JP2013071917A - Dentine calcification agent and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a dentine calcification agent that can seal the dental canaliculi by the deposition of HAp onto the depths of the dental canaliculi.SOLUTION: The dentine calcification agent includes acid calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C), wherein this dentine calcification agent includes, on the basis of 100 pts.wt. of the whole amount of this dentine calcification agent, 15-80 pts.wt. of the acid calcium phosphate particles (A), and 15-84 pts.wt. of water (C), and has 0.1-80 pts.wt. of the alkali metal salt of phosphoric acid (B) relative to 100 pts.wt. of the acid calcium phosphate particles (A).

Description

  The present invention relates to a dentin calcification agent capable of sealing an exposed dentinal tubule.

  With the so-called 8020 exercise (improving oral hygiene, preserving tooth quality (MI)) that tries to keep more than 20 teeth even after the age of 80, there is a rate that many teeth remain in the elderly Increased dramatically. However, along with this, problems of dentin exposure due to new dental diseases (tooth wear, alveolar bone loss due to periodontal disease, etc.) have occurred. Unlike the enamel, the exposed dentin has a low mineral concentration in the tissues that make up the dentin, so the caries resistance is not good, and the dentinal tubules are opened by the action of acid in the oral cavity, resulting in hypersensitivity. Cause sickness. As a method for improving this, there are known a method of coating a polymer material and a method of sealing dentinal tubules by applying two kinds of materials alternately to precipitate an inorganic salt to form a physical barrier. It has been. However, these methods only cover a shallow portion or surface near the opening of the dentinal tubule and have a problem of being easily destroyed when worn by a toothbrush or the like. Moreover, although it is a material with high biocompatibility, there also existed a problem which became the cause of inflammation and a root caries because plaque adheres by application | coating of material.

Calcium phosphate cement combining tetracalcium phosphate (hereinafter sometimes abbreviated as “TTCP”) and anhydrous calcium monohydrogen phosphate (hereinafter sometimes abbreviated as “DCPA”) as a calcium phosphate composition having curability (Hereinafter may be abbreviated as “CPC”), and is bioabsorbable hydroxyapatite (hereinafter abbreviated as “HAp” in vivo or in the oral cavity; Ca ₁₀ (PO ₄ ) ₆ ( It is said that it is gradually converted to OH) ₂ ) and can be integrated with living hard tissue while maintaining its form. On the other hand, as a calcium phosphate cement that does not use TTCP, a calcium phosphate cement that combines an acidic calcium phosphate such as DCPA and a calcium compound that does not contain phosphate ions is known.

For example, Non-Patent Document 1 describes a self-setting calcium phosphate cement composed of acidic calcium phosphate typified by DCPA and the like and a calcium compound such as calcium hydroxide and calcium carbonate. Further, it is described that an alkali metal salt of phosphoric acid such as disodium monohydrogen phosphate (Na ₂ HPO ₄ ) may be added to increase the phosphate concentration. However, it is described that it has a remarkable effect on the surface of the dentin, for example, by blocking the dentinal tubules by mixing a certain amount of acidic calcium phosphate represented by DCPA and the like, and alkali metal salt of phosphoric acid. Was not.

  Patent Document 1 discloses an oral care composition for topical oral administration to humans or other animals, a chewable solid containing a retention agent containing hydroxyethyl cellulose and carboxymethyl cellulose, and a local oral care carrier. A unit dosage composition is described. According to this, it is said that the oral care active agent can be delivered directly to the tooth surface using a chewable solid unit dosage form. As one of the oral care active agents, for example, remineralization Agents are mentioned. However, it is described that it has a remarkable effect on the surface of the dentin, for example, by blocking the dentinal tubules by mixing a certain amount of acidic calcium phosphate represented by DCPA and the like, and alkali metal salt of phosphoric acid. Was not.

On the other hand, Patent Document 2 describes that a calcium phosphate composition containing tetracalcium phosphate and calcium hydrogen phosphate anhydride reacts in the presence of water to produce hydroxyapatite. The hydroxyapatite thus obtained can be gradually replaced into bone by contact with the living hard tissue, and the calcium phosphate composition has a calcification ability, and therefore can be used as a mineralizing agent. It is said that. On the other hand, it is described that an alkali metal salt of phosphoric acid such as disodium monohydrogen phosphate (Na ₂ HPO ₄ ) is added for the purpose of rapidly curing the calcium phosphate composition. However, there has been no description about adding an alkali metal salt of phosphoric acid for the purpose of improving the effect of calcification.

  Patent Document 3 describes a composition for healing hypersensitivity comprising tetracalcium phosphate, calcium phosphate having a Ca / P molar ratio of less than 1.67, and a thickener. According to this, it is said that hypersensitivity can be remarkably reduced by applying to a hypersensitive part of a tooth and holding it for a predetermined time. The reason why the hypersensitivity is remarkably reduced is that calcium ions and phosphate ions eluted from the mixture of water and the like of the composition diffuse and penetrate into the dentinal tubule, and hydroxyapatite precipitates and deposits in the dentinal tubule This is to block mechanical stimulation, thermal stimulation, and chemical stimulation from the outside. On the other hand, hydroxyapatite, calcium fluoride, titanium oxide, calcium hydroxide, sodium phosphate, ammonium phosphate, alumina for the above-mentioned composition for healing hypersensitivity to adjust kneadability with water and paste viscosity. It is described that other components such as silica may be added. However, there has been no description about adding an alkali metal salt of phosphoric acid for the purpose of improving the effect of calcification.

JP 2007-314564 A Japanese Patent No. 3017536 JP-A-1-163127

S. Takagi et al., Formation ofhydroxyapatite in new calcium phosphate cements, Biomaterials 19 1998, p.1593-1599

  The present invention has been made to solve the above-mentioned problems, and not only penetrates into the dentinal tubule and physically seals it, but in the long term, HAp precipitates deep into the dentinal tubule and seals the dentinal tubule. An object of the present invention is to provide a dentin mineralizing agent that can be used.

  The above-mentioned problem is a dentin mineralizing agent containing acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C), and the total amount of the dentin mineralizing agent is 100 parts by weight. Containing 15 to 80 parts by weight of acidic calcium phosphate particles (A) and 15 to 84 parts by weight of water (C), and blending of alkali metal salt of phosphoric acid (B) with respect to 100 parts by weight of acidic calcium phosphate particles (A) This is solved by providing a dentin mineralizing agent characterized in that the amount is 0.1 to 80 parts by weight.

At this time, acidic calcium phosphate particles (A) are anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles, anhydrous calcium dihydrogen phosphate [Ca (H ₂ PO ₄ ) ₂ ] particles, tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ] particles, calcium pyrophosphate [Ca ₂ P ₂ O ₇ ] particles, acidic calcium pyrophosphate [CaH ₂ P ₂ O ₇ ] particles, calcium monohydrogen phosphate dihydrate [CaHPO ₄ .2H ₂ O] particles, octacalcium phosphate pentahydrate _{[Ca 8 H 2 (PO 4} ) 6 · 5H 2 O], calcium pyrophosphate dihydrate _{[Ca 2 P 2 O 7 ·} 2H 2 O], and calcium dihydrogen phosphate 1 It is preferably at least one selected from the group consisting of hydrate [Ca (H ₂ PO ₄ ) ₂ .H ₂ O] particles, and acidic calcium phosphate particles (A ) Are anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles and / or calcium monohydrogen phosphate dihydrate [CaHPO ₄ .2H ₂ O] particles. It is preferable that the alkali metal salt (B) of phosphoric acid is disodium monohydrogen phosphate and / or monosodium dihydrogen phosphate. It is preferable that the phosphorus source and calcium source contained in the dentin calcification agent consist only of acidic calcium phosphate particles (A) and an alkali metal salt of phosphoric acid (B). Furthermore, it is preferable to contain a fluorine compound (D), and it is preferable that the fluorine compound (D) is sodium fluoride. The average particle diameter of the acidic calcium phosphate particles (A) is preferably 0.1 to 20 μm, and the dentin mineralizing agent is preferably used for sealing the dentinal tubules by rubbing on the dentin surface. It is.

  Further, powders, pastes and the like containing a dentin calcifying agent are suitable material types of the present invention, and a tooth surface treatment material containing a dentin calcifying agent is a preferred embodiment of the present invention. A hypersensitivity inhibitor made of a tooth surface treatment material or a root caries preventive agent made of a tooth surface treatment material is a preferred embodiment of the present invention. A dentifrice containing a dentin calcification agent is also a preferred embodiment of the present invention.

  Moreover, it is a manufacturing method of the dentin mineralizing agent which mixes the liquid or aqueous paste which has acidic calcium phosphate particle (A), the alkali metal salt (B) of phosphoric acid, and water (C) as a main component, and is acidic calcium phosphate 0.1-80 parts by weight of alkali metal salt (B) of phosphoric acid is added to 100 parts by weight of particles (A), and the amount of acidic calcium phosphate particles (A) to 100 parts by weight of the total amount of dentin calcifying agent 15 to 80 parts by weight, and a liquid or water-based paste containing water as a main component is added so that the blending amount of water (C) is 15 to 84 parts by weight with respect to 100 parts by weight of the total amount of dentin mineralizing agent. It is a preferred embodiment of the present invention to provide a method for producing a dentin mineralizing agent to be mixed.

  At this time, it is preferable that the phosphorus source and calcium source contained in the dentin mineralizing agent are composed of only the acidic calcium phosphate particles (A) and the alkali metal salt of phosphoric acid (B), and the acidic calcium phosphate particles (A) and It is preferable to add a liquid or water-based paste containing water (C) as a main component to a powder or non-aqueous paste containing an alkali metal salt of phosphoric acid (B) and mix. In addition, it is preferable to add a liquid or aqueous paste containing water (C) as a main component and an alkali metal salt of phosphoric acid (B) to a powder or non-aqueous paste containing acidic calcium phosphate particles (A) and mixing them. Yes, a liquid or aqueous paste containing water (C) as a main component and containing acidic calcium phosphate particles (A) is added to a liquid or aqueous paste containing water (C) as a main component and containing an alkali metal salt of phosphoric acid (B). Mixing is preferred.

  The subject is dentin calcification comprising a powder or non-aqueous paste containing acidic calcium phosphate particles (A) and an alkali metal salt (B) of phosphoric acid, and a liquid or water-based paste containing water (C) as a main component. It is solved by providing a drug kit.

  The above-mentioned problem is a dentin calcification comprising a powder or non-aqueous paste containing acidic calcium phosphate particles (A) and a liquid or aqueous paste containing water (C) as a main component and containing an alkali metal salt of phosphoric acid (B). It is solved by providing a drug kit.

  The above-mentioned problem is a powder or non-aqueous paste containing acidic calcium phosphate particles (A), a powder or non-aqueous paste containing an alkali metal salt of phosphoric acid (B), and a liquid mainly composed of water (C) or It is solved by providing a dentin mineralizer kit comprising an aqueous paste.

  In addition, the above-described problems are a liquid or aqueous paste containing water (C) as a main component and containing acidic calcium phosphate particles (A), and a liquid or aqueous system containing water (C) as a main component and containing an alkali metal salt of phosphoric acid (B). It is also solved by providing a dentin mineralizer kit comprising a paste.

  According to the present invention, there is provided a dentin mineralizing agent that not only penetrates and physically seals into the dentinal tubule, but also allows HAp to deposit into the deep part of the dentinal tubule to seal the dentinal tubule. This makes it possible to treat hypersensitivity. Moreover, it is possible to seal a dentinal tubule with the dentin mineralizer of this invention by rubbing the dentin mineralizer of this invention on the dentin surface. The dentin mineralizing agent of the present invention can be stored for a long time even in the state of a paste containing water.

In Example 1, it is the SEM photograph which compared the bovine dentin surface where the dentinal tubule was sealed with HAp, and the bovine dentin surface where the dentinal tubule was exposed. In Example 1, it is a SEM photograph of the bovine dentin surface where the dentinal tubule before a test was exposed. In Example 1, it is a SEM photograph of the bovine dentin surface where the dentinal tubule was blocked with the dentin mineralization agent of this invention. In Example 1, it is a SEM photograph of the bovine dentin cross section in which the dentinal tubule was blocked with the dentin mineralization agent of this invention.

  The dentin mineralizing agent of the present invention contains a certain amount of acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C). By the use of a dentin mineralizing agent containing a certain amount of acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C) by the present inventors, the calcification effect is particularly high. It was revealed that HAp can be deposited to the deep part of the dentinal tubule to seal the dentinal tubule. Although the reason for this is not necessarily clear, the following mechanism is presumed.

  That is, when preparing and using a dentin mineralizer containing a certain amount of acidic calcium phosphate particles (A), alkali metal salt of phosphoric acid (B), and water (C), the acidic calcium phosphate particles (A) Calcium ions and phosphate ions obtained by dissolution and phosphate ions obtained by dissolving alkali metal salt (B) of phosphoric acid react in the dentinal tubules with HAp in the tooth as the nucleus, and energy It appears that stable HAp is precipitated. As a result, it appears that HAp is deposited deep in the dentinal tubule and the dentinal tubule is blocked. In this way, since HAp is deposited to the deep part of the dentinal tubule and the dentinal tubule is blocked, it is possible to treat hypersensitivity. Further, the apparent dentin mineral concentration is improved and the wear resistance is also improved. Here, the present inventors presume that the balance of the rate at which calcium ions and phosphate ions are supplied and the ion concentration in the liquid preparation are important in order to achieve the above effects. Moreover, when the solubility of the compound which supplies calcium ion and the compound which supplies phosphate ion is extremely low or extremely high, it has confirmed that precipitation of HAp is not favorable. Therefore, by containing a certain amount of acidic calcium phosphate particles (A), alkali metal salt of phosphoric acid (B) and water (C), the supply rate and supply balance of calcium ions and phosphate ions to the dentin are appropriate. It is significant to adopt the configuration of the present invention.

The acidic calcium phosphate particles (A) used in the present invention are not particularly limited, and any acidic calcium phosphate compound having a Ca / P molar ratio of less than 1.67 can be suitably used, and anhydrous calcium monohydrogen phosphate [CaHPO ₄ ]. Particles, anhydrous calcium dihydrogen phosphate [Ca (H ₂ PO ₄ ) ₂ ] particles, tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ] particles (amorphous calcium phosphate [Ca ₃ (PO ₄ ) ₂ .nH ₂ O] particles), calcium pyrophosphate [Ca ₂ P ₂ O ₇ ] particles, acidic calcium pyrophosphate [CaH ₂ P ₂ O ₇ ] particles, calcium monohydrogen phosphate dihydrate [CaHPO ₄ .2H ₂ O] particles , eight calcium phosphate pentahydrate _{[Ca 8 H 2 (PO 4} ) 6 · 5H 2 O], calcium pyrophosphate dihydrate _{[Ca 2 P} 2 O · _2H 2 O], and calcium dihydrogen phosphate monohydrate _{[Ca (H 2} PO ₄₎ is preferably at least one selected from the group consisting of 2 · _H 2 O] particles. Among these, the hardly soluble acidic calcium phosphate particles (A) are preferably used from the viewpoint of good precipitation of HAp and penetration into the dentinal tubule and sealing the dentinal tubule. Here, “slightly soluble” means that the solubility is less than 0.1 g in 100 g of water at 25 ° C. As the hardly soluble acidic calcium phosphate particles (A), anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles, tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ] particles, calcium pyrophosphate [Ca ₂ P ₂ O ₇ ] particles , octacalcium phosphate pentahydrate _{[Ca 8 H 2 (PO 4} ) 6 · 5H 2 O], calcium pyrophosphate dihydrate _{[Ca 2 P 2 O 7 ·} 2H 2 O], calcium hydrogen phosphate 2 At least one selected from the group consisting of hydrated [CaHPO ₄ .2H ₂ O] particles is preferably used. Among these, anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles, calcium monohydrogen phosphate dihydrate [CaHPO ₄ .2H ₂ O] particles, and tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ] particles are used. More preferably, at least one selected from the group is used, and from the group consisting of anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles and calcium monohydrogen phosphate dihydrate [CaHPO ₄ · 2H ₂ O] particles At least one selected is more preferably used.

  The average particle diameter of the acidic calcium phosphate particles (A) used in the present invention is preferably 0.1 to 20 μm. When the average particle size is less than 0.1 μm, the dissolution in the liquid becomes excessive, so that not only the supply balance of calcium ions and phosphate ions is lost, but the ion concentration in the liquid may be excessive. Furthermore, the viscosity of the paste obtained by mixing with the liquid may be too high, and the applicability may be reduced, resulting in a decrease in dentin sealing performance. The average particle diameter of the acidic calcium phosphate particles (A) is more preferably 0.3 μm or more, and even more preferably 1 μm or more. On the other hand, when the average particle diameter exceeds 20 μm, the acidic calcium phosphate particles (A) are difficult to dissolve in the liquid agent, so that the supply balance of calcium ions and phosphate ions is lost and the concentration of these ions in the liquid agent is too small. As a result, the precipitation of hydroxyapatite is not smooth, and the calcification effect may be reduced. In addition, the acidic calcium phosphate particles (A) cannot enter the dentinal tubule, and there is a possibility that the sealing property is lowered. The average particle diameter of the acidic calcium phosphate particles (A) is more preferably 15 μm or less, further preferably 10 μm or less, particularly preferably 5 μm or less, and most preferably 2 μm or less. The average particle diameter of the acidic calcium phosphate particles (A) is measured and calculated using a laser diffraction particle size distribution analyzer.

  The method for producing acidic calcium phosphate particles (A) having such an average particle diameter is not particularly limited, and may be used as long as a commercially available product is available, but it is preferable to further grind the commercially available product. There are many. In that case, a pulverizing apparatus such as a ball mill, a likai machine, or a jet mill can be used. Moreover, acidic calcium phosphate raw material powder is pulverized with a liquid medium such as alcohol using a lykai machine, a ball mill or the like to prepare a slurry, and the resulting slurry is dried to obtain acidic calcium phosphate particles (A). it can. A ball mill is preferably used as the pulverizer at this time, and alumina or zirconia is preferably used as the material of the pot and ball.

  The present invention contains 15 to 80 parts by weight of acidic calcium phosphate particles (A) with respect to 100 parts by weight of the total amount of dentin mineralizing agent. If the content of the acidic calcium phosphate particles (A) is less than 15 parts by weight, the precipitation of HAp may be inhibited and the calcification effect may not be obtained, and when rubbed into the dentin surface, it enters the dentinal tubules. However, there is a possibility that gaps increase and the dentinal tubules cannot be effectively sealed. The content of the acidic calcium phosphate particles (A) is preferably 20 parts by weight or more, more preferably 25 parts by weight or more, and further preferably 30 parts by weight or more. On the other hand, if the content of the acidic calcium phosphate particles (A) exceeds 80 parts by weight, precipitation of HAp may be inhibited and a calcification effect may not be obtained. When rubbing on the surface of dentin, it may be difficult to rub. The content of the acidic calcium phosphate particles (A) is preferably 75 parts by weight or less, more preferably 72 parts by weight or less, and still more preferably 70 parts by weight or less.

  The alkali metal salt of phosphoric acid (B) used in the present invention is not particularly limited, and is disodium monohydrogen phosphate, dipotassium monohydrogen phosphate, dilithium monohydrogen phosphate, monosodium dihydrogen phosphate, phosphorus Examples include monopotassium dihydrogen acid, trisodium phosphate, tripotassium phosphate, and hydrates thereof, and one or more of these are used. Especially, it is preferable that the alkali metal salt (B) of phosphoric acid is disodium monohydrogen phosphate and / or monosodium dihydrogen phosphate from a viewpoint that a raw material with high safety and high purity can be easily obtained.

  The compounding quantity of the alkali metal salt (B) of phosphoric acid used by this invention is 0.1-80 weight part with respect to 100 weight part of acidic calcium phosphate particles (A). When the blending amount of the alkali metal salt of phosphoric acid (B) is less than 0.1 parts by weight, the precipitation of HAp may be inhibited, and the calcification effect may not be obtained, and may be 0.2 parts by weight or more. It is preferably 1 part by weight or more, more preferably 2 parts by weight or more. On the other hand, when the content of the alkali metal salt (B) of phosphoric acid exceeds 80 parts by weight, precipitation of HAp may be inhibited and a calcification effect may not be obtained, and is preferably 60 parts by weight or less. The amount is more preferably 50 parts by weight or less, and still more preferably 40 parts by weight or less.

  The average particle size of the alkali metal salt (B) of phosphoric acid is preferably 1 to 20 μm. When the average particle size is less than 1 μm, dissolution in the liquid is too early, and the phosphate ion concentration in the dentin mineralizing agent composition becomes high, so the supply balance of calcium ions and phosphate ions is disrupted, and hydroxyapatite There is a possibility that the precipitation rate of slag decreases and the calcification effect decreases. Furthermore, secondary aggregation of alkali metal salt particles of phosphoric acid occurs, and the dispersibility with other particles mixed at the same time may be reduced. The average particle diameter of the alkali metal salt of phosphoric acid (B) is more preferably 3 μm or more. On the other hand, when the average particle size exceeds 20 μm, the alkali metal salt (B) of phosphoric acid becomes difficult to dissolve in the liquid agent, the HAp precipitation rate is lowered, and the calcification effect may be lowered. The average particle diameter of the alkali metal salt of phosphoric acid (B) is more preferably 15 μm or less. The average particle size of the alkali metal salt (B) of phosphoric acid is measured and calculated using a laser diffraction particle size distribution measuring device.

  The manufacturing method of the alkali metal salt (B) of phosphoric acid having such an average particle diameter can be performed in the same manner as the acidic calcium phosphate particles (A) described above.

  In addition to the acidic calcium phosphate particles (A) and the alkali metal salt of phosphoric acid (B), the dentin mineralizing agent of the present invention further contains water (C) with respect to 100 parts by weight of the total amount of the dentin mineralizing agent. It is blended in an amount of 15 to 84 parts by weight. When the blending amount of water is less than 15 parts by weight, precipitation of HAp may be hindered and a calcification effect may not be obtained, and since paste properties are poor and applicability is reduced, when rubbed into the dentin surface, There is a risk that it will be difficult to rub. The blending amount of water is preferably 20 parts by weight or more, and more preferably 30 parts by weight or more. On the other hand, if the amount of water exceeds 84 parts by weight, the precipitation of HAp may be hindered and the calcification effect may not be obtained. There is a risk that the dentinal tubules cannot be effectively sealed. The blending amount of water is preferably 80 parts by weight or less, and more preferably 70 parts by weight or less.

  The dentin calcifying agent of the present invention is a two-material type comprising a combination of a powder and a liquid containing acid calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C), or a paste, or In addition, it is possible to provide a one-material type using a paste containing acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C). By applying a dentin mineralizing agent to dentin, calcium ions and phosphate ions are supplied, and a reaction occurs with HAp in the tooth as a nucleus, and HAp seems to precipitate. Applying these to the lesioned part of the tooth, applying a resin-based tooth surface coating material, etc., and curing it prevents the active ingredient from dissipating to other parts and enables long-term treatment. It is also possible to use the dentin mineralizing agent by rubbing it onto the dentin surface with an applicator or the like. The dentin calcifying agent of the present invention is preferably a one-material type using a paste containing acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C).

It is preferable that the phosphorus source and calcium source contained in the dentin mineralizing agent of the present invention consist only of acidic calcium phosphate particles (A) and an alkali metal salt (B) of phosphoric acid. Anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles exemplified as acidic calcium phosphate particles (A) are mixed with basic calcium phosphate represented by tetracalcium phosphate or basic calcium represented by calcium hydroxide, It hardens on contact with water and produces HAp. When it is going to provide a dentin mineralizing agent with one aqueous paste, it is not preferred that basic calcium phosphate or basic calcium is contained because the composition solidifies during storage and cannot be used.

  It is preferable that the dentin mineralizing agent of this invention contains a fluorine compound (D) further. This makes it possible to impart acid resistance to the tooth and promote calcification. The fluorine compound (D) used in the present invention is not particularly limited, and is sodium fluoride, potassium fluoride, ammonium fluoride, lithium fluoride, cesium fluoride, magnesium fluoride, calcium fluoride, strontium fluoride, fluorine. Barium fluoride, copper fluoride, zirconium fluoride, aluminum fluoride, tin fluoride, sodium monofluorophosphate, potassium monofluorophosphate, hydrofluoric acid, sodium titanium fluoride, potassium titanium fluoride, hexylamine hydrofluor Rides, laurylamine hydrofluoride, glycine hydrofluoride, alanine hydrofluoride, fluorosilanes, fluorinated diamine silver and the like can be mentioned. Among these, sodium fluoride, sodium monofluorophosphate, and tin fluoride are preferably used from the viewpoint of high calcification promoting effect.

  The usage-amount of the fluorine compound (D) used by this invention is not specifically limited, The conversion fluoride ion of a fluorine compound (D) is 0.01-3 weight part with respect to 100 weight part of whole quantity of a dentine mineralizing agent. It is preferable to include. When the usage-amount of the fluoride ion of a fluorine compound (D) is less than 0.01 weight part, there exists a possibility that the effect which accelerates | stimulates calcification may fall, and it is more preferable that it is 0.05 weight part or more. On the other hand, when the usage-amount of the fluoride ion of a fluorine compound (D) exceeds 3 weight part, safety | security may be impaired and it is more preferable that it is 1 weight part or less.

  The dentin mineralizing agent of the present invention may contain components other than the acidic calcium phosphate particles (A), the alkali metal salt of phosphoric acid (B), and the fluorine compound (D) as long as the effects of the present invention are not impaired. Absent. For example, a thickener can be mix | blended as needed. Specific examples of the thickener include carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyethylene glycol, polyacrylic acid, polystyrene sulfonic acid, polystyrene sulfonate, polyglutamic acid, polyglutamate, Polyaspartic acid, polyaspartate, poly L lysine, poly L lysine salt, starch other than cellulose, alginic acid, alginate, carrageenan, guar gum, chitansan gum, cellulose gum, hyaluronic acid, hyaluronate, pectin, pectin salt, chitin , Polysaccharides such as chitosan, acidic polysaccharide esters such as propylene glycol alginate, collagen, gelatin and these One or two or more selected from polymers such as proteins such as conductors may be mentioned. From the viewpoint of solubility in water and viscosity, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, alginic acid, At least one selected from alginate, chitosan, polyglutamic acid, polyglutamate is preferred. The thickener may be blended into the powder, the liquid, or the paste being mixed.

  If necessary, inorganic fillers such as silica, polyhydric alcohols such as glycerin, ethylene glycol, propylene glycol and diglycerin, sugar alcohols such as xylitol, sorbitol and erythritol, polyethers such as polyethylene glycol and polypropylene glycol Artificial sweeteners such as aspartame, acesulfame potassium, licorice extract, saccharin, and saccharin sodium may be added. Furthermore, any pharmacologically acceptable drug or the like can be blended. Antibacterial agents typified by cetylpyridinium chloride, antiseptics, anticancer agents, antibiotics, blood circulation improving agents such as actosine and PEG1, growth factors such as bFGF, PDGF and BMP, osteoblasts, odontoblasts, and undifferentiated Bone marrow-derived stem cells, embryonic stem (ES) cells, induced pluripotent stem (iPS) cells obtained by dedifferentiation and production of differentiated cells such as fibroblasts by gene transfer, and cells such as these differentiated cells Cells or the like that promote tissue formation can be added.

  In the present invention, a paste-like dentin mineralizing agent is obtained by mixing a liquid or aqueous paste mainly composed of acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C). Can be obtained. This pasty dentin mineralizing agent containing water (C) can be stored for a long period of time, and can also be prepared by mixing immediately before use in a medical field. Accordingly, a paste-form dentin calcification agent containing water (C) that is a one-part type is a preferred embodiment of the present invention, and a dentin calcification that is a two-part type that is appropriately prepared at a medical site. Agents are also a preferred embodiment of the present invention. The mixing operation is not particularly limited, and hand mixing, mixing using a static mixer, and the like are preferably employed. Here, when mixing the acid calcium phosphate particles (A), the alkali metal salt of phosphoric acid (B), and the liquid or aqueous paste containing water (C) as a main component, The alkali metal salt (B) may be added and mixed as it is, or may be added and mixed as a liquid agent. In any case, a dentin mineralizing agent having a high calcifying effect can be obtained. I have confirmed that. From the viewpoint of obtaining a dentin calcifying agent having a higher calcifying effect, a method of adding and mixing an alkali metal salt (B) of phosphoric acid as a liquid agent is suitably employed.

  The dentin mineralizing agent thus obtained is preferably used by applying it to the dentin surface or by rubbing it onto the dentin surface. Here, the liquid containing water as a main component may be pure water, or a liquid containing water as a main component and containing other components, and the water-based paste containing water as a main component. The paste-like liquid which has water as a main component and contains another component is shown. Examples of other components include, but are not limited to, polyhydric alcohols such as glycerin, ethylene glycol, propylene glycol, and diglycerin, sugar alcohols such as xylitol, sorbitol, and erythritol, and polyethers such as polyethylene glycol and polypropylene glycol. .

  Here, it became clear that the dentinal tubule can be effectively sealed by rubbing the dentin mineralizing agent of the present invention on the dentin surface. The following mechanism is presumed for this reason. That is, when the dentin mineralizing agent of the present invention is prepared in the presence of water and rubbed into the dentin surface, calcium ions and phosphate ions are supplied, and the reaction occurs with HAp in the tooth as the nucleus, It seems that HAp is precipitated. As a result, the precipitated HAp is crystal-grown by calcium ions and phosphate ions, densified and seems to be integrated with the dentin. As a result, the sealing performance of the dentinal tubules is improved, and the effect of particularly suppressing hypersensitivity is enhanced. Accordingly, a dentin mineralizing agent that is used to seal dentinal tubules by rubbing onto the dentin surface is a preferred embodiment of the present invention. Moreover, the dentin hypersensitivity suppression method by rubbing such a dentin mineralizing agent on the dentin surface is also a preferred embodiment of the present invention.

  In the present invention, a liquid or aqueous paste containing water (C) as a main component is added to and mixed with a powder or non-aqueous paste containing acidic calcium phosphate particles (A) and an alkali metal salt of phosphoric acid (B). A pasty dentin mineralizing agent can be obtained. Moreover, in this invention, the liquid or aqueous paste which contains water (C) as a main component and contains the alkali metal salt (B) of phosphoric acid is added and mixed with the powder or non-aqueous paste containing acidic calcium phosphate particles (A). The paste-like dentin calcification agent can also be obtained. Furthermore, in the present invention, a liquid or aqueous paste containing water (C) as a main component and containing acidic calcium phosphate particles (A), or a liquid or aqueous paste containing water (C) as a main component and containing an alkali metal salt of phosphoric acid (B). A paste-like dentin mineralizing agent can also be obtained by adding and mixing the paste.

  A non-aqueous paste mainly composed of a powder containing acidic calcium phosphate particles (A) and an alkali metal salt of phosphoric acid (B) or a solvent other than water (C), and a liquid mainly composed of water (C) Alternatively, a method of mixing with an aqueous paste is preferably employed. Further, a powder containing acidic calcium phosphate particles (A) or a non-aqueous paste mainly containing a solvent other than water (C), and an alkali metal salt of phosphoric acid (B) mainly containing water (C) A method of mixing with the liquid or aqueous paste to be included is also preferably employed. Furthermore, a liquid or aqueous paste containing water (C) as a main component and containing acidic calcium phosphate particles (A) and a liquid or aqueous paste containing water (C) as a main component and containing an alkali metal salt of phosphoric acid (B) are mixed. This method is also preferably employed. These methods also have an advantage that the operation when mixing and preparing just before use is simple. The solvent other than water used for the non-aqueous paste is not particularly limited, and examples thereof include polyhydric alcohols such as glycerin, ethylene glycol, propylene glycol, and diglycerin, and polyethers such as polyethylene glycol and polypropylene glycol. .

  The dentin mineralizing agent of the present invention is preferably used for various uses of tooth surface treatment materials and dentifrices. The acidic calcium phosphate particles (A) and the alkali metal salt (B) of phosphoric acid supply calcium ions and phosphate ions in the presence of water. These penetrate into the dentin and cause remineralization of the dentin by depositing HAp in the dentin as a nucleus. It is also possible to rub the dentin mineralizing agent of the present invention on the surface of the dentin and allow the dentin mineralizing agent to penetrate into the dentinal tubule and physically seal it. Therefore, among these, a tooth surface treatment material containing a dentin calcification agent is a preferred embodiment of the present invention, and in particular, from a hypersensitivity inhibitor comprising a tooth surface treatment material and / or a tooth surface treatment material. The root caries preventive agent is a more preferred embodiment of the present invention. A dentifrice containing a dentin calcification agent is also a preferred embodiment of the present invention.

  As described above, in the presence of water, the dentin mineralizing agent containing acidic calcium phosphate particles (A) and an alkali metal salt of phosphoric acid (B) supplies calcium ions and phosphate ions. These powders contain acidic calcium phosphate particles (A) and alkali metal salts of phosphoric acid (B) because they penetrate into the dentin and cause remineralization of the dentin by depositing HAp in the dentin as a core. One embodiment of the present invention is a dentin mineralizer kit comprising a body or a non-aqueous paste and a liquid or water-based paste containing water (C) as a main component. A dentin mineralizer kit comprising a powder or non-aqueous paste containing acidic calcium phosphate particles (A) and a liquid or aqueous paste containing water (C) as a main component and an alkali metal salt of phosphoric acid (B) This is one of the embodiments of the present invention. Further, a powder or non-aqueous paste containing acidic calcium phosphate particles (A), a powder or non-aqueous paste containing an alkali metal salt (B) of phosphoric acid, and a liquid or aqueous paste containing water (C) as a main component It is one of the embodiments of the present invention that it is a dentin mineralizer kit comprising: Further, the liquid or water-based paste containing water (C) as a main component and containing acidic calcium phosphate particles (A), and the liquid or water-based paste containing water (C) as a main component and containing an alkali metal salt (B) of phosphoric acid. It is one of the embodiments of the present invention that it is a dentin calcification agent kit.

  Hereinafter, the present invention will be described more specifically with reference to examples. In this example, the average particle size of the acidic calcium phosphate particles (A), the alkali metal salt of phosphoric acid (B), and the sodium fluoride (D) particles is determined by a laser diffraction particle size distribution analyzer (“SALD, manufactured by Shimadzu Corporation). -2100 type "), and the median diameter calculated from the measurement results was defined as the average particle diameter.

[Preparation of bovine teeth for calcification]
The center of the buccal side of the healthy bovine incisor was polished with a rotary polishing machine using # 80, # 1000 polishing paper to expose the dentin. The polished surface of the bovine teeth was further polished and smoothed using a wrapping film (# 1200, # 3000, # 8000, manufactured by Sumitomo 3M). This dentin part was left with a window of a 7 mm test part in each of the vertical axis direction and the horizontal axis direction with respect to the teeth (hereinafter referred to as “dentin window”), and the surroundings were masked with nail polish and air-dried for 1 hour. A solution obtained by diluting a 0.5 M EDTA solution (manufactured by Wako Pure Chemical Industries, Ltd.) five times with respect to the bovine teeth was allowed to act on the dentin window for 30 seconds, followed by washing with water for 30 minutes or more. Further, a 10% sodium hypochlorite solution (Neo Cleaner “SEKINE”, manufactured by Neo Pharmaceutical Co., Ltd.) was allowed to act for 2 minutes for cleaning, and then washed with water for about 1 hour to prepare bovine teeth used for calcification.

[Preparation of simulated saliva]
Sodium chloride (8.77 g, 150 mmol), potassium dihydrogen phosphate (122 mg, 0.9 mmol), calcium chloride (166 mg, 1.5 mmol), and Hepes (4.77 g, 20 mmol) were weighed into weighing pans, respectively. The mixture was sequentially added to a 2000 ml beaker containing 800 ml of distilled water with stirring. After confirming that the solute was completely dissolved, the acidity of this solution was measured with a pH meter (F55, manufactured by HORIBA, Ltd.), and a 10% aqueous sodium hydroxide solution was added dropwise to adjust the pH to 7.0. Next, this solution was added to a 1000 ml volumetric flask and the volume was increased to obtain 1000 ml of simulated saliva.

[Acid calcium phosphate particles (A)]
DCPA: 10.2 .mu.m anhydrous calcium hydrogen phosphate [CaHPO _4] manufactured by Wako Pure Chemical Industries, Ltd. DCPD: 5.1 .mu.m calcium hydrogen phosphate dihydrate [CaHPO ₄ · 2H ₂ O] by Taihei Chemical Industrial Co., Ltd. β-TCP: 1.0 μm β-tricalcium phosphate [β-Ca ₃ (PO ₄ ) ₂ ] manufactured by Taihei Chemical Industry Co., Ltd. [alkali metal salt of phosphoric acid (B)]
Na ₂ HPO ₄ : Disodium hydrogen phosphate manufactured by Wako Pure Chemical Industries, Ltd. NaH ₂ PO ₄ : Sodium dihydrogen phosphate manufactured by Wako Pure Chemical Industries, Ltd. [fluorine compound (D)]
NaF: sodium fluoride, manufactured by Wako Pure Chemical Industries, Ltd. MFP: sodium monofluorophosphate, manufactured by Wako Pure Chemical Industries, Ltd. [silica particles (E)]
Ar130: “Aerosil 130 (trade name)” manufactured by Nippon Aerosil Co., Ltd. [Other calcium phosphates]
TTCP: 10.8 μm Tetracalcium phosphate [Ca ₄ (PO ₄ ) ₂ O] Taihei Chemical Industrial Co., Ltd.

[Preparation of each powder]
DCPA: Preparation of average particle size 1.1 μm DCPA: Average particle size 1.1 μm is DCPA: 10.2 μm 50 g, 95% ethanol (“Ethanol (95)” manufactured by Wako Pure Chemical Industries, Ltd.) 240 g, and diameter A slurry obtained by adding 480 g of 10 mm zirconia balls into a 1000 ml alumina grinding pot (“HD-B-104 pot mill” manufactured by Nikkato Co., Ltd.) and performing wet vibration grinding for 15 hours at a rotational speed of 1500 rpm, Ethanol was distilled off with a rotary evaporator, and then dried at 60 ° C. for 6 hours. 0.7 μm and 5.0 μm DCPA were obtained in the same manner as in the above method, and the grinding time was 30 hours and 7 hours, respectively.

DCPD: Preparation of average particle size 1.1 μm DCPD: Average particle size 1.1 μm is DCPD: 5.1 μm 50 g, 95% ethanol (“Ethanol (95)” manufactured by Wako Pure Chemical Industries, Ltd.) 240 g, and diameter 10 mm The slurry obtained by adding 480 g of zirconia balls in 1000 ml of an alumina grinding pot (“HD-B-104 pot mill” manufactured by Nikkato Co., Ltd.) for 10 hours at a rotational speed of 1500 rpm, After the ethanol was distilled off with an evaporator, it was obtained by drying at 60 ° C. for 6 hours.

Na ₂ HPO _4: Preparation of 4.6 .mu.m Na ₂ HPO _4: average particle size 4.6 .mu.m is a nanojet mizer (NJ-100 Model manufactured by Aisin Nanotechnologies)), the raw material supply pressure grinding pressure conditions: 0. The pressure was 7 MPa / grinding pressure: 0.7 MPa, and the treatment amount condition was 8 kg / hr.

Na ₂ HPO ₄ : Preparation of 9.7 μm Na ₂ HPO ₄ : The average particle size is 9.7 μm, and Na ₂ HPO ₄ is supplied with a nanojet mizer (NJ-100 type, manufactured by Aisin Nano Technology Co., Ltd.), and pulverization pressure conditions are supplied as raw materials. The pressure was 0.3 MPa / grinding pressure: 0.3 MPa, and the treatment amount condition was 8 kg / hr.

Na ₂ HPO ₄ : Preparation of 19.7 μm Na ₂ HPO ₄ : The average particle size of 19.7 μm is Na ₂ HPO ₄ supplied by NanoJet Mizer (NJ-100 type, manufactured by Aisin Nanotechnology Co., Ltd.). The pressure was 0.2 MPa / grinding pressure: 0.1 MPa, and the treatment amount condition was 20 kg / hr.

Na ₂ HPO _4: Preparation of 1.45μm Na ₂ HPO _4: average particle size 1.45 .mu.m _is the Na 2 HPO ₄ in nanojet mizer (NJ-100 type Aisin Nanotechnology Inc.), the raw material supplying grinding pressure conditions The pressure was 1.3 MPa / grinding pressure: 1.3 MPa, and the treatment amount condition was 1 kg / hr.

NaH ₂ PO ₄ : Preparation of 4.8 μm NaH ₂ PO ₄ : The average particle size is 4.8 μm, and NaH ₂ PO ₄ is supplied with a nanojet mizer (NJ-100 type, manufactured by Aisin Nanotechnology Co., Ltd.) as a raw material under pulverization pressure conditions. The pressure was 0.7 MPa / grinding pressure: 0.7 MPa, and the treatment amount condition was 8 kg / hr.

[Preparation of dentin mineralizing agent]
(1) Preparation of powder for dentin mineralizing agent Each powder component weighed with the composition shown in Tables 1 and 2 is added to a high-speed rotary mill (As One Co., Ltd. “SM-1”) at a rotational speed of 22000 rpm. Dentin mineralizing agent powder was prepared by mixing for 3 minutes. The powder which does not need to be mixed was used as it was as a powder of dentin mineralizing agent.

(2) Preparation of solution for dentin calcification agent Each solution component weighed with the composition shown in Tables 1 and 2 was dissolved in distilled water to obtain a solution for dentin calcification agent. In the case of a composition not containing a liquid component, distilled water was used as it was as a liquid agent for a dentin mineralizing agent.

(3) Preparation of dentin mineralizing agent A dentin mineralizing agent is prepared by adding and mixing the powder obtained in the above (1) having the composition shown in Tables 1 and 2 and the liquid obtained in (2) above. did.

Examples 1-27
A dentin mineralizing agent was prepared with the composition described in Tables 1 to 5 according to the procedures (1) to (3), and a calcification test was performed. In addition, SEM observation and a curing time measurement test were performed. The obtained evaluation results are summarized in Table 6.

(4) Preparation of tooth mineralizing agent paste Components other than purified water and glycerin weighed in the compositions shown in Tables 3 to 4 were added to a high-speed rotating mill (As One Co., Ltd. “SM-1”) and rotated at 22000 rpm. After mixing for 3 minutes at a speed, weighed purified water and glycerin were added and mixed to prepare a dentin mineralizing agent.

Examples 28-43
A dentin calcification agent was prepared with the composition described in Tables 3 to 4 in the procedure of (4) above, and a contact calcification test was performed for a short time as well as for a long time. Moreover, the hardening time measurement test was done. The obtained evaluation results are summarized in Table 6.

Comparative Examples 1-5
The dentin mineralizing agent described in Table 2 was prepared by the procedures (1) to (3) above, and a contact calcification test was performed for a short time as well as for a long time. Moreover, the hardening time measurement test was done. The obtained evaluation results are summarized in Table 6.

Example 44
DCPA: 1.1 μm 30 g, NaF 0.21 g, Ar130 0.5 g, and glycerol (manufactured by Wako Pure Chemical Industries, Ltd.) 19.29 g were mixed to prepare a first liquid paste. 3 g of Na ₂ HPO ₄ , 0.5 g of sodium saccharinate (manufactured by Wako Pure Chemical Industries, Ltd.), 3 g of polyethylene glycol (Macrogor 400, manufactured by Sanyo Chemical Industries, Ltd.), 5 g of glycerin, propylene glycol (Wako Pure Chemical Industries, Ltd.) 5 g), cetylpyridinium chloride monohydrate (manufactured by Wako Pure Chemical Industries, Ltd.) 0.05 g, Ar130 3.5 g, and distilled water 29.95 g were mixed to prepare a second liquid paste. A dentin mineralizing agent was prepared by adding and mixing 50 g of the first liquid paste prepared above and 50 g of an aqueous paste. In the same manner as in Example 1, a short-time and long-time contact calcification test was performed. Moreover, the hardening time measurement test was done. The obtained evaluation results are summarized in Table 6.

Example 45
The dentin mineralizing agent described in Table 5 was prepared in the same manner as in Example 44, and a contact calcification test was conducted for a short time as well as for a long time. Moreover, the hardening time measurement test was done. The obtained evaluation results are summarized in Table 6.

[Evaluation of dentin mineralizing agent]
(1) Preparation of bovine disc for calcification The center of the buccal side of a healthy bovine incisor was trimmed with a rotary polishing machine using # 80, # 1000 abrasive paper, and a disc shape having a diameter of about 7 mm and a thickness of 0.9 mm Molded into. The polished surface of the bovine teeth was further polished with a wrapping film (# 1200, # 3000, # 8000, manufactured by Sumitomo 3M Co.) and polished to a thickness of 0.7 mm to make it smooth. About 60 seconds after demineralization was performed by applying a solution obtained by diluting a 0.5M EDTA solution (manufactured by Wako Pure Chemical Industries, Ltd.) 5 times to both sides of the bovine tooth disk for 30 seconds on the dentin window. Washed with water. Further, a 10% sodium hypochlorite solution (Neo Cleaner “SEKINE”, manufactured by Neo Pharmaceutical Co., Ltd.) was allowed to act for 1 minute for cleaning to prepare a bovine tooth disk used for evaluation of dentin permeation inhibition rate.

(2) Preparation of calcification test (initial stage of rubbing) Dentin calcification agent prepared as above using a spatula on the buccal dentin surface of the calcification bovine disc prepared in (1) above About 0.1 g is adhered, and then, using a microbrush (MICROBRUSH INTERNATIONAL “REGULAR SIZE (2.0 mm), MRB400”), it is rubbed for 30 seconds against a dentin having a diameter of 5 mm at the center of the dentin-treated surface. I did. Thereafter, the paste on the dentin surface was removed with distilled water, and a dentin permeation inhibition rate evaluation test and SEM observation were immediately performed (n = 5).

(3) Preparation of calcification test (long-term rubbing) sample Dentin calcification agent prepared above with a spatula on the buccal dentin surface of the bovine disc for calcification prepared in (1) above About 0.1 g is adhered, and then, using a microbrush (MICROBRUSH INTERNATIONAL “REGULAR SIZE (2.0 mm), MRB400”), it is rubbed for 30 seconds against a dentin having a diameter of 5 mm at the center of the dentin-treated surface. I did. Thereafter, the paste on the dentin surface was removed with distilled water and immersed in simulated saliva for 2 weeks, and then a dentin permeation inhibition rate evaluation test and SEM observation were performed (n = 5).

(4) Dentin permeation inhibition rate evaluation test For evaluation of dentin permeation inhibition rate, the method of Pasley et al. (DH PASHLEY et al., J. Dent. Res. 65: 417-420, 1986 .; K) C.Y.TAY et al., J. Endod.33: 1438-1443, 2007.). A similar device was installed, and the calcified bovine teeth obtained above were installed and fixed in a chamber jig that could be divided so that the liquid could penetrate from the pulp toward the enamel. Dentin surface to which pressure of Phosphate-buffered saline (Dulbecco's PBS, Grand Island Biological Company, Grand Island, NY) is standardized to a surface area of 78.5 mm ² (diameter 5 mm) using an O-ring, 10 psi (69 kPa) And the amount of permeation after 24 hours was measured. Moreover, the dentin permeation | transmission suppression rate was computed using the following formula from the permeation | transmission amount measurement result of the same bovine disc before performing said calcification (dentinal tubule sealing) by the same operation. The dentin permeation suppression rate (initial stage of scouring) of the bovine tooth disc calcified according to Example 1 was 67%, and the dentin permeation suppression rate (long-term scouring period) was 69%. The results obtained are summarized in Table 6.
Dentin permeation inhibition rate (%) = {1− (permeation amount of calcified (dentinal tubule sealed) bovine disc) / (permeation amount of bovine disc not calcified (dentinal tubule sealed))} × 100

(5) SEM observation After calcified bovine teeth were taken out from the immersion liquid, washed with water, vacuum-dried at room temperature for 1 hour and subjected to metal vapor deposition, and then the calcified surface was scanned with a scanning electron microscope (S-3500N, stock) (Manufactured by Hitachi High-Technologies Corporation) was observed at a magnification of 3000 times. The surface of the bovine dentin of the bovine disc calcified in Example 1 was observed, and it was confirmed that the dentinal tubules were sealed with a dentin calcification agent. Moreover, the bovine disc was cut and the cross section of the bovine dentin was observed, and it was confirmed that the blockade had intruded to a depth of about 10 μm.

(6) Curing time measurement About 30 mg of paste-like dentin calcification agent was taken out on a microscope slide glass, and then sandwiched between another microscope slide glass and pressed to apply a shearing force. It was visually inspected whether a uniform portion was generated. The time when the non-uniform portion occurred was defined as the curing time. The sample for curing time measurement was stored at 25 ° C. after preparation, and the measurement was also performed at 25 ° C. The case where it was preserve | saved for 30 days or more and hardening was not recognized was determined not to harden | cure.

1 Untreated part 2 Ivory tubules sealed with HAp

Claims (22)

  A dentin calcifying agent containing acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C), wherein the calcium phosphate is based on 100 parts by weight of the total amount of the dentinal calcifying agent 15 to 80 parts by weight of particles (A) and 15 to 84 parts by weight of water (C), and the blending amount of alkali metal salt (B) of phosphoric acid with respect to 100 parts by weight of acidic calcium phosphate particles (A) is 0. A dentin calcification agent characterized by being 1 to 80 parts by weight. The acidic calcium phosphate particles (A) are anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles, anhydrous calcium dihydrogen phosphate [Ca (H ₂ PO ₄ ) ₂ ] particles, tricalcium phosphate [Ca ₃ (PO ₄ ) _2. ] Particles, calcium pyrophosphate [Ca ₂ P ₂ O ₇ ] particles, acidic calcium pyrophosphate [CaH ₂ P ₂ O ₇ ] particles, calcium monohydrogen phosphate dihydrate [CaHPO ₄ .2H ₂ O] particles, eight phosphates calcium pentahydrate _{[Ca 8 H 2 (PO 4} ) 6 · 5H 2 O], calcium pyrophosphate dihydrate _{[Ca 2 P 2 O 7 ·} 2H 2 O], and calcium dihydrogen phosphate monohydrate The dentin calcification agent according to claim 1, which is at least one selected from the group consisting of [Ca (H ₂ PO ₄ ) ₂ · H ₂ O] particles. The ivory according to claim 1, wherein the acidic calcium phosphate particles (A) are anhydrous calcium monohydrogen phosphate [CaHPO ₄ ] particles and / or calcium monohydrogen phosphate dihydrate [CaHPO ₄ .2H ₂ O] particles. Quality mineralizer.   The dentin mineralizing agent according to any one of claims 1 to 3, wherein the alkali metal salt (B) of phosphoric acid is disodium monohydrogen phosphate and / or monosodium dihydrogen phosphate.   The dentin mineralizing agent according to any one of claims 1 to 4, wherein the phosphorus source and calcium source contained in the dentin mineralizing agent consist only of acidic calcium phosphate particles (A) and an alkali metal salt (B) of phosphoric acid.   Furthermore, the dentin mineralizing agent in any one of Claims 1-5 containing a fluorine compound (D).   The dentin mineralizing agent according to claim 6, wherein the fluorine compound (D) is sodium fluoride.   The dentin mineralizing agent according to any one of claims 1 to 7, wherein the average particle diameter of the acidic calcium phosphate particles (A) is 0.1 to 20 µm.   The dentin mineralizing agent according to any one of claims 1 to 8, wherein the dentin mineralizing agent is used for sealing dentinal tubules by rubbing on the dentin surface.   A tooth surface treatment material containing the dentin mineralizing agent according to any one of claims 1 to 9.   A hypersensitivity inhibitor comprising the tooth surface treating material according to claim 10.   A root caries preventive agent comprising the tooth surface treatment material according to claim 10.   A dentifrice containing the dentin calcification agent according to any one of claims 1 to 9. A method for producing a dentin calcification agent comprising mixing a liquid or aqueous paste mainly composed of acidic calcium phosphate particles (A), an alkali metal salt of phosphoric acid (B), and water (C),
0.1-80 parts by weight of alkali metal salt (B) of phosphoric acid is blended with 100 parts by weight of acidic calcium phosphate particles (A), and the amount of acidic calcium phosphate particles (A) with respect to 100 parts by weight of the total amount of dentin calcifying agent. A liquid or water-based paste containing water as a main component so that the blending amount is 15 to 80 parts by weight and the blending amount of water (C) is 15 to 84 parts by weight with respect to 100 parts by weight of the total amount of dentin calcification agent. The method for producing a dentin calcification agent according to claim 1, which is additionally mixed.   The method for producing a dentin mineralizing agent according to claim 14, wherein the phosphorus source and calcium source contained in the dentin mineralizing agent are composed of only the acidic calcium phosphate particles (A) and the alkali metal salt (B) of phosphoric acid.   The ivory of Claim 14 which adds and mixes the liquid or aqueous paste which has water (C) as a main component to the powder or non-aqueous paste containing acidic calcium phosphate particle (A) and the alkali metal salt (B) of phosphoric acid. Of producing a calcifying agent.   The ivory according to claim 14, wherein a liquid or an aqueous paste containing water (C) as a main component and an alkali metal salt of phosphoric acid (B) is added to and mixed with powder or non-aqueous paste containing acidic calcium phosphate particles (A). Of producing a calcifying agent.   To a liquid or aqueous paste containing water (C) as a main component and containing acidic calcium phosphate particles (A), a liquid or aqueous paste containing water (C) as a main component and containing an alkali metal salt of phosphoric acid (B) is added and mixed. The manufacturing method of the dentin mineralizing agent of Claim 14.   A dentin calcification agent kit comprising a powder or non-aqueous paste containing acidic calcium phosphate particles (A) and an alkali metal salt of phosphoric acid (B), and a liquid or aqueous paste containing water (C) as a main component.   A dentin calcification agent kit comprising a powder or non-aqueous paste containing acidic calcium phosphate particles (A), and a liquid or aqueous paste containing water (C) as a main component and an alkali metal salt of phosphoric acid (B).   From a powder or non-aqueous paste containing acidic calcium phosphate particles (A), a powder or non-aqueous paste containing an alkali metal salt (B) of phosphoric acid, and a liquid or aqueous paste containing water (C) as a main component Dentin mineralizer kit.   A dentin comprising a liquid or aqueous paste containing water (C) as a main component and containing acidic calcium phosphate particles (A), and a liquid or aqueous paste containing water (C) as a main component and containing an alkali metal salt of phosphoric acid (B) Calcifying agent kit.