WO2014050144A1

WO2014050144A1 - Dentinal tubule blocking agent

Info

Publication number: WO2014050144A1
Application number: PCT/JP2013/005784
Authority: WO
Inventors: 田中　智子; 隆嗣小林
Original assignee: 江崎グリコ株式会社
Priority date: 2012-09-28
Filing date: 2013-09-27
Publication date: 2014-04-03
Also published as: JPWO2014050144A1; JP5977835B2

Abstract

Provided is a dentinal tubule blocking agent including a calcium-containing component, the calcium-containing component being (i) a phosphorylated saccharide calcium salt, (ii) a combination of a phosphorylated saccharide salt other than a phosphorylated saccharide calcium salt or a phosphorylated saccharide and a calcium salt other than a phosphorylated saccharide calcium salt or (iii) a mixture of (i) and (ii), and the phosphorylated saccharide being composed of a saccharide moiety and a phosphate group. The dentinal tubule blocking agent may either contain 0.1 weight% or more of hydroxyapatite, or not contain hydroxyapatite or contain less than 0.1 weight% of hydroxyapatite.

Description

Ivory tubule sealant

The present invention relates to a dentinal tubule sealant, a dentin dentin enhancer, and an oral composition, medicinal composition and food containing these.

It is known that phosphorylated oligosaccharide calcium salt (also referred to as POs-Ca) is useful for the initial caries of tooth enamel. Many calcium salts used in foods or pharmaceuticals are water-insoluble or poorly water-soluble, but POs-Ca has the property of being neutral and soluble while being a calcium salt. POs-Ca exhibits remineralization and recrystallization effects due to calcium ions.

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). Conventionally, 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. However, it is known that 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.

In normal healthy teeth, the pulp is in the dentin, and the enamel covers the dentin in the crown. 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. Or 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.

On the other hand, the hydroxyapatite content of dentin is as low as about 70%, and it contains a large amount of organic matter, so it is vulnerable to caries. Enamel withstands up to about pH 5.5, whereas dentin dissolves at about pH 6.7. Enamel is caries by the strong acid that can be produced when you eat sugar, but dentin can also be carved by the weak acid that can be produced when you eat a weak starch such as rice. In the dentin, there are many holes called dentinal tubules. The diameter of the dentinal tubule is usually about 0.5 to 2.2 μm. Since 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.

Usually, 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. However, if the caries progresses to the dentin, 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. Furthermore, in hypersensitivity, the opening of the dentinal tubule has been confirmed, and the opening of the dentinal tubule is considered to be a cause of hypersensitivity. When cold or hot infiltrates from the dentinal tubule or pressure is applied, it is thought that stimulation reaches the pulp nerve and causes pain. For the above reasons, it is considered preferable to prevent the dentin from being exposed and fill the opening of the dentinal tubule.

As mentioned above, since the composition and structure of enamel and dentin are completely different, it was common sense that even a therapeutic agent that can be used to treat enamel cannot be used to treat dentin.

General methods for dealing with dentine caries and hypersensitivity include a method of applying a dentinal tubule-blocking agent such as a calcium agent and a fluorine agent in the form of a paste to the root surface and a method of introducing fluorine ions. However, in these methods, it is difficult to completely block all the openings, and it is impossible to confirm whether or not the openings are completely blocked. Applying a dentinal tubule sealant as much as possible to all the openings as much as possible takes time and puts a heavy burden on the patient. Therefore, excessive treatment must be performed, which is technically difficult, and requires an excessive amount of the fluorine agent to be used. Moreover, even if bacteria have already invaded the dentinal tubule, 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. In addition, when the opening of the dentinal tubule is filled with 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.

As an application related to POs-Ca, there is, for example, 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. In Patent Document 1, phosphorylated oligosaccharides are used for blocking dentinal tubules, but do not describe the use alone, but use hydroxyapatite as a necessary component. As is clear from the description in paragraphs 0172 and 0173 of Patent Document 1, in the method described in Patent Document 1, 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.

As conventional techniques related to substances related to POs-Ca, there are Patent Document 2 (Patent No. 3466350), Patent Document 3 (Patent No. 2964182) and 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. Here, 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.

When 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.

In contrast, in 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. Examples of 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.

By using phosphorylated saccharide calcium salt (or other phosphorylated saccharide salt or a combination of phosphorylated saccharide and other calcium salt) as in the present invention, it is possible to prevent aggregation over a suitable use concentration. It is. 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.

Patent Document 4 discloses that a polyol phosphate metal salt can be used for sealing dentinal tubules, and a polyol phosphate metal salt generally has high solubility in a water-soluble medium, so that this metal salt is used for a mouthwash or a dentifrice. It is described that a transparent material can be obtained. Therefore, it is considered that the polyol phosphate metal salt described in Patent Document 4 does not form colloids or particles. However, Patent Document 4 does not describe a calcium salt as a metal salt. In addition, the state of sealing of the dentinal tubules is unknown.

As described above, by using 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.

It is said that hypersensitivity occurs when the dentinal tubules originally present in the dentin open to the outside. Many dentinal tubule sealants used for the purpose of suppressing hypersensitivity are known. However, most of these dentinal tubule blocking agents are solids mainly composed of aluminum salts, silicates, calcium salts, phosphates and the like. Although 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. In addition, when used as a medicinal preparation, there is a problem that the feeling of use is bad.

As a 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. However, 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.

As a result of intensive studies to solve the above problems, 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. The present invention has been completed based on the finding that it is effective in promoting the remineralization of the quality and suppressing the demineralization of the healthy part of the dentin.
(Item 1) A dentinal tubule sealant containing a calcium-containing component, wherein 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 dentinal tubule sealant, which is a mixture of i) and (ii), wherein the phosphorylated saccharide comprises a saccharide moiety and a phosphate group.
(Item 2) The dentinal tubule sealant according to item 1, further comprising a fluoride.
(Item 3) 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.
(Item 4) The dentinal tubule sealant according to

item

1 or 2, further comprising 0.1% by weight or more of hydroxyapatite.
(Item 5) The dentinal tubule sealant according to any one of Items 1 to 4, wherein the sugar moiety is a glucan residue or a reduced glucan residue.
(Item 6) 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.
(Item 10) 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.
(Item 11) The dentin dentin reinforcing agent of item 10 which further contains a fluoride.
(Item 12) The dentin dentin enhancer according to item 10 or 11, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
(Item 13) The dentin dentin enhancer according to item 10 or 11, further comprising 0.1% by weight or more of hydroxyapatite.
(Item 14) The dentin dentin enhancing agent according to any one of items 10 to 13, wherein the sugar moiety is a glucan residue or a reduced glucan residue.
(Item 15) The dentin dentin enhancer according to item 14, wherein the degree of polymerization of the sugar moiety is 3 to 9.
(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.
(Item 19) 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.
(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.

In certain embodiments, the following are also provided:
(Item 1A) A dentinal tubule sealant containing a calcium-containing component, wherein 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 dentinal tubule sealant, which is a mixture of i) and (ii), wherein the phosphorylated saccharide comprises a saccharide moiety and a phosphate group.
(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.
(Item 6A) The dentinal tubule sealant according to any one of items 1A to 5A, wherein the calcium-containing component is a phosphorylated saccharide calcium salt.
(Item 7A) The dentinal tubule sealant according to any one of Items 1A to 6A, wherein the calcium salt in (ii) is a water-soluble calcium salt.
(Item 8A) The dentinal tubule sealant according to any one of items 1A to 7A, which contains fluoride so that the fluoride ion concentration in saliva when used in the oral cavity is 100 ppm or less.
(Item 9A) 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. The dentinal tubule sealant according to item.
(Item 10A) 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. Dentin dentin strengthening agent as described in claim | item.
(Item 17A) An oral 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. Oral composition.
(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 The oral composition according to any one of items 17A to 19A.
(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. As a result, it is possible to alleviate hypersensitivity (for example, a phenomenon in which a cold object looks into a tooth) caused by opening of a dentinal tubule.

Phosphorus in saliva (or phosphorus provided from a phosphorus-containing component other than the phosphorylated saccharide calcium salt contained as necessary in the dentinal tubule sealant of the present invention) and a phosphorylated saccharide calcium salt (preferably POs-Ca); , It is possible to exert an effect that could not be obtained with other conventional dentinal tubule sealants. That is, 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. In addition, a film can be formed and a rapid reaction can be caused by the solution.

Furthermore, the combined use of fluoride and phosphorylated saccharide calcium salt (preferably POs—Ca) can strengthen the dentin surface and increase acid resistance. Furthermore, 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. By using this invention with respect to healthy dentin, acid resistance can be strengthened and pressure resistance can be strengthened.

In addition, 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.

In the present invention, a film that coats dentin is formed instead of a method of filling a mainstream dentinal tubule with a paste in the prior art. When 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.

According to the present invention, 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.

When the dentinal tubule sealant of the present invention is used, a coating that is so smooth that it cannot be achieved by the conventional techniques so far is formed.

It is desirable that the ivory tubules can be repeatedly sealed at home and the colored film can be peeled off with tea astringency. 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. .

Since the 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, and 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, and the right is a photograph of a part subjected to acid treatment after strengthening the tooth. In the upper row, the scale is 50 μm, and in the lower row, the scale is 20 μm. 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, and 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, and the right is a photograph of a part subjected to acid treatment after strengthening the tooth. In the upper row, the scale is 50 μm, and in the lower row, the scale is 20 μm. 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, and 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, and the right is a photograph of a part subjected to acid treatment after strengthening the tooth. In the upper row, the scale is 50 μm, and in the lower row, the scale is 20 μm. 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, and 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, and the right is a photograph of a part subjected to acid treatment after strengthening the tooth. In the upper row, the scale is 50 μm, and in the lower row, the scale is 20 μm. 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. The thick line shows the result of area 2 (remineralization part), and the thin line shows the result of area 3 (decalcification part). 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. 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. The thick line shows the result of area 2 (remineralization part), and the thin line shows the result of area 3 (decalcification part). 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.

Hereinafter, the present invention will be described in detail.

(1. Definition)
As used herein, “dentin” refers to the dentin of a tooth.

In the present specification, 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.

In this specification, “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.

The term “quasi-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.

(2. Materials used in the present invention)
In the present invention, 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) 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).

(2a. Phosphorylated sugar and phosphorylated sugar salt)
The phosphorylated saccharide used in the present invention consists of a saccharide moiety and a phosphate group. As used herein, the term “phosphorylated sugar” refers to a sugar having at least one phosphate group in the molecule. As used herein, the term “phosphorylated saccharide salt” refers to a phosphorylated saccharide salt. As used herein, the term “phosphorylated saccharide inorganic salt” refers to an inorganic salt of phosphorylated saccharide. As used herein, the term “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. In the present specification, those having a degree of polymerization of the sugar moiety in the phosphorylated saccharide of 10 or less are also referred to as phosphorylated oligosaccharides. In the present specification, the “degree of polymerization” refers to the number of structural units, that is, the number of monosaccharide residues. For example, the 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). In the present invention, the ionized form of phosphorylated saccharide (that is, the hydrogen of the phosphate group is dissociated and separated into a phosphate ion) may be used, or the salt form (ie, phosphate ion and base). May be used). In certain embodiments, preferably 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. Preferably, 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. Here, 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, that is, the number of glucose residues 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.

It is known that phosphorylated saccharide calcium has a tooth remineralization effect, a calcium absorption promoting effect, and a taste improving effect.

In a preferred embodiment, 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. In yet another preferred embodiment, 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.

In a further preferred embodiment, 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. In yet another preferred embodiment, 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.

In yet another preferred embodiment, the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or the reduced glucan residue is an α-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.

In yet another preferred embodiment, the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or the reduced glucan residue is an α-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.

In yet another preferred embodiment, 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 α-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.

In yet another preferred embodiment, 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 α-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.

In still another preferred embodiment, the sugar moiety is a glucan residue or a reduced glucan residue, wherein the glucan residue or reduced glucan residue has α-1,4-linked glucose as a main chain, and α Phosphorylated saccharides having a side chain of glucose with -1,6 bonds or α-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. 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.

Examples of the sugar that is a raw material for producing phosphorylated saccharide and salts thereof include glucan, mannan, dextran, agar, cyclodextrin, fucoidan, gellan gum, locust bean gum, guar gum, tamarind gum, and xanthan gum. Hereinafter, the case of glucan will be described. A general crude plant starch, 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. Furthermore, it is also possible to use various carbohydrates chemically bonded with phosphate groups. In potato starch, a relatively large number of phosphate groups are ester-bonded at the 3rd and 6th positions of glucose constituting the starch. Phosphate groups are mainly present in amylopectin.

In a preferred embodiment, when the sugar is glucan, it can be obtained by decomposing starch having a phosphate group or modified starch.

In a preferred embodiment, starch having a phosphate group or modified starch, amylolytic enzyme, glycosyltransferase, or α-glucosidase, or one or more combinations thereof (excluding only one α-glucosidase) Act.

In a preferred embodiment, the amylolytic enzyme is composed of one or more combinations of α-amylase, β-amylase, glucoamylase, isoamylase, pullulanase, or neopullulanase. In a preferred embodiment, the glycosyltransferase is a cyclodextrin glucanotransferase.

In a preferred embodiment, 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.

As the phosphorylated saccharide and its salt, a high-purity one or a low-purity one may be used. For example, phosphorylated saccharides and salts thereof may be used as a mixture with other saccharides. In addition, when mentioning about the density | concentration and content of phosphorylated saccharide | sugar and its salt in this specification, this density | concentration and content are calculated based on the quantity of pure phosphorylated saccharide | sugar and its salt. Therefore, when using a mixture containing a substance other than phosphorylated saccharide and its salt, the concentration and content are calculated based on the amount of phosphorylated saccharide and its salt in the mixture, not the total amount of the mixture .

(2b. Calcium salt)
In certain embodiments of the invention, calcium salts are used. The calcium salt may be water-soluble, water-insoluble, or poorly water-soluble. A water-soluble calcium salt is preferred. As used herein, “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. Examples of 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. In the present specification, “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. Examples of the poorly water-soluble calcium salt include calcium gluconate, calcium dihydrogen phosphate and calcium benzoate. In the present specification, 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. is preferably about 2% by weight or more, more preferably about 3% by weight or more, and further preferably about 4% by weight or more. Particularly preferably, it is about 5% by weight or more. The definition of 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.

(2c. Fluoride)
In certain embodiments of the invention, 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.

Conventionally, fluoride is often used at a high concentration of 1000 ppm or more. In the present invention, by using 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. In use, an effect equivalent to or higher than the conventional high concentration can be obtained. According to the present invention, for example, 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. Examples of such fluorides include sodium fluoride, potassium fluoride, monofluorophosphoric acid and its salts (eg, sodium monofluorophosphate), calcium fluoride, strontium fluoride, cryolite, monofluoroacetic acid Etc. In certain embodiments, it is preferred to use potassium fluoride, sodium monofluorophosphate, strontium fluoride or tea-derived fluorine as the fluoride in the food or composition of the present invention. In the invention of food, it is preferable to use fluorine (eg, fluorine derived from tea, well water, seawater, salt, seafood, seaweed, etc.) that can be used as food as the fluoride. When the intraoral composition of the present invention is a pharmaceutical product, the fluoride is a fluoride that is approved for incorporation into a pharmaceutical product. When the intraoral composition of the present invention is a quasi-drug, the fluoride is a fluoride that is approved for incorporation into a quasi-drug.

(2d. Phosphate source compound)
Hydroxyapatite (which is represented by Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), which is the main component of dental dentin, has a Ca / P ratio of about 1.67, which constitutes the dentin of the tooth In the composition, the Ca / P ratio is about 1.0 to about 1.67 (P / Ca ratio = 0.6 to 1.0). Accordingly, the Ca / P ratio is made to approach about 1.0 to about 1.67 (P / Ca ratio = 0.6 to 1.0), preferably about 1.67 (P / Ca ratio = 0.6). Furthermore, remineralization of dentin can be promoted by supplying phosphate ions and calcium ions.

In the present invention, when only a phosphorylated saccharide calcium salt is used or only a phosphorylated saccharide salt other than calcium salt or a combination of phosphorylated saccharide and calcium salt is used, only calcium ions are supplied. In order to strengthen the tooth quality, the phosphate ions are insufficient.

It is known that a large amount of phosphoric acid is present in saliva. In the case of a normal human body, the molar ratio of calcium: phosphate in saliva (hereinafter referred to as “Ca / P ratio”) is generally about 0.25 to about 0.67 (P / Ca = about 1.45). To about 3.9) and there is an excess of phosphoric acid (ie, approximately 3 moles phosphate to 2 moles calcium to 3.9 moles phosphorus to 1 mole calcium). Therefore, in the case of foods that are often chewed in the oral cavity, such as chewing gums, phosphoric acid is hardly deficient without adding phosphoric acid.

However, when using foods that dilute saliva, such as beverages, or calcium-containing compositions that are applied directly to the dentin surface of teeth, calcium ions must be used for more effective dentin strengthening. On the other hand, there may be a relative shortage of phosphate ions. Therefore, in the composition and food of the present invention, it is preferable to use a phosphate ion supply source at the same time depending on the assumed calcium ion concentration at the time of contact with the dentin surface. In this specification, 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. Examples of such 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. Examples of potassium phosphate 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 phosphate source compound has a Ca / P ratio of about 1.0 to about 2.0 (preferably when used in the oral cavity) (P / Ca ratio = about 0.5 to about 1.0), preferably Alone or in combination so as to approach about 1.67 (P / Ca ratio = about 0.6), the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal use of the present invention It can be added to compositions and foods.

(2f. Other materials)
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.

When the oral composition, medicinal composition or food of the present invention is a chewing gum, for example, it contains a gum base, sweetener, gelatin, flavor, brightener, colorant, thickener, acidulant, pH adjuster, etc. obtain. Examples of gum bases include chicle, vinyl acetate, ester gum, polyisobutylene and styrene butadiene rubber. The sweetener can be a sugar, a sugar alcohol, or a high intensity sweetener. The sweetener is preferably non-cariogenic to prevent caries. The sweetener is more preferably selected from maltitol, reduced palatinose, palatinose, lactitol, erythritol, sorbitol, xylitol, aspartame L-phenylalanine compound, trehalose and mannitol. The chewing gums can be blended according to blends known in the art.

When the oral composition, medicinal composition or food of the present invention is a candy, for example, sugars such as sucrose and starch syrup, wheat flour, condensed milk, salt, agar, gelatin, nuts (such as peanuts), shortening, butter , Acidulants, flavorings, pH adjusters, colorants and the like. The sugar can be a sugar, a sugar alcohol, or a high intensity sweetener. The saccharide is preferably a non-cariogenic saccharide in order to prevent caries. 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 (also referred to as 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. Examples of 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.

On the other hand, 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. Examples of bactericides and antibacterial agents include benzalkonium chloride, cetylpyridinium chloride, parapenes, benzoic acid, alcohols such as ethanol, and the like. Examples of 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, β-glucans, 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 dentin enhancer, oral composition, and medicinal composition of the present invention contain a bactericidal agent or antibacterial agent for killing bacteria in the dentinal tubule.

(3. Ivory tubule blocking agent of the present invention)
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). 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. In one specific embodiment, the dentinal tubule sealant of the present invention is for a patient performing treatment with hydroxyapatite, and in another specific embodiment, the dentinal tubule sealant of the present invention is For patients who are not treated with hydroxyapatite. For example, when the dentinal tubule sealant of the present invention does not contain hydroxyapatite, the dentinal tubule sealant 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. Further, for example, 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. In the present specification, 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.

(4. Dentin tooth enhancer of the present invention)
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. A salt of phosphorylated saccharide other than or a combination of phosphorylated saccharide and a calcium salt other than phosphorylated saccharide calcium salt; or (iii) a mixture of (i) and (ii) above. The dentin dentin enhancer of the present invention may contain hydroxyapatite or may not contain hydroxyapatite substantially. In one embodiment, 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. In one particular embodiment, 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. 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 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. That is, when 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. In the present specification, 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.

In the present specification, 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. Preferably, 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. Moreover, since 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.

As described above, since 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.

(5. Oral composition)
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. In one particular embodiment, 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. For example, when the oral composition of the present invention does not contain hydroxyapatite, the oral composition 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. Further, for example, when the oral composition of the present invention does not contain hydroxyapatite, the oral composition 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. For example, when used in the oral cavity, 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. Examples of 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.). It is preferable that 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. For example, 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.

When 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.

When the oral composition of the present invention is a liquid, 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.

In one embodiment, 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. For example, 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. For example, 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.

As used herein with respect to an oral composition, “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.

When the oral composition is used in a form such as a dentifrice and a mouthwash that acts at the same concentration without being diluted in the oral cavity, phosphorus in the oral composition of the present invention is used. 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. In this case, for example, 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. More preferably about 12 mM or less, particularly preferably about 10 mM or less, and most preferably about 9.0 mM or less. When 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.

In one embodiment, 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. Can be set to For example, 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. For example, 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. Hereinafter, 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.

Calcium in the oral composition of the present invention when the oral composition is used in a form such as a dentifrice and a mouthwash that acts at the same concentration without being diluted in the oral cavity. 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. Is about 12 mM or less, particularly preferably about 10 mM or less, and most preferably about 9.0 mM or less. When 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. For example, 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. Hereinafter, the amount is appropriate to be about 6 ppm or less, about 4 ppm or less, or about 2 ppm or less. These apply to all oral compositions of the present invention.

When the oral composition is used in a form such as a dentifrice and a mouthwash that operates at the same concentration without being diluted in the oral cavity, 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. In this case, for example, 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. When 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.

When the concentration of fluorine is too high, the action effect of phosphorylated saccharide and calcium may be inhibited, and as a result, it is difficult to obtain a sufficient tooth strengthening effect. When the concentration of fluorine is too low, it is difficult to obtain an effect of improving tooth quality by fluorine.

In certain embodiments, 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. In this case, 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. It is more preferably 002 times or more, particularly preferably about 0.003 times or more, and most preferably about 0.004 times or more. In this specific embodiment, 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.

In one embodiment, when the oral composition of the present invention contains a phosphoric acid source compound, 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. When the phosphoric acid source compound in the composition of the present invention is used in the oral cavity, the concentration of the Ca / P ratio in the oral cavity is preferably adjusted so as to be within the above-mentioned preferable range. In a specific embodiment, 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 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 or more, particularly preferably about 3.6 mM or more, and most preferably about 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.

When the oral composition is used in a form such as a dentifrice and a mouthwash that acts at the same concentration without being diluted in the oral cavity, phosphorus in the oral composition of the present invention is used. 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. In this case, 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.

Examples of oral compositions other than foods include dentifrices, mouthwashes (also referred to as mouthwashes), and medicated chewing gums. Examples of 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. In this container or package, 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”), etc. Preferably it is described. Alternatively, an instruction sheet in which such an instruction is described may be inserted.

(6. Medicinal composition)
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. In certain embodiments, 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. For example, when used in the oral cavity, 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. There is no particular upper limit on the intake of the medicinal composition of the present invention, but for example, about 1000 g or less, about 750 g or less, about 500 g or less, about 250 g or less, about 100 g or less, about 50 g or less, about 40 g or less, About 30 g or less, about 20 g or less, about 10 g or less, about 7.5 g or less, about 5 g or less, about 4 g or less, about 3 g or less, about 2 g or less, about 1 g or less.

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. There is no upper limit to 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.

When the medicinal composition of the present invention is in the form of chewing gum, chewing tablets, troches, etc., one tablet may be taken at a time, or a plurality (eg, 2 to 10) may be taken at a time. Also good. When ingesting a plurality at a time, a plurality may be ingested at once, or a plurality may be ingested one by one. When 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.

When the medicinal composition of the present invention is in the form of chewing gum, 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.

When the medicinal composition of the present invention is in the form of a chewable tablet, 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.

When the medicinal composition of the present invention is in the form of a troche, 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. In this container or package, instructions regarding the intake amount, intake timing, and intake method of the pharmaceutical composition 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”) are described. It is preferable that Alternatively, an instruction sheet in which such an instruction is described may be inserted.

(7. Food of the present invention)
In one embodiment, the food of the present invention is a food for dentinal tubule sealing, and includes the dentinal tubule sealing agent of the present invention. In a specific embodiment, 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.

In one embodiment, the food of the present invention is a food for dentin dentin strengthening and includes the dentin dentin fortifying agent of the present invention. In a specific embodiment, 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. For example, when ingested in the oral cavity, 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.

(7a. Food production method of the present invention)
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. Combinations with salts; or (iii) may be made by any method known in the art to include a mixture of (i) and (ii) above.

In the case of the above (ii), 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.

In the case of (ii) above, 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. In this case, in the food of the present invention, 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.

In the food of the present invention, 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.

These apply to all foods and compositions of the present invention.

(7b. Food of the present invention)
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. When the food of the present invention contains a phosphorylated saccharide calcium salt, the food of the present invention does not need to contain any other phosphorylated saccharide or a salt thereof, but may contain it.

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.

When the food of the present invention is a chewing gum, 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.

When the food of the present invention is a candy, 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.

When the food of the present invention is a tablet confection, 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. For example, 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. For example, when the food of the present invention is a compound beverage, yogurt or the like, there is no particular shape.

In one embodiment, when the food of the present invention contains phosphorylated saccharide or a salt thereof (excluding a calcium salt), 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. For example, 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. For example, 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.

As used herein with respect to food, “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. Then, every time the eater feels that saliva has accumulated in the oral cavity, the saliva is exhaled, and a method of collecting the exhaled liquid is possible. However, be careful not to exhale food when exhaling saliva. The same is true for other concentrations. In this specification, the term “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. In this case, 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. When the single intake of food is large, it is blended so as to have a lower content than when the intake is small. For example, in order to achieve the same use amount, 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.

When the food is a chewing gum containing phosphorylated sugar or a salt thereof, when the gum is chewed in the mouth for about 20 minutes, almost all the phosphorylated sugar and the salt contained in the gum are saliva in 20 minutes. Elute in.

If 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.

When the food is a chewing gum containing a phosphate source compound, when the gum is chewed in the mouth for about 20 minutes, almost all the phosphate source compound contained in the gum is dissolved in saliva within 20 minutes. .

In one embodiment, 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. For example, 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. For example, 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.

For example, when a calcium salt (including phosphorylated saccharide calcium) is added to chewing gum, 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. In order to increase the calcium concentration in saliva in the oral cavity at the time of performing 1 mM to 15 mM, 0.8 mg to 12 mg of calcium may be included as a single intake (40 × 1 (mM) × 0.02 (L) = 0.8 mg, 40 x 15 (mM) x 0.02 (L) = 12 mg). Therefore, assuming that 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 Determines the blending amount. For example, when the weight of the gum is 2 g, the blending amount as calcium is 0.04 to 0.6% by weight. For example, if the weight of the gum is 1 g, the blending amount as calcium is 0.08 to 1.2% by weight. If 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.

In one embodiment, 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. For example, 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. An amount suitable to be 5 ppm or less, most preferably about 1 ppm or less.

When the concentration of fluorine is too high, the action effect of the phosphorylated oligosaccharide may be inhibited, and as a result, it is difficult to obtain a sufficient tooth strengthening effect. When the concentration of fluorine is too small, it is difficult to obtain an effect of improving tooth quality by fluorine.

For example, when fluoride is blended into chewing gum containing phosphorylated sugar or salt thereof, 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. In order to adjust the fluorine concentration in the saliva in the oral cavity when the food is present in the oral cavity to 0.2 to 100 ppm, 0.004 to 2 mg of fluorine may be included as a single intake (20 (G) × (0.2 to 100) × 10 ⁻⁶ = 0.004 to 2 (mg)). Therefore, assuming that the weight of the gum is Xg and the blending amount of fluoride (converted as fluorine) is Y%, Y (%) = {0.004 to 2 (mg) / (X (g) × 1000)} × 100 determines the amount. For example, when the weight of the gum is 2 g, the blending amount as fluorine is 0.0002 to 0.1% by weight. For example, when the weight of the gum is 1 g, the blending amount as fluorine is 0.0004 to 0.2% by weight, and when the gum weight is 10 g, 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.

In one embodiment, when the food of the present invention contains a phosphate source compound, 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. Can be set to For example, 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.

In one embodiment, 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. For example, when a phosphoric acid source compound is blended in chewing gum, 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 In order to increase the concentration of phosphate in saliva by 0.1 mM to 10 mM, 0.196 mg to 19.6 mg of phosphate may be included as a single intake (98 × 0.1 (mM) × 0. 02 (L) = 0.196 mg, 98 × 10 (mM) × 0.02 (L) = 19.6 mg). Therefore, assuming that the weight of the gum is Xg and the blending amount (converted as phosphoric acid) is Y%, Y (%) = {(0.196 to 19.6 (mg)) / (X (g) × 1000) } × 100 determines the blending amount. For example, when the weight of the gum is 2 g, the blending amount as phosphoric acid is 0.0098 to 0.98% by weight. For example, if the weight of the gum is 1 g, 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 most suitable range of amounts to be added to the gum in certain embodiments is summarized below:
Ca / P ratio = about 1-2 (desirably about 1.67), which is a value taking into account about 3.6 mM of phosphoric acid in saliva, added calcium / average in saliva = about 3.6 mM + added The amount of phosphoric acid;
Suitable amount of addition concentration:
Calcium concentration = about 1-12 mM, preferably the calcium is derived from POs-Ca;
Phosphoric acid concentration = about 0-9 mM (desirably about 0.002-0.02%);
Fluorine concentration = about 0.5 ppm to 100 ppm (desirably about 0.5 to 10 ppm).

(7c. Food Eating Method of the Present Invention)
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. There is no particular upper limit on the intake of the food of the present invention, but for example, about 1000 g or less, about 750 g or less, about 500 g or less, about 250 g or less, about 100 g or less, about 50 g or less, about 40 g or less, about 30 g per serving. Hereinafter, about 20 g or less, about 10 g or less, about 7.5 g or less, about 5 g or less, about 4 g or less, about 3 g or less, about 2 g or less, about 1 g or less.

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, and 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.

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. When the food of the present invention is 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. Alternatively, an instruction sheet in which such an instruction is described may be inserted.

(8. Summary of preferred embodiments)
The dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention are used in the oral cavity. When 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. Therefore, 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.

Although the 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. For the effect of the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition and food of the present invention, artificial saliva and bovine samples such as cattle are used without using the actual human body. Can be confirmed.

Although certain embodiments of the present invention relate to the Ca / P ratio and fluoride ion concentration in human saliva, 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.
In certain embodiments, the dentinal tubule sealant, dentin dentin enhancer, oral composition, medicinal composition, and food of the present invention against phosphorus ions in the saliva of the oral cavity when used in the oral cavity. 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.

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 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 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).

In certain embodiments, 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). Features.

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 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.

In certain embodiments, 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).

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 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 samples that mimic saliva in the oral cavity. When used in a sample, 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

In certain embodiments, 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

(1. Phosphorylated saccharide calcium salt used)
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 α-1,4, and calcium is bonded to each of these phosphorylated saccharides. It is a mixture of calcium. In this 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. Here, the molar ratio of the one having one phosphate group bonded to the one having two phosphate groups bonded is about 8: 2. In the following experiments, the salt thus prepared was used. In addition to this method using an ion exchange resin, phosphorylated saccharides of various metal salts can be easily prepared by adding each metal salt after desalting by general electrodialysis. In addition, about the calcium salt of phosphorylated saccharide, what is marketed as phosphorylated oligosaccharide calcium from Ezaki Glico Co., Ltd. can be used suitably.

(2. Fluorine-containing tea extract)
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, and 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.

(3. Method of TMR)
In the following experiments, transversal microradiography (TMR) analysis was performed by the following method. After the final treatment, thin parallel sections were cut from dentin blocks using a water-cooled diamond saw. This thin slice was polished to a parallel horizontal plane to a thickness of 300 μm. This thin section of dentin was X-rayed with Cu-Kα X-rays generated by 25 kV and 15 mA for 20 minutes using a high-resolution plate, developed and microscopically analyzed (PW-3830, Philips, The Netherlands). At the time of X-ray photography, various known amounts of aluminum were used as a standard substance, and images were taken at the same time and used to prepare a calibration curve for calcium content. Mineral profiles were delineated from digital images observed under a microscope, and mineral parameters (Decalcification Depth (Ld) and Mineral Density (ML)) were calculated by the software of Inspector Research Systems BV (The Netherlands). Mean values were calculated per sample and analyzed statistically.

(Experiment 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. Thus, a mixed solution was prepared by adding to water. The photograph of the obtained liquid mixture is shown in FIG. As can be seen from FIG. 1, the phosphorylated oligosaccharide calcium salt formed a transparent solution, but the other calcium agents did not dissolve in water and formed a cloudy suspension. Thus, it was confirmed that 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.

(Experiment 2: Experiments on dentinal tubule sealing and remineralization)
In the following experiments, the effect of POs-Ca on the root surface and dentin and the application of POs-Ca to root surface caries were examined. Briefly, POs-Ca and fluoride (yes / no) were added to artificial saliva and the bovine dentin was immersed to investigate dentin strengthening, dentinal tubule sealing, remineralization, and the like.

I-1. Summary of procedure In this experiment, in order to reduce the variation in the results of the samples, dentinal tubule sealing evaluation and remineralization evaluation were performed using the same samples. Each experiment used 5 bovine dentin samples. In this procedure, processing was performed in the following order.
(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 3) Remineralization treatment; and (Step 4) Capillary blockage evaluation and remineralization evaluation.

I-2. Details of treatment method in each procedure Step 0: Dentin sample preparation A bovine tooth dentin block (7 mm x 15 mm) was cut from a bovine incisor, and this block was then attached to a resin. The block was polished with wet abrasive paper (# 1000 and # 2000, manufactured by 3M) to expose a new flat dentin surface.

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.

That is, in 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.

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 | covered the dentine surface area 1 with the nail burnish (Step 2: acid treatment).

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).

The following table 1 summarizes each area processing method of this dentin sample.

In the acid treatment of Step 2, a solution having a composition common to all experimental sections was used. The composition of the solution is shown in Table 2 below.

In each experiment, a solution having the same composition was used in the Step 1 dental enhancement treatment and the Step 3 remineralization treatment. The composition of the solution used in each experiment is shown in Table 3 below.

I-3. Evaluation method (A) Tooth quality evaluation = Microradiography method (B) Remineralization part = Microradiography method (C) Dentin tubule sealing / film formation = Scanning electron microscope Step 1 to Step 3 Thereafter, the bovine tooth pieces were collected and the nail varnish was peeled off, and then Step 4 capillary blockage evaluation / recalcification evaluation was performed. Regarding the evaluation of the tooth quality and the recalcification part, the microscopic photograph of the X-ray photography was performed on the four areas by performing a transversal microradiography (TMR) analysis according to the above-mentioned “4. Method of TMR”. The mineral profile was delineated and the demineralization depth (Ld) and mineral density (ML) were calculated. Regarding dentinal tubule sealing and film formation, the surface and cross section of four areas were evaluated by scanning electron microscopy.

I-4. Results (A) The results of tooth quality evaluation by microradiography are shown in FIGS. FIG. 2 shows the microradiograph of experiment 2A, FIG. 3 shows the microradiograph of experiment 2D, and FIG. 4 shows the microradiograph of experiment 2B. In FIGS. 2 to 4, the gray line indicates the result of area 1 (healthy part), the thin black line indicates the result of area 2 (decalcification part), and the thick black line indicates area 3 (dentinal enhancement part). The results are shown.

As a result, when the decalcification process was performed without the tooth strengthening process (Area 2), the mineral density significantly decreased at the depth of 0 to 50 μm. On the other hand, when the tooth densification treatment is performed using POs-Ca, the demineralization of the dentin hardly occurs even if the acid treatment is performed, and the healthy portion which is not subjected to the acid treatment or the dentin strengthening treatment is almost the same. Equivalent or more minerals were observed. In FIG. 3, in area 3, the mineral density is markedly reduced at 0 to 50 μm, indicating that calcium chloride has a weak dentin strengthening action. By comparing FIG. 2 and FIG. 3, it can be seen that POs—Ca has a dentin dentin strengthening action superior to CaCl ₂ .

(B) The results of the recalcification part by the microradiography method are shown in FIGS. FIG. 5 shows the microradiograph of experiment 2A, FIG. 6 shows the microradiograph of experiment 2D, and FIG. 7 shows the microradiograph of experiment 2B. In FIGS. 5-7, the gray line shows the result of area 1 (healthy part), the thin black line shows the result of area 2 (decalcification part), and the thick black line shows area 4 (recalcification part) The results are shown. As described above, the data of area 1 and area 2 is the same data as the data used in the tooth quality evaluation of (a).

As a result, it was found that the treatment with POs-Ca after the decalcification treatment causes remineralization to the same degree or more as the healthy part. On the other hand, when it was treated with CaCl ₂ , it was found that the remineralization effect was weaker than that of POs—Ca, and it was not possible to remineralize to the same state as the healthy part. In addition, when a solution containing POs—Ca and F is used, as shown in FIG. 7, it can be seen that the remineralization effect is superior at the outermost layer portion as compared with the case of POs—Ca.

Generally, initial caries can occur in exposed dentin. It was confirmed that POs-Ca has a higher remineralization effect than a general calcium agent.

(C) Confirmation of dentinal tubule sealing and film formation with a scanning electron microscope The observation results with a scanning electron microscope are shown in FIGS.

FIG. 8 shows the results of Experiment 2A. In FIG. 8, Ca / P = 1.73, and 6.25 mM of POs-Ca-derived Ca is included. In Experiment 2A, capillary blockage and film formation were observed.

FIG. 9 shows the result of Experiment 2B. In FIG. 9, Ca / P = 1.73, POs—Ca-derived Ca is contained at 6.25 mM, and F is contained at 1 ppm. In Experiment 2B, capillary blockage, film formation, and demineralization suppression were observed.

FIG. 10 shows the result of Experiment 2C. In FIG. 10, Ca / P = 1.67, CaCl ₂ -derived Ca is contained at 6 mM, and F is contained at 10 ppm. In Experiment 2C, 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. In Figure 11, a Ca / P = 0.41, containing 1.5mM of Ca from CaCl _2. In 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. In each of Experiments 2A to 2D, a film was formed on the surface of the dentin without filling the inside of the dentinal tubule by remineralization. In Experiments 2C and 2D, the film was removed by acid treatment. Ivory tubules were exposed.

Conventionally, there is a method of plugging a capillary tube part for blocking the capillary tube. Since POs-Ca reaches the affected area in a solubilized state, a deposited layer containing POs-Ca-derived calcium and saliva-derived phosphate can be formed on the entire root surface. In general blockage, granules are packed into holes, but when POs-Ca is used, the dentinal tubules are blocked by forming a film over the entire surface of the dentin without filling the dentinal tubules. . Therefore, in the case of POs-Ca, it is considered more efficient than partially blocking the tubules with granules.

From the results of (A) to (C), the following were confirmed as functions of POs—Ca alone or a combination of POs—Ca and F:
For healthy dentin, (1) acid resistance is enhanced and (2) pressure resistance is enhanced.

For the initial carious dentin, (1) 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.

(Experiment 3 and Comparative Experiment 3: Comparison between POs-Ca and G-1-P • Ca (glucose-1-phosphate calcium salt))
In Experiment 3, a POs-Ca aqueous solution was used, and in Comparative Experiment 3, a remineralized solution shown in Table 4 having the same composition was used except that a G-1-P · Ca aqueous solution was used instead of the POs-Ca aqueous solution. Bovine dentin was treated in the same procedure as in Steps 0 to 3 of 2. In the solution prepared using G-1-P · Ca, precipitate formation was already observed at the time of preparation, and the calcium concentration in the solution was 6.0 mM or less, and the suitable conditions for remineralization could be maintained. It wasn't.

(Experiment 4)
Dentin strengthening, dentinal tubule sealing, remineralization, etc. were investigated when POs-Ca or calcium chloride was used as the calcium source at various calcium / phosphorus molar ratios (Ca / P).

I-1. Summary of procedure In this experiment, in order to reduce the variation in the results of the samples, dentinal tubule sealing evaluation and remineralization evaluation were performed using the same samples. Each experiment used 5 bovine dentin samples. In this procedure, processing was performed in the following order.
(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); and (Step 3) Capillary blockage evaluation and remineralization evaluation.

I-2. Details of treatment method in each procedure Step 0: Dentin sample preparation A bovine tooth dentin block (7 mm x 15 mm) was cut from a bovine incisor, and this block was then attached to a resin. The block was polished with moistened abrasive paper (# 1000 and # 2000, 3M) to expose a new flat dentin surface.

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.

That is, in Step 1 “dentin 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.

The dentin sample was thoroughly washed before Step 2. Thereafter, the area 3 on the dentin surface was covered with nail burnish. With the areas 1 and 3 on the dentin surface covered with nail burnish, the sample was immersed in a remineralization solution having the composition shown in Table 7 at 37 ° C. for 72 hours (Step 2: remineralization treatment of the demineralized site) . In this remineralization solution, POs—Ca or calcium chloride was used as the calcium source, and potassium dihydrogen phosphate was used as the phosphate source, and the ratio was as shown in Table 7.

The following table 6 summarizes each area processing method of this dentin sample.

In the 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.

I-3. Evaluation method (A) Remineralization part = Microradiography method (B) Ivular tubule sealing / film formation = Scanning electron microscope

After the treatment with the solution of Step 1 and Step 2, the bovine tooth pieces were collected, the nail burnish was peeled off, and then the capillary blockage evaluation and the remineralization evaluation were performed. Regarding the evaluation of the tooth quality and the remineralized part, the X-ray photomicrograph was obtained by conducting a transversal microradiography (TMR) analysis on the three areas according to the above-mentioned “TMR method”. The mineral profile was delineated and the demineralization depth (Ld) and mineral density (ML) were calculated. About the dentinal tubule sealing and film formation, the surface of the area of the remineralized part was evaluated by scanning electron microscopy.

The results are shown in 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). .

Result 1-1
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. In the case of POs-Ca, recovery by remineralization is observed in a shallow portion at Ca / P = 0.1 and Ca / P = 2.0, whereas calcium chloride has any Ca / P ratio. No change in mineral distribution due to remineralization was observed. Therefore, it was shown that POs—Ca significantly promotes remineralization in a range up to Ca / P = 2.0 compared with calcium chloride, which is normal calcium.

Result 1-2:
When the surface of each area was observed with a scanning electron microscope, when the calcium source was POs-Ca, dentinal tubules were blocked at Ca / P = 0.1 and 2.0, whereas the calcium source was chlorinated. When calcium was used, dentinal tubules that could not be blocked at Ca / P = 0.1 remained in the form of dots. Furthermore, at Ca / P = 2.0, the dentinal tubule was not sealed at all. Therefore, it was shown that POs—Ca has an effect of sealing dentinal tubules more advantageously than calcium chloride in the range up to Ca / P = 2.0.

Table 8 summarizes the results 1-1 and 1-2.

(Experiment 5)
Dentin strengthening, dentinal tubule sealing, remineralization, etc. were investigated when POs-Ca or calcium chloride was used as a calcium source at various fluoride concentrations under the conditions of Ca / P = 1.67.

II-1. Summary of procedure In this experiment, in order to reduce the variation in the results of the samples, dentinal tubule sealing evaluation and remineralization evaluation were performed using the same samples. Each experiment used 5 bovine dentin samples. In this procedure, processing was performed in the following order.

(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.

II-2. Details of processing method in each procedure Step 0 to Step 1 were processed in the same manner as I-2 in Experiment 4 above.
The dentin sample was thoroughly washed before Step 2. Thereafter, the sample was immersed in a remineralization solution having the composition shown in Table 9 at 37 ° C. for 72 hours with the area 3 on the dentin surface covered with nail burnish.

II-3. Evaluation Method Evaluation was performed in the same manner as in I-3 of Experiment 4.

Result 2-1
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. In the case of POs—Ca, 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. On the other hand, in the case of calcium chloride, remineralization occurs in the presence of 10 ppm fluoride, whereas in the absence of fluoride (0 ppm), there is no effect of promoting remineralization, and 100 ppm of fluoride exists. Even underneath, remineralization was not promoted at all (FIG. 16). Therefore, POs-Ca was remarkably compared with calcium chloride, and showed a property of promoting remineralization even with a fluoride concentration exceeding 10 ppm. In both POs-Ca and calcium chloride, precipitation occurred at fluoride concentrations exceeding 1000 ppm.

Result 2-2
The observation result of the surface by a scanning electron microscope is shown in FIG. When the surface of each area was observed with a scanning electron microscope, when the calcium source was POs-Ca, some indentations remained in the absence of fluoride (0 ppm), but the dentinal tubules were completely blocked. . At 1 ppm, the unevenness of the surface was conspicuous, but the dentinal tubules were completely sealed until they were not visible. A complete dentinal tubule blockage with a smooth surface in the presence of 10 ppm fluoride was seen with the best results. In the presence of 100 ppm fluoride, a slightly unblocked dentinal tubule was observed, but a state of blocking was observed.

On the other hand, when the calcium source was calcium chloride, dentinal tubules were not blocked in the absence of fluoride and in the presence of 1 ppm fluoride. In the presence of 10 ppm of fluoride, it was not completely blocked and a part was open. When the fluoride concentration was increased to 100 ppm, the effect of blocking the dentinal tubule was hardly observed. Therefore, it was shown that POs—Ca has a better dentinal tubule sealing effect than calcium chloride in the presence of fluoride up to 100 ppm.

Table 10 summarizes the results 2-1 and 2-2.

As described above, the present invention has been exemplified using the preferred embodiment of the present invention, but the present invention should not be construed as being limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention. Patents, patent applications, and documents cited herein should be incorporated by reference in their entirety, as if the contents themselves were specifically described herein. Understood.

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.

According to the dentin dentin reinforcing agent, 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.

Particularly, according to the present invention, since 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.

Claims

A dentinal tubule sealant containing a calcium-containing component, wherein 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 dentinal tubule sealant, which is a mixture of i) and (ii), wherein the phosphorylated saccharide comprises a saccharide moiety and a phosphate group.
The dentinal tubule sealant according to claim 1, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
The dentinal tubule sealant according to claim 1, further comprising at least 0.1% by weight of hydroxyapatite.
The dentinal tubule blocking agent according to claim 1, wherein the sugar moiety is a glucan residue.
The dentinal tubule blocking agent according to claim 4, wherein the degree of polymerization of the sugar moiety is 3 to 9, and the number of phosphate groups is 1 to 2.
The dentinal tubule sealant according to claim 1, wherein the calcium-containing component is a phosphorylated saccharide calcium salt.
The dentinal tubule sealant according to claim 1, wherein the calcium salt in (ii) is a water-soluble calcium salt.
The dentinal tubule sealant according to claim 1, comprising fluoride so that the fluoride ion concentration in saliva when used in the oral cavity is 100 ppm or less.
The ivory of Claim 1 containing a calcium containing component so that the molar ratio (Ca / P ratio) of the calcium ion with respect to the phosphorus ion in the saliva in an oral cavity may be 5.0 or less when used in the oral cavity. Capillary sealant.
An intraoral composition, comprising the dentinal tubule sealant according to claim 1.
The oral composition according to claim 10, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
The intraoral composition according to claim 10, further comprising 0.1% by weight or more of hydroxyapatite.
A 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 intraoral composition described in 1.
A medicinal composition comprising the dentinal tubule sealant according to claim 1.
The medicinal composition according to claim 14, which does not contain hydroxyapatite or has a hydroxyapatite content of less than 0.1% by weight.
The medicinal composition according to claim 14, further comprising 0.1% by weight or more of hydroxyapatite.
The medicinal composition according to claim 14, which is a chewing gum, a chewing tablet or a troche.