[go: up one dir, main page]

WO2024204726A1 - Composition orale contenant lactobacillus sporogenes - Google Patents

Composition orale contenant lactobacillus sporogenes Download PDF

Info

Publication number
WO2024204726A1
WO2024204726A1 PCT/JP2024/013069 JP2024013069W WO2024204726A1 WO 2024204726 A1 WO2024204726 A1 WO 2024204726A1 JP 2024013069 W JP2024013069 W JP 2024013069W WO 2024204726 A1 WO2024204726 A1 WO 2024204726A1
Authority
WO
WIPO (PCT)
Prior art keywords
lactic acid
acid bacteria
oral composition
spore
oral
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/JP2024/013069
Other languages
English (en)
Japanese (ja)
Inventor
一成 松田
美希 田中
大二朗 杉山
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Daiichi Sankyo Healthcare Co Ltd
Original Assignee
Daiichi Sankyo Healthcare Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Daiichi Sankyo Healthcare Co Ltd filed Critical Daiichi Sankyo Healthcare Co Ltd
Priority to CN202480021900.6A priority Critical patent/CN120897735A/zh
Publication of WO2024204726A1 publication Critical patent/WO2024204726A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor

Definitions

  • the present invention relates to an oral composition containing spore-forming lactic acid bacteria that can form an effective bacterial flora in the oral cavity.
  • Lactic acid bacteria are widely known to be beneficial for human health, and are used as intestinal regulators, particularly because they have the effect of suppressing the growth of harmful bacteria in the digestive tract. Furthermore, the usefulness of lactic acid bacteria beyond intestinal regulation is also being investigated.
  • Patent Document 1 describes a composition for preventing and/or treating oral diseases, which contains at least one selected from the group consisting of live lactic acid bacteria, substances containing said lactic acid bacteria, culture filtrates of said lactic acid bacteria, and processed products thereof, and at least one selected from specified sugars and specified plant extracts.
  • Patent Document 2 describes an oral composition containing the lactic acid bacteria Streptococcus faecalis as an active ingredient.
  • the present invention provides an oral composition that is excellent at forming an effective bacterial flora in the oral cavity, can prevent or treat the onset of dental caries and periodontal disease caused by oral pathogens, and can also prevent or eliminate bad breath.
  • compositions containing spore-forming lactic acid bacteria are excellent at forming an effective bacterial flora in the oral cavity, can prevent or treat the onset of dental caries and periodontal disease caused by oral pathogens, and can also prevent or eliminate bad breath, leading to the completion of the present invention.
  • an oral composition containing spore-forming lactic acid bacteria (2) The oral composition described in (1), wherein the spore-forming lactic acid bacteria are in an ungerminated state. (3) An oral composition described in (1) or (2), in which the spore-forming lactic acid bacteria germinate in the oral cavity. (4) An oral composition described in any one of (1) to (3) containing a bactericide. (5) An oral composition described in any one of (1) to (4) which is a dentifrice or a solid preparation.
  • the oral composition according to (12), wherein the periodontal disease is gingivitis and/or periodontitis.
  • P. intermedia Prevotella intermedia
  • Spore-forming lactic acid bacteria can suppress bacteria that cause periodontal disease and dental caries, such as Streptococcus mutans, and can control plaque, while normalizing the oral flora without disrupting it. Therefore, the oral composition of the present invention containing spore-forming lactic acid bacteria exhibits a plaque formation inhibitory effect and is useful for preventing or treating the onset of periodontal disease, and is also useful for preventing the occurrence of or eliminating bad breath.
  • FIG. 1 shows the results of PCR analysis of spore-forming lactic acid bacteria in the oral cavity before and after 4-week intake of an oral composition containing spore-forming lactic acid bacteria.
  • 2 shows the results of confirming the growth inhibitory effect of an oral composition containing spore-forming lactic acid bacteria on P. intermedia.
  • FIG. 3 shows the results of confirming whether or not spore-forming lactic acid bacteria germinate in artificial saliva.
  • FIG. 4 shows the results of confirming whether or not spore-forming lactic acid bacteria germinate in artificial saliva containing no D-glucose.
  • the composition may contain each component alone or in combination of two or more.
  • ⁇ indicating a numerical range means greater than or equal to or less than, and includes both of the numerical values at both ends.
  • the oral composition of the present invention contains spore-forming lactic acid bacteria.
  • a composition contains aspore-forming lactic acid bacteria, it was unclear whether the aspore-forming lactic acid bacteria are alive in the composition (especially a composition containing a bactericide) over a long period of time, including storage and distribution of the composition.
  • the present invention focuses on this new problem and solves the above problem by using spore-forming lactic acid bacteria instead of aspore-forming lactic acid bacteria.
  • the presence of live spore-forming lactic acid bacteria makes it possible to form an effective bacterial flora in the oral cavity, thereby preventing or treating the onset of dental caries and periodontal disease caused by oral pathogens, and further preventing or eliminating bad breath, making it possible to provide an oral composition.
  • the spore-forming lactic acid bacteria are not particularly limited, but examples thereof include bacteria of the genus Bacillus, etc.
  • Bacillus bacteria Bacillus coagulans is preferable from the viewpoints of ease of availability and ease of handling, and among them, live Bacillus coagulans bacteria are preferable because the effects of the present invention are easily exerted in the oral cavity.
  • Spore-forming lactic acid bacteria are lactic acid bacteria that form spores, and commercially available ones can be used as appropriate, such as Rakubon (registered trademark) and Lacris (registered trademark).
  • spore-forming lactic acid bacteria that can be used is Bacillus coagulans SANK70258.
  • lactic acid bacteria powder can be used, which is produced by mixing spore-forming lactic acid bacteria with a suitable excipient such as lactose, white sugar, dextrin, starch, or a mixture of these.
  • the spore-forming lactic acid bacteria are preferably in an ungerminated state (forming spores) until they are administered to the oral cavity.
  • the spore-forming lactic acid bacteria preferably germinate in the oral cavity, and preferably germination occurs due to food residues in the oral cavity, more preferably due to sugars, and even more preferably due to glucose.
  • the proportion of spore-forming lactic acid bacteria in the oral composition of the present invention is not particularly limited and may be appropriately adjusted depending on the various forms. However, from the viewpoints of being excellent at forming an effective bacterial flora in the oral cavity, being able to prevent or treat the onset of caries and periodontal disease caused by oral pathogens, and being able to prevent or remove bad breath, the proportion of spore-forming lactic acid bacteria in the oral composition is preferably 0.0001 to 75% by mass, more preferably 0.0005 to 50% by mass, and even more preferably 0.001 to 25% by mass.
  • the proportion of spore-forming lactic acid bacteria in the oral composition is preferably 5.0 x 10 to 5.0 x 10 per gram of the oral composition, more preferably 2.5 x 10 to 2.5 x 10 , and even more preferably 5.0 x 10 to 1.3 x 10 .
  • the proportion of spore-forming lactic acid bacteria in the oral composition is preferably 0.0001 to 10% by mass, more preferably 0.0005 to 5% by mass, and even more preferably 0.001 to 1% by mass.
  • the proportion of spore-forming lactic acid bacteria in the oral composition is preferably 5.0 x 10 to 5.0 x 10 cells per gram of the oral composition, more preferably 2.5 x 10 to 2.5 x 10 cells, and even more preferably 5.0 x 10 to 5.0 x 10 cells.
  • the proportion of spore-forming lactic acid bacteria in the oral composition is preferably 1 to 75% by mass, more preferably 2 to 50% by mass, and even more preferably 5 to 25% by mass, from the viewpoints of being excellent at forming an effective bacterial flora in the oral cavity, being able to prevent or treat the onset of caries and periodontal disease caused by oral pathogens, and being able to prevent or eliminate bad breath.
  • the proportion of spore-forming lactic acid bacteria in the oral composition is preferably 5.0 x 10 to 5.0 x 10 per gram of the oral composition, from the viewpoints of excellent formation of an effective bacterial flora in the oral cavity, ability to prevent or treat the onset of dental caries and periodontal disease caused by oral pathogens, and ability to prevent or remove bad breath, more preferably 5.0 x 10 to 5.0 x 10 per gram of the oral composition, even more preferably 5.0 x 10 to 3.8 x 10 per gram , still more preferably 1.0 x 10 to 2.5 x 10 per gram , and particularly preferably 2.5 x 10 to 1.3 x 10 per gram .
  • the spore-forming lactic acid bacteria bulk powder preferably contains 1.0 ⁇ 10 7 to 1.0 ⁇ 10 12 spore-forming lactic acid bacteria per gram, more preferably 1.0 ⁇ 10 8 to 1.0 ⁇ 10 11 spore-forming lactic acid bacteria, and even more preferably 1.0 ⁇ 10 9 to 1.0 ⁇ 10 10 spore-forming lactic acid bacteria per gram.
  • the oral composition of the present invention preferably contains a bactericide.
  • bactericide commercially available bactericides can be appropriately used, examples of which include cationic bactericides such as cetylpyridinium chloride (cetylpyridinium chloride hydrate, etc.), benzethonium chloride, benzalkonium chloride, etc., nonionic bactericides such as isopropylmethylphenol, triclosan, thymol, etc., anionic bactericides such as sodium lauroyl sarcosine, etc.
  • cationic bactericides are preferred, and cetylpyridinium chloride is particularly preferred, from the viewpoint of their characteristic of being easily adsorbed to the tooth surface and exhibiting their effect.
  • the amount of the bactericide in the oral composition of the present invention is preferably 0.001-1% of the oral composition, more preferably 0.01-0.5%, from the viewpoint of making it difficult to kill spore-forming lactic acid bacteria, suppressing bacteria that cause periodontal disease and dental caries, and making it easier to exert an inhibitory effect on plaque formation.
  • the mass ratio of the spore-forming lactic acid bacteria content to the bactericide content in the oral composition is preferably 0.01 or more, more preferably 0.05 or more, and even more preferably 0.1 or more, from the viewpoint of making it difficult to kill the spore-forming lactic acid bacteria, suppressing the bacteria that cause periodontal disease and dental caries, and making it easier to exert the plaque formation inhibitory effect.
  • the above mass ratio is preferably 10 or less, more preferably 5 or less, and further preferably 1 or less.
  • the mass ratio of spore-forming lactic acid bacteria to the bactericide in the oral composition is preferably 0.01-10, more preferably 0.05-5, and even more preferably 0.1-1. Furthermore, the ratio of the number of spore-forming lactic acid bacteria to the content of the bactericide in the oral composition (number of spore-forming lactic acid bacteria/per gram of bactericide) is, from the viewpoint of making it difficult to kill the spore-forming lactic acid bacteria, suppressing the bacteria that cause periodontal disease and dental caries, and making it easier to exert the plaque formation inhibitory effect, preferably 5.0 x 105 cells/g or more, more preferably 5.0 x 107 cells/g or more, even more preferably 2.5 x 108 cells/g or more, and particularly preferably 5.0 x 108 cells/g or more.
  • the above ratio (number of spore-forming lactic acid bacteria/g of disinfectant) is preferably 5.0 ⁇ 10 12 cells/g or less, more preferably 5.0 ⁇ 10 10 cells/g or less, even more preferably 2.5 ⁇ 10 10 cells/g or less, and particularly preferably 5.0 ⁇ 10 9 cells/g or less.
  • the above ratio (number of spore-forming lactic acid bacteria/g of bactericide) in the oral composition is preferably 5.0 x 10 to 5.0 x 10 /g, more preferably 5.0 x 10 to 5.0 x 10 /g, even more preferably 2.5 x 10 to 2.5 x 10 /g, and particularly preferably 5.0 x 10 to 5.0 x 10 /g.
  • the oral composition of the present invention is a non-aqueous oral composition.
  • the non-aqueous oral composition means an oral composition that does not contain water or contains almost no water.
  • the non-aqueous oral composition is an oral composition that contains 5% by mass or less (i.e., 0 to 5% by mass), preferably 0 to 1% by mass, more preferably 0 to 0.1% by mass, and further preferably does not contain any water, based on the total amount of the oral composition. Even if no water is added, trace amounts of water may be contained in ingredients such as commercially available 1,3-butylene glycol that are added to the composition. Taking these reasons into consideration, the product does not contain any water other than these ingredients.
  • the oral composition of the present invention is preferably substantially free of sugars.
  • substantially free of sugars means that the content of sugars relative to the total amount of the oral composition is preferably 5% by mass or less (i.e., 0 to 5% by mass), more preferably 0 to 3% by mass, even more preferably 0 to 1% by mass, even more preferably 0 to 0.1% by mass, and particularly preferably an oral composition that does not contain any sugars at all. Even if no sugar is added, commercially available lactic acid bacteria and other ingredients used in the composition may contain trace amounts of sugar as excipients, etc., so taking these reasons into consideration, the product does not contain any other sugars.
  • the sugars referred to here are not particularly limited as long as they are easy for spore-forming lactic acid bacteria to germinate, and examples thereof include polysaccharides (excluding cellulose, etc.), disaccharides, monosaccharides, etc., but do not include sugar alcohols such as xylitol.
  • the oral composition of the present invention may contain the following components in appropriate amounts, if necessary, depending on the form of the composition.
  • Abrasives include silica-based abrasives such as silica gel, precipitated silica, pyrogenic silica, hydrated silicic acid, anhydrous silicic acid, zeolite, aluminosilicate, and zirconosilicate, as well as crystalline cellulose, dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydrate, calcium pyrophosphate, tribasic magnesium phosphate, tribasic calcium phosphate, aluminum hydroxide, alumina, light calcium carbonate, heavy calcium carbonate, magnesium carbonate, zirconium silicate, and synthetic resin abrasives. One or more of these may be used in combination.
  • the amount of these abrasives is generally 0 to 60% by mass, and preferably 10 to 45% by mass, based on the total amount of the oral composition.
  • Humectants include polyhydric alcohols such as glycerin, concentrated glycerin, diglycerin, sorbitol, maltitol, dipropylene glycol, propylene glycol, 1,3-butylene glycol, xylitol, and polyethylene glycol, and one or more of these can be used.
  • polyhydric alcohols such as glycerin, concentrated glycerin, diglycerin, sorbitol, maltitol, dipropylene glycol, propylene glycol, 1,3-butylene glycol, xylitol, and polyethylene glycol, and one or more of these can be used.
  • Binders include carrageenan ( ⁇ , ⁇ , ⁇ ), alginic acid, sodium alginate, propylene glycol alginate, calcium-containing sodium alginate, potassium alginate, calcium alginate, ammonium alginate and other alginic acid and derivatives thereof, xanthan gum, guar gum, gelatin, agar, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium polyacrylate, etc., and one or more of these can be used in combination.
  • carrageenan ⁇ , ⁇ , ⁇
  • alginic acid sodium alginate
  • propylene glycol alginate calcium-containing sodium alginate
  • potassium alginate calcium alginate
  • ammonium alginate and other alginic acid and derivatives thereof xanthan gum, guar gum, gelatin, agar, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium polyacrylate, etc., and one or more
  • Sweetening agents include sodium saccharin, aspartame, trehalose, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, and perillartine.
  • Preservatives include parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride.
  • fragrance ingredients one or more of the following can be used in combination: l-menthol, anethole, menthone, cineole, limonene, carvone, methyl salicylate, ethyl butyrate, eugenol, thymol, cinnamic aldehyde, trans-2-hexenal, etc.
  • these ingredients can be used alone, or essential oils containing them can be used.
  • fragrance components such as aliphatic alcohols and their esters, terpene hydrocarbons, phenol ethers, aldehydes, ketones, lactones, and essential oils may be added to the composition as long as they do not interfere with the effects of the present invention.
  • the amount of the above flavoring ingredients is generally in the range of 0.02 to 2% by mass based on the total amount of the oral composition.
  • the oral composition of the present invention may contain further active ingredients in addition to those mentioned above.
  • active ingredients include lysozyme chloride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, polyethylene glycol, polyvinylpyrrolidone, hinokitiol, ascorbic acid, ascorbate salts, tocopherol acetate, ⁇ -aminocaproic acid, tranexamic acid, aluminum hydroxyl allantoin, aluminum lactate, dihydrocholesterol, glycyrrhetinic acid, glycyrrhizinate salts, copper gluconate, copper chlorophyllin salt, zinc oxide, sodium chloride, guaiazulene sulfonate, dextranase, pyridoxine hydrochloride, medicinal hydroxyapatite, and the like, and one or more of these may be contained.
  • the oral composition of the present invention can be manufactured in accordance with conventional methods, and the manufacturing method is not particularly limited.
  • the oral composition of the present invention can be filled into aluminum tubes, laminated tubes, glass vapor deposition tubes, plastic tubes, plastic bottles, aerosol containers, glass bottles, PTP packages, pouch packages, stick packages, etc.
  • the oral composition of the present invention has the property of inhibiting the growth of bacteria that cause oral diseases and discomforts such as dental caries, periodontal disease, and bad breath, and can be used as a caries prevention agent, a preventive and/or treatment agent for periodontal disease, an agent for improving and/or preventing bad breath, or an agent for improving oral flora.
  • Periodontal disease is an inflammatory disease of periodontal tissues caused by plaque bacteria. Periodontal disease is classified as gingivitis and periodontitis. Gingivitis is when inflammation is limited to the gums. Periodontitis is when inflammation extends to the periodontal ligament and alveolar bone, destroying the attachment of the periodontal ligament. The advanced stage of periodontal disease is sometimes called pyorrhea.
  • the preventive and/or therapeutic agent for periodontal disease can be preferably used as an agent for inhibiting the proliferation of P. intermedia.
  • the agent for improving and/or preventing bad breath is preferably capable of suppressing the production amounts of hydrogen sulfide and dimethyl sulfide.
  • the agent for improving and/or preventing bad breath can be preferably used as an agent for inhibiting the proliferation of P. intermedia.
  • the oral composition of the present invention can be provided in various forms, such as dentifrices (toothpaste, powdered dentifrices, liquid dentifrices, etc.), solid preparations (tablets, capsules, pills, granules, powders, fine granules, orally disintegrating tablets, chewable tablets, effervescent tablets, etc.), mouthwashes, mouth fresheners, denture cleaners, gingival massage creams, etc.
  • dentifrices or solid preparations are preferred, and dentifrices are particularly preferred.
  • the oral composition of the present invention can be incorporated into food.
  • Dosage forms include lozenges, tablets (tablets, etc.), gum, yogurt, drinks, fermented products, etc. Among the above, tablets are particularly preferred.
  • Bacillus coagulans SANK70258 was used as the spore-forming lactic acid bacterium.
  • Test Example 1 Evaluation of the caries bacteria ratio before and after 4-week intake of oral composition containing spore-forming lactic acid bacteria
  • Ten subjects were administered tablets containing spore-forming lactic acid bacteria (see Table 1 for composition) for 4 weeks.
  • the intake method is as follows. One tablet was taken three times a day after meals and brushing teeth. When ingesting, the tablet was not chewed but rolled around in the mouth and licked to dissolve. The ratio of various bacteria in the saliva before and after ingestion was analyzed using standard methods. The subjects chewed saliva-collecting gum for five minutes on the day the vaccination began and four weeks after the start of the vaccination to collect saliva samples.
  • the spore-forming lactic acid bacteria in the spore-forming lactic acid bacteria-containing tablets were prepared so that there were approximately 800 million spore-forming lactic acid bacteria per 300 mg tablet.
  • Test Example 2 Evaluation of bad breath before and after 4-week intake of oral composition containing spore-forming lactic acid bacteria
  • 10 subjects were asked to take tablets containing spore-forming lactic acid bacteria (see Table 1 for composition) for 4 weeks.
  • the concentration of volatile sulfur compounds (VSCs) (hydrogen sulfide, methyl mercaptan, dimethyl sulfide, and their total) that cause bad breath was evaluated before and after ingestion.
  • the evaluation method is as follows. The subject lightly bit 2 cm from the tip of the tube with teeth, closed lips tightly, and breathed through the nose. After 1 minute, the breath was aspirated with a syringe. The aspirated breath was measured with Oralchroma (registered trademark).
  • Oralchroma registered trademark
  • a decrease in the concentrations of hydrogen sulfide, methyl mercaptan, dimethyl sulfide, and TOTAL was observed 4 weeks after ingestion compared to the start of ingestion (week 0). Furthermore, a significant decrease in the concentrations of hydrogen sulfide, dimethyl sulfide, and TOTAL was observed 4 weeks after ingestion compared to the start of ingestion (week 0).
  • Test Example 3 Evaluation of gingivitis before and after 4-week intake of oral composition containing spore-forming lactic acid bacteria
  • 10 subjects were made to take tablets containing spore-forming lactic acid bacteria (see Table 1 for composition) for 4 weeks.
  • the presence or absence of anterior gingivitis was evaluated before and after intake.
  • the evaluation criteria were 0: absent, 1: present, and the examination sites were 34 sites on the labial gingiva of the following 12 teeth (P: interdental papilla, M: marginal gingiva, A: attached gingiva).
  • Test Example 4 Confirmation of spore-forming lactic acid bacteria in the oral cavity before and after 4-week intake of oral composition containing spore-forming lactic acid bacteria As in Test Example 1, 10 subjects were asked to take tablets containing spore-forming lactic acid bacteria (see Table 1 for composition) for 4 weeks. Before and after ingestion, the presence or absence of spore-forming lactic acid bacteria in the oral cavity was detected by the PCR method described below.
  • PCR method 200 ⁇ L of saliva was placed in a 1.5 mL microtube and centrifuged (20,000 g, 10 min). The supernatant was discarded and washed twice with 500 ⁇ L of PBS. After collecting the sediment, 200 ⁇ L of InstaGene matrix was added and suspended, and incubated at 56 ° C for 15 min. Then, it was treated at 100 ° C for 8 min, centrifuged (4500 rpm, 5 min), and the supernatant was collected in another tube, which was used as a DNA extract.
  • the PCR reaction solution and reaction conditions were as follows. The number of cycles for each of the 1st PCR and 2nd PCR was 30 cycles.
  • the obtained PCR product was electrophoresed by a conventional method to confirm the presence or absence of spore-forming lactic acid bacteria in the oral cavity based on the presence or absence of a specific band.
  • Test Example 5 Confirmation of the effect of oral compositions containing spore-forming lactic acid bacteria in inhibiting the proliferation of P. intermedia
  • P. intermedia was cultured anaerobic on an aneroColumbia rabbit blood agar medium (Becton Dickinson Japan) at 35°C for 48 to 72 hours, and then suspended in 10 mL of GAM broth to a McFarland concentration of 1, to prepare a bacterial solution of about 3.0 x 10 8 CFU/mL. Furthermore, two bacterial concentrations of 1 x 10 6 and about 5 x 10 5 CFU/mL were prepared using GAM broth.
  • the spore-forming lactic acid bacteria were prepared by adding lactic acid bacteria powder (Bacillus Coagulans (Sanzyme): SANK70258) to GAM broth and re-cultivating the bacteria under anaerobic conditions at 35°C for 48 to 72 hours, and then confirming their growth in the liquid medium and measuring the pH (first time: pH 5.78, second time: pH 5.81, third time: 5.80).
  • the cultured bacterial solution was transferred to a new GAM broth and cultured anaerobically at 35°C for 48 to 72 hours.
  • the bacteria were suspended in 10 mL of GAM broth to a McFarland concentration of 1, and a bacterial solution of approximately 3.0 x 10 8 CFU/mL was prepared. The bacteria were further adjusted to 1 x 10 6 and 1 x 10 4 CFU/mL using GAM broth.
  • a mixed culture was prepared according to the combination of test strains and bacterial amount shown in Table 8. That is, each test strain and spore-forming lactic acid bacteria were mixed in equal amounts of 10 mL according to Table 8 to prepare a mixed culture of 20 mL in total, and then 4 mL was dispensed into test tubes for each measurement point. In the case of a single culture using one type of strain, GAM broth was used instead of the bacterial liquid.
  • the measurement results are shown in FIG. It was shown that increasing the amount of spore-forming lactic acid bacteria can inhibit the growth of P. intermedia. It has been shown that the growth of P. intermedia is inhibited or killed by an oral composition containing spore-forming lactic acid bacteria. It has been found that an oral composition containing spore-forming lactic acid bacteria can prevent or treat the onset of dental caries, periodontal disease, and bad breath caused by oral pathogens and bad breath-causing bacteria. It has been found that the use of oral compositions containing spore-forming lactic acid bacteria allows for the formation of an effective bacterial flora in the oral cavity.
  • Composition 1 NaCl 0.85g KCl 1.2g CaCl2.2H2O 0.2g MgCl2.6H2O 0.05g K2HPO4 0.35g D-glucose 2g BBL Trypticase Peptone 5g/L
  • ⁇ Spore culture in artificial saliva to simulate the oral cavity 5 mL of artificial saliva was dispensed into a 14 mL polypropylene round tube, 0.1 g of spore-forming lactic acid bacteria was added, and the tube was vortexed. After that, the tube was left to stand at 37°C under aerobic conditions with the cap loosened, and spore culture was performed in artificial saliva to simulate the oral cavity.
  • Test Example 6-2 In addition, the same procedure as in Test Example 6 was repeated except that 2 g of sugar (D-glucose) was replaced with purified water to confirm whether or not spore-forming lactic acid bacteria would germinate in saliva, simulating the oral cavity ( Figure 4).
  • Lactic acid bacteria formulations were prepared as shown in Tables 9 and 10. Specifically, the bactericide components were dispersed or dissolved in 1,3-butylene glycol (BG). Hydroxypropyl cellulose was then added and dissolved. Lactic acid bacteria (spore-forming or non-spore-forming lactic acid bacteria) were then added and dispersed. Silica anhydride was then added and dispersed. Calcium hydrogen phosphate was then added and dispersed.
  • BG 1,3-butylene glycol
  • the spore-forming lactic acid bacteria were prepared so that there were approximately 3 billion bacteria in 100 g of the formulation, and the non-spore-forming lactic acid bacteria (Streptococcus faecalis) were prepared so that there were approximately 100 to 500 million bacteria in 100 g of the formulation.
  • Cetylpyridinium chloride hydrate also abbreviated as CPC.
  • Sodium lauroyl sarcosine also abbreviated as Laur.
  • Isopropylmethylphenol also abbreviated as IPMP.
  • the viable lactic acid bacteria count in the preparation was determined according to the following procedure. (1) 0.1 g of the preparation was weighed out, and then 20 mL of MRS broth was added thereto and pipetted to thoroughly disperse the preparation. (2) The mixture was filtered through a 0.2 ⁇ m analytical filter unit (Thermo Scientific), and 50 mL of MRS broth was passed through the analytical filter unit after filtration three times to wash the membrane. (3) After removing the filter from the analytical filter unit, the membrane surface was washed 10 times with MRS broth. (4) The liquid obtained in (3) above was used as a stock solution (10 ⁇ 1 ) and a 10-fold serial dilution was prepared.
  • the oral compositions containing spore-forming lactic acid bacteria survived for long periods (one month and one year) even in the presence of a bactericide.
  • the spore-forming lactic acid bacteria survive in an oral composition containing spore-forming lactic acid bacteria that contains 0.001% by mass or more of spore-forming lactic acid bacteria and 0.001% by mass or more of a bactericide.
  • the moisture content in each of the oral compositions containing spore-forming lactic acid bacteria was 5% or less.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Wood Science & Technology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Birds (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention aborde le problème de la fourniture d'une composition orale qui présente une excellente capacité à former une flore bactérienne efficace dans la cavité buccale, qui permet de prévenir l'apparition de caries dentaires ou d'une maladie parodontale provoquée par des pathogènes buccaux ou qui permet de traiter une telle maladie, et qui permet également de prévenir ou de traiter une halitose. La présente invention concerne une composition orale contenant Lactobacillus sporogenes.
PCT/JP2024/013069 2023-03-31 2024-03-29 Composition orale contenant lactobacillus sporogenes Pending WO2024204726A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202480021900.6A CN120897735A (zh) 2023-03-31 2024-03-29 含芽孢乳酸菌的口腔用组合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2023-057477 2023-03-31
JP2023057477 2023-03-31

Publications (1)

Publication Number Publication Date
WO2024204726A1 true WO2024204726A1 (fr) 2024-10-03

Family

ID=92905889

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2024/013069 Pending WO2024204726A1 (fr) 2023-03-31 2024-03-29 Composition orale contenant lactobacillus sporogenes

Country Status (2)

Country Link
CN (1) CN120897735A (fr)
WO (1) WO2024204726A1 (fr)

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002523372A (ja) * 1998-08-24 2002-07-30 ガネデン バイオテック， インコーポレイテッド 共生乳酸産生細菌およびその使用
JP2002234825A (ja) * 2001-02-08 2002-08-23 Nippon Zettoc Co Ltd 口腔用組成物
WO2003017951A2 (fr) * 2001-08-24 2003-03-06 The Procter & Gamble Company Compositions a croquer a agents probiotiques
JP2004250374A (ja) * 2003-02-20 2004-09-09 Nippon Zettoc Co Ltd 口腔用組成物
JP2010100597A (ja) * 2008-10-21 2010-05-06 Hinode Sangyo Kk 有胞子菌からなる静菌組成物及び悪臭防止生菌剤
WO2012124214A1 (fr) * 2011-03-11 2012-09-20 アース・バイオケミカル株式会社 Agent de retenue intra-buccale pour une utilisation par un animal, agent d'amélioration d'environnement intra-buccal pour une utilisation par un animal, et procédé d'amélioration d'environnement intra-buccal pour une utilisation par un animal
JP2014000039A (ja) * 2012-06-19 2014-01-09 Lion Corp 乳酸菌及びその培養由来物、ならびにこれらを含有する組成物
JP2017193538A (ja) * 2016-04-13 2017-10-26 第一三共ヘルスケア株式会社 銅化合物、亜鉛化合物、及びｌ−メントールを含有する組成物
JP3216201U (ja) * 2018-03-01 2018-05-17 インテリジェンス エンジニアリング インコーポレーテッド デンタルガム
JP2020534014A (ja) * 2017-09-21 2020-11-26 サミ ラブズ リミテッド バチルス・コアグランスを含有するアルコール飲料組成物
US20210085729A1 (en) * 2018-05-04 2021-03-25 Boris Slavinovich FARBER Food, cosmetic and pharmaceutical formulation with an immunomodulatory and protective anti-viral effect
CN114806930A (zh) * 2022-03-31 2022-07-29 青岛东海药业有限公司 一种益生菌组合物及其应用
CN115607577A (zh) * 2022-10-09 2023-01-17 微康益生菌(苏州)股份有限公司 一种具有缓解口腔炎症功效的益生菌剂及其制备方法和应用

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002523372A (ja) * 1998-08-24 2002-07-30 ガネデン バイオテック， インコーポレイテッド 共生乳酸産生細菌およびその使用
JP2002234825A (ja) * 2001-02-08 2002-08-23 Nippon Zettoc Co Ltd 口腔用組成物
WO2003017951A2 (fr) * 2001-08-24 2003-03-06 The Procter & Gamble Company Compositions a croquer a agents probiotiques
JP2004250374A (ja) * 2003-02-20 2004-09-09 Nippon Zettoc Co Ltd 口腔用組成物
JP2010100597A (ja) * 2008-10-21 2010-05-06 Hinode Sangyo Kk 有胞子菌からなる静菌組成物及び悪臭防止生菌剤
WO2012124214A1 (fr) * 2011-03-11 2012-09-20 アース・バイオケミカル株式会社 Agent de retenue intra-buccale pour une utilisation par un animal, agent d'amélioration d'environnement intra-buccal pour une utilisation par un animal, et procédé d'amélioration d'environnement intra-buccal pour une utilisation par un animal
JP2014000039A (ja) * 2012-06-19 2014-01-09 Lion Corp 乳酸菌及びその培養由来物、ならびにこれらを含有する組成物
JP2017193538A (ja) * 2016-04-13 2017-10-26 第一三共ヘルスケア株式会社 銅化合物、亜鉛化合物、及びｌ−メントールを含有する組成物
JP2020534014A (ja) * 2017-09-21 2020-11-26 サミ ラブズ リミテッド バチルス・コアグランスを含有するアルコール飲料組成物
JP3216201U (ja) * 2018-03-01 2018-05-17 インテリジェンス エンジニアリング インコーポレーテッド デンタルガム
US20210085729A1 (en) * 2018-05-04 2021-03-25 Boris Slavinovich FARBER Food, cosmetic and pharmaceutical formulation with an immunomodulatory and protective anti-viral effect
CN114806930A (zh) * 2022-03-31 2022-07-29 青岛东海药业有限公司 一种益生菌组合物及其应用
CN115607577A (zh) * 2022-10-09 2023-01-17 微康益生菌(苏州)股份有限公司 一种具有缓解口腔炎症功效的益生菌剂及其制备方法和应用

Also Published As

Publication number Publication date
CN120897735A (zh) 2025-11-04

Similar Documents

Publication Publication Date Title
US20070110684A1 (en) Morinda Citrifolia-Based Oral Care Compositions and Methods
US20080069783A1 (en) Oral cavity cleaning composition
CN113679632A (zh) 抗菌肽化合物DM80Bu20在制备抑菌牙膏中的应用
JPH03240721A (ja) 口腔用組成物
EP1967179A1 (fr) Composition à usage oral
JP7393823B2 (ja) 歯周病菌用口腔組成物
KR20170103476A (ko) 금앵자 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
WO2024204726A1 (fr) Composition orale contenant lactobacillus sporogenes
CN104491840A (zh) 一种抗辐射防龋消炎的口腔药物组合物及其制剂
Marsh et al. Dental caries
JP7308561B2 (ja) 動物用の口腔用組成物
JP6918529B2 (ja) 口腔用組成物
KR102548925B1 (ko) 스코폴레틴을 포함하는 구강질환 예방 또는 치료용 조성물
KR102415612B1 (ko) 과체 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
WO2025132965A1 (fr) Formulations et dispositifs comprenant des bactéries productrices de lantibiotiques
KR102580941B1 (ko) 쿼세틴 3-글루코시드를 포함하는 구강질환 예방 또는 치료용 조성물
KR101818211B1 (ko) 우방자 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
KR20170103482A (ko) 연전초 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
KR20240067539A (ko) 신이 추출물을 포함하는 치아우식증 치료용 조성물
KR20170120399A (ko) 제니스테인을 포함하는 구강질환 예방 또는 치료용 조성물
KR102562830B1 (ko) 지부자 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
KR20250082746A (ko) 락티카제이바실러스 파라카제이 ok 균주 및 이의 용도
KR102541843B1 (ko) 악틴을 포함하는 구강질환 예방 또는 치료용 조성물
KR102564564B1 (ko) 2-메톡시신남알데하이드를 포함하는 구강질환 예방 또는 치료용 조성물
KR102562829B1 (ko) 고량강 추출물을 포함하는 구강질환 예방 또는 치료용 조성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24780821

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2025511274

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2025511274

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 202480021900.6

Country of ref document: CN

NENP Non-entry into the national phase

Ref country code: DE

WWP Wipo information: published in national office

Ref document number: 202480021900.6

Country of ref document: CN