Dental curable composition having high collagen decomposition inhibition rate

Abstract

To provide a dental curable composition that satisfies both caries inhibitory effect and hyperesthesia inhibitory effect in dentin.SOLUTION: A dental curable composition contains calcium phosphate (A) and aldose (B), and the mass ratio (A) / (B) between the content of (A) and the content of (B) is 1.2 to 60. It is preferable that the dental curable composition further contains water (C), and comprises a first material containing calcium phosphate (A) and a second material containing water (C), where at least one of the first material or the second material contain aldose (B).SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a dental hardenable composition having a high collagen degradation inhibition rate. [Background technology]

[0002] As a result of the so-called 8020 movement (improvement of oral hygiene and preservation of tooth quality (MI: Minimal Intervention)), which encourages people to keep more than 20 of their own teeth even at the age of 80, the rate at which elderly people have retained their teeth has increased dramatically. However, as the percentage of remaining teeth has increased, gingival recession due to aging and periodontal disease has become more likely to occur. Compared to enamel, dentin contains only about 70% less hydroxyapatite, so caries progresses more quickly. In other words, while enamel caries can be cured by remineralization in the early stages, dentin caries also breaks down organic matter such as collagen, which serves as a scaffold for remineralization, making remineralization difficult, and caries progresses more easily. Furthermore, while the critical pH of enamel is around 5.5, the critical pH of dentin is around 6.1, making it vulnerable to acid. Therefore, as gingival recession increases, the root surface is exposed to the acid produced by bacteria that cause caries, and root caries is increasing. Therefore, the challenge is to provide a caries-inhibiting material for dentin that can inhibit root caries.

[0003] Another issue is that exposed dentin can easily cause hypersensitivity. Normally, dentin is covered by enamel, which has a higher critical pH than dentin, so the dentinal tubules are not exposed. However, the dentin on the exposed root surface due to gingival recession is covered with cementum. The critical pH of cementum is around pH 6.1, which is similar to that of dentin, so it is weak against acid and dentin is relatively easily exposed. Dentin has dentinal tubules with a diameter of about 1 μm to about 3 μm that connect the surface of dentin to the dental pulp. When the dentinal tubules are opened by the action of acid, stimuli are transmitted to the dental pulp through the dentinal tubules, causing dentin hypersensitivity.

[0004] A method of suppressing the progression of caries in dentin is known in which a composition containing diammine silver fluoride is applied to the affected area such as exposed dentin. This method utilizes the fact that diammine silver fluoride acts on collagen in dentin, suppressing the decomposition of collagen, which serves as a scaffold for remineralization. In other words, the suppression of collagen decomposition is achieved by immobilizing collagen with the silver contained in the composition, providing it with antienzymatic properties, which leads to the suppression of the progression of caries in dentin.

[0005] On the other hand, as a method for suppressing dentin hypersensitivity, a hardenable calcium phosphate composition is known, etc. As an example of this calcium phosphate composition, a dental calcification agent that combines tetracalcium phosphate and anhydrous calcium hydrogen phosphate has been proposed (for example, Patent Documents 1 and 2). When such a calcium phosphate composition is rubbed onto the dentinal tubules, the calcium phosphate composition seals the dentinal tubules that cause hypersensitivity. Then, hydroxyapatite (Ca 10 By gradually converting to (PO4)6(OH)2) and integrating with living hard tissues while maintaining its shape, the dentinal tubules are more securely sealed and dentin hypersensitivity is suppressed.

[0006] Patent Document 1 discloses a tooth mineralizing agent containing tetracalcium phosphate particles and an alkali metal salt of phosphoric acid, the composition of which contains 1 to 80 parts by mass of tetracalcium phosphate and 0.5 to 50 parts by mass of the alkali metal salt of phosphoric acid relative to a total amount of 100 parts by mass of the tooth mineralizing agent. Patent Document 1 discloses that, as an effect, a tooth calcifying agent having a high calcifying effect is provided, which enables treatment at the early stage of caries. Furthermore, it is possible to strengthen healthy enamel and healthy tooth structure, and it can be used as a material to prevent dental caries. However, Patent Document 1 does not disclose the caries-inhibiting effect on dentin, nor the effect of suppressing hypersensitivity.

[0007] Patent Document 2 describes a composition for treating dentin hypersensitivity that comprises tetracalcium phosphate, calcium phosphate having a Ca / P molar ratio of less than 1.67, and a thickener, and a composition obtained by kneading the composition with water. Calcium hydrogen phosphate is disclosed as a calcium phosphate having a Ca / P molar ratio of less than 1.67, and carboxymethylcellulose sodium salt and the like are disclosed as thickeners. It is disclosed that application to hypersensitive areas reduces dentin hypersensitivity. However, Patent Document 2 does not disclose the caries-inhibiting effect on dentin.

[0008] In addition, although no suggestion is made as to the effect of suppressing dentin hypersensitivity or caries in dentin, patent document 3 proposes an oral dissolving gelling tablet that provides an excellent feeling when used in the oral cavity. Patent Document 3 discloses a tablet-type simultaneous dissolving and gelling oral hygiene composition that is convenient and has a pleasant feel when used, and can be used for a variety of purposes, such as a chewable tablet, an oral dissolving and gelling tablet, or a toothbrush-attached dissolving and gelling tablet. The composition according to Patent Document 3 essentially comprises a porous plastic granule material, a binder, a gelling agent and a water penetration enhancer. As porous plastic granule materials, sorbitol, dibasic calcium phosphate, etc. are disclosed, as binders, carboxymethylcellulose, etc. are disclosed, as gelling agents, carboxymethylcellulose, etc. are disclosed, and as water penetration promoters, fructose, etc. are disclosed. Patent Document 3 discloses, for example, that when the tablet is chewed in the oral cavity, the agent is simultaneously dissolved and gelled by water or saliva in the oral cavity, and that simply rinsing with water can refresh the oral cavity and alleviate and prevent oral diseases. Although it is disclosed that the dicalcium phosphate contained in the composition of Patent Document 3 also functions as a remineralizing agent and a caries prevention agent, there is no disclosure of its caries suppressing effect on dentin, nor of its effect of suppressing dentin hypersensitivity. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] International Publication No. 2010 / 113801 [Patent Document 2] Japanese Patent Publication No. 1-163127 [Patent Document 3] Special Publication No. 2009-526040 Summary of the Invention [Problem to be solved by the invention]

[0010] Conventional hardenable calcium phosphate compositions are generally used as dentin hypersensitivity inhibitors and remineralizing agents because of their excellent sealing and remineralizing properties for dentinal tubules. Such calcium phosphate compositions can remineralize enamel. On the other hand, they cannot inhibit collagen decomposition, and therefore have a small caries inhibitory effect on dentin, which contains about 30% organic matter, mainly collagen.

[0011] Therefore, an object of the present invention is to provide a dental hardenable composition which has both an effect of inhibiting caries in dentin and an effect of inhibiting hypersensitivity. [Means for solving the problem]

[0012] As a result of extensive investigations, the present inventors have found that a dental hardenable composition having a specific composition can solve the above problems, and have completed the present invention through further investigations.

[0013] That is, the present invention includes the following inventions. [1] A dental hardenable composition comprising calcium phosphate (A) and an aldose (B), wherein the mass ratio (A) / (B) of the content of (A) to the content of (B) is 1.2 to 60. [2] Further containing water (C), The composition comprises a first material containing calcium phosphate (A) and a second material containing water (C), At least one of the first material and the second material contains an aldose (B); [1] The dental hardenable composition according to the present invention. [3] Further containing a curing accelerator (D), The dental hardenable composition according to [1] or [2], wherein the aldose (B) and the hardening accelerator (D) are separately packaged. [4] The dental hardenable composition according to [2] or [3], wherein the first material contains an aldose (B). [5] The dental hardenable composition according to any one of [1] to [4], wherein the content of the calcium phosphate (A) is 30 to 70 mass% in 100 mass% of the total amount of the dental hardenable composition. [6] The dental hardenable composition according to any one of [1] to [5], wherein the content of the calcium phosphate (A) is 40 to 66 mass% in 100 mass% of the total amount of the dental hardenable composition. [7] The dental hardenable composition according to any one of [1] to [6], wherein the calcium phosphate (A) comprises a mixture of a non-acidic calcium phosphate (A-1) and an acidic calcium phosphate (A-2). [8] The dental hardenable composition according to [7], wherein the non-acidic calcium phosphate (A-1) has an average particle size of 0.5 to 40 μm. [9] The dental hardenable composition according to [7] or [8], wherein the average particle size of the acidic calcium phosphate (A-2) is 0.1 to 7 μm.

[10] The dental hardenable composition according to any one of [7] to [9], wherein the molar ratio (A-1 / A-2) of the content of the non-acidic calcium phosphate (A-1) to the content of the acidic calcium phosphate (A-2) is 40 / 60 to 60 / 40.

[11] The dental hardenable composition according to any one of [7] to

[10] , wherein the acidic calcium phosphate (A-2) comprises at least one selected from the group consisting of anhydrous calcium hydrogen phosphate, anhydrous calcium dihydrogen phosphate, α-tricalcium phosphate, β-calcium phosphate, amorphous calcium phosphate, acidic calcium pyrophosphate, calcium hydrogen phosphate dihydrate, and calcium dihydrogen phosphate monohydrate.

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

[11] , wherein the aldose (B) has 100 or less carbon atoms.

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

[12] , wherein the content of the aldose (B) is 2 to 20 mass % relative to 100 mass % of the total amount of the dental hardenable composition.

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

[13] , wherein the content of water (C) is 20 to 79 mass% in 100 mass% of the total amount of the dental hardenable composition.

[15] The dental hardenable composition according to any one of [3] to

[14] , wherein the content of the hardening accelerator (D) is 0.01 to 4.0 mass% in 100 mass% of the total amount of the dental hardenable composition.

[16] The dental curable composition according to any one of [1] to

[15] , further comprising an inorganic filler (E), the inorganic filler (E) comprising at least one selected from the group consisting of light anhydrous silicic acid having an average particle size of 0.002 to 2 μm and metal oxides having an average particle size of 0.002 to 2 μm.

[17] The dental hardenable composition according to any one of [1] to

[16] , further comprising a fluoride salt, the content of the fluoride salt being 1.0 to 5.0 mass% relative to 100 mass% of the total amount of the dental hardenable composition.

[18] The dental hardenable composition according to any one of [1] to

[17] , further comprising a pH adjuster, the pH adjuster comprising disodium hydrogen phosphate and / or monosodium dihydrogen phosphate. Effect of the Invention

[0014] According to the present invention, a dental hardenable composition can be provided that has both a caries-inhibiting effect and a dentin hypersensitivity-inhibiting effect. The caries-inhibiting effect in dentin can be indexed by the collagen decomposition inhibition rate, and the dentin hypersensitivity-inhibiting effect can be indexed by the dentin tubule blocking ability. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The present invention will be described in detail below. The dental hardenable composition of the present invention is a dental hardenable composition that contains calcium phosphate (A) and an aldose (B), and has a mass ratio (A) / (B) of the content of (A) to the content of (B) of 1.2 to 60.

[0016] By adopting the above-mentioned configuration, a dental hardenable composition can be obtained which satisfies both the collagen decomposition inhibition rate, which is an index of the caries-inhibiting effect in dentin, and the dentinal tubule sealing ability, which is an index of the hypersensitivity-inhibiting effect.

[0017] In this specification, the upper and lower limit values ​​of the numerical ranges (content of each component, average particle size, etc.) can be appropriately combined.

[0018] Although not intended to limit the present invention in any way, the reasons why the above-mentioned excellent effects are obtained are thought to be as follows. It is believed that when the dental hardenable composition of the present invention is applied to a tooth structure, calcium phosphate (A) seals the dentinal tubules and reduces the fluidity of the fluid in the dentinal tubules, thereby suppressing dentin hypersensitivity. In this case, it is preferable that calcium phosphate (A) is a particle smaller than the diameter of the dentinal tubules, so that the tubules can be more easily sealed. Calcium phosphate (A) produces hydroxyapatite from calcium phosphate particles or calcium and phosphate ions in saliva within the dentinal tubules, which is thought to help seal the dentinal tubules and have the effect of suppressing dentin hypersensitivity.

[0019] Furthermore, the aldehyde group of the aldose (B) contained in the dental hardenable composition of the present invention reacts with an amino group in collagen to form an imine, which makes the composition less susceptible to degradation by collagen-degrading enzymes. In the dental hardenable composition of the present invention, calcium phosphate (A) provides a weakly basic reaction field in the entire system, which acts to enhance the imine formation reaction by aldose (B). As a result, the surface of collagen is further modified by the formation of imine, and the recognition of collagen by the enzyme (collagenase) during collagen decomposition by the enzyme is inhibited, which is thought to further enhance the inhibitory effect on the enzyme activity (collagen decomposition action), and thus improve the collagen decomposition suppression effect. Furthermore, if collagen remains in dentin, it can serve as a scaffold for remineralization, and is therefore thought to have an excellent caries-inhibiting effect on dentin.

[0020] <Calcium phosphate (A)> The dental hardenable composition of the present invention contains calcium phosphate (A). When the dental hardenable composition of the present invention contains calcium phosphate (A), it is possible to enhance the collagen decomposition inhibitory function of the aldose (B) while exhibiting excellent sealing properties for dentinal tubules. The calcium phosphate (A) may be used alone or in combination of two or more kinds.

[0021] The calcium phosphate (A) is not particularly limited, but preferably includes at least one selected from the group consisting of tetracalcium phosphate, octacalcium phosphate, anhydrous calcium hydrogen phosphate, anhydrous calcium dihydrogen phosphate, α-tricalcium phosphate, β-tricalcium phosphate, amorphous calcium phosphate, acid calcium pyrophosphate, calcium hydrogen phosphate dihydrate, and calcium dihydrogen phosphate monohydrate.

[0022] Calcium phosphate (A) can be divided into non-acidic calcium phosphate (A-1) and acidic calcium phosphate (A-2). In view of the ease of forming hydroxyapatite and the resulting excellent sealing properties for dentinal tubules, a mixture of non-acidic calcium phosphate (A-1) and acidic calcium phosphate (A-2) is preferred, and a combination of tetracalcium phosphate and anhydrous calcium hydrogen phosphate is most preferred. The non-acidic calcium phosphate (A-1) is not particularly limited, but examples thereof include tetracalcium phosphate and octacalcium phosphate. The acidic calcium phosphate (A-2) is not particularly limited, but examples thereof include anhydrous calcium hydrogen phosphate, anhydrous calcium dihydrogen phosphate, α-tricalcium phosphate, β-tricalcium phosphate, amorphous calcium phosphate, acidic calcium pyrophosphate, calcium hydrogen phosphate dihydrate, and calcium dihydrogen phosphate monohydrate.

[0023] The content of calcium phosphate (A) used in the present invention is preferably 20% by mass or more in the total amount (100% by mass) of the dental hardenable composition, since this improves the sealing property of dentinal tubules. The content of calcium phosphate (A) is preferably 80% by mass or less, since the paste-like properties make it easy to apply to tooth structure. The calcium phosphate (A) is preferably 20 to 80% by mass, and when the aldose (B) is present in a specified ratio, it can provide a weakly basic reaction field for the entire system, making it easier to form imines, further modifying the collagen surface, and making it more difficult for enzymes to recognize the collagen during enzymatic decomposition, thereby enhancing the inhibitory effect on enzyme activity and providing a superior effect of inhibiting the decomposition of collagen. The calcium phosphate (A) is more preferably 30 to 70% by mass, and even more preferably 40 to 66% by mass, providing a superior ability to seal dentinal tubules.

[0024] When using a hydrate of calcium phosphate (A), the calcium phosphate content is calculated by converting it into the mass of the anhydrous form. For example, calcium hydrogen phosphate hydrate has a molecular weight of 172.09 g / mol, while anhydrous calcium hydrogen phosphate has a molecular weight of 136.06 g / mol, so the converted mass of 100 g of calcium hydrogen phosphate hydrate is 100 x 136.06 / 172.09 = 79.063 g.

[0025] The molar ratio (A-1 / A-2) of the content of non-acidic calcium phosphate (A-1) to the content of acidic calcium phosphate (A-2) is not particularly limited, but it is preferable to use them in a blend ratio of 40 / 60 to 60 / 40 in order to enhance the remineralization effect. The above molar ratio (A-1 / A-2) is more preferably 45 / 55 to 55 / 45, and further preferably 50 / 50.

[0026] The method for producing the calcium phosphate (A) used in the present invention is not particularly limited. Commercially available calcium phosphate (A) may be used as is, or may be used after being appropriately pulverized to adjust the particle size.

[0027] The average particle size of the calcium phosphate (A) is not particularly limited, but is preferably in the range of 0.1 μm or more and less than 500 μm. The average particle size of calcium phosphate (A) is preferably 0.1 μm or more, more preferably 0.5 μm or more, and even more preferably 1.0 μm or more, since calcium phosphate (A) is less likely to aggregate and is easy to handle. In addition, the average particle size of calcium phosphate (A) is preferably less than 500 μm, more preferably 40 μm or less, even more preferably 20 μm or less, even more preferably 10 μm or less, particularly preferably 5 μm or less, and most preferably 2 μm or less, from the viewpoints of reducing roughness during kneading, improving the kneading feel, and making it easy to maintain good operability, and of showing sufficient viscosity in the paste obtained by mixing with a liquid, which is the second material described later. The average particle size of the calcium phosphate (A) can be appropriately changed as necessary, and may be, for example, 250 μm or less, 100 μm or less, 50 μm or less, or 25 μm or less. One preferred embodiment is a dental hardenable composition containing calcium phosphate (A) having an average particle size of 2.2 μm or less, because this is smaller than the diameter of dentinal tubules and makes it easier to seal the tubules. Here, the average particle size of the calcium phosphate (A) used in the present invention is measured using a laser diffraction particle size distribution measuring device and calculated on a volume basis.

[0028] The average particle size of the non-acidic calcium phosphate (A-1) is preferably 40 μm or less, more preferably 30 μm or less, even more preferably 20 μm or less, even more preferably 10 μm or less, and particularly preferably 5 μm or less. The average particle size of the non-acidic calcium phosphate (A-1) is more preferably 0.5 μm or more, and further preferably 1.0 μm or more. The average particle size of the acidic calcium phosphate (A-2) is preferably 7 μm or less, more preferably 6 μm or less, even more preferably 5 μm or less, even more preferably 4 μm or less, particularly preferably 3 μm or less, and most preferably 2 μm or less. The average particle size of the acidic calcium phosphate (A-2) is preferably 0.1 μm or more, more preferably 0.5 μm or more, and even more preferably 1.0 μm or more.

[0029] <Aldose (B)> The dental hardenable composition of the present invention comprises an aldose (B). As used herein, "aldose" refers to a monosaccharide having one aldehyde group (-CHO) at the end of the chain. The dental hardenable composition of the present invention contains the aldose (B), which acts integrally with the calcium phosphate (A) to provide an excellent effect of inhibiting collagen decomposition. The aldose (B) may be used alone or in combination of two or more kinds.

[0030] Examples of the aldose (B) include glyceraldehyde, xylose, arabinose, erythrose, threose, ribose, lyxose, allose, altrose, glucose, mannose, gulose, idose, galactose, and talose, and xylose, arabinose, erythrose, threose, ribose, lyxose, allose, altrose, glucose, mannose, gulose, idose, galactose, and talose are preferred.

[0031] The shorter the carbon chain of the aldose (B), the greater the proportion of aldehyde groups per molecule, and the higher the rate of inhibiting collagen decomposition. Specifically, C n H 2n O nAmong the aldoses represented by (n≧3), n=100 or less (the number of carbon atoms of the aldose (B) is 100 or less), more preferably n=50 or less, even more preferably n=10 or less, and most preferably n=6 or less. The aldose may be modified as long as the aldehyde group is not modified. The lower limit of n is not particularly limited, but is preferably 4 or more, and more preferably 5 or more.

[0032] In order to adjust the hardening time of the dental hardenable composition to an appropriate length, the content of the aldose (B) is preferably 20 mass% or less, based on the total amount (100 mass%) of the dental hardenable composition. In order to minimize the impairment of the sealing ability of the calcium phosphate (A) for dentinal tubules, the content of the aldose (B) is more preferably 17 mass% or less, and even more preferably 15 mass% or less. In view of the excellent sealing ability of the dentinal tubules and the further improvement of the caries-inhibiting effect in dentin, the aldose (B) is preferably 2% by mass or more, more preferably 3% by mass or more, and even more preferably 4% by mass or more, of the total amount (100% by mass) of the dental hardenable composition.

[0033] The mass ratio (A) / (B) of the content of (A) to the content of (B) in the dental hardenable composition of the present invention is 1.2 or more, and from the viewpoint of having a high collagen degradation inhibition rate while being superior in dentinal tubule occlusion rate, it is preferably 2.0 or more, more preferably 3.0 or more, and even more preferably 4.0 or more. If the mass ratio (A) / (B) is less than 1.2, the composition will not become a paste suitable for application to tooth structure, hardening will be insufficient, and the dentinal tubule occlusion rate will decrease. The mass ratio (A) / (B) is 60 or less, preferably 50 or less, and from the viewpoint of further promoting the formation of imines by the reaction of the aldehyde groups of the aldose (B) with the amino groups in collagen and thus achieving a higher collagen degradation inhibition rate, is more preferably 40 or less, even more preferably 30 or less, particularly preferably 20 or less, and most preferably 10 or less. When the mass ratio (A) / (B) is 60 or less, a high collagen degradation inhibition rate is achieved.

[0034] <Water(C)> The dental hardenable composition of the present invention may further contain water (C). Since a dental curable composition with good workability can be prepared, the content of water (C) is not particularly limited, but is preferably 20 mass % or more, more preferably 25 mass % or more, and even more preferably 30 mass % or more, based on 100 mass % of the total amount of the dental curable composition. Furthermore, the content of water (C) is preferably 79 mass% or less, more preferably 70 mass% or less, even more preferably 60 mass% or less, and most preferably 50 mass% or less, based on 100 mass% of the total amount of the dental curable composition.

[0035] <Curing accelerator (D)> The dental hardenable composition of the present invention may further contain a hardening accelerator (D). By adding the hardening accelerator (D), the hardening time can be easily adjusted, suitable sealing of the dentinal tubules can be easily obtained, and a higher collagen decomposition inhibition rate can be easily obtained.

[0036] The hardening accelerator (D) is not particularly limited as long as it can impart a hardening acceleration effect to the dental hardenable composition, and examples thereof include carboxyl group-containing compounds and phenols. The curing accelerator (D) may be used alone or in combination of two or more kinds. Examples of the carboxyl group-containing compound include aliphatic carboxylic acids and aromatic carboxylic acids. Examples of aliphatic carboxylic acids include monocarboxylic acids such as acetic acid and propionic acid; dicarboxylic acids such as malonic acid, succinic acid and oxalic acid; hydroxy acids such as citric acid, lactic acid, benzoic acid, malic acid and tartaric acid; and aminocarboxylic acids such as diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA). Examples of the aromatic carboxylic acid include protocatechuic acid and gallic acid. Examples of phenols include tannic acid, pyrocatechol-3,5-disulfonic acid disodium monohydrate (also known as "Tiron"), pyrogallol, catechol, and catechin. Specifically, the hardening accelerator (D) is preferably at least one selected from the group consisting of citric acid, lactic acid, acetic acid, propionic acid, benzoic acid, malonic acid, succinic acid, oxalic acid, malic acid, tartaric acid, diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), tannic acid, disodium pyrocatechol-3,5-disulfonate monohydrate, catechol, protocatechuic acid, pyrogallol, and catechin, and more preferably citric acid.

[0037] In the dental hardenable composition further containing a hardening accelerator (D), the aldose (B) and the hardening accelerator (D) can be packaged separately to prolong the storage stability. For example, one preferred embodiment is a dental hardenable composition in which the first material contains an aldose (B) and the second material contains a hardening accelerator (D), because this has better sealing properties for dentinal tubules.

[0038] In order to obtain a curing acceleration effect and good paste properties, the content of the curing accelerator (D) is preferably 0.01 mass % or more and 4.0 mass % or less in relation to 100 mass % of the total amount of the dental curable composition.

[0039] The content of the hardening accelerator (D) is preferably 0.01 to 4.0 mass%, more preferably 0.01 to 3.0 mass%, even more preferably 0.2 to 2.0 mass%, and particularly preferably 0.2 to 1.0 mass%, relative to 100 mass% of the total amount of the dental hardenable composition, in order to obtain a hardening acceleration effect and good paste properties.

[0040] <Fluoride salts> Fluoride salts are known to promote the remineralization of dentin, and if necessary, fluoride salts can be incorporated within a range that does not affect the effects of the present invention. The fluoride salts are not particularly limited, and examples include sodium fluoride, potassium fluoride, ammonium fluoride, lithium fluoride, cesium fluoride, magnesium fluoride, calcium fluoride, strontium fluoride, barium fluoride, copper fluoride, zirconium fluoride, aluminum fluoride, tin fluoride, sodium monofluorophosphate, potassium monofluorophosphate, hydrofluoric acid, sodium titanium fluoride, potassium titanium fluoride, hexylamine hydrofluoride, laurylamine hydrofluoride, glycine hydrofluoride, alanine hydrofluoride, fluorosilanes, silver diamine fluoride, zinc fluoride, etc. Among them, sodium fluoride, potassium fluoride, and zinc fluoride are preferably used.

[0041] The content of the fluoride salt is preferably 5.0% by mass or less, more preferably 4.0% by mass or less, and even more preferably 3.0% by mass or less in 100% by mass of the total amount of the dental curable composition of the present invention. Also, the content of the fluoride salt is preferably 1.0% by mass or more, more preferably 1.2% by mass or more, and even more preferably 1.4% by mass or more.

[0042] <pH adjuster> The dental curable composition of the present invention may further contain a pH adjuster. The pH adjuster is not particularly limited, and examples include disodium hydrogen phosphate, trisodium phosphate, calcium hydroxide, sodium hydroxide, monosodium dihydrogen phosphate, etc. Among them, disodium hydrogen phosphate and / or monosodium dihydrogen phosphate are preferred, and disodium hydrogen phosphate is more preferred.

[0043] The pH of the paste 30 seconds after kneading is preferably 5.5 or more, more preferably 6.0 or more, and even more preferably 6.5 or more. The pH is preferably 14 or less, more preferably 12 or less, and even more preferably 10 or less. The pH adjuster can be used to adjust the pH to the range of 6.5 to 10, where the solubility of hydroxyapatite is lowest, thereby accelerating the setting time and making the pH suitable for use in the oral cavity.

[0044] Inorganic filler (E) If necessary, an inorganic filler (E) may be contained within a range that does not affect the effects of the present invention. Examples of the inorganic filler (E) include metal oxides. Examples of the metal oxide include zirconium oxide, titanium oxide, barium oxide, lanthanum oxide, ytterbium oxide, strontium oxide, hafnium oxide, zinc oxide, and aluminum oxide. When the inorganic filler (E) contains silicon dioxide, light anhydrous silicic acid (having an SiO2 content of 98.0% or more) is preferred. Certain preferred embodiments include dental hardenable compositions in which the inorganic filler (E) comprises silicon dioxide and at least one other metal oxide. In this specification, silicon does not qualify as a metal but is considered to be a non-metal.

[0045] The average particle size (primary particle size) of the inorganic filler (E) is preferably from 0.001 to 5 μm, and more preferably from 0.002 to 2 μm.

[0046] The inorganic filler (E) more preferably contains at least one selected from light anhydrous silicic acid having an average particle size of 0.002 to 2 μm and metal oxides having an average particle size of 0.002 to 2 μm, and further preferably contains light anhydrous silicic acid particles having an average particle size of 0.002 to 2 μm.

[0047] The dental hardenable composition may further contain any pharmacologically acceptable drug, etc. Antibacterial agents such as cetylpyridinium chloride, disinfectants, anticancer agents, antibiotics, blood circulation improving agents 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 undifferentiated bone marrow-derived stem cells, embryonic stem (ES) cells, differentiated cells such as fibroblasts, etc., induced pluripotent stem (iPS) cells prepared by dedifferentiating and preparing differentiated cells by gene transfer, as well as cells differentiated from these.

[0048] The dental curable composition of the present invention will be described below. However, the present invention is not limited to the embodiments described below.

[0049] The dental curable composition of the present invention is applied to a tooth in a paste state. The dental curable composition of the present invention may be in the form of a one-material product or may be packaged in two or more materials. In the case of a one-component type, it is in a paste form. In the case of a one-material type, there is no need to mix the material, and the operation is simple. Calcium phosphate (A) reacts with saliva in the mouth and hardens.

[0050] In the case of a two-material type, the first material (eg, powder or non-aqueous paste) and the second material (eg, liquid containing water as a main component or aqueous paste) can be packaged separately. By packaging the powder first material and the liquid second material separately, it is possible to prevent calcium phosphate (A) and water (C) from reacting and hardening during storage, while also incorporating water (C) to promote hardening. When packaged in this way, they are mixed together just before use and then applied to the tooth structure.

[0051] A preferred embodiment of the present invention is a dental hardenable composition which further contains water (C) in addition to calcium phosphate (A) and aldose (B), and which is composed of a first material containing calcium phosphate (A) and a second material containing water (C), and at least one of the first material and the second material contains aldose (B). That is, the dental hardenable composition may contain aldose (B) in the first material or aldose (B) in the second material, or aldose (B) in both the first material and the second material. Another preferred embodiment is a two-material dental hardenable composition comprising a first material containing the calcium phosphate (A) and a second material containing water (C), the first material containing an aldose (B).

[0052] When the first material is a powder, it is preferable to premix powders such as calcium phosphate (A), aldose (B), and powders of fluoride salt, pH adjuster, inorganic filler (E), etc., which may be blended as necessary. This has the advantage of improving usability without the need to measure each powder during clinical use. The mixing method is not particularly limited, and a known device can be used. In the mixing, it is preferable to use at least one selected from the group consisting of a high-speed mixer, a V-type mixer, a lab mill, a touch mixer, a wonder crusher, a jet mill, a Raikai machine, a ball mill, a high-speed rotary mill, a planetary mill, a hybridizer, a mechanofusion, and a mixing extruder. In order to mix the ingredients without causing excessive pulverization during mixing, it is preferable to use at least one selected from the group consisting of a high-speed mixer, a V-type mixer, a laboratory mill, a touch mixer, and a Wonder Crusher, and more preferably a high-speed mixer, a V-type mixer, or a Wonder Crusher.

[0053] The dental hardenable composition of the present invention can be used as a filling and restorative material, a lining material, a bonding material, a temporary sealing material, a root canal filling material, a temporary adhesive material, a coating material, a sealant material, a toothpaste, a dentin hypersensitivity inhibitor, a dentin caries inhibitor, etc., which are used by filling cavities or defects in tooth structure, and is particularly suitable as a toothpaste, a dentin hypersensitivity inhibitor, and a dentin caries inhibitor.

[0054] In the dental hardenable composition of the present invention, the calcium phosphate (A) dissolves in the presence of water and undergoes a reaction of gradually converting to hydroxyapatite, so the powder and liquid materials are mixed immediately before use. In addition, the dental hardenable composition of the present invention can precipitate hydroxyapatite deep within the dentinal tubules, sealing them.

[0055] The present invention includes embodiments in which all or part of the above-described configurations are combined in various ways within the scope of the technical idea of ​​the present invention, as long as the effects of the present invention are achieved. EXAMPLES

[0056] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. The average particle diameters of calcium phosphate (A) and inorganic filler were measured on a volume basis using a laser diffraction particle size distribution measuring device ("SALD-2300" manufactured by Shimadzu Corporation), and the average diameter calculated from the measurement results was taken as the average particle diameter. The evaluation methods for dental hardenable compositions employed in the following Examples and Comparative Examples are shown below.

[0057] Preparation of calcium phosphate (A): tetracalcium phosphate (TTCP) The tetracalcium phosphate particles (average particle size: 4.4 μm) used in this example were obtained by preparing crude tetracalcium phosphate as follows, and pulverizing it as follows. First, commercially available anhydrous calcium hydrogen phosphate particles (Product No. 1430, JT Baker Chemical Co., NJ) and calcium carbonate (Product No. 1288, JT Baker Chemical Co., NJ) were added to water in an equimolar amount, stirred for 1 hour, and then filtered and dried to obtain a cake-like equimolar mixture. This was heated in an electric furnace (FUS732PB, Advantec Toyo Co., Ltd.) at 1500°C for 24 hours and then cooled to room temperature in a desiccator to prepare tetracalcium phosphate mass. The mixture was then roughly crushed in a mortar and sieved to remove fine powder and lumps of tetracalcium phosphate, and the particle size was adjusted to a range of 0.5 to 3 mm to obtain crude tetracalcium phosphate. 100 g of this crude tetracalcium phosphate and 200 g of zirconia balls with a diameter of 20 mm were added to a 400 ml alumina grinding pot (Nikkato Corporation's "Type A-3 HD Pot Mill") and ground at a rotation speed of 150 rpm for 15 hours to obtain tetracalcium phosphate particles.

[0058] Preparation of calcium phosphate (A): dibasic calcium phosphate anhydrous (DCPA) The anhydrous calcium hydrogen phosphate particles (average particle size: 1.5 μm) used in this example were obtained by adding 50 g of commercially available anhydrous calcium hydrogen phosphate particles (Product No. 1430, JT Baker Chemical Co., NJ, average particle size: 10.2 μm), 240 g of 95% ethanol ("Ethanol (95)" manufactured by Wako Pure Chemical Industries, Ltd.), and 480 g of zirconia balls having a diameter of 10 mm to a 1000 ml alumina grinding pot ("HD-B-104 Pot Mill" manufactured by Nikkato Corporation), and subjecting the mixture to wet vibration grinding at a rotation speed of 1500 rpm for 15 hours. The slurry was then distilled off with a rotary evaporator to remove the ethanol, and then vacuum dried at 60° C. for 6 hours.

[0059] Preparation of the first material (powder) (Example 3) The tetracalcium phosphate 60.0 g (119.9 parts by mass) obtained above, anhydrous calcium hydrogen phosphate 21.1 g (42.1 parts by mass), xylose 10.0 g (20.0 parts by mass), zinc fluoride 2.50 g (5.0 parts by mass), disodium hydrogen phosphate 5.00 g (10.0 parts by mass), and light anhydrous silicic acid 1.50 g (3.0 parts by mass) were added to a high-speed rotating mill (Osaka Chemical Co., Ltd.'s "Wonder Crusher") and mixed at a rotation speed of 3500 rpm for 10 minutes to obtain the first material (powder). On the other hand, the preparation of the first materials (powders) in Examples 1, 2, 4 to 16 and Comparative Examples 2 to 6 was carried out in the same manner as in Example 3, except that the materials and the amounts of the materials were changed as shown in Tables 1 and 2. In the preparation of all the first materials, the total amount of the first materials (powders) was adjusted to 100 g.

[0060] Preparation of second material (liquid) (Example 3) 0.990 g of citric acid, 0.230 g of cetylpyridinium chloride, and 98.8 g of water were stirred with a stirrer to obtain a second material (liquid). On the other hand, the preparation of the second materials in Examples 1, 2, 4 to 16 and Comparative Examples 1 to 6 was carried out in the same manner as in Example 3, except that the materials and the amounts of the materials were changed as shown in Tables 1 and 2. All the second materials were prepared so that the total amount of the second material (liquid) was 100 g.

[0061] Powder-liquid mixing method (Example 3) Using the first and second materials prepared as described above for Example 3, 1.33 g (200 parts by mass) of the first material (powder) and 0.667 g (100 parts by mass) of the second material (liquid) were mixed with a spatula for 30 seconds. This resulted in the dental curable composition of Example 3. On the other hand, the powder-liquid mixing of Examples 1, 2, 4 to 16 and Comparative Examples 2 to 6 was carried out in the same manner as in Example 3, except that the mass ratio of the first material and the second material was changed as shown in Tables 1 and 2, to obtain dental curable compositions. All dental curable compositions were mixed so that the total amount after mixing was 2.0 g. In Comparative Example 1, the second material was used as it was as the dental curable composition.

[0062] [Examples 1 to 16, Comparative Examples 1 to 6] The dental curable compositions of Examples 1 to 16 and Comparative Examples 1 to 6 are shown in Tables 1 and 2. The first and second materials shown in Tables 1 and 2 were mixed as described above to prepare dental hardenable compositions, and the following properties were evaluated.

[0063] Evaluation of collagen degradation inhibition rate (1) Reagents used in the measurement Collagen Type I High-strength collagen sheet: Made by Nippi Co., Ltd. Tris-HCl buffer: Fujifilm Wako Pure Chemical Corporation Collagenase: Sigma Aldrich Ninhydrin ethanol solution: manufactured by Tokyo Chemical Industry Co., Ltd. (2)Measurement method Collagen Type I A high-strength collagen sheet (diameter 12 mm, thickness 0.2 mm) was entirely immersed in 2.0 g of the dental hardenable composition of each of the Examples and Comparative Examples and was kept in contact for 30 seconds. The collagen sheet was immersed in distilled water, ultrasonically cleaned for 5 minutes, and then washed with water. The collagen sheet was then immersed three times in 1.0 mL of 0.05 N Tris-HCl buffer, pH 7.2 (containing 0.001 M CaCl2). Next, the collagen sheet was immersed in 1.2 mL of 0.05N Tris-HCl buffer (pH 7.2, containing 0.001M CaCl2) containing 100 units of collagenase, and left to stand at 37°C for 4 hours to allow the enzyme to react. Then, 300 μL of ethanol was added to stop the enzyme reaction. 0.4 mL of the supernatant of the solution was taken, and 0.4 mL of ninhydrin-ethanol solution was added to the supernatant, and the solution sample was incubated at 50°C for 90 minutes, after which the absorbance (λ=515 nm) of the solution sample was measured using a spectrophotometer (U-1900, Hitachi, Ltd.). The collagen decomposition inhibition rate was calculated using the following formula (n=3). The average values ​​of the obtained evaluation results are shown in Tables 1 and 2. Collagen degradation inhibition rate (%) = 100-(absorbance of sample / absorbance of distilled water sample)

[0064] The collagen decomposition inhibition rate was evaluated according to the following criteria. A: 23% or more B: 17% or more but less than 23% C: 12% or more but less than 17% D: 6% or more but less than 12% E: Less than 6%

[0065] Evaluation of dentinal tubule occlusion rate The buccal center of a healthy bovine incisor was polished and trimmed with a rotary polisher using #80 and #1000 abrasive paper to prepare a dentin plate with a thickness of 2 mm with exposed buccal dentin as a sample. The buccal dentin surface of the sample was further polished and smoothed using abrasive paper (#1200, #3000, #8000, manufactured by Sumitomo 3M Limited). On the buccal dentin surface, two adjacent sections were set as test areas of 5 mm squares in the vertical and horizontal directions of the tooth, with marks. One section was to be coated with the dental hardenable composition, and the other section was not. The bovine tooth was immersed in a 3% EDTA (ethylenediaminetetraacetic acid) solution and exposed to ultrasonic waves for 10 minutes to demineralize the two sections of the dentin, and then washed with water to prepare a bovine tooth to be used for evaluation of the dentinal tubule occlusion rate. A sufficient amount of the dental hardenable composition of the present invention prepared as described above was applied to one of the sections of the buccal dentin surface of the bovine tooth, and the dental hardenable composition was rubbed into the section of the buccal dentin surface to be applied with the dental hardenable composition using a microbrush (Microbrush International (USA) "REGULAR SIZE (2.0 mm), MRB400") for 30 seconds. The paste on the buccal dentin surface was then removed with distilled water (n=3). When washing the paste, distilled water was run from the section to which the dental hardenable composition was not applied to the section to which the dental hardenable composition was applied, to prevent the dental hardenable composition from adhering to the section to which the dental hardenable composition was not applied.

[0066] 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.

[0067] For SEM observation, an SU-3500 (Hitachi High-Tech Corporation) was used. The morphological observation was performed on the sections where the dental hardenable composition was not applied and the sections where the dental hardenable composition was applied, under the condition of an acceleration voltage of 5 kV. One arbitrary point was observed for each section where the dental hardenable composition was not applied, and three arbitrary points were observed for each section where the dental hardenable composition was applied. The dentinal tubule occlusion rate is expressed by the following formula. The average values ​​of the obtained evaluation results are shown in Tables 1 and 2. Dentinal tubule occlusion rate (%) = 100 - average number of dentinal tubules observed in the section where the dental hardenable composition is applied (number of dentinal tubules) / number of dentinal tubules observed in the section where the dental hardenable composition is not applied (number of dentinal tubules) × 100

[0068] The dentinal tubule occlusion rate was evaluated according to the following criteria. A: 90% or more B: 80% or more but less than 90% C: 70% or more but less than 80% D: 60% or more but less than 70% E: 50% or more but less than 60% F: Less than 50%

[0069] [Table 1]

[0070] [Table 2]

[0071] As is clear from the above results, it was confirmed that the dental curable compositions according to the present invention (Examples 1 to 16) exhibited a high collagen decomposition inhibition rate and a high ability to seal dentinal tubules. [Industrial Applicability]

[0072] INDUSTRIAL APPLICABILITY According to the present invention, the composition can be suitably used in the field of dentistry as an agent for suppressing dentin hypersensitivity and an agent for suppressing dentin caries.

Claims

1. A dental hardening composition comprising calcium phosphate (A) and aldose (B), wherein the mass ratio of the content of (A) to the content of (B), (A) / (B), is 1.2 to 60.

2. It further contains water (C), It consists of a first material containing calcium phosphate (A) and a second material containing water (C), At least one of the first or second material contains aldose (B), The dental curable composition according to claim 1.

3. It further contains a curing accelerator (D), and The dental curable composition according to claim 1 or 2, wherein aldose (B) and a curing accelerator (D) are packaged separately.

4. The dental curable composition according to claim 2, wherein the first material comprises aldose (B).

5. The dental curable composition according to claim 1 or 2, wherein the content of calcium phosphate (A) is 30 to 70% by mass of the total amount of the dental curable composition.

6. The dental curable composition according to claim 1 or 2, wherein the content of calcium phosphate (A) is 40 to 66% by mass of the total amount of the dental curable composition.

7. The dental curable composition according to claim 1 or 2, wherein calcium phosphate (A) comprises a mixture of non-acidic calcium phosphate (A-1) and acidic calcium phosphate (A-2).

8. The dental curable composition according to claim 7, wherein the average particle size of non-acidic calcium phosphate (A-1) is 0.5 to 40 μm.

9. The dental curable composition according to claim 7, wherein the average particle size of acidic calcium phosphate (A-2) is 0.1 to 7 μm.

10. The dental curable composition according to claim 7, wherein the molar ratio (A-1 / A-2) of the content of non-acidic calcium phosphate (A-1) to the content of acidic calcium phosphate (A-2) is 40 / 60 to 60 / 40.

11. The dental curing composition according to claim 7, wherein the acidic calcium phosphate (A-2) comprises at least one selected from the group consisting of anhydrous calcium hydrogen phosphate, anhydrous calcium dihydrogen phosphate, α-tricalcium phosphate, β-calcium phosphate, amorphous calcium phosphate, acidic calcium pyrophosphate, calcium hydrogen phosphate dihydrate, and calcium dihydrogen phosphate monohydrate.

12. The dental curable composition according to claim 1 or 2, wherein the number of carbon atoms in aldose (B) is 100 or less.

13. The dental curable composition according to claim 1 or 2, wherein the content of aldose (B) is 2 to 20% by mass of the total amount of the dental curable composition.

14. The dental curable composition according to claim 1 or 2, wherein the water (C) content is 20 to 79% by mass of the total amount of the dental curable composition.

15. The dental curable composition according to claim 3, wherein the content of the curing accelerator (D) is 0.01 to 4.0% by mass of the total amount of the dental curable composition.

16. The dental curable composition according to claim 1 or 2, further comprising an inorganic filler (E), wherein the inorganic filler (E) comprises at least one selected from light anhydrous silicic acid having an average particle size of 0.002 to 2 μm and a metal oxide having an average particle size of 0.002 to 2 μm.

17. The dental curable composition according to claim 1 or 2, further comprising a fluoride salt, wherein the content of the fluoride salt is 1.0 to 5.0% by mass of 100% by mass of the total amount of the dental curable composition.

18. The dental curable composition according to claim 1 or 2, further comprising a pH adjusting agent, wherein the pH adjusting agent comprises disodium hydrogen phosphate and / or monosodium dihydrogen phosphate.