Dental composition

Abstract

To provide a dental composition that can suitably seal a dentinal tubule, suppresses dentinal collagen degradation in dental caries occurring at root dentin, and also can promote remineralization of mineral-eluted (decalcified) dentin.SOLUTION: A dental composition comprises tetracalcium phosphate (A), acidic calcium phosphate (B), fluorine compound (C), carbodiimide compound (D) and nonaqueous dispersant (E).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a dental composition, and more particularly to a dental composition that inhibits collagen degradation in dentin in caries that occurs on the root surface and promotes remineralization of dentin. [Background technology]

[0002] In the oral cavity, tooth dentin is normally protected by enamel. However, when gums recede due to the onset of periodontal disease, the roots of teeth that were previously covered by gums become exposed. In the roots, dentin exists without enamel. This dentin possesses numerous tubule structures and contains a large amount of organic material, primarily collagen, resulting in a low mineral density of approximately 50%. This makes it physically and chemically fragile compared to enamel, which has a mineral density of approximately 97%. Therefore, the exposed roots are prone to caries. Here, "dental caries" refers to substantial tooth loss caused by demineralization (dissolution of mineral components) of enamel and dentin by acids produced by oral bacteria metabolizing carbohydrates. Dentin caries occurring in the roots of teeth is called "root caries."

[0003] Caries that develop in the dentin on the root surface is thought to progress not only because minerals are dissolved by acids produced by microorganisms in the oral cavity, but also because the breakdown of collagen, an organic substance that is contained in large quantities in dentin (Non-Patent Documents 1 and 2), and is fundamentally different from cavities that develop in the enamel, which contains almost no organic matter.

[0004] Therefore, even if the elution of tooth minerals is simply prevented, the progression of dentin collagen degradation will further worsen root caries. Conversely, if this collagen is degraded, the scaffolding for mineral deposition will be lost, making remineralization difficult and significantly hindering the healing or recovery of caries.

[0005] Therefore, in order to treat caries that occurs in the root dentin, it is necessary to inhibit the breakdown of dentin collagen and then promote the recovery of minerals (remineralization).

[0006] Patent Document 1 proposes that a paste-type dentinal tubule sealant containing calcium phosphate, fluoride, and a non-aqueous dispersant has excellent dentinal tubule sealing properties. Patent Document 2 proposes that a dentin mineralizing agent containing calcium phosphate, fluoride, and water has excellent dentinal tubule sealing properties and can be used as a root caries preventive material.

[0007] A known technique for preventing root caries is described in Patent Document 3. Patent Document 3 proposes an oral composition containing a lactam compound having a lactam skeleton and an acidic group, for the purpose of inhibiting dentin caries and suppressing dentin hypersensitivity. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2015 / 019601 [Patent Document 2] Japanese Patent Application Laid-Open No. 2013-71917 [Patent Document 3] International Publication No. 2013 / 47826 [Non-patent literature]

[0009] [Non-Patent Document 1] Katz, S.; Park, KK; and Palenik, CJ, Journal of Oral Medicine 42, 40-48, 1987 [Non-patent document 2] P. Schupbach, B. Guggenheim, F. Lutz, Journal of Oral Pathology & Medicine 18(3): 146-156,1989 Summary of the Invention [Problem to be solved by the invention]

[0010] As a result of investigations by the present inventors, it was found that the composition described in Patent Document 1 is excellent in durability of dentinal tubule sealing ability and storage stability, and the composition described in Patent Document 2 is excellent in dentinal tubule sealing ability. However, these compositions have the drawback that calcium phosphate and fluoride cannot protect exposed collagen in root caries, and therefore cannot inhibit collagen decomposition, and there is room for further improvement.

[0011] Pyrrolidone carboxylic acid (hereinafter also referred to as "PCA") and salts thereof, which are exemplified as lactam compounds in Patent Document 3, have the effect of inhibiting collagen degradation, but have the problem of insufficient remineralization ability.

[0012] Therefore, an object of the present invention is to provide a dental composition that has excellent dentinal tubule sealing properties, inhibits collagen degradation in dentin during caries that occurs in root surface dentin, and promotes remineralization of dentin that has undergone mineral elution (demineralization). [Means for solving the problem]

[0013] As a result of extensive research, the present inventors have found that a dental composition having a specific composition can solve the above problems, and after further research, have completed the present invention.

[0014] That is, the present invention includes the following inventions. [1] A dental composition comprising tetracalcium phosphate (A), acidic calcium phosphate (B), a fluorine compound (C), a carbodiimide compound (D), and a non-aqueous dispersant (E). [2] The dental composition according to [1], wherein the acidic calcium phosphate (B) is at least one selected from the group consisting of anhydrous calcium phosphate monobasic [CaHPO4], anhydrous calcium phosphate dibasic [Ca(H2PO4)2], acidic calcium pyrophosphate [CaH2P2O7], calcium phosphate monobasic dihydrate [CaHPO4·2H2O], and calcium phosphate dibasic monohydrate [Ca(H2PO4)2·H2O]. [3] The dental composition according to [1] or [2], wherein the fluorine compound (C) is an inorganic fluorine compound. [4] The dental composition according to [1] or [2], wherein the fluorine compound (C) is at least one selected from the group consisting of sodium fluoride, potassium fluoride, ammonium fluoride, lithium fluoride, cesium fluoride, magnesium fluoride, calcium fluoride, strontium fluoride, barium fluoride, copper fluoride, zirconium fluoride, aluminum fluoride, zinc fluoride, tin fluoride, sodium monofluorophosphate, potassium monofluorophosphate, hydrofluoric acid, sodium titanium fluoride, potassium titanium fluoride, diamminesilver fluoride, hexylamine hydrofluoride, laurylamine hydrofluoride, glycine hydrofluoride, alanine hydrofluoride, and fluorosilanes. [5] The dental composition according to any one of [1] to [4], wherein the carbodiimide compound (D) is a carbodiimide compound having 5 to 30 carbon atoms. [6] The dental composition according to any one of [1] to [5], wherein the carbodiimide compound (D) is at least one selected from the group consisting of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, 1,3-diisopropylcarbodiimide, 1-ethyl-3-tert-butylcarbodiimide, and 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate. [7] The dental composition according to any one of [1] to [6], further comprising an alkali metal salt of phosphoric acid (F). [8] The dental composition according to [7], wherein the alkali metal salt of phosphoric acid (F) is disodium monohydrogen phosphate and / or monosodium dihydrogen phosphate. [9] The dental composition according to any one of [1] to [8], further comprising an inorganic filler (G).

[10] The dental composition according to any one of [1] to [9], further comprising an antibacterial agent (H).

[11] The dental composition according to any one of [1] to

[10] , wherein the non-aqueous dispersant (E) is at least one selected from the group consisting of polyethers, monohydric alcohols, and polyhydric alcohols.

[12] The dental composition according to any one of [1] to

[11] , wherein the content of the tetracalcium phosphate (A) is 5 to 75 parts by mass per 100 parts by mass of the total of the tetracalcium phosphate (A) and the acidic calcium phosphate (B).

[13] The dental composition according to any one of [1] to

[11] , wherein the content of the acidic calcium phosphate (B) is 10 to 70 parts by mass per 100 parts by mass of the total of the tetracalcium phosphate (A) and the acidic calcium phosphate (B).

[14] The dental composition according to any one of [1] to

[13] , which is a one-component type.

[15] A tooth surface treatment material comprising the dental composition according to any one of [1] to

[14] .

[16] A root caries treatment material comprising the dental composition according to any one of [1] to

[14] . [Effects of the Invention]

[0015] According to the present invention, a dental composition can be provided that has excellent dentinal tubule sealing properties, inhibits collagen degradation in dentin during caries that occurs in root surface dentin, and further promotes remineralization of dentin that has undergone mineral elution (demineralization). DETAILED DESCRIPTION OF THE INVENTION

[0016] Each component used in the dental composition of the present invention will be described below, although the present invention is not limited to the embodiments described below.

[0017] The dental composition of the present invention comprises tetracalcium phosphate (A), acidic calcium phosphate (B), a fluorine compound (C), a carbodiimide compound (D), and a non-aqueous dispersant (E).

[0018] The reasons why the dental composition of the present invention inhibits collagen degradation in dentin in caries occurring on the root surface and promotes dentin remineralization are unclear, but are presumed to be as follows: The dental composition of the present invention has dentinal tubule sealing properties, and the sealant remains on the tooth surface, which is thought to improve the mineral strengthening and collagen cross-linking effects described below. Specifically, when the dental composition of the present invention is applied to the affected area, tetracalcium phosphate (A) and acidic calcium phosphate (B) physically seal open dentinal tubules. Subsequently, upon contact with gargling or saliva during treatment, the tetracalcium phosphate (A) and acidic calcium phosphate (B) that have sealed the dentinal tubules react with water to form hydroxyapatite. Furthermore, the presence of fluoride ions produces fluoroapatite and calcium fluoride, which deposit in the dentin and strengthen the mineral. It is believed that the two effects of the mineral reinforcement and collagen molecular chains work synergistically, so that the dental composition of the present invention has the effect of suppressing collagen degradation in dentin and promoting dentin remineralization.

[0019] The components contained in the dental composition of the present invention will be described below.

[0020] The tetracalcium phosphate (A) used in the present invention is preferably, but not limited to, particulate. By using tetracalcium phosphate (A) together with acidic calcium phosphate (B), the dental composition of the present invention exhibits excellent dentinal tubule sealing properties. Furthermore, tetracalcium phosphate (A), together with acidic calcium phosphate (B), the fluorine compound (C), and the carbodiimide compound (D), synergistically promotes remineralization of demineralized dentin, resulting in excellent mineral density recovery. The average particle size of the tetracalcium phosphate (A) particles is preferably 0.5 to 10 μm. If the average particle size is less than 0.5 μm, excessive dissolution of tetracalcium phosphate (A) occurs, resulting in a high pH of the aqueous solution. This may result in insufficient precipitation of hydroxyapatite, potentially reducing the durability of dentinal tubule sealing properties. The average particle size is preferably 1.0 μm or more, more preferably 2.0 μm or more. On the other hand, if the average particle size exceeds 10 μm, the particle size becomes too large relative to the dentinal tubule diameter, and there is a risk that the initial dentinal tubule occlusion ability will decrease. The average particle size is preferably 8.0 μm or less, more preferably 6.0 μm or less. Here, the average particle size of the tetracalcium phosphate (A) used in the present invention is calculated as the median diameter by volumetric measurement using a laser diffraction particle size distribution analyzer.

[0021] The method for producing tetracalcium phosphate (A) is not particularly limited. Commercially available tetracalcium phosphate particles may be used as is, or may be appropriately pulverized to adjust the particle size before use. Pulverization can be performed using a pulverizer such as a ball mill, a mortar and pestle mill, or a jet mill. Alternatively, commercially available tetracalcium phosphate particles can be pulverized with a liquid medium such as alcohol using a mortar and pestle mill, a ball mill, or the like to prepare a slurry, and the resulting slurry can be dried to obtain tetracalcium phosphate (A). The pulverizer used for pulverization is not particularly limited, and any known pulverizer can be used. A ball mill is preferred, and alumina or zirconia is preferably used as the material for the pot and balls. When prepared by pulverization as described above, the particles usually have an irregular shape.

[0022] In the dental composition of the present invention, the content of tetracalcium phosphate (A) is 5 to 85 parts by mass relative to 100 parts by mass of the total of tetracalcium phosphate (A) and acidic calcium phosphate (B). If the content is less than 5 parts by mass, the durability of the dentinal tubule occlusion property decreases. The content of tetracalcium phosphate (A) is preferably 15 parts by mass or more, more preferably 25 parts by mass or more, relative to the total of 100 parts by mass. On the other hand, if the content of tetracalcium phosphate (A) exceeds 75 parts by mass, the durability of the dentinal tubule occlusion property also decreases. The content of tetracalcium phosphate (A) is preferably 80 parts by mass or less, more preferably 75 parts by mass or less, relative to the total of 100 parts by mass. Furthermore, in the dental composition of the present invention, the content of tetracalcium phosphate (A) is preferably 10 to 70 parts by mass, more preferably 15 to 65 parts by mass, and even more preferably 20 to 60 parts by mass, relative to the total of 100 parts by mass of the dental composition.

[0023] The acidic calcium phosphate (B) used in the present invention is not particularly limited, but is preferably in a particulate form. The acidic calcium phosphate (B) may be anhydrous or hydrated, but is preferably anhydrous. By using the acidic calcium phosphate (B) together with the tetracalcium phosphate (A), the dental composition of the present invention has excellent dentinal tubule sealing properties. Furthermore, the acidic calcium phosphate (B) can synergistically promote the remineralization of demineralized dentin together with the tetracalcium phosphate (A), the fluorine compound (C), and the carbodiimide compound (D), and therefore the dental composition of the present invention has excellent mineral density recovery ability. The acidic calcium phosphate (B) may be used alone or in combination of two or more types.

[0024] The acidic calcium phosphate (B) is preferably at least one selected from the group consisting of anhydrous calcium monohydrogen phosphate [CaHPO4], anhydrous calcium dihydrogen phosphate [Ca(H2PO4)2], acidic calcium pyrophosphate [CaH2P2O7], calcium monohydrogen phosphate dihydrate [CaHPO4·2H2O], and calcium dihydrogen phosphate monohydrate [Ca(H2PO4)2·H2O], and more preferably anhydrous calcium monohydrogen phosphate [CaHPO4].

[0025] The average particle size of the acidic calcium phosphate (B) particles used in the present invention is preferably 0.1 to 7.5 μm. If the average particle size is less than 0.1 μm, the viscosity of the dental composition may become too high, resulting in poor application properties and poor dentinal tubule sealing properties. The average particle size of the acidic calcium phosphate (B) is more preferably 0.3 μm or more. On the other hand, if the average particle size of the acidic calcium phosphate (B) exceeds 7.5 μm, the acidic calcium phosphate (B) becomes less soluble in the dentinal tubule sealant, resulting in excessive dissolution of the tetracalcium phosphate (A). This increases the pH of the composition, hindering smooth precipitation of hydroxyapatite and potentially reducing the mechanical strength of the cured product. The average particle size of the acidic calcium phosphate (B) particles is more preferably 5.0 μm or less, and even more preferably 3.0 μm or less. The average particle size of the acidic calcium phosphate (B) was measured and calculated in the same manner as for the tetracalcium phosphate (A) that hardens upon reaction with water.

[0026] The method for producing the acidic calcium phosphate (B) is not particularly limited. Commercially available acidic calcium phosphate particles may be used as they are, or may be used after being appropriately pulverized to adjust the particle size in the same manner as the above-mentioned tetracalcium phosphate (A).

[0027] In the dental composition of the present invention, the content of acidic calcium phosphate (B) is 10 to 70 parts by mass per 100 parts by mass of the total of tetracalcium phosphate (A) and acidic calcium phosphate (B). If the content is less than 10 parts by mass, the initial dentinal tubule occlusion ability and the durability of the dentinal tubule occlusion ability decrease. The content of acidic calcium phosphate (B) is preferably 15 parts by mass or more, more preferably 20 parts by mass or more, per 100 parts by mass of the total. On the other hand, if the content of acidic calcium phosphate (B) exceeds 70 parts by mass, the durability of the dentinal tubule occlusion ability also decreases. The content of acidic calcium phosphate (B) is preferably 60 parts by mass or less, more preferably 50 parts by mass or less, per 100 parts by mass of the total. Furthermore, in the dental composition of the present invention, the content of acidic calcium phosphate (B) is preferably 1 to 60 parts by mass, more preferably 5 to 50 parts by mass, and even more preferably 8 to 40 parts by mass, per 100 parts by mass of the total amount of the dental composition.

[0028] The blending ratio (A / B) of tetracalcium phosphate (A) and acidic calcium phosphate (B) is not particularly limited, but is preferably in the range of 40 / 60 to 60 / 40 in molar ratio. This allows for the production of a dental composition with high mechanical strength after curing. The blending ratio (A / B) is more preferably 45 / 55 to 55 / 45, and optimally substantially 50 / 50.

[0029] The dental composition of the present invention further contains a fluorine compound (C) from the viewpoint of acid resistance. The fluorine compound (C), together with the tetracalcium phosphate (A), the acidic calcium phosphate (B), and the carbodiimide compound (D), synergistically promotes the remineralization of demineralized dentin, and therefore the dental composition of the present invention has excellent mineral density recovery ability. The fluorine compound (C) used in the present invention is not particularly limited, and examples thereof include inorganic fluorine compounds and organic fluorine compounds. Specific examples of the fluorine compound (C) include inorganic fluorine compounds such as sodium fluoride, potassium fluoride, ammonium fluoride, lithium fluoride, cesium fluoride, magnesium fluoride, calcium fluoride, strontium fluoride, barium fluoride, copper fluoride, zirconium fluoride, aluminum fluoride, zinc fluoride, tin fluoride, sodium monofluorophosphate, potassium monofluorophosphate, hydrofluoric acid, sodium titanium fluoride, potassium titanium fluoride, and diammine silver fluoride; and organic fluorine compounds such as hexylamine hydrofluoride, laurylamine hydrofluoride, glycine hydrofluoride, alanine hydrofluoride, and fluorosilanes (e.g., fluoroalkylsilanes such as perfluoroalkylsilanes). These compounds may be used alone or in combination of two or more. Among these, zinc fluoride, strontium fluoride, and sodium fluoride are preferably used from the viewpoint of safety.

[0030] The content of the fluorine compound (C) used in the present invention is not particularly limited, but the dental composition preferably contains 0.01 to 10 parts by mass of fluoride ions in terms of the fluorine compound (C) in terms of fluoride ions per 100 parts by mass of the total amount. To further enhance the acid resistance of the sealant in the dentinal tubules, the content of fluorine compound (C) in terms of fluoride ions is more preferably 0.05 parts by mass or more per 100 parts by mass of the total amount. Furthermore, from the viewpoint of safety, the content of fluorine compound (C) in terms of fluoride ions in terms of fluoride ions is more preferably 5 parts by mass or less per 100 parts by mass of the total amount.

[0031] The dental composition of the present invention further contains a carbodiimide compound (D) from the viewpoint of inhibiting the degradation of dentin collagen in dental caries and synergistically promoting the remineralization of demineralized dentin together with other components. Examples of the carbodiimide compound (D) used in the present invention include carbodiimide compounds having a cyclic structure and carbodiimide compounds not having a cyclic structure. As the carbodiimide compound (D), a carbodiimide compound having 5 to 30 carbon atoms is preferred, a carbodiimide compound having 6 to 28 carbon atoms is more preferred, and a carbodiimide compound having 7 to 25 carbon atoms is even more preferred. Within the range of the specific carbodiimide compound (D) used in the present invention, the effect of inhibiting the degradation of dentin collagen and promoting the remineralization of demineralized dentin is more excellent.

[0032] Examples of the cyclic structure include a cycloalkyl group, an aryl group, and a heterocyclic group. The dental composition of the present invention uses the carbodiimide compound (D) to inhibit collagen degradation in dentin caused by caries that develops in root dentin. Furthermore, the carbodiimide compound (D) synergistically promotes remineralization of demineralized dentin in conjunction with other components. Therefore, the dental composition of the present invention has excellent mineral density recovery ability. Therefore, the dental composition also has excellent therapeutic effects against root caries.

[0033] The carbon number of the cycloalkyl group may be 3 to 8. Examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. The cycloalkyl group may have a substituent.

[0034] The number of carbon atoms in the aryl group may be 6 to 10. Examples of the aryl group include a phenyl group and a naphthyl group. The aryl group may have a substituent.

[0035] Examples of heterocyclic groups include 5- or 6-membered monocyclic aromatic heterocyclic groups containing at least one atom selected from a nitrogen atom, an oxygen atom, and a sulfur atom; and fused bicyclic or tricyclic aromatic heterocyclic groups having fused 3- to 8-membered rings and containing at least one atom selected from a nitrogen atom, an oxygen atom, and a sulfur atom. The 5- or 6-membered monocyclic aromatic heterocyclic groups are preferred. Examples of the 5- or 6-membered monocyclic aromatic heterocyclic groups include a morpholino group, a piperazino group, a piperidino group, and a pyrrolidinyl group. The heterocyclic groups may have a substituent.

[0036] Examples of the substituents that the cyclic structure has include an alkyl group having 1 to 6 carbon atoms, a halogen atom (a chlorine atom, a bromine atom, an iodine atom), and an alkylamino group having 1 to 6 carbon atoms. The number of the substituents that the cyclic structure has is not particularly limited, but is preferably 1 to 5, more preferably 1 to 4, and even more preferably 1 to 3.

[0037] The number of rings in the carbodiimide compound having a cyclic structure is not particularly limited, and is preferably 1 to 5, more preferably 1 to 4, and even more preferably 1 to 3. When the carbodiimide compound having a cyclic structure has two or more cyclic structures, the two or more cyclic structures may be the same or different.

[0038] The carbodiimide compound having a cyclic structure may be a compound in which the cyclic structure and the carbodiimide bond are directly bonded to each other.

[0039] In another embodiment, the carbodiimide compound having a cyclic structure may include a divalent hydrocarbon group bonded to the cyclic structure and the carbodiimide bond. In other words, the carbodiimide compound having a cyclic structure may be a compound including a portion in which the cyclic structure is bonded to the carbodiimide bond via a divalent hydrocarbon group.

[0040] Examples of compounds containing a portion in which a cyclic structure is bonded to a carbodiimide bond via a divalent hydrocarbon group include compounds in which all cyclic structures are bonded to a carbodiimide bond via a divalent hydrocarbon group; and compounds having a portion in which a cyclic structure is directly bonded to a carbodiimide bond and a portion in which a cyclic structure is bonded to a carbodiimide bond via a divalent hydrocarbon group.

[0041] When the carbodiimide compound having a cyclic structure is a compound containing a portion in which the cyclic structure is bonded to a carbodiimide bond via a divalent hydrocarbon group and the cyclic structure is a nitrogen-containing heterocyclic group, the nitrogen-containing heterocyclic group may be bonded to the divalent hydrocarbon group and a nitrogen atom.

[0042] Examples of the divalent hydrocarbon group include an alkylene group and an alkenylene group.

[0043] The alkylene group may be linear or branched. Examples of the alkylene group include alkylene groups having 1 to 12 carbon atoms, such as methylene, ethylene, n-propylene, isopropylene, cyclopropylene, n-butylene, isobutylene, s-butylene, t-butylene, cyclobutylene, 1-methylcyclopropylene, 2-methylcyclopropylene, n-pentylene, and n-hexylene. The number of carbon atoms in the alkylene group is preferably 1 to 10, more preferably 1 to 8, and even more preferably 1 to 6.

[0044] The carbodiimide compound having no cyclic structure preferably contains a chain structure. Examples of the chain structure include hydrocarbon groups such as alkyl groups and alkenyl groups, with alkyl groups being preferred. The chain structure may be linear or branched. The number of carbon atoms in the alkyl group is preferably 1 to 10, more preferably 1 to 8, and even more preferably 1 to 6. Examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, a sec-pentyl group, a neopentyl group, and an n-hexyl group. When the carbodiimide compound having no cyclic structure contains alkyl groups, the two alkyl groups may be the same or different.

[0045] The chain structure may have a substituent. Examples of the substituent include an alkyl group having 1 to 6 carbon atoms, a halogen atom (a chlorine atom, a bromine atom, an iodine atom), an alkylamino group having 1 to 6 carbon atoms, etc. The chain structure may be, for example, an alkyl group having 1 to 6 carbon atoms substituted with two alkylamino groups having 1 to 6 carbon atoms.

[0046] The carbodiimide compound (D) may be in the form of a salt, such as a hydrochloride, a sulfate, a sulfonate, or a p-toluenesulfonate.

[0047] Specifically, the carbodiimide compound (D) is preferably at least one selected from the group consisting of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, 1,3-diisopropylcarbodiimide, 1-ethyl-3-tert-butylcarbodiimide, and 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate. Among these carbodiimide compounds (D), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride and 1,3-diisopropylcarbodiimide are particularly preferred from the viewpoint of biocompatibility. One type of carbodiimide compound (D) may be used alone, or two or more types may be used in combination. The content of the carbodiimide compound (D) is preferably 0.01 to 30 parts by mass per 100 parts by mass of the total dental composition, from the viewpoint of inhibiting the decomposition of collagen in dentin during caries and synergistically promoting the remineralization of demineralized dentin together with other components. In order to achieve a more excellent effect of inhibiting the decomposition of collagen in dentin and promoting the remineralization of demineralized dentin, the content of the carbodiimide compound (D) is more preferably 0.05 to 25 parts by mass, and even more preferably 0.1 to 20 parts by mass per 100 parts by mass of the total dental composition.

[0048] The non-aqueous dispersant (E) is a component that makes the dental composition paste-like and improves its handleability. The non-aqueous dispersant (E) may be used singly or in combination of two or more. The non-aqueous dispersant (E) used in the present invention is not particularly limited, but is preferably at least one selected from the group consisting of polyethers, monohydric alcohols, and polyhydric alcohols. Examples of monohydric alcohols include methanol, ethanol, and isopropanol. Examples of polyethers include polyethylene glycol (hereinafter sometimes abbreviated as PEG) and polypropylene glycol. Examples of polyhydric alcohols include glycerin, ethylene glycol, propylene glycol, and diglycerin. Among these, glycerin, ethylene glycol, propylene glycol, and polyethylene glycol are particularly preferred.

[0049] The content of the non-aqueous dispersant (E) is preferably 20 to 90 parts by mass per 100 parts by mass of the total amount of the dental composition of the present invention. If it is less than 20 parts by mass, the viscosity of the paste may be high, and the operability may be reduced. The content of the non-aqueous dispersant (E) is more preferably 25 parts by mass or more, and even more preferably 30 parts by mass or more, per 100 parts by mass of the dental composition. On the other hand, if the content of the non-aqueous dispersant (E) exceeds 90 parts by mass, the dentinal tubule occlusion property may be reduced. The content of the non-aqueous dispersant (E) is more preferably 85 parts by mass or less, and even more preferably 82 parts by mass or less, per 100 parts by mass of the dental composition.

[0050] The dental composition of the present invention preferably further contains an alkali metal salt of phosphoric acid (F). By including the alkali metal salt of phosphoric acid (F), the setting time can be further shortened, thereby improving operability and dentinal tubule sealing properties. The alkali metal salt of phosphoric acid (F) used is not particularly limited, but examples include disodium monohydrogen phosphate, dipotassium monohydrogen phosphate, monolithium dihydrogen phosphate, monosodium dihydrogen phosphate, monopotassium dihydrogen phosphate, trisodium phosphate, and tripotassium phosphate, and one or more of these may be used. Among these, from the viewpoints of safety and ease of obtaining high-purity raw materials, it is preferred that the alkali metal salt of phosphoric acid (F) be disodium monohydrogen phosphate and / or monosodium dihydrogen phosphate.

[0051] In the dental composition of the present invention, the content of the alkali metal salt of phosphoric acid (F) is 0.5 to 15 parts by mass relative to 100 parts by mass of the total of tetracalcium phosphate (A) and acidic calcium phosphate (B). If the content is less than 0.5 parts by mass, the addition of the alkali metal salt of phosphoric acid (F) will not significantly improve the durability of dentinal tubule occlusion. The content of the alkali metal salt of phosphoric acid (F) is preferably 1 part by mass or more, more preferably 2 parts by mass or more, relative to 100 parts by mass of the total. On the other hand, if the content of the alkali metal salt of phosphoric acid (F) exceeds 15 parts by mass, the initial dentinal tubule occlusion will be poor. The content of the alkali metal salt of phosphoric acid (F) is preferably 12 parts by mass or less, more preferably 10 parts by mass or less, relative to 100 parts by mass of the total. The content of the alkali metal salt of phosphoric acid (F) refers to the proportion of the alkali metal salt of phosphoric acid (F) relative to 100 parts by mass of the total of calcium phosphate (A) and acidic calcium phosphate (B), calculated as 100 parts by mass of the total mass of calcium phosphate (A) and acidic calcium phosphate (B). This standard does not include compounds other than tetracalcium phosphate (A) and acidic calcium phosphate (B) (for example, other calcium-containing compounds described below).

[0052] The alkali metal salt of phosphoric acid (F) used in the present invention is not particularly limited, but is preferably in a particulate form. The average particle size of the particles of the alkali metal salt of phosphoric acid (F) is preferably 1.0 to 12 μm. If the average particle size of the alkali metal salt of phosphoric acid (F) is less than 1.0 μm, it will dissolve too quickly upon contact with water, resulting in a high phosphate ion concentration, which may disrupt the balance between the supply of calcium ions and phosphate ions and result in a decrease in the precipitation rate of hydroxyapatite. The average particle size of the alkali metal salt of phosphoric acid (F) is more preferably 3.0 μm or more. On the other hand, if the average particle size of the alkali metal salt of phosphoric acid (F) exceeds 12 μm, it will become difficult for the alkali metal salt of phosphoric acid (F) to dissolve in water, which may result in a decrease in the precipitation rate of hydroxyapatite. The average particle size of the alkali metal salt of phosphoric acid (F) is more preferably 8.0 μm or less. The average particle size of the alkali metal salt of phosphoric acid (F) is calculated in the same manner as the average particle size of the particles of tetracalcium phosphate (A) described above.

[0053] The method for producing the alkali metal salt of phosphoric acid (F) is not particularly limited. Commercially available alkali metal salts of phosphoric acid may be used as they are, or may be used after being appropriately pulverized to adjust the particle size in the same manner as the above-mentioned tetracalcium phosphate (A).

[0054] The dental composition of the present invention may further contain an inorganic filler (G). The type of inorganic filler (G) used in the present invention is not particularly limited, and examples include quartz, silica, alumina, zirconia, titania, silica-titania, silica-titania-barium oxide, silica-zirconia, silica-alumina, lanthanum glass, borosilicate glass, soda glass, barium glass, strontium glass, glass ceramic, aluminosilicate glass, barium boroaluminosilicate glass, strontium boroaluminosilicate glass, fluoroaluminosilicate glass, calcium fluoroaluminosilicate glass, strontium fluoroaluminosilicate glass, barium fluoroaluminosilicate glass, and strontium calcium fluoroaluminosilicate glass. One or more of these is preferably used. Among these, at least one selected from the group consisting of barium glass, fluoroaluminosilicate glass, silica, and zirconia is more preferably used.

[0055] The inorganic filler (G) used in the present invention has an average particle size of 0.002 to 0.5 μm. If the average particle size of the inorganic filler (G) is less than 0.002 μm, the viscosity of the dental composition increases, resulting in poor handleability. The average particle size is preferably 0.003 μm or more, and more preferably 0.005 μm or more. On the other hand, if the average particle size of the inorganic filler (G) exceeds 0.5 μm, the dentinal tubule occlusion rate decreases. The average particle size is preferably 0.2 μm or less, and more preferably 0.1 μm or less. The average particle size of the inorganic filler (G) is calculated by taking a photograph of primary particles dispersed in an epoxy resin using a transmission electron microscope, measuring the particle sizes of 100 or more randomly selected primary particles, and then calculating the arithmetic mean.

[0056] In the dental composition of the present invention, the content of the inorganic filler (G) is 0.1 to 50 parts by mass relative to 100 parts by mass of the total of tetracalcium phosphate (A) and acidic calcium phosphate (B). If the content is less than 0.1 part by mass, the effect of improving dentinal tubule occlusion is reduced. The content of the inorganic filler (G) is preferably 1 part by mass or more, more preferably 2 parts by mass or more, relative to the total of 100 parts by mass. On the other hand, if the content of the inorganic filler (G) exceeds 50 parts by mass, the viscosity of the dental composition increases, reducing handleability. The content of the inorganic filler (G) is preferably 30 parts by mass or less, more preferably 30 parts by mass or less, relative to the total of 100 parts by mass. The standards for the content of the inorganic filler (G) are the same as those for the content of the alkali metal salt of phosphoric acid (F).

[0057] The dental composition of the present invention may further contain an antibacterial agent (H) as needed. Examples of the antibacterial agent (H) include quaternary ammonium salts such as cetylpyridinium chloride, benzethonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, stearyltrimethylammonium chloride, lauryltrimethylammonium chloride, and laurylpyridinium chloride; cationic antibacterial agents such as biguanide antibacterial agents such as chlorhexidine hydrochloride, chlorhexidine acetate, chlorhexidine gluconate, alexidine hydrochloride, alexidine acetate, and alexidine gluconate; anionic antibacterial agents such as sodium n-lauroylsarconate; nonionic antibacterial agents such as triclosan and isopropylmethylphenol; and zinc compounds such as zinc oxide and zinc chloride. These agents may be used alone or in combination of two or more.

[0058] The content of the antibacterial agent (H) used in the present invention is not particularly limited, and is preferably 0.01 to 10 parts by mass per 100 parts by mass of the total dental composition. To further enhance the acid resistance of the blockage in the dentinal tubules, the content of the antibacterial agent (H) is more preferably 0.05 parts by mass or more per 100 parts by mass of the total composition. Furthermore, from the viewpoint of safety, the content of the antibacterial agent (H) is more preferably 10 parts by mass or less per 100 parts by mass of the total composition.

[0059] The dental composition of the present invention may contain a thickener other than the inorganic filler (G) as needed, because this allows the viscosity of the paste to be adjusted and the paste properties to be adjusted to make it easier for the practitioner to handle. Examples of thickeners include synthetic polymers such as polyvinyl alcohol, polyacrylic acid, polystyrene sulfonic acid, and polystyrene sulfonate; polyamino acids or salts thereof such as polyglutamic acid, polyglutamates, polyaspartic acid, polyaspartates, poly-L-lysine, and poly-L-lysine salts; cellulose compounds such as carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose; polysaccharides such as starches other than cellulose (e.g., starches having an amylose content of 10 to 70%, such as corn starch, potato starch, and tapioca starch), dextran, alginic acid, alginates, carrageenan, guar gum, xanthan gum, cellulose gum, hyaluronic acid, hyaluronates, pectin, pectate, chitin, and chitosan; acidic polysaccharide esters such as propylene glycol alginate; collagen; gelatin; and derivatives thereof. These may be used alone or in combination of two or more.

[0060] The content of the thickener other than the inorganic filler (G) used in the present invention is not particularly limited, and is preferably 0.01 to 10 parts by mass per 100 parts by mass of the total dental composition. Because this can increase the fluidity of the paste and further improve its operability, the content of the thickener is more preferably 0.05 parts by mass or more per 100 parts by mass of the total. Furthermore, because this can prevent a decrease in the fluidity of the paste, the content of the thickener is more preferably 8 parts by mass or less per 100 parts by mass of the total.

[0061] The dental composition of the present invention can be blended with any pharmacologically acceptable drug, etc., as needed. Examples of drugs include disinfectants, anticancer agents, antibiotics, blood circulation improvers such as actosin and PEG1, growth factors such as bFGF, PDGF, and BMP, and cells that promote hard tissue formation, such as osteoblasts, odontoblasts, and further induced pluripotent stem (iPS) cells prepared by gene transfer from differentiated cells such as undifferentiated bone marrow-derived stem cells, embryonic stem (ES) cells, and fibroblasts, as well as cells differentiated from these.

[0062] The dental composition of the present invention may contain a lactam compound having a lactam skeleton, either a γ-lactam skeleton, a δ-lactam skeleton, or an ε-lactam skeleton, and an acidic group, for the purposes of improving the inhibitory effect on dentin caries, inhibiting dentin hypersensitivity, etc. Examples of the lactam compound include pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3-(2-oxo-1-azepanyl)propanoic acid.

[0063] The dental composition of the present invention preferably contains substantially no polymerizable monomer. In the present invention, "substantially no polymerizable monomer" means that the content of a certain component is preferably less than 5 parts by mass, more preferably less than 1 part by mass, and even more preferably less than 0.1 part by mass, based on 100 parts by mass of the total amount of the dental composition.

[0064] The dental composition of the present invention may contain calcium-containing compounds other than tetracalcium phosphate (A) and acidic calcium phosphate (B) (hereinafter also referred to as "other calcium-containing compounds") to enhance the sustained release of calcium ions. Examples of other calcium-containing compounds include calcium silicates such as tricalcium silicate, dicalcium silicate, and calcium silicate hydrate; and calcium salts such as calcium oxide, calcium hydroxide, calcium chloride, calcium carbonate, calcium sulfate, calcium sulfite, calcium phosphate, and calcium pyrophosphate. The content of the other calcium-containing compounds is not particularly limited, but may be less than 5 parts by weight, less than 1 part by weight, or less than 0.1 parts by weight per 100 parts by weight of the total amount of the dental composition.

[0065] The dental composition of the present invention is obtained as a paste containing at least tetracalcium phosphate (A), acidic calcium phosphate (B), a fluorine compound (C), a carbodiimide compound (D), and a non-aqueous dispersant (E). The dental composition (paste) of the present invention can be prepared as a one-component formulation.

[0066] The method for preparing the paste containing tetracalcium phosphate (A), acidic calcium phosphate (B), fluorine compound (C), carbodiimide compound (D), and non-aqueous dispersant (E) is not particularly limited, and it can be obtained by mixing using, for example, a twin-screw kneader, a triple-screw kneader, or a planetary kneader.

[0067] The dental composition of the present invention is preferably used by applying it to the dentin surface or by rubbing it into the dentin surface. The rubbing operation can be performed by simply rubbing the dentin surface with a microbrush, cotton swab, rubber cup, toothbrush, or the like for about 30 seconds, which produces a sealant in the dentinal tubules to a depth of about 5 μm.

[0068] Suitable embodiments of the dental composition of the present invention include tooth surface treatment materials, root caries treatment materials, dentin hypersensitivity suppressants, dentifrice, etc. When used for the above purposes, the dental composition of the present invention exhibits good sealing properties within dentinal tubules, inhibits collagen degradation in dentin, and is expected to promote dentin remineralization. Furthermore, the dental composition of the present invention is converted to hydroxyapatite upon contact with water in the oral cavity and becomes integrated with the tooth at the application site, resulting in excellent biocompatibility.

[0069] The present invention includes embodiments in which the above-described configurations are combined in various ways within the scope of the technical concept of the present invention, as long as the effects of the present invention are achieved. [Example]

[0070] The present invention will be specifically explained below using examples, but the present invention is not limited to these examples in any way, and many modifications can be made by a person having ordinary skill in the art within the technical spirit of the present invention.

[0071] In the present example, the average particle diameters of tetracalcium phosphate (A) and alkali metal salt of phosphoric acid (F) were measured on a volume basis using a laser diffraction particle size distribution analyzer ("SALD-2300" manufactured by Shimadzu Corporation), and the median diameter calculated from the measurement results was used as the average particle diameter.

[0072] [Preparation of each component] (1) Preparation of tetracalcium phosphate (A) Tetracalcium phosphate particles (TTCP, average particle size 1.1 μm) used in this example as tetracalcium phosphate (A) were prepared as follows: 50 g of commercially available tetracalcium phosphate particles (manufactured by Taihei Chemical Industry Co., Ltd., average particle size 5.2 μm), 120 g of 95% ethanol ("Ethanol (95)" manufactured by Fujifilm Wako Pure Chemical Industries Co., Ltd.), and 240 g of 10 mm diameter zirconia balls were added to a 400 ml alumina milling pot ("Type A-3 HD Pot Mill" manufactured by Nikkato Corporation), wet-milled at a rotation speed of 120 rpm for 24 hours, sieved, and the zirconia balls were removed. The resulting slurry was used to remove the ethanol using a rotary evaporator, dried at 60°C for 6 hours, and then vacuum-dried at 60°C for 24 hours to obtain tetracalcium phosphate particles (TTCP).

[0073] (2) Preparation of acidic calcium phosphate (B) Anhydrous monobasic calcium phosphate particles (DCPA, average particle size: 5.0 μm) used in this example as acidic calcium phosphate (B) were prepared by adding 50 g of commercially available anhydrous monobasic calcium phosphate particles (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., average particle size 10.2 μm), 240 g of 95% ethanol, and 480 g of zirconia balls with a diameter of 10 mm to a 1000 ml alumina milling pot (Nikkato Corporation, "HD-B-104 Pot Mill") and subjecting the mixture to wet vibration milling at a rotation speed of 1500 rpm for 7 hours. The resulting mixture was sieved to remove the zirconia balls, and the resulting slurry was used to remove the ethanol using a rotary evaporator. The slurry was then dried at 60°C for 6 hours and further dried in vacuum at 60°C for 24 hours to obtain anhydrous monobasic calcium phosphate particles (DCPA).

[0074] (3) Fluorine compounds (C) The fluorine compound (C) used in this example was the following compound, which was used as it was. ZnF2: Zinc fluoride (Fluorochem) SrF2: Strontium fluoride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.)

[0075] (4) Carbodiimide compound (D) The carbodiimide compound (D) used in this example was the following compound, which was used as is. EDC: 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (Tokyo Chemical Industry Co., Ltd.) DCC: 1,3-diisopropylcarbodiimide (Tokyo Chemical Industry Co., Ltd.)

[0076] (5) Non-aqueous dispersant (E) The non-aqueous dispersant (E) used in this example was the following compound, which was used as is. Glycerin (Tokyo Chemical Industry Co., Ltd.)

[0077] (6) Preparation of alkali metal salts of phosphoric acid (F) Disodium monohydrogen phosphate particles (NaHPO, average particle size 5.2 μm) used in this example as particles of the alkali metal salt of phosphoric acid (F) were obtained by treating commercially available disodium monohydrogen phosphate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) once using a nanojetmizer (NJ-100 model, manufactured by Aisin Nano Technologies Co., Ltd.) under the following milling pressure conditions: raw material supply pressure: 0.7 MPa / milling pressure: 0.7 MPa, and processing amount: 8 kg / hr.

[0078] (7) Inorganic filler (G) The inorganic filler (G) used in this example was the following compound, which was used as is. Ar130 (Aerosil (registered trademark) 130, manufactured by Nippon Aerosil Co., Ltd., average particle size: 16 μm)

[0079] (8) Antibacterial agents (H) The antibacterial agent (H) used in this example was the following compound, which was used as is. CPC: cetylpyridinium chloride (Combi-Blocks)

[0080] [Preparation of dental composition] Tetracalcium phosphate (A), acidic calcium phosphate (B), fluorine compound (C), carbodiimide compound (D), non-aqueous dispersant (E), alkali metal salt of phosphoric acid (F), inorganic filler (G), and antibacterial agent (H), weighed according to the composition shown in Table 1, were added to a universal mixer (Dalton Co., Ltd., "Mixer Twin Mix STM-08") and mixed for 60 minutes at a rotation speed of 130 rpm and a revolution speed of 37 rpm to obtain a one-component dental composition.

[0081] [Evaluation of dentinal tubule occlusion] (1) Preparation of bovine teeth for evaluating dentinal tubule occlusion The central buccal area of ​​a healthy bovine incisor was polished and trimmed using a rotary polisher with #80 and #1000 grit abrasive paper to prepare a 2 mm thick flat dentin plate with exposed buccal dentin. The surface of this dentin plate (polished surface) was further polished using lapping film (#1200, #3000, #8000, 3M Japan Ltd.) to obtain a smooth surface. Lines were drawn on the smooth surface of this dentin plate so that two adjacent 2 mm squares were formed in the vertical and horizontal directions, defining two test windows (hereafter referred to as "dentin windows") (dentin windows A and B). This flat dentin plate was immersed in a 3% EDTA (ethylenediaminetetraacetic acid) solution and exposed to ultrasound for 10 minutes to demineralize the two dentin windows, followed by rinsing with water to prepare bovine teeth for use in evaluating dentinal tubule occlusion. A sufficient amount of the dental composition prepared as described above was applied to one dentin window (dentin window B) on the smooth surface of the buccal dentin of the bovine tooth, and the entire surface of the dentin window was rubbed with a microbrush (MICROBRUSH INTERNATIONAL "REGULAR SIZE (2.0 mm), MRB400") for 30 seconds. The paste on the dentin surface was then removed by rinsing with distilled water for 30 seconds (n=3).

[0082] (2) Preparation of samples for SEM observation After the above treatment, the bovine teeth were dried with an air blower to prepare samples for dentinal tubule observation.

[0083] (3) SEM observation A scanning electron microscope (product name "SU3500", manufactured by Hitachi High-Technologies Corporation) was used for SEM observation. The accelerating voltage was 5 kV, and morphological observations were performed on both the dentin window on the side where the dental composition had not been applied after demineralization (dentin window A) and the other dentin window on which the dental composition had been applied and then removed (dentin window B) (n=3). Three randomly selected points were observed per SEM sample, and dentinal tubule occlusion was evaluated using the dentinal tubule occlusion rate (%), calculated using the following formula: Dentinal tubule occlusion rate (%) = occluded dentinal tubules (number) / observed dentinal tubules (number) × 100 Here, "observed dentinal tubules" refers to the number of dentinal tubules observed in the dentinal window (dentinal window A) on the side where the dental composition was not applied. "Obstructed dentinal tubules" refers to the number obtained by subtracting the number of unobstructed dentinal tubules observed in the dentinal window (dentinal window B) after the dental composition was applied and then removed from the number of "observed dentinal tubules" described above. In the above evaluation, the two dentin windows were the same size and had undergone the same treatment except for the application of the dental composition. Therefore, the number of dentin tubules observed in the dentin window on the side where the dental composition was not applied (dentin window A) was considered to be the number of dentin tubules observed in dentin window B before the application of the dental composition.

[0084] The average dentinal tubule occlusion rate of the three samples was evaluated according to the following criteria. The evaluation results are summarized in Table 1. 〇: Dentinal tubule occlusion rate is 80% or more △: Dentinal tubule occlusion rate is 40% or more but less than 80% ×: Dentinal tubule occlusion rate is less than 40%

[0085] [Evaluation of mineral density recovery ability] The ability to promote remineralization of demineralized dentin was evaluated as mineral density recovery ability using the following method. (1) Preparation of decalcification solution A 50 mM aqueous solution of acetic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) and a 50 mM aqueous solution of sodium acetate trihydrate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were mixed and adjusted to pH 4.5.

[0086] (2) Preparation of artificial saliva 87.6 mg of sodium chloride (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.), 122 mg of potassium dihydrogen phosphate (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.), 166 mg of calcium chloride (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.), and 477 mg of 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid (HEPES) (manufactured by Dojindo Laboratories, Inc.) were dissolved in approximately 800 mL of water, the pH was adjusted to 7.0 with a saturated aqueous solution of NaOH (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.), and the solution was diluted to 1.0 L.

[0087] (3) Reagents used to prepare test specimens The following compounds were used as reagents for preparing the test pieces. Ethanol: manufactured by Kanto Chemical Co., Ltd. Propylene oxide: Fujifilm Wako Pure Chemical Industries, Ltd. Epoxy resin base: (Epocure 2 base, manufactured by BUEHLER) Hardener (Epocure 2 hardener, manufactured by BUEHLER)

[0088] (4) Preparation of test specimens Test specimens were prepared from the cervical region of bovine teeth. The surface of the cervical region was polished with #80 abrasive paper to expose the dentin, followed by further polishing with #1000 abrasive paper and ultrasonic treatment for 5 minutes. A test window measuring approximately 5 mm x 2 mm was created on the surface of the cervical specimen. The specimen was then divided into two halves symmetrically about the dividing plane using a diamond cutter (Isomet 1000, Buehler). Nail polish was applied to the remaining portions of both specimens, excluding the test window, to create two specimens, each with a 5 mm x 1 mm test window. Both specimens were immersed in decalcifying solution and decalcified at 37°C for two weeks. The decalcifying solution was changed every three days. One of the test windows (test window A) was painted with nail polish and allowed to dry. A sample (dental composition of each Example and Comparative Example) was rubbed onto the test window of the other test piece (test window B) for 30 seconds. Both test pieces were stored in a thermo-hygrostat at 37°C and 95% RH for 30 minutes. After storage, the test pieces were immersed in artificial saliva, and the artificial saliva was changed five times within seven days of the start of immersion. The test pieces were then stored at 37°C for two weeks. The nail polish was removed from the resulting test pieces, and they were immersed in 70% ethanol, 80% ethanol, 90% ethanol, 99% ethanol, and 100% ethanol for 10 minutes each, followed by 100% ethanol for 1 day. They were immersed in a 1 / 1 propylene oxide / ethanol mixture and propylene oxide for 10 minutes each, followed by propylene oxide for 1 day. They were immersed in a 1 / 1 epoxy resin / propylene oxide mixture, a 4 / 1 epoxy resin / propylene oxide mixture, and an epoxy resin for 2 hours each, followed by 4 / 1 epoxy resin / hardener mixture. They were then stored at 60°C for 1 day while immersed and allowed to cure. The cured test specimens were cut perpendicular to the long sides of the test window using a diamond cutter (Isomet 1000, manufactured by BUEHLER) to a thickness of approximately 1.2 mm, and wrapping film (#1200, #3000, #8000, manufactured by 3M Japan Ltd.) was used to reduce the thickness of the test specimens to 0.060 mm to 0.110 mm.

[0089] (5)CMR(Contact Micro Radiography) For both test specimens obtained, the entire test specimen was photographed using a soft X-ray inspection device (product name "CMR-2", manufactured by Softex Co., Ltd.) and a glass dry plate (HIGH PRECISION PHOTO PLATE HPP-SN2 2x2, manufactured by Konica Minolta, Inc.) at a tube voltage of 10 kV, a tube current of 2.0 mA, and an exposure time of 10 minutes. The photographed test specimen (dry plate) was immersed in a developer (medical X-ray liquid developer "Hilendor", manufactured by Fujifilm Corporation) for 5 minutes, washed in distilled water for 1 minute, immersed in a fixer (fixer "Hilenfix", manufactured by Fujifilm Corporation) for 5 minutes, and washed in distilled water for 30 seconds.

[0090] (6) Analysis The obtained CMR images were photographed with a microscope (Nikon DS-Ri1, manufactured by Nikon Solutions Corporation), and the brightness value was measured from the surface of the test window in the depth direction of the test window (n=3) using image analysis software (ImageJ, open source, public domain) with the brightness value at 100 μm directly below the nail polish protection of the undecalcified area as the standard, and the mineral density recovery ability (%) was calculated using the following formula: In each of the following formulas, "control" means the case where no treatment was performed with the sample (dental composition of each Example and Comparative Example).

[0091] Control mineral density at any depth = Control brightness value at any depth / brightness value 100 μm below the nail polish protection of the undecalcified area

[0092] Treatment surface mineral density at any depth = Brightness value of treated surface at any depth / Brightness value 100 μm below the nail polish protection of the undecalcified area

[0093]

number

[0094] The average value (n=3) of the mineral density recovery ability was evaluated according to the following criteria. The evaluation results are summarized in Table 1. 〇: Mineral density recovery ability is 20% or more △: Mineral density recovery ability is 15% or more but less than 20% ×: Mineral density recovery ability is less than 15%

[0095] [Evaluation of collagen degradation inhibition rate] (1) Reagents used in the measurement Collagen type I: Sigma-Aldrich Japan LLC Tris-HCl buffer: Fujifilm Wako Pure Chemical Corporation Collagenase: Sigma-Aldrich Japan LLC Ninhydrin ethanol solution: manufactured by Tokyo Chemical Industry Co., Ltd.

[0096] (2)Measurement method 100 mg of sample (dental composition of each Example and Comparative Example) was contacted with 10 mg of collagen type I for 30 seconds. The sample was immersed in distilled water, ultrasonically cleaned for 5 minutes, rinsed with water, filtered, and then dried under reduced pressure. 3 mg of the dried product was immersed in 1.2 mL of 0.05 N Tris-HCl buffer, pH 7.2 (containing 0.001 M CaCl2). 100 units of collagenase was added, and the mixture was incubated for 4 hours. 300 μL of ethanol was added to terminate the enzymatic reaction. 0.5 mL of ninhydrin ethanol solution was added to 0.5 mL of the supernatant obtained by centrifugation (3000 rpm, 5 min). After incubation at 50°C for 90 minutes, the absorbance (λ = 515 nm) was measured using a spectrophotometer (trade name "U-1900", manufactured by Hitachi High-Technologies Corporation). Separately, the absorbance (λ = 515 nm) of distilled water was measured. The collagen degradation inhibition rate was calculated using the following formula. Collagen degradation inhibition rate (%) = (1 - (absorbance of sample / absorbance of distilled water sample)) x 100

[0097] The average values ​​(n=3) of the collagen degradation inhibition rate were evaluated based on the following evaluation criteria, and the evaluation results are summarized in Table 1. 〇: Collagen degradation inhibition rate is 50% or more △: Collagen degradation inhibition rate is 25% or more but less than 50% ×: Mineral density recovery ability is less than 25%

[0098] [Table 1]

[0099] As is clear from the above results, it was confirmed that the dental compositions of the present invention (Examples 1 to 3) exhibit high dentinal tubule sealing properties and are high in both mineral density recovery ability and collagen degradation inhibition rate.

[0100] In contrast, Comparative Example 1, which did not contain a carbodiimide compound, had a low collagen degradation inhibition rate and also insufficient mineral density recovery ability. Comparative Example 2, which did not contain a fluorine compound, had low mineral density recovery ability, and Comparative Example 3, which did not contain tetracalcium phosphate or acidic calcium phosphate, was confirmed to have low dentinal tubule occlusion ability and mineral density recovery ability. [Industrial Applicability]

[0101] The dental composition according to the present invention is suitably used in the field of dentistry as a tooth surface treatment material (for example, a root caries treatment material, a material for suppressing dentin hypersensitivity, etc.) and a toothpaste.

Claims

1. The composition contains tetracalcium phosphate (A), acidic calcium phosphate (B), a fluorine compound (C), a carbodiimide compound (D), and a non-aqueous dispersant (E), The acidic calcium phosphate (B) is anhydrous calcium hydrogen phosphate [CaHPO 4 ], and calcium hydrogen phosphate dihydrate [CaHPO 4 ・2H 2 O], the fluorine compound (C) is at least one selected from the group consisting of sodium fluoride, potassium fluoride, ammonium fluoride, lithium fluoride, cesium fluoride, magnesium fluoride, calcium fluoride, strontium fluoride, barium fluoride, copper fluoride, zirconium fluoride, aluminum fluoride, zinc fluoride, tin fluoride, sodium monofluorophosphate, potassium monofluorophosphate, hydrofluoric acid, sodium titanium fluoride, potassium titanium fluoride, and diamminesilver fluoride; the carbodiimide compound (D) is 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride or 1,3-diisopropylcarbodiimide; A dental composition, wherein the non-aqueous dispersant (E) is at least one selected from polyhydric alcohols.

2. The dental composition according to claim 1 , further comprising an alkali metal salt of phosphoric acid (F).

3. 3. The dental composition according to claim 2, wherein the alkali metal salt of phosphoric acid (F) is disodium monohydrogen phosphate and / or monosodium dihydrogen phosphate.

4. The dental composition according to any one of claims 1 to 3, further comprising an inorganic filler (G).

5. The dental composition according to any one of claims 1 to 4, further comprising an antibacterial agent (H).

6. 6. The dental composition according to claim 1, wherein the content of the tetracalcium phosphate (A) is 5 to 75 parts by mass per 100 parts by mass of the total of the tetracalcium phosphate (A) and the acidic calcium phosphate (B).

7. 7. The dental composition according to claim 1, wherein the content of the acidic calcium phosphate (B) is 10 to 70 parts by mass per 100 parts by mass of the total of the tetracalcium phosphate (A) and the acidic calcium phosphate (B).

8. The dental composition according to any one of claims 1 to 7, which is a one-component type.

9. A tooth surface treatment material comprising the dental composition according to any one of claims 1 to 8.

10. A root caries treatment material comprising the dental composition according to any one of claims 1 to 8.

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