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WO2014125977A1 - Composition pour la cavité buccale - Google Patents

Composition pour la cavité buccale Download PDF

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Publication number
WO2014125977A1
WO2014125977A1 PCT/JP2014/052676 JP2014052676W WO2014125977A1 WO 2014125977 A1 WO2014125977 A1 WO 2014125977A1 JP 2014052676 W JP2014052676 W JP 2014052676W WO 2014125977 A1 WO2014125977 A1 WO 2014125977A1
Authority
WO
WIPO (PCT)
Prior art keywords
oral
composition
bacteria
ascorbic acid
oil
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.)
Ceased
Application number
PCT/JP2014/052676
Other languages
English (en)
Japanese (ja)
Inventor
眞里 阿部
貴士 近澤
苗穂 鈴木
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.)
Lion Corp
Original Assignee
Lion Corp
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 Lion Corp filed Critical Lion Corp
Priority to KR1020157021957A priority Critical patent/KR20150118144A/ko
Priority to CN201480009052.3A priority patent/CN104994835B/zh
Priority to JP2015500204A priority patent/JP6222217B2/ja
Publication of WO2014125977A1 publication Critical patent/WO2014125977A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • 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
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations

Definitions

  • the present invention has an excellent bactericidal effect against oral bacteria, particularly porphyromonas gingivalis, a periodontal disease-causing bacterium, and an oral cytostatic effect, and is effective in preventing and treating periodontal disease.
  • the present invention relates to an oral composition.
  • Periodontal disease is an infection caused by bacteria, mainly anaerobic gram-negative bacteria such as Porphyromonas gingivalis, and exotoxins (such as leukotoxin) and endotoxins (such as lipopolysaccharide) produced by the bacteria. ) Induces inflammation and damages the tissue.
  • exotoxins such as leukotoxin
  • endotoxins such as lipopolysaccharide
  • human defensin a host-derived peptide
  • Patent Document 1 Japanese Patent Laid-Open No. 2001-288105
  • human ⁇ -defensin has a strong antibacterial activity against a periodontitis-causing fungus, Actinobacillus actinomycetemcomitans, and Porphyromonas gingivalis
  • periodontitis-causing bacteria such as (Porphyromonas gingivalis) also have antibacterial activity, and a human ⁇ -defensin-containing dentifrice has been proposed.
  • Patent Document 2 Japanese Patent Laid-Open No. 2009-155214 proposes a composition for oral cavity in which the antibacterial effect of oral biofilm is improved by using human defensin and dextranase in combination.
  • human defensins cannot be said to have a sufficient bactericidal effect on periodontopathic bacteria, and improvement of bactericidal power has been a problem.
  • ascorbic acid esters such as ascorbic acid phosphates or salts thereof eliminate excess active oxygen produced in the living body and protect the living tissue from oxidative stress injury. Although it is known that it suppresses inflammation and has an effect of inhibiting the damage of oral cells, the effect of inhibiting the cytotoxicity still has room for improvement. In addition, ascorbic acid ester or a salt thereof does not have a bactericidal effect on periodontal disease-causing bacteria.
  • the present invention has been made in view of the above circumstances, and has an excellent bactericidal effect against oral bacteria, especially periodontal disease-causing bacteria and oral cell injury-suppressing effect, and is effective for the prevention and treatment of periodontal disease.
  • the purpose is to provide goods.
  • human defensin which is a peptide derived from the host, has antibacterial activity against periodontal disease-causing bacteria and is known as a safe component to the human body.
  • P. of periodontal disease-causing bacteria g It was found that there is a problem that there is not enough bactericidal effect against bacteria.
  • the oral bacterial bactericidal effect of human defensin is not sufficient, the cytotoxicity-inhibiting effect is not observed, and the cytotoxicity-inhibiting effect of ascorbic acid ester or its salt is not sufficient.
  • the combination system of (A) and (B) It was able to enhance the bactericidal effect of oral bacteria and the effect of suppressing cytotoxicity beyond the additive effect of the single compound system.
  • the present invention provides the following oral composition.
  • An oral composition comprising (A) human defensin and (B) an ascorbic acid ester or a salt thereof.
  • oral bacteria particularly P. g. It is possible to provide a composition for oral cavity containing human defensin which is excellent in bactericidal effect against bacteria and suppressive effect on cell damage in the oral cavity, is safe for the human body, and is effective for prevention and treatment of periodontal disease.
  • composition for oral cavity of the present invention is characterized in that (A) human defensin and (B) ascorbic acid ester or a salt thereof are used in combination. The effect and the cytotoxic effect are improved.
  • Human defensin includes human defensin ⁇ , human defensin ⁇ -1, human defensin ⁇ -2, and human defensin ⁇ -3, and one or more types selected from these are used.
  • human defensin ⁇ -2 and human defensin ⁇ -3 are particularly preferable in terms of the bactericidal effect of periodontal disease-causing bacteria.
  • a commercially available human defensin can be used, and examples thereof include human defensin ⁇ -2 manufactured by Peptide Institute, and human defensin ⁇ -3 manufactured by Anygen.
  • the blending amount of human defensin is preferably 0.000005 to 0.0005% (mass%, the same applies hereinafter) of the whole composition, and more preferably 0.00005 to 0.0005%.
  • the blending amount increases, the bactericidal effect on oral bacteria and the effect of inhibiting cell damage are improved, and blending 0.000005% or more is suitable for effect expression.
  • the amount is too large, not only can the effect not be improved any longer, but there may be a case where the taste is lowered and the feeling of use may be lowered, and 0.0005% or less is suitable for securing a good feeling of use. It is.
  • Ascorbic acid ester of component (B), one or more of hydroxyl groups at any of positions 2, 3, 5, and 6 of ascorbic acid is phosphoric acid, polyphosphoric acid, sulfuric acid, fatty acid, or other pharmaceutically acceptable. This is an ester of a compound.
  • As the ascorbic acid ester or a salt thereof an ascorbic acid phosphate or a salt thereof, or an ascorbic acid sulfate or a salt thereof is particularly preferable.
  • Ascorbic acid phosphoric acid ester and ascorbic acid sulfuric acid ester are phosphoric acid compounds such as phosphoric acid and polyphosphoric acid, or an ester of sulfuric acid.
  • ascorbic acid-2-phosphate ascorbic acid-3-phosphate, ascorbic acid-6-phosphate, ascorbic acid-2-polyphosphate, ascorbic acid -2-Sulfate ester.
  • the salt include alkali metal salts such as sodium salt, potassium salt, calcium salt, and magnesium salt, and alkaline earth metal salts.
  • the component (B) one or more selected from these can be used. Particularly, it is used for the oral cavity, and is an ascorbic acid phosphate ester from the viewpoint of a gingivitis preventing effect, particularly a cytotoxicity suppressing effect.
  • the magnesium salt and sodium salt are preferably used.
  • the amount of ascorbic acid ester or salt thereof is preferably 0.1 to 2%, more preferably 0.2 to 1% of the total composition. As the amount is increased, the bactericidal effect on oral bacteria and the effect of suppressing cytotoxicity are improved, and it is preferable to add 0.1% or more to improve the oral bacterial sterilizing effect and the effect of suppressing cytotoxicity. Moreover, 2% or less is suitable for improving the bactericidal effect of oral bacteria and ensuring a good feeling of use. If too much is added, the bactericidal effect of oral bacteria may be reduced. Moreover, a nasty taste may appear and a feeling of use may be reduced.
  • (A) ascorbic acid ester or a salt thereof (B) is preferably 20 times or more, particularly 200 to 400,000 times, more preferably 400 to 400 times by mass with respect to human defensin. 200,000 times the amount, more preferably 1,000 to 100,000 times the amount, and particularly preferably 1,000 to 10,000 times the amount. When blended in such a ratio, the effect of the present invention is further improved. To do.
  • the oral composition of the present invention can be produced by adopting conventional methods for various dosage forms such as toothpaste, toothpaste such as toothpaste, liquid toothpaste, liquid toothpaste, and toothpaste, and mouthwash. Especially suitable for dentifrice.
  • appropriate known components can be blended in addition to the above components as long as the effects of the present invention are not hindered.
  • dentifrices contain abrasives, thickeners, binders, surfactants, and if necessary, flavors, sweeteners, colorants, preservatives, active ingredients, and the like.
  • silica-based abrasives such as silica gel, precipitated silica, aluminosilicate, zirconosilicate, dicalcium phosphate dihydrate and anhydrous, tricalcium phosphate, tetracalcium phosphate, calcium pyrophosphate, calcium carbonate, water
  • examples thereof include aluminum oxide, alumina, magnesium carbonate, tribasic magnesium phosphate, zeolite, hydroxyapatite, and synthetic resin abrasive.
  • the blending amount of the abrasive is adjusted depending on the dosage form, and is preferably 2 to 40%, particularly 10 to 30% for toothpaste, and 0% for liquid toothpaste.
  • the thickener examples include sugar alcohols such as sorbit, xylit, malt, and lactite, and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol.
  • the blending amount is usually 5 to 50%, particularly 20 to 45%. preferable.
  • binder examples include cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose, and hydroxyethyl cellulose, gums such as xanthan gum and gum arabic, organic binders such as carrageenan, polyvinyl alcohol, and sodium polyacrylate, gelling silica, gel Inorganic binders such as curable aluminum silica, bee gum, and laponite.
  • the blending amount is usually 0.1 to 5% for toothpaste and 0 to 5% for liquid toothpaste and mouthwash.
  • an anionic surfactant As the surfactant, an anionic surfactant, a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant can be blended.
  • the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate, N-acyl sarcosine salts such as N-lauroyl sarcosine sodium and N-myristoyl sarcosine sodium, N-acyl glutamates such as sodium N-palmitoyl glutamate, Examples include sodium N-methyl-N-acyl taurine, sodium N-methyl-N-acylalanine, sodium ⁇ -olefin sulfonate, and the like.
  • Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters and maltose fatty acid esters, sugar alcohol fatty acid esters such as maltitol fatty acid esters and lactitol fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, hexaglyceryl monolaurate, Polyglycerin fatty acid esters such as hexaglyceryl monomyristate, decaglyceryl monolaurate, decaglyceryl monomyristic acid, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene Polyoxyethylene fatty acid esters such as hydrogenated castor oil and polyoxyethylene higher alcohols such as polyoxyethylene lauryl ether Ethers, fatty acid alkanolamides, such as lauric acid diethanolamide, polyoxyethylene polyoxypropylene copo
  • Examples of the cationic surfactant include alkyl ammonium and alkyl benzyl ammonium salts, and examples of the amphoteric surfactant include betaines such as alkyl betaines, fatty acid amidopropyl betaines, and alkyl imidazolinium betaines.
  • the blending amount of the surfactant is preferably 0.001 to 10%, particularly preferably 0.1 to 5% of the entire composition.
  • Perfumes include peppermint oil, spearmint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, Lime oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie Natural fragrances such as oil, coconut oil, Iris concrete, absolute peppermint, absolute rose, orange flower, and processing of these natural fragrances (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, Powdered fragrance etc.) and menthol Carvone, Anethole, Cineol, Methyl salicylate, Synamic aldehyde, Eugenol, 3-l-Mentoxypropane
  • the blending amount is not particularly limited, but the above fragrance material is preferably used at 0.000001 to 1% in the preparation composition. Further, as the flavoring fragrance using the fragrance material, it is preferable to use 0.1 to 2% in the preparation composition.
  • sweetener examples include saccharin sodium, stevioside, paramethoxycinnamic aldehyde, perilartin and the like.
  • colorant examples include blue No. 1, yellow No. 4, titanium dioxide and the like.
  • preservative examples include benzoic acid such as paraoxybenzoic acid ester and sodium benzoate, or a salt thereof.
  • Active ingredients include those other than human defensin and ascorbic acid esters and salts thereof, for example, nonionic fungicides such as isopropylmethylphenol, cationic fungicides such as cetylpyridinium chloride, chlorhexidine hydrochloride, benzalkonium chloride, and benzethonium chloride , Tranexamic acid, epsilon aminocaproic acid, allantoin, glycyrrhetinic acid, glycyrrhizic acid and other anti-inflammatory agents, dextranase, mutanase, amylase, protease and other enzymes, sodium fluoride, sodium monofluorophosphate fluoride, positive phosphorus Water-soluble phosphate compounds such as potassium salts of sodium and sodium salts, copper compounds such as copper gluconate and copper chlorophyllin sodium, sodium chloride, potassium nitrate, aluminum lactate, zinc chloride, zinc citrate, Inorgan
  • Examples and Comparative Examples A sample solution having the composition shown in Table 1 was prepared by a conventional method, and the cytotoxicity-inhibiting effect and the oral bacterial bactericidal effect were evaluated by the methods shown in the following experimental examples. The results are shown in the table.
  • a 1 mM hydrogen peroxide aqueous solution (assuming active oxygen) was added for 60 minutes.
  • the sample solution was removed, and 400 ⁇ L of a solution containing 1 mM hydrogen peroxide (D-MEM containing 10% FBS) was added and treated for 60 minutes.
  • Cytotoxicity inhibition rate is 90% or more.
  • O Cytotoxicity inhibition rate is 70% or more and less than 90%.
  • ⁇ Cytotoxicity inhibition rate is 50% or more and less than 70%.
  • X Cytotoxicity inhibition rate is less than 50%.
  • the solution was diluted 10-fold with physiological saline four times and smeared on a blood agar plate using a spiral plater.
  • a mixture of physiological saline and bacterial solution at 1: 1 (volume ratio) instead of the drug was used.
  • the blood plate was cultured at 37 ° C. under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide) for 5 days, and the number of colonies formed was counted.
  • Evaluation criteria for bactericidal effect in oral cavity A: The viable cell rate is less than 10% compared to the control. A: The viable cell rate is 10% to less than 40% compared to the control. B: The viable cell rate is 40% to less than 80% compared to the control. More than 80% viable bacteria compared to control

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Birds (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention fournit une composition pour la cavité buccale qui se révèle excellente en termes d'effets inhibiteurs de cytotoxicité à l'intérieur de la cavité buccale, et d'effets bactéricides sur des bactéries internes à la cavité buccale, et plus spécifiquement sur le porphyromonas gingivalis qui est une bactérie facteur de parodontopathie, qui est efficace pour prévenir ou traiter une parodontopathie, et qui comprend (A) une défensine humaine, et (B) un ascorbate d'ester ou un sel de celui-ci.
PCT/JP2014/052676 2013-02-14 2014-02-05 Composition pour la cavité buccale Ceased WO2014125977A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
KR1020157021957A KR20150118144A (ko) 2013-02-14 2014-02-05 구강용 조성물
CN201480009052.3A CN104994835B (zh) 2013-02-14 2014-02-05 口腔用组合物
JP2015500204A JP6222217B2 (ja) 2013-02-14 2014-02-05 口腔用組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2013026574 2013-02-14
JP2013-026574 2013-02-14

Publications (1)

Publication Number Publication Date
WO2014125977A1 true WO2014125977A1 (fr) 2014-08-21

Family

ID=51353984

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2014/052676 Ceased WO2014125977A1 (fr) 2013-02-14 2014-02-05 Composition pour la cavité buccale

Country Status (4)

Country Link
JP (1) JP6222217B2 (fr)
KR (1) KR20150118144A (fr)
CN (1) CN104994835B (fr)
WO (1) WO2014125977A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001288105A (ja) * 2000-04-05 2001-10-16 Yoshihiro Abiko 歯周炎用医薬
WO2005027893A1 (fr) * 2003-09-19 2005-03-31 Otsuka Pharmaceutical Co., Ltd. Promoteur de secretion de $g(b)-defensine
JP2009155214A (ja) * 2007-12-25 2009-07-16 Lion Corp 口腔用組成物
JP2012180330A (ja) * 2011-03-03 2012-09-20 Lion Corp 口腔用組成物及び歯肉繊維芽細胞の活性酸素傷害抑制剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001288105A (ja) * 2000-04-05 2001-10-16 Yoshihiro Abiko 歯周炎用医薬
WO2005027893A1 (fr) * 2003-09-19 2005-03-31 Otsuka Pharmaceutical Co., Ltd. Promoteur de secretion de $g(b)-defensine
JP2009155214A (ja) * 2007-12-25 2009-07-16 Lion Corp 口腔用組成物
JP2012180330A (ja) * 2011-03-03 2012-09-20 Lion Corp 口腔用組成物及び歯肉繊維芽細胞の活性酸素傷害抑制剤

Also Published As

Publication number Publication date
JPWO2014125977A1 (ja) 2017-02-02
CN104994835A (zh) 2015-10-21
CN104994835B (zh) 2017-09-01
JP6222217B2 (ja) 2017-11-01
KR20150118144A (ko) 2015-10-21

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