WO2021079921A1 - Ralentisseur de croissance de bactérie pathogène interne à la cavité buccale, agent améliorant la flore bactérienne interne à la cavité buccale, et composition pour cavité buccale - Google Patents

Ralentisseur de croissance de bactérie pathogène interne à la cavité buccale, agent améliorant la flore bactérienne interne à la cavité buccale, et composition pour cavité buccale Download PDF

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WO2021079921A1
WO2021079921A1 PCT/JP2020/039636 JP2020039636W WO2021079921A1 WO 2021079921 A1 WO2021079921 A1 WO 2021079921A1 JP 2020039636 W JP2020039636 W JP 2020039636W WO 2021079921 A1 WO2021079921 A1 WO 2021079921A1
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oral
pathogenic bacteria
oral cavity
growth
streptococcus
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PCT/JP2020/039636
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English (en)
Japanese (ja)
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悠菜 瀧本
隆太郎 城
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ライオン株式会社
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Priority to JP2021553507A priority Critical patent/JPWO2021079921A1/ja
Publication of WO2021079921A1 publication Critical patent/WO2021079921A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/10—Chewing gum characterised by the composition containing organic or inorganic compounds characterised by the carbohydrates used, e.g. polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A61Q11/02—Preparations for deodorising, bleaching or disinfecting dentures

Definitions

  • the present invention relates to a growth inhibitor for pathogenic bacteria in the oral cavity, a bacterial flora improving agent in the oral cavity, and an oral composition using these.
  • bacterial flora a bacterial population
  • This bacterial flora is a mixture of so-called non-pathogenic indigenous bacteria and pathogenic bacteria, but it is usually a so-called healthy state in which the bacterial flora is balanced and pathogenic. Diseases caused by bacteria are suppressed.
  • the pathogenic bacteria are Streptococcus mutans, which is the causative agent of caries, and Porphyromonas gingivalis, which is the causative agent of periodontal disease and bad odor.
  • Streptococcus mutans which is the causative agent of caries
  • Porphyromonas gingivalis which is the causative agent of periodontal disease and bad odor.
  • Streptococcus show no pathogenicity to humans Gorudoniai (Streptococcus Gordonii), Streptococcus mitis (Streptococcus mitis), Streptococcus oralis (Streptococcus oralis), Streptococcus Perorisu (Streptococcus peroris), Streptococcus Rakutariusu (Streptococcus lactarius)
  • Streptococcus bacteria such as the Mitis group, Streptococcus bacteria such as Neisseria subflava, and Actinomyces naeslundii such as Actinomyces naeslundii. It is a non-pathogenic Streptococcus. Therefore, in order to prevent oral diseases, it is important to maintain and form a well-balanced and healthy bacterial flora composed of these non-pathogenic indigenous bacteria in the oral cavity.
  • Patent Document 1 Japanese Patent No. 5982376
  • Patent Document 2 Patent Document 2: Patent No. 6235138
  • Patent Document 3 Japanese Patent Application Laid-Open No. 2012-77053
  • sugar alcohol which is a sweetener
  • sugar alcohol is used as a substitute component for sugar because it has the effect of suppressing the growth of caries-causing bacteria and its pH production, but the effect is not sufficient and it is an oral bacterium.
  • the balance control of the flora was not reached.
  • the present invention has been made in view of the above circumstances, and provides an agent for suppressing the growth of pathogenic bacteria in the oral cavity, an agent for improving the flora of the oral cavity, and an oral composition using these.
  • the purpose is.
  • (A) milk oligosaccharide has a growth-suppressing effect on pathogenic bacteria in the oral cavity, and moreover, non-pathogenic bacteria in the oral cavity. It has the effect of promoting the growth of (resident bacteria in the oral cavity, the same applies hereinafter), and when this (A) milk oligosaccharide and (B) sugar alcohol are used in combination, the growth of non-pathogenic bacteria in the oral cavity is selective.
  • Bacterial flora that promotes the growth of pathogenic bacteria, selectively suppresses the growth of pathogenic bacteria, increases the abundance ratio of non-pathogenic bacteria to pathogenic bacteria, and improves the balance of bacterial composition ratio of the bacterial flora mainly to non-pathogenic bacteria. It was found that the effect of improvement is excellent. Then, it was found that by blending the above-mentioned combination system into the oral composition, the above-mentioned excellent bacterial flora improving effect can be imparted, and it can be applied to the prevention or suppression of oral diseases, particularly caries, and the present invention has been developed. I came to the eggplant.
  • the present inventors attempted to develop an oral composition for improving the bacterial flora in the oral cavity into a bacterial flora mainly composed of non-pathogenic indigenous bacteria.
  • (A) milk oligosaccharide does not have a growth-suppressing effect on pathogenic bacteria in the oral cavity, but in the oral cavity in which non-pathogenic indigenous bacteria, particularly Streptococcus perolis or Streptococcus lactalius, are present.
  • the component (A) promotes the growth of Streptococcus perolis or Streptococcus lactalius, and exerts a remarkably excellent growth promoting effect on non-pathogenic bacteria in the oral cavity.
  • the two interact with each other, and at the same time, the above-mentioned action of the component (A) itself, particularly the growth promoting action of non-pathogenic bacteria is further enhanced, and at the same time, ( The action of the component B) on pathogenic bacteria, particularly caries-causing bacteria, was improved, and the action of suppressing its growth was enhanced.
  • the non-pathogenic bacteria and the pathogenic bacteria in the oral cavity coexist by the combined system of the components (A) and (B), and in the bacterial flora formed by a plurality of bacterial species in this way, the non-pathogenic bacteria Selectively promotes growth, increases the number of bacteria to increase the abundance ratio, and selectively suppresses the growth of pathogenic bacteria that cause caries, and decreases the number of bacteria to increase the abundance ratio.
  • the growth of non-pathogenic bacteria can be remarkably promoted, and the abundance ratio of non-pathogenic bacteria to pathogenic bacteria can be increased to a high ratio, which gives an excellent flora improving effect. I was able to.
  • a peculiar and remarkable bacterial flora improving effect was obtained by using the components (A) and (B) in combination, and the bacterial flora improving effect was low with the component (A) alone or the component (B) alone.
  • the oral composition containing the components (A) and (B) of the present invention is treated against a plurality of non-pathogenic bacteria and a mixed bacterial solution of pathogenic bacteria, The number of caries-causing bacteria (iii) after treatment is low and the abundance ratio is low, and the number of non-pathogenic bacteria (i) + (ii) after treatment is high and the abundance ratio of these is high.
  • the abundance ratio of non-pathogenic bacteria to pathogenic bacteria was higher than that of the untreated control (sample untreated), and the effect of improving the flora was excellent. ..
  • the oral composition in which the component (A) is not blended can be used as an untreated control (sample untreated).
  • the number of caries-causing bacteria decreased slightly after the treatment, but the abundance ratio of non-pathogenic bacteria to pathogenic bacteria hardly changed, and the effect of improving the flora was low.
  • Streptococcus mutans Streptococcus sobrinus, Porphyromonas streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus streptococcus
  • Streptococcus Streptococcus (Streptococcus) bacteria, Neisseria Sabufuraba (Neisseria Subflava) Neisseria bacteria such as, Actinomyces Ness
  • the growth of Streptococcus genus bacteria such as Randy (Actinomyces naeslundii) is selectively promoted, and the bacterial flora balance in the oral cavity can be improved mainly by non-pathogenic indigenous bacteria. Therefore, according to the present invention, it is possible to maintain and form a bacterial flora in the oral cavity in a healthy state mainly composed of non-pathogenic indigenous bacteria, which is effective for prevention or suppression of oral diseases, especially caries. Oral composition can be provided.
  • the present invention provides the following oral composition, an agent for suppressing the growth of pathogenic bacteria in the oral cavity for blending the oral composition, and an agent for improving the flora of the oral cavity.
  • A Milk oligosaccharides and
  • B An oral composition comprising a sugar alcohol.
  • A The milk oligosaccharide is at least one selected from 2'-fucosyl lactose, 3'-sialyl lactose, 6'-sialyl lactose, lacto-N-tetraose and lacto-N-fucopentaose I [1].
  • the above-mentioned oral composition is at least one selected from 2'-fucosyl lactose, 3'-sialyl lactose, 6'-sialyl lactose, lacto-N-tetraose and lacto-N-fucopentaose I [1].
  • An oral composition selected from agents, tongue care agents and mouthwashes.
  • the present invention it is possible to provide a growth inhibitor for pathogenic bacteria in the oral cavity, a bacterial flora improving agent in the oral cavity, and an oral composition to which these are applied.
  • the oral composition containing the components (A) and (B) of the present invention promotes the growth of non-pathogenic bacteria in the oral cavity, suppresses the growth of pathogenic bacteria, and has a bacterial composition ratio of the flora. It has an excellent flora improving effect that improves the balance mainly of non-pathogenic bacteria.
  • This oral composition is particularly effective in promoting the growth of non-pathogenic bacteria and further improving the bacterial flora, and can also be effectively used for preventing or suppressing oral diseases, particularly caries.
  • the oral composition of the present invention contains (A) milk oligosaccharide, or (A) milk oligosaccharide and (B) sugar alcohol.
  • non-pathogenic bacteria in the oral cavity (resident bacteria in the oral cavity, hereinafter referred to as "non-pathogenic bacteria") and pathogenic bacteria coexist.
  • non-pathogenic bacteria in a bacterial flora formed by multiple bacterial species, it selectively promotes the growth of non-pathogenic bacteria and selectively suppresses the growth of pathogenic bacteria, which in particular promotes the growth of non-pathogenic bacteria.
  • the components (A) and (B) are active ingredients for the growth of non-pathogenic bacteria in the oral cavity and the improvement of the flora in the oral cavity, and the above-mentioned action and effect can be obtained by blending them. be able to.
  • the improvement of the flora in the oral cavity means that the treatment increases the number of non-pathogenic bacteria and increases the abundance ratio, and the pathogenic bacteria in the oral cavity decrease and the abundance ratio decreases.
  • the abundance ratio of non-pathogenic bacteria is increasing, and the flora in the oral cavity is improving the balance of healthy conditions mainly composed of non-pathogenic bacteria.
  • Milk oligosaccharide is a bacterial flora in which a plurality of bacterial species exist as described above, and has an action of promoting the growth of non-pathogenic bacteria and increasing non-pathogenic bacteria, and is also a component of (B). It also has the effect of enhancing the growth inhibitory effect on non-pathogenic bacteria.
  • the milk oligosaccharide (A) the milk oligosaccharides shown below can be used, and one or more selected from these can be used.
  • the milk oligosaccharide has a free lactose unit on the reducing end side, and N-acetylglucosamine (GlcNAc), galactose (Gal), fucose (Fuc), and N-acetylneuraminic acid (Neu5Ac) are added.
  • Examples of milk oligosaccharides are 2'-fucosyl lactose, 3-fucosyl lactose, 3'-sialyl lactose, 6'-sialyl lactose, lacto-N-tetraose, lacto-N-neotetraose, lacto-N-fucopentaose I.
  • Lact-N-Fucopentaose II Lactose-N-Fucopentaose III, Lact-N-Difucohexaose I, Lact-N-Difucohexaose II, Lactose-N-Hexaose, Lact-N-Neohexaose, 6 '-N-Acetylneuraminyl lactose, 3'-N-acetylneuraminyl lactose and the like can be mentioned.
  • 2'-fucosyl lactose, 3'-sialyl lactose, 6'-sialyl lactose, lacto-N-tetraose, lacto-N-fucopentaose I are preferable, and more preferably 2'-fucosyl lactose, 3'-sialyl lactose, 6'-sialyl lactose, more preferably 3'-sialyl lactose, 6'-sialyl lactose.
  • lactulose can be used as the milk oligosaccharide.
  • Lactulose is a disaccharide in which galactose and fructose are ⁇ -1,4-glycosidic bonded, and is used for improving constipation and the like.
  • Lactulose can also be preferably used as the milk oligosaccharide.
  • the milk oligosaccharide (A) a commercially available product can be used, and for example, a product manufactured by Carbosynth can be used.
  • the amount of the milk oligosaccharide (A) to be blended is preferably 0.01% (mass%, the same applies hereinafter) or more, preferably 0.1% or more, from the viewpoint of promoting the growth of non-pathogenic bacteria and improving the bacterial flora. Is more preferable, and 0.5% or more is further preferable.
  • the blending amount is 0.01% or more, the growth promoting effect of non-pathogenic bacteria and the bacterial flora improving effect can be sufficiently obtained.
  • the above effect increases as the blending amount increases, and the upper limit thereof is not particularly limited.
  • the blending amount of the component (A) is 50% or less of the entire composition. Is preferable, 10% or less is more preferable, and 5% or less is further preferable.
  • sugar alcohol is a bacterial flora in which a plurality of bacterial species exist as described above, has an effect of suppressing the growth of pathogenic bacteria and reducing pathogenic bacteria, and is non-pathogenic of the component (A). It also has the effect of enhancing the growth promoting effect on bacteria.
  • the sugar alcohol include xylitol, sorbitol, maltitol, erythritol, mannitol, glycerin, lactitol, isomalt and the like, and one or more selected from these can be used.
  • xylitol, sorbitol, maltitol, erythritol, and mannitol are preferable, and xylitol and sorbitol, particularly xylitol, are preferable from the viewpoint of suppressing the growth of pathogenic bacteria and improving the bacterial strength.
  • sugar alcohol a commercially available product can be used, and for example, a product manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. can be used.
  • the blending amount of the sugar alcohol is preferably 1% or more, more preferably 5% or more, still more preferably 10% or more of the entire composition from the viewpoint of suppressing the growth of pathogenic bacteria and improving the bacterial flora.
  • the blending amount is 1% or more, the effect of suppressing the growth of pathogenic bacteria and the effect of improving the flora can be sufficiently obtained.
  • the larger the blending amount, the higher the effect, and the upper limit thereof is not particularly limited, but it is preferable to adjust the amount according to the mass ratio of (A) / (B) described later. If too much is added, the stability of the preparation may be lowered, and the amount of the component (B) is preferably 1 to 90% of the whole composition, particularly 5 to 50%, particularly 10 to 20%. preferable.
  • (A) / (B) which indicates the quantitative ratio of the component (A) to the component (B), preferably has a mass ratio of 0.0005 to 1, more preferably 0.005 to 0.5. Particularly preferably, it is 0.025 to 0.10.
  • the mass ratio of (A) / (B) is within the above range, the effect of promoting the growth of non-pathogenic bacteria and the effect of suppressing the growth of pathogenic bacteria are further enhanced, and a more excellent effect of improving the flora can be obtained. ..
  • the oral composition of the present invention can be prepared in various shapes such as liquid (liquid, liquid), paste, and solid (solid, solid), and the dosage form is not particularly limited.
  • the oral composition is mainly intended to be used in the oral cavity, and is not only an oral preparation discharged from the oral cavity after use, but also an ingestible food and drink.
  • toothpaste teethpaste, liquid toothpaste, liquid toothpaste, powdered toothpaste, etc.
  • mouthwash coating agent, mouth spray, patch, sheet agent, oral sustained release agent, chewing agent, oral dissolving agent, oral cavity
  • It can be prepared as a general oral preparation such as an internal disintegrant, a dentifrice care agent, a tongue care agent, and a mouth refreshing agent.
  • the form of the food or drink is preferably chewing gum, tablet confectionery, candy, gummies, or edible film from the viewpoint of convenience and portability that can be used anytime and anywhere.
  • the oral composition of the present invention may optionally contain other known components in addition to the above components, if necessary.
  • Optional ingredients include, for example, surfactants, abrasives, thickeners, binders, colorants, sweeteners, preservatives, flavors, active ingredients, as well as pH adjusters, brighteners, fluidizers. , Static eliminators, binders, acidulants, lubricants, preservatives, disintegrants, excipients, solvents, etc., and the blending amounts thereof may be appropriately adjusted as long as the effects of the present invention are not impaired. , Ordinary dose may be used.
  • oral preparations such as dentifrices and mouthwashes
  • surfactants abrasives, thickeners, binders, colorants, sweeteners, preservatives, fragrances, active ingredients, pH adjusters and the like
  • foods and drinks such as chewing gum, tablets, candies and gummies, gum bases, colorants, sweeteners, flavors, brighteners, fluidizers, binders, acidulants, lubricants, preservatives, disintegrants, excipients Etc. can be blended.
  • an anionic surfactant As the surfactant, an anionic surfactant, a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant, which are generally used for oral use, can be blended.
  • the anionic surfactant is an alkyl sulfate such as sodium lauryl sulfate
  • the nonionic surfactant is a sugar fatty acid ester, a sugar alcohol fatty acid ester, a sorbitan fatty acid ester, a glycerin fatty acid ester, a polyoxyethylene fatty acid ester or a higher alcohol ester.
  • the nonionic surfactant is a sugar fatty acid ester, a sugar alcohol fatty acid ester, a sorbitan fatty acid ester, a glycerin fatty acid ester, a polyoxyethylene fatty acid ester or a higher alcohol ester.
  • Examples of the cationic surfactant include an alkylammonium salt, and examples of the amphoteric surfactant include a betaine type and an imidazoline type.
  • the blending amount of the surfactant is usually 0 to 10%, particularly 0.01 to 5% of the total composition.
  • abrasive examples include silica-based abrasives, calcium phosphate-based abrasives, and calcium carbonate-based abrasives, and the blending amount thereof is usually 2 to 50% of the total composition of dentifrices such as dentifrice.
  • the thickener examples include polyhydric alcohols such as propylene glycol and glycerin. Since the component (B) also acts as a thickener, it is not necessary to add any thickener.
  • the blending amount of these arbitrary thickeners is preferably 0 to 89% of the entire composition, and the total blending amount combined with the blending amount of the component (B) is 90% or less, particularly 50% or less, and further 20% or less. It is preferable to have.
  • binder examples include cellol derivatives such as sodium carboxymethyl cellulose and gums as organic binders, and gelling silica and the like as inorganic binders.
  • the blending amount is usually 0.5 to 10% of the total composition.
  • Colorants include Red No. 2, Blue No. 1, etc.
  • sweeteners include saccharin sodium, etc.
  • preservatives include paraoxybenzoic acid ester, etc.
  • Fragrances are peppermint oil, sparemint oil, anis oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamon oil, coriander oil, mandarin oil, lime.
  • fragrance lavender oil, rosemary oil, laurel oil, camomill oil, caraway oil, majorum oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie oil , Yuzu oil, iris concrete, absolute peppermint, absolute rose, orange flower and other natural fragrances, and processing of these natural fragrances (pre-reservoir cut, rear-reservoir cut, distilling, liquid extraction, essence, powder fragrance Perfume, menthol, carboxylic, anator, cineole, methyl salicylate, synamic aldehyde, eugenol, 3-l-mentoxypropane-1,2-diol, timole, linalol, linaryl acetate, limonene, menton , Menthylacetate, N-substituted-paramentan-3-carboxamide, pinen, octylaldehyde, citral, pregon, calvier
  • the amount of these flavors to be added to the composition is usually preferably 0.00001 to 1% for oral preparations such as dentifrices and mouthwashes, and 0. 001 to 50% is good. It is preferable to use 0.1 to 10% of the perfume for perfume using the above perfume material in the composition.
  • a known one that is usually blended in an oral composition can be blended.
  • nonionic bactericides such as isopropylmethylphenol
  • cationic bactericides such as cetylpyridinium chloride
  • anti-inflammatory agents such as tranexamic acid and epsilon aminocaproic acid
  • enzymes such as dextranase, sodium fluoride and monofluorophosphate.
  • fluorides such as sodium, water-soluble phosphoric acid compounds, copper compounds, potassium nitrate, aluminum lactate, various vitamins, and plant extracts.
  • the blending amount of the active ingredient can be set within a range that does not interfere with the effects of the present invention.
  • non-selective fungicide that kills not only pathogenic bacteria in the oral cavity but also non-pathogenic bacteria.
  • the non-selective bactericide is often found in bactericides widely used in oral preparations, and examples thereof include cationic bactericides such as cetylpyridinium chloride and nonionic bactericides such as isopropylmethylphenol. ..
  • cationic bactericides such as cetylpyridinium chloride
  • nonionic bactericides such as isopropylmethylphenol. ..
  • These non-selective bactericides can be blended within the range in which the effects of the present invention are exhibited, but when blended, 0.1% or less, particularly 0.05% or less of the entire composition is preferable, and it is best not to blend them. preferable.
  • non-selective bactericidal agents have a non-selective bactericidal action that kills not only pathogenic bacteria but also non-pathogenic indigenous bacteria in the oral cavity.
  • the balance of the bacterial flora inside may be lost and control may be lost. Therefore, in the present invention, it is more preferable that the non-selective bactericidal agent is not blended for selective improvement of the oral flora and balance control.
  • the present invention is composed of (A) a growth inhibitor for pathogenic bacteria in the oral cavity composed of milk oligosaccharide, and (A) milk oligosaccharide and (B) sugar alcohol, preferably (B) / (A). ) Provided an agent for promoting the growth of non-pathogenic bacteria in the oral cavity having a mass ratio of 0.0005 to 1, and an agent for improving the flora of the oral cavity.
  • it is sufficient to contain only the component (A) or the components (A) and (B), but if necessary, any component may be added as described above.
  • the details of the types, amounts, ratios, etc. of the components (A), (B), and other components are the same as described above.
  • the growth inhibitor for pathogenic bacteria in the oral cavity according to the present invention contains the component (A), and in particular, by making an oral composition containing the component (A), the growth inhibitor for the pathogenic bacteria in the oral cavity is suppressed.
  • the effect is obtained.
  • Streptococcus perolis or Streptococcus lactalius present in the oral cavity has a growth-suppressing effect on pathogenic bacteria in the oral cavity.
  • the component (A) itself does not have a growth-suppressing effect on pathogenic bacteria in the oral cavity, by applying these components in the oral cavity, the pathogenicity of Streptococcus perolis or Streptococcus lactalius in the oral cavity It has the effect of dramatically promoting the growth-suppressing effect on bacteria, and a remarkable growth-suppressing effect on pathogenic bacteria in the oral cavity can be obtained. From the above, the component (A) is effective as an accelerator for promoting the growth inhibitory effect of Streptococcus perolis or Streptococcus lactalius on pathogenic bacteria in the oral cavity.
  • the oral bacterial flora improving agent according to the present invention contains a component (A) and a component (B), and in particular, by preparing an oral composition containing these components, as described above, A growth-suppressing effect on pathogenic bacteria in the oral cavity is obtained, and a growth-promoting effect is obtained on non-pathogenic bacteria in the oral cavity, whereby the balance of bacterial composition ratio of the bacterial flora in the oral cavity is non-pathogenic. A remarkable effect of improving the flora can be obtained, which improves mainly on sex bacteria.
  • Examples, comparative examples The oral compositions having the compositions shown in Tables 1 to 3 were evaluated for their influence on the bacterial composition ratio by the method shown below, and the effect of improving the bacterial flora in the oral cavity was evaluated.
  • THBHM human liver hematoma
  • 20 mL of THBHM was inoculated with 1% of this culture solution, and anaerobically cultured at 37 ° C. for 24 hours.
  • the bacterial composition ratio is a ratio to the total viable cell count of the viable cell count of each bacterium after treatment.
  • bacterial composition ratio of each bacterial in the control (sample untreated) ⁇ (I) + (ii) ⁇ / (iii) the bacterial flora improving effect was as shown in Tables 1 to 3. Since the number of each bacterium in the mixed bacterial solution varies from the initial number even after preparation, the viable number of each bacterium after culturing the control (sample untreated) was used as a reference.
  • the effect of improving the bacterial flora of the present invention is evaluated by the ratio of the number of non-pathogenic bacteria to the ratio of the number of pathogenic bacteria (caries-causing bacteria) in the oral cavity, and the higher the ratio, the higher the effect.
  • the number of bacteria increases by culturing even in the control (sample untreated). Therefore, if the number of caries-causing bacteria is smaller than the number of control (sample untreated) bacteria, there is an effect of suppressing the growth of caries-causing bacteria, and the number of non-pathogenic bacteria is controlled (sample untreated).
  • the abundance ratio of non-pathogenic bacteria to pathogenic bacteria (caries-causing bacteria) ⁇ (i) + (ii) ⁇ / (iii) is controlled (sample untreated).
  • the abundance ratio in the above is preferably 2 times or more, particularly 4 times or more, particularly 6 times or more, and such an abundance ratio is excellent in the effect of improving the bacterial flora.
  • the bacterial solution after culturing was centrifuged at 11,000 rpm for 5 minutes, and the precipitate was prepared using Todd Hevitbros medium to obtain the above-mentioned S. cerevisiae. peroris, S.M.
  • the bacterial solution was prepared by resuspending each lactarius so as to have a turbidity (OD550 nm) of 1.0.
  • 1% of the prepared bacterial solution was added to 40 mL of Todd Hevitbros medium to which 1% of the component (A) was added, and the cells were anaerobically cultured at 37 ° C. for 24 hours.
  • the obtained culture broth was centrifuged at 11,000 rpm for 5 minutes, and the supernatant was collected.
  • the cells were removed by filtration through a 0.22 ⁇ filter.
  • the turbidity (OD550 nm) was adjusted to 1.0 in the same manner as above.
  • 30 ⁇ L of Gingivalis bacterium solution was added, and the turbidity (OD550 nm) was measured after anaerobic culture at 37 ° C. for 24 hours.
  • the turbidity of the evaluation sample (component (A) or a combination system of component (A) and S. peroris or S. lactarius) was set to a, and the turbidity was controlled (no non-pathogenic bacteria, distilled water instead of component (A)).
  • X (a / b) x 100
  • S. peroris or S. Lactarius has a growth-suppressing effect on oral pathogenic bacteria.
  • the component (A) itself does not have a growth-suppressing effect on oral pathogenic bacteria, S. peroris or S.
  • S. peroris or S When used in combination with lactarius, S. peroris or S. It has the effect of dramatically promoting the growth-suppressing effect of lactarius on oral pathogenic bacteria, and a remarkable growth-suppressing effect on oral pathogenic bacteria was obtained.
  • the component (A) can be applied to the oral cavity in which Streptococcus perolis or Streptococcus lactalius is present. It was found that Streptococcus perolis or Streptococcus lactose has the effect of dramatically promoting the growth-suppressing effect on oral pathogenic bacteria.
  • the concentrations (%) in Tables 8 and 9 are the concentrations in Todd Hevitbros medium.
  • Ts turbidity of the evaluation sample addition
  • Tc turbidity of the control (distilled water addition)
  • the raw materials used are the same as above.
  • the oral composition of the formulation example can increase the abundance ratio of non-pathogenic bacteria to pathogenic bacteria (ratio of ⁇ (i) + (ii) ⁇ / (iii)), and is excellent in the effect of improving the flora. It was.

Abstract

L'invention fournit un ralentisseur de croissance de bactérie pathogène interne à la cavité buccale destiné à être mélangé à une composition pour cavité buccale, un agent améliorant la flore bactérienne interne à la cavité buccale, et une composition pour cavité buccale mettant en œuvre ceux-ci.　La composition pour cavité buccale de l'invention comprend (A) un oligosaccharide de lait et (B) un alcool de sucre.　Plus précisément, l'invention concerne : un ralentisseur de croissance de bactérie pathogène interne à la cavité buccale destiné à être mélangé à une composition pour cavité buccale, lequel ralentisseur de croissance comprend le composant (A) ; un agent améliorant la flore bactérienne interne à la cavité buccale destiné à être mélangé à une composition pour cavité buccale, lequel agent améliorant la flore bactérienne comprend ledit ralentisseur de croissance de bactérie pathogène interne à la cavité buccale et le composant (B) ; et une composition pour cavité buccale comprenant le composant (A).
PCT/JP2020/039636 2019-10-25 2020-10-22 Ralentisseur de croissance de bactérie pathogène interne à la cavité buccale, agent améliorant la flore bactérienne interne à la cavité buccale, et composition pour cavité buccale WO2021079921A1 (fr)

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WO2022090111A1 (fr) * 2020-10-30 2022-05-05 Dsm Ip Assets B.V. Comprimés solubles non effervescents comprenant des hmo

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JP2019506460A (ja) * 2016-02-25 2019-03-07 アプライド バイオロジカル ラボラトリーズ インコーポレイテッド 浮遊病原体および刺激物に対して防御するための組成物および方法
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WO2017085956A1 (fr) * 2015-11-16 2017-05-26 欽也 斉藤 Poudre pour prévenir une carie dentaire dans la bouche et son procédé de fabrication
JP2019506460A (ja) * 2016-02-25 2019-03-07 アプライド バイオロジカル ラボラトリーズ インコーポレイテッド 浮遊病原体および刺激物に対して防御するための組成物および方法
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WO2022090111A1 (fr) * 2020-10-30 2022-05-05 Dsm Ip Assets B.V. Comprimés solubles non effervescents comprenant des hmo

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