[go: up one dir, main page]

WO2014050144A1 - Agent de blocage de tubule dentinaire - Google Patents

Agent de blocage de tubule dentinaire Download PDF

Info

Publication number
WO2014050144A1
WO2014050144A1 PCT/JP2013/005784 JP2013005784W WO2014050144A1 WO 2014050144 A1 WO2014050144 A1 WO 2014050144A1 JP 2013005784 W JP2013005784 W JP 2013005784W WO 2014050144 A1 WO2014050144 A1 WO 2014050144A1
Authority
WO
WIPO (PCT)
Prior art keywords
dentin
calcium
less
present
phosphorylated saccharide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2013/005784
Other languages
English (en)
Japanese (ja)
Inventor
田中　智子
隆嗣 小林
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ezaki Glico Co Ltd
Original Assignee
Ezaki Glico Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ezaki Glico Co Ltd filed Critical Ezaki Glico Co Ltd
Priority to JP2014538205A priority Critical patent/JP5977835B2/ja
Publication of WO2014050144A1 publication Critical patent/WO2014050144A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/16—Fluorine compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/20—Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
    • A61K6/831—Preparations for artificial teeth, for filling teeth or for capping teeth comprising non-metallic elements or compounds thereof, e.g. carbon
    • A61K6/838—Phosphorus compounds, e.g. apatite
    • 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
    • A61K8/19—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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; 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

  • POs-Ca is (1) a food material prepared from potato starch; (2) highly water-soluble calcium; (3) inhibits the precipitation of neutral calcium phosphate; (4) mutans streptococci (5) has an in vitro plaque formation inhibitory effect; (6) has a pH buffering action, can increase the calcium ion concentration in saliva, and can create an oral environment that is easy to remineralize; Has the advantage.
  • Fluoride ions are known to promote remineralization and recrystallization and serve to strengthen teeth (hardness and acid resistance).
  • fluoride ions have a drawback that they react with normal calcium ions and become insoluble. If insolubilized, it will be difficult to penetrate the teeth and a smooth remineralization reaction cannot be expected.
  • the coexistence of POs—Ca with fluoride provides the advantage that both calcium and fluoride derived from POs—Ca are dissolved. That is, the fluoride can coexist with calcium derived from POs—Ca in an ionized state, and can deliver both ions to the affected area in an ionized state. Both calcium ions and fluoride ions dissolve in saliva, making it possible to create a good environment for teeth.
  • Dentin and enamel differ in composition, structure, critical pH, hardness and the like. Enamel is the hardest part of the body's hard tissue. In the tooth structure, dentin hardness (generally KHN about 68) is much softer than enamel hardness (generally Knoop hardness (KHN) about 343), and the elastic modulus is about 84 GPa. In contrast, the dentin is 13 to 17 GPa. In this way, since dentin has a more flexible property than enamel, in dentin, caries easily progresses rapidly, or dentine easily wears or causes erosion.
  • the enamel has a high content of hydroxyapatite [Ca 10 (PO 4 ) 6 (OH) 2 ] of about 96%, and the others are composed of organic matter, water, and the like.
  • Hydroxyapatite is a crystal structure of calcium and phosphoric acid.
  • the diameter of the dentinal tubule is larger than the diameter of the bacterium, when the dentinal tubule is exposed, the bacteria can enter the dentinal tubule and propagate there. Therefore, when the dentinal tubule is exposed, bacteria enter and propagate easily, and the progress of caries is accelerated.
  • the dentin at the crown is covered with enamel and the dentin at the root is covered with gingiva, so it is not exposed in the oral cavity and caries does not easily occur.
  • the collagen matrix structure collapses due to aging and the gums retract, or the gums retract due to periodontal treatment, poor occlusion, excessive brushing, etc.
  • the surface dentin may be exposed. That is, the dentinal tubule may be exposed. When the dentinal tubule is exposed, the carious bacteria invade the dentinal tubule as described above and become caries.
  • the opening of the dentinal tubule has been confirmed, and the opening of the dentinal tubule is considered to be a cause of hypersensitivity.
  • the opening of the dentinal tubule is considered to be a cause of hypersensitivity.
  • the dentinal tubule may be applied as it is, and caries may be further deteriorated. In that case, it is difficult to remove the solid matter only at the invasion site of the bacteria, and it is necessary to scrape the whole.
  • an adhesive resin which is a conventional dental material
  • the resin is easily soiled, deteriorated, diminished, or scraped and difficult to maintain. Therefore, it is preferable to fill the opening by a method other than resin.
  • Other methods for treating hypersensitivity include blocking the pulp nerve with potassium ions. However, this method is not a fundamental treatment method because it has neither an effect of treating caries nor an effect of blocking dentinal tubules.
  • Patent Document 1 Japanese Patent Laid-Open No. 2009-167135
  • Patent Document 1 describes a caries treatment kit.
  • This caries treatment kit includes (1) a hydroxyapatite particle-containing composition and (2) a phosphorylated saccharide calcium-containing composition.
  • phosphorylated oligosaccharides are used for blocking dentinal tubules, but do not describe the use alone, but use hydroxyapatite as a necessary component.
  • the dentinal tubules are sealed by applying hydroxyapatite particles to the dentinal tubules. Therefore, this method has a drawback that complete sealing is difficult as in the conventional method using a paste-like dentinal tubule sealing agent.
  • Patent Document 2 Patent No. 3466350
  • Patent Document 3 Patent No. 2964182
  • Patent Document 4 Japanese Patent Laid-Open No. 05-117153
  • Patent Document 2 relates to a dental composition for dentin hypersensitivity.
  • This composition comprises (A) (1) polymer particles having a particle diameter smaller than the dentinal tubule diameter and forming an aggregate larger than the dentinal tubule diameter by reacting with a calcium compound as emulsion particles. And (2) an aqueous emulsion component that has been purified by ultrafiltration through ultrafiltration to have a metal ion concentration in the dispersion medium of 1000 ppm or less, and (B) a water-soluble organic acid or a water-soluble salt component thereof.
  • the calcium salt of the organic acid is insoluble or hardly soluble in water.
  • This composition may be used after being mixed and stored in a container containing the component (A) and the component (B) together, and forming a film by coating.
  • the component (A) and the component (B) May be stored in separate containers, and the respective components may be sequentially applied in any order or mixed immediately before use to form a film by application.
  • the component (A) and the component (B) are mixed and contained, a water-insoluble or poorly water-soluble calcium salt is formed during storage, and there is a problem that precipitation larger than the dentinal tubule diameter is formed. Further, even when the component (A) and the component (B) are stored in separate containers and used, the composition is an emulsion, so that there is a problem that the application to the dentin tends to be uneven. is there.
  • the present invention not a emulsion but a composition that forms a clear solution is used. Therefore, it has the advantage that uniform application to dentin is possible and aggregation is less likely to occur in terms of storage stability. Further, the present invention is different in that it does not form an aggregate by reacting with a calcium compound but forms a film by contact with the tooth surface.
  • Patent Document 3 relates to a dentinal hypersensitivity therapeutic agent.
  • the dentin hypersensitivity therapeutic agent of Patent Document 3 includes the following component (A) and / or component (B): (A) (a) a water-soluble zinc salt and (b) a polyol phosphate ester and / or a salt thereof. A colloid of zinc hydroxide and / or zinc oxide obtained by mixing in an aqueous medium; (B) a zinc salt of a polyol phosphate.
  • Patent Document 3 shows that a polyol phosphate metal salt is effective for blocking dentinal tubules.
  • polyol phosphate esters include monosaccharides, oligosaccharides, polysaccharides and polyol phosphate esters, and specifically glucose-1-phosphate, glucose-6-phosphate, and the like. Yes. However, Patent Document 3 does not describe calcium salts.
  • phosphorylated saccharide calcium salt or other phosphorylated saccharide salt or a combination of phosphorylated saccharide and other calcium salt
  • phosphorylated saccharide calcium salt or other phosphorylated saccharide salt or a combination of phosphorylated saccharide and other calcium salt
  • Glucose-1-phosphate zinc salt (G-1-P-Zn) and its calcium salt G-1-P-Ca in the examples of Patent Document 3 are insoluble salts even when contacted with saliva. Whereas the effect is reduced, the dentinal tubule blocker containing the phosphorylated saccharide calcium salt of the present invention can be insolubilized only on the tooth surface to form a film, and thus can work efficiently. it can.
  • Patent Document 4 relates to an agent for preventing and treating dentine hypersensitivity and an oral composition containing the same.
  • the agent for preventing and treating dentine hypersensitivity disclosed in Patent Document 4 comprises a polyol phosphate metal salt as an active ingredient.
  • the metal of the metal salt is one selected from Fe, Ti, Al, Sn, Cu, Ni, Si, Mg, Ba, Sr, V, Mn, Mo, Ag, Nb, Zr, Sb, In, and a lanthanoid or It is described that there are two or more kinds.
  • a phosphorylated saccharide calcium salt as in the present invention, it is possible to prevent aggregation over a suitable use concentration, and to form an insolubilized film only on the tooth surface. Therefore, compared with Glucose-1-phosphate zinc salt (G-1-P-Zn) and its calcium salt G-1-P-Ca in the example of Patent Document 4, a high effect is obtained with a small amount of calcium. be able to.
  • JP 2009-167135 A Japanese Patent No. 3466350 Japanese Patent No. 2964182 JP 05-117153 A
  • An object of the present invention is to provide a novel dentinal tubule sealant, dentin dentin enhancer and an oral composition, medicinal composition and food containing these.
  • dentinal tubules originally present in the dentin open to the outside.
  • dentinal tubule sealants used for the purpose of suppressing hypersensitivity are known.
  • dentinal tubule blocking agents are solids mainly composed of aluminum salts, silicates, calcium salts, phosphates and the like.
  • these sequestering agents can be used for pastes and the like, they contain particles having a particle size that functions as a sequestering agent, and are not suitable for edible use because of their rough texture and poor taste.
  • the feeling of use is bad.
  • liquid dentinal tubule blocking agent that can be used as food
  • those using a polyol phosphate metal salt described in Patent Document 4 are known.
  • the conventional liquid dentinal tubule sealant is a colloidal solution and thus has a problem of poor stability, or a two-liquid mixed type and complicated handling.
  • the present inventors have found that a specific material containing calcium (for example, phosphorylated saccharide calcium salt (preferably POs-Ca)) is used to seal dentinal tubules and ivory.
  • a specific material containing calcium for example, phosphorylated saccharide calcium salt (preferably POs-Ca)
  • POs-Ca phosphorylated saccharide calcium salt
  • the dentinal tubule sealant according to item 1 or 2 which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • the dentinal tubule sealant according to Item 5 wherein the sugar moiety has a degree of polymerization of 3 to 9.
  • (Item 7) The dentinal tubule sealant according to any one of Items 1 to 6, wherein the number of the phosphate groups is 1 to 2.
  • (Item 8) The dentinal tubule sealant according to any one of items 1 to 7, wherein the calcium-containing component is a phosphorylated saccharide calcium salt.
  • (Item 9) The dentinal tubule sealant according to any one of Items 1 to 8, wherein the calcium salt in (ii) is a water-soluble calcium salt.
  • a dentin dentin enhancer containing a calcium-containing component The calcium-containing component is (Ii) a phosphorylated saccharide calcium salt; or (ii) a phosphorylated saccharide salt or phosphorylated saccharide other than the phosphorylated saccharide calcium salt and a calcium salt other than the phosphorylated saccharide calcium salt; or (iii) the ( A dentin dentin strengthening agent which is a mixture of i) and (ii), wherein the phosphorylated saccharide is composed of a saccharide moiety and a phosphate group.
  • the dentin dentin reinforcing agent of item 10 which further contains a fluoride.
  • (Item 16) The dentin dentin enhancer according to any one of items 10 to 15, wherein the number of the phosphate groups is 1 to 2.
  • (Item 17) The dentin dentin reinforcing agent according to any one of items 10 to 16, wherein the calcium-containing component is a phosphorylated saccharide calcium salt.
  • (Item 18) The dentin dentin enhancer according to any one of Items 10 to 17, wherein the calcium salt in (ii) is a water-soluble calcium salt.
  • An oral composition comprising the dentinal tubule blocker according to any one of items 1 to 9, or the dentin dentin enhancer according to any one of items 10 to 18. Oral composition.
  • (Item 20) The oral cavity composition according to item 19, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • (Item 21) The intraoral composition according to item 19, further comprising 0.1% by weight or more of hydroxyapatite.
  • (Item 22) Dentifrice, mouthwash, troche, gel, spray, coating agent, ointment, chewing tablet, medicated chewing gum, chewable tablet, orally disintegrating tablet, wax matrix tablet, multilayer tablet or continuous tablet The oral composition according to any one of items 19 to 21.
  • (Item 23) A medicinal composition comprising the dentinal tubule blocker according to any one of items 1 to 9 or the dentin dentin enhancer according to any one of items 10 to 18.
  • composition Composition.
  • (Item 24) The medicinal composition according to item 23, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • (Item 25) The medicinal composition according to item 23, further comprising 0.1% by weight or more of hydroxyapatite.
  • (Item 26) The medicinal composition according to any one of items 23 to 25, which is a chewing gum, a chewing tablet or a troche.
  • (Item 2A) The dentinal tubule sealant according to item 1 or 2A, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • (Item 3A) The dentinal tubule sealant according to Item 1A or 2A, further comprising 0.1% by weight or more of hydroxyapatite.
  • (Item 4A) The dentinal tubule sealant according to any one of Items 1A to 3A, wherein the sugar moiety is a glucan residue.
  • (Item 5A) The dentinal tubule blocking agent according to Item 4A, wherein the sugar moiety has a degree of polymerization of 3 to 9, and the number of phosphate groups is 1 to 2.
  • Items 1A to 8A Any one of Items 1A to 8A including a calcium-containing component so that a molar concentration ratio of calcium ions to phosphorus ions in saliva in the oral cavity when used in the oral cavity is 5.0 or less.
  • a dentin tooth enhancer containing a calcium-containing component The calcium-containing component is (Ii) a phosphorylated saccharide calcium salt; or (ii) a phosphorylated saccharide salt or phosphorylated saccharide other than the phosphorylated saccharide calcium salt and a calcium salt other than the phosphorylated saccharide calcium salt; or (iii) the ( A dentin dentin enhancer, which is a mixture of i) and (ii), wherein the phosphorylated saccharide comprises a glucan residue having a polymerization degree of 3 to 9 and 1 to 2 phosphate groups.
  • (Item 11A) The dentin dentin enhancer according to Item 10A, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • (Item 12A) The dentin dentin enhancer according to item 10A or 11A, further comprising 0.1% by weight or more of hydroxyapatite.
  • (Item 13A) The dentin dentin enhancer according to any one of items 10A to 12A, wherein the calcium-containing component is a phosphorylated saccharide calcium salt.
  • (Item 14A) The dentin dentin enhancer according to any one of items 10A to 13A, wherein the calcium salt in (ii) is a water-soluble calcium salt.
  • (Item 15A) The dentin dentin enhancer according to any one of items 10A to 14A, which contains fluoride so that the fluoride ion concentration in saliva when used in the oral cavity is 100 ppm or less.
  • (Item 16A) Any one of Items 10A to 15A including a calcium-containing component so that a molar concentration ratio of calcium ions to phosphorus ions in saliva in the oral cavity when used in the oral cavity is 5.0 or less.
  • (Item 18A) The oral cavity composition according to Item 17A, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • (Item 19A) The intraoral composition according to Item 17A, further comprising 0.1% by weight or more of hydroxyapatite.
  • (Item 20A) Dentifrice, mouthwash, troche, gel, spray, coating agent, ointment, chewing tablet, medicated chewing gum, chewable tablet, orally disintegrating tablet, wax matrix tablet, multilayer tablet or continuous tablet.
  • (Item 21A) A medicinal composition comprising the dentinal tubule blocker according to any one of items 1A to 9A or the dentin dentin enhancer according to any one of items 10A to 16A Composition.
  • (Item 22A) The medicinal composition according to item 21A, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • (Item 23A) The medicinal composition according to Item 21A, further comprising 0.1% by weight or more of hydroxyapatite.
  • (Item 24A) The medicinal composition according to any one of items 21A to 23A, which is a chewing gum, a chewing tablet or a troche.
  • the dentinal tubule sealant of the present invention works by mixing with saliva, forms a smooth and acid-resistant coating on the exposed dentin surface, and opens without filling the dentinal tubule with a granular sealant Block the part.
  • hypersensitivity for example, a phenomenon in which a cold object looks into a tooth
  • the dentinal tubule sealant of the present invention not only has the effect of sealing the dentinal tubules, but also remineralizes the dentin by using the present invention for the initial carious dentin, thereby sealing the dentinal tubules.
  • a film can be formed and a rapid reaction can be caused by the solution.
  • the combined use of fluoride and phosphorylated saccharide calcium salt can strengthen the dentin surface and increase acid resistance.
  • fluoride and phosphorylated saccharide calcium salt preferably POs—Ca
  • the conventional dentinal tubule sealant used in paste form cannot remineralize dentin, but the dentinal tubule sealant of the present invention can remineralize dentinal tubule defects.
  • acid resistance can be strengthened and pressure resistance can be strengthened.
  • the dentinal tubule sealant of the present invention is made only of a material that does not greatly affect the taste of food and is safe even when continuously ingested. For example, even if the concentration of fluorine is 1/1000 compared to around 1000 ppm which is conventionally used, the acid resistance effect is exhibited.
  • a film that coats dentin is formed instead of a method of filling a mainstream dentinal tubule with a paste in the prior art.
  • fluorine is added to the film, the acid resistance increases, and the film becomes difficult to disintegrate by acid.
  • the coating obtained by the present invention is smooth and covers the dentin surface layer without gaps, and thus has a high sealing ability.
  • remineralization or enhancement of acid resistance or pressure resistance of healthy dentin can be performed simultaneously with capillary blockage.
  • the dentinal tubule sealant according to the present invention can be used as a liquid, and since the molecules of the component effective for sealing are very small, the dentinal tubules spread throughout the oral cavity and fine grooves of the teeth, and the exposed dentinal tubules in the mouth are efficiently used. Can be well sealed.
  • the dentin film obtained by using the dentinal tubule sealant of the present invention normally covers the dentin firmly, but can be easily peeled off by a special treatment and can be injected into the dentinal tubule. It also protects the dentin from coloring and acts as a coating that is mechanically easy to remove.
  • the dentinal tubule sealant and dentin dentin enhancer of the present invention are excellent in stability because they are liquids that are not particle suspensions or colloids.
  • the dentinal tubule sealant and dentin dentin enhancer of the present invention can be used in household dental care products such as dentifrices and mouthwashes to prevent hypersensitivity, and dental materials such as pastes, dental fillers, and chewable tablets. .
  • dentinal tubule sealant and dentin dentin enhancer of the present invention have a good taste and can be composed only of materials that can be used as food materials, they can be added to food as unique applications.
  • FIG. 1 is a photograph showing the results of Experiment 1.
  • FIG. 1 shows that the water solubility of POs—Ca is excellent.
  • FIG. 2 is a microradiograph showing dentin enhancement of Experiment 2A.
  • FIG. 3 is a microradiograph showing dentin enhancement of Experiment 2D.
  • FIG. 4 is a microradiograph showing dentin strengthening from Experiment 2B.
  • FIG. 5 is a microradiograph showing the remineralization effect of dentin in Experiment 2A.
  • FIG. 6 is a microradiograph showing the effect of remineralization of dentin in Experiment 2D.
  • FIG. 7 is a microradiograph showing the remineralization effect of dentin in Experiment 2B.
  • FIG. 8 is a scanning electron micrograph showing the result of Experiment 2A.
  • the upper row is a photograph taken obliquely from above the dentin surface so as to include the dentin cross section
  • the lower row is a photograph taken from above the dentin surface.
  • the left is a photograph of a demineralized part
  • the middle is a photograph of a remineralized part
  • the right is a photograph of a part subjected to acid treatment after strengthening the tooth.
  • the scale is 50 ⁇ m
  • the lower row the scale is 20 ⁇ m.
  • FIG. 9 is a scanning electron micrograph showing the results of Experiment 2B.
  • the upper row is a photograph taken obliquely from above the dentin surface so as to include the dentin cross section
  • the lower row is a photograph taken from above the dentin surface.
  • the left is a photograph of a demineralized part
  • the middle is a photograph of a remineralized part
  • the right is a photograph of a part subjected to acid treatment after strengthening the tooth.
  • the scale is 50 ⁇ m
  • the scale is 20 ⁇ m.
  • FIG. 10 is a scanning electron micrograph showing the result of Experiment 2C.
  • the upper row is a photograph taken obliquely from above the dentin surface so as to include the dentin cross section
  • the lower row is a photograph taken from above the dentin surface.
  • the left is a photograph of a demineralized part
  • the middle is a photograph of a remineralized part
  • the right is a photograph of a part subjected to acid treatment after strengthening the tooth.
  • the scale is 50 ⁇ m
  • the scale is 20 ⁇ m.
  • FIG. 11 is a scanning electron micrograph showing the result of Experiment 2D.
  • the upper row is a photograph taken obliquely from above the dentin surface so as to include the dentin cross section
  • the lower row is a photograph taken from above the dentin surface.
  • the left is a photograph of a demineralized part
  • the middle is a photograph of a remineralized part
  • the right is a photograph of a part subjected to acid treatment after strengthening the tooth.
  • the scale is 50 ⁇ m
  • the scale is 20 ⁇ m.
  • FIG. 12 is a microradiograph showing the results of Experiments 4A to 4D.
  • FIG. 12 shows the results when POs—Ca is used as the calcium source.
  • FIG. 13 is a microradiograph showing the results of Experiments 4A to 4D. In Figure 13, it shows the results of using a CaCl 2 as a calcium source. The thick line shows the result of area 2 (remineralization part), and the thin line shows the result of area 3 (decalcification part).
  • FIG. 14 is a scanning electron micrograph showing the results of Experiments 4A to 4C. These photographs are taken from above the dentin surface. The upper row is a photograph when the POs-Ca treatment is performed, and the lower row is a photograph when the CaCl 2 treatment is performed. FIG.
  • FIG. 15 is a microradiograph showing the results of Experiments 5A to 5D.
  • FIG. 15 shows the results when POs—Ca as a calcium source was used in combination with various concentrations of fluoride.
  • the thick line shows the result of area 2 (remineralization part), and the thin line shows the result of area 3 (decalcification part).
  • FIG. 16 is a microradiograph showing the results of Experiments 5A, 5C and 5D.
  • FIG. 16 shows the results when CaCl 2 is used in combination with various concentrations of fluoride as a calcium source. In the case of a fluoride concentration of 1 ppm, the sample was broken and data could not be obtained.
  • FIG. 17 is a scanning electron micrograph showing the results of Experiments 5C and 5D. These photographs are taken from above the dentin surface. The upper row is a photograph when the POs-Ca treatment is performed, and the lower row is a photograph when the CaCl 2 treatment is performed. The photograph on the left is a photograph when the fluoride concentration is 10 ppm, and the photograph on the right is a photograph when the fluoride concentration is 100 ppm.
  • tooth refers to the dentin of a tooth.
  • the term “dental tubule blocking agent” refers to a substance or a combination thereof that contributes to blockage of a part or all of dentinal tubules. It is preferable that the dentinal tubule sealing agent is mainly composed of a substance that contributes to dentinal tubule sealing.
  • dentin remineralization means that part or all of the dentin surface exposed in the oral cavity is remineralized. In the present invention, it is preferable that about 10% or more of the dentin surface area exposed in the oral cavity can be remineralized.
  • the proportion of exposed dentin surface area that is remineralized is preferably about 20% or more, more preferably about 30% or more, even more preferably about 40% or more, particularly preferably about 50% or more, and even more preferably about 60%. % Or more, even more preferably about 70% or more, still more preferably about 80% or more, and most preferably about 90% or more.
  • the term “medicament” is intended for use in the diagnosis, treatment or prevention of human or animal disease and is not a mechanical instrument, dental material, medical article or hygiene article; or person or Items intended to affect the structure or function of the animal's body, but not mechanical instruments, dental materials, medical supplies and hygiene items.
  • the definition of medicine does not include quasi drugs and cosmetics.
  • quadsi-drug refers to (1) prevention of vomiting and other discomfort or bad breath or body odor; prevention of blisters and sores; prevention of hair loss, hair growth or hair removal; or for human or animal health It is intended for the control or prevention of rats, flies, mosquitoes, etc., and has a mild effect on the human body, and is not a mechanical instrument, dental material, medical article or sanitary article, or (2 ) Of those intended to be used for diagnosis, treatment or prevention of human or animal diseases, or intended to affect the structure or function of the human or animal body, Those designated by the Minister of Health, Labor and Welfare. In countries other than Japan, the definition of “pharmaceuticals” and “quasi-drugs” takes precedence over the laws of that country.
  • a calcium-containing component that is, (i) a phosphorylated saccharide calcium salt; or (ii) a phosphorylated saccharide salt or phosphorylated saccharide other than the phosphorylated saccharide calcium salt and calcium other than the phosphorylated saccharide calcium salt Combinations with salts; or (iii) mixtures of (i) and (ii) above are used.
  • Other materials eg, fluoride
  • fluoride can also be used if desired.
  • a phosphorylated saccharide salt or phosphorylated saccharide other than the phosphorylated saccharide calcium salt of (ii) and a calcium salt other than the phosphorylated saccharide calcium salt can form a phosphorylated saccharide calcium salt in an aqueous solution. It can act in the same way as oxidized calcium calcium salt. Therefore, it is considered that the effect on the phosphorylated saccharide calcium salt referred to in the present specification can be obtained similarly for the combination (ii).
  • the phosphorylated saccharide used in the present invention consists of a saccharide moiety and a phosphate group.
  • phosphorylated sugar refers to a sugar having at least one phosphate group in the molecule.
  • phosphorylated saccharide salt refers to a phosphorylated saccharide salt.
  • phosphorylated saccharide inorganic salt refers to an inorganic salt of phosphorylated saccharide.
  • calcium salt of phosphorylated saccharide refers to a calcium salt of phosphorylated saccharide.
  • the number of phosphate groups in the phosphorylated saccharide is not particularly limited, but is preferably 10 or less per molecule of phosphorylated saccharide, more preferably 5 or less. More preferably, the number of phosphate groups in the phosphorylated saccharide is one, two or three, and particularly preferably one or two, per phosphorylated saccharide molecule.
  • the degree of polymerization of the sugar moiety in the phosphorylated saccharide is preferably 2 or more, more preferably 3 or more.
  • the degree of polymerization of the saccharide in the phosphorylated saccharide is preferably about 100 or less, more preferably about 90 or less, more preferably about 80 or less, more preferably about 70 or less, more preferably about 60 or less, more preferably about 50 or less, more preferably about 40 or less, more preferably about 30 or less, more preferably about 20 or less, more preferably about 10 or less, More preferably, it is about 9 or less, More preferably, it is about 8 or less, More preferably, it is about 7 or less, More preferably, it is about 6 or less, Most preferably, it is about 5 or less.
  • degree of polymerization refers to the number of structural units, that is, the number of monosaccharide residues.
  • degree of polymerization of a sugar consisting of 3 glucose units is 3. In some cases, it refers to the number of structural units of the average polymer molecule.
  • the molecular weight of the phosphorylated saccharide is preferably about 400 or more, more preferably about 500 or more, still more preferably about 600 or more, and particularly preferably about 700 or more.
  • the molecular weight of the phosphorylated saccharide is preferably about 1 million or less, more preferably about 100,000 or less, and even more preferably about 10,000 or less, for example, about 9000 or less, about 8000 or less, about 7000 or less, About 6000 or less, about 5000 or less, about 4000 or less, about 3000 or less, particularly preferably 2000 or less, and in one embodiment 1000 or less.
  • the phosphorylated saccharide is in the form of an acid (that is, hydrogen is bonded to the phosphate group).
  • the ionized form of phosphorylated saccharide that is, the hydrogen of the phosphate group is dissociated and separated into a phosphate ion
  • the salt form ie, phosphate ion and base. May be used.
  • an inorganic salt of a phosphorylated saccharide is used.
  • the inorganic salt of phosphorylated saccharide is preferably a calcium salt, magnesium salt, potassium salt, zinc salt, iron salt or sodium salt.
  • a phosphorylated saccharide in the form of a calcium salt is also referred to as phosphorylated saccharide calcium.
  • the magnesium salt of phosphorylated saccharide is also referred to as phosphorylated saccharide magnesium.
  • the potassium salt of phosphorylated saccharide is also referred to as phosphorylated saccharide potassium.
  • the zinc salt of phosphorylated saccharide is also referred to as phosphorylated saccharide zinc.
  • the iron salt of phosphorylated sugar is also called phosphorylated sugar iron.
  • a phosphorylated saccharide in the form of a sodium salt is also referred to as phosphorylated saccharide sodium. The same applies to other inorganic salts.
  • the phosphorylated saccharide and its salt used in the present invention are the phosphorylated saccharide and its salt described in JP-A-8-104696.
  • the sugar moiety of the phosphorylated saccharide can be any sugar residue.
  • the sugar moiety is preferably a residue of a sugar selected from the group consisting of glucan, reduced glucan, mannan, dextran, agar, cyclodextrin, fucoidan, gellan gum, locust bean gum, guar gum, tamarind gum, and xanthan gum.
  • Glucan residues or reduced glucan residues are preferred.
  • reduced glucan refers to a product obtained by reducing an aldehyde at the reducing end of glucan to an alcohol. Reduced glucan is obtained, for example, by hydrogenating glucan to reduce aldehyde to alcohol.
  • the degree of polymerization in the glucan residue or reduced glucan residue is preferably 2 or more, more preferably 3 or more.
  • the number of glucose residues is preferably about 100 or less, more preferably about 90 or less, more preferably about 80 or less, more preferably about 70 or less, more preferably about 60 or less. More preferably, it is about 50 or less, more preferably about 40 or less, more preferably about 30 or less, more preferably about 20 or less, more preferably about 10 or less, more preferably about 9 or less, more preferably about 8 or less, still more preferably about 7 or less, more preferably about 6 or less, and particularly preferably about 5 or less.
  • the number of inorganic ions in the phosphorylated saccharide inorganic salt is not particularly limited, and inorganic ions may be bonded to all of the phosphate groups present in the phosphorylated saccharide, or inorganic ions may be bonded to only a part. Also good. Only one inorganic ion may be present in one molecule of phosphorylated saccharide inorganic salt, two may be present, or three or more may be present.
  • the number of inorganic ions in one molecule of phosphorylated saccharide inorganic salt is preferably about 20 or less, more preferably about 10 or less, and still more preferably about 5 or less.
  • the number of calcium ions in phosphorylated saccharide calcium is not particularly limited. Calcium ions may be bound to all phosphate groups present in phosphorylated saccharide, or calcium ions may be bound to only a part. Good. Only one calcium ion may be bound to one phosphorylated saccharide molecule, two may be bound, or three or more may be bound.
  • the number of calcium ion bonds per molecule of phosphorylated saccharide is preferably about 20 or less, more preferably about 10 or less, and still more preferably about 5 or less.
  • phosphorylated saccharide calcium has a tooth remineralization effect, a calcium absorption promoting effect, and a taste improving effect.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein the phosphorylated saccharide or inorganic thereof has at least one phosphate group bound to the glucan residue or reduced glucan residue. Salt is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein 1 to 2 phosphate groups are bound to the glucan residue or reduced glucan residue, A phosphorylated saccharide inorganic salt in which an inorganic ion is bonded to each of these phosphate groups is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein at least one phosphate group is bound to the glucan residue or reduced glucan residue, Phosphorylated saccharide calcium having calcium bound to at least one of the groups is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein 1 to 2 phosphate groups are bound to the glucan residue or reduced glucan residue, Phosphorylated sugar calcium in which calcium is bound to each of these phosphate groups is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or the reduced glucan residue is an ⁇ -1,4 linked 3-5 glucose residue.
  • a phosphorylated saccharide inorganic salt comprising a group and having one phosphate group bonded to the glucan residue or reduced glucan residue and having an inorganic ion bonded to the phosphate group is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or the reduced glucan residue is an ⁇ -1,4 linked 3-5 glucose residue.
  • a phosphorylated saccharide calcium having a group and having one phosphate group bound to the glucan residue or reduced glucan residue and calcium bound to the phosphate group is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or reduced glucan residue comprises 2-8 glucose residues that are ⁇ -1,4 linked. 1 to 2 phosphate groups bound to the glucan residue or reduced glucan residue, and inorganic ions are bound to at least one, preferably all of these phosphate groups.
  • An inorganic salt of phosphorylated saccharide is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or reduced glucan residue is from 2-8 glucose ⁇ -1,4 linked. And 1 to 2 phosphate groups are bound to the glucan residue or reduced glucan residue, and calcium is bound to at least one, preferably all of these phosphate groups. Phosphorylated sugar calcium is used.
  • the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or reduced glucan residue has ⁇ -1,4-linked glucose as a main chain, and ⁇ Phosphorylated saccharides having a side chain of glucose with -1,6 bonds or ⁇ -1,4 bonds are used.
  • the phosphorylated saccharide and its salt that can be used in the present invention may be used as a pure one type of compound or as a mixture of a plurality of types.
  • the phosphorylated saccharide and its salt used in the present invention are preferably the phosphorylated saccharide and its salt described in JP-A-8-104696.
  • JP-A-8-104696 When produced according to the method described in JP-A-8-104696, a mixture of a plurality of types of phosphorylated saccharide or a salt thereof is obtained.
  • the mixture may be used as it is, or after separation into a pure compound, only one kind of compound may be selected and used.
  • the phosphorylated saccharide and its salt exhibit excellent performance both when used alone and when used as a mixture.
  • the phosphorylated saccharide can be produced, for example, by phosphorylating a known saccharide.
  • the phosphorylated saccharide inorganic salt can be produced, for example, by phosphorylating a known saccharide to obtain an acid-form phosphorylated saccharide, and then converting the acid-form phosphorylated saccharide into an inorganic salt.
  • the phosphorylated saccharide calcium can be produced, for example, by phosphorylating a known saccharide to obtain an acid-form phosphorylated saccharide, and then converting the acid-form phosphorylated saccharide into a calcium salt.
  • a method for producing phosphorylated saccharide and salts thereof is described in JP-A-8-104696.
  • Phosphorylated sugar calcium is also sold as phosphorylated oligosaccharide calcium by Ezaki Glico Co., Ltd.
  • sugar that is a raw material for producing phosphorylated saccharide and salts thereof examples include glucan, mannan, dextran, agar, cyclodextrin, fucoidan, gellan gum, locust bean gum, guar gum, tamarind gum, and xanthan gum.
  • glucan preferably a starch having many phosphate groups bound thereto, such as a potato crude starch, is suitable, but a refined product may also be used. Modified starch can also be suitably used.
  • the sugar when it is glucan, it can be obtained by decomposing starch having a phosphate group or modified starch.
  • starch having a phosphate group or modified starch amylolytic enzyme, glycosyltransferase, or ⁇ -glucosidase, or one or more combinations thereof (excluding only one ⁇ -glucosidase) Act.
  • the amylolytic enzyme is composed of one or more combinations of ⁇ -amylase, ⁇ -amylase, glucoamylase, isoamylase, pullulanase, or neopullulanase.
  • the glycosyltransferase is a cyclodextrin glucanotransferase.
  • the above production method causes a glycosyltransferase to act on a sugar having a phosphate group.
  • the glycosyltransferase is cyclodextrin glucanotransferase.
  • the phosphorylated saccharide inorganic salt is produced, for example, by allowing an alkaline earth metal salt or an iron salt to act on an acid phosphorylated saccharide.
  • the phosphorylated saccharide calcium is produced, for example, by allowing a calcium salt to act on the phosphorylated saccharide in the acid form.
  • phosphorylated saccharide and its salt a high-purity one or a low-purity one may be used.
  • phosphorylated saccharides and salts thereof may be used as a mixture with other saccharides.
  • concentration and content are calculated based on the quantity of pure phosphorylated saccharide
  • the calcium salt may be water-soluble, water-insoluble, or poorly water-soluble.
  • a water-soluble calcium salt is preferred.
  • water-insoluble calcium salt refers to a calcium salt having a solubility in water at 20 ° C. of less than 1 g / 100 ml H 2 O.
  • water-insoluble calcium salts include calcium fluoride, calcium carbonate, calcium oxalate, hydroxyapatite, calcium monohydrogen phosphate, calcium malate, calcium oxide, calcium citrate, calcium sulfate, calcium hydroxide, calcium stearate and An example is calcium phosphate.
  • “poorly water-soluble calcium salt” refers to a calcium salt having a solubility in water of 20 ° C. of 1 g / 100 ml H 2 O or more and 5 g / 100 ml H 2 O or less.
  • the poorly water-soluble calcium salt include calcium gluconate, calcium dihydrogen phosphate and calcium benzoate.
  • the “water-soluble calcium salt” refers to a calcium salt having a solubility in water at 20 ° C. higher than 5 g / 100 ml H 2 O. The solubility of the water-soluble calcium salt used in the present invention in water at 20 ° C.
  • water-soluble calcium salt includes phosphorylated saccharide calcium salt.
  • Other examples of such water-soluble calcium salts include calcium chloride, water-soluble organic acid calcium salts (for example, calcium lactate, calcium acetate, calcium glutamate, calcium lactobinate, calcium formate, calcium propionate, calcium ascorbate, Glycerophosphate calcium and the like), polyol calcium phosphate, calcium nitrate, casein phosphopeptide calcium and the like.
  • the water-soluble calcium salt is selected from the group consisting of calcium lactate, calcium acetate, calcium formate, calcium ascorbate, calcium propionate, calcium lactobionate, calcium polyol phosphate, calcium glycerophosphate, casein phosphopeptide calcium, calcium chloride and calcium nitrate It is preferable.
  • fluoride is used. It is known that fluoride ions react easily with calcium ions and precipitate, but the presence of phosphorylated saccharide maintains the states of calcium ions and fluoride ions. Therefore, remineralization can be promoted by supplying fluoride simultaneously with calcium ions and phosphate ions. Furthermore, acquisition or strengthening of acid resistance can be expected by incorporating fluoride ions into the remineralization site.
  • fluoride is often used at a high concentration of 1000 ppm or more.
  • a phosphorylated saccharide or a salt thereof together with a fluoride, a sufficient amount of fluoride ions can be secured even if a fluoride having a lower concentration than before is used.
  • an effect equivalent to or higher than the conventional high concentration can be obtained.
  • a sufficient effect can be obtained even by adding fluoride of 100 ppm or less, preferably using 10 ppm or less.
  • Fluoride is preferably a compound that dissolves in water and releases fluoride ions.
  • the fluoride is preferably a fluoride that is approved for incorporation into foods, pharmaceuticals or quasi drugs.
  • fluorides include sodium fluoride, potassium fluoride, monofluorophosphoric acid and its salts (eg, sodium monofluorophosphate), calcium fluoride, strontium fluoride, cryolite, monofluoroacetic acid Etc.
  • potassium fluoride, sodium monofluorophosphate, strontium fluoride or tea-derived fluorine as the fluoride in the food or composition of the present invention.
  • fluorine eg, fluorine derived from tea, well water, seawater, salt, seafood, seaweed, etc.
  • the fluoride is a fluoride that is approved for incorporation into a pharmaceutical product.
  • the fluoride is a fluoride that is approved for incorporation into a quasi-drug.
  • Ca / P ratio the molar ratio of calcium: phosphate in saliva
  • P / Ca about 1.45
  • phosphate ion supply source at the same time depending on the assumed calcium ion concentration at the time of contact with the dentin surface.
  • the source of phosphate ions is referred to as a phosphate source compound.
  • a phosphoric acid source compound means a phosphoric acid compound.
  • the phosphate source compound that can be used in the present invention may be any compound as long as it is a compound that releases phosphate ions when dissolved in water.
  • the phosphate source compound is preferably a water-soluble phosphate or inorganic phosphoric acid.
  • phosphate source compounds include phosphoric acid, sodium phosphate, potassium phosphate, polyphosphoric acid and salts thereof, cyclic phosphoric acid and salts thereof, and the like.
  • Examples of sodium phosphate include sodium metaphosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, sodium pyrophosphate, sodium hydrogen pyrophosphate, and the like.
  • potassium phosphate examples include potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and tripotassium phosphate.
  • Polyphosphoric acid is a compound formed by condensation of two or more phosphoric acids. The degree of polymerization in the polyphosphoric acid is arbitrary as long as it is 2 or more. For example, it is 2 or more and 10 or less.
  • Examples of polyphosphoric acid include pyrophosphoric acid, triphosphoric acid, trimetaphosphoric acid, tetrametaphosphoric acid, and cyclopolyphosphoric acid. These polyphosphoric acid salts may also be used, preferably sodium, potassium or magnesium salts.
  • Examples of cyclic phosphoric acid include hexametaphosphoric acid. These cyclic phosphate salts may also be used, preferably sodium, potassium or magnesium salts.
  • the oral composition, medicinal composition and food of the present invention are usually used in the intended composition and food as long as they do not interfere with the dentinal tubule sealing action, remineralization action and acid resistance or pressure resistance strengthening action. Any material can be used.
  • the saccharide is more preferably selected from maltitol, reduced palatinose, palatinose, lactitol, erythritol, sorbitol, xylitol, aspartame L-phenylalanine compound, trehalose and mannitol.
  • the compounding of candy can be according to the compounding known in the art.
  • Tablets are foods that are formed by compression molding powders or granules, are gradually dissolved or disintegrated in the mouth, and are designed to act in the mouth for a long time.
  • the time it takes for tablet confection to start melting in the oral cavity and to finish melting depends on the size and ingredients of the tablet confection.
  • a person skilled in the art can arbitrarily design and manufacture a tablet confection suitable for achieving a desired time from when the tablet confection starts to melt until it finishes melting.
  • raw materials used in tablet confectionery include the following: sugars, calcium carbonate, calcium phosphate, calcium sulfate, powdered cellulose, emulsifiers, acidulants, flavorings, pH adjusters and colorants.
  • the saccharide is preferably a non-cariogenic saccharide in order to prevent caries.
  • the sugar can be a sugar (sucrose, starch syrup, lactose, glucose, starch, etc.), a sugar alcohol or a high intensity sweetener.
  • the saccharide is more preferably selected from maltitol, reduced palatinose, palatinose, lactitol, erythritol, sorbitol, xylitol, aspartame L-phenylalanine compound, trehalose and mannitol.
  • the blending of tablet confectionery can be in accordance with a blend known in the art.
  • caries is a disease caused by bacteria. Therefore, combined use with an antibacterial agent or a plaque formation inhibitor is also effective in the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention. It is also known that hydroxyapatite adsorbs cariogenic bacteria.
  • bactericides and antibacterial agents include benzalkonium chloride, cetylpyridinium chloride, parapenes, benzoic acid, alcohols such as ethanol, and the like.
  • relatively safe substances include combinations with chitin, chitosan, chitosan oligosaccharide, lactoferrin, polyphenol, and the like.
  • a drug that suppresses inflammation caused by bacteria can also be used in combination.
  • the main anti-inflammatory agents include flavonoids such as genistein and naringenin, polyamines, ⁇ -glucans, alkaloids, hesperidin, hesperetin, glycosylated hesperidin and the like.
  • flavonoids such as genistein and naringenin
  • polyamines such as genistein and naringenin
  • ⁇ -glucans such as alkaloids
  • hesperidin hesperetin
  • glycosylated hesperidin and the like.
  • these various drugs can be included in the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food as required. If the dentinal tubules are sealed with bacteria, they may grow in the dentinal tubules and cause secondary caries. Therefore, it is preferable that the dentinal tubule sealant, dentin den
  • the dentinal tubule sealant of the present invention is a dentinal tubule sealant comprising a specific component containing calcium (hereinafter referred to as “component (A)” in the present specification), wherein the component (A) is: (Ii) a phosphorylated saccharide calcium salt; or (ii) a phosphorylated saccharide salt other than phosphorylated saccharide calcium salt or a combination of a phosphorylated saccharide and a calcium salt other than phosphorylated saccharide calcium salt; or (iii) above ( a mixture of i) and (ii).
  • component (A) is: (Ii) a phosphorylated saccharide calcium salt; or (ii) a phosphorylated saccharide salt other than phosphorylated saccharide calcium salt or a combination of a phosphorylated saccharide and a calcium salt other than phosphorylated saccharide calcium salt; or (iii) above ( a mixture of i) and (i
  • the dentinal tubule sealant of the present invention may contain hydroxyapatite or may contain substantially no hydroxyapatite.
  • the dentinal tubule sealant of the present invention in one embodiment, does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • the dentinal tubule sealant of the present invention may be used by a patient who performs treatment using hydroxyapatite, or may be used by a patient who does not perform treatment using hydroxyapatite.
  • the dentinal tubule sealant of the present invention is for a patient performing treatment with hydroxyapatite
  • the dentinal tubule sealant of the present invention is For patients who are not treated with hydroxyapatite.
  • the dentinal tubule sealant of the present invention may be used by patients who do not undergo treatment using hydroxyapatite. That is, according to the present invention, dentinal tubule sealing without using hydroxyapatite is also possible.
  • the dentinal tubule sealant of the present invention when the dentinal tubule sealant of the present invention does not contain hydroxyapatite, the dentinal tubule sealant may be used by a patient who performs treatment using hydroxyapatite. That is, when the dentinal tubule sealant of the present invention does not contain hydroxyapatite, the treatment with the dentinal tubule sealant may be combined with the treatment using hydroxyapatite.
  • the dentinal tubule sealant of the present invention can be used as a raw material for preparing an oral composition, a medicinal composition, a food, or a dentinal tubule sealant.
  • a composition mainly composed of active ingredients for sealing dentinal tubules is referred to as a “dental tubule blocking agent” and is a composition for blocking dentinal tubules, which is shaped in addition to the dentinal tubule blocking agent.
  • An oral composition containing an agent or the like is referred to as an oral composition for dentinal tubule sealing.
  • “Mainly composed of active ingredients” means that the total of active ingredients in the composition is about 90% by weight or more of the total weight of the composition.
  • An intraoral composition refers to a composition for use in the oral cavity.
  • the amount of component (A) in the dentinal tubule sealant of the present invention can be arbitrarily set, but the lower limit is preferably about 50% by weight or more, more preferably about 60% by weight or more, and further preferably About 70% by weight or more, particularly preferably about 80% by weight or more, and most preferably about 90% by weight or more.
  • the upper limit of the amount of component (A) can be appropriately set in combination with other active ingredients.
  • the amount of the component (A) in the dentinal tubule sealant of the present invention is set in consideration of the amount of phosphoric acid preliminarily present in saliva. This amount is such that the molar ratio of calcium ions to phosphorus present as ions in saliva when ingesting the dentinal tubule sealant is about 5.0 or less (more preferably about 3 or less, more preferably about 0.1 to about 2.0, most preferably about 1.67 to about 2.0).
  • the dentinal tubule sealant of the present invention may further contain a fluoride.
  • the lower limit of the fluoride concentration in the dentinal tubule sealant is preferably about 0.00001% by weight or more, more preferably about 0.00005% by weight or more, and further preferably about 0.00008% by weight or more. And most preferably at least about 0.0001% by weight. In some cases, the lower limit of the concentration of fluoride in the dentinal tubule sealant may be about 5% by weight or more.
  • the upper limit of the fluoride concentration in the dentinal tubule sealant is preferably about 50% by weight or less, more preferably about 40% by weight or less, still more preferably about 30% by weight or less, and particularly preferably about 20% by weight or less, and most preferably about 10% by weight or less.
  • the dentin dentin enhancer of the present invention is a dentin dentin enhancer containing the component (A), and the component (A) is (i) phosphorylated saccharide calcium salt; or (ii) phosphorylated saccharide calcium salt.
  • the dentin dentin enhancer of the present invention may contain hydroxyapatite or may not contain hydroxyapatite substantially.
  • the dentin dentin enhancer of the present invention does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
  • the dentin dentin enhancer of the present invention may be used by a patient who performs treatment using hydroxyapatite, or may be used by a patient who does not perform treatment using hydroxyapatite.
  • the dentin dentin enhancer of the present invention is for a patient performing treatment with hydroxyapatite, and in another particular embodiment, treatment with hydroxyapatite is performed. For patients who do not.
  • the dentin dentin enhancer of the present invention when the dentin dentin enhancer of the present invention does not contain hydroxyapatite, the dentin dentin enhancer may be used by a patient who does not perform treatment using hydroxyapatite. That is, according to the present invention, dentin dentin strengthening without using hydroxyapatite is also possible. Further, for example, when the dentin dentin enhancer of the present invention does not contain hydroxyapatite, the dentin dentin enhancer may be used by a patient who performs treatment using hydroxyapatite.
  • the dentin dentin strengthening agent of the present invention does not contain hydroxyapatite
  • the treatment with the dentin dentin strengthening agent and the treatment using hydroxyapatite may be combined.
  • the dentin dentin strengthening agent of the present invention can be used as a raw material for preparing an oral composition, a medicinal composition, a food or a composition for dentin dentin strengthening.
  • the composition mainly composed of active ingredients for dentin dentin strengthening is referred to as “dentin dentin enhancer”, and is a composition for strengthening dentin dentin,
  • An intraoral composition containing an excipient or the like in addition to a dentin dentin enhancer is referred to as an intraoral composition for dentin dentin strengthening.
  • the term “dentin dentin enhancement” means improving the performance of the dentin portion of the tooth as a tooth, specifically, enhancing the hardness and / or acid resistance of the dentin. That means.
  • the dentin dentin enhancing agent of the present invention enhances both dentin hardness and acid resistance.
  • the dentin dentin enhancer of the present invention has an action of promoting remineralization in the demineralized portion of the dentin and suppressing the demineralization in the healthy portion of the dentin. Therefore, from this viewpoint, it can be said that the dentin dentin reinforcing agent of the present invention is a dentin remineralizing agent or a dentin demineralization inhibitor.
  • acid resistance improves by suppressing demineralization of dentin, it can be said that the dentin tooth strengthening agent of this invention is a dentin acid resistance improver.
  • the dentin dentin enhancer of the present invention acts on both the demineralized portion of the dentin and the healthy portion of the dentin
  • the dentin dentin enhancer of the present invention demineralizes the dentin. It is also useful for patients having a part, and also useful for a healthy person having only a healthy part that does not have a demineralized part in dentin.
  • the amount of the component (A) in the dentin enhancer of the present invention can be arbitrarily set, but the lower limit is preferably about 50% by weight or more, more preferably about 60% by weight or more, Preferably it is about 70% by weight or more, particularly preferably about 80% by weight or more, and most preferably about 90% by weight or more.
  • the upper limit of the amount of component (A) can be appropriately set in combination with other active ingredients.
  • the amount of the component (A) in the dentin dentin enhancer of the present invention is set in consideration of the amount of phosphoric acid present in advance in saliva. This amount is such that the molar ratio of calcium ions to phosphorus present as ions in saliva when ingesting a dentin dentin enhancer is about 5.0 or less (more preferably about 3 or less, more preferably about 0.1). To about 2.0, most preferably about 1.67 to about 2.0).
  • the dentin dentin enhancer of the present invention may further contain fluoride.
  • the lower limit of the fluoride concentration in the dentin enhancer is preferably about 0.00001% by weight or more, more preferably about 0.00005% by weight or more, and further preferably about 0.00008% by weight. And most preferably about 0.0001% by weight or more. In some cases, the lower limit of the concentration of fluoride in the dentin dentin enhancer may be about 5% by weight or more.
  • the upper limit of the fluoride concentration in the dentin enhancer is preferably about 50% by weight or less, more preferably about 40% by weight or less, still more preferably about 30% by weight or less, and particularly preferably Is about 20% by weight or less, and most preferably about 10% by weight or less.
  • the intraoral composition of the present invention contains the dentinal tubule blocker of the present invention or the dentin dentin enhancer of the present invention.
  • the intraoral composition of the present invention can be used for dentinal tubule sealing or dentin dentin strengthening.
  • the intraoral composition of the present invention can also be used for the purpose of simultaneously performing both dentinal tubule sealing and dentin dentin strengthening.
  • the oral composition of the present invention may be used by a patient who performs treatment using hydroxyapatite, or may be used by a patient who does not perform treatment using hydroxyapatite.
  • the oral composition of the invention is for a patient undergoing treatment with hydroxyapatite, and in another particular embodiment, the oral composition of the invention comprises For patients who are not treated with hydroxyapatite.
  • the intraoral composition of the present invention may contain hydroxyapatite or may contain substantially no hydroxyapatite.
  • the oral composition of the present invention may be used by patients who do not perform treatment with hydroxyapatite. That is, according to the present invention, treatment without using hydroxyapatite is possible.
  • the oral composition of the present invention may be used by a patient who performs treatment using hydroxyapatite. That is, when the oral composition of the present invention does not contain hydroxyapatite, the treatment with the oral composition may be combined with the treatment using hydroxyapatite.
  • the content of the dentinal tubule sealant or dentin dentin enhancer in the oral composition of the present invention can be appropriately set according to a method known in the art.
  • the amount of phosphate ions may be 2 to 4 mM.
  • the oral composition of the present invention contains an excipient.
  • the intraoral composition of the present invention may contain materials other than excipients.
  • excipients and other materials that may be included in the oral compositions of the present invention include excipients (eg, powdered cellulose, starch, water, etc.), antibacterial agents, bactericides, gelling agents, Examples include stickers, binders, and lubricants (eg, stearic acid, magnesium stearate, etc.).
  • the oral composition of the present invention does not contain a component that can cause caries such as sucrose, or its content is extremely small to the extent that it does not cause caries.
  • the content of saccharides that can cause caries is preferably 10% by weight or less of the weight of the oral composition.
  • the oral composition of the present invention is preferably a pharmaceutical or a quasi drug.
  • the composition, production method and use of pharmaceuticals and quasi drugs are known to those skilled in the art.
  • the oral composition of the present invention is a powder
  • the composition comprises component (A): (i) phosphorylated saccharide calcium salt; or (ii) a salt or phosphorylated phosphorylated saccharide other than phosphorylated saccharide calcium salt. Combination of sugar and calcium salt other than phosphorylated sugar calcium salt; or (iii) Mixture of (i) and (ii) above is mixed with other conventionally known materials as required by a conventionally known method. Can be manufactured.
  • the composition comprises component (A): (i) phosphorylated saccharide calcium salt; or (ii) phosphorylated saccharide salt or phosphorylated other than phosphorylated saccharide calcium salt.
  • a combination of a saccharide and a calcium salt other than a phosphorylated saccharide calcium salt; or (iii) a mixture of (i) and (ii) above is added to a conventionally known solvent and mixed by a conventionally known method. obtain.
  • the total content of the phosphorylated saccharide or a salt thereof in the oral composition of the present invention is arbitrarily set in consideration of the form of the oral composition, the dilution rate during use, and the like. Can be done.
  • the total content of phosphorylated saccharide or a salt thereof (excluding phosphorylated saccharide calcium) in the oral composition of the present invention is the composition in the oral cavity when the composition is used in the oral cavity.
  • the concentration of phosphorylated saccharide in the mixture of saliva and saliva is preferably about 1.0 mM or more, more preferably about 1.5 mM or more, further preferably about 2.0 mM or more, particularly preferably about 3.0 mM or more, and most preferably Is an appropriate amount to be about 4.0 mM or more.
  • the content (total) of the phosphorylated saccharide and its salt in the composition of the present invention is determined by phosphorylation in a mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity.
  • the amount of the sugar is preferably about 20 mM or less, more preferably about 15 mM or less, further preferably about 12 mM or less, particularly preferably about 10 mM or less, and most preferably about 9.0 mM or less.
  • the content is 1.0 mM when the composition in the oral cavity is used in the oral cavity and its concentration in the saliva mixture is 1.0 mM.
  • “It is an amount suitable for achieving the above concentration” means that a liquid produced in the oral cavity is collected for 20 minutes after the use of the oral composition of the present invention, and the concentration of the component in the liquid is collected. Is an amount appropriate for a concentration of 1.0 mM. The same is true for other concentrations.
  • the liquid that accumulates in the oral cavity is a mixture of pure saliva, a liquid portion derived from the oral composition, and various solutes derived from the oral composition.
  • the total content of oxidized sugars or salts thereof is preferably about 1.0 mM or more, more preferably about 1.5 mM or more, and further preferably about 2.0 mM or more in terms of phosphorylated sugar concentration. And particularly preferably about 3.0 mM or more, and most preferably about 4.5 mM or more.
  • the total content of phosphorylated saccharides or salts thereof in the oral composition of the present invention is preferably about 20 mM or less, more preferably about 15 mM or less in terms of calcium content.
  • the intraoral composition is a composition intended to be used diluted in the oral cavity, the components are blended in consideration of the dilution factor. For example, in the case of an oral composition intended to be diluted about 20 times, it is formulated at a concentration of 20 times.
  • the content of the calcium salt (including phosphorylated saccharide calcium) in the oral composition of the present invention is arbitrary in consideration of the form of the oral composition, the dilution rate during use, and the like.
  • the calcium salt content in the oral composition of the present invention is preferably such that the concentration of calcium in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity is about The amount is 1.0 mM or more, more preferably about 1.5 mM or more, further preferably about 2.0 mM or more, particularly preferably about 3.0 mM or more, and most preferably about 4.5 mM or more.
  • the content of the calcium salt in the composition of the present invention is such that the calcium concentration in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity is preferably about 20 mM.
  • it is an amount suitable to be about 15 mM or less, more preferably about 12 mM or less, particularly preferably 10 mM or less, and most preferably about 9.0 mM or less.
  • the total salt content is preferably about 1.0 mM or more, more preferably about 1.5 mM or more, still more preferably about 2.0 mM or more, particularly preferably in terms of calcium content. About 3.0 mM or more, and most preferably about 4.5 mM or more. In this case, for example, the total content of calcium salts in the oral composition of the present invention is preferably about 20 mM or less, more preferably about 15 mM or less, even more preferably in terms of calcium content.
  • the intraoral composition is a composition intended to be used diluted in the oral cavity, the components are blended in consideration of the dilution factor. For example, in the case of an oral composition intended to be diluted about 20 times, it is formulated at a concentration of 20 times.
  • the amount of the component (A) in the intraoral composition of the present invention is set in consideration of the amount of phosphoric acid preliminarily present in the saliva. This amount is such that the molar ratio of calcium ions to phosphorus present as ions in saliva when the oral composition is ingested is about 5.0 or less (more preferably about 3 or less, more preferably about 0.1 to about 2.0, most preferably about 1.67 to about 2.0).
  • the content of fluoride in the oral composition of the present invention can be arbitrarily set in consideration of the form of the oral composition, the dilution rate during use, and the like.
  • the content of fluoride in the oral composition of the present invention is determined by the fluorine concentration (“fluoride ion” in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity. Concentration ”) is preferably about 0.01 ppm or more, more preferably about 0.1 ppm or more, still more preferably about 0.2 ppm or more, still more preferably about 0.3 ppm or more, particularly preferably about 0.4 ppm or more. The most suitable amount is about 0.5 ppm or more.
  • the fluoride content is preferably the fluorine concentration in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity, for example, about 100 ppm or less, about 10 ppm or less, about 8 ppm.
  • the amount is appropriate to be about 6 ppm or less, about 4 ppm or less, or about 2 ppm or less.
  • the foot composition in the oral composition of the present invention is used.
  • the content of the compound is preferably about 0.01 ppm or more, more preferably about 0.1 ppm or more, still more preferably about 0.2 ppm or more, and still more preferably about 0.01 ppm or more, in terms of fluorine content. It is 0.3 ppm or more, particularly preferably about 0.4 ppm or more, and most preferably about 0.5 ppm or more.
  • the total content of fluoride in the oral composition of the present invention is preferably about 100 ppm or less, about 10 ppm or less, about 8 ppm or less, about 6 ppm, in terms of fluorine content. Below, it can be about 4 ppm or less, or about 2 ppm or less.
  • the intraoral composition is a composition intended to be used diluted in the oral cavity, the components are blended in consideration of the dilution factor. For example, in the case of an oral composition intended to be diluted about 20 times, it is formulated at a concentration of 20 times.
  • component (A) (ie (i) phosphorylated saccharide calcium salt; or (ii) phosphorylated saccharide salt or phosphorylated saccharide other than phosphorylated saccharide calcium salt and other than phosphorylated saccharide calcium salt) Or (iii) a mixture of (i) and (ii) above) in a concentration of 1 mM to 12 mM as a calcium concentration.
  • the fluoride concentration is preferably about 0.001 times or more, more preferably about 0.0015 times or more, and more preferably about 0.001 times or more the calcium concentration derived from the component (A) as the fluorine concentration.
  • the fluoride concentration is preferably about 15 times or less, more preferably about 10 times or less, and more preferably about 5 times the calcium concentration derived from component (A) as the fluorine concentration. It is more preferably 0.0 times or less, particularly preferably about 1.0 times or less, and most preferably about 0.5 times or less.
  • the concentration of the phosphoric acid source compound in the composition depends on the form of the oral composition, the dilution rate in use, etc. It can be set arbitrarily in consideration.
  • the concentration of the Ca / P ratio in the oral cavity is preferably adjusted so as to be within the above-mentioned preferable range.
  • the content of the phosphate source compound in the composition of the present invention is such that the phosphate concentration in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity.
  • the amount is appropriate to be 4.0 mM or more.
  • the content of the phosphate source compound in the composition of the present invention is such that the phosphate concentration in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity is preferably about 15 mM or less. More preferably about 10 mM or less, still more preferably about 9 mM or less, particularly preferably about 7 mM or less, most preferably about 5 mM or less.
  • the content of the acid source compound is preferably about 1.0 mM or more, more preferably about 2.0 mM or more, more preferably about 3.0 mM or more, still more preferably about 3.0 mM, in terms of phosphoric acid content. As described above, it is particularly preferably about 3.6 mM or more, and most preferably about 4.0 mM or more.
  • the content of the phosphoric acid source compound in the oral composition of the present invention is preferably about 15 mM or less, more preferably about 10 mM or less, and still more preferably about 0.1 mM in terms of the phosphoric acid content. 9 mM or less, particularly preferably about 7 mM or less, and most preferably about 5 mM or less.
  • the oral composition of the present invention is preferably retained in the oral cavity for a certain period of time when administered into the oral cavity.
  • the time for the oral composition of the present invention to stay in the oral cavity is preferably about 10 seconds or longer, more preferably about 30 seconds or longer. More preferably, it is about 1 minute or more, and particularly preferably about 5 minutes or more. In one preferred embodiment it is about 10 minutes or more, and in a more preferred embodiment it is about 15 minutes or more.
  • There is no particular upper limit to the time for the oral composition of the present invention to stay in the oral cavity and it may be, for example, about 1 hour or less, about 50 minutes or less, about 40 minutes or less, about 30 minutes or less, about 20 minutes or less. If the residence time is too short, it may be difficult to obtain a dentinal tubule sealing effect and a dentin strengthening effect.
  • oral compositions other than foods include dentifrices, mouthwashes (also referred to as mouthwashes), and medicated chewing gums.
  • oral composition forms include, for example, lozenges, gels, sprays, coatings, ointments, chewable tablets, chewable tablets, orally disintegrating tablets, wax matrix tablets, multilayer tablets, and sustained-release tablets. It is done. It is also possible to use a form such as a wiping cloth in which a nonwoven fabric or the like is impregnated with the liquid composition of the oral composition of the present invention, or a form such as a cotton swab.
  • the oral composition of the present invention is usually sold in a container or packaged.
  • This container may be a commonly used container such as plastic.
  • This packaging may be a commonly used packaging such as paper, plastic, cellophane and the like.
  • instructions regarding the amount of intake of the oral composition of the present invention, the intake timing, the intake method for example, in the case of gum, “it is preferable to continue to chew two tablets for about 20 minutes or more”
  • it is described.
  • an instruction sheet in which such an instruction is described may be inserted.
  • the medicinal composition of the present invention contains the dentinal tubule sealant of the present invention or the dentin dentin enhancer of the present invention.
  • the medicinal composition of the present invention may be a pharmaceutical, a quasi drug or a health food.
  • the medicinal composition of the present invention is preferably a pharmaceutical product or a quasi drug.
  • the medicinal composition of the present invention is for patients who are not treated with hydroxyapatite.
  • the content of the dentinal tubule blocker or dentin dentin enhancer in the medicinal composition of the present invention can be appropriately set according to a method known in the art.
  • the amount of phosphate ions may be 2 to 4 mM.
  • the content of the phosphorylated saccharide or its salt, calcium salt, fluoride, and phosphate source compound in the medicinal composition of the present invention is preferably in the same range as the amount described for the oral composition.
  • the medicinal composition of the present invention is preferably used under the supervision of a doctor, or purchased according to a prescription and used in accordance with a doctor's instructions.
  • the medicinal composition of the present invention is different from general foods.
  • the medicinal composition of the present invention is preferably retained in the oral cavity for a certain period of time when administered into the oral cavity.
  • the time for retaining the medicinal composition of the present invention in the oral cavity is preferably about 10 seconds or more, more preferably about 30 seconds or more. More preferably, it is about 1 minute or more, and particularly preferably about 5 minutes or more. In one preferred embodiment it is about 10 minutes or more, and in a more preferred embodiment it is about 15 minutes or more.
  • There is no particular upper limit to the time for the medicinal composition of the present invention to stay in the oral cavity and it may be, for example, about 1 hour or less, about 50 minutes or less, about 40 minutes or less, about 30 minutes or less, about 20 minutes or less. If the residence time is too short, it may be difficult to obtain a dentinal tubule sealing effect and a dentin strengthening effect.
  • the intake amount of the medicinal composition of the present invention is preferably about 0.1 g or more, more preferably about 0.2 g or more, still more preferably about 0.5 g or more, even more preferably. Is about 1 g or more.
  • the intake frequency of the medicinal composition of the present invention can be appropriately set by a doctor. For example, at least once a week, at least twice a week, at least 3 times a week, at least 4 times a week, at least 5 times a week, at least 6 times a week, at least 7 times a week It may be once a day or more, twice a day or more, three times a day or more.
  • the frequency of intake of the medicinal composition of the present invention for example, 3 times or less per day, 2 times or less per day, 1 time or less per day, 7 times or less per week, 6 times or less per week, 1 week 5 times or less, 4 times or less per week, 3 times or less per week, 2 times or less per week, 1 time or less per week, or the like.
  • the timing of ingestion of the medicinal composition of the present invention may be before a meal, after a meal, or between meals, but is preferably after a meal.
  • the intake period of the medicinal composition of the present invention can be appropriately determined by a doctor.
  • the medicinal composition of the present invention can be taken preferably for about 1 day or more, more preferably for about 3 days or more, and most preferably for about 5 days or more.
  • the ingestion period of the medicinal composition of the present invention may be about 1 month or less, about 2 weeks or less, or about 10 days or less. Since demineralization in the oral cavity can occur on a daily basis, the medicinal composition of the present invention is preferably taken almost permanently.
  • one tablet may be taken at a time, or a plurality (eg, 2 to 10) may be taken at a time. Also good.
  • a plurality may be ingested at once, or a plurality may be ingested one by one.
  • the medicinal composition of the present invention is in the form of chewing gum, it is preferable to continue chewing for a long time, and when the medicinal composition of the present invention is a chewable tablet, it is preferable to chew for a long time, and the medicinal composition of the present invention is a troche When it is an agent, it is preferable that it is licked to the end without chewing.
  • Examples of the dosage form of the medicinal composition of the present invention include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules and the like.
  • the medicinal composition of the present invention may also be in the form of chewing gum, chewing tablets or lozenges.
  • the medicinal composition of the present invention is preferably in the form of chewing gum, chewing tablet or troche.
  • the weight taken at one time is preferably about 0.5 g or more, more preferably about 1 g or more, and further preferably about 1.5 g or more. is there.
  • the weight of the chewing gum is preferably about 5 g or less, more preferably about 4 g or less, and even more preferably about 3 g or less.
  • the weight taken at one time is preferably about 0.05 g or more, more preferably about 0.1 g or more, and further preferably about 0.00. It is 5 g or more.
  • the weight of the chewable tablet is preferably about 5 g or less, more preferably about 4 g or less, and still more preferably about 3 g or less.
  • the weight taken at one time is preferably about 0.5 g or more, more preferably about 1 g or more, and even more preferably about 1.5 g or more. It is.
  • the weight of the lozenge is preferably about 5 g or less, more preferably about 4 g or less, and still more preferably about 3 g or less.
  • the amount of each component can be designed in the same manner as the amount of each component in the following food.
  • the medicinal composition of the present invention is usually sold in a container or packaged.
  • This container may be a commonly used container such as plastic.
  • This packaging may be a commonly used packaging such as paper, plastic, cellophane and the like.
  • instructions regarding the intake amount, intake timing, and intake method of the pharmaceutical composition of the present invention are described. It is preferable that Alternatively, an instruction sheet in which such an instruction is described may be inserted.
  • the food of the present invention is a food for dentinal tubule sealing, and includes the dentinal tubule sealing agent of the present invention.
  • the food of the present invention is a dentinal tubule-sealing food for a patient who is not treated with hydroxyapatite, and includes the dentinal tubule-sealing agent of the present invention.
  • the food of the present invention is a food for dentin dentin strengthening and includes the dentin dentin fortifying agent of the present invention.
  • the food product of the present invention is a dentin tooth strengthening food product for a patient who is not treated with hydroxyapatite, and includes the dentin tooth enhancer of the present invention.
  • the content of the dentinal tubule blocker or dentin dentin enhancer in the food of the present invention can be appropriately set according to a method known in the art.
  • the amount of phosphate ions may be 2 to 4 mM.
  • the food of the present invention may be a food having a complicated structure such as the food described in WO2010 / 061932.
  • the food of the present invention may be, for example, chewing gums, single layer or multiple layers of candy, confectionery in which the gum is wrapped with candy, single layer or multiple layers of tablet confectionery, ice cream, frozen confectionery including solid foods, etc. Good. These foods can be produced by the method described in WO2010 / 061932.
  • the food of the present invention substantially uniformly contains a phosphorylated saccharide salt other than phosphorylated saccharide calcium salt or a combination of phosphorylated saccharide and a calcium salt other than phosphorylated saccharide calcium salt. It is preferable.
  • a food containing these uniformly has the advantage of being easy to manufacture.
  • a phosphorylated saccharide salt or a portion containing a phosphorylated saccharide may be separated from a portion containing a calcium salt other than the phosphorylated saccharide calcium salt.
  • a phosphorylated saccharide salt other than the phosphorylated saccharide calcium salt or a calcium salt other than the phosphorylated saccharide calcium salt is present at the same time or after the release. Should be designed to be released from food. This is because if calcium salts other than phosphorylated saccharide calcium salts are released earlier than phosphorylated saccharide or salts thereof, calcium ions are deposited randomly on the tooth surface, which is not preferable.
  • Fluoride is also used in the food of the present invention.
  • the fluoride should be designed to be released simultaneously with the phosphorylated saccharide salt or phosphorylated saccharide or after the phosphorylated saccharide salt or phosphorylated saccharide.
  • a phosphoric acid source compound may also be used, in which case the phosphoric acid source compound is simultaneously with the phosphorylated saccharide salt or phosphorylated saccharide or from the phosphorylated saccharide salt or phosphorylated saccharide. Is also preferably designed to be released later.
  • the food of the present invention comprises: component (A): (i) phosphorylated saccharide calcium salt; or (ii) phosphorylated saccharide salt or phosphorylated saccharide other than phosphorylated saccharide calcium salt and calcium other than phosphorylated saccharide calcium salt. In combination with salt; or (iii) any food comprising a mixture of (i) and (ii) above.
  • component (A) (i) phosphorylated saccharide calcium salt; or (ii) phosphorylated saccharide salt or phosphorylated saccharide other than phosphorylated saccharide calcium salt and calcium other than phosphorylated saccharide calcium salt.
  • Examples of the food of the present invention include, for example, chewing gums; candies; tablet confectionery; compound beverages; semi-fluid foods such as yogurt; baked confectionery such as biscuits and rice crackers; frozen confectionery such as ice cream; And noodles.
  • Chewing gums, candies and tablet confections are suitable as foods of the present invention because active ingredients can be retained in the oral cavity for a long time.
  • Stimulated saliva is known to contain calcium ions at a concentration of about 1 to 1.5 mM in advance, and it is desirable to consider when designing products.
  • the weight of the food of the present invention can be any weight.
  • the weight of the food of the present invention eaten at a time is preferably about 0.05 g or more, more preferably about 0.1 g or more, and further preferably about 0.5 g or more.
  • the weight of the food of the present invention eaten at a time is preferably about 5 g or less, more preferably about 4 g or less, and even more preferably about 3 g or less.
  • the weight of the chewing gum consumed at one time is preferably about 0.05 g or more, more preferably about 0.1 g or more, and further preferably about 0.5 g. That's it.
  • the weight of chewing gum eaten at a time is preferably about 5 g or less, more preferably about 4 g or less, and even more preferably about 3 g or less.
  • the weight of the candy eaten at a time is preferably about 0.5 g or more, more preferably about 1 g or more, and further preferably about 1.5 g or more.
  • the weight of candy eaten at a time is preferably about 5 g or less, more preferably about 4 g or less, and still more preferably about 3 g or less.
  • the weight of the tablet confection consumed at a time is preferably about 0.05 g to about 10 g, more preferably about 0.1 g to about 5 g, and even more preferably about 0 .2g to about 3g.
  • the food of the present invention can have any shape.
  • the food of the present invention when the food of the present invention is a chewing gum, candy, or tablet confectionery, it may be disc-shaped, spherical, rugby ball-shaped, heart-shaped, or the like.
  • the food of the present invention when the food of the present invention is a compound beverage, yogurt or the like, there is no particular shape.
  • the content of the phosphorylated saccharide and the salt in the food of the present invention is the form of the food, It can be set arbitrarily in consideration of the dilution rate during feeding.
  • the content (total) of the phosphorylated saccharide and its salt in the food of the present invention is preferably about 1.0 mM or more in the saliva in the oral cavity when the food is present in the oral cavity. More preferably about 1.5 mM or more, more preferably about 2.0 mM or more, particularly preferably about 2.5 mM or more, and most preferably about 3.0 mM or more.
  • the content (total) of the phosphorylated saccharide and its salt in the food of the present invention is such that the phosphorylated saccharide in saliva in the oral cavity when the food is present in the oral cavity is preferably about 12 mM or less.
  • the amount is preferably about 6 mM or less, more preferably about 5 mM or less, particularly preferably about 4.5 mM or less, and most preferably about 4 mM or less.
  • the content is such that when the food is present in the oral cavity, the concentration in the saliva in the oral cavity is such that its concentration is 1.0 mM or higher. "There is” means that the liquid produced in the oral cavity within 20 minutes after starting to eat the food of the present invention, and the concentration of the component in the liquid is measured to be 1.0 mM. An appropriate amount. For example, a method of collecting 20 times per minute is possible, and in this case, a combination of liquids collected 20 times can be used as a measurement sample.
  • the food is preferably kept in the oral cavity for 20 minutes without being swallowed. Alternatively, food may be put in the mouth little by little during 20 minutes and chewed.
  • saliva is not pure saliva secreted from the oral glands, but refers to fluid that accumulates in the oral cavity when food is chewed in the oral cavity.
  • the liquid that accumulates in the oral cavity is a mixture of pure saliva, a liquid portion derived from food, and various solutes derived from food. The amount of each component added to the food varies depending on the weight and size of the food.
  • the single intake of food When the single intake of food is large, it is blended so as to have a lower content than when the intake is small.
  • the amount (%) in 2 g of food is about 0.5 times the amount (%) in 1 g of food.
  • About 20 mL of human saliva is secreted on average in 20 minutes. Therefore, the blending amount into the food is set in consideration of how much is eluted with respect to 20 mL of saliva. Such a blending amount can be easily set by those skilled in the art.
  • the food is a chewing gum containing fluoride with phosphorylated sugar or salt thereof
  • chewing the gum in the mouth for about 20 minutes will result in about 50% of the fluoride contained in the gum within 20 minutes. ⁇ 60% of fluoride is eluted in saliva.
  • the content of the calcium salt (including calcium phosphate sugar) in the food of the present invention can be arbitrarily set in consideration of the form of the food, the dilution rate during feeding, and the like.
  • the content of the calcium salt in the food of the present invention is such that the concentration of calcium in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 1.0 mM or more, more preferably about The amount is 1.5 mM or more, more preferably about 2.0 mM or more, particularly preferably about 3.0 mM or more, and most preferably about 4.5 mM or more.
  • the content of the calcium salt in the food of the present invention is such that the concentration of calcium in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 15 mM or less, more preferably about 10 mM or less.
  • the amount is preferably about 9 mM or less, particularly preferably about 7 mM or less, and most preferably about 5 mM or less.
  • a calcium salt including phosphorylated saccharide calcium
  • the amount of saliva produced during 20 minutes of chewing is 20 mL and the molecular weight of calcium is about 40, so the food is present in the oral cavity.
  • the weight of the gum is Xg and the blending amount (calculated as calcium) is Y%
  • Y (%) ⁇ (0.8 to 12 (mg)) / (X (g) ⁇ 1000) ⁇ ⁇ 100
  • the blending amount as calcium is 0.04 to 0.6% by weight.
  • the blending amount as calcium is 0.08 to 1.2% by weight.
  • the gum weight is 10 g
  • the blending amount as calcium is 0.008 to 0%. .12% by weight.
  • the same calculation is performed when the weight of the gum is another weight.
  • a similar design can be applied to foods other than gum.
  • the amount of the component (A) in the food of the present invention is set in consideration of the amount of phosphoric acid preliminarily present in the saliva. This amount is such that the molar ratio of calcium ions to phosphorus present as ions in saliva when ingesting food is about 5.0 or less (more preferably about 3 or less, more preferably about 0.1 to about 2.0). The amount is preferably about 1.67 to about 2.0).
  • the concentration of fluoride in the food product of the present invention is such that when used in the oral cavity, the concentration of fluoride ions in the oral cavity is from about 0.2 ppm to about 100 ppm, more preferably from about 0.2 ppm to about 1 ppm. It is preferable to adjust so that.
  • the concentration of fluoride in the food of the present invention can be arbitrarily set in consideration of the form of the food, the dilution rate at the time of eating, and the like.
  • the fluoride concentration in the food of the present invention is preferably about 0.01 ppm or more, more preferably about 0.1 ppm or more in the saliva in the oral cavity when the food is present in the oral cavity. More preferably about 0.2 ppm or more, still more preferably about 0.3 ppm or more, particularly preferably about 0.4 ppm or more, most preferably about 0.5 ppm or more.
  • the concentration of fluoride is preferably about 100 ppm or less, more preferably about 50 ppm or less, still more preferably about 10 ppm or less, particularly preferably about fluorine concentration in saliva in the mouth when the food is present in the mouth.
  • the amount of saliva that appears during 20 minutes of chewing is 20 mL, and about 50% to about 60% of the blended amount is released.
  • the blending amount as fluorine is 0.0002 to 0.1% by weight.
  • the blending amount as fluorine is 0.0004 to 0.2% by weight
  • the blending amount as fluorine is 0.00004 to 0%. 0.02% by weight.
  • the same calculation is performed when the weight of the gum is another weight.
  • a similar design can be applied to foods other than gum.
  • component (A) (ie (i) phosphorylated saccharide calcium salt; or (ii) phosphorylated saccharide salt or phosphorylated saccharide other than phosphorylated saccharide calcium salt and other than phosphorylated saccharide calcium salt) Or (iii) a mixture of (i) and (ii) above) in a concentration of 1 mM to 12 mM as a calcium concentration.
  • the fluoride concentration is preferably about 0.001 times or more, more preferably about 0.0015 times or more, and more preferably about 0.001 times or more the calcium concentration derived from the component (A) as the fluorine concentration.
  • the fluoride concentration is preferably about 15 times or less, more preferably about 10 times or less, and more preferably about 5 times the calcium concentration derived from component (A) as the fluorine concentration. It is more preferably 0.0 times or less, particularly preferably about 1.0 times or less, and most preferably about 0.5 times or less.
  • the content of the phosphate source compound in the food is arbitrary in consideration of the form of the food, the dilution rate at the time of eating, and the like.
  • the content of the phosphate source compound in the food of the present invention is such that when the food is present in the oral cavity, the phosphate concentration in the saliva in the oral cavity is preferably about 1.0 mM or more. More preferably about 2.0 mM or more, even more preferably about 3.0 mM or more, still more preferably about 3.0 mM or more, particularly preferably about 3.6 mM or more, most preferably about 4.0 mM or more. Appropriate amount.
  • the content of the phosphate source compound in the food of the present invention is such that the phosphate concentration in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 15 mM or less, more preferably about 10 mM or less, The amount is more preferably about 9 mM or less, particularly preferably about 7 mM or less, and most preferably about 5 mM or less.
  • the content of the phosphate source compound in the food of the present invention can be arbitrarily set in consideration of the form of the food, the dilution rate during feeding, and the like.
  • the amount of saliva that appears during 20 minutes of chewing is 20 mL and the molecular weight of phosphoric acid is about 98, so the oral cavity when the food is present in the oral cavity
  • 0.196 mg to 19.6 mg of phosphate may be included as a single intake (98 ⁇ 0.1 (mM) ⁇ 0.
  • the blending amount as phosphoric acid is 0.0196 to 1.96 wt%, and if the weight of the gum is 10 g, the blending amount as phosphoric acid is 0.00196. To 0.196% by weight. The same calculation is performed when the weight of the gum is another weight. A similar design can be applied to foods other than gum.
  • the food of the present invention can be used for any application.
  • the food of the present invention can be used by both healthy people and those in need of hypersensitive treatment.
  • the intake amount, intake frequency, and intake period of the food of the present invention are not particularly limited, and can be taken arbitrarily.
  • the intake amount of the food of the present invention is preferably about 0.1 g or more, more preferably about 0.2 g or more, still more preferably about 0.5 g or more, and still more preferably about 0.1 g or more. 1 g or more.
  • the intake frequency of the food of the present invention can be set arbitrarily. For example, at least once a week, at least twice a week, at least 3 times a week, at least 4 times a week, at least 5 times a week, at least 6 times a week, at least 7 times a week It may be once a day or more, twice a day or more, three times a day or more. There is no upper limit to the intake frequency of the food of the present invention, for example, 3 times or less per day, 2 times or less per day, 1 time or less per day, 7 times or less per week, 6 times or less per week, 5 times per week Or less, 4 or less per week, 3 or less per week, 2 or less per week, 1 or less per week, or the like.
  • the timing of intake of the food of the present invention may be before a meal, after a meal, or between meals, but is preferably after a meal.
  • Pre-meal means from about immediately before meal to about 30 minutes before eating
  • post-meal means from immediately after meal to about 30 minutes after meal
  • between meals is about 2 after eating. It means the time about two hours or more before the next meal after more than an hour.
  • the intake period of the food of the present invention can be arbitrarily determined.
  • the food of the present invention can be ingested preferably for about 1 day or more, more preferably for about 3 days or more, and most preferably for about 5 days or more.
  • the intake period of the food of the present invention may be about 1 month or less, about 2 weeks or less, or about 10 days or less. Since demineralization in the oral cavity can occur on a daily basis, the food of the present invention is preferably ingested almost permanently.
  • the food of the present invention is preferably retained in the oral cavity for a certain period of time without being swallowed at the time of ingestion, that is, at the time of eating.
  • the time for allowing the food of the present invention to stay in the oral cavity is preferably about 1 minute or longer, more preferably about 2 minutes or longer. More preferably, it is about 3 minutes or more, and particularly preferably about 5 minutes or more. In one preferred embodiment it is about 10 minutes or more, and in a more preferred embodiment it is about 15 minutes or more.
  • There is no particular upper limit on the time for which the food of the present invention is retained in the oral cavity and it may be, for example, about 1 hour or less, about 50 minutes or less, about 40 minutes or less, about 30 minutes or less, about 20 minutes or less. When the residence time is too short, it is difficult to obtain a tooth strengthening effect.
  • the food of the present invention When the food of the present invention is a chewing gum, candy, tablet confectionery, etc., it may be taken one at a time, or a plurality (eg, 2 to 10) may be taken at a time. When ingesting a plurality at a time, a plurality may be ingested at once, or a plurality may be ingested one by one.
  • a chewing gum it is preferable to continue chewing for a long time, and when the food of the present invention is a candy or a tablet confectionery, it is preferably licked to the end without chewing.
  • the food of the present invention is usually packaged and sold.
  • This packaging may be a commonly used packaging such as paper, plastic, cellophane and the like.
  • This packaging contains instructions on the intake amount, timing of intake, and intake method of the food of the present invention (for example, in the case of gum, “it is preferable to continue to chew 2 capsules for about 20 minutes or more”). Is preferred.
  • an instruction sheet in which such an instruction is described may be inserted.
  • the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention are used in the oral cavity.
  • calcium ions (and possibly fluoride ions) that are soluble in saliva from the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and foods of the present invention Melts out.
  • a large amount of phosphoric acid is usually present in saliva in the oral cavity.
  • pre-existing phosphoric acid and calcium ions (and possibly fluoride ions) eluted from the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food Interacts to block dentinal tubules and strengthen dentin teeth.
  • composition of saliva can vary from individual to individual, it can generally be imitated by a sample (artificial saliva) that mimics saliva.
  • An example of the composition of artificial saliva is an aqueous solution containing 20 mM Hepes-K (pH 6.5) and 100 mM KCl.
  • artificial saliva and bovine samples such as cattle are used without using the actual human body. Can be confirmed.
  • the effects of the Ca / P ratio and fluoride ion concentration in artificial saliva are related to the Ca / P ratio in saliva. It can be regarded as an effect similar to the effect of P ratio and fluoride ion concentration.
  • Calcium ion molar ratio (Ca / P ratio) of about 5.0 or less (preferably about 3 or less, more preferably about 0.1 to about 2.0, most preferably about 1.67 to about 2.0) It contains the calcium containing component so that it may become.
  • the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention are samples that mimic saliva in the oral cavity.
  • the molar ratio of calcium ions to phosphorus ions in the sample (Ca / P ratio) when used in a sample is about 5.0 or less (preferably about 3 or less, more preferably about 0.1 to about 2.0, most Preferably, the composition contains a calcium-containing component so as to be about 1.67 to about 2.0).
  • the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention comprise a molar ratio of calcium ions to phosphorus ions in saliva in the oral cavity (Ca / P Ratio) is about 5.0 or less (preferably about 3 or less, more preferably about 0.1 to about 2.0, most preferably about 1.67 to about 2.0).
  • the dentinal tubule sequestering agent, dentin dentin enhancing agent, oral composition, medicinal composition, and food of the present invention are phosphorous ions in a sample that mimics saliva.
  • the molar ratio of calcium ions to calcium (Ca / P ratio) is about 5.0 or less (preferably about 3 or less, more preferably about 0.1 to about 2.0, most preferably about 1.67 to about 2.0. It is used so that it may become.
  • the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention have a fluoride ion concentration in the saliva of about 1 when used in the oral cavity. It is characterized by containing fluoride so as to be 100 ppm or less (preferably about 0.2 ppm to about 100 ppm, more preferably about 0.2 ppm to about 10 ppm, and still more preferably about 1.0 ppm to about 10 ppm).
  • the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention are samples that mimic saliva in the oral cavity.
  • the fluoride ion concentration in the sample is about 100 ppm or less (preferably about 0.2 ppm to about 100 ppm, more preferably about 0.2 ppm to about 10 ppm, more preferably about 1.0 ppm to about 10 ppm). It is characterized by containing fluoride so that
  • the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition, and food of the present invention have a fluoride ion concentration in saliva of about 100 ppm or less (preferably about 0.1. 2 ppm to about 100 ppm, more preferably about 0.2 ppm to about 10 ppm, and still more preferably about 1.0 ppm to about 10 ppm).
  • This embodiment can be understood to be substantially equivalent to the embodiment relating to a sample that mimics saliva. That is, this embodiment is equivalent in the oral cavity and artificial saliva. Therefore, in an embodiment that is substantially the same as the above embodiment, the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition, and food of the present invention are used in a sample that mimics saliva. Characterized in that the chloride ion concentration is about 100 ppm or less (preferably about 0.2 ppm to about 100 ppm, more preferably about 0.2 ppm to about 10 ppm, still more preferably about 1.0 ppm to about 10 ppm). And
  • the phosphorylated saccharide calcium (POs-Ca) used in the following experiment was prepared from potato starch using calcium chloride instead of sodium chloride in the procedure of Example 1 of JP-A-8-104696. Refers to calcium. That is, phosphorylated saccharides in which 1 to 2 phosphate groups are bonded in the molecule to oligosaccharides composed of 2 to 8 glucoses linked with ⁇ -1,4, and calcium is bonded to each of these phosphorylated saccharides. It is a mixture of calcium.
  • phosphorylated saccharide calcium one phosphate group is bonded to an oligosaccharide consisting of 3, 4 or 5 glucose in the molecule, and calcium is bonded to this phosphate group.
  • This is a mixture of an oligosaccharide composed of 7 or 8 glucoses with two phosphate groups bound in the molecule and calcium bound to the phosphate groups.
  • the molar ratio of the one having one phosphate group bonded to the one having two phosphate groups bonded is about 8: 2.
  • the salt thus prepared was used.
  • phosphorylated saccharides of various metal salts can be easily prepared by adding each metal salt after desalting by general electrodialysis.
  • about the calcium salt of phosphorylated saccharide what is marketed as phosphorylated oligosaccharide calcium from Ezaki Glico Co., Ltd. can be used suitably.
  • the fluorine-containing tea extract used in the following experiments was obtained from Mitsui Norin Co., Ltd.
  • This fluorine-containing tea extract is obtained by extracting normal Japanese tea (sencha) with hot water at 30 ° C. to 100 ° C., preferably 40 ° C. to 70 ° C., removing tannin, and further adding catechin by activated carbon and chromatography column. It is a material that has been removed and can be used as food.
  • the polyphenol content is a value measured by a colorimetric method
  • the fluorine content is a value measured by an electrode method.
  • Fluorine-containing green tea extract 1 used in Experiment 1 and the like had a fluorine content of 1000 ppm and a polyphenol content of 3% by weight or less.
  • the polyphenols contained in these fluorine-containing tea extracts are mainly composed of a mixture of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.
  • the total amount of these polyphenols was about 70% or more of the total weight of the polyphenols.
  • the material having the same quality as these fluorine-containing tea extracts is obtained by hot water extraction of Japanese tea (sencha) with hot water at 30 ° C. to 100 ° C., preferably 40 ° C. to 70 ° C. to remove tannins, activated carbon and It can be produced by further removing polyphenols such as catechin by a chromatography column.
  • TMR transversal microradiography
  • Example 1 Water solubility experiment
  • the water solubility of phosphorylated oligosaccharide calcium salt was compared with other calcium agents that could be used in the oral cavity.
  • Each of calcium carbonate (Ca carbonate), calcium monohydrogen phosphate (Ca hydrogen phosphate), calcium gluconate (Ca gluconate) and phosphorylated oligosaccharide calcium salt (POs-Ca) has a concentration of 700 mg / 100 mL.
  • a mixed solution was prepared by adding to water.
  • the photograph of the obtained liquid mixture is shown in FIG.
  • the phosphorylated oligosaccharide calcium salt formed a transparent solution, but the other calcium agents did not dissolve in water and formed a cloudy suspension.
  • the phosphorylated oligosaccharide calcium salt can dissolve in water, increase the calcium ion concentration in saliva, and create an oral environment that is easily remineralized.
  • Step 0 Dentin sample preparation;
  • Step 1 Dental dentin strengthening treatment of the dentin healthy site (24 hours, 37 ° C.);
  • Step 2) acid treatment (8 days, 37 ° C.);
  • Step 4 Capillary blockage evaluation and remineralization evaluation.
  • the surface of the dentin sample was fractionated into 4 areas, and each area was treated with the following solution. "-" Indicates that the treatment with the solution was prevented by applying a nail burnish to the area. “ ⁇ ” indicates that the area was treated with a solution without a nail burnish.
  • Step 1 “Dental enhancement treatment of healthy part of dentin”
  • nail varnish is applied to areas 1, 2 and 4 on the surface of the dentin to cover the surface of the dentin at 37 ° C. Soaked for 24 hours.
  • Step 2 Prior to Step 2, this dentin sample was thoroughly washed and the nail varnish in areas 2 and 4 on the dentin surface was peeled off. Then, the sample was immersed in the solution containing an acid at 37 degreeC for 8 days in the state which coat
  • Step 3 This dentin sample was thoroughly washed before Step 3. Thereafter, the sample was immersed in the test solution at 37 ° C. for 24 hours in a state where nail varnish was applied to the areas 2 and 3 on the dentin surface (Step 3: remineralization treatment).
  • FIGS. 1 shows the microradiograph of experiment 2A
  • FIG. 3 shows the microradiograph of experiment 2D
  • FIG. 4 shows the microradiograph of experiment 2B.
  • the gray line indicates the result of area 1 (healthy part)
  • the thin black line indicates the result of area 2 (decalcification part)
  • the thick black line indicates area 3 (dentinal enhancement part). The results are shown.
  • FIGS. 5 and 6 show the microradiograph of experiment 2A
  • FIG. 6 shows the microradiograph of experiment 2D
  • FIG. 7 shows the microradiograph of experiment 2B.
  • the gray line shows the result of area 1 (healthy part)
  • the thin black line shows the result of area 2 (decalcification part)
  • the thick black line shows area 4 (recalcification part)
  • the results are shown.
  • the data of area 1 and area 2 is the same data as the data used in the tooth quality evaluation of (a).
  • FIG. 8 shows the results of Experiment 2A.
  • Ca / P 1.73, and 6.25 mM of POs-Ca-derived Ca is included.
  • Experiment 2A capillary blockage and film formation were observed.
  • FIG. 9 shows the result of Experiment 2B.
  • Ca / P 1.73
  • POs—Ca-derived Ca is contained at 6.25 mM
  • F is contained at 1 ppm.
  • capillary blockage, film formation, and demineralization suppression were observed.
  • FIG. 10 shows the result of Experiment 2C.
  • Ca / P 1.67
  • CaCl 2 -derived Ca is contained at 6 mM
  • F is contained at 10 ppm.
  • tubule sealing and film formation were observed by remineralization treatment, but the coating was removed by acid treatment, and dentinal tubules were exposed.
  • FIG. 11 shows the result of Experiment 2D.
  • a Ca / P 0.41, containing 1.5mM of Ca from CaCl 2.
  • Experiment 2D neither capillary blockage nor film formation was seen.
  • the size of the hole in the upper diagram of FIG. 11 is different from the size of the hole in the upper diagram of FIGS. 8 to 10, but this is the ivory that originally existed in the bovine tooth piece from which each photograph was taken. This is because the size of the capillaries was different.
  • a film was formed on the surface of the dentin without filling the inside of the dentinal tubule by remineralization.
  • the film was removed by acid treatment. Ivory tubules were exposed.
  • the dentin is remineralized, (2) dentine capillaries and film formation are obtained, and (3) the solution can react quickly, A uniform effect is obtained throughout the exposed dentin.
  • Step 0 Dentin sample preparation;
  • Step 1 Dentin decalcification treatment (24 hours, 37 ° C.);
  • Step 2 Remineralization treatment of demineralized site (37 ° C., 72 hours);
  • Step 3 Capillary blockage evaluation and remineralization evaluation.
  • the surface of the dentin sample was fractionated into 3 areas, and each area was treated with the following solution. "-" Indicates that the treatment with the solution was prevented by applying a nail burnish to the area. “ ⁇ ” indicates that the area was treated with a solution without a nail burnish.
  • Step 1 nail decalcification treatment (24 hours, 37 ° C.)
  • a nail burnish was applied only to the dentin surface area 1 and the dentin surface was coated at 37 ° C. Soaked for 24 hours.
  • Step 1 dentin decalcification treatment a solution having a composition common to all experimental sections was used.
  • the composition of the solution is shown in Table 7.
  • the bovine tooth pieces were collected, the nail burnish was peeled off, and then the capillary blockage evaluation and the remineralization evaluation were performed.
  • the X-ray photomicrograph was obtained by conducting a transversal microradiography (TMR) analysis on the three areas according to the above-mentioned “TMR method”.
  • TMR transversal microradiography
  • the mineral profile was delineated and the demineralization depth (Ld) and mineral density (ML) were calculated.
  • Ld demineralization depth
  • ML mineral density
  • FIG. 12 (remineralization by POs-Ca treatment), FIG. 13 (recalcification by calcium chloride treatment), and FIG. 14 (observation result of remineralization portion (area 2) surface by scanning electron microscope). .
  • FIG. 12 shows the results of mineral distribution before and after remineralization by TMR in the surface layer when the calcium source is POs—Ca and FIG. 13 shows the calcium source is calcium chloride.
  • the calcium source is calcium chloride.
  • Table 8 summarizes the results 1-1 and 1-2.
  • Step 0 Dentin sample preparation; (Step 1) Dentin decalcification treatment (24 hours, 37 ° C.); (Step 2) Remineralization treatment of demineralized site (37 ° C., 24 hours); and (Step 3) Evaluation of capillary blockage and remineralization.
  • FIG. 15 shows the result of mineral distribution before and after remineralization by TMR of the surface layer when the calcium source is POs—Ca and FIG. 16 shows the calcium source is calcium chloride.
  • remineralization was promoted in the presence of 0 ppm, 10 ppm and 100 ppm fluoride (FIG. 15). Among them, the most remarkable acceleration of remineralization was observed in the presence of 10 ppm of fluoride.
  • Table 10 summarizes the results 2-1 and 2-2.
  • the present invention provides foods and oral compositions that enable self-care for dentin strengthening. Furthermore, according to the present invention, there is provided an oral composition that enables food and self-care for dentinal tubule sealing.
  • dentin dentin strengthening composition and food of the present invention phosphoric acid and calcium can be stably provided to the carious dentin.
  • Dentin provided with phosphoric acid and calcium is strengthened in the dentine, so that at least part of the dentin lost due to caries can be restored, and acid resistance or pressure resistance is enhanced in the healthy part of the dentin be able to.
  • a buffering agent is added to the oral cavity, it is expected that a pH buffering action can be obtained in the oral cavity. Due to the pH buffer action in the oral cavity, phosphate and calcium present in the saliva and the like in the oral cavity are stably used for dentin dentin strengthening. Therefore, it becomes possible to repair dentin, which was conventionally considered difficult or impossible.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Inorganic Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Birds (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Mycology (AREA)
  • Polymers & Plastics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Food Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Nutrition Science (AREA)
  • Molecular Biology (AREA)
  • Plastic & Reconstructive Surgery (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
PCT/JP2013/005784 2012-09-28 2013-09-27 Agent de blocage de tubule dentinaire Ceased WO2014050144A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2014538205A JP5977835B2 (ja) 2012-09-28 2013-09-27 象牙細管封鎖剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012218417 2012-09-28
JP2012-218417 2012-09-28

Publications (1)

Publication Number Publication Date
WO2014050144A1 true WO2014050144A1 (fr) 2014-04-03

Family

ID=50387575

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/005784 Ceased WO2014050144A1 (fr) 2012-09-28 2013-09-27 Agent de blocage de tubule dentinaire

Country Status (2)

Country Link
JP (1) JP5977835B2 (fr)
WO (1) WO2014050144A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014156138A1 (fr) * 2013-03-26 2014-10-02 クラレノリタケデンタル株式会社 Composition durcissable à usage dentaire
JP2019206486A (ja) * 2018-05-29 2019-12-05 日本ゼトック株式会社 口腔用組成物
JP2020514351A (ja) * 2017-03-14 2020-05-21 ザ ユニバーシティー オブ メルボルンＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ ｏｆ Ｍｅｌｂｏｕｒｎｅ 過敏症を治療するための複合体
US11717537B2 (en) 2013-07-23 2023-08-08 The University Of Melbourne Compositions and methods for dental mineralization
US12239723B2 (en) 2013-12-24 2025-03-04 The University Of Melbourne Stabilized stannous compositions

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009167135A (ja) * 2008-01-17 2009-07-30 Masaharu Kato 齲蝕治療用キット
WO2010061932A1 (fr) * 2008-11-28 2010-06-03 江崎グリコ株式会社 Aliment et composition comprenant chacun un saccharide phosphorylé, un polyphénol et du fluor

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009167135A (ja) * 2008-01-17 2009-07-30 Masaharu Kato 齲蝕治療用キット
WO2010061932A1 (fr) * 2008-11-28 2010-06-03 江崎グリコ株式会社 Aliment et composition comprenant chacun un saccharide phosphorylé, un polyphénol et du fluor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
INABA D ET AL.: "Remineralization of Enamel and Dentin by A Chewing Gum Containing Phosphoryl- Oligosaccharide Calcium(POs-Ca) in situ.", IWATE MEDICAL UNIVERSITY SHIGAKU ZASSHI, vol. 27, no. 3, 2002, pages 203 - 209 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014156138A1 (fr) * 2013-03-26 2014-10-02 クラレノリタケデンタル株式会社 Composition durcissable à usage dentaire
JPWO2014156138A1 (ja) * 2013-03-26 2017-02-16 クラレノリタケデンタル株式会社 歯科用硬化性組成物
US10231905B2 (en) 2013-03-26 2019-03-19 Kuraray Noritake Dental Inc. Dental curable composition
US11717537B2 (en) 2013-07-23 2023-08-08 The University Of Melbourne Compositions and methods for dental mineralization
US12128068B2 (en) 2013-07-23 2024-10-29 The University Of Melbourne Compositions and methods for dental mineralization
US12239723B2 (en) 2013-12-24 2025-03-04 The University Of Melbourne Stabilized stannous compositions
JP2020514351A (ja) * 2017-03-14 2020-05-21 ザ ユニバーシティー オブ メルボルンＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ ｏｆ Ｍｅｌｂｏｕｒｎｅ 過敏症を治療するための複合体
JP7138352B2 (ja) 2017-03-14 2022-09-16 ザ ユニバーシティー オブ メルボルン 過敏症を治療するための複合体
US12303548B2 (en) 2017-03-14 2025-05-20 The University Of Melbourne Complexes for treating sensitivity
JP2019206486A (ja) * 2018-05-29 2019-12-05 日本ゼトック株式会社 口腔用組成物
JP7076748B2 (ja) 2018-05-29 2022-05-30 日本ゼトック株式会社 口腔用組成物

Also Published As

Publication number Publication date
JP5977835B2 (ja) 2016-08-24
JPWO2014050144A1 (ja) 2016-08-22

Similar Documents

Publication Publication Date Title
JP6101712B2 (ja) 多成分系口腔ケア組成物
JP5726533B2 (ja) リン酸化糖、ポリフェノールおよびフッ素を含む、食品および組成物
KR20000052950A (ko) 콜로이드성 염기성 구연산 비스머스를 포함하는 추잉검
HU218971B (hu) Kétkomponensű fogászati készítmény a fogak túlérzékenységének kezelésére és eljárás fogérzékenység csökkentésére
RU2696495C2 (ru) Средство для ухода за полостью рта и пищевой продукт или напиток
JP5977835B2 (ja) 象牙細管封鎖剤
JP7330098B2 (ja) 歯牙の再石灰化を促進できる口腔用組成物
EP3378466A1 (fr) Composition à utiliser dans la cavité buccale
JP3650705B2 (ja) パラチニット含有食品
JP5461198B2 (ja) 初期う蝕治療効果を有する食品および初期う蝕治療用キット
JP5633998B2 (ja) 歯の再石灰化促進剤およびこれを含む口腔または経口用組成物
JP2010126510A (ja) ラクトビオン酸カルシウムを含む口腔用組成物および食品
KR100963619B1 (ko) 치질 강화제, 이를 함유하는 구강용 조성물과 음식물 및 이들의 제조방법
KR20080008363A (ko) 치아 에나멜질의 재석회화 촉진제, 그리고 그것을 함유하는구강용 조성물 및 음식물
JP4763441B2 (ja) 歯垢形成抑制剤並びにそれを含む口腔剤組成物及び食品
JP2005263777A (ja) 口腔用組成物
US20180042262A1 (en) Dental product, use of a dental product and methods of use of a dental product
KR20200050801A (ko) 유게놀 및 죽염을 유효성분으로 포함하는 구강 위생 조성물
US20210236391A1 (en) Dental Product, use of a Dental Product and methods of use of a dental product
EP1454618B1 (fr) Composition anti-carie comprenant la Phaseolamine
KR20220080874A (ko) 구강용 조성물
EP2432322A1 (fr) Compositions et méthodes de traitement optimales d'affections et de douleurs bucco-dentaires
JPH06501698A (ja) 口腔衛生調剤
MXPA99001686A (en) Anti-carious chewing gums, candies, gels, toothpastes and dentifrices
KR20140109648A (ko) 용뇌 및 죽염을 포함하는 구강 조성물

Legal Events

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

Ref document number: 13841319

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2014538205

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13841319

Country of ref document: EP

Kind code of ref document: A1