Classifications

• • 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
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
• • 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
  • A61K8/604—Alkylpolyglycosides; Derivatives thereof, e.g. esters
• • 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
  • 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
  • A61K8/678—Tocopherol, i.e. vitamin E
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
  • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
  • A61K8/86—Polyethers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/59—Mixtures
  • A61K2800/592—Mixtures of compounds complementing their respective functions

Definitions

• the present invention relates to an oral composition containing an ascorbic acid phosphate ester or a salt thereof, exhibiting a high periodontal disease prevention or improvement effect and excellent in storage stability over time.
• an ascorbic acid phosphate ester or a salt thereof exhibiting a high periodontal disease prevention or improvement effect and excellent in storage stability over time.
• the effect of improving bad breath and gingival crevicular fluid volume increase is particularly high, and the storage stability of ascorbic acid phosphate or its salt over time is excellent, and separation and discoloration are prevented and the appearance
• the present invention relates to a composition for oral cavity that is also excellent in stability.
• Periodontal disease is counted as one of the major causes of tooth loss, and its prevention is expected to lead to an improvement in QOL (Quality of Life).
• QOL Quality of Life
• Many periodontal diseases are thought to be infections caused by bacteria, mainly obligate anaerobic gram-negative bacilli, resulting in destruction of connective tissue and alveolar bone. Redness, swelling, bleeding, drainage, bad breath, etc. are observed as clinical findings in this process. There is also a bacterial-host reaction between cause and effect.
• neutrophils In the living body, neutrophils have a function of sterilizing bacteria and protecting the living body. However, particularly in chronic inflammation, leakage of cellular components and production of excessive active oxygen adversely affect living tissues. Therefore, it is useful to prevent tissue destruction by active oxygen by using an antioxidant such as ascorbic acid phosphate or a salt thereof. It is described in, for example, Patent Document 1 that blending an ascorbic acid phosphate ester or a derivative thereof into an oral composition is effective in preventing periodontal disease. However, ascorbic acid phosphate is easily decomposed in the preparation, and there is a problem that storage stability is not sufficient when water or an anionic surfactant is present.
• Vitamin E also known as tocopherol
• Patent Document 2 discloses that blending a vitamin E derivative into an oral composition is effective in preventing periodontal disease.
• vitamin E derivatives are easily decomposed in the preparation and it is difficult to ensure storage stability.
• Patent Document 3 It is described in, for example, Patent Document 3 and the like that a bactericidal agent that exhibits an effect by directly reducing the number of oral bacteria that cause inflammation of gums is effective in preventing and improving periodontal diseases.
• a surfactant it is common to use a surfactant to solubilize a bactericidal agent in an oral composition and stably mix it, but depending on the amount of surfactant, micelles formed by the surfactant may be rigid. Therefore, there was a problem that the bactericide incorporated in the micelle was not released at the target site, making it difficult to exert its effect.
• ascorbic acid ester or a salt thereof, vitamin E or a derivative thereof, and a bactericidal agent still have room for improvement in terms of stably blending them into the oral composition and sufficiently exerting these effects. It has been difficult to stably blend the ingredients at the same time to achieve high effects and to improve storage stability over time.
• Patent Document 4 discloses a dentifrice composition containing an ascorbic acid phosphate salt, a vitamin E derivative, and a cationic fungicide, a vitamin E derivative, a cationic fungicide, and polyoxyethylene hydrogenated castor oil (hereinafter, polyoxyethylene is POE).
• polyoxyethylene polyoxyethylene
• Patent Document 6 describes a composition using an ascorbic acid phosphate ester salt, a vitamin E derivative and a nonionic fungicide in combination as a caries prevention coating composition containing no abrasive. However, solubilization and blending stability of vitamin E derivatives and nonionic fungicides are not sufficient.
• Patent Document 7 describes a composition using a combination of anaerobic fungicide.
• this composition it is difficult to say that the mixing ratio of each component is appropriate. For this reason, the micelle formed by the surfactant becomes too rigid, and the vitamin E derivative and the bactericide incorporated in the micelle are in the target site. It was not released sufficiently and there was room for improvement in the manifestation of the effect.
• Patent Document 8 describes a composition in which an ascorbic acid phosphate ester salt, a vitamin E derivative, a POE alkyl ether, and a nonionic fungicide are blended as an oral composition containing vitamin E or a derivative thereof.
• this composition it is difficult to say that the blending ratio of each component, in particular, the blending ratio of the POE alkyl ether to the vitamin E derivative and the nonionic fungicide is appropriate. For this reason, the stability of the vitamin E derivative and the nonionic fungicide That is not enough.
• Patent Document 8 does not define the alkyl group part of the POE alkyl ether, and there is a description that the ascorbic acid derivative stabilizes vitamin E. However, simultaneous stabilization of vitamin E and ascorbic acid derivative is described. Is not shown.
• Applicant has formulated an oral composition containing an ascorbic acid phosphate ester salt with POE hydrogenated castor oil having an EO average addition mole number of 5 to 10 and adjusting the pH to 6.5 to 9.0.
• a product was proposed in Japanese Patent Application No. 2007-326959 (Japanese Patent Laid-Open No. 2009-149537).
• This application includes ascorbic acid phosphate salt, vitamin E derivative, PEO hydrogenated castor oil with 5 and 20 EO average addition moles, POE cetyl ether with 7 EO average addition moles and isopropylmethylphenol in Example 30.
• the composition to contain is described.
• this technology improves the oral retention and mucosal permeability of ascorbic acid phosphate ester salt by blending specific POE hydrogenated castor oil and adjusting the pH, and is derived from ascorbic acid phosphate ester salt.
• the effect can be effectively exhibited, and the technical idea is different from the present invention.
• the composition for oral cavity which has solved the above-mentioned problems, has a higher preventive or ameliorating effect on periodontal diseases, and has excellent storage stability over time, and appearance stability typified by prevention of separation and discoloration. Development of things is desired.
• the present invention has been made in view of the above circumstances, and ascorbic acid phosphate or a salt thereof, vitamin E or a derivative thereof, and a bactericidal agent are stably and effectively blended, and has an excellent periodontal disease prevention or improvement effect.
• An object of the present invention is to provide an oral composition that is effective and has excellent storage stability over time.
• the present inventors have (A) ascorbic acid phosphate ester or salt thereof, (B) vitamin E or derivative thereof, and (C) EO average added mole number. 10 to 60 mol of POE hydrogenated castor oil, POE alkyl ether having an alkyl group with 14 to 18 carbon atoms and EO average addition mole number of 5 to 8 mol, and an alkyl glucoside with an alkyl group having 10 to 14 carbon atoms
• One or more selected surfactants are blended, and (D) a nonionic germicide or (E) a cationic germicide is blended as a germicide, and the blending amounts and blending ratios of these components are shown below.
• composition for oral cavity in such a suitable range is excellent in preventing or ameliorating periodontal disease and excellent in storage stability over time.
• ascorbic acid phosphate or a salt thereof, vitamin E or a derivative thereof, and a bactericidal agent are stably blended at the same time, the effects derived from these components are effectively expressed, and bad breath and gums derived from periodontal diseases.
• a high effect of improving the increase in the amount of cough exudate (hereinafter referred to as GCF) and a high bactericidal effect on periodontal disease-causing bacteria are exhibited at the same time.
• Acid ester or a salt thereof and vitamin E or a derivative thereof are blended stably over a long period of time, and separation and discoloration do not occur over time, and the storage stability over time is excellent.
• the composition described above can provide an oral composition having both a high periodontal disease improving effect and excellent storage stability over time, which could not be achieved by conventional techniques.
• Ascorbic acid phosphate or a salt thereof, vitamin E or a derivative thereof, and a bactericidal agent are known to be effective in preventing or ameliorating periodontal diseases.
• a bactericidal agent are known to be effective in preventing or ameliorating periodontal diseases.
• these ingredients act synergistically, and in particular, among the symptoms associated with periodontal diseases, a high effect of improving the bad breath and the increase in the amount of GCF is exhibited.
• This GCF is present in the gingiva and gingival crevice, and actively blocks foreign substances such as bacteria and toxins by antibody components, etc., and contributes to biological defense.
• interleukin (hereinafter referred to as IL) Abbreviations) -1, cytokines such as IL-6, IL-8, and the like have been suggested to be associated with periodontal diseases (Non-patent Document 2).
• IL interleukin
• cytokines such as IL-6, IL-8, and the like
• the periodontal disease is remarkably improved, the amount of GCF once increased is decreased, the substrate of bad breath production is reduced, and the bactericidal agent sterilizes the bad breath producing bacteria. It is speculated that this can be suppressed.
• the amount of GCF increases when suffering from a periodontal disease and decreases when it improves, it is used as an index for measuring the degree of severity and improvement of the periodontal disease.
• composition of the present invention further contains (F) glycyrrhetinic acid, ⁇ -aminocaproic acid, glycyrrhizinate, tranexamic acid, buckwheat extract, and allantoin to prevent periodontal disease.
• the improvement effect is further improved, and the amount of GCF that has increased with the onset of periodontal disease can be more effectively reduced.
• the present invention provides the following oral composition.
• Claim 1 (A) Ascorbic acid phosphate or a salt thereof, (B) Vitamin E or a derivative thereof, (C) polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 10 to 60 moles, polyoxyethylene alkyl having an alkyl group carbon number of 14 to 18 and an average addition mole number of ethylene oxide of 5 to 8 moles
• D) contains a nonionic fungicide, the total content of the components (A), (B) and (D) is 0.2 to 1.5% by mass, and (C) / ((B) A composition for oral cavity, wherein (D) is 8 to 20 by mass ratio.
• Claim 2 The composition for oral cavity according to claim 1, wherein the nonionic fungicide is isopropylmethylphenol or triclosan.
• Claim 3 (A) Ascorbic acid phosphate or a salt thereof, (B) Vitamin E or a derivative thereof, (C) polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 10 to 60 moles, polyoxyethylene alkyl having an alkyl group carbon number of 14 to 18 and an average addition mole number of ethylene oxide of 5 to 8 moles
• One or more surfactants selected from ethers and alkyl glucosides having 10 to 14 carbon atoms in the alkyl group (E) a cationic fungicide, the total content of the components (A), (B) and (E) is 0.2 to 1.3% by mass, and (C) / ((B) + The composition for oral cavity, wherein (E)) is 8 to 18 by mass ratio.
• Claim 4 (E) The composition for oral cavity according to claim 3, wherein the cationic fungicide is at least one selected from cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine gluconate, and chlorhexidine hydrochloride.
• Claim 5 The total content of the component (A), the component (B), and the component (D) or (E) is 0.2 to 1.0% by mass, and (C) / [(B) + (( The oral composition according to any one of claims 1 to 4, wherein D) or (E))] is 8 to 15 in terms of mass ratio.
• Claim 6 6.
• composition according to claim 1 further comprising (F) one or more selected from glycyrrhetinic acid, ⁇ -aminocaproic acid, glycyrrhizinate, tranexamic acid, buckwheat extract, and allantoin. Oral composition.
• the oral composition of the present invention exhibits a high effect of improving an increase in halitosis and the amount of GCF, among other symptoms associated with periodontal diseases, and a high bactericidal effect on periodontal disease-causing bacteria, and preservation over time Excellent stability and excellent appearance stability represented by separation and discoloration. Furthermore, the inhibitory effect of the higher increase in the amount of GCF is exhibited by mix
• composition for oral cavity of the present invention comprises (A) ascorbic acid phosphate or a salt thereof, (B) vitamin E or a derivative thereof, (C) a specific surfactant, And (D) a nonionic fungicide or (E) a cationic fungicide as a fungicide.
• Ascorbic acid phosphoric acid ester and its salt one or two or more hydroxyl groups at any of the 2, 3, 5, and 6 positions of ascorbic acid became esters of compounds such as phosphoric acid and polyphosphoric acid.
• examples thereof include ascorbic acid-2-phosphate, ascorbic acid-3-phosphate, ascorbic acid-6-phosphate, ascorbic acid-2-polyphosphate, and salts thereof.
• Alkali metal salts such as sodium salt, potassium salt, calcium salt and magnesium salt, and alkaline earth metal salts.
• magnesium salt and sodium salt of ascorbic acid phosphate ester that is, L-ascorbyl magnesium phosphate and L-ascorbyl sodium phosphate are preferably used.
• L-ascorbyl magnesium phosphate is Showa Denko K.K. (trade name: ascorbic acid PM), Wako Pure Chemical Industries, Ltd. (trade name: phosphorus L-ascorbyl sodium phosphate, such as L-ascorbyl acid phosphate, is available from DSM Nutrition Japan (trade name: Stay-C50), BASF Japan Ltd. (trade name: L-ascorbyl sodium phosphate), etc. it can.
• the amount of ascorbic acid phosphate ester or salt thereof is 0.05 to 0.8% (mass%, the same applies hereinafter) of the whole composition from the viewpoint of periodontal disease prevention effect and storage stability over time, and particularly 0. .1 to 0.5% is preferable. If the compounding amount is less than 0.05%, the effect of preventing or improving periodontal disease cannot be obtained sufficiently, and if it exceeds 0.8%, discoloration may occur over time, and irritation will be adversely affected. There is a case.
• Vitamin E or a derivative thereof includes d- ⁇ -tocopherol, dl- ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol and acetic acid thereof. Further, esters or salts with organic acids such as nicotinic acid, succinic acid and linolenic acid can be used.
• VE derivative examples include d- ⁇ -tocopherol acetate, dl- ⁇ -tocopherol acetate, d- ⁇ -tocopherol nicotinate, dl- ⁇ -tocopherol nicotinate, d- ⁇ -tocopherol succinate, dl- ⁇ -succinate.
• Tocopherol, linolenic acid d- ⁇ -tocopherol, linolenic acid dl- ⁇ -tocopherol, tocopherol calcium succinate and the like can be mentioned.
• Vitamin E or a derivative thereof is particularly dl- ⁇ -tocopherol, dl- ⁇ -tocopherol acetate, dl-nicotinic acid dl in that it has high physiological activity and is colorless to pale yellow and hardly affects the color and appearance of the preparation.
• - ⁇ -Tocopherol is preferred.
• VE or its derivative (s) can be mix
• VE or a derivative thereof those conforming to the former cosmetic raw material standard (Making basic group) or quasi-drug raw material standard 2006 can be used, and those generally used in cosmetics and oral compositions can be used.
• a commercial product sold by DSM Nutrition Japan, Eisai Food Chemical, BASF Japan, or the like can be used.
• the blending amount of VE or a derivative thereof is preferably 0.05 to 0.5%, particularly 0.05 to 0.3% of the whole composition from the viewpoint of periodontal disease prevention effect and storage stability over time. If the blending amount is less than 0.05%, the periodontal disease prevention / amelioration effect cannot be sufficiently obtained, and if it exceeds 0.5%, it is difficult to solubilize in the preparation, and separation or discoloration occurs over time, It may become oily and have a poor taste.
• Component (C) comprises POE alkyl ether having an EO average addition mole number of 5 to 8 moles and an alkyl group having 14 to 18 carbon atoms, POE hydrogenated castor oil having an EO average addition mole number of 10 to 60 moles, and an alkyl group.
• the POE alkyl ether preferably has an alkyl group having 14 to 18 carbon atoms, preferably 16 to 18 carbon atoms. If the alkyl group has less than 14 carbon atoms, the lipophilicity is low, so that the oil-soluble component is not sufficiently solubilized, and sufficient foaming properties cannot be obtained. Due to its small size, the oil-soluble component is insufficiently solubilized, and a unique taste and oiliness are produced during use of the preparation.
• Specific examples of the POE alkyl ether include POE cetyl ether, POE myristyl ether, POE stearyl ether and the like, and POE stearyl ether is particularly preferable.
• the average EO addition mole number of the POE alkyl ether is in the range of 5 to 8 moles. When the EO average added mole number is lower than 5 moles, the solubilizing ability is insufficient, so that the oil-soluble liquid component is separated in the preparation. Deterioration occurs and the feeling of use becomes inferior.
• POE alkyl ether commercially available products such as EMALEX 105, 107, 605, and 608 of Nippon Emulsion Co., Ltd. can be used.
• the POE hydrogenated castor oil one having an EO average added mole number of 10 to 60 can be used.
• an EO average addition mole number of 10 to 30 is particularly preferable
• an EO average addition mole number of 40 to 60 is particularly preferable. If the EO average added mole number is less than 10 moles, the solubilizing ability of the oil-soluble component is insufficient, and particularly when it is prepared as a toothpaste, rough skin at a low temperature may occur and the appearance may deteriorate.
• oil-soluble components such as vitamin E or its derivatives and bactericides, as well as oil-soluble active ingredients and fragrance ingredients may be inferior and the oil-soluble ingredients may be separated.
• oil-soluble components such as vitamin E or its derivatives and bactericides, as well as oil-soluble active ingredients and fragrance ingredients may be inferior and the oil-soluble ingredients may be separated.
• POE hydrogenated castor oil commercially available products such as NIKKOL HCO-10, HCO-20, HCO-30, HCO-40, HCO-50, and HCO-60 from Nikko Chemicals Co., Ltd. can be used. .
• alkyl glucoside an alkyl group having 10 to 14 carbon atoms, preferably 10 to 12 carbon atoms, is used. If the number of carbon atoms is less than 10, sufficient foaming properties cannot be obtained, and if it exceeds 14, a unique taste or oiliness is produced during use.
• commercially available products such as planter care 1200UP and planter care 2000UP manufactured by Cognis can be used.
• (C) As a component, you may mix
• a POE-cured castor having an alkyl group with 16 to 18 carbon atoms and an EO average addition mole number of 5 to 8 moles and an EO average addition mole number of 10 to 30 Oil is preferably used in a mass ratio of 3: 7 to 7: 3.
• a POE alkyl ether having an alkyl group with 16 to 18 carbon atoms and an EO addition mole number of 6 or less is used, a POE hydrogenated castor oil having an EO average addition mole number of 20 to 40 is used in combination.
• the total blending amount of the nonionic surfactant of component (C) is 0.5 to 5% of the total composition from the viewpoint of solubilizing ability of oil-soluble ingredients, expression of effects of oil-soluble ingredients, and usability. 0.5 to 3% is preferable. If the blending amount is less than 0.5%, sufficient oil-soluble component solubilizing ability cannot be obtained, and VE or its derivatives and nonionic fungicides are not sufficiently solubilized, resulting in insufficient storage stability. is there.
• the micelle due to component (C) becomes too rigid and the oil-soluble active ingredient taken into the micelle is not released into the oral cavity, so it is sufficient to prevent and improve periodontal disease and bad breath May not be obtained, or bitterness or irritation may occur and the preparation cannot be applied to the oral cavity for a long time.
• the blending amount is most preferably 1 to 3%.
• a nonionic fungicide or (E) a cationic fungicide is blended in the composition of the present invention as a fungicide.
• Nonionic fungicides include isopropylmethylphenol, triclosan, hinokitiol, phenol, etc., and one or more of these can be used.
• isopropylmethylphenol Phenol and triclosan are preferred.
• Commercially available non-ionic disinfectants can be used.
• Isopropylmethylphenol can be obtained from Osaka Kasei Co., Ltd. (trade name: isopropylmethylphenol), and triclosan can be obtained from Ciba Specialty Chemicals Co., Ltd. (trade name: Irgasan DP-300). Can do.
• the compounding amount of the nonionic fungicide is preferably 0.01 to 0.3%, particularly 0.02 to 0.1% of the whole composition from the viewpoint of periodontal disease prevention effect and usability. If the blending amount is less than 0.01%, the bactericidal effect is inferior, the periodontal disease and bad breath amelioration effect by sterilization is not sufficiently obtained, and even if the blending amount exceeds 0.3%, it is not solubilized and separated over time Or discoloration may occur, or bitterness may occur, resulting in poor usability.
• Cationic fungicides include quaternary ammonium compounds such as cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and decalinium chloride, bisguanides such as chlorhexidine gluconate and chlorhexidine hydrochloride, and alkyldiaminoethylglycine hydrochloride. 1 type or 2 types or more are used, and quaternary ammonium type and bisguanide type are particularly preferable in terms of bactericidal power and taste. Among them, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, gluconic acid Most preferred are chlorhexidine and chlorhexidine hydrochloride.
• cetylpyridinium chloride is Wako Pure Chemical Industries (trade name: cetylpyridinium chloride), benzethonium chloride is Lonza Japan (trade name: Hyamine 1622), and benzalkonium chloride is sweet potato chemistry.
• Sangyo Co., Ltd. (trade name: 10% benzalkonium chloride solution)
• Chlorhexidine Gluconate is Dainippon Sumitomo Pharma Co., Ltd. (trade name: Hibiten Gluconate Solution)
• Chlorhexidine Hydrochloride is Dainippon Sumitomo Pharma Co., Ltd. (trade name: 5% Hibiten) Liquid) or the like.
• the blending amount of the cationic fungicide is preferably 0.001 to 0.1%, particularly 0.01 to 0.05% of the whole composition from the viewpoint of periodontal disease prevention effect and feeling of use. If the blending amount is less than 0.001%, the bactericidal effect is inferior, the periodontal disease and bad breath improving effect due to sterilization cannot be sufficiently obtained, and if it exceeds 0.1%, bitterness etc. occurs and the feeling of use becomes worse, May cause discoloration.
• the total amount of (A) ascorbic acid phosphate or a salt thereof, (B) vitamin E or a derivative thereof, and (D) a nonionic bactericidal agent is effective for preventing periodontal diseases and appearance stability. From the viewpoint, it is 0.2 to 1.5% of the whole composition, and 0.2 to 1.0% is particularly preferable. If the total blending amount is less than 0.2%, the periodontal disease prevention effect is not sufficiently exhibited, and if it exceeds 1.5%, the component (A), (B) or (D) is separated over time or discoloration occurs. Arise.
• the blending ratio of the components (C), (B) and (D) is (C) / ((B) + (D) from the viewpoint of the periodontal disease prevention effect, the stability of the component (B) and the suppression of separation. )) Is a mass ratio of 8 to 20, particularly preferably 8 to 15. If the blending ratio is less than 8, the component (B) or the component (D) is not solubilized, resulting in insufficient storage stability or separation in the preparation, and if it exceeds 20, the micelle by the component (C) becomes too rigid, and the component (B) and component (D) incorporated in the micelle are not released into the oral cavity, and the periodontal disease prevention effect is not sufficiently exhibited.
• the total amount of (A) ascorbic acid phosphate or a salt thereof, (B) vitamin E or a derivative thereof, and (E) a cationic fungicide is a point of periodontal disease prevention effect and appearance stability. Therefore, it is 0.2 to 1.3% of the whole composition, and particularly preferably 0.2 to 1.0%. If the total blending amount is less than 0.2%, the periodontal disease prevention effect is not sufficiently exhibited, and if it exceeds 1.3%, the component (A), (B) or (E) is separated over time or discoloration occurs. Arise.
• the blending ratio of the components (C), (B) and (E) is (C) / ((B) + (E) in terms of periodontal disease prevention effect, stability of the component (B) and appearance stability. )) Is a mass ratio of 8 to 18, particularly preferably 8 to 15.
• the blending ratio is less than 8, the component (B) is not solubilized, so the storage stability becomes insufficient and separation occurs in the preparation.
• the micelle by the component (C) becomes too rigid.
• the components (B) and (E) incorporated in the micelles are not released into the oral cavity, and the effects derived from these components are not fully exhibited.
• the total content of the component (A), the component (B), and the component (D) or (E) is 0.2 to 1.0%, and (C) / ((B ) + ((D) or (E)) in the mass ratio of 8 to 15 is most effective because the effect of preventing or ameliorating periodontal disease is further improved and the storage stability with time is excellent.
• the oral composition of the present invention further contains one or more active ingredients selected from (F) glycyrrhetinic acid, ⁇ -aminocaproic acid, glycyrrhizinate, tranexamic acid, buckwheat extract and allantoins. It is preferable. By blending the component (F), the periodontal disease prevention / amelioration effect can be further improved, and as a result, the leaching of GCF associated with the periodontal disease can be further suppressed. Allantoins include allantoin, allantoinchlorohydroxyaluminum, and allantoindihydroxyaluminum (also known as aldioxa).
• the component may be a natural product or a synthetic product, and a commercially available product can be used.
• glycyrrhetinic acid is Maruzen Pharmaceutical Co. (trade name: glycyrrhetinic acid)
• ⁇ -aminocaproic acid is Daiichi Chemicals (trade name: epsilon-aminocaproic acid) and Ajinomoto Co. (trade name: epsilon-aminocaproic acid)
• Examples of glycyrrhizinate include dipotassium glycyrrhizinate Maruzen Pharmaceutical Co., Ltd.
• tranexamic acid is Daiichi Pharmatech (trade name: tranexamic acid)
• Awaku Extract is Oshiro Pharmaceutical Co., Ltd. (trade name: Awaku Extract) and Iwase Cosfa (trade name: Awaku Liquid E)
• Allantoin is DSM Nutrition Japan (trade name: Allantoin)
• Allantoin Chloroxyaluminum is Merck (trade name: RonaCare Alla toin (registered trademark)), allantoin dihydroxy aluminum Kawaken Fine Chemicals Co., Ltd. (trade name: ALDA) include those available from the like.
• the blending amount is preferably 0.01 to 0.5%, particularly 0.01 to 0.3% of the entire composition from the viewpoint of periodontal disease prevention effect and feeling of use. If the blending amount is less than 0.01%, the GCF amount increase inhibitory effect may not be satisfactorily exhibited and the periodontal disease prevention effect may not be sufficiently improved. It can happen.
• Dextranase can be further blended into the oral composition of the present invention.
• dextranase it becomes easy to decompose and remove plaque, which is one of the causes of periodontal diseases, and the effect of preventing and improving periodontal diseases can be further enhanced.
• Dextranase is an enzyme produced by the genus Ketomium, Penicillium, Aspergillus, Spicaria, Lactobacillus, Servibrio, etc., and has a plaque-degrading action. Dextranase can be obtained from Daiichi Sankyo Propharma Co., Ltd. (trade name: dextranase).
• the blending amount is preferably 2 to 200 units / g, particularly 10 to 50 units / g, from the viewpoint of plaque decomposition effect and formulation stability.
• One unit of dextranase is the amount of dextranase that produces a free reducing sugar corresponding to 1 ⁇ mol of glucose per minute when the reaction is carried out using dextran as a substrate.
• the blending amount is preferably 0.016 to 1.5%, particularly 0.08 to 0.38% of the total composition. If the blending amount is less than 2 units / g, the blending effect, for example, a sufficient plaque removing effect may not be obtained. If it exceeds 200 units / g, discoloration of the preparation may occur.
• Fluoride ion source can be further blended in the oral composition of the present invention.
• a fluoride ion supply source By compounding a fluoride ion supply source, it is possible to reinforce the tooth quality of the root part exposed as a result of gingival retraction due to periodontal disease, and to prevent or suppress the development or progression of root caries.
• the tooth root part is easily dissolved in acid, so it tends to be caries. However, in the case of healthy gingiva, the tooth root part is inside the gingiva, so it does not come into contact with acid and does not become caries. . However, if the gingiva retreats due to periodontal disease, the root of the tooth is exposed and dissolved by contact with acid, resulting in caries. This is called “root caries”.
• the tooth quality at the root portion is strengthened and hardly dissolved in the acid, and the development or progression of root caries can be prevented or suppressed.
• Fluorine ion supply sources include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, potassium monofluorophosphate, sodium silicon fluoride, calcium calcium fluoride, etc. It is done. These can use 1 type (s) or 2 or more types, However, Sodium fluoride and sodium monofluorophosphate are preferable especially in terms of taste.
• a commercially available fluorine ion supply source can be used, for example, sodium fluoride can be obtained from Stella Chemifa Corporation, and sodium monofluorophosphate can be obtained from Albright & Wilson Corporation.
• the blending amount is preferably 0.02 to 10.0%, particularly 0.05 to 1.5% of the entire composition from the viewpoint of root caries prevention effect and solubility.
• the blending amount of the fluoride ion source is less than 0.02%, a satisfactory blending effect may not be obtained, and if it exceeds 10.0%, solubilization in the preparation may be difficult.
• the composition for oral cavity of the present invention includes various kinds of toothpastes such as toothpaste, toothpaste, foam toothpaste, liquid toothpaste, liquid toothpaste, mouthwash, mouth freshener, oral pasta, gargle tablets, chewing gum and the like. And can be suitably prepared as a dentifrice or mouthwash.
• the composition for oral cavity can be blended with other known components in addition to the above components according to various dosage forms within a range not impairing the effects of the present invention, and can be prepared by a usual method. it can.
• abrasives As optional components that can be blended, abrasives, wetting agents, binders, solvents, surfactants other than the above component (C), further sweeteners, preservatives, various active ingredients, pH adjusters, if necessary, A coloring agent, a fragrance
• abrasive examples include silica-based abrasives such as silica gel, precipitated silica, aluminosilicate, zirconosilicate, and amorphous anhydrous silicic acid, dicalcium phosphate dihydrate, dibasic calcium phosphate anhydride, tricalcium phosphate, fourth Calcium phosphate, eighth calcium phosphate, calcium pyrophosphate, aluminum hydroxide, alumina, titanium dioxide, insoluble calcium metaphosphate, light calcium carbonate, heavy calcium carbonate, magnesium carbonate, tribasic magnesium phosphate, zeolite, polymethyl methacrylate, nylon powder, Examples thereof include silk powder, cellulose powder, and glucomannan.
• the blending amount of the abrasive is usually 0 to 50%, and 2 to 40% is particularly preferable in the dentifrice composition.
• wetting agent examples include sorbitol, glycerin, propylene glycol, polyethylene glycol having an average molecular weight of 200 to 6000, 1,3-butylene glycol, xylitol, erythritol, lactitol, palatinose, palatinit, trehalose and other sugar alcohols and polyhydric alcohols. (The amount is usually 0 to 50%, particularly 5 to 45%).
• Binders include xanthan gum, sodium polyacrylate, carrageenan, sodium alginate, propylene glycol alginate, carboxyvinyl polymer, tragacanth gum, guar gum, hydroxypropyl guar gum, tara gum, locust bean gum, karaya gum, quince seed gum, tamarind gum, carboxy Sodium methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, cellulose, gellan gum, gelatin, curdlan, gum arabic, agar, pectin, sodium caseinate, polyvinyl alcohol, polyvinylpyrrolidone, pullulan, thickening silica, beegum, smectite , Laponite, montmorillonite, bentona Doo and the like (the amount is usually 0-5%. Preferably from 0.1 to 5%).
• water As a solvent, water is generally used. When it contains water, the amount is usually 1 to 99%, and it is usually 1 to 50% in the dentifrice composition.
• a lower alcohol such as ethanol may be blended as a solvent, and the blending amount of the lower alcohol is preferably 0.1 to 30%.
• the total amount of the solvent is usually 0 to 99%.
• surfactant in addition to the surfactant of component (C), other nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants can be blended.
• POE polyoxypropylene copolymer sucrose fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE glycol fatty acid ester POE alkyl ether phosphate and its salt, POE alkyl ether sulfate, POE phytosterol and phytostanol, POE alkyl phenyl ether phosphate and its salt, POE lanolin and lanolin alcohol, POE alkylamine and fatty acid amide, POE alkylphenyl formaldehyde condensation Products, POE polyoxypropylene al
• anionic surfactants such as sodium and sodium dioctylsulfosuccinate
• cationic surfactants such as alkylammonium and alkylbenzylammonium salts
• amphoteric surfactants such as betaine acetate, imidazolinium betaine, and fatty acid amidopropyl betaine.
• the amount of these surfactants is usually 0 to 5%.
• nonionic surfactants other than the component (C) may not be added, and may be 0%.
• the amount of the surfactant as the optional component described above is preferably in the range where the total amount of the component (C) and the surfactant is 0.5 to 6%.
• Sweetening agents include saccharin sodium, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perilartin, thaumatin, sucralose, acesulfame potassium, aspartame and the like.
• preservative examples include parabens (paraoxybenzoic acid ester) such as methylparaben, butylparaben, and ethylparaben, benzoic acid and its salt, salicylic acid and its ester or salt, and the like.
• parabens paraoxybenzoic acid ester
• benzoic acid and its salt such as methylparaben, butylparaben, and ethylparaben
• salicylic acid and its ester or salt and the like.
• dextranase other than the fluoride ion source, for example, ascorbic acid and its derivatives, riboflavin, Vitamins such as pyridoxine hydrochloride, cyanocobalamin, ⁇ -carotene, ergocalciferol, menadione, ubiquinone, plant extracts such as auren, ougon, hamamelis, clove, chamomile, latania, myrrh, toki, rosemary, safflower, mutanase, lysozyme , Enzymes such as amylase, protease, lytic enzyme, superoxide dismutase, salts such as sodium chloride, potassium nitrate, sodium polyphosphate, carbonate, bicarbonate, sesquicarbonate, ⁇ -oryzanol, dihydrocholesterol, ⁇ -bisabolol, azulene
• pH adjusters examples include citric acid, malic acid, lactic acid, tartaric acid, succinic acid, acetic acid, phosphoric acid, pyrophosphoric acid, glycerophosphoric acid, various salts such as potassium salt, sodium salt and ammonium salt, sodium hydroxide, hydrochloric acid Etc. These can be blended singly or in combination of two or more so that the pH of the composition is in the range of 5-9 (the blending amount is usually 0-2%).
• Red No. 2 Red No. 3, Red No. 225, Red No. 226, Yellow No. 4, Yellow No. 5, Yellow No. 205, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 204, Green No. 3 and other legal dyes, safflower dyes, gardenia dyes, cochineal dyes, anato dyes, bengara, mica titanium, titanium oxide and the like.
• 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, iris concrete, absolute Natural fragrances such as peppermint, absolute rose, orange flower, and processed natural fragrances such as front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder fragrance, and the like, and Menthol, Carvone, Anethole, Cineol, Salicyl Methyl, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol
• flavor raw material can be used and it is not limited to the fragrance
• 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 a flavoring fragrance using the above fragrance material, it is preferable to use 0.1 to 2.0% in the preparation composition.
• composition for oral cavity of the present invention is applied to containers such as aluminum laminated tubes, glass-deposited plastic tubes, dispenser containers by mechanical or differential pressure, bottle containers such as polyethylene terephthalate and glass, and film packaging containers such as pillow packaging. Can be filled.
• the present invention will be specifically described using examples, comparative examples, and formulation examples, but the present invention is not limited to the following examples.
• the blending amount is mass%.
• materials that conform to cosmetic raw material standards or quasi-drug raw material standards were used.
• the composition of the fragrance is as shown in Tables 9-15.
• Ethylene oxide was abbreviated as EO
• polyoxyethylene was abbreviated as POE.
• Examples and comparative examples A composition comprising the common composition shown in Table 2 below and the components (A) to (C), (D) or (E), and further the component (F) in the types and amounts shown in Tables 3 to 8.
• the dentifrice composition was degassed and mixed using a kneader and prepared by a conventional method. The amount of the dentifrice composition charged was 5 kg.
• the obtained dentifrice composition was filled in a tube A made of the material described later and evaluated by the following method. The results are shown in Tables 3-8.
• Tube A From the outermost layer, LDPE55 / PET12 / LDPE20 / white LDPE60 / EMAA20 / AL10 / EMAA30 / LDPE20 / LLDPE30 (thickness 257 ⁇ m, diameter 26 mm, filling amount 50 g) A numerical value shows thickness (micrometer).
• LDPE Low density polyethylene
• White LDPE White low density polyethylene
• LLDPE Linear low density polyethylene
• AL Aluminum PET: Polyethylene terephthalate EMAA: Copolymer resin of ethylene / methacrylic acid
• a beagle dog (4 years old, female, 4 each group) was used for evaluation with bad breath and GCF amount as indicators. After the evaluation of halitosis and measurement of the amount of GCF before the start of the test, administration was performed twice a day for 1 month to evaluate halitosis and the amount of GCF. Administration of the test preparation was carried out by brushing the entire oral cavity of a beagle dog by taking 0.5 g of the test preparation in the case of a dentifrice and 0.5 mL in the case of a mouthwash. Details of the evaluation method are shown below.
• Improvement of bad breath derived from periodontal disease S1-S2 This average value was determined according to the criteria described below. It was judged that an oral composition having a degree of improvement in bad breath derived from periodontal disease was ⁇ or ⁇ was an oral composition having an effect of preventing or improving periodontal disease.
• GCF gingival crevicular fluid
• GCF change rate is calculated according to the following formula, the average value of 4 test sites of 4 beagle dogs is determined according to the criteria described later, periodontal disease with ⁇ , ⁇ oral composition as index of gingival crevicular fluid Judged to have a preventive effect.
• GCF change rate (%) ((GCF amount at start of test ⁇ GCF amount at end of test) / GCF amount at start of test) ⁇ 100
• Evaluation of storage stability of ascorbic acid phosphate or its salt over time The test sample was stored for 1 month in a thermostatic bath at 50 ° C. Thereafter, the sample was allowed to stand at room temperature and then used for evaluating the storage stability of ascorbic acid phosphate ester or a salt thereof. The residual rate was calculated from the initial value on the day of manufacture. All reagents were manufactured by Kanto Chemical.
• test preparation is a dentifrice
• 10 mmol / L phosphate buffer 1.5 mmol / L potassium dihydrogen phosphate, 23.5 mmol / L dipotassium hydrogen phosphate, pH 8.0
• Ascorbic acid phosphate ester or a salt thereof is extracted, and high performance liquid chromatography (pump: JASCO PU1580, autosampler: Shimadzu SIL-10A, UV detector: Shimadzu SPD-6A, recording device: Shimadzu
• the quantification was carried out by the absolute calibration curve method using Seisakusho C-R4A, column thermostat: JASCO CO-966).
• the column is a stainless steel tube having a diameter of about 4.6 mm and a length of about 150 mm, and a 5 ⁇ m liquid chromatograph.
• TSK-gel ODS-80Ts manufactured by Tosoh Corporation
• a column temperature of about 40 ° C.
• a detection wavelength of 240 nm and a flow rate of 0.8 mL / min.
• Residual rate of ascorbic acid phosphate or salt thereof (Evaluation sample value (%) / initial value (%)) ⁇ 100
• Residual rate of ascorbic acid phosphate or salt thereof ⁇ : 95% or more ⁇ : less than 95% ⁇ : less than 90% ⁇ : less than 80%
• test sample was stored for 1 month in a thermostatic bath at 50 ° C. After leaving this at room temperature, if the test preparation is a dentifrice or oral pasta, 10 g is taken and extracted with methanol, followed by liquid chromatography (pump: JASCO PU-980, autosampler: JASCO) AS-950, detector: JASCO UV-970, recording device: system instrument Chromatocoder 21J, column thermostatic chamber: JASCO CO-966).
• the measurement conditions were as follows: a stainless steel tube with an inner diameter of 4.6 mm and a length of 15 cm was filled with a 5 ⁇ m octadecylsilylated silica gel for liquid chromatography, methanol was used as the mobile phase, the column temperature was 25 ° C., and 1.0 mL / min. was measured by an absolute calibration curve method with an ultraviolet absorptiometry (measurement wavelength: 284 nm). In addition, in the case of a mouthwash, it diluted with methanol and measured on the same conditions. This result was determined according to the criteria described below, and it was determined that the storage stability of the vitamin E derivative was ensured for the oral compositions of A and B.
• Residual rate of vitamin E or its derivative (Evaluation sample value (%) / initial value (%)) ⁇ 100
• test preparation When the test preparation was a dentifrice, 40 mL of artificial saliva was added to 10 g of the composition and stirred, followed by centrifugation (10,000 rotations / minute, 10 minutes), and the resulting supernatant was used as a sample stock solution.
• test preparation When the test preparation was a mouthwash, 40 mL of artificial saliva was added to 10 g of the composition and diluted to obtain a sample stock solution. After 2 mL of the sample stock solution was allowed to act on 2 mL of the bacterial solution for 30 seconds, 50 ⁇ L was collected to obtain a sample solution for bactericidal evaluation.
• Bactericidal power evaluation is performed by adding a bactericidal power evaluation sample solution (50 ⁇ L) to a THB liquid medium (4 mL) and culturing (37 ° C., 8 hours), and then measuring the amount of grown bacteria using turbidity (OD660) as an index. Evaluations were made on the assumption that a smaller number gave a higher bactericidal activity.
• OD660 is less than 1 ⁇ : OD660 is 1 or more and less than 1.2 ⁇ : OD660 is 1.2 or more and less than 2 ⁇ : OD660 is 2 or more
• evaluation of appearance stability (separation, discoloration) over time: The test sample was stored for 1 month in a thermostatic bath at 50 ° C. Then, after leaving the sample to room temperature, it was used for evaluation of appearance stability.
• the test sample was a toothpaste
• the sample was extruded about 10 cm onto a straw half paper, and the presence or absence of separation and discoloration was observed and evaluated.
• the test sample was a mouthwash
• the container was allowed to stand for 1 day, and then the presence or absence of separation and discoloration was observed and evaluated.
• discoloration was evaluated on the basis of the thing which preserve
• the evaluation criteria are as follows.
• composition for oral cavity of the present invention is effective in suppressing bad breath derived from periodontal disease, periodontal disease preventive effect using GCF as an index, bactericidal activity, ascorbic acid phosphate ester or salt thereof And Vitamin E or its derivatives have excellent storage stability over time and appearance stability (no separation, no discoloration), high periodontal disease prevention or improvement effect, and excellent storage stability over time It has been found.
• composition for oral cavity of the present invention is effective in preventing bad breath derived from periodontal disease, periodontal disease preventive effect using GCF as an index, bactericidal activity, ascorbic acid phosphate ester or salt thereof And Vitamin E or its derivatives have excellent storage stability over time and appearance stability (no separation, no discoloration), high periodontal disease prevention or improvement effect, and excellent storage stability over time It has been found.
• composition for oral cavity of the present invention is a periodontal disease using GCF as an index by further blending glycyrrhetinic acid, ⁇ -aminocaproic acid, glycyrrhizinate, tranexamic acid, buckwheat extract or allantoins. It was found that the prevention / improvement effect is improved. Similar results were obtained when perfumes B to I were used in place of perfume A.

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• 2010
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