Oral composition

Abstract

To provide oral compositions containing particles having dentinal tubule sealing properties and having excellent adhesion in dentinal tubules.SOLUTION: Provided is an oral composition containing hydroxyapatite particles, the ratio of the diffraction peak intensity around 2θ=32° with respect to the diffraction peak intensity around 2θ=26° in the X-ray diffraction pattern being 0.8 to 1.5.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an oral composition, and more particularly to an oral composition containing hydroxyapatite particles. The contents of all documents described in this specification (particularly JP 2017-036176 A) are incorporated herein by reference. [Background technology]

[0002] Dental hypersensitivity develops when the dentin of the tooth is exposed due to physical abrasion such as brushing, chemical abrasion by acid, etc. When the dentin is exposed, external stimuli stimulate the nerves in the dentinal tubules in the dentin, making it more likely to cause pain.

[0003] For hypersensitivity, for example, the dentinal tubules are blocked with particles of fluoride, aluminum salts (see Patent Document 1 for an example), etc., to prevent external stimuli from reaching the nerves. However, most of the conventional methods have insufficient adhesion after blocking, and there is a problem with the durability of the effect. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2010-222325 A [Patent Document 2] JP Patent No. 2017-036176 Public Relations Summary of the Invention [Problem to be solved by the invention]

[0005] The objective of the present invention is to provide particles that have the ability to seal dentinal tubules and have excellent adhesion within the dentinal tubules. [Means for solving the problem]

[0006] In view of the above problems, the present inventors have conducted intensive research and found that specific hydroxyapatite particles (hydroxyapatite particles having a ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° in an X-ray diffraction pattern of 0.8 to 1.5) can solve the above problems. Based on this finding, further investigations have been conducted.

[0007] The present invention includes, for example, the aspects described in the following sections. Section 1. An oral composition containing hydroxyapatite particles, The hydroxyapatite particles have a ratio of a diffraction peak intensity around 2θ=32° to a diffraction peak intensity around 2θ=26° in a powder X-ray diffraction pattern measured with CuKα characteristic X-rays of 0.8 to 1.5. Oral composition. Section 2. Item 2. The oral composition according to item 1, wherein the hydroxyapatite particles have a Ca / P molar ratio of less than 1.67 (preferably 1.60 or less). Section 3. Item 3. The oral composition according to item 1 or 2, wherein the hydroxyapatite particles have a median diameter of 5 μm or less. Section 4. The specific surface area of ​​the hydroxyapatite particles is 55 to 200 m 2 / g of the oral composition according to any one of Items 1 to 3. Section 5. Item 5. The oral composition according to any one of Items 1 to 4, wherein the hydroxyapatite particles have a ratio of a diffraction peak intensity at about 2θ=34° to a diffraction peak intensity at about 2θ=32° in a powder X-ray diffraction pattern measured using CuKα characteristic X-rays of 1 or less. Section 6. The hydroxyapatite particles are aggregates of hydroxyapatite platelet crystals. Item 6. The oral composition according to any one of Items 1 to 5. Section 7. Item 7. The oral composition according to any one of Items 1 to 6, further comprising potassium nitrate and / or aluminum lactate. Section 8. Item 8. The oral composition according to any one of Items 1 to 7, which is for preventing or improving dentin hypersensitivity. Section 9. Item 9. The oral composition according to any one of Items 1 to 8, wherein the hydroxyapatite particles are produced by a method for producing hydroxyapatite particles, the method comprising the steps of mixing an aqueous solution of an alkali phosphate having a pH of 4 or more and less than 7 with a calcium hydroxide slurry and reacting the mixture at 35 to 85°C. Section 10. Item 10. The oral composition according to item 9, wherein the calcium hydroxide slurry is a ground calcium hydroxide slurry. Section 11. Item 11. The oral composition according to item 9 or 10, wherein the oxalic acid reactivity of the calcium hydroxide slurry is 40 minutes or less (the time (minutes) required for the pH to reach 7.0 after the addition of 40 g of an aqueous oxalic acid solution having a concentration of 0.5 mol / L and kept at 25±1° C. to 50 g of calcium hydroxide slurry prepared to a concentration of 5% by mass and kept at 25±1° C.). Section 12. The BET specific surface area of ​​the calcium hydroxide slurry is 5 m 2 / g or more. Effect of the Invention

[0008] An oral composition is provided which has the ability to seal dentinal tubules and has excellent adhesion within the dentinal tubules. [Brief description of the drawings]

[0009] [Figure 1] 1 shows the X-ray diffraction peaks of the hydroxyapatite particles of Example 1. [Diagram 2] The X-ray diffraction peaks of commercially available reagent hydroxyapatite particles are shown. [Diagram 3] 1 shows an SEM photograph of the hydroxyapatite particles of Example 1. [Figure 4] 3 shows the X-ray diffraction peaks of the hydroxyapatite particles of Example 2. [Diagram 5]1 shows an SEM photograph of the hydroxyapatite particles of Example 2. [Figure 6] 3 shows the X-ray diffraction peaks of the hydroxyapatite particles of Example 3. [Figure 7] 1 shows an SEM photograph of the hydroxyapatite particles of Example 3. [Figure 8] 1 shows the X-ray diffraction peaks of the hydroxyapatite particles of Example 4. [Figure 9] 1 shows an SEM photograph of the hydroxyapatite particles of Example 4. [Figure 10] 1 shows X-ray diffraction peaks of the hydroxyapatite microparticles of Example 5. [Figure 11] 1 shows an SEM photograph of the hydroxyapatite microparticles of Example 5. [Figure 12] 1 shows X-ray diffraction peaks of hydroxyapatite particles of Comparative Example 1. [Figure 13] 1 shows an SEM photograph of hydroxyapatite particles of Comparative Example 1. [Figure 14] This shows the X-ray diffraction peaks of the sample of Comparative Example 2. The peaks indicated by black circles are the diffraction peaks of monetite. [Figure 15] 3 shows an SEM photograph of the sample of Comparative Example 2. [Figure 16] 3 shows the X-ray diffraction peaks of the sample of Comparative Example 3. [Figure 17] 3 shows an SEM photograph of the sample of Comparative Example 3. [Figure 18] 1 shows X-ray diffraction peaks of hydroxyapatite particles of Comparative Example 4. [Figure 19] 1 shows an SEM photograph of hydroxyapatite particles of Comparative Example 4. [Figure 20] 1 shows the X-ray diffraction peaks of the sample of Comparative Example 5. The peaks indicated by black circles are the diffraction peaks of monetite. [Figure 21] 1 shows an SEM photograph of the sample of Comparative Example 5. [Figure 22] 1 shows X-ray diffraction peaks (Test Example 1) of hydroxyapatite particles before and after immersion in artificial saliva. [Diagram 23] 4 shows SEM photographs of dentinal tubules before and after brushing (Test Example 2). [Figure 24] 4 shows SEM photographs of dentinal tubules before and after water pressure treatment (Test Example 3). [Diagram 25] 1 shows SEM photographs (Test Example 4) of dentinal tubules before and after brushing with a dentifrice solution containing hydroxyapatite particles. [Figure 26] 1 shows SEM photographs (Test Example 5) of dentinal tubules before and after a gel preparation containing hydroxyapatite particles was applied to dentin with a soft pick. [Figure 27] 1 shows the flow of a clinical trial using a gel formulation containing hydroxyapatite particles. [Figure 28] This shows the results of evaluating the degree of abrasion pain using the VAS scale in a clinical trial using a gel preparation containing hydroxyapatite particles. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Each embodiment included in the present invention will be described in more detail below. Note that the present invention preferably includes oral compositions, particularly oral compositions containing specific hydroxyapatite particles, but is not limited thereto, and the present invention includes all of the compositions disclosed in this specification and recognizable by a person skilled in the art.

[0011] The oral composition included in the present invention contains specific hydroxyapatite particles. In this specification, the oral composition may be referred to as the "oral composition of the present invention."

[0012] The specific hydroxyapatite particles are hydroxyapatite particles having a ratio of a diffraction peak intensity at about 2θ=32° to a diffraction peak intensity at about 2θ=26° in an X-ray diffraction pattern of 0.8 to 1.5. In this specification, the hydroxyapatite particles may be referred to as "particles of the present invention".

[0013] The diffraction peak near 2θ=26° is a hydroxyapatite peak, specifically, a diffraction peak at 2θ=25.5 to 26.5°, preferably a diffraction peak at 2θ=25.8 to 26.2°. When there are multiple diffraction peaks near 2θ=26°, the diffraction peak with the highest intensity is the one with the highest intensity.

[0014] The diffraction peak near 2θ=32° is a hydroxyapatite peak, specifically, a diffraction peak at 2θ=31.5 to 32.5°, preferably a diffraction peak at 2θ=31.8 to 32.2°. When there are multiple diffraction peaks near 2θ=32°, the diffraction peak with the highest intensity is the one with the highest intensity.

[0015] In this specification, the X-ray diffraction pattern is a powder X-ray diffraction pattern measured by CuKα characteristic X-rays. An example of the measurement conditions is as follows: target: Cu, tube voltage: 40 kV, tube current: 30 mA, sampling width: 0.02°, scan speed: 2.00° / min, divergence slit: 1.0°, scattering slit: 1.0°, receiving slit: 0.3 mm.

[0016] The particles of the present invention have a ratio (32° / 26°) of the diffraction peak intensity at about 2θ=32° to the diffraction peak intensity at about 2θ=26° of 0.8 to 1.5. The peak intensity ratio is preferably 0.9 to 1.3, more preferably 1.0 to 1.25, even more preferably 1.05 to 1.2, and still more preferably 1.05 to 1.15.

[0017] The particles of the present invention are preferably each an aggregate of hydroxyapatite plate crystals. The shape of the plate crystals constituting the particles of the present invention is not particularly limited, and may be circular, polygonal (particularly hexagonal), rod-like, or a combination of these. The plate crystals may be in either a state in which the faces are folded or in a state in which the faces are not folded and the plane structure is maintained. Generally, plate hydroxyapatite crystals have a structure called a hexagonal crystal, with the top face of the plate being the c-plane and the side face being the a-plane. When a particle is formed by a plurality of crystals, the crystals are called crystallites.

[0018] The particles of the present invention are particles containing hydroxyapatite as a main component, and preferably particles essentially consisting of hydroxyapatite. In the X-ray diffraction pattern of the particles of the present invention, even if other substances (such as monetite, etc.) are contained, the peaks are not observed separately, or the peak intensities are relatively low. Therefore, the particles of the present invention are distinguished from particles having high peak intensities of these peaks.

[0019] Although not wishing to be limited in any way, it is believed that the particles of the present invention have a shape and structure represented by a specific X-ray diffraction pattern and are composed of aggregates of plate-like particles, which, in combination, result in excellent sealing of dentinal tubules and excellent adhesion within the dentinal tubules.

[0020] The particles of the present invention preferably have a ratio (34° / 32°) of the diffraction peak intensity around 2θ=34° to the diffraction peak intensity around 2θ=32° in the X-ray diffraction pattern of 1 or less. The diffraction peak around 2θ=34° is specifically a diffraction peak at 2θ=33.5 to 34.5°, preferably a diffraction peak at 2θ=33.8 to 34.2°. When there are multiple diffraction peaks around 2θ=34°, it means the diffraction peak with the highest intensity. The peak intensity ratio is preferably 0.1 to 1, more preferably 0.2 to 0.9, even more preferably 0.3 to 0.8, even more preferably 0.4 to 0.7, and particularly preferably 0.4 to 0.6.

[0021] The particles of the present invention preferably have a total sum of the areas of all diffraction peaks in the range of 25.5°≦2θ≦26.5° and the area of ​​all diffraction peaks in the range of 31.5°≦2θ≦32.5° of 30-45% relative to the total sum of the areas of all diffraction peaks in the range of 25°≦2θ≦35° being 100%. The value is preferably 33-42%, more preferably 35-40%. In addition, the particles of the present invention preferably have a crystallite size calculated from the diffraction peak of the (130) plane near 2θ=40° of 4-12 nm, more preferably 5-10 nm. Although not intended to be limited in interpretation, it is considered that the crystal growth in the dentinal tubules is enhanced after sealing due to the relatively low crystallinity, which leads to improved fixation in the tubules.

[0022] The Ca / P molar ratio of the particles of the present invention is not particularly limited as long as it is a value that hydroxyapatite can take. Although not wishing to be interpreted restrictively, it is considered that in the particles of the present invention, a part of calcium is replaced with other elements (sodium, etc.), and therefore the Ca / P molar ratio may be a relatively low value. From this viewpoint, the Ca / P molar ratio of the particles of the present invention is preferably less than 1.67, more preferably 1.65 or 1.60 or less, even more preferably 1.55 or 1.50 or less, and even more preferably 1.45 or 1.40 or less. The lower limit of the Ca / P molar ratio of the particles of the present invention is not particularly limited, and may be, for example, 1.0, 1.1, or 1.2. The Ca / P molar ratio is a value calculated from the measured values ​​of the Ca and P contents of the particles of the present invention measured by inductively coupled plasma atomic emission spectrometry.

[0023] The median diameter (d50) of the particles of the present invention is not particularly limited, but is preferably 5 μm or less, more preferably 4.5 μm or less, from the viewpoint of dentinal tubule sealing property, adhesion property, etc. The lower limit of the median diameter is not particularly limited, but may be, for example, 1 μm or more, 2 μm or more, or 3 μm or more. More specifically, it may be, for example, 1 to 5 μm. The median diameter is a value measured by a laser diffraction / scattering method. More specifically, it is a value measured by dry particle size distribution measurement using a laser diffraction particle size distribution measurement device.

[0024] The specific surface area of ​​the particles of the present invention is not particularly limited, but from the viewpoint of dentinal tubule sealing property, adhesion property, etc., it is preferably, for example, 30 m 2 / g or more, preferably 40m 2 / g or more, more preferably 50m 2 / g or more, more preferably 55m 2 The upper limit of the specific surface area is not particularly limited, but is, for example, 150 m 2 / g, 120m 2 / g, 100m 2 / g, 90m 2 The specific surface area is a value measured by a nitrogen gas adsorption method.

[0025] The particles of the present invention preferably react with saliva to improve their crystallinity. Here, the improvement in crystallinity means that in a powder X-ray diffraction pattern measured by CuKα characteristic X-rays, the sharpness of at least one (preferably 1, 2, 3, 4 or more) peaks improves (more specifically, the diffraction intensity improves) after the reaction with saliva compared to before the reaction. As the saliva, artificial saliva (CaCl2: 1.5 mM, KH2PO4: 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH)) is used. The reaction is performed by immersing the particles in saliva for 7 days.

[0026] The particles of the present invention can be prepared, for example, by a method for producing hydroxyapatite particles, which includes a step of mixing an aqueous solution of an alkali phosphate having a pH of 4 or more and less than 7 with a calcium hydroxide slurry and reacting them at 35 to 85°C.

[0027] The alkali phosphate salt is not particularly limited and includes hydrates and anhydrides. Examples of the alkali phosphate salt include sodium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, tetrasodium pyrophosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, tripotassium phosphate, etc., preferably sodium phosphate salts such as sodium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, etc., more preferably sodium dihydrogen phosphate.

[0028] The concentration of the alkali phosphate in the aqueous alkali phosphate solution is not particularly limited and is, for example, 3 to 50% by mass, preferably 3 to 30% by mass, more preferably 5 to 20% by mass, and further preferably 7 to 15% by mass.

[0029] The pH of the aqueous solution of alkali phosphate is preferably 4 or more and less than 7. The pH is more preferably 5 to 6.5. As described later, when the pH of the aqueous solution of alkali phosphate is relatively low (for example, pH 4 or more and less than 5), it is desirable to use an anhydride as the alkali phosphate and set the reaction temperature to a relatively high temperature, for example, 65 to 85°C, preferably 70 to 85°C, more preferably 75 to 85°C.

[0030] The calcium hydroxide slurry has oxalic acid reactivity, and the calcium hydroxide slurry is preferably a slurry of calcium hydroxide having a specific reactivity with oxalic acid.

[0031] The reactivity towards oxalic acid can be expressed, for example, by the following definition: Oxalic acid reactivity: 40 g of 0.5 mol / L oxalic acid aqueous solution kept at 25±1°C is added all at once to 50 g of calcium hydroxide slurry prepared to a concentration of 5% by mass and kept at 25±1°C, and the time (minutes) until the pH reaches 7.0 after the addition.

[0032] The specific reactivity to oxalic acid, as defined above, is preferably 1 to 40 minutes, more preferably 5 to 30 minutes, and further preferably 10 to 20 minutes.

[0033] The BET specific surface area of ​​the calcium hydroxide slurry is preferably 5 m 2 / g or more, more preferably 6m 2 The upper limit of the BET specific surface area is not particularly limited, but is, for example, 20 m 2 / g, 15m 2 / g, 10m 2 / g.

[0034] A calcium hydroxide slurry having high oxalic acid reactivity (e.g., reactivity to the specific oxalic acid described above) can typically be obtained by grinding a calcium hydroxide slurry. The grinding process can further increase the oxalic acid reactivity (shorten the time defined above). The grinding process is performed, for example, using a bead mill. The conditions for the grinding process are not particularly limited, and for example, the conditions according to the method described in JP 2017-036176 A can be adopted.

[0035] Calcium hydroxide slurry can be prepared, for example, by reacting water with quicklime (calcium oxide) obtained by calcining limestone. For example, limestone is calcined in a kiln at about 1000°C to generate quicklime, and about 10 times the amount of hot water is added to the quicklime and stirred for 30 minutes to prepare calcium hydroxide slurry.

[0036] The solid content concentration of the calcium hydroxide slurry is not particularly limited, but is, for example, 1 to 30 mass %, preferably 3 to 20 mass %, more preferably 5 to 15 mass %, and further preferably 6 to 12 mass %.

[0037] The ratio of the amount of the aqueous alkali phosphate solution to the amount of the calcium hydroxide slurry is not particularly limited as long as it is a ratio that allows the production of hydroxyapatite particles. It is desirable to adjust the ratio so that the Ca / P molar ratio is preferably 0.3 to 0.7, more preferably 0.4 to 0.6, and even more preferably 0.45 to 0.55.

[0038] The mode of mixing the aqueous alkali phosphate solution and the calcium hydroxide slurry is not particularly limited. For example, the mode of adding the calcium hydroxide slurry to a reaction vessel containing the aqueous alkali phosphate solution (mode 1), the mode of adding the aqueous alkali phosphate solution to a reaction vessel containing the calcium hydroxide slurry (mode 2), and the mode of adding the aqueous alkali phosphate solution and the calcium hydroxide slurry to the reaction vessel simultaneously (mode 3) can be mentioned. Among these, mode 1 is preferable. During the above-mentioned addition to the reaction vessel, the liquid in the reaction vessel is usually stirred.

[0039] The addition to the reaction vessel is desirably carried out over a certain period of time, for example, 10 to 90 minutes, preferably 20 to 60 minutes, and more preferably 20 to 40 minutes.

[0040] The reaction is usually carried out under stirring. The reaction temperature is 35 to 85°C. The reaction temperature is preferably 40 to 75°C, more preferably 45 to 70°C, even more preferably 50 to 70°C, and even more preferably 55 to 65°C. When the pH of the aqueous solution of alkali phosphate is relatively low (for example, when the pH is 4 or more and less than 5), the reaction temperature is relatively high, for example, 65 to 85°C, preferably 70 to 85°C, and more preferably 75 to 85°C. The reaction time (the time starting from when the aqueous solution of alkali phosphate and the calcium hydroxide slurry are completely mixed, and in the above embodiments 1 to 3, the time starting from the time when the addition of the aqueous solution of alkali phosphate and the calcium hydroxide slurry is completed) is, for example, 10 to 180 minutes, preferably 20 to 120 minutes, more preferably 40 to 90 minutes, and even more preferably 50 to 70 minutes.

[0041] The particles of the present invention produced by the above steps may be subjected to a purification treatment, such as filtration or washing, if necessary. If necessary, the particles may be subjected to a drying treatment.

[0042] The particles of the present invention have a property of sealing dentinal tubules and have excellent adhesion within the dentinal tubules. Therefore, an oral composition containing the particles of the present invention (i.e., the oral composition of the present invention) can be preferably used for preventing or improving dentin hypersensitivity.

[0043] The oral composition of the present invention can be manufactured by a conventional method, and can be used as, for example, a pharmaceutical product, a quasi-drug product, or a cosmetic product. The form of the oral composition of the present invention is not particularly limited, but can be made into, for example, an ointment, a paste, a gel, a liquid, a spray, a mouthwash, a liquid dentifrice, a toothpaste, a coating agent, or the like (formulation) according to a conventional method. Among them, mouthwash, liquid dentifrice, toothpaste, a paste, a liquid, a spray, a gel, or a coating agent is preferable, and toothpaste, a paste, or a gel is more preferable. In addition, it is preferable to brush the oral composition by placing it on a toothbrush or applying the oral composition to the oral cavity, and therefore, it is preferable that the oral composition is in a form suitable for brushing. By brushing, the particles of the present invention can be pushed into the cavity of the dentin of the tooth, and the effect of the present invention can be obtained more preferably.

[0044] In addition to the particles of the present invention, the oral composition of the present invention may further contain any optional components that can be incorporated into the oral composition, either alone or in combination of two or more, as long as the effects of the present invention are not impaired.

[0045] For example, the surfactant may be a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant.Specifically, examples of the nonionic surfactant include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers having a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group having 13 to 15 carbon atoms; polyoxyethylene alkylphenyl ethers having a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan; and the like.Examples of the anionic surfactant include sulfate ester salts such as sodium lauryl sulfate and polyoxyethylene lauryl ether sodium sulfate; sulfosuccinate salts such as sodium lauryl sulfosuccinate and polyoxyethylene lauryl ether sodium sulfosuccinate; acylamino acid salts such as sodium cocoyl sarcosine and sodium lauroyl methyl alanine; and sodium cocoyl methyl taurine. Examples of amphoteric surfactants include acetate betaine type surfactants such as lauryl dimethylamino acetate betaine and coconut oil fatty acid amidopropyl dimethylamino acetate betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; and amino acid type surfactants such as N-lauryl diaminoethyl glycine. These surfactants can be blended alone or in combination of two or more. The blending amount is usually 0.1 to 5% by mass based on the total amount of the composition.

[0046] In addition, sweeteners such as saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, and p-methoxycinnamic aldehyde may be added. These may be used alone or in combination of two or more. These may be added in an amount of 0.01 to 1% by mass based on the total amount of the composition.

[0047] In addition, as the binder, for example, one or a combination of two or more of the following can be used: cellulose derivatives such as sodium carboxymethylcellulose, carboxymethylethylcellulose salts, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose; microbially produced polymers such as xanthan gum and gellan gum; natural polymers or natural rubbers such as tragacanth gum, karaya gum, gum arabic, carrageenan, and dextrin; synthetic polymers such as polyvinyl alcohol and polyvinylpyrrolidone; inorganic binders such as thickening silica and Veegum; and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride.

[0048] Furthermore, as a wetting agent, sorbitol, glycerin, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, etc. can be blended alone or in combination of two or more kinds.

[0049] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate, phenoxyethanol, alkyldiaminoethylglycine hydrochloride, etc. can be blended alone or in combination of two or more kinds.

[0050] As colorants, legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, Green No. 3, mineral pigments such as ultramarine, enhanced ultramarine, and Prussian blue, titanium oxide, etc. may be used alone or in combination of two or more kinds.

[0051] As a pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically possible salts thereof, sodium hydroxide, etc. may be blended. These may be blended alone or in combination of two or more kinds so that the pH of the composition is in the range of 4 to 8, preferably 5 to 7. The blending amount of the pH adjuster is, for example, 0.01 to 2% by weight.

[0052] As a medicinal component, a bactericide may be blended. For example, cationic bactericides such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate, amphoteric bactericides such as dodecyldiaminoethylglycine, nonionic bactericides such as triclosan and isopropylmethylphenol, and hinokitiol may be blended. Furthermore, medicinal components other than bactericides may be blended. For example, aluminum lactate, potassium nitrate, vitamin E such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, sodium fluoride, etc. may be blended. The medicinal components may be blended alone or in combination of two or more. Among them, aluminum lactate and potassium nitrate are medicinal components for preventing dentin hypersensitivity, and are therefore particularly preferred for blending in the oral cavity composition of the present invention.

[0053] Furthermore, as a base, for example, alcohols, silicone, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase, etc. can be added alone or in combination of two or more kinds.

[0054] The above descriptions of optional components are merely examples and do not limit the optional components that can be used.

[0055] In addition, in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present invention includes all arbitrary combinations of the constituent elements described in this specification.

[0056] Furthermore, the various characteristics (properties, structures, functions, etc.) described in each embodiment of the present invention above may be combined in any way to specify the subject matter included in the present invention. In other words, the present invention includes all subject matter consisting of all combinations of the combinable characteristics described in this specification. EXAMPLES

[0057] The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

[0058] Example 1 A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a ground calcium hydroxide slurry (BET specific surface area: 6.7 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g Oxalic acid reactivity: 15 minutes 30 seconds (JP Patent Publication No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker and heated to 60°C while stirring, and maintained at this temperature until the stirring was stopped. A 10% aqueous solution of NaOH was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was stirred for another hour, then filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

[0059] The obtained hydroxyapatite particles were subjected to X-ray crystal diffraction, specific surface area measurement, particle size distribution measurement, Ca / P molar ratio measurement, and morphology observation.

[0060] Measurements were performed in the range of 2θ = 25 to 45° using an X-ray diffraction device MultiFlex (manufactured by Rigaku Corporation). The measurement conditions were as follows: target: Cu, tube voltage: 40 kV, tube current: 30 mA, sampling width: 0.02°, scan speed: 2.00° / min, divergence slit: 1.0°, scattering slit: 1.0°, receiving slit: 0.3 mm. The results are shown in Figure 1. Figure 2 also shows the X-ray diffraction pattern of hydroxyapatite (reagent HAp), a commercially available reagent product. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity ratio due to the (002) plane near 2θ = 26° was 1.1, which was clearly lower than the peak intensity ratio of 2.7 for reagent HAp. This revealed that the obtained hydroxyapatite particles were aggregates of plate-like crystals with relatively large amounts of c-planes exposed. In addition, the sum of the areas of all diffraction peaks in the range of 25°≦2θ≦35° was 100%, while the sum of the areas of all diffraction peaks in the range of 25.5°≦2θ≦26.5° and the range of 31.5°≦2θ≦32.5° was 37.2%. This is clearly lower than the 52.1% shown by the reagent HAp, and the X-ray diffraction pattern is relatively broad, which indicates low crystallinity. In addition, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 7 nm, which is clearly smaller than the 52 nm shown by the reagent HAp, and this also indicates low crystallinity.

[0061] The specific surface area of ​​the hydroxyapatite particles was measured by nitrogen gas adsorption using a fully automatic specific surface area measuring device, Macsorb HM model-1208 (manufactured by Mountec Co., Ltd.). The specific surface area was 61.9 m 2 / g.

[0062] The particle size distribution of the hydroxyapatite particles was measured by dry particle size distribution measurement using a laser diffraction particle size distribution measuring device MASTER SIZER 3000. As a result, the median diameter (d50) was 3.76 μm.

[0063] The Ca / P molar ratio of the hydroxyapatite particles was calculated from the Ca and P contents measured by inductively coupled plasma optical emission spectrometry using an iCAP 6000 ICP-OES (manufactured by ThermoFisher). As a result, the Ca / P molar ratio was calculated to be 1.33.

[0064] The shape of the hydroxyapatite particles was observed using a scanning electron microscope (manufactured by JEOL Ltd.: hereinafter referred to as SEM). The results are shown in Figure 3. The results showed that the obtained hydroxyapatite particles were aggregates of plate-like crystals.

[0065] Example 2 A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a ground calcium hydroxide slurry (BET specific surface area: 7.9 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g Oxalic acid reactivity: 12 minutes 30 seconds (JP Patent Publication No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker and heated to 60°C while stirring, and maintained at this temperature until the stirring was stopped. A 10% aqueous solution of NaOH was added to adjust the pH to 6.0. Calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed and the mixture was stirred for another hour, it was filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

[0066] The obtained hydroxyapatite particles were subjected to X-ray crystal diffraction, specific surface area measurement, and shape observation in the same manner as in Example 1.

[0067] The results of X-ray crystal diffraction are shown in FIG. 4. The ratio of the diffraction peak intensity due to the (211) plane near 2θ=32° to the diffraction peak intensity due to the (002) plane near 2θ=26° was 1.1, which was the same value as in Example 1. In addition, the sum of the areas of all diffraction peaks in the range of 25°≦2θ≦35° was 100%, and the sum of the areas of all diffraction peaks in the range of 25.5°≦2θ≦26.5° and the sum of the areas of all diffraction peaks in the range of 31.5°≦2θ≦32.5° was 38.6%. In addition, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 7 nm.

[0068] The specific surface area is 75.4 m 2 / g.

[0069] The results of the shape observation are shown in Figure 5. As in Example 1, it was confirmed that the particles were aggregates of plate-like crystals.

[0070] Example 3 A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a ground calcium hydroxide slurry (BET specific surface area 7.9 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g Oxalic acid reactivity: 12 minutes 30 seconds (JP Patent Publication No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker and heated to 40°C while stirring, and maintained at this temperature until the stirring was stopped. A 10% aqueous solution of NaOH was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over a period of 50 minutes. After the addition was completed, the mixture was stirred for another hour, then filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

[0071] The obtained hydroxyapatite particles were subjected to X-ray crystal diffraction, specific surface area measurement, and shape observation in the same manner as in Example 1.

[0072] The results of X-ray crystal diffraction are shown in FIG. 6. The ratio of the diffraction peak intensity due to the (211) plane near 2θ=32° to the diffraction peak intensity due to the (002) plane near 2θ=26° was 1.2, which was the same value as in Example 1. In addition, the sum of the areas of all diffraction peaks in the range of 25°≦2θ≦35° was 100%, and the sum of the areas of all diffraction peaks in the range of 25.5°≦2θ≦26.5° and the sum of the areas of all diffraction peaks in the range of 31.5°≦2θ≦32.5° was 36.0%. In addition, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 6 nm.

[0073] The specific surface area is 81.5 m 2 / g.

[0074] The results of the shape observation are shown in Figure 7. As in Example 1, it was confirmed that the obtained hydroxyapatite particles were aggregates of plate-like crystals.

[0075] Example 4 A 10.7% by mass anhydrous aqueous solution of sodium dihydrogen phosphate and a ground calcium hydroxide slurry (BET specific surface area 7.9 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g Oxalic acid reactivity: 12 minutes 30 seconds (JP Patent Publication No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate anhydride was placed in a stainless steel beaker and heated to 80°C while stirring. The pH was left at 4.2 without adjustment. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was stirred for another hour, filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

[0076] The obtained hydroxyapatite particles were subjected to X-ray crystal diffraction, specific surface area measurement, and shape observation in the same manner as in Example 1.

[0077] The results of X-ray crystal diffraction are shown in FIG. 8. The ratio of the diffraction peak intensity due to the (211) plane near 2θ=32° to the diffraction peak intensity due to the (002) plane near 2θ=26° was 1.4, which was the same value as in Example 1. In addition, the sum of the areas of all diffraction peaks in the range of 25°≦2θ≦35° was 100%, and the sum of the areas of all diffraction peaks in the range of 25.5°≦2θ≦26.5° and the sum of the areas of all diffraction peaks in the range of 31.5°≦2θ≦32.5° was 37.8%. In addition, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 9 nm.

[0078] The specific surface area is 163.4 m 2 / g.

[0079] The results of the shape observation are shown in Figure 9. As in Example 1, it was confirmed that the obtained hydroxyapatite particles were aggregates of plate-like crystals.

[0080] Example 5 A 10.7% by mass anhydrous aqueous solution of sodium dihydrogen phosphate and a ground calcium hydroxide slurry (BET specific surface area 7.9 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g Oxalic acid reactivity: 12 minutes 30 seconds (JP Patent Publication No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate anhydride was placed in a stainless steel beaker and heated to 60°C while stirring. The pH was left at 4.2 without adjustment. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was stirred for another hour, filtered, washed with water, and dried at 80°C to obtain hydroxyapatite microparticles (powder).

[0081] The obtained hydroxyapatite microparticles were subjected to X-ray crystal diffraction, specific surface area measurement, and shape observation in the same manner as in Example 1.

[0082] The results of X-ray crystal diffraction are shown in FIG. 10. The ratio of the diffraction peak intensity due to the (211) plane near 2θ=32° to the diffraction peak intensity due to the (002) plane near 2θ=26° was 1.1, which was the same value as in Example 1. In addition, the sum of the areas of all diffraction peaks in the range of 25°≦2θ≦35° was 100%, and the sum of the areas of all diffraction peaks in the range of 25.5°≦2θ≦26.5° and the sum of the areas of all diffraction peaks in the range of 31.5°≦2θ≦32.5° was 31.6%. In addition, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 7 nm.

[0083] The specific surface area is 94.7m 2 / g.

[0084] The results of the shape observation are shown in Fig. 11. As in Example 1, it was confirmed that the particles were aggregates of plate-like fine particles.

[0085] Comparative Example 1 A 10.7% by mass anhydrous aqueous solution of sodium dihydrogen phosphate and a ground calcium hydroxide slurry (BET specific surface area 7.9 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g Oxalic acid reactivity: 12 minutes 30 seconds (JP Patent Publication No. 2017-036176) was prepared. The calcium hydroxide slurry was placed in a stainless steel beaker and heated to 40°C while stirring. An aqueous solution of anhydrous sodium dihydrogen phosphate (pH: 4.2) was added thereto over 30 minutes. After the addition was completed, the mixture was stirred for another hour, filtered, washed with water, and dried at 80°C to obtain hydroxyapatite (hydroxyapatite particles (powder)).

[0086] The obtained hydroxyapatite particles were subjected to X-ray crystal diffraction, specific surface area measurement, and shape observation in the same manner as in Example 1.

[0087] The results of X-ray crystal diffraction are shown in Figure 12. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity due to the (002) plane near 2θ = 26° was 1.7, which was clearly higher than that of Example 1. In addition, the diffraction peak due to the (300) plane near 2θ = 33° appeared separately.

[0088] The specific surface area is 50.9 m 2 / g.

[0089] The results of the shape observation are shown in Figure 13. It was confirmed that the obtained hydroxyapatite particles were formed by agglomeration of spindle-shaped crystals.

[0090] Comparative Example 2 A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a ground calcium hydroxide slurry with a solid content of 8.6% by mass (JP Patent Publication No. 2017-036176) were prepared so that the Ca / P molar ratio was 0.5. The aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker and heated to 60°C while stirring, and maintained at this temperature until the stirring was stopped. The pH was left at 4.2 without adjustment. The calcium hydroxide slurry was added thereto over a period of 45 minutes. After the addition was completed, the mixture was stirred for another hour, then filtered, washed with water, and dried at 80°C to obtain a sample.

[0091] The obtained sample was subjected to X-ray crystal diffraction and shape observation in the same manner as in Example 1.

[0092] The results of X-ray crystal diffraction are shown in Figure 14. In addition to the diffraction peaks of hydroxyapatite, diffraction peaks of other substances were confirmed. The peaks indicated by black circles in the figure are the diffraction peaks of monetite, a calcium phosphate that is easily formed under acidic conditions.

[0093] The results of the morphology observation are shown in Figure 15. Large plate-like particles of monetite were confirmed.

[0094] Comparative Example 3 A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a high-purity calcium hydroxide slurry (BET specific surface area: 2.4 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g, oxalic acid reactivity: 25 seconds (JP Patent Publication No. 2011-126772) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker and heated to 60°C with stirring, and maintained at this temperature until the stirring was stopped. A 10% aqueous solution of NaOH was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed and the mixture was stirred for another hour, it was filtered, washed with water, and dried at 80°C to obtain a sample.

[0095] The obtained sample was subjected to X-ray crystal diffraction in the same manner as in Example 1.

[0096] The results of X-ray crystal diffraction are shown in Figure 16. In addition to the diffraction peaks of hydroxyapatite, diffraction peaks of calcium hydroxide were confirmed near 2θ = 28° and 34°.

[0097] The results of the shape observation are shown in Figure 17. Large plate-like particles of calcium hydroxide were confirmed. The difference from Example 1 was thought to be due to the physical properties of the raw material calcium hydroxide.

[0098] Comparative Example 4 A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a ground calcium hydroxide slurry (BET specific surface area 7.9 m) with a solid content of 8.6% by mass were mixed so that the Ca / P molar ratio was 0.5. 2 / g Oxalic acid reactivity: 12 minutes 30 seconds (JP Patent Publication No. 2017-036176) was prepared. The sodium dihydrogen phosphate dihydrate aqueous solution was placed in a stainless steel beaker, and a 10% NaOH aqueous solution was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over 50 minutes. After the addition was completed, the mixture was stirred for another hour, then stopped and allowed to stand at room temperature for 9 days. It was then filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

[0099] The obtained hydroxyapatite particles were subjected to X-ray crystal diffraction and shape observation in the same manner as in Example 1.

[0100] The results of X-ray crystal diffraction are shown in Figure 18. The ratio of the diffraction peak intensity due to the (211) plane near 2θ=32° to the diffraction peak intensity due to the (002) plane near 2θ=26° was 1.3.

[0101] The results of the shape observation are shown in Figure 19. It was confirmed that the particles were shaped like aggregates of minute spindle-shaped particles.

[0102] Comparative Example 5 A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a ground calcium hydroxide slurry with a solid content of 8.6% by mass (JP Patent Publication No. 2017-036176) were prepared so that the Ca / P molar ratio was 0.5. The aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker and heated to 80°C while stirring, and maintained at this temperature until the stirring was stopped. The pH was left at 4.2 without adjustment. The calcium hydroxide slurry was added thereto over a period of 50 minutes. After the addition was completed, the mixture was stirred for another hour, then filtered, washed with water, and dried at 80°C to obtain a sample.

[0103] The obtained sample was subjected to X-ray crystal diffraction and shape observation in the same manner as in Example 1.

[0104] The results of X-ray crystal diffraction are shown in Figure 20. In addition to the diffraction peaks of hydroxyapatite, diffraction peaks of other substances were confirmed. The peaks indicated by black circles in the figure are the diffraction peaks of monetite, a calcium phosphate that is easily formed under acidic conditions.

[0105] The results of the morphology observation are shown in Figure 21. Large plate-like particles of monetite were confirmed.

[0106] Test Example 1. Crystallinity Change Confirmation Test [Test Purpose] To evaluate the reactivity of hydroxyapatite particles in the oral cavity, the change in crystallinity before and after immersion in artificial saliva was measured using a powder X-ray diffractometer.

[0107] [Test Method] 0.5 g of hydroxyapatite particles obtained in the same manner as in Example 1 was immersed in 200 mL of artificial saliva (CaCl2: 1.5 mM, KH2PO4: 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH)) for 7 days. The powder separated by suction filtration was measured using a powder X-ray diffractometer to observe the change in crystallinity before and after immersion in artificial saliva.

[0108] [Measurement conditions] -Model used: Miniflex II (Rigaku Corporation) ·Starting angle: 20° End angle: 40° Sampling width: 0.02° Scan speed: 4.0° / min Target: Cu, Tube voltage: 30kV ·Tube current: 15mA Divergence slit: 1.25° Scattering slit: 8.0mm Receiving slit: 0.3mm.

[0109] The results are shown in Figure 22. It was confirmed that immersion in artificial saliva improved crystallinity (increased peak sharpness, and broad, hidden peaks appeared). This confirmed that the hydroxyapatite particles of the present invention are particles that change (have reactivity) in the oral cavity.

[0110] When a similar study was carried out using known hydroxyapatite particles instead of the hydroxyapatite particles obtained in the same manner as in Example 1, the peak did not change at all before and after immersion in artificial saliva, and the crystallinity did not change.

[0111] Test Example 2. Dentinal tubule occlusion test of hydroxyapatite particles [Test Purpose] To evaluate the ability of hydroxyapatite particles to seal dentinal tubules, bovine dentin surfaces were brushed with a solution of hydroxyapatite particles, and the degree of seal of dentinal tubules was examined by scanning electron microscopy (SEM).

[0112] [Test Method] Preparation of dentin block (sample) 1. Dentin from the root surface of an extracted bovine tooth was cut into pieces measuring 5 x 5 mm. 2. The cut tooth pieces were embedded in resin (polymethyl methacrylate) to create blocks, which were then polished using waterproof abrasive paper to bring out the surface. 3. The dentin block was immersed in a 5% w / w EDTA aqueous solution (pH 7.0) for 2 minutes. 4. Sonicate in distilled water for 5 minutes.

[0113] Preparation of hydroxyapatite particle solution 5. Hydroxyapatite particles (0.3 g) obtained in the same manner as in Example 1 were suspended in 39.7 g of a viscous diluent to obtain hydroxyapatite particles. The viscous diluent was an aqueous solution containing 0.5 w / w% sodium carboxymethylcellulose and 10 w / w% glycerin.

[0114] Brushing process 6. The dentin block was brushed with a toothbrush (GUM #211) in the hydroxyapatite particle solution (40 g) for 30 seconds (stroke: 150 rpm, load: 160 g). 7. The dentin block was rinsed with water and then immersed in artificial saliva (CaCl2: 1.5 mM, KH2PO4: 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH)) for 5 minutes. 8. The above steps 1 and 2 were repeated six times.

[0115] SEM observation 9. After the surface was subjected to deposition treatment, it was observed under an electron microscope.

[0116] [Observation and measurement conditions] {Vapor deposition processing} -Model used: MCI1000 (Hitachi High-Technologies Corporation) ·Current: 20mA Processing time: 120 seconds {SEM observation} -Model used: S-3400N (Hitachi High-Technologies Corporation) Detector: SE (secondary electron image) Applied voltage: 5kV Probe current: 50mA ·Magnification: 25000x.

[0117] The results are shown in Figure 23. It was confirmed that the dentinal tubules were blocked by brushing in the hydroxyapatite particle solution. This confirmed that the hydroxyapatite particles were particles that blocked the dentinal tubules present on the dentin surface.

[0118] Test Example 3: Adhesion test [Test Purpose] To evaluate the ability of hydroxyapatite particles to adhere within dentinal tubules, the surface of bovine dentin was brushed with a hydroxyapatite particle solution, and then water pressure was applied from the back side of the dentin. The ability of the hydroxyapatite particles to withstand the water pressure was examined using a scanning electron microscope (SEM).

[0119] [Test Method] Preparation of dentin discs (samples) 1. Dentin from the root surface of an extracted bovine tooth was cut into pieces measuring 5 x 5 mm. 2. The cut tooth pieces were polished with waterproof abrasive paper. 3. The obtained dentin disk was immersed in a 5% w / w aqueous solution of EDTA (pH 7.0) for 2 minutes. 4. Sonicate in distilled water for 5 minutes.

[0120] Preparation of hydroxyapatite particle solution 5. Hydroxyapatite particle liquid was obtained by suspending 1 g of hydroxyapatite particles obtained in the same manner as in Example 1 in 39 g of a viscous diluent. The viscous diluent was an aqueous solution containing 0.5 w / w% sodium carboxymethylcellulose and 10 w / w% glycerin.

[0121] Brushing process 6. The dentin disk was brushed with a toothbrush (GUM #211) in the hydroxyapatite particle solution (40 g) for 30 seconds (stroke: 150 rpm, load: 160 g). 7. After rinsing the disk with water, it was immersed in artificial saliva (CaCl2: 1.5 mM, KH2PO4: 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH)) for 5 minutes. 8. The above steps 1 and 2 were repeated six times. 9. Immersed in artificial saliva for 7 days.

[0122] Water Pressure Treatment 10. After brushing, the dentin disks were pressurized at 0.1 MPa for 30 minutes using an apparatus based on the report by Pashley et al. (Pashley DH, Galloway SE. The effects of oxalate treatment on the smear layer of ground surfaces of human dentin. Arch Oral Biol 1983; 30: 731-737.).

[0123] SEM observation 11. After the surface was subjected to deposition treatment, it was observed under an electron microscope.

[0124] [Observation and measurement conditions] {Vapor deposition processing} -Model used: MCI1000 (Hitachi High-Technologies Corporation) ·Current: 20mA Processing time: 120 seconds {SEM observation} -Model used: S-3400N (Hitachi High-Technologies Corporation) Detector: SE (secondary electron image) Applied voltage: 5kV Probe current: 50mA ·Magnification: 25000x.

[0125] The results are shown in Figure 24. It was confirmed that the dentinal tubules remained sealed even after the water pressure treatment. This confirmed that the hydroxyapatite particles were fixed inside the dentinal tubules and maintained a sealed state.

[0126] Test Example 4. Dentinal tubule occlusion test of toothpaste [Test Purpose] To confirm the ability of toothpaste formulations containing the materials to seal dentinal tubules, bovine dentin surfaces were brushed with the material solutions, and the degree of sealing of dentinal tubules was examined using a scanning electron microscope (SEM).

[0127] [Test Method] Preparation of dentin block (sample) 1. Dentin from the root surface of an extracted bovine tooth was cut into pieces measuring 5 x 5 mm. 2. The cut tooth pieces were embedded in resin (polymethyl methacrylate) to create blocks, which were then polished using waterproof abrasive paper to bring out the surface. 3. The dentin block was immersed in a 5 w / w% EDTA aqueous solution (pH 7.0) for 2 minutes. 4. Sonicate in distilled water for 5 minutes.

[0128] Preparation of Dentifrice Solutions 5. 10 g of a dentifrice containing 3 w / w% of the hydroxyapatite particles obtained in the same manner as in Example 1 was prepared by a conventional method. The composition of the dentifrice is shown in Table 1 below. In the following, the unit of "%" for the amount of the blend in the table indicates % by mass.

[0129] [Table 1]

[0130] Brushing process 6. 10 g of the dentifrice was diluted 4 times with distilled water to obtain a dentifrice solution. In the dentifrice solution (40 g), the dentin block was brushed with a toothbrush (GUM #211) for 30 seconds (stroke: 150 rpm, load: 160 g). 7. The dentin block was rinsed with water and then immersed in artificial saliva (CaCl2: 1.5 mM, KH2PO4: 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH)) for 5 minutes. 8. The above steps 1 and 2 were repeated six times.

[0131] SEM observation 9. After the surface was subjected to deposition treatment, it was observed under an electron microscope.

[0132] [Observation and measurement conditions] {Vapor deposition processing} -Model used: MCI1000 (Hitachi High-Technologies Corporation) ·Current: 20mA Processing time: 120 seconds {SEM observation} -Model used: S-3400N (Hitachi High-Technologies Corporation) Detector: SE (secondary electron image) Applied voltage: 5 kV Probe current 50mA ·Magnification: 25000x

[0133] The results are shown in Figure 25. It was confirmed that the dentinal tubules were sealed by brushing in a dentifrice solution containing hydroxyapatite particles. This confirmed that the dentifrice containing the hydroxyapatite particles is highly effective in sealing the dentinal tubules.

[0134] Test Example 5. Dentinal tubule occlusion test when gel preparation is applied with a soft pick [Test Purpose] To confirm the ability of a gel formulation containing hydroxyapatite particles to seal dentinal tubules, the gel formulation was applied to the surface of bovine dentin using a soft pick (a rubber interdental brush), and the degree of sealing of the dentinal tubules was examined using a scanning electron microscope (SEM).

[0135] [Test Method] Preparation of dentin block (sample) 1. Dentin from the root surface of an extracted bovine tooth was cut into pieces measuring 5 x 5 mm. 2. The cut tooth pieces were embedded in resin (polymethyl methacrylate) to create blocks, which were then polished using waterproof abrasive paper to bring out the surface. 3. The dentin block was immersed in a 5 w / w% EDTA aqueous solution (pH 7.0) for 2 minutes. 4. Sonicate in distilled water for 5 minutes. 5. The two dentin blocks were fixed with tape so that their dentin surfaces faced each other with a gap of 1.1 mm between them to create a pseudo interdental space.

[0136] Coating Treatment 6. The gel preparation containing (or not containing) hydroxyapatite particles obtained in the same manner as in Example 1 was placed on the brush part of a soft pick (Gum Soft Pick Curved Type: Sunstar Corporation), and the soft pick was inserted into the gap and slid back and forth five times. The composition of the gel preparation is shown in Table 2 below. 7. The dentin block was rinsed with water.

[0137] [Table 2]

[0138] SEM observation 8. After the surface was subjected to deposition treatment, it was observed under an electron microscope.

[0139] [Observation and measurement conditions] {Vapor deposition processing} -Model used: MCI1000 (Hitachi High-Technologies Corporation) ·Current: 20mA Processing time: 120 seconds {SEM observation} -Model used: S-3400N (Hitachi High-Technologies Corporation) Detector: SE (secondary electron image) Applied voltage: 5 kV Probe current 50mA ·Magnification: 25000x

[0140] The results are shown in Figure 26. It was confirmed that the dentinal tubules were sealed by applying the gel preparation containing hydroxyapatite particles using a soft pick.

[0141] Test Example 6. Clinical trial of gel formulation [Test Purpose] The clinical effect of a gel preparation containing hydroxyapatite particles on anti-hypersensitivity was examined. In this examination, hydroxyapatite particles obtained in the same manner as in Example 1 were used as the hydroxyapatite particles.

[0142] [Study design] Three formulations were compared: (i) a gel formulation containing hydroxyapatite particles, aluminum lactate, and potassium nitrate (HAp+Al+K), (ii) a gel formulation containing aluminum lactate and potassium nitrate (Al+K), and (iii) a gel formulation containing potassium nitrate (K). The compositions of these gel formulations are shown in Table 3 below.

[0143] [Table 3]

[0144] Twenty subjects were asked to use each gel formulation, and the degree of abrasion pain (a probe was placed on the exposed root surface and scraped horizontally) was recorded on a VAS scale 1, 2, or 4 weeks after use. The VAS scale is a visual scale in which the patient is shown a 10 cm long black line (the left end is "no pain at all" and the right end is "most painful / strong pain") to indicate the current level of pain. The flow of the study is shown in Figure 27. In Figure 27, "dentin hypersensitivity care set (gel formulation (test product))" refers to the gel formulations (i) to (iii) above, and "dentin hypersensitivity care set (gel formulation (placebo product))" refers to the gel formulation (iii) above without potassium nitrate.

[0145] [How to use the test sample] The subjects were instructed to use the gel preparation (test product) twice a day (morning and evening) (no restrictions were placed on when to use the gel preparation after waking up, after meals, or before going to bed, but rather on their own oral hygiene habits). Specifically, they first brushed their teeth with a designated toothbrush (Gum Pros Dental Brush #3C: Sunstar Co., Ltd.) and dentifrice (Coop Non-Foam Toothpaste N), then rinsed their mouths with about 10 ml of water for 20 seconds (no restrictions were placed on brushing time), and then used the gel preparation. Specifically, the gel preparation was applied to the test site with a tuft brush (Butler Single Tuft Brush #01F: Sunstar Co., Ltd.) at about 0.04 g (about the size of a grain of rice) of the gel preparation (test product) for each test tooth, and the test site and both adjacent teeth were brushed for at least 5 seconds per tooth. If it was possible to insert a designated interdental cleaner (Gum Soft Pick Curved Type: Sunstar Corporation) between the test site and both adjacent teeth, the interdental cleaner was inserted from the cheek side into the gap between the test site and both adjacent teeth and moved back and forth five times. After using the gel preparation (test product), the subjects were asked to rinse their mouths with approximately 10 ml of water for 20 seconds.

[0146] The results of evaluating the degree of abrasion pain using the VAS scale are shown in Figure 28. The group using the hydroxyapatite-containing preparation showed a significant improvement in abrasion pain one week after use compared to the group using no preparation. This shows that the hydroxyapatite-containing preparation is effective in suppressing hypersensitivity symptoms early when used in combination with aluminum lactate and potassium nitrate, which are known medicinal ingredients for preventing hypersensitivity.

Claims

1. An oral composition containing hydroxyapatite particles, the hydroxyapatite particles have a ratio of a diffraction peak intensity at about 2θ=32° to a diffraction peak intensity at about 2θ=26° in a powder X-ray diffraction pattern measured with CuKα characteristic X-rays of 0.8 to 1.5; The hydroxyapatite particles have a Ca / P molar ratio of less than 1.67; the hydroxyapatite particles are aggregates of hydroxyapatite platelet crystals, The specific surface area of ​​the hydroxyapatite particles is 55 to 200 m ２ / g, The hydroxyapatite particles have a median diameter of 5 μm or less, and the hydroxyapatite particles have a crystallite size of 5 to 10 nm calculated from a diffraction peak due to a (130) plane around 2θ=40°, Further, the composition contains potassium nitrate and / or aluminum lactate. Oral composition.

2. The oral composition according to claim 1 , which contains potassium nitrate and aluminum lactate.

3. 3. The oral composition according to claim 1, wherein the hydroxyapatite particles have a ratio of a diffraction peak intensity at about 2θ = 34° to a diffraction peak intensity at about 2θ = 32° in a powder X-ray diffraction pattern measured using CuKα characteristic X-rays of 1 or less.

4. The oral composition according to any one of claims 1 to 3, which is for preventing or improving hypersensitivity.

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