JP7808951B2 - Dental Composition - Google Patents

Description

The present invention relates to a dental composition. More specifically, it relates to a dental composition that inhibits collagen degradation in dentin caused by caries that occurs on the root surface and promotes dentin remineralization.

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

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

Therefore, even if the elution of tooth minerals is simply prevented, the caries on the root surface will worsen if the decomposition of dentin collagen progresses. Conversely, if this collagen is decomposed, the scaffolding for mineral deposition is lost, making remineralization difficult and severely detrimental to the healing or recovery of caries.

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

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. Furthermore, 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 preventative.

A known technology for preventing root caries is described in Patent Document 3. Patent Document 3 proposes an oral composition containing a lactam compound with a lactam skeleton and an acidic group, with the aim of inhibiting dentin caries and suppressing dentin hypersensitivity.

International Publication No. 2015/019601 JP 2013-71917 A WO 2013/47826

Katz, S. ; Park, K.; K. ; and Palenik, C.; J. , Journal of Oral Medicine 42, 40-48, 1987 P. Schupbach, B. Guggenheim, F. Lutz, Journal of Oral Pathology & Medicine 18(3): 146-156, 1989

As a result of the inventors' investigations, it was found that the composition described in Patent Document 1 has excellent durability and storage stability in terms of dentinal tubule sealing, and the composition described in Patent Document 2 has excellent dentinal tubule sealing properties. However, these compositions have the drawback that calcium phosphate and fluoride cannot protect exposed collagen in root caries, and therefore cannot inhibit collagen degradation, leaving room for further improvement.

Pyrrolidone carboxylic acid (hereinafter also referred to as "PCA") and its salts, 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.

The present invention aims to provide a dental composition that has excellent dentinal tubule sealing properties, inhibits dentin collagen degradation during caries that occurs in root surface dentin, and promotes remineralization of dentin that has undergone mineral leaching (demineralization).

After extensive research, the inventors discovered that a dental composition with a specific composition could solve the above-mentioned problems, and after further research, they completed the present invention.

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 described in [1], wherein the acidic calcium phosphate (B) is 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 ]} .
[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].

The present invention provides a dental composition that has excellent dentinal tubule sealing properties, inhibits dentin collagen degradation during caries that occurs in root surface dentin, and promotes remineralization of dentin that has undergone mineral leaching (demineralization).

The components used in the dental composition of the present invention are described below. However, the present invention is not limited to the embodiments described below.

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).

While the reasons why the dental composition of the present invention inhibits collagen degradation in dentin in caries that develops on the root surface and promotes dentin remineralization are unclear, they 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 dental composition of the present invention has the effect of inhibiting collagen degradation in dentin and promoting dentin remineralization due to the synergistic effects of the two aforementioned mineral reinforcement and collagen molecular chains.

The components contained in the dental composition of the present invention are described below.

The tetracalcium phosphate (A) used in the present invention is not particularly limited, but is preferably 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, raising the pH of the aqueous solution. This can result in insufficient precipitation of hydroxyapatite and potentially reduced durability of dentinal tubule sealing. The average particle size is preferably 1.0 μm or greater, and more preferably 2.0 μm or greater. On the other hand, if the average particle size exceeds 10 μm, the particle size will be too large compared to the dentinal tubule diameter, which may result in a decrease in initial dentinal tubule occlusion. The average particle size is preferably 8.0 μm or less, and 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.

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, with alumina and zirconia being preferred as the pot and ball materials. When prepared by pulverization as described above, the particles typically have an irregular shape.

In the dental composition of the present invention, the content of tetracalcium phosphate (A) is 5 to 85 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 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, and more preferably 25 parts by mass or more, per 100 parts by mass of the total. 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, and more preferably 75 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 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, per 100 parts by mass of the total amount of the dental composition.

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

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 is more preferably anhydrous calcium monohydrogen phosphate [ _{CaHPO4 ]} .

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 and reduced dentinal tubule sealing properties. The average particle size of the acidic calcium phosphate (B) is more preferably 0.3 μm or greater. 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 hydroxyapatite precipitation 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.

The method for producing acidic calcium phosphate (B) is not particularly limited. Commercially available acidic calcium phosphate particles may be used as is, or they may be crushed appropriately to adjust the particle size, as with the above-mentioned tetracalcium phosphate (A), before use.

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.

The blending ratio (A/B) of tetracalcium phosphate (A) and acidic calcium phosphate (B) is not particularly limited, but it is preferable to use them in a blending ratio 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.

The dental composition of the present invention further contains a fluorine compound (C) from the standpoint of acid resistance. The fluorine compound (C), together with the tetracalcium phosphate (A), acidic calcium phosphate (B), and 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 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 diamminesilver 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 these, zinc fluoride, strontium fluoride, and sodium fluoride are preferred from the standpoint of safety.

The content of the fluorine compound (C) used in the present invention is not particularly limited, but it is preferable that the dental composition contain 0.01 to 10 parts by mass of fluoride ions in terms of the fluorine compound (C) per 100 parts by mass of the total amount. In order to further enhance the acid resistance of the sealant within the dentinal tubules, it is more preferable that the content of fluoride ions in terms of the fluorine compound (C) is 0.05 parts by mass or more per 100 parts by mass of the total amount. Furthermore, from the standpoint of safety, it is more preferable that the content of fluoride ions in terms of the fluorine compound (C) is 5 parts by mass or less per 100 parts by mass of the total amount.

The dental composition of the present invention further contains a carbodiimide compound (D) from the viewpoint of inhibiting the degradation of dentin collagen during 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 with a cyclic structure and carbodiimide compounds without a cyclic structure. Carbodiimide compounds (D) preferably have 5 to 30 carbon atoms, more preferably have 6 to 28 carbon atoms, and even more preferably have 7 to 25 carbon atoms. 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.

Examples of the cyclic structure include a cycloalkyl group, an aryl group, and a heterocyclic group. By using the carbodiimide compound (D), the dental composition of the present invention can inhibit collagen degradation in dentin during caries that develops in root surface dentin. Furthermore, the carbodiimide compound (D) can synergistically promote the remineralization of demineralized dentin in conjunction with other components, resulting in the dental composition of the present invention having excellent mineral density recovery ability. Therefore, it also has excellent therapeutic effects against root surface caries.

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

The aryl group may have 6 to 10 carbon atoms. Examples of the aryl group include a phenyl group and a naphthyl group. The aryl group may have a substituent.

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 formed by condensing 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 5- or 6-membered monocyclic aromatic heterocyclic groups include a morpholino group, a piperazino group, a piperidino group, and a pyrrolidinyl group. The heterocyclic group may have a substituent.

Substituents on the cyclic structure include alkyl groups having 1 to 6 carbon atoms, halogen atoms (chlorine atoms, bromine atoms, iodine atoms), and alkylamino groups having 1 to 6 carbon atoms. The number of substituents on the cyclic structure is not particularly limited, but is preferably 1 to 5, more preferably 1 to 4, and even more preferably 1 to 3.

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

A carbodiimide compound having a cyclic structure may be a compound in which the cyclic structure and the carbodiimide bond are directly bonded.

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 a carbodiimide bond via a divalent hydrocarbon group.

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.

When a carbodiimide compound having a cyclic structure includes 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 a nitrogen atom of the divalent hydrocarbon group.

Examples of the divalent hydrocarbon group include alkylene groups and alkenylene groups.

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.

A carbodiimide compound without a 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 alkyl group preferably contains 1 to 10 carbon atoms, more preferably 1 to 8, and even more preferably 1 to 6. Examples of the alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, and n-hexyl groups. When a carbodiimide compound without a cyclic structure contains alkyl groups, the two alkyl groups may be the same or different.

The chain structure may have a substituent. Examples of the substituent include an alkyl group having 1 to 6 carbon atoms, a halogen atom (chlorine atom, bromine atom, iodine atom), and an alkylamino group having 1 to 6 carbon atoms. 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.

The carbodiimide compound (D) may be in the form of a salt. Examples include hydrochloride, sulfate, sulfonate, and p-toluenesulfonate.

Specific examples of the carbodiimide compound (D) include 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 standpoint 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 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 degradation of dentin collagen 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 degradation of dentin collagen and promoting the remineralization of demineralized dentin, the content of 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.

The non-aqueous dispersant (E) is a component that transforms the dental composition into a paste, making it easier to handle. The non-aqueous dispersant (E) may be used alone 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.

The content of 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, reducing operability. The content of 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 non-aqueous dispersant (E) exceeds 90 parts by mass, the dentinal tubule occlusion ability may be reduced. The content of 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.

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. From the standpoints of safety and ease of obtaining high-purity raw materials, it is preferable that the alkali metal salt of phosphoric acid (F) be disodium monohydrogen phosphate and/or monosodium dihydrogen phosphate.

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 per 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, and more preferably 2 parts by mass or more, per 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 ability decreases. The content of the alkali metal salt of phosphoric acid (F) is preferably 12 parts by mass or less, and more preferably 10 parts by mass or less, per 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. This standard does not include compounds other than tetracalcium phosphate (A) and acidic calcium phosphate (B) (for example, other calcium-containing compounds described below).

The alkali metal salt of phosphoric acid (F) used in the present invention is not particularly limited, but is preferably particulate. The average particle size of the alkali metal salt of phosphoric acid (F) particles 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 calcium ion and phosphate ion supply and reduce the rate of hydroxyapatite precipitation. The average particle size of the alkali metal salt of phosphoric acid (F) is more preferably 3.0 μm or greater. On the other hand, if the average particle size of the alkali metal salt of phosphoric acid (F) exceeds 12 μm, it will become less soluble upon contact with water, which may reduce the rate of hydroxyapatite precipitation. 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 tetracalcium phosphate (A) particles described above.

There are no particular limitations on the method for producing the alkali metal phosphate (F). Commercially available alkali metal phosphate may be used as is, or it may be crushed to an appropriate particle size, as with the above-mentioned tetracalcium phosphate (A), before use.

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 are preferably used. Of these, at least one selected from the group consisting of barium glass, fluoroaluminosilicate glass, silica, and zirconia is more preferably used.

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, making it difficult to handle. 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.

In the dental composition of the present invention, the content of inorganic filler (G) is 0.1 to 50 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 0.1 part by mass, the effect of improving dentinal tubule sealing is reduced. The content of inorganic filler (G) is preferably 1 part by mass or more, and more preferably 2 parts by mass or more, per 100 parts by mass of the total. On the other hand, if the content of inorganic filler (G) exceeds 50 parts by mass, the viscosity of the dental composition increases, reducing handleability. The content of inorganic filler (G) is preferably 30 parts by mass or less, and more preferably 30 parts by mass or less, per 100 parts by mass of the total. The standards for the content of inorganic filler (G) are the same as those for the content of alkali metal phosphate (F).

The dental composition of the present invention may further contain an antibacterial agent (H) if necessary. Examples of antibacterial agents (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 may be used alone or in combination of two or more.

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. In order to further increase the acid resistance of the sealant within 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 standpoint 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.

The dental composition of the present invention may contain a thickener other than the inorganic filler (G) as needed. This is because it allows the viscosity of the paste to be adjusted, making it easier for the practitioner to handle. Examples of thickeners include synthetic polymers such as polyvinyl alcohol, polyacrylic acid, polystyrene sulfonic acid, and polystyrene sulfonates; 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.

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 operability, the content of the thickener is more preferably 0.05 parts by mass or more per 100 parts by mass of the total composition. 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 composition.

The dental composition of the present invention can be formulated with any pharmacologically acceptable drug or medication, 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 induced pluripotent stem (iPS) cells created by dedifferentiating differentiated cells such as undifferentiated bone marrow-derived stem cells, embryonic stem (ES) cells, and fibroblasts through gene transfer, as well as cells differentiated from these.

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 effect of inhibiting dentin caries and inhibiting dentin hypersensitivity. Examples of such lactam compounds include pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3-(2-oxo-1-azepanyl)propanoic acid.

The dental composition of the present invention preferably contains substantially no polymerizable monomers. In the present invention, "substantially no polymerizable monomers" means that the amount of a component contained is preferably less than 5 parts by mass, more preferably less than 1 part by mass, and even more preferably less than 0.1 parts by mass, per 100 parts by mass of the total amount of the dental composition.

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 dental composition.

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.

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. For example, it can be obtained by mixing using a twin-screw kneader, a triple-screw kneader, or a planetary kneader.

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

Suitable embodiments of the dental composition of the present invention include tooth surface treatment materials, root caries treatment materials, dentin hypersensitivity suppressants, dentifrices, and the like. When the dental composition of the present invention is used for the above purposes, it 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.

The present invention includes embodiments that combine the above configurations 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.

The present invention will be explained in detail below using examples, but the present invention is not limited to these examples in any way, and many modifications can be made by those skilled in the art within the technical spirit of the present invention.

In this example, the average particle sizes 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 size.

[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 zirconia balls with a diameter of 10 mm were added to a 400 ml alumina milling pot ("Type A-3 HD Pot Mill" manufactured by Nikkato Corporation), and wet-milled at a rotation speed of 120 rpm for 24 hours. The resulting slurry was sieved to remove the zirconia balls. The ethanol was removed using a rotary evaporator, and the resulting slurry was dried at 60°C for 6 hours and further dried in vacuum at 60°C for 24 hours to obtain tetracalcium phosphate particles (TTCP).

(2) Preparation of Acidic Calcium Phosphate (B) Anhydrous monohydrogen 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 monohydrogen 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 monohydrogen calcium phosphate particles (DCPA).

(3) Fluorine Compound (C)
The fluorine compound (C) used in this example was the following compound, which was used as it was.
ZnF ₂ : zinc fluoride (manufactured by Fluorochem)
SrF ₂ : Strontium fluoride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.)

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

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

(6) Preparation of alkali metal salt of phosphoric acid (F) Disodium hydrogen phosphate particles (Na ₂ HPO ₄ , average particle size 5.2 μm) used in this example as particles of alkali metal salt of phosphoric acid (F) were obtained by treating commercially available disodium hydrogen phosphate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) once using a nanojetmizer (NJ-100 model, manufactured by Aisin Nano Technologies Co., Ltd.) under grinding pressure conditions of raw material supply pressure: 0.7 MPa/grinding pressure: 0.7 MPa and processing volume conditions of 8 kg/hr.

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

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

[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 out according to the composition shown in Table 1, were added to a universal mixer stirrer (Dalton Co., Ltd., "Mixer Stirrer Twin Mix STM-08") and mixed for 60 minutes at a rotation speed of 130 rpm and a revolution speed of 37 rpm, thereby obtaining a one-component dental composition.

[Evaluation of dentinal tubule occlusion]
(1) Preparation of bovine teeth for evaluation of dentinal tubule occlusion properties The central buccal side of a healthy bovine incisor was polished and trimmed using a rotary polisher with #80 and #1000 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 and smoothed using lapping films (#1200, #3000, #8000, 3M Japan Ltd.).
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 (hereinafter 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 decalcify 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).

(2) Preparation of Samples for SEM Observation After the above treatment, the bovine teeth were dried with air blow to prepare samples for dentinal tubule observation.

(3) SEM Observation A scanning electron microscope (product name "SU3500", manufactured by Hitachi High-Technologies Corporation) was used for SEM observation. The morphology of both dentin windows was observed at an acceleration voltage of 5 kV (n = 3): the dentin window on the side where the dental composition was not applied after demineralization (dentin window A) and the dentin window on the other side where the dental composition had been applied and then removed (dentin window B). Three randomly selected points were observed for each SEM observation sample, and the dentinal tubule occlusion was evaluated using the dentinal tubule occlusion rate (%), which is 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 dental composition was applied.

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%

[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 Decalcifying 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.

(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, and 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.

(3) Reagents used in preparing test pieces The following compounds were used as reagents in preparing the test pieces.
Ethanol: manufactured by Kanto Chemical Co., Ltd. Propylene oxide: manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Epoxy resin base: (Epocure 2 base, manufactured by Buehler)
Curing agent (Epocure 2 curing agent, manufactured by Buehler)

(4) Preparation of Test Specimens Test specimens were prepared using the cervical region of bovine teeth. The surface of the cervical region of bovine teeth 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 a portion of the surface of the cervical region of bovine teeth. Using a diamond cutter (Isomet 1000, manufactured by BUEHLER), the cervical region of bovine teeth was divided into two halves symmetrically about the divided surface. Nail polish was applied to the areas of both divided specimens other than the test window, producing two test specimens each with a 5 mm x 1 mm test window. Both specimens were immersed in a decalcifying solution and decalcified at 37°C for two weeks. The decalcifying solution was replaced every three days from the start of immersion in the decalcifying solution.
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 base/propylene oxide mixture, a 4/1 epoxy resin base, and an epoxy resin base/curing agent mixture for 2 hours each, followed by immersion in a 4/1 epoxy resin base, followed by storage at 60°C for 1 day while immersed, and then cured. The test specimens, which were the cured products, 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 the thickness of the test specimens was adjusted to 0.060 mm to 0.110 mm using wrapping film (#1200, #3000, #8000, manufactured by 3M Japan Ltd.).

(5) CMR (Contact Micro Radiography)
For both test pieces obtained, a soft X-ray inspection device (trade 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.) were used to photograph the entire test piece at a tube voltage of 10 kV, a tube current of 2.0 mA, and an irradiation time of 10 minutes. The photographed test piece (dry plate) was immersed in a developer (medical X-ray liquid developer "Hirendol", Fujifilm Corporation) for 5 minutes, washed with distilled water for 1 minute, immersed in a fixer (fixer "Hirenfix", Fujifilm Corporation) for 5 minutes, and washed with distilled water for 30 seconds.

(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. The mineral density recovery ability (%) was then calculated using the following formula. In each of the following formulas, "control" refers to the case where no treatment was performed with the sample (dental composition of each Example and Comparative Example).

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

Mineral density at treatment surface at any depth =
Brightness value of treated surface at any depth / Brightness value 100 μm directly below the nail polish protection of the undecalcified part

The average value (n=3) of the mineral density recovery ability was evaluated according to the following criteria. The obtained evaluation results are summarized in Table 1.
◯: 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%

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

(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 (3,000 rpm, 5 min). The mixture was incubated at 50°C for 90 minutes, and 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

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.
◯: Collagen decomposition inhibition rate is 50% or more △: Collagen decomposition inhibition rate is 25% or more but less than 50% ×: Mineral density recovery ability is less than 25%

As is clear from the above results, the dental compositions of the present invention (Examples 1 to 3) exhibited high dentinal tubule sealing properties and were confirmed to have high mineral density recovery ability and collagen degradation inhibition rate.

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 and mineral density recovery ability.

The dental composition of the present invention is suitable for use in the field of dentistry as a tooth surface treatment material (e.g., a root caries treatment material, a dentin hypersensitivity suppressant, etc.) and a toothpaste.

Claims (10)

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 at least one selected from the group consisting of 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 . The dental composition according to claim 1 , further comprising an alkali metal salt of phosphoric acid (F). 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. The dental composition according to any one of claims 1 to 3 , further comprising an inorganic filler (G). The dental composition according to any one of claims 1 to 4 , further comprising an antibacterial agent (H). 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. 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). The dental composition according to any one of claims 1 to 7 , which is a one-component type. A tooth surface treatment material comprising the dental composition according to any one of claims 1 to 8 . A root caries treatment material comprising the dental composition according to any one of claims 1 to 8 .