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
  • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
  • A61K8/24—Phosphorous; Compounds thereof
• • 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
  • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
  • A61K8/20—Halogens; Compounds thereof
  • A61K8/21—Fluorides; Derivatives thereof
• • 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
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
  • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
• • 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
  • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
  • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic 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
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only 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
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
  • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
• • 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
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
  • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
• • 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
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
  • A61K8/73—Polysaccharides
  • A61K8/731—Cellulose; Quaternized cellulose derivatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

• the present invention relates to an oral composition.
• dentin caries As the onset mechanism of dentin caries (root caries), first, plaque adheres to the dentin surface exposed in the oral cavity, and metabolism of sugar occurs by bacteria in the plaque and acid is produced. Dentin mineral components are eluted (decalcified) by the acid, and the organic (collagen) layer is exposed. Furthermore, the collagen layer is physically and chemically destroyed, and the root of the tooth is substantially lost.
• Patent Document 1 discloses dentin mineral elution using an oral composition containing hydrolyzed silk and light calcium carbonate having an average primary particle size of 0.04 to 0.5 ⁇ m as components. Inhibiting is described.
• Patent Document 2 discloses a dental remineralization accelerator comprising (a) a monomer having a hydroxyl group and (b) a monomer having a phosphorus atom-containing acidic group in an amount of 5 to 200% by weight based on the component (a). Is used to promote remineralization.
• Patent Document 3 uses an oral composition having (A) a zinc compound and (B) at least one selected from the group consisting of an aldehyde-based compound, a phenol-based compound, and a tea-extracted polyphenol compound. It describes the prevention of quality caries, especially root caries.
• Patent Document 4 discloses that collagen decomposition and decalcification are suppressed using a tooth root caries preventive agent comprising flavanones and / or glycosides thereof.
• dentin caries root caries
• the collagen layer becomes a scaffold for remineralization, and it consumes calcium ions and phosphate ions in saliva and crystals are exposed in the exposed collagen layer.
• the possibility of deposition is pointed out. Therefore, it can be said that the inhibition of degradation of the exposed collagen layer is essential for prevention of dentin caries.
• fluoride is mainly used, and fluoride sustained release / retention techniques such as a combined use technique with metal ions such as calcium (Patent Documents 5 to 7) have been disclosed. These may have a certain effect on enamel caries, but fluoride cannot sufficiently protect the exposed collagen layer during dentin caries (root caries). Collagen breaks down.
• Patent Documents 8 and 9 a tooth surface coating technique using phosphoric acid ester or polymer
• Patent Document 10 a tooth protection technique using aluminum, fluoride, and calcium
• Polyphenol can be coated on the exposed collagen layer.
• Polyphenol also has a function of reducing collagenase enzyme activity, and as a result, it is known as a substance that is expected to have an effect of inhibiting degradation of the exposed collagen layer.
• acid strengthening technology for tooth substance blended with tea polyphenol, fluoride and aluminum salt (Patent Document 11), and a combination of longan seed extract, fluoride and sugar alcohol (Patent Document 12) or Hesperidin (Patent Document)
• Patent Document 11 acid strengthening technology for tooth substance blended with tea polyphenol, fluoride and aluminum salt
• Patent Document 12 a combination of longan seed extract, fluoride and sugar alcohol
• Hesperidin Patent Document
• polyphenols have the disadvantage of easily causing discoloration and turbidity due to oxidation, pH change, complex formation, etc., so it is difficult to maintain stability in dosage forms such as dentifrices and mouthwashes. .
• problems such as reduced efficacy after storage of the preparation and unnecessary coloring of the exposed collagen layer after application of the preparation. Therefore, the development of an active ingredient that can suppress the degradation of collagen exposed to dentin even after storage of the preparation, prevents coloring of the exposed collagen layer, and exhibits high preparation stability when prepared as a preparation. Is desired.
• dentifrices To prevent and improve (relieve) dentin hypersensitivity with oral hygiene products such as dentifrices, methods such as blocking dentinal tubules with aluminum lactate, etc., and reducing pain by blunting nerves with potassium nitrate, etc. Can be mentioned.
• Aluminum lactate is known to have an action of blocking the opening of the dentinal tubule and improving the sensitivity of the dentinal perception (Patent Document 14). However, it takes time until the effect of aluminum lactate is obtained, and there is a drawback that it lacks immediate effect. The expression of the peculiarity of aluminum lactate and the appearance of metallic taste has also been a problem.
• potassium nitrate has been adopted in large numbers as a nerve blunt component (Patent Document 15), it has an immediate effect, but its effect is hardly sustained. In other words, the effect of potassium nitrate is limited. Potassium nitrate has a strong bitter taste and may be uncomfortable to use.
• Teeth colored stains are called stains or stained pellicles, and are colored by coloring polyphenols (tannin, chlorogenic acid, etc.), metal ions, tobacco tar, etc. derived from foods and drinks on pellicles where saliva proteins are adsorbed on the tooth surface. It is considered. Of these, the most frequently observed stain is called brown stain, which is said to involve polyphenol compounds in food and drink such as tannin and chlorogenic acid.
• a liquid oral composition containing polyphosphoric acid or a salt thereof and an acyl taurine salt and exhibiting a predetermined pH Patent Document 20
• A polyphosphoric acid or a salt thereof
• B a specific disaccharide
• C It has been proposed that a liquid oral composition (patent document 21) containing malic acid, tartaric acid and salts thereof has an effect of preventing tooth coloring.
• the stain is to be removed by the mechanical action of the abrasive, there is a concern that the tooth may be damaged due to excessive brushing, or the stain may remain at a portion where the brush tip does not reach.
• dentin caries root caries
• dentin hypersensitivity As described above, suppression of dentin caries (root caries), suppression and improvement of dentin hypersensitivity, and suppression and removal of stains have been studied by various conventional methods. Accordingly, the present situation is that it is desired to provide new means capable of appropriately suppressing and improving dentin caries (root caries) and dentin hypersensitivity, and suppressing and removing stains.
• dentin caries (root caries) and dentine hypersensitivity continue to increase with the aging of the population, and their suppression and improvement are urgent.
• pyrrolidone carboxylic acid and / or a salt thereof is known as a component of a gelled topical composition that is applied to the skin, scalp, hair, nails and / or mucous membrane for cosmetic treatment (Patent Document 22).
• Patent Document 22 pyrrolidone carboxylic acid and / or a salt thereof is known as a component of a gelled topical composition that is applied to the skin, scalp, hair, nails and / or mucous membrane for cosmetic treatment.
• Patent Document 22 pyrrolidone carboxylic acid and / or a salt thereof
• An object of the present invention is to provide an agent that exhibits various functions such as suppression of dentin caries, suppression or improvement of dentin hypersensitivity, suppression or removal of stain formation, or an oral composition.
• various functions such as suppression of dentin caries, suppression or improvement of dentin hypersensitivity, suppression or removal of stain formation, or an oral composition.
• the following four are mentioned as the object of the present invention.
• the first object of the present invention is to provide an oral composition having a dentin caries inhibitory effect, a dentin hypersensitivity inhibitory or improving effect, and a stain inhibitory or removing effect.
• the second object of the present invention is to provide a composition for oral cavity that remarkably suppresses degradation and coloring of the exposed collagen layer and exhibits high formulation stability when it is prepared.
• a third object of the present invention is to provide a composition for oral cavity that remarkably reduces pain due to hypersensitivity and has a good feeling of use (taste).
• the opening of dentinal tubules can be sealed early (early dentinal tubule sealing effect), and the pain felt by the patient can be reduced (pain reducing effect). It is to provide an oral composition having no or almost no expression (good feeling of use (taste)).
• the fourth object of the present invention is to provide a composition for oral cavity useful for tooth whitening, which has both a stain removal effect and a stain formation inhibitory effect, has a gloss effect, and is excellent in preparation feeling. That is.
• a fifth object of the present invention is to provide an oral composition that can suppress collagen coloring.
• Component (A) An oral composition containing a lactam compound having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton and having an acidic group.
• Component (A) An oral composition containing a lactam compound having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton and having an acidic group.
• the composition for oral cavity according to the above [1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof [3]
• the content of the component (A) is 0.3 to 10% by mass
• Component (1-B) The composition for oral cavity according to the above [1] or [2], which further contains a fluorine compound.
• Component (B) is at least one selected from sodium fluoride and sodium monofluorophosphate.
• Component (1-C) The oral cavity according to any one of the above [4] to [6], further comprising a protein containing 1.0 to 6.0% by mass of a sulfur-containing amino acid residue Composition.
• Component (2-B) The composition for oral cavity according to the above [1] or [2], further comprising one or more polyphenol compounds selected from the group consisting of longan seed extract, proanthocyanidins, catechins and hesperidins .
• Component (3-B) The composition for oral cavity according to the above [1] or [2], which further contains aluminum lactate.
• Component (3-C) The composition for oral cavity according to the above [10], further containing a monofluorophosphate.
• Component (3-D) The composition for oral cavity according to [10] or [11], further containing an inorganic water-soluble potassium salt.
• Component (4-B) The composition for oral cavity according to [1] or [2], further containing an inorganic water-soluble potassium salt.
• Component (4-C) The composition for oral cavity according to the above [13], further containing a water-soluble fluorine compound.
• Component (5-B) The composition for oral cavity according to the above [1] or [2], further containing cationized cellulose.
• Component (A) A collagen degradation inhibitor comprising as an active ingredient a lactam compound having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton and having an acidic group.
• Component (A) Dentin hypersensitivity comprising as an active ingredient a lactam compound having an acid group and having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton. Inhibitor or improver.
• the inventors of the present invention obtain an oral composition that is superior to conventional oral compositions in inhibiting collagen degradation, inhibiting collagen coloration, inhibiting or improving dentin hypersensitivity, and removing stains.
• a lactam compound having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton and having an acidic group typified by pyrrolidonecarboxylic acid and / or a salt thereof. It has been found that the composition for oral cavity contains excellent effects of inhibiting collagen degradation, inhibiting collagen coloring, inhibiting or improving dentin hypersensitivity, and removing stains.
• the present invention provides the following oral compositions [0-1] to [0-4].
• Component (A) An oral composition comprising a lactam compound having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton and having an acidic group.
• [0-2] The composition for oral cavity according to [0-1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
• [0-3] The composition for oral cavity according to the above [0-1] or [0-2], wherein the content of the component (A) is 0.3 to 10% by mass.
• [0-4] The composition for oral cavity according to any one of the above [0-1] to [0-3], which is for a person with hypersensitivity to dentin.
• composition for oral cavity (1) The inventors of the present invention have made extensive studies in order to obtain an oral composition superior in dentin caries prevention effect as compared with conventional oral compositions.
• a lactam compound having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton and having an acidic group represented by pyrrolidonecarboxylic acid and / or a salt thereof.
• a fluorine compound were simultaneously used as ingredients to prepare an oral composition.
• This oral composition was used for a carious sample, and its dentin caries inhibitory effect was evaluated by applying Transverse Microradiography (hereinafter abbreviated as TMR method).
• the TMR method is a technique for measuring the demineralization depth and the amount of mineral loss by obtaining a tooth mineral amount profile by luminance equivalent conversion according to the aluminum thickness using a microradiograph of the tooth flake cross section, As a method for measuring the degree of caries, this is a method for which reliability is officially recognized.
• the present invention provides the following oral composition (1).
• Component (A) A lactam compound having at least one lactam skeleton selected from the group consisting of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, or an ⁇ -lactam skeleton, and having an acidic group, or a salt thereof
• (1-B) component a fluorine compound.
• Component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
• (1-B) component is at least one selected from sodium fluoride and sodium monofluorophosphate.
• [1-6] The composition for oral cavity according to [1-5] above, wherein the (1-C) component is casein.
• composition for oral cavity (2) As a result of intensive studies to achieve the above object, the present inventor has found that the combination of a predetermined polyphenol compound and a predetermined lactam compound suppresses the degradation of the exposed collagen layer as compared with the case where each is used alone (dentin) It was found that the effect of inhibiting collagen degradation) and the effect persisted after storage of the preparation (inhibition effect of dentin collagen degradation after storage).
• the lactam compound suppresses the discoloration of the preparation itself after storage of the preparation with the polyphenol compound, has no problem with the shape retention (preparation stability), and suppresses coloring of the dentin with polyphenol for a long period of time ( The effect of inhibiting dentin collagen coloring after storage was also found. In this way, the present invention has been made.
• the present invention provides the following oral composition (2).
• Component (A) a compound having at least one lactam skeleton selected from the group consisting of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton, and having an acidic group, or a salt thereof;
• (2-B) component An oral composition containing one or more polyphenol compounds selected from the group consisting of longan seed extract, proanthocyanidins, catechins and hesperidins.
• component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
• composition for oral cavity (3) The present invention provides the following oral composition (3).
• Component (A) a compound having at least one lactam skeleton selected from the group consisting of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton and an ⁇ -lactam skeleton, and having an acidic group, or a salt thereof;
• (3-B) Component: An oral composition containing aluminum lactate.
• Component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
• Component (3-C) The composition for oral cavity according to the above [3-1] or [3-2], which further contains a monofluorophosphate.
• Component (3-D) The composition for oral cavity according to any one of [3-1] to [3-3], further containing an inorganic water-soluble potassium salt.
• [3-5] The composition for oral cavity according to any one of the above [3-1] to [3-4], which is for a person with hypersensitivity to dentin.
• composition for oral cavity (4) The present inventors have found that oral compositions containing a combination of a specific lactam compound having an acidic group or a salt thereof and an inorganic water-soluble potassium salt significantly reduce pain due to hypersensitivity, and have good use. It has been found that it has a feeling (taste).
• the present invention provides the following oral composition (4).
• (4-B) component An oral composition containing an inorganic water-soluble potassium salt.
• the component (A) is selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, and salts thereof
• the composition for oral cavity according to the above [4-1] which is the above compound.
• [4-4] The composition for oral cavity according to any one of the above [4-1] to [4-3], which is for a person with hypersensitivity to dentin.
• composition for oral cavity (5) The present invention provides the following oral composition (5).
• Oral composition (6) The present invention provides the following oral composition (6).
• (6-B) component Oral composition containing polyphenol compound.
• composition (A) Collagen coloring suppression containing a lactam compound having an acid group and having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton.
• Agent [7-2] Component (A): Inhibition of collagen degradation containing a lactam compound having an acid group and having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, or an ⁇ -lactam skeleton. Agent.
• Component (A) A dentinal tubule blockade containing a lactam compound having an acid group and having a lactam skeleton of any one of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton, and an ⁇ -lactam skeleton.
• Agent [7-4]
• Component (A) Stain remover having as an active ingredient a lactam compound having any lactam skeleton of ⁇ -lactam skeleton, ⁇ -lactam skeleton, or ⁇ -lactam skeleton and having an acidic group .
• Component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
• oral compositions and agents useful for suppressing dentine caries, suppressing or improving dentin hypersensitivity, and suppressing or removing stain formation are provided.
• an oral composition (1) which is excellent in dentine caries inhibitory effect and excellent in formulation stability.
• the composition for oral cavity (1) is composed of components that can be absorbed into the body. Therefore, the oral composition (1) provides an excellent dentine caries prevention effect in simple forms such as quasi-drugs such as dentifrices and mouthwashes, and foods such as gums, candy and tablet confections. can do.
• an oral composition (2) capable of remarkably suppressing the degradation of the exposed collagen layer. The effect can be maintained after storage of the formulation.
• the composition for oral cavity (2) can also suppress coloring to exposed collagen and discoloration and turbidity in the preparation caused by the polyphenol compound after storage of the preparation.
• oral compositions (3) and (4) that remarkably reduce pain due to hypersensitivity and have a good feeling of use (taste).
• the composition for oral cavity (3) is further excellent in dentinal tubule sealing effect.
• the oral compositions (3) and (4) are useful for suppressing or improving (relaxing) dentin hypersensitivity.
• an oral composition (5) capable of exhibiting a stain removal effect, a stain formation inhibitory effect, a gloss effect, and an excellent feeling in use of the preparation.
• an oral composition (6) that exhibits an effect of inhibiting collagen coloring.
• a collagen coloring inhibitor a collagen degradation inhibitor, a dentinal tubule blocker, a hypersensitivity inhibitor or ameliorating agent, and a stain remover, which comprise the component (A) as an active ingredient.
• the component (A) in the present invention is a compound having at least one lactam skeleton selected from the group consisting of a ⁇ -lactam skeleton, a ⁇ -lactam skeleton and an ⁇ -lactam skeleton, and having an acidic group (hereinafter referred to as a lactam compound). And / or a salt thereof.
• the lactam compound or a salt thereof is not particularly limited as long as it is a lactam compound or a salt thereof having any one of the above three specific lactam skeletons and having an acidic group.
• the molecule may have two or more lactam skeletons, may have two or more acidic groups, or have two or more lactam skeletons and two or more acidic groups. May be.
• the lactam skeleton is a ⁇ -lactam skeleton.
• Examples of the acidic group possessed by the lactam compound or a salt thereof include a phenolic hydroxyl group, a carboxyl group, and a sulfonic acid group. Of these, a carboxyl group is preferred as the acidic group.
• lactam compound having a ⁇ -lactam skeleton and having an acidic group examples include pyrrolidone carboxylic acid, 4- (3-hydroxyphenyl) -4-Aza-tricyclo (5.2.1.0 (2, 6 )) Dec-8-ene-3,5-dione, 2- (3,5-dioxo-4-Aza-tricyclo (5.2.1.0 (2,6)) Dec-8-ene-4- yl) benzoic acid and salts thereof, pyrrolidone carboxylic acid and salts thereof are preferred.
• lactam compound having a ⁇ -lactam skeleton and an acidic group examples include 6-oxo-2-piperidinecarboxylic acid, 4- (2-oxo-1-piperidinyl) butanoic acid, 1-ethyl-6- Examples include oxo-3-piperidinecarboxylic acid and salts thereof, and 6-oxo-2-piperidinecarboxylic acid is preferable.
• lactam compounds having an ⁇ -lactam skeleton and an acidic group examples include 3- (2-oxo-1-azepanyl) propanoic acid, 3- (2-bromo-5-hydroxyphenyl) -1-methyl Examples include -2-azepanone and salts thereof, and 3- (2-oxo-1-azepanyl) propanoic acid is preferable.
• the salt of the lactam compound is not particularly limited as long as it is a pharmacologically acceptable salt.
• pharmacologically acceptable salts include acid addition salts, base addition salts, and amino acid salts. Specific examples thereof include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, hydroiodide, nitrate, phosphate; citrate, oxalate, acetate, formate, propion Acid salt, benzoate salt, trifluoroacetate salt, maleate salt, tartrate salt, methanesulfonate salt, benzenesulfonate salt, paratoluenesulfonate salt, etc .; sodium salt, potassium salt, calcium salt, magnesium Inorganic base salts such as salts and ammonium salts; organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt and diisopropylammonium salt; and amino acid salts such as arg
• the lactam compound is preferably pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, or 3- (2-oxo-1-azepanyl) propanoic acid, and more preferably pyrrolidone carboxylic acid or a salt thereof.
• Lactam compounds and salts thereof can be synthesized according to known schemes. Commercial products may be used for the lactam compound and its salt.
• lactam compounds having a ⁇ -lactam skeleton examples include “AJIDEW A-100 (registered trademark)” sold by Ajinomoto Co., Inc.
• the kind of the lactam compound as the component (A) in the composition of the present invention may be a single kind or a combination of two or more kinds.
• the component (1-B) in the present invention is a fluorine compound.
• the fluorine compound include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, potassium monofluorophosphate, sodium silicon fluoride, and calcium calcium fluoride. It is done.
• Preferred fluorine compounds are sodium fluoride and sodium monofluorophosphate.
• Fluorine compound may be a commercially available product.
• sodium fluoride “sodium fluoride” marketed by Stella Chemifa Corporation can be mentioned.
• sodium monofluorophosphate sodium monofluorophosphate marketed by Rhodia Nikka Co., Ltd. can be mentioned.
• the component (1-C) in the present invention is a protein containing 1.0 to 6.0% by mass of sulfur-containing amino acid residues.
• a sulfur-containing amino acid residue means a residue obtained by removing one or more hydrogens from a sulfur-containing amino acid.
• the sulfur-containing amino acid is an amino acid containing sulfur, and examples thereof include methionine and cysteine.
• the (1-C) component preferably contains a phosphate group.
• the number average molecular weight of the protein is preferably 1,000 to 100,000, more preferably 10,000 to 100,000.
• affinity with dentin can be maintained, it is difficult to be washed away by saliva, and sufficient dentin caries inhibitory effect can be exhibited.
• the number average molecular weight is 100,000 or less, the adsorptivity to the teeth can be maintained, and the effect of suppressing dentine caries can be sufficiently obtained.
• the method for measuring the number average molecular weight of the protein is as follows.
• Examples of the method for calculating the number average molecular weight generally include a method of calculating using gel filtration chromatography (GPC) and a method of calculating by analysis nitrogen value calculation.
• GPC gel filtration chromatography
• the latter method is often used to calculate the number average molecular weight of proteins and polypeptide compounds.
• the number average molecular weight of the (1-C) component protein can also be measured by the latter method.
• the number average molecular weight of the component (1-C) can be calculated by, for example, the following formula (1-1) based on the total nitrogen amount in the molecule, the amino nitrogen amount, and the average molecular weight of the constituent amino acids.
• the average molecular weight of the constituent amino acids is calculated by multiplying the abundance ratio (%) of the constituent amino acids determined by ordinary amino acid analysis and the molecular weight of each amino acid.
• the total nitrogen amount can be measured by the first nitrogen determination method of the cosmetic raw material standard general test method or by gas chromatography (GC).
• the amount of amino nitrogen can be measured by a formol titration method.
• Examples of the “protein containing 1.0 to 6.0% by mass of sulfur-containing amino acid residues and having an average molecular weight of 1,000 to 100,000” include lactoferrin, collagen degradation products, and casein.
• Lactoferrin is an iron-binding glycoprotein with a molecular weight of about 80,000 that is widely distributed in the body of animals.
• the origin and production method of lactoferrin are not limited.
• colostrum, transitional milk, regular milk, end milk, etc. of mammals eg, humans, cows, sheep, goats, horses, etc.
• processed products of these milks eg, skim milk, whey, etc.
• lactoferrin separated by ion exchange chromatography or the like Lactoferrin prepared by a known method may be used.
• lactoferrin bovine-derived lactoferrin is preferably used.
• lactoferrin Commercial products may be used as lactoferrin.
• examples of commercial products of bovine derived lactoferrin include “Lactoferrin (derived from milk) (trade name)” sold by Wako Pure Chemical Industries, Ltd., “MLF-1” “ MLF-EX ”and“ Lactoferrin ”available from Nippon Shinyaku Co., Ltd.
• the (1-C) component one type of lactoferrin may be used, or two or more types of lactoferrin having different origins or separation conditions may be used in combination.
• collagen degradation products examples include collagen degradation products produced from pork skin and collagen degradation products produced from fish scales, of which collagen degradation products produced from fish scales are preferred.
• one type of collagen degradation product may be used, or a combination of two or more types of collagen degradation products having different raw materials may be used.
• a commercially available product may be used as the collagen degradation product.
• a trade name “HACP-U2” sold by Zeiras Co., Ltd. may be mentioned.
• Casein is contained in dairy products such as milk and cheese, and occupies about 80% by mass of milk protein contained in milk.
• Casein is a protein containing a phosphate group, that is, a type of phosphoprotein (phosphorylated protein). Phosphoric acid is bound to many serine residues constituting casein.
• one type of collagen degradation product may be used, or a combination of two or more types of collagen degradation products having different raw materials may be used.
• a commercially available product may be used as casein.
• casein derived from milk
• trade name “casein (derived from milk)” sold by Wako Pure Chemical Industries, Ltd. may be mentioned.
• the content of the sulfur-containing amino acid residue of the protein in the (1-C) component is 1.0 to 6.0% by mass per mass of the protein.
• the content of the sulfur-containing amino acid residue is 1.0% or more, the affinity with dentin can be improved and the effect of inhibiting dentin caries can be sufficiently obtained.
• the (1-C) component does not become so bulky as to cause a steric hindrance with other components, and the dentin is obtained.
• the (1-C) component or other components of the present invention can be effectively prevented from lowering the adsorptivity, and the effect of suppressing dentine caries can be sufficiently obtained.
• the component (2-B) is one or more polyphenol compounds selected from the group consisting of longan seed extract, proanthocyanidins, catechins and hesperidins.
• Longan (Euphoria longana) is a plant belonging to the family Mucaceae grown in tropical America and Southeast Asia. Longan pulp is used as a traditional Chinese medicine for tonic and sedation. Longan is sometimes called Longan.
• Longan seed extract is an extract extracted from longan seeds.
• Longan seed extract contains polyphenol (Japanese Patent Application Laid-Open No. 2003-327596, The effect of Longan seeded polyphenols on collective carcinoma cells. Eur J Clin Invest. and quantification of polyphenolic compounds in Longan (Euphoria longana Lam.) fruit. J Agric Food Chem. (2005, 53 (5), p1387-1392).
• the extraction method of longan seed extract from longan seeds is not particularly limited.
• Examples of the extraction method include a method of crushing longan seeds and solvent extraction using a known extraction method.
• the solvent water, monohydric alcohol, polyhydric alcohol, a mixture thereof and the like can be usually used.
• Examples of the solvent include water, lower monohydric alcohols such as methanol, ethanol and isopropanol, ethylene glycol, and polyethylene.
• polyhydric alcohols such as glycol, propylene glycol, polypropylene glycol, and 1,3-butylene glycol. These can be used alone or in combination of two or more.
• a solvent extract may be used as it is, or a concentrate obtained by distilling off the solvent and concentrating may be used. You may use the powder obtained by removing a solvent by drying (example: freeze-drying etc.) a solvent extract or a concentrate. Further, an excipient or the like may be added. A powder obtained by re-dissolving a solvent extract such as a lyophilized product in a solvent and adjusting the concentration appropriately may be used. In addition, the yield at the time of extracting longan seed extract is not specifically limited.
• a commercially available product may be used as longan seed extract.
• Examples of commercially available products include Agetect manufactured by Katakura Chikkarin Co., Ltd. and Longan Seed Extract Powder SD manufactured by the same company.
• Agetect is extracted from a longan seed pulverized product, concentrated and lyophilized, and then dissolved in 1,3-butylene glycol and water so that the extract concentration is 1.0%. (Longan seed extract concentration in Agetect is 1.0%).
• Longan seed extract powder SD is a powdery extract prepared by adding dextrin as an excipient to powder obtained by extraction and freeze-drying in the same manner as above (in Longan seed extract powder SD) Longan seed extract concentration of 83%).
• Proanthocyanidins are a kind of polyphenol having a structure in which a plurality of catechin skeletons are bonded.
• the origin of proanthocyanidins is not particularly limited, and may be derived from plants (for example, fruits, wheat, beans, etc.), or may be artificial synthetic products. Among these, proanthocyanidins derived from plants are preferable, and proanthocyanidins derived from grape seeds are preferable. This is because grape seeds are rich in proanthocyanidins.
• the method for extracting proanthocyanidins from grape seeds is not particularly limited.
• the extraction method include a method of crushing grape seeds and solvent extraction using a known extraction method.
• the solvent usually include water, monohydric alcohol, polyhydric alcohol, or a mixture thereof.
• water, lower monohydric alcohol such as methanol, ethanol, isopropanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene And polyhydric alcohols such as glycol and 1,3-butylene glycol. These can be used alone or in combination of two or more.
• the solvent extract can be used as it is, but a concentrate obtained by distilling off the solvent and concentrating may be used. Powder obtained by removing the solvent by drying (eg, freeze-drying, etc.) the solvent extract or concentrate may be used, and an excipient or the like may be further added. And you may use what re-dissolved powder, such as a lyophilized product, in the solvent, and adjusted it to the density
• the yield at the time of extracting proanthocyanidins is not specifically limited.
• Gravinol-SL manufactured by Kikkoman Corp.
• Gravinol-N manufactured by the same company, or the like can be used.
• Gravinol-SL is an extract and purified product of grape seeds, and is a brown powder whose main component is proanthocyanidins (the concentration of proanthocyanidins in gravinol-SL is 82%).
• Gravinol-N is also a grape seed extract and purified, and is a light brown powder (the concentration of proanthocyanidins in Gravinol-N is 38%).
• Catechin is a general term for a kind of flavonoid (C 15 H 14 O 6 ) and its derivatives.
• Examples of catechin include catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, gallocatechin gallate, epigallocatechin gallate and the like.
• catechin may be one of these, or two or more.
• the origin of catechin is not particularly limited, and may be derived from a plant (for example, tea) or an artificial synthetic product. Among these, catechins derived from plants are preferable, catechins derived from tea are more preferable, and catechins derived from tea leaves are more preferable. This is because tea leaves are rich in catechins.
• the method for extracting catechins from tea leaves is not particularly limited.
• the solvent usually include water, monohydric alcohol, polyhydric alcohol, or a mixture thereof.
• water, lower monohydric alcohol such as methanol, ethanol, isopropanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene
• polyhydric alcohols such as glycol and 1,3-butylene glycol, and these can be used singly or in combination of two or more.
• a solvent extract can be used as it is, but a concentrate obtained by distilling off the solvent and concentrating may be used. Powder obtained by removing the solvent by drying (eg, freeze-drying, etc.) the solvent extract or concentrate may be used, and an excipient or the like may be further added. And what lyophilized
• the yield at the time of extracting catechin is not specifically limited.
• catechin a commercially available product may be used.
• Sanphenon EGCG Sunphenon 90S manufactured by Taiyo Kagaku Co., Ltd. can be used.
• Sanphenone EGCG is an extraction product of green tea and is a white to light gray powder containing epigallocatechin gallate with high purity (the concentration of epigallocatechin gallate in sunphenone EGCG is 95%).
• Sunphenon 90S is also a green tea extraction and refined product, and is a pale yellow to reddish brown powder (the concentration of catechin in sunphenone 90S (total concentration of various catechins) is 70%).
• Hesperidin is a polyphenol also called vitamin P.
• the origin of hesperidin is not particularly limited, and it may be derived from a plant (for example, citrus fruits such as Wenzhou mandarin orange or Hassaku) or an artificial synthetic product. Among them, hesperidin derived from plants is preferable, hesperidin derived from citrus is preferable, and hesperidin derived from citrus peel is more preferable. This is because citrus peels are rich in hesperidin.
• the method for extracting hesperidin from pericarp is not particularly limited.
• the solvent usually include water, monohydric alcohol, polyhydric alcohol, or a mixture thereof.
• water, lower monohydric alcohol such as methanol, ethanol, isopropanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene
• polyhydric alcohols such as glycol and 1,3-butylene glycol, and these can be used alone or in combination of two or more.
• the solvent extract can be used in the form of a solution as it is, but it is also possible to use a solvent obtained by distilling off the solvent and concentrating to an appropriate concentration. These may be freeze-dried or the like, and may be used in the form of a powder obtained by removing the solvent, or may be used as it is or after adding an excipient or the like. A powdery product such as a freeze-dried product may be used by re-dissolving in a solvent and adjusting the concentration appropriately.
• the yield when extracting hesperidin is not particularly limited.
• hesperidin manufactured by Wako Pure Chemical Industries, Ltd., methyl hesperidin manufactured by Tokyo Chemical Industry, etc. can be used. Hesperidin is extracted and purified from the crushed peel and is a yellow powder (hesperidin concentration is 92%). Methyl hesperidin is obtained by methylating hesperidin with dimethyl sulfate and making it soluble in water, and is a light yellow to red yellow powder (methyl hesperidin concentration is 90%).
• one or more longan seed extracts, one or more proanthocyanidins, one or more catechins, or one or more hesperidins may be used, or a plurality of these may be used in appropriate combination.
• longan seed extract and / or proanthocyanidins are preferably used, and more preferably longan seed extract is used.
• the component (3-B) in the present invention is aluminum lactate.
• component (3-B) Commercially available products may be used as the component (3-B).
• aluminum lactate manufactured by Wako Pure Chemical Industries, Ltd. may be mentioned.
• the oral composition (3) contains the component (A) together with the component (3-B). Ogumi and metallic taste are prevented from being generated, and the feeling of use (taste) can be improved.
• the (3-C) component is a monofluorophosphate.
• the monofluorophosphate only needs to be able to supply monofluorophosphate ions, and water-soluble monofluorophosphate is preferable.
• the monofluorophosphate include alkali metal salts of monofluorophosphoric acid, alkaline earth metal salts of monofluorophosphoric acid, ammonium salts of monofluorophosphoric acid, etc. Among them, sodium monofluorophosphate, monofluorophosphate, etc. Potassium phosphate, ammonium monofluorophosphate and the like are preferable, and sodium monofluorophosphate is more preferable.
• (3-C) Commercially available products may be used.
• monofluorophosphate “sodium monofluorophosphate” marketed by Rhodia Nikka Co., Ltd. may be mentioned.
• the (3-C) component may be a single monofluorophosphate or a combination of two or more monofluorophosphates.
• the total amount of fluorine contained in the oral composition (3) is preferably 0.01% by mass (100 ppm) or more, and 0.02% by mass (200 ppm) with respect to the total amount of the oral composition (3). More preferably.
• the upper limit is preferably 1% by mass (10000 ppm) or less, and more preferably 0.5% by mass (5000 ppm) or less.
• the amount of fluorine contained in the composition for oral cavity (3) of the present invention is preferably 0.01 to 1% by mass (100 to 10000 ppm), more preferably 0.02 to 0.5% by mass (200 to 5000 ppm).
• the (3-D) component and the (4-B) component are inorganic water-soluble potassium salts.
• inorganic water-soluble potassium salt refers to an inorganic potassium salt that can be dissolved in 2 g or more in 100 g of water at 20 ° C.
• Examples of the inorganic water-soluble potassium salt include potassium nitrate, potassium chloride, potassium dihydrogen phosphate, potassium sulfate, potassium carbonate, potassium hydrogen carbonate, and alum.
• potassium nitrate and potassium chloride are preferable from the viewpoint of a remarkable alleviating effect on pain due to hypersensitivity and a feeling of use (taste).
• These inorganic water-soluble potassium salts may use commercially available reagents (available from suppliers such as Wako Pure Chemical Industries, Ltd.).
• Each of the (3-D) component and the (4-B) component may be a single type or a combination of two or more types.
• the component (4-B) has a problem that the effect of reducing the pain due to hypersensitivity is limited, resulting in a bitter taste and poor usability (taste).
• potassium nitrate has a certain effect in reducing pain due to hypersensitivity, but has a strong bitter taste and a poor feeling of use (taste).
• the effect of reducing pain due to hypersensitivity of the component (4-B) is significantly improved, 4-B)
• the bitterness derived from the component is suppressed, and even when potassium nitrate is used, a good feeling of use (taste) has been achieved.
• the (4-C) component is a water-soluble fluorine compound.
• the “water-soluble fluorine compound” refers to a fluorine compound that can be dissolved in 2 g or more in 100 g of water at 20 ° C.
• the water-soluble fluorine compound is a well-known component that has been conventionally used in oral compositions as a source of fluoride ions having tooth remineralization action. It has been found that a functional fluorine compound can further enhance the effect of the component (A) (that is, the remarkable improvement in the effect of reducing the component (B) against pain due to hypersensitivity).
• Examples of the water-soluble fluorine compound that can be suitably used as the component (4-C) include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, and monofluorolin. Examples include potassium acid, sodium silicon fluoride, and calcium calcium fluoride.
• a water-soluble fluorine compound sodium fluoride and sodium monofluorophosphate are preferable.
• commercially available reagents for example, available from suppliers such as Stella Chemifa and Rhodia Nikka may be used.
• the component (5-B) is cationized cellulose.
• Examples of the cationized cellulose include cellulose derivatives to which a cationic group is added.
• Examples of the cationic group include dimethyldiallylammonium and 2-hydroxy-3 (trimethylammonio) propyl.
• Examples of the cellulose derivative to which a cationic group is added include hydroxyethyl cellulose dimethyl diallyl ammonium chloride, O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethyl cellulose chloride, and derivatives thereof.
• the cationized cellulose preferably has a nitrogen content of 0.1 to 3% by mass.
• the component may be a single type or a combination of two or more types.
• hydroxyethyl cellulose dimethyl diallylammonium chloride can be preferably used because it is excellent in the effect of inhibiting dental stain formation and the gloss effect.
• the component (6-B) is a polyphenol compound.
• the polyphenol compound include flavonoids, phenylcarboxylic acid, chlorogenic acid, lignan, curcumin, and examples of the component (2-B).
• composition or agent of the present invention contains the lactam compound and / or its salt which are (A) components.
• a lactam compound and / or a salt thereof is contained as an active ingredient.
• the content of the component (A) in the composition or agent of the present invention is not particularly limited.
• the content of the component (A) is preferably 0.3% by mass or more, more preferably 0.5%, based on the total amount of the composition. It is at least mass%. Thereby, the effect by mix
• the component (A) is a lactam compound having a ⁇ -lactam skeleton and / or an ⁇ -lactam skeleton, the blending amount is more preferably 1% by mass or more.
• the amount of the component (A) is preferably 10% by mass or less, and preferably 5% by mass or less with respect to the total amount of the composition. Is more preferable. This is because the contribution to improving each effect is limited even if blended in a large amount.
• the compounding amount of the component (A) in the agent of the present invention is preferably 0.3 to 10% by mass, more preferably 0.5 to 5% by mass with respect to the total amount of the composition.
• composition of the present invention is an oral composition
• composition for oral cavity (1) The oral composition of the present invention may contain a component (A) and a component (1-B).
• the oral composition containing the component (A) and the component (B-1) is referred to as an oral composition (1).
• the content of the component (A) in the oral composition (1) is not particularly limited, but is preferably 0.1% by mass or more, more preferably 0.8%, based on the total amount of the oral composition (1). It is 5 mass% or more, More preferably, it is 1 mass% or more. When the content of the component (A) is 0.1% by mass or more, a dentine caries inhibitory effect can be sufficiently obtained.
• the upper limit of the content of the component (A) in the oral composition (1) is preferably 10% by mass or less, and more preferably 5% by mass or less.
• the content of the component (A) is preferably 0.1 to 10% by mass, more preferably 0.5 to 5% by mass based on the total amount of the oral composition (1).
• the content of the component (A) is more preferably 1 to 5% by mass.
• composition (1) of the present invention the actions of both the component (1-B), which is a source of fluoride ions in the oral cavity, and the component (A) are additively and synergistically combined.
• the component (1-B) which is a source of fluoride ions in the oral cavity
• the component (A) are additively and synergistically combined.
• the effect of the component (1-B) used in the present invention is borne by the fluorine in the component (1-B). Therefore, the amount of the component (1-B) depends on the amount of the component in the oral composition (1). It is more useful to define in terms of fluorine content. Therefore, in the following description, the content of the component (1-B) in the oral composition (1) is indicated by the fluorine content in the oral composition (1).
• the content of the component (1-B) in the oral composition (1) is preferably 0.01% by mass (100 ppm) or more in terms of the fluorine content relative to the total amount of the oral composition (1). 02 mass% (200 ppm) or more is more preferable. Thereby, sufficient dentine caries inhibitory effect can be acquired.
• the upper limit of the content of the component (1-B) in the oral composition (1) is preferably 1% by mass (10000 ppm) or less in terms of the fluorine content relative to the total amount of the oral composition (1). 0.5 mass% (5000 ppm) or less is more preferable.
• the amount of fluorine is 1% by mass (10000 ppm) or less, formulation stability can be maintained. Examples of maintaining the stability of the preparation include prevention of reduction in gelling ability of the thickener in the oral composition (1).
• oral composition (1) is a liquid formulation, prevention of generation
• the content of the component (1-B) in the oral composition (1) of the present invention is 0.01 to 1% by mass (100 to 100%) in terms of the fluorine content relative to the total amount of the oral composition (1). 10,000 ppm) is preferable, and 0.02 to 0.5 mass% (200 to 5000 ppm) is more preferable.
• the blending ratio of the component (A) and the component (1-B) has a preferable range.
• the mass ratio of the component (A) to the component (1-B) in the oral composition (1) can be expressed as the mass ratio of the component (A) to the fluorine content [component (A) / fluorine content]. it can.
• (A) component / fluorine content] is preferably 1 or more, more preferably 2 or more.
• the upper limit of the mass ratio of the component (A) to the fluorine content in the oral composition (1) is preferably 250 or less, and more preferably 100 or less.
• the mass ratio of the component (A) to the fluorine content in the composition for oral cavity (1) is preferably 1 to 250, and more preferably 2 to 100.
• the oral composition (1) of the present invention may further contain a component (1-C). This is preferable because the effect of preventing dentin caries of the oral composition (1) is further increased.
• the content of the (1-C) component is not particularly limited, but is preferably 0.1% with respect to the total amount of the oral composition (1). Is 10 to 10% by mass, and more preferably 0.1 to 5% by mass. A dentine caries inhibitory effect can fully be acquired because content is 0.1 mass% or more. On the other hand, when the content is 10% by mass or less, discoloration can be prevented, and deterioration in feeling of use due to generation of a base odor derived from the component (1-C) can be prevented.
• the oral composition (1) includes the (1-C) component
• the mass ratio of the (1-C) component to the (1-B) component is (with respect to the fluorine content in the oral composition (1)
• the mass ratio of the 1-C component, that is, the mass of the (1-C) component / the fluorine content can be expressed.
• the mass ratio of the (1-C) component to the fluorine content in the oral composition (1) is preferably 0.3 to 800, preferably 0.5 to 80 is more preferable.
• the mass ratio is 0.3 or more, the amount of fluoride ions relative to the (1-C) component is appropriate, so that precipitation of fluoride ions on the dentin surface is prevented and sufficient dentin caries inhibition is achieved. An effect can be obtained.
• the mass ratio is 800 or less, since the amount of fluoride ions is within an appropriate range with respect to the (1-C) component, a synergistic effect can be obtained for the dentine caries inhibitory effect.
• composition for oral cavity (2) The oral composition of the present invention may contain a component (A) and a component (2-B).
• the oral composition containing the component (A) and the component (B-2) is referred to as an oral composition (2).
• the content of the component (A) in the oral composition (2) is not particularly limited, but is preferably 0.5% or more, more preferably 1 with respect to the total amount of the oral composition (2) of the present invention. % Or more. Thereby, by using together with the component (2-B), the effect of inhibiting dentin collagen degradation after storage and the effect of inhibiting dentin collagen coloring after storage can be sufficiently exhibited.
• the upper limit of the content of the component (A) in the oral composition (2) is preferably 10% or less, and more preferably 5% or less. Thereby, formulation stability can fully be exhibited and the dentine collagen degradation inhibitory effect after a preservation
• the content of component (A) is preferably 0.5 to 10%, more preferably 1 to 5%.
• the content of the component (2-B) in the oral composition (2) is not particularly limited, but is preferably 0.001% or more with respect to the total amount of the oral composition (2), 0.01% More preferably.
• the upper limit of the content of the component (2-B) is preferably 0.5% or less, and more preferably 0.2% or less. Thereby, the coloring inhibitory effect and formulation stability to dentin collagen after a preservation
• the content of the component (2-B) is preferably 0.001 to 0.5%, and more preferably 0.01 to 0.2%.
• the mass ratio of the component (A) to the component (2-B) ((A) / (2-B)) is not particularly limited, but is usually 5 or more, preferably 10 That's it. Thereby, the dentin collagen coloring inhibitory effect after a preservation
• the upper limit of the mass ratio of the component (A) to the component (2-B) is usually 3000 or less, preferably 300 or less. Thereby, the dentin collagen degradation inhibitory effect can be sufficiently exerted even after storage.
• the mass ratio ((A) / (2-B)) of the component (A) to the component (2-B) in the composition for oral cavity (2) is preferably 5 to 3000, and preferably 10 to 300. Is more preferable.
• composition for oral cavity (3) The oral composition of the present invention may contain a component (A) and a component (3-B).
• the oral composition containing the component (A) and the component (3-B) is referred to as an oral composition (3).
• the content of the component (A) in the oral composition (3) is not particularly limited, but is preferably 0.1% by mass or more, more preferably based on the total amount of the oral composition (3) of the present invention. It is 0.5 mass% or more. Thereby, the dentinal tubule early blockage effect and the pain reduction effect can be sufficiently obtained.
• the component (A) is a compound having a ⁇ -lactam skeleton and having an acidic group and / or a compound having an ⁇ -lactam skeleton and having an acidic group
• the content is more preferably 1% by mass or more.
• the upper limit of the content of component (A) is preferably 10% by mass or less, and more preferably 5% by mass or less. This is because even if it exceeds 10% by mass, there is a possibility that the improvement of the early occlusion effect of dentinal tubules may not be obtained.
• the content of the component (A) is preferably 0.1 to 10% by mass, and more preferably 0.5 to 5% by mass.
• the content of the component (A) is 1 to More preferably, it is 5 mass%.
• the content of the component (3-B) in the oral composition (3) is not particularly limited, but is preferably 0.01% by mass or more based on the total amount of the oral composition (3) of the present invention. Preferably it is 0.1 mass% or more. Thereby, the dentinal tubule early blockage effect and the pain reduction effect can be sufficiently obtained.
• the upper limit of the content of the (3-B) component is preferably 10% by mass or less, and more preferably 5% by mass or less. Thereby, a feeling of use (taste) can be kept favorable, and generation
• the content of the component (3-B) is preferably 0.01 to 10% by mass, more preferably 0.1 to 5% by mass.
• the mass ratio [(A) / (3-B)] of the component (A) to the component (3-B) is preferably 0.1 or more, more preferably 0.5 or more. It is more preferable that Thereby, the use feeling (taste) improving effect can be more fully exhibited.
• the upper limit is preferably 500 or less, and more preferably 45 or less. Thereby, the dentinal tubule sealing effect of the (3-B) component is sufficiently exhibited, and the synergistic effect of the (A) component and the (3-B) component can be remarkably exhibited.
• the mass ratio of the component (A) to the component (3-B) is preferably 0.1 to 500, and more preferably 0.5 to 45.
• the oral composition (3) may further contain a component (3-C).
• the content of the component (C) in the oral composition (3) is the total fluorine content contained in the oral composition (3).
• the amount of fluorine contained in the oral composition of the present invention is preferably 0.01 to 1% by mass (100 to 10,000 ppm), more preferably 0.02 to 0.5% by mass (200 to 5000 ppm).
• the content of the (3-C) component in the oral composition (3) is preferably 0.076% by mass or more, more preferably 0.15% by mass or more. preferable. Thereby, the dentinal tubule early blockage effect and the pain reduction effect can be sufficiently obtained.
• the upper limit of the content of the (3-C) component in the oral composition (3) is preferably 7.6% by mass or less, and more preferably 3.8% by mass or less. Thereby, a feeling of use (taste) can be kept favorable.
• the content of the (3-C) component is preferably 0.076 to 7.6% by mass, more preferably 0.15 to 3.8% by mass.
• the oral composition (3) may further contain a component (3-D).
• the content of the component (3-D) in the oral composition (3) is not particularly limited, but is preferably 0.005% by mass or more based on the total amount of the oral composition (3) of the present invention. More preferably, it is 1% by mass or more. Thereby, the pain reduction effect can be sufficiently obtained.
• the upper limit is preferably 10% by mass, and more preferably 7% by mass or less. Thereby, a feeling of use (taste) can be kept favorable.
• the content of the (3-D) component is preferably 0.005 to 10% by mass, and more preferably 0.1 to 7% by mass.
• composition for oral cavity (4) may contain a component (A) and a component (4-B).
• the oral composition containing the component (A) and the component (4-B) is referred to as an oral composition (4).
• the content of the component (A) in the composition for oral cavity (4) is preferably 0.1% by mass or more from the viewpoint of a remarkable alleviating effect on pain due to hypersensitivity and an effect of improving the feeling of use (taste). More preferably, the content is 0.5% by mass or more.
• the content of the component (A) in the oral composition is a pain caused by hypersensitivity. From the viewpoint of a remarkable reduction effect on the content, it is particularly preferably 1% by mass or more.
• the upper limit of the content of the component (A) in the oral composition (4) is not particularly limited. However, even if it is a large amount, the contribution to a remarkable reduction effect on pain due to hypersensitivity is limited. % Or less is preferable and 5 mass% or less is more preferable.
• the content of the component (A) in the oral composition (4) is preferably 0.1 to 10% by weight, and preferably 0.5 to 5% by weight with respect to the total amount of the oral composition (4). % Is particularly preferred.
• the content of the component (A) in the oral composition is particularly preferably 1 to 5% by mass.
• composition (4) Component in Oral Composition (4)
• the content of the component (4-B) in the oral composition (4) is preferably 0.1% by mass or more, and more preferably 1.0% by mass or more, from the viewpoint of a remarkable alleviating effect on pain due to hypersensitivity. .
• the content of the component (4-B) in the oral composition (4) is preferably 10% by mass or less, and more preferably 7% by mass or less.
• the content of the component (4-B) in the oral composition (4) is preferably 0.1 to 10% by mass, particularly preferably 1.0 to 7% by mass.
• the mass ratio of the (A) component to the (4-B) component [(A) component / (4-B) component] is preferably 0.02 to 80. 0.1 to 10 is more preferable, and 0.1 to 5 is still more preferable.
• the oral composition (4) may further contain a component (4-C).
• the effect of the water-soluble fluorine compound used in the present invention is attributed to fluorine in the (4-C) component, so the content of the (4-C) component is the fluorine content in the oral composition (4). It is more useful to prescribe it in terms of quantity. Therefore, in the following description, the content of the component (4-C) is indicated by replacing the fluorine content in the oral composition (4).
• the content of the component (4-C) in the oral composition (4) further enhances the effect of the component (A) to further reduce the pain due to hypersensitivity of the oral composition (4). From the viewpoint of increasing, it is preferably 0.01% by mass (100 ppm) or more, more preferably 0.02% by mass (200 ppm) or more in terms of fluorine content relative to the total amount of the oral composition (4).
• the content of the component (4-C) in the oral composition of the present invention is fluorine, and is 1% by mass (10,000 ppm) with respect to the total amount of the oral composition (4).
• the following is preferable, and 0.5 mass% (5000 ppm) or less is more preferable.
• the content of the component (4-C) in the oral composition of the present invention is 0.01 to 1% by mass (in terms of fluorine content) with respect to the total amount of the oral composition (4) ( 100 to 10000 ppm) is preferable, and 0.02 to 0.5 mass% (200 to 5000 ppm) is more preferable.
• the mass ratio of the component (A) to the component (4-C) is: There is a preferred range. That is, in the composition for oral cavity (4), the mass ratio of the (4-C) component to the (A) component [(4-C) component / (A) component] is preferably 0.002 to 5. 0.005 to 0.5 is more preferable (however, the mass of the component (C) is a fluorine content conversion value).
• composition for oral cavity (5) The composition of the present invention may contain a component (A) and a component (5-B).
• the composition for oral cavity containing the component (A) and the component (5-B) is referred to as oral composition (5).
• the content of the component (A) in the oral composition (5) is not particularly limited, but is preferably 0.1% by mass or more based on the total amount of the oral composition (5) of the present invention. Thereby, a stain removal effect and a stain formation inhibitory effect are sufficiently obtained.
• the content of the component (A) in the oral composition (5) is preferably 10% by mass or less based on the total amount of the oral composition (5) of the present invention. As a result, good solubility and appearance can be obtained, and a sense of incongruity can be suppressed and the usability can be improved.
• the content of the component (A) in the oral composition (5) is preferably 0.1 to 10% by mass, and preferably 0.5 to 5% by mass with respect to the total amount of the oral composition (5) of the present invention. % Is more preferable.
• the content of the component (5-B) in the oral composition (5) is preferably 0.005% by mass or more based on the total amount of the oral composition (5). Thereby, the stain formation suppressing effect and the gloss effect can be sufficiently exhibited.
• the content of the component (5-B) in the oral composition (5) is preferably 0.1% by mass or less based on the total amount of the oral composition (5). Thereby, the discomfort derived from a cationized cellulose can be suppressed and a favorable usability
• the content of the component (5-B) in the oral composition (5) is preferably 0.005 to 0.1% by mass relative to the total amount of the oral composition (5) of the present invention. It is more preferably 0.01 to 0.05% by mass in terms of the stain formation inhibiting effect and the gloss effect.
• the mass ratio ((A) / (5-B)) of the component (A) to the component (5-B) is not particularly limited, but is usually 3 or more, preferably 15 That's it.
• the mass ratio of the component (A) to the component (5-B) is usually 600 or less, preferably 300 or less.
• the ratio is 3 or more, the stain formation suppressing effect and the stain removing effect can be sufficiently exhibited.
• the ratio of the component (A) to the component (5-B) is preferably 3 to 600, more preferably 15 to 300.
• composition for oral cavity (5) [Effect of composition for oral cavity (5)]
• the components (A) and (5-B) are presumed to exhibit a stain formation inhibitory effect, a stain removal effect, a gloss effect and an excellent feeling in use of the preparation by the following actions. .
• (5-B) component effectively suppresses the adhesion of stain to the enamel surface and imparts gloss to the teeth.
• the component (A) has an action of softening and dissolving the calcified substance after adsorption to the stain adhering to the enamel surface or further calcified after adhesion, and an action of suppressing the lamination of the stain.
• the combination of the component (A) and the component (5-B) makes it possible to strongly suppress the adhesion and lamination of the stain on the tooth surface, whereby the composition for oral cavity (5) becomes a stain for teeth. It can have both removal effect, stain formation suppression effect and gloss effect. Both the component (A) and the component (5-B) have no discomfort or taste problems with the oral mucosa of the conventional condensed phosphoric acid, enzyme, and surfactant.
• the composition (5) can also exhibit an excellent feeling of use of the preparation.
• the composition of the present invention may contain a component (A) and a component (6-B).
• the oral composition containing the component (A) and the component (6-B) is referred to as an oral composition (6).
• Component (6-B) Since the polyphenol compound contains each compound of component (3-B), the composition for oral cavity (6) can be said to be a superordinate concept of the composition for oral cavity (3). However, they are different in effect.
• the content of the component (A) in the oral composition (6) is not particularly limited, but is preferably 0.3% by mass or more based on the total amount of the oral composition (6) of the present invention. Thereby, the collagen coloring suppression effect by the (6-B) component can be sufficiently obtained.
• the content of the component (A) in the oral composition (6) is preferably 10% by mass or less based on the total amount of the oral composition (6) of the present invention. As a result, good solubility and appearance can be obtained, and a sense of incongruity can be suppressed and the usability can be improved.
• the content of the component (A) in the oral composition (6) is preferably 0.3 to 10% by mass, and preferably 0.5 to 5% by mass with respect to the total amount of the oral composition (6) of the present invention. % Is more preferable.
• the content of the component (6-B) in the oral composition (6) is preferably 0.001% by mass or more based on the total amount of the oral composition (6).
• the component (6-B) causes coloration of the collagen, and the effect of inhibiting collagen coloration by the combined use of the components (A) and (6-B) can be expected.
• the content of the component (6-B) in the oral composition (6) is preferably 5% by mass or less based on the total amount of the oral composition (6). Thereby, the collagen coloring inhibitory effect by (A) component can fully be exhibited.
• the content of the component (6-B) in the oral composition (6) is preferably 0.001 to 5% by mass relative to the total amount of the oral composition (6) of the present invention, 0.01 to More preferably, it is 1 mass%.
• the mass ratio of the component (A) to the component (6-B) ((A) / (6-B)) is not particularly limited, but is usually 0.5 or more, preferably Is 3 or more.
• the mass ratio of the component (A) to the component (6-B) is usually 1000 or less, preferably 200 or less. By being in this range, the collagen coloring suppression effect by the component (A) can be sufficiently exerted.
• the ratio of the component (A) to the component (6-B) is preferably 0.5 to 200, and more preferably 3 to 1000.
• content of each component in a composition is based on the preparation amount of each component at the time of manufacturing a composition.
• the dosage form of the composition of the present invention is not particularly limited.
• oral administration eg, oral administration, sublingual administration, etc.
• parenteral administration intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.
• a less invasive dosage form is preferable, and oral administration is more preferable.
• the dosage form of the composition of the present invention can be appropriately determined according to the dosage form and is not particularly limited.
• dosage forms for oral administration include liquid (liquid), syrup (syrup), tablets (tablets, tablets), capsules (capsules), powders (granules, fine granules), soft capsules (Soft capsule), solid, semi-solid (gummy etc.), film, semi-liquid, cream, paste, chewing gum and the like. Of these, granular, capsule, powder, soft capsule, and solid are preferable, and granular (tablet) is more preferable.
• dosage forms for transdermal administration include aerosols, creams, lotions, sprays, sticks, and the like.
• the dosage form when the composition of the present invention is a composition for oral cavity is preferably liquid (liquid, liquid, paste) or solid (solid, solid, semi-solid, film).
• the oral composition of the present invention may contain a pharmacologically acceptable carrier (optional component) as necessary.
• pharmacologically acceptable carrier optional component
• examples of optional components include surfactants, binders, thickeners, sweeteners, preservatives, fragrances, acidulants, lubricants, abrasives, coloring agents, preservatives, brighteners, fluidizing agents, A binder, a disintegrant, a medicinal component, a solvent (solvent) such as water, and an excipient can be blended within a range that does not impair the stability and the decalcification inhibiting effect.
• solvent solvent
• abrasive examples include silica-based abrasives such as silicic anhydride, crystalline silica, amorphous silica, silica gel, aluminosilicate, zeolite, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, Calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tertiary magnesium phosphate, zirconium silicate, tertiary calcium phosphate, hydroxyapatite, quaternary calcium phosphate, synthetic resin-based abrasive and the like.
• silica-based abrasives such as silicic anhydride, crystalline silica, amorphous silica, silica gel, aluminosilicate, zeolite, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, Calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tertiary
• Abrasives can be used singly or in combination of two or more.
• the blending amount of the dentifrice is preferably 2 to 40%, more preferably 5 to 20% of the entire composition.
• the mouthwash it is preferably 0 to 10%, more preferably 0 to 5% of the entire composition.
• binder examples include thickening silica, pullulan, gelatin, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, carrageenan, sodium alginate, xanthan gum, sodium polyacrylate, gum arabic, guar gum, locust bean gum, Polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, etc. are mentioned.
• a binder can be used individually by 1 type or in combination of 2 or more types. The amount of the binder used is usually 0.01 to 3% with respect to the total amount of the composition.
• thickening agent examples include sorbitol, propylene glycol, butylene glycol, glycerin, polyethylene glycol and the like.
• a thickener can be used individually by 1 type or in combination of 2 or more types. When a thickener is used, its content can be determined within a range not impeding the effects of the present invention, and is usually 1 to 60% with respect to the total amount of the composition.
• surfactant examples include an anionic surfactant and a nonionic surfactant.
• anionic surfactants include N-acyl amino acid salts, ⁇ -olefin sulfonates, N-acyl sulfonates, alkyl sulfates, glycerol fatty acid ester sulfates, POE alkyl sulfosuccinates, POE alkyl ether sulfates. Examples thereof include salts and POE alkyl ether phosphates.
• N-acylamino acid salts, ⁇ -olefin sulfonates, alkyl sulfates and the like are preferable from the viewpoint of versatility, and lauroyl sarcosine sodium, alkyl chain carbon chain length from the viewpoint of foamability and hard water resistance. More preferred are sodium ⁇ -olefin sulfonates having 10 to 16 carbon atoms, sodium lauryl sulfate, and the like.
• Nonionic surfactants include, for example, polyoxyethylene alkyl ether, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene hydrogenated castor oil, glycerin ester polyoxyethylene ether, sucrose fatty acid ester, alkylolamide And glycerin fatty acid ester.
• polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, alkylolamide, sorbitan fatty acid ester and the like are preferably used from the viewpoint of versatility.
• the carbon chain length of the alkyl chain is preferably 14 to 18 carbon atoms.
• the polyoxyethylene alkyl ether preferably has an average addition mole number of ethylene oxide of 15 to 30.
• the polyoxyethylene hydrogenated castor oil preferably has an average ethylene oxide addition mole number (average addition EO) of 20 to 100.
• the alkyl chain preferably has a carbon chain length of 12 to 14 carbon atoms.
• the sorbitan fatty acid ester preferably has 12 to 18 carbon atoms in the fatty acid.
• the polyoxyethylene sorbitan fatty acid ester preferably has 16 to 18 carbon atoms in the fatty acid.
• the polyoxyethylene sorbitan fatty acid ester preferably has an average added mole number of ethylene oxide of 10 to 40.
• Surfactants can be used alone or in combination of two or more.
• the content is usually 0 to 10%, preferably 0.01 to 5%, based on the total amount of the composition.
• sweetening agent examples include saccharin sodium, stevioside, neohesperidin hydrochalcone, glycyrrhizin, perilartin, p-methoxycinnamic aldehyde, thaumatin, palatinose, maltitol, xylitol, arabitol and the like.
• a sweetener can be used individually by 1 type or in combination of 2 or more types. When using a sweetener, content can be suitably determined in the range which does not impair the effect of this invention.
• preservative examples include paraoxybenzoic acid esters such as sodium benzoate, methylparaben, ethylparaben, and butylparaben, ethylenediaminetetraacetate, benzalkonium chloride, and the like.
• a preservative can be used individually by 1 type or in combination of 2 or more types. When using a preservative, the content can be appropriately determined within a range not impairing the effects of the present invention.
• fragrances examples include natural fragrances, synthetic fragrances (single fragrances), blended fragrances (oil and fat fragrances (oil-based fragrances), powdered fragrances, and the like).
• flavor can be used individually by 1 type or in combination of 2 or more types.
• natural flavors include mastic oil, parsley oil, anise oil, eucalyptus oil, winter green oil, cassia oil, menthol oil, spearmint oil, peppermint oil, lemon oil, coriander oil, orange oil, mandarin oil, lime oil.
• fragrance for example, carvone, anethole, methyl salicylate, cinnamic aldehyde, linalool, linalyl acetate, limonene, menthone, menthyl acetate, pinene, octyl aldehyde, citral, pregon, carbyl acetate, anisaldehyde, ethyl acetate, Ethyl butyrate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl anthranilate, vanillin, undecalactone, hexanal, ethinone alcohol, propyl alcohol, butanol, isoamyl alcohol, hexenol, dimethylsulfide, cycloten, furfural , Trimethylpyrazine, ethyl lactate, ethyl lioacetate, cineol, eugen
• the blended fragrance is a fragrance made by blending a single fragrance and / or a natural fragrance.
• Examples include menthol micron, strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, tropical fruit flavor, butter flavor, milk flavor, yogurt flavor, fruit mix flavor, herbal mint flavor and the like.
• the form of the fragrance is not limited, and any of essential oils, extracts, solids, and powders obtained by spray drying any of these may be used.
• the above fragrance material is preferably used at 0.000001 to 1% in the preparation composition.
• the fragrance for flavoring using the above fragrance material is preferably used in an amount of 0.1 to 2.0% in the preparation composition.
• Medicinal components include, for example, the following components: anticalculus agents such as condensed phosphates and ethane hydroxydiphosphonates; astringents such as sodium chloride; suppression of hypersensitivity such as strontium chloride, strontium acetate and zinc chloride Agents.
• anticalculus agents such as condensed phosphates and ethane hydroxydiphosphonates
• astringents such as sodium chloride
• suppression of hypersensitivity such as strontium chloride, strontium acetate and zinc chloride Agents.
• Content in the case of using a medicinal component can be suitably set within a pharmaceutically acceptable range for each medicinal component.
• the colorant examples include natural pigments such as safflower red pigment, gardenia yellow pigment, gardenia blue pigment, perilla pigment, sockeye pigment, red cabbage pigment, carrot pigment, hibiscus pigment, cacao pigment, spirulina pigment, and coumarindo pigment.
• the content is preferably 0.00001 to 3% with respect to the total amount of the composition.
• the brightener examples include waxes such as shellac, carnauba wax and candelilla wax, calcium stearate, and the like.
• the content is preferably 0.01 to 5% with respect to the total amount of the composition.
• the pH (20 ° C.) is usually 6 to 10, preferably 7 to 9.
• the pH adjuster include acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, Examples include acids and alkalis such as sodium citrate, sodium hydrogen citrate, sodium phosphate, and sodium dihydrogen phosphate, and buffers.
• it contains a pH adjuster its content can be appropriately determined within a range not impairing the effects of the present invention.
• the solvent examples include water and lower alcohols having 3 or less carbon atoms such as ethanol and propanol.
• the solvent is usually contained in a liquid oral composition.
• water is contained as a solvent, the content is preferably 20 to 95% with respect to the total amount of the composition.
• a lower alcohol is contained as a solvent, its content is preferably 1 to 20% with respect to the total amount of the composition.
• excipients examples include syrup, glucose, fructose, invert sugar, dextrin, oligosaccharide and the like.
• an excipient is usually contained. In the case of containing an excipient, the content can be appropriately determined within a range not impairing the effects of the present invention.
• the pH (20 ° C.) of the oral composition of the present invention is usually 5 to 10, preferably 6 to 10, more preferably 6 to 9, and further preferably 6 to 8 or 7 to 9. It is.
• the pH adjuster include acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, Examples include acids such as sodium citrate, sodium hydrogen citrate, sodium phosphate, and sodium dihydrogen phosphate, alkalis, and buffers. When it contains a pH adjuster, its content can be appropriately determined within a range not impairing the effects of the present invention.
• the shape and dosage form of the composition for oral cavity of the present invention are not particularly limited.
• it can be prepared in various shapes such as a liquid system (liquid, liquid, paste) and a solid system (solid, solid).
• dosage forms include toothpaste compositions such as toothpaste, liquid dentifrice, liquid dentifrice, powder dentifrice, mouthwash composition, coating composition, oral pasta, mouth freshener composition, food form (for example, Chewing gum, tablet confectionery, candy, gummi, film, troche, etc.).
• food form for example, Chewing gum, tablet confectionery, candy, gummi, film, troche, etc.
• tablet candy, candy, chewing gum, gummi and film are preferred from the viewpoint of convenience and portability that can be used regardless of time and place.
• Examples of candy include soft candy such as caramel and nougat, and hard candy such as drop and toffee, and are not particularly limited, but hard candy is preferable in terms of imparting a high functional feeling.
• the hard candy can be produced by a conventional method, and is not particularly limited. For example, water is added to raw materials other than the functional ingredient and the fragrance, and the mixture is boiled at a high temperature (eg, 140 to 200 ° C.) and then cooled (eg, 70 Up to 130 ° C.), adding functional components and fragrance, cooling and molding.
• Chewing gum is a chewing elastic food mainly made from a gum base and sugar, and may have a sugar coating.
• Chewing gum can be produced by a conventional method and is not particularly limited.
• the active ingredient in the present invention such as the component (A).
• the active ingredient in the present invention such as the component (A) may be contained in either or both of sugar-coated and gum base, but is preferably contained in sugar-coated. Thereby, the storage stability of sugar-coated chewing gum can be improved.
• Such sugar-coated chewing gum can be manufactured, for example, by mixing and molding each raw material mainly composed of chewing gum and then coating with sugar coating containing the active ingredient in the present invention such as the component (A).
• the content of the active ingredient in the present invention such as the component (A) in the sugar coating layer in the case of sugar-coating chewing gum is preferably mass% of each of the above-described components relative to the total amount of sugar coating.
• the gum base blended mainly in chewing gum those usually used for chewing gum can be used.
• the gum base is, for example, a polyvinyl acetate resin (average polymerization degree of about 100 to about 1000), natural resins (such as chicle, gelton, and solver), polyisobutylene, polybutene, ester gum, and other gum base resins (base agents), Emulsifier, calcium carbonate, calcium phosphate, filler (such as talc), lanolin, stearic acid, sodium stearate, potassium stearate, glyceryl triacetate, plasticizer or softener such as glycerin, natural wax, petroleum wax, paraffin, etc.
• blended the component is mentioned.
• a commercially available product can be used as the gum base.
• a gum base manufactured by Natural Base Co., Ltd. and a gum base manufactured by Youth Co., Ltd. are suitable.
• the said gum base may contain coloring agents, such as natural pigment
• the gum base content is preferably 10 to 50%, more preferably 15 to 30%, based on the total amount of the composition.
• Tablet confectionery is a product made from sugar as a main raw material and compression-molded with a device such as a tableting machine, and may have a sugar coating.
• Tablet confectionery can be produced by a conventional method, and is not particularly limited. For example, it can be produced by mixing each component and compressing it with a device such as a tableting machine (for example, under a pressure condition of 5 to 20 kN). Can do.
• an example of the application amount of the oral composition of the present invention to humans is as follows.
• the amount used per time is 0.5 to 2 g, preferably about 0.5 to 1 g.
• the amount can be adjusted as appropriate.
• compositions of the present invention are not particularly limited, but from the viewpoint of the application site, for example, oral compositions (including food and beverage compositions) can be mentioned.
• oral compositions include dentifrice compositions such as toothpaste, liquid dentifrice, liquid dentifrice, and powder dentifrice, mouthwash compositions, mouth freshener compositions, and food and beverage compositions.
• composition of the present invention examples include a collagen coloring inhibitory composition, a collagen degradation inhibitory composition, a dentin caries inhibitory composition, a dentinal tubule sealing composition, a composition for reducing pain due to hypersensitivity, and a stain formation inhibitory composition. Or a stain removal composition, a tooth surface gloss imparting composition, etc. are mentioned.
• the application target of the composition of the present invention is not particularly limited.
• dentinal hypersensitivity, dentinal caries patients, dentinal hypersensitivity and dentinal caries are not affected or have not been confirmed, but dentinal hypersensitivity and dentinal For example, those who want to prevent dental caries.
• composition of the present invention may be any of pharmaceuticals, quasi drugs, cosmetics, and foods and drinks.
• Collagen coloring inhibitor Since the lactam compound or salt thereof as the component (A) has an effect of suppressing coloring to collagen, it is useful as an active ingredient of a collagen coloring inhibitor.
• Collagen is present in animal tissues. Human collagen is classified into several tens of types, and the main collagen is type I.
• the collagen targeted by the collagen coloring inhibitor of the present invention is not particularly limited, but is preferably collagen containing type I collagen.
• Collagen coloring means a change from the original color of collagen to another color.
• Collagen coloring targeted by the collagen coloring inhibitor is preferably collagen coloring generated in the living body, and more preferably coloring of the dentin collagen layer.
• Examples of collagen coloring include coloring of dentin collagen layers by drugs, food and drink, and oral bacteria. When suffering from dentine caries, the dentin may be colored by oral bacteria, or the dentin collagen layer may be colored by applying a drug in the treatment of dentine caries. Moreover, the same coloring may arise by ingestion of food and drink.
• the main example of a drug that causes collagen coloring is polyphenol.
• polyphenol examples include flavonoids, phenylcarboxylic acid, chlorogenic acid, lignan, curcumin, and examples of the component (2-B).
• foods and drinks containing a large amount of the above polyphenol for example, black tea or green tea containing catechin, coffee containing chlorogenic acid, etc. can also cause coloring.
• the administration form of the collagen coloring inhibitor of the present invention is not particularly limited.
• oral administration eg, oral administration, sublingual administration, etc.
• parenteral administration intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.
• a less invasive dosage form is preferable, and oral administration or transdermal administration is more preferable.
• Examples of subjects who take the collagen coloring inhibitor of the present invention include subjects who have already developed collagen coloring and want to improve, subjects who have not developed collagen coloring but want to prevent, etc. .
• the administration time of the agent of the present invention is not particularly limited.
• Collagen degradation inhibitor Since the lactam compound or salt thereof as the component (A) has a collagen degradation inhibitory effect, it is useful as an active ingredient of a collagen degradation inhibitor.
• the collagen targeted by the collagen degradation inhibitor of the present invention is not particularly limited, but is preferably collagen containing type I collagen.
• Periodontal collagen degradation causes periodontal tissue troubles such as gingival retraction and alveolar bone resorption. Collagen degradation can be suppressed by the collagen degradation inhibitor of the present invention, so that troubles in periodontal tissue can be prevented.
• the administration mode of the collagen degradation inhibitor of the present invention is not particularly limited. Examples of dosage forms and preferred examples are the same as the examples and preferred examples given in the description of the collagen coloring inhibitor.
• the subject of intake of the collagen degradation inhibitor or ameliorating agent of the present invention has already developed symptoms due to collagen degradation (eg, progression of dentin caries, periodontal tissue trouble (gingival recession, alveolar bone resorption, etc.)) And subjects who want to improve and those who do not develop these symptoms but want to prevent.
• the administration time of the agent of the present invention is not particularly limited.
• the lactam compound and / or salt thereof as the component (A) is useful as a dentinal tubule sealing agent because it has an early dentinal tubule blocking effect.
• the administration form of the dentinal tubule blocking agent of the present invention is not particularly limited. Examples of dosage forms and preferred examples are the same as the examples and preferred examples given in the description of the collagen degradation inhibitor.
• the subject who ingested the dentinal tubule-blocking agent of the present invention has already developed dentinal hypersensitivity, and the subject who wants to block the dentinal tubule, whether the symptom has not developed or has developed Although it is not, there are subjects who want to prevent it.
• the administration time of the agent of the present invention is not particularly limited.
• the lactam compound and / or salt thereof as the component (A) is useful as an agent for suppressing or improving dentinal hypersensitivity because it has an effect of early blocking of dentinal tubules and a pain reducing effect.
• the administration mode of the agent for suppressing or improving dentin hypersensitivity of the present invention is not particularly limited.
• Examples of dosage forms and preferred examples are the same as the examples and preferred examples given in the description of the collagen degradation inhibitor.
• the subject who takes the dentin hypersensitivity suppression or amelioration agent of the present invention is a subject who has already developed dentine hypersensitivity and wants to improve his / her symptoms.
• the target person is considered.
• the administration time of the agent of the present invention is not particularly limited.
• the lactam compound or a salt thereof as the component (A) is useful as an active ingredient of a stain remover because it has an effect of removing stains that are tooth stains.
• the subject who ingests the stain remover of the present invention includes a subject who wants to remove stains due to stains on the teeth.
• the administration time and administration form of the agent of the present invention are not particularly limited, but may be the same as the administration form of the composition described above.
• Examples 1-1 to 1-30 and Comparative Examples 1-1 to 1-4 [Main ingredients used] [(A) component] (1) Pyrrolidone carboxylic acid ( ⁇ -lactam compound): Product name “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc. (2) 6-Oxo-2-piperidinecarboxylic acid ( ⁇ -lactam compound): Product name “(S) -6-Oxo-2-piperidine carboxylic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
• Active ingredients and additive ingredients blended in Phase A, Phase B and Phase C Active ingredients for phase A: pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, sodium fluoride, sodium monofluorophosphate, casein, Additives for lactoferrin, hydrolyzed collagen (ii) A phase: sorbite solution, sodium saccharin, citric acid, sodium hydroxide (iii) Additives for phase B: propylene glycol, sodium polyacrylate, sodium carboxymethylcellulose (iv) Additives for Phase C: Silicic anhydride, sodium lauryl sulfate, fragrance
• dentin caries inhibitory effect and formulation stability were evaluated as follows.
• a dentin block having a window formed on the surface from a bovine tooth root was prepared and immersed in a decalcification solution of acetic acid 100 mmol / L and pH 4.8 at 37 ° C. for 6 hours to obtain a carious tooth sample.
• each dentifrice was diluted 3 times with distilled water to obtain each dentifrice treatment solution.
• the carious tooth sample was immersed in each dentifrice treatment solution for 3 minutes at room temperature, and then the dentifrice treatment solution was lightly removed.
• a remineralization solution having a pH of 6.5 containing Sigma) was prepared. Each carious tooth sample after the treatment of (2) was immersed in a remineralization solution at 37 ° C. for 18 hours.
• each carious tooth sample was rinsed well with distilled water and perpendicular to the sample window with a microcutter (Malto Co., Ltd., “MC-201 (trade name)”). Then, a section having a thickness of about 200 ⁇ m was carefully cut out under running water.
• a sample slice cut in a wet state is placed on a soft X-ray film (“SO-343 (trade name)” manufactured by Kodak Co., Ltd.), and then a soft X-ray generator (Softex Corporation) ), “CMRII (trade name)”) was irradiated with soft X-rays (2.8 mA, 18 kVp) for 60 minutes, and a TMR (Transverse Micro Radiography) image of each slice sample was obtained.
• SO-343 trade name
• Softex Corporation Softex Corporation
• the dentin caries prevention effect of each Example and Comparative Example was evaluated based on the following five-step criteria. If the following evaluation score is 3 or more, it may be considered that there is a good dentine caries prevention effect.
• Dentin caries inhibition rate is 70% or more 4 points: Dentine caries inhibition rate is 50% or more and less than 70% 3 points: Dentin caries inhibition rate is 30% or more and less than 50% 2 points: Dentine Caries inhibition rate is 10% or more and less than 30% 1 point: Dentin caries inhibition rate is less than 10%
• Example 1-1 to 1-5 shown in Table 1 above the component (1-C) which is an optional active component is not added, and pyrrolidone carboxylic acid is used as the component (A).
• Sodium fluoride is used as a component.
• the evaluation of the effect of inhibiting dentin caries in Examples 1-1 to 1-5 is 3 or more, which is good.
• the evaluation of the dentin caries inhibitory effect of the oral composition of the example using the component (A) and the component (1-B) as active ingredients simultaneously is 3 or more. 1-1 to 1-3 have a rating of 4. Therefore, by using both the component (A) and the component (1-B) as active ingredients at the same time, an effect that is more than additive, that is, a synergistic effect of the components (A) and (1-B) can be obtained.
• Example 1-6 the (1-C) component is not added, and sodium fluoride is used as the (1-B) component.
• 6-oxo-2-piperidinecarboxylic acid was used as component (A)
• Example 1-7 3- (2-oxo-1-azepanyl) propanoic acid was used as component (A). Yes.
• Examples 1-6 and 1-7 have a good evaluation of dentin caries inhibitory effect of 3, which is good.
• Examples 1-8 to 1-11 shown in Table 3 above as in Examples 1-1 to 1-5 in Table 1, the (1-C) component was not added, and pyrrolidone was used as the (A) component.
• Carboxylic acid is used, and sodium fluoride is used as the (1-B) component.
• Examples 1-8 to 1-11 have good evaluation of dentin caries inhibitory effect of 3 or more. Among them, the evaluation of Examples 1-8 and 1-9 is 4. This shows that a synergistic effect of the component (A) and the component (1-B) is obtained.
• Examples 1-12 to 1-15 shown in Table 4 the (1-C) component is not added, and pyrrolidone carboxylic acid is used as the (A) component.
• pyrrolidone carboxylic acid is used as the (A) component.
• sodium monofluorophosphate was used as the component (1-B)
• Examples 1-14 and 1-15 sodium fluoride was used.
• Example 1-12 to 1-15 have a good evaluation of dentin caries inhibitory effect of 3 or more. Among them, Examples 1-12 and 1-13 have a rating of 4. This shows that a synergistic effect of the component (A) and the component (1-B) is obtained.
• Example 1-20 component (1-C) is added.
• lactoferrin is used as the (1-C) component
• hydrolyzed collagen is used as the (1-C) component.
• pyrrolidone carboxylic acid is used as the component (A)
• sodium fluoride is used as the component (1-B).
• Examples 1-22 to 1-26 shown in Table 7 plural kinds of compounds are used in combination as active ingredients.
• Example 1-22 pyrrolidonecarboxylic acid ( ⁇ -lactam compound) and 6-oxo-2-piperidinecarboxylic acid ( ⁇ -lactam compound) are used in combination as component (A).
• Example 1-23 as component (A), pyrrolidone carboxylic acid ( ⁇ -lactam compound) and 3- (2-oxo-1-azepanyl) propanoic acid ( ⁇ -lactam compound) are used in combination.
• Example 1-24 as component (A), 6-oxo-2-piperidinecarboxylic acid ( ⁇ -lactam compound) and 3- (2-oxo-1-azepanyl) propanoic acid ( ⁇ -lactam compound) were used. Used together.
• Example 1-25 as component (A), pyrrolidone carboxylic acid ( ⁇ -lactam compound), 6-oxo-2-piperidinecarboxylic acid ( ⁇ -lactam compound), 3- (2-oxo-1- Azepanyl) propanoic acid ( ⁇ -lactam compound).
• Example 1-26 pyrrolidonecarboxylic acid ( ⁇ -lactam compound) is used as the component (A), and sodium fluoride and sodium monofluorophosphate are used in combination as the component (1-B).
• Examples 1-27 to 1-30 shown in Table 8 a plurality of types of compounds are used in combination as active ingredients.
• Example 1-27 casein and lactoferrin are used in combination as component (1-C).
• Example 1-28 casein and hydrolyzed collagen are used in combination as the (1-C) component.
• Example 1-29 lactoferrin and hydrolyzed collagen are used in combination as the component (1-C).
• Example 1-30 casein, lactoferrin, and hydrolyzed collagen are used in combination as the (1-C) component.
• Comparative Example 1-1 uses sodium fluoride as the component (1-B) without using the component (A).
• Comparative Examples 1-2 and 1-3 use a lactam compound and a similar lactam compound as a comparative product of component (A).
• polyvinylpyrrolidone is used as a comparative product of component (A).
• Polyvinylpyrrolidone is a lactam compound having no acidic group.
• proline is used instead as a comparative product of component (A).
• Proline is a cyclic amino acid.
• Comparative Example 1-4 uses pyrrolidone carboxylic acid as the component (A) without using the component (1-B).
• Comparative Example 1-1 uses sodium fluoride as the component (1-B) without using the component (A). It is well known that fluorine compounds are effective in suppressing caries. However, evaluation of the dentine caries inhibitory effect by this fluorine compound alone is 2, which is insufficient in practical use.
• the components (A) and (1-B) are used as effective components at the same time. More than the additive effect can be obtained.
• Examples 2-1 to 2-36 and Comparative Examples 2-1 to 2-6 [Main ingredients used] [(A) component] (1) Pyrrolidone carboxylic acid ( ⁇ -lactam compound): Product name “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc. (2) 6-Oxo-2-piperidinecarboxylic acid ( ⁇ -lactam compound): Product name “(S) -6-Oxo-2-piperidine carboxylic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
• the blending ratio of each polyphenol compound shown in Tables 12 to 16 is the blending ratio of the polyphenol contained in each commercially available product in the raw material of each composition.
• This sample was immersed in a 3-fold water dilution of the composition of each Example and Comparative Example for 5 minutes at room temperature, washed with distilled water, and then artificial saliva (CaCl 2 : 2.2 mmol / L, KH 2 at 37 ° C. It was immersed in PO 4 : 2.2 mmol / L, acetic acid: 0.1 mol / L, collagenase derived from Clostridium histolyticum (Type 1A, manufactured by Sigma): 1.0 unit / mL, pH 6.5). The composition treatment was performed 3 times / day in the morning, noon, and night, and was immersed in artificial saliva containing collagenase at other times and repeated for a total of 4 days.
• the collagen degradation inhibition rate was calculated by the following formula and evaluated according to the following criteria.
• the example or comparative group represents a group treated with the composition shown in the example or comparative example
• Dentin collagen degradation inhibition rate is 70% or more and less than 90%
• B Dentin collagen degradation inhibition rate is 50% or more and less than 70%
• C Dentin collagen degradation inhibition rate is 20% or more and less than 50%
• D Dentin collagen Decomposition rate is 0% or more and less than 20%
• this sample was immersed in a 3-fold water dilution of the composition of each Example and Comparative Example for 5 minutes at room temperature, washed with distilled water, and then at 37 ° C. artificial saliva (CaCl 2 : 2.2 mmol / L).
• KH 2 PO 4 2.2 mmol / L
• acetic acid 0.1 mol / L
• collagenase derived from Clostridium histolyticum Type 1A, manufactured by Sigma
• the composition treatment was performed 3 times / day in the morning, noon, and night, and was immersed in artificial saliva containing collagenase at other times and repeated for a total of 4 days.
• Experimental Example 2-4 Evaluation of formulation stability (after storage at 50 ° C for 1 month) Similarly to Experimental Example 2-1, dentifrices having the compositions shown in Tables 12 to 16 were prepared and stored in a high-temperature bath at 50 ° C. for 1 month. The appearance after storage was visually confirmed, and the preparation stability (discoloration and shape retention) was evaluated based on the following evaluation criteria.
• Tables 12 to 16 show the results of Experimental Examples 2-1 to 2-4 for the compositions for oral cavity of each Example and Comparative Example.
• composition for oral cavity in which the component (A) and the component (2-B) are blended, each of the component (A) and the component (2-B) is used alone, or the component (A) and the component (2) -B)
• Dentin collagen degradation inhibition rate is significantly higher than oral compositions using comparative products of each component (comparative example), and the dentin is high even after the preparation is stored at 50 ° C for 1 month It was confirmed that the collagen degradation inhibitory effect was sustained.
• coloring of the dentin collagen by the polyphenol component is remarkably suppressed.
• discoloration after storage of the preparation was significantly suppressed.
• the oral composition of the present invention has a well-balanced balance between dentin collagen degradation inhibitory effect, dentin collagen degradation inhibitory effect after storage, dentin collagen coloration inhibitory effect after storage, and formulation stability. It is shown to be demonstrated. These results show that the oral composition (2) is remarkable in any of the dentin collagen degradation inhibitory effect, the dentin collagen degradation inhibitory effect after storage, the dentin collagen coloration inhibitory effect after storage, and the formulation stability. It also shows that it is excellent.
• Examples 3-1 to 3-26 and Comparative Examples 3-1 to 3-3 [Main ingredients used] [(A) component] (1) Pyrrolidone carboxylic acid ( ⁇ -lactam compound): Product name “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc. (2) 6-Oxo-2-piperidinecarboxylic acid ( ⁇ -lactam compound): Product name “(S) -6-Oxo-2-piperidine carboxylic acid” manufactured by Sigma Aldrich Japan Co., Ltd.
• Active ingredients blended in Phase A, Phase B, Phase C and other additive ingredients Active ingredients blended in Phase A: pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, aluminum lactate, sodium monofluorophosphate, potassium nitrate (ii )
• Active ingredients for phase A 70% by weight sorbitol, sodium saccharin, sodium hydroxide
• Additives for phase B propylene glycol, xanthan gum, sodium carboxymethylcellulose, methylparaben
• Additives for phase C anhydrous silica Acid, sodium lauryl sulfate, fragrance
• a dentin disc having a thickness of 3 mm was cut out from the crown portion of a human molar tooth, polished with water-resistant abrasive paper # 2000, further etched with a 37% phosphoric acid aqueous solution, and a dentinal tubule opened to obtain a sample.
• 0 g of artificial saliva was mixed to give a 3-fold diluted solution, which was used as a treatment solution.
• the reason for the 3-fold dilution is that it is assumed that the dentifrice is diluted 3-fold with saliva during tooth brushing.
• the sample was immersed in this treatment solution for 3 minutes, rinsed lightly with distilled water to remove excess treatment solution, and immersed in the artificial saliva at 37 ° C. for 15 hours. Rinse the sample thoroughly with distilled water, drain the water, fix it on the device, run distilled water under constant pressure for 5 minutes, measure the amount of distilled water per unit time (5 minutes) passing through the sample, before treatment
• the passability suppression rate of each of the examples and the comparative example with respect to the passing amount of was calculated.
• the average value was 60% or more, the example or comparative example Evaluated that dentinal tubules had an early sealing effect.
• the passing amount means the amount of distilled water ( ⁇ L) passing through for 5 minutes.
• Example 3-2 Evaluation of Pain Relieving Effect Three subjects with hypersensitivity having teeth that felt transient pain during water rinsing after brushing were used as subjects. The subject brushed his teeth twice a day using the dentifrice prepared in the same manner as in Experimental Example 3-1. The degree of pain during water rinsing immediately after brushing after 2 days was scored based on the following rating criteria (1 to 5 points), and the pain-reducing effect was evaluated from the average of the scores of the three people. In addition, the pain level before the start of the test was one point of the following rating criteria for all subjects.
• (A) Component and (3-B) Dentifrice (Examples 3-1 to 3-25) containing dentinal tubules early blocking effect, pain reducing effect, feeling of use (taste) Compared to the dentifrice (Example 3-26, Comparative Examples 3-1 to 3-3) using the component (3-B) alone or using a comparative product (polyvinylpyrrolidone or proline) of the component (A). It was remarkably superior. In the dentifrice (Examples 3-16 to 3-19) containing the component (3-C) in addition to the component (A) and the component (3-B), the effect of early blockage of dentinal tubules was very excellent.
• the dentifrice (Examples 3-24 and 3-25) containing the component (D) was very excellent in pain reduction effect. Further, the dentifrice (Examples 3-20 to 3-23) containing the (3-C) component and the (3-D) component was very excellent in the effect of early blockage of dentinal tubules and the effect of reducing pain.
• composition for oral cavity of the present invention is excellent in the early blockage effect of dentinal tubules, the pain reduction effect and the feeling of use (taste).
• composition for oral cavity (3) of the present invention is remarkably excellent in dentinal tubule early-sealing effect, pain-reducing effect, and feeling of use (taste).
• Examples 4-1 to 4-22 and Comparative Example 4-1 [Main ingredients used] [(A) component] (A-1): Pyrrolidonecarboxylic acid “AJIDEW A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc. (A-2): 6-oxo-2-piperidinecarboxylic acid Sigma-Aldrich Japan, trade name “(S) -6-Oxo-2-piperidine carboxylic acid” (A-3): 3- (2-oxo-1-azepanyl) propanoic acid manufactured by Sigma Aldrich Japan Co., Ltd., trade name “3- (2-Oxoazepan-1-yl) propanoic acid”
• Component (C)] (C-1): Sodium fluoride, manufactured by Stella Chemifa, trade name “Sodium fluoride” (C-2): Sodium monofluorophosphate, Rhodia Nikka Co., Ltd., trade name “Sodium monofluorophosphate”
• 1.0 kg (100 parts by mass) of a dentifrice was prepared by the following conventional method for preparing a dentifrice according to the blending ratio (parts by mass) shown in Tables 33 to 35.
• Phase II Active ingredients blended in Phase I, Phase II, Phase III and other additive ingredients
• Active ingredients for phase I pyrrolidone carboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, potassium nitrate, sodium fluoride (ii) for phase I
• Addiii) Additive components for phase II: propylene glycol, sodium carboxymethylcellulose, methylparaben
• Phase III additive components silicic anhydride, sodium lauryl sulfate, flavor
• Tables 33 to 35 also show the alleviation effect and feeling of use (taste) on pain caused by hypersensitivity in each Example and Comparative Example evaluated according to the above evaluation methods and evaluation criteria.
• the dentifrice of Comparative Example 4-1 containing no component (A) and no component (4-B) is pain due to hypersensitivity at the time of water rinsing immediately after brushing one week after switching to a placebo dentifrice. Almost no reduction effect was observed, and the feeling of use (taste) was poor (Table 35).
• Example 4-22 containing no component (4-B) containing component (A) is one week after switching to a placebo dentifrice compared to the toothpaste of Comparative Example 4-1.
• the effect of reducing the pain due to hypersensitivity and the feeling of use (taste) were excellent (Table 35).
• the dentifrices of Examples 4-1 to 4-21 containing the component (A) in combination with the component (4-B) were used at the time of rinsing with water just after brushing one week after switching to a placebo dentifrice.
• the pain due to hypersensitivity was effectively reduced, and it was confirmed that the pain due to hypersensitivity was significantly reduced (Tables 33 and 34). It was also confirmed that the dentifrices of Examples 4-1 to 4-21 had a good feeling of use (taste).
• the toothpastes of Examples 4-16 to 4-21 containing the component (4-C) in addition to the component (A) and the component (4-B) are immediately after brushing one week after switching to a placebo dentifrice. Even when rinsing with water, the pain due to hypersensitivity is hardly felt or not felt at all, and by containing (4-C) component, the effect of component (A) is further enhanced. It was confirmed that the remarkable alleviation effect on pain due to hypersensitivity was further increased (contrast between Example 4-11 and Examples 4-16 to 4-19, and Examples 4-2 and 4-20, 4). (Contrast with -21).
• Examples 5-1 to 5-14 and comparative examples 5-1 to 5-5 Dentifrices having the compositions shown in Tables 39 to 41 were prepared. That is, a phase A was prepared by mixing and dissolving water-soluble components (component (A), component (5-B), sodium fluoride, sodium saccharin, sorbitol, etc.) in purified water at room temperature. On the other hand, a B phase was prepared by dissolving or dispersing an oil-soluble component such as methylparaben, sodium polyacrylate, sodium alginate and the like in propylene glycol at room temperature. Next, B phase was added and mixed in A phase under stirring, and C phase was prepared.
• component (A) component
• component (5-B) component
• sodium fluoride sodium saccharin
• sorbitol sorbitol
• fragrance, anhydrous silicic acid and other components were mixed at room temperature using a 1.5 L kneader, depressurized to 4 kPa and defoamed to prepare each composition.
• the unit of the blending amount of each component in Tables 39 to 41 is mass%.
• Green tea extract was prepared by the extraction method described in Food ingredient analysis. That is, a tea pack containing 3 g of green tea leaves (a farmer's own tea 980, manufactured by ITO EN) was added to 100 mL of tap water at about 90 ° C., and extracted for 2 minutes.
• the dentifrice of each example was diluted 3 times with distilled water, and the centrifugal supernatant (room temperature, 20 minutes, 10,000 rotations) was diluted. These HA discs were immersed for 5 minutes. Thereafter, it was rinsed lightly with distilled water, and excess water was blotted with a filter paper. The reason why the three-fold diluted solution is used is that it is assumed that the dentifrice is diluted with saliva during brushing. The reason for rinsing with distilled water is that a mouthwash after using the dentifrice was assumed.
• model stain After the surface of HA (Hydroxyapatite) disk (APP-735; manufactured by HOYA Co., Ltd.) was rough-polished with sand blast, the HA disk was added to a 0.5% by weight albumin solution for 20 minutes.
• a model stain was prepared by repeating 20 times in the prepared concentrated black tea extract for 20 minutes and 20 minutes in a 0.3 mass% ferric chloride solution for 20 minutes in total.
• Example 5-14 containing the component (A) was excellent in stain removal effect and preparation feeling (Table 41).
• the compositions of Examples 5-1 to 5-13 containing the component (A) and the component (5-B) were excellent in balance with respect to the stain formation inhibitory effect, the stain removal effect, the gloss effect and the feeling of use of the preparation (Table 39 and 40).
• none of the compositions of Comparative Examples lacking the component (B) satisfied all the four effects (Table 41).
• the composition for oral cavity of the present invention contains the component (A) and the component (5-B), and is excellent in the stain formation suppressing effect, the stain removing effect, the gloss effect and the feeling of use of the preparation. It is shown that.
• a specified amount of purified water is put into a stainless steel vessel equipped with a three-one motor and a stirrer having rotating blades.
• the sex component was added and dissolved while stirring.
• a specified amount of organic solvent such as ethanol is added and oil-soluble components such as fragrance and methylparaben are added while stirring. , Dissolved. Further, the oil-soluble component was added to the container in which the water-soluble component was dissolved, and the mixture was stirred for 30 minutes to prepare a mouthwash as a uniform solution.
• Examples 6-1 to 6-14 and Comparative Examples 6-1 to 6-2 A dentifrice was prepared in the same manner as in Example 5-1, except that the composition was changed to the compositions shown in Tables 45 and 46. Dentin collagen coloring inhibition evaluation of each dentifrice was performed under the following conditions.
• this sample was immersed in a 3-fold water dilution of the composition of each Example and Comparative Example for 3 minutes at room temperature, washed with distilled water, and then at 37 ° C. artificial saliva (CaCl 2 : 2.2 mmol / L).
• KH 2 PO 4 2.2 mmol / L
• acetic acid 0.1 mol / L
• collagenase derived from Clostridium histolyticum Type 1A, manufactured by Sigma
• 0.2 unit / mL pH 6.5
• Colored liquid (1) 0.3% instant black tea (Kroger (registered trademark) Instant Tea) aqueous solution
• compositions of Comparative Examples 6-1 to 6-2 containing no component (A) did not show the dentin collagen coloring effect, whereas those of Examples 6-1 to 6-14 containing the component (A)
• the composition was excellent in dentin collagen coloring suppression effect.
• (A) component is useful as an active ingredient of a dentin collagen coloring inhibitor.
• this result has suggested that the composition for oral cavity (6) can exhibit a collagen coloring inhibitory effect.

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