WO2023175655A1 - 口腔疾患用剤 - Google Patents

口腔疾患用剤 Download PDF

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Publication number
WO2023175655A1
WO2023175655A1 PCT/JP2022/011206 JP2022011206W WO2023175655A1 WO 2023175655 A1 WO2023175655 A1 WO 2023175655A1 JP 2022011206 W JP2022011206 W JP 2022011206W WO 2023175655 A1 WO2023175655 A1 WO 2023175655A1
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WO
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Prior art keywords
oral diseases
agent
oral
nicotinamide mononucleotide
periodontal disease
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Ceased
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PCT/JP2022/011206
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English (en)
French (fr)
Japanese (ja)
Inventor
めぐみ 田中
経丸 田中
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Mirailab Bioscience Inc
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Mirailab Bioscience Inc
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Filing date
Publication date
Application filed by Mirailab Bioscience Inc filed Critical Mirailab Bioscience Inc
Priority to US18/847,268 priority Critical patent/US20250205266A1/en
Priority to JP2024507200A priority patent/JPWO2023175655A1/ja
Priority to EP22931940.5A priority patent/EP4494485A4/en
Priority to CN202280093721.4A priority patent/CN118900640A/zh
Priority to KR1020247033707A priority patent/KR20250019018A/ko
Priority to PCT/JP2022/011206 priority patent/WO2023175655A1/ja
Publication of WO2023175655A1 publication Critical patent/WO2023175655A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/13—Nucleic acids or derivatives thereof
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • 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
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/312—Foods, ingredients or supplements having a functional effect on health having an effect on dental health

Definitions

  • the present invention relates to an agent for oral diseases containing nicotinamide mononucleotide as an active ingredient.
  • gingivitis is inflammation localized to the gums in the early stages of periodontal disease, and the border between the teeth and gums becomes inflamed, causing symptoms such as redness, swelling, and bleeding, and is common in young people under the age of 20. .
  • periodontitis is more common among people in their 30s and older.
  • gingivitis inflammation not only causes swelling and bleeding of the gums, but also destroys the periodontal ligament fibers that support the teeth and causes the alveolar bone to dissolve. As a result, the periodontal pockets grow deeper inward, causing the gums to become thinner and the teeth to gradually become loose and loose, and eventually to fall out. Severe periodontitis is the leading cause of tooth loss.
  • periodontal disease makes it difficult to chew food properly, it can cause cardiovascular diseases, diabetes, digestive system diseases, etc.
  • periodontal pathogenic bacteria get on the bloodstream through the blood vessels exposed in your gums and travel throughout your body, resulting in secondary problems such as lifestyle-related diseases, respiratory diseases, low birth weight babies, and premature births. It is said that this is more likely to occur.
  • periodontal disease not only has local effects on teeth and periodontal tissues, but can also cause systemic lesions and symptoms.
  • Periodontal pathogenic bacteria accumulate in periodontal pockets, exude pus and cause bad breath.
  • This bad breath caused by periodontal disease is characterized by a smell similar to rotten onions due to methyl mercaptan, which is much stronger than general physiological bad breath caused by dirt on the tongue (tongue coating). be.
  • Physiological bad breath can be largely eliminated by, for example, cleaning the tongue and removing the coating, but in order to fundamentally eliminate bad breath caused by periodontal disease, it is necessary to address the root cause of the problem. It is necessary to treat periodontal disease.
  • periodontal disease is related to the health of the whole body, so it is important to provide appropriate treatment as early as possible if the patient develops the disease.
  • typical plaque control methods include physical methods such as brushing, flossing, scaling, and root planing, as well as chemical methods using drugs.
  • Medications include antibacterial agents such as minocycline hydrochloride dental ointment, tetracycline/presterone dental ointment, and hinopolon oral ointment (Showa Yakuhin Kako Co., Ltd.), which contains hinokitiol, which has an antibacterial effect, and hydrocortisone acetate, which has an anti-inflammatory effect.
  • antibacterial agents such as minocycline hydrochloride dental ointment, tetracycline/presterone dental ointment, and hinopolon oral ointment (Showa Yakuhin Kako Co., Ltd.), which contains hinokitiol, which has an antibacterial effect, and hydrocortisone acetate, which has an anti-inflammatory effect.
  • Drugs containing a complex combination of ingredients with antibacterial and anti-inflammatory effects are widely used.
  • antibacterial agents especially antibiotics
  • long-term use of antibacterial agents, especially antibiotics may lead to the emergence of resistant bacteria and bacterial replacement, so it is desirable to avoid long-term use as much as possible.
  • (A) contains polyphenols, which are water-soluble medicinal ingredients, in an amount of 0.001 to 10% by mass in component (A) as a medicinal ingredient, and further contains water-soluble medicinal ingredients and water.
  • Patent Document 1 A product has been reported (Patent Document 1).
  • Lactobacillus crispatus YIT 12319 (FERM BP-11500) and Lactobacillus fermentum YIT 12320 (FERM BP-11501) use new lactic acid bacteria strains that are safe in the oral cavity.
  • Lactobacillus gasseri YIT 12321 (FERM BP-11502)
  • Streptococcus mitis YIT 12322 (FERM BP-11503).
  • Patent Document 2 A preventive and/or therapeutic agent for internal diseases has been reported (Patent Document 2).
  • amino acids that make up body proteins include one or more amino acids selected from glycine, alanine, leucine, histidine, and proline, and the number of constituent amino acids is 1 to 4.
  • An oral composition for preventing periodontal disease which contains the following ingredients as an effective ingredient for neutralizing periodontal bacterial endotoxins, has been reported (Patent Document 3).
  • An object of the present invention is to provide an agent for oral diseases that is safe even when used over a long period of time and is useful for the prevention and treatment of periodontal diseases and the like.
  • nicotinamide mononucleotide which is an intermediate metabolite involved in the biosynthesis of coenzyme NAD (nicotinamide adenine dinucleotide), is effective in preventing periodontal disease, etc.
  • coenzyme NAD nicotinamide adenine dinucleotide
  • the present invention is as follows.
  • a method for improving oral diseases (excluding medical treatment for humans), which comprises ingesting an effective amount of nicotinamide mononucleotide to a subject who needs it.
  • the agent for oral diseases according to the present invention is effective in preventing or treating oral diseases such as periodontal disease, and contains nicotinamide mononucleotide, which is an intermediate metabolite involved in the biosynthesis of NAD + in vivo, as an active ingredient. It is safe and can be used for a long period of time.
  • FIG. 2 is an explanatory diagram showing metabolic pathways involved in niacin (generic term for nicotinamide and nicotinic acid).
  • the agent for oral diseases according to the present invention contains nicotinamide mononucleotide (including its salt) as an active ingredient, and is effective in improving oral diseases such as periodontal disease.
  • improvement of oral diseases includes not only improvement of oral diseases in a narrow sense, but also alleviation of various symptoms caused by oral diseases, prevention of oral diseases, and halting and delaying the progression of oral diseases.
  • nicotinamide mononucleotide As an active ingredient is currently under investigation, It is thought to be effective against oral diseases such as periodontal disease by promoting effects of nicotinamide mononucleotide, resulting in phenomena such as increased resistance in periodontal tissue and increased saliva secretion.
  • the agent for oral diseases according to the present invention which has the effect of improving oral diseases as described above, can be used as pharmaceuticals (including quasi-drugs) and foods such as functional foods. The present invention will be explained in detail below.
  • Nicotinamide mononucleotide (chemical formula: C 11 H 15 N 2 O 8 P) is a compound represented by the following structural formula [Formula 1], which is produced in the bodies of many organisms including humans. It is generally called NMN (Nicotinamide mononucleotide) and is known as an intermediate metabolite involved in the biosynthesis of the coenzyme NAD + .
  • nicotinamide mononucleotide which is the active ingredient of the drug for oral diseases, is involved in the synthesis of nicotinamide adenine dinucleotide (NAD) from quinolinic acid via the NAD metabolic pathway by the liver tissue, that is, the kynurenine pathway. It is produced in This point will be specifically explained with reference to FIG. 1.
  • FIG. 1 is an explanatory diagram showing the metabolic pathway involved in niacin (a generic term for nicotinamide and nicotinic acid) known as vitamin B3 . Nicotinic acid ingested through food is taken up by the liver and converted to nicotinamide, which is then distributed throughout the body via the bloodstream. Each cell takes in nicotinamide from the blood and converts it into NAD and NADP for use. Nicotinamide is also biosynthesized from tryptophan.
  • niacin a generic term for nicotinamide and nicotinic
  • Nicotinamide (NaM) is converted to nicotinamide mononucleotide by nicotinamide phosphoribosyltransferase (NAMPT), which is then converted by nicotinamide mononucleotide adenyltransferase (NMNAT) to generate NAD.
  • NAMPT nicotinamide phosphoribosyltransferase
  • NMNAT nicotinamide mononucleotide adenyltransferase
  • NR nicotinamide riboside
  • Nicotinamide mononucleotide has two types of optical isomers, ⁇ -form and ⁇ -form, and the ⁇ -form is used in the present invention. Nicotinamide mononucleotide is produced by, for example, synthesizing nicotinamide riboside from nicotinamide and ribose (see Bioorg. Med. Chem. Lett., 12, 1135-1137 (2002)), and then synthesizing the 5-hydroxyl group of the ribose moiety. It can be obtained by phosphorylation (see Chem. Comm., 1999, 729-730).
  • nicotinamide and L-ribose tetraacetate are dissolved in anhydrous acetonitrile, and after adding an excess amount of trimethylsilyltrifluorosulfonic acid under a nitrogen stream, the mixture is stirred at room temperature, and methanol is added.
  • the reaction solution, in which the reaction has been stopped, is applied to a column packed with activated carbon, washed with distilled water, and then eluted with methanol to recover the product.
  • the agent for oral diseases according to the present invention is easily produced by using nicotinamide mononucleotide alone or by mixing other components.
  • Other components are not particularly limited as long as they achieve the effects of the present invention.
  • ingredients include chamomile tincture, latania tincture, myrrh tincture, hinokitiol, chamazulene, azulene, latanine, tannin, tocopherol acetate, cetylpyridinium chloride hydrate, glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, tranexam.
  • Acid isopropyl methylphenol, epsilon aminocaproic acid, methyl salicylate, chlorhexidine hydrochloride, benzethonium chloride, lysozyme chloride, sodium chloride, chlorhexidine gluconate, triclosan, allantoin, auricularis extract, sodium lauroyl sarcosine, hinokitiol, thymol, propolis, clove oil, canavanine
  • medicinal ingredients having antibacterial and/or anti-inflammatory effects.
  • auxiliary ingredients commonly used in the food field such as various vitamins, trace elements, citric acid, malic acid, fragrances, and inorganic salts, may also be included as other ingredients.
  • resveratrol can be mentioned as another component that is particularly effective in enhancing its oral disease-improving effect.
  • Resveratrol is known as an antioxidant found in grape skins, red wine, peanut skins, Japanese knotweed, gunemon, etc.
  • Resveratrol includes resveratrol derivatives such as trans and cis isomers, trans-cis isomer mixtures, dimers, and methylated resveratrol.
  • the trans isomer which is stable against heat, is used in health foods and the like.
  • resveratrol may be prepared by extraction and purification from any raw material, or may be synthetically prepared.
  • resveratrol should be in an amount of 1 to 100 mass in the daily intake for adults. It is preferable to adjust the blending ratio of the two so that the amount of nicotinamide mononucleotide is 1 to 25 parts by mass.
  • the agent for oral diseases according to the present invention can be used for the purpose of improving various oral diseases, but is mainly used for the purpose of improving periodontal disease, bad breath, or xerostomia (dry mouth). be done.
  • periodontal disease includes gingivitis and periodontitis, both of which are applicable to the present invention.
  • gingivitis includes gingivitis and periodontitis, both of which are applicable to the present invention.
  • the agent for oral diseases according to the present invention by applying or rubbing the agent for oral diseases according to the present invention to the affected area where periodontal disease has occurred, it is possible to cause symptoms such as redness, swelling, bleeding, pus from the gums, itching of the gums, and stickiness in the mouth. It is expected to alleviate various symptoms caused by peripheral diseases.
  • halitosis derived from periodontal disease and physiological halitosis derived from tongue coating
  • the agent for oral diseases according to the present invention is effective against both types of halitosis. Applicable.
  • the bad breath will also be improved as the periodontal disease is improved by the oral disease agent of the present invention, as described above.
  • physiological halitosis originating from tongue coating for example, by removing the tongue coating and orally ingesting the agent for oral diseases of the present invention, it is expected that the symptoms of the bad breath will be alleviated.
  • Xerostomia is a condition in which the inside of the oral cavity becomes excessively dry due to decreased secretion of saliva, resulting in unpleasant symptoms such as a sore throat, a feeling of dry mouth, a sticky feeling of saliva, and a sticky mouth.
  • saliva secretion is promoted, saliva becomes smoother, and symptoms such as dry mouth are expected to be alleviated.
  • the manufacturing method of the oral disease agent is not particularly limited, and any general manufacturing method used to manufacture the agent may be appropriately selected depending on the form thereof.
  • the form is a dentifrice, it is necessary to use equipment with sufficient shearing force and kneading force to manufacture the product.
  • It can be manufactured by suitably blending ingredients such as a polishing agent, an abrasive, a filler, a sweetener, a preservative, a pH adjuster, an adhesive, a pigment, a dye, a fragrance, etc., and uniformly dispersing and kneading the mixture.
  • nicotinamide mononucleotide which is an active ingredient, is available on the market and can be obtained commercially.
  • the agent for oral diseases according to the present invention can be used as a drug (including quasi-drugs) for improving oral diseases in the pharmaceutical field, and can be applied orally or parenterally.
  • the dosage form of the drug for oral diseases is not particularly limited, but examples include powders, tablets, long-acting tablets, chewable tablets, effervescent tablets, troches, buccal tablets, and sublingual tablets. , capsules, fine granules, granules, pills, dry syrups, solutions, suspensions, syrups, elixirs and the like.
  • oral preparations such as powders, tablets, and capsules are preferred in consideration of ease of administration, stability of active ingredients, and the like.
  • the dosage form of the agent for oral diseases includes external preparations, injections, and infusions.
  • External preparations are preferred because they can be applied to.
  • External preparations include dentifrice (paste-like ⁇ Neri'', fluid low-viscosity ⁇ liquid'', ⁇ liquid'' with approximately the same viscosity as water, moist powder ⁇ Junsei'', ), mouthwash, mouthspray, ointment, cream, etc.
  • the above-mentioned drug may be appropriately blended with known pharmaceutically acceptable additives for formulations that are appropriate for the dosage form.
  • additives for formulations include excipients (lactose, starch, crystalline cellulose, sodium phosphate, etc.), solvents (water, soybean oil, saline, non-aqueous solvents for injection, etc.), binders ( Starch, gelatin, gum arabic, sodium alginate, carmellose sodium, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, etc.), disintegrants (starch, carmellose sodium, etc.), lubricants (talc, stearic acid) Magnesium, calcium stearate, macrogol, sucrose fatty acid ester, etc.), coating agents (white sugar, HPC, shellac, gelatin, glycerin, hydroxypropyl methyl
  • the dosage of the above drug varies depending on the age, sex, weight, expected effects, symptoms, etc. of the subject and cannot be uniformly prescribed, but the dosage of the drug is based on the applicable nicotine per day for adults.
  • the amount of amide mononucleotide is usually 1 mg to 500 mg, preferably 5 mg to 250 mg, and more preferably 50 mg to 200 mg. If the amount is less than 1 mg, the effects of the present invention may not be obtained, while if the amount is more than 500 mg, the effect obtained will not be particularly different, and this will be economically disadvantageous.
  • the proportion of nicotinamide mononucleotide in the drug should be adjusted according to the dosage form of the drug, the number of administrations, etc., so that the amount of nicotinamide mononucleotide administered per day for an adult falls within the above range. It can be set as appropriate.
  • the number of administrations of the drug can be appropriately set depending on the age, weight, symptoms, and dosage of the drug per administration of the subject.
  • An example of the number of times the drug is administered per day is 1 to 3 times.
  • the agent for oral diseases according to the present invention can be used as a food.
  • the agent for oral diseases can be provided as a food for improving oral diseases in the food field.
  • it is particularly effective in improving oral diseases because it continuously exerts its effect on improving oral diseases.
  • the types of foods covered by the present invention are not particularly limited, and include general foods, functional foods, foods for specified health uses, nutritional supplements, food additives, feeds, nursing foods, dietary therapy foods, and therapeutic foods. , diet food, etc.
  • the form of the food is not limited, and in particular, in the case of functional foods and foods for specified health uses, examples thereof include powders, tablets, pills, granules, hard capsules, soft capsules, jelly, liquid, It can be processed into a paste, chewing gum, etc. and provided.
  • the amount of food intake varies depending on the type of food, the age, sex, weight, expected effects, symptoms, etc. of the person being ingested, but the daily dosage of nicotinamide mononucleotide contained in food for adults is: Usually 1 mg to 500 mg, preferably 5 mg to 250 mg, more preferably 50 mg to 200 mg. If the amount is less than 1 mg, the effect of the present invention may not be obtained, while if the amount is more than 500 mg, the effect obtained will not be particularly different and it will be economically disadvantageous.
  • the blending ratio of nicotinamide mononucleotide in the food may be adjusted within a range of 100% or less based on the total weight of the food so that the amount of nicotinamide mononucleotide ingested per day by an adult is within the above range. Can be set.
  • the food Since the food is safe and has no particular side effects, it can be ingested over a long period not only for the purpose of treating oral diseases, but also for the purpose of preventing oral diseases. Therefore, it can be applied not only to subjects for whom it is desired to treat oral diseases, but also to healthy subjects so as not to cause oral diseases.
  • nicotinamide mononucleotide has the effect of improving oral diseases, so the present invention is further characterized in that an effective amount of nicotinamide mononucleotide is ingested by a subject who needs it.
  • an effective amount of nicotinamide mononucleotide is ingested by a subject who needs it.
  • the subjects to be ingested are preferably mammals such as humans, mice, rats, rabbits, dogs, cats, cows, horses, pigs, and monkeys, with humans being particularly preferred.
  • the amount of nicotinamide mononucleotide taken, the number of times of intake per day, etc. are as described for the oral disease agent.
  • the oral disease agent can be ingested by a subject at any time and over a long period of time.
  • Periodontal disease improvement was evaluated for 10 subjects (2 in their 30s, 2 in their 40s, 3 in their 50s, and 3 in their 70s) with symptoms of periodontal disease (gingivitis).
  • Approximately 1 g of the above dentifrice (containing 7.0% ⁇ -NMN) was placed on a toothbrush, and teeth were brushed for approximately 10 minutes once in the morning and once in the afternoon every day for 7 consecutive days.
  • the toothpaste was stored in the refrigerator when not in use.
  • the periodontal disease-improving effects of the above toothpaste include Bleeding on Probing (BOP) before and after 7 days of brushing (29 to 143 days after the start of tooth brushing);
  • the influence on Red complex was evaluated as follows.
  • Bleeding on probing For each subject, before and after brushing the teeth as described above for 7 days, the ratio of areas where bleeding occurred during probing was determined for a total of 9〜30 gingival grooves and pockets, and the average value of the ratio for all subjects was calculated. Bleeding during probing was evaluated by calculating the above. The presence or absence of bleeding during probing was determined by lightly inserting the pocket probe into the gingival sulcus/pocket (approximately 15 to 20 g of force) and pulling it out, based on the presence or absence of bleeding 20 to 30 seconds later.

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PCT/JP2022/011206 2022-03-14 2022-03-14 口腔疾患用剤 Ceased WO2023175655A1 (ja)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US18/847,268 US20250205266A1 (en) 2022-03-14 2022-03-14 Agent for oral diseases
JP2024507200A JPWO2023175655A1 (https=) 2022-03-14 2022-03-14
EP22931940.5A EP4494485A4 (en) 2022-03-14 2022-03-14 AGENT FOR ORAL DISEASES
CN202280093721.4A CN118900640A (zh) 2022-03-14 2022-03-14 用于口腔疾病的药物
KR1020247033707A KR20250019018A (ko) 2022-03-14 2022-03-14 구강질환용 제
PCT/JP2022/011206 WO2023175655A1 (ja) 2022-03-14 2022-03-14 口腔疾患用剤

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PCT/JP2022/011206 WO2023175655A1 (ja) 2022-03-14 2022-03-14 口腔疾患用剤

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JPH10158131A (ja) 1996-11-26 1998-06-16 Lion Corp 口腔用組成物
JP2014094959A (ja) 2008-01-23 2014-05-22 Kao Corp 歯周病用歯磨組成物
JP5982376B2 (ja) 2011-08-05 2016-08-31 株式会社ヤクルト本社 口腔内疾患の予防又は治療剤
WO2019078177A1 (ja) * 2017-10-16 2019-04-25 めぐみ 田中 ニコチンアミドモノヌクレオチドを含む化粧品組成物
US20210069096A1 (en) * 2019-09-06 2021-03-11 BeautyPaste LLC Enhanced Toothpaste And Kits
WO2021070829A1 (ja) * 2019-10-11 2021-04-15 国立大学法人静岡大学 ニコチンアミドリボシドを産生する乳酸菌、並びにニコチンアミドモノヌクレオチド及びニコチンアミドリボシドを産生する乳酸菌
WO2021230146A1 (ja) * 2020-05-11 2021-11-18 サントリーホールディングス株式会社 Ｎｒ及び／又はｎｍｎとセサミン類とを含有する組成物
JP2022035271A (ja) * 2020-08-20 2022-03-04 株式会社ディーエイチシー Ｎａｄ産生促進剤

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