria that promote dental plaque formation.

[0103] Experiment 7 was carried out in the same manner as Experiment 6, except that P. gordonii was used as the bacterium to verify antibacterial activity. P. gordonii was pre-cultured according to the medium and culture conditions listed in Table 15. P. gordonii was suspended in GAM broth and incubated with McFarland No. 0.5 (approximately 1 x 10 ８ ~2 x 10 ８ This was further diluted 10-fold to prepare P. gordonii bacterial solution 11 (approximately 1 × 10 ７ ~2 x 10 ７ cfu / mL). 100 μL of Lactobacillus gordonii bacterial solution 11 was dropped onto a measurement agar medium 12 and uniformly spread with a conlarger. Once the surface of the agar medium had dried, 10 μL of Lactobacillus plantarum bacterial cell preparation 13 was dropped onto the agar medium and cultured at 35°C for 24 hours. The results of the antibacterial activity against Lactobacillus gordonii are shown in Table 16. A lactic acid bacteria medium (MRS Broth) was used as a negative control. SensiDisc "TC" (manufactured by Nippon Becton Dickinson) containing 30 μg / 6 mmφ of tetracycline was used as a positive control. ATCC-11454 is a lactic acid bacterium (Lactococcus subsp. lactis) that produces nisin A.

[0104]

[0105]

[0106] The bacterial cultures of NITE BP-03198, NITE BP-03199, NITE BP-03200, NITE BP-03201 and NITE BP-03202 all formed growth inhibition circles on the growth medium for P. gordonii. It was shown that the bacterial cultures of Lactobacillus plantarum can inhibit the growth of Lactobacillus plantarum.

[0107] [Experiment 8: Evaluation test of antibacterial activity of Lactobacillus plantarum against oral resident bacteria] It was examined whether the bacterial cell preparations NITE BP-03198, NITE BP-03199, NITE BP-03200, NITE BP-03201, and NITE BP-03202 inhibit the growth of oral resident bacteria.

[0108] Experiment 8 was conducted in the same manner as Experiment 6, except that Lactobacillus salivarius was used as the bacterium to verify antibacterial activity. Lactobacillus salivarius was pre-cultured according to the medium and culture conditions listed in Table 17. Lactobacillus salivarius was suspended in GAM broth and incubated with McFarland No. 0.5 (approximately 1 x 10 ８ ~2 x 10 ８ This was further diluted 10-fold to prepare Bacillus salivarius solution 11 (approximately 1 × 10 ７ ~2 x 10 ７ cfu / mL). 100 μL of Lactobacillus salivarius bacterial solution 11 was dropped onto measurement agar medium 12 and uniformly spread with a conlarger. Once the surface of the agar medium had dried, 10 μL of Lactobacillus plantarum bacterial cell preparation 13 was dropped onto the agar medium and cultured at 35°C for 24 hours. The results of the antibacterial activity against Lactobacillus salivarius are shown in Table 18. A lactic acid bacteria medium (MRS Broth) was used as a negative control. SensiDisc "TC" (manufactured by Nippon Becton Dickinson) containing 30 μg / 6 mmφ of tetracycline was used as a positive control. ATCC-11454 is a lactic acid bacterium (Lactococcus subsp. lactis) that produces nisin A.

[0109]

[0110]

[0111] None of the bacterial cultures NITE BP-03198, NITE BP-03199, NITE BP-03200, NITE BP-03201, and NITE BP-03202 formed growth inhibition zones in the growth medium for Lactobacillus salivarius. It was shown that the bacterial culture of Lactobacillus plantarum has little effect on the normal oral flora. Meanwhile, tetracycline also inhibited the growth of normal oral flora.

[0112] 11 Bacterial liquid of bacteria that cause periodontal disease, bacteria that promote plaque formation, or bacteria that are resident in the oral cavity, 12 Agar medium for measurement, 13 Bacterial preparation of Lactobacillus plantarum, 14 Growth inhibition circle.

Claims

1. An oral composition comprising cells or cell cultures of Lactobacillus plantarum or extracts thereof.

2. The composition according to claim 1, which is a food.

3. The composition according to claim 2, wherein the food is a fermented food.

4. The composition according to claim 1, which is a mouthwash or dentifrice.

5. The composition according to claim 1 or 4, further comprising a fluorine compound.

6. The composition according to claim 1 or 2, wherein the Lactobacillus plantarum is at least one selected from NITE-BP-03198, NITE-BP-03199, NITE-BP-03200, NITE-BP-03201, and NITE-BP-03202.

7. The composition according to any one of claims 1 to 4, which is a composition for preventing or treating oral diseases.

8. The composition according to claim 7, wherein the oral disease is periodontal disease.

9. A method for preventing or treating oral diseases, comprising applying cells or cell cultures of Lactobacillus plantarum or extracts thereof to the oral cavity of an animal (excluding humans).

10. The method according to claim 9, wherein the oral disease is periodontal disease.

11. A growth inhibitor or bactericide against periodontal disease-causing bacteria, comprising cells or cell cultures of Lactobacillus plantarum or extracts thereof.

12. The growth inhibitor or bactericide according to claim 11, wherein the periodontal disease-causing bacteria include at least one selected from Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola.

13. A method for inhibiting the growth or killing periodontal disease-causing bacteria (excluding medical acts on humans), comprising contacting cells or cell cultures of Lactobacillus plantarum or extracts thereof with periodontal disease-causing bacteria.