Oral composition

Abstract

To provide a composition for the oral cavity containing particles which have a property of blocking dentinal tubules with an excellent property of sticking into the dentinal tubules.SOLUTION: The composition for the oral cavity contains hydroxyapatite particles. In the hydroxyapatite particles, the ratio of the diffraction peak intensity near 2θ=32° to the diffraction peak intensity near 2θ=26°in a powder X-ray diffraction pattern measured with the CuKα characteristic X-ray is from 0.8 to 1.6.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to oral compositions and the like, and more particularly to oral compositions containing hydroxyapatite particles. The contents of all documents described in this specification (especially, Japanese Patent Application Laid-Open No. 2017-036176) are incorporated herein by reference.

Background Art

[0002] Tooth hypersensitivity is caused by the exposure of dentin in teeth due to physical abrasion such as brushing or chemical abrasion by acid. When dentin is exposed, external stimuli stimulate nerves in the dentinal tubules in the dentin, making pain more likely to occur.

[0003] For tooth hypersensitivity, for example, the dentinal tubules are blocked with particles such as fluoride and aluminum salts (as an example, Patent Document 1) to suppress the reach of external stimuli to nerves. However, many of the conventional methods have insufficient adhesion after blocking and problems with the sustainability of the effect.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object is to provide particles having sealing properties for dentinal tubules and excellent adhesion within the dentinal tubules.

Means for Solving the Problems

[0006] As a result of intensive research in view of the above problems, the inventors of the present invention have found that specific hydroxyapatite particles (hydroxyapatite particles having a ratio of the diffraction peak intensity near 2θ = 32° to the diffraction peak intensity near 2θ = 26° in the X-ray diffraction pattern of 0.8 to 1.6) can solve the above problems. And further studies were carried out based on this finding.

[0007] This disclosure includes, for example, the subject matter described in the following items. Item 1. Hydroxyapatite particles, Potassium nitrate, Polyoxyethylene hydrogenated castor oil, and At least one selected from the group consisting of xanthan gum and alginic acid or a salt thereof, containing, wherein the ratio of the diffraction peak intensity near 2θ = 32° to the diffraction peak intensity near 2θ = 26° in the powder X-ray diffraction pattern measured by CuKα characteristic X-rays of the hydroxyapatite particles is 0.8 to 1.6, An oral composition. Item 2. The oral composition according to Item 1, wherein the Ca / P molar ratio of the hydroxyapatite particles is less than 1.67. Item 3. The oral composition according to Item 1 or 2, wherein the median diameter of the hydroxyapatite particles is 5 μm or less. Item 4. The oral composition according to any one of Items 1 to 3, wherein the specific surface area of the hydroxyapatite particles is 30 to 200 m 2 / g. Item 5. The oral composition according to any one of Items 1 to 4, wherein the ratio of the diffraction peak intensity near 2θ = 34° to the diffraction peak intensity near 2θ = 32° in the powder X-ray diffraction pattern measured by CuKα characteristic X-rays of the hydroxyapatite particles is 1 or less. Item 6. The hydroxyapatite particles are aggregates of hydroxyapatite plate-like crystals, The oral composition according to any one of Items 1 to 5. Item 7. Furthermore, the oral composition according to any one of Items 1 to 6, which contains aluminum lactate. Item 8. The oral composition according to any one of Items 1 to 7, which is for preventing or improving tooth sensitivity.

Advantages of the Invention

[0008] An oral composition having occlusivity of dentinal tubules and excellent adhesiveness within dentinal tubules is provided. Furthermore, after repeated studies to obtain an oral composition containing hydroxyapatite particles and potassium nitrate and excellent in all of drawability, foaming property, and dispersibility, it has been found that an oral composition excellent in all of these effects can be obtained by using potassium nitrate, a specific surfactant, a specific binder, and specific hydroxyapatite particles.

Brief Description of the Drawings

[0009]

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Mode for Carrying Out the Invention

[0010] Hereinafter, each embodiment included in the present disclosure will be described in more detail. The present disclosure preferably includes oral compositions, particularly oral compositions containing specific hydroxyapatite particles, but is not limited thereto, and the present disclosure includes all that are disclosed in this specification and can be recognized by those skilled in the art.

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

[0012] The specific hydroxyapatite particles are hydroxyapatite particles in which the ratio of the diffraction peak intensity near 2θ = 32° to the diffraction peak intensity near 2θ = 26° in the X-ray diffraction pattern is 0.8 to 1.6. In this specification, the hydroxyapatite particles may be referred to as "the particles of the present disclosure".

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

[0014] The diffraction peak near 2θ = 32° is the peak of hydroxyapatite, specifically, the diffraction peak at 2θ = 31.5 - 32.5°, preferably the diffraction peak at 2θ = 31.8 - 32.2°. When there are multiple diffraction peaks near 2θ = 32°, it means the diffraction peak 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. The measurement conditions are any of the following. Measurement condition 1 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. Measurement condition 2 Target: Cu, tube voltage 40 kV, tube current: 15 mA, sampling width: 0.02°, scan speed: 2.00° / min, divergence slit: 1.25°, scattering slit: 1.25°, receiving slit: 0.3 mm.

[0016] As the measuring device, for example, an X-ray diffractometer MultiFlex 2kW (manufactured by Rigaku Corporation), or an X-ray diffractometer Miniflex500 (manufactured by Rigaku Corporation) can be used. When using the former, it is preferable to measure under the conditions of Measurement condition 1, and when using the latter, it is preferable to measure under the conditions of Measurement condition 2.

[0017] The particles of the present disclosure have a ratio (32° / 26°) of the diffraction peak intensity near 2θ = 32° to the diffraction peak intensity near 2θ = 26° of 0.8 to 1.6. The upper or lower limit of the peak intensity ratio may be, for example, 0.85, 0.9, 0.95, 1.0, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, or 1.55. For example, preferably it is 0.8 to 1.5, more preferably 0.9 to 1.3, still more preferably 1.0 to 1.25, even more preferably 1.05 to 1.2, and particularly preferably 1.05 to 1.15. Note that the upper limit of the peak intensity ratio may be 1.59 or 1.58.

[0018] It is preferable that each particle of the present disclosure itself is an aggregate of hydroxyapatite plate-like crystals. The shape of the plate-like crystals constituting the particles of the present disclosure is not particularly limited, and examples include circular, polygonal (particularly hexagonal), a shape close to rod-like, or a shape combining these. Further, the plate-like crystals may be in any state, either a state where the surface is bent or a state where the surface maintains a planar structure without being bent. Usually, plate-like hydroxyapatite crystals have a structure called a hexagonal crystal with the top surface of the plate as the c-plane and the side surface as the a-plane. Further, when the particles are formed by a plurality of crystals, the crystals are called crystallites.

[0019] The particles of the present disclosure are particles containing hydroxyapatite as a main component, and are preferably particles consisting essentially of hydroxyapatite. In the X-ray diffraction pattern of the particles of the present disclosure, even when other substances (such as monetite, etc.) are contained, their peaks are not observed separately or their peak intensities are relatively low. For this reason, the particles of the present disclosure are distinguished from particles with high peak intensities of these peaks.

[0020] Although not wishing to be limited, it is considered that the particles of the present disclosure exhibit excellent sealing properties of the dentinal tubules and excellent adhesion within the dentinal tubules due to having a shape and structure represented by a specific X-ray diffraction pattern and being composed of aggregated plate-like particles.

[0021] The particles of the present disclosure preferably have a ratio (34° / 32°) of the diffraction peak intensity near 2θ = 34° to the diffraction peak intensity near 2θ = 32° in the X-ray diffraction pattern of 1 or less. The diffraction peak near 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 near 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, still more preferably 0.3 to 0.8, even more preferably 0.4 to 0.7, and particularly preferably 0.4 to 0.6.

[0022] The particles of the present disclosure preferably have a total sum of the areas of all diffraction peaks within the range of 25.5° ≤ 2θ ≤ 26.5° and the total sum of the areas of all diffraction peaks within the range of 31.5° ≤ 2θ ≤ 32.5° of 30 to 45% with respect to 100% of the total sum of the areas of all diffraction peaks within the range of 25° ≤ 2θ ≤ 35°. This value is preferably 33 to 42%, more preferably 35 to 40%. Further, for the particles of the present disclosure, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° is preferably 4 to 12 nm, more preferably 5 to 10 nm. Although not wishing to be bound by a limiting interpretation, it is considered that due to relatively low crystallinity, the crystal growth property in the canal after canal obturation is further enhanced, thereby further improving the adhesion property in the canal. It is considered that it can be improved.

[0023] The Ca / P molar ratio of the particles of the present disclosure is not particularly limited as long as it is a value that hydroxyapatite can take. Although not wishing to be bound by a limiting interpretation, in the particles of the present disclosure, it is also considered that a part of calcium is substituted with other elements (such as sodium), and for this reason, the Ca / P molar ratio can be a relatively low value. From this perspective, the Ca / P molar ratio of the particles of the present disclosure is preferably less than 1.67, more preferably 1.65 or less or 1.60 or less, still more preferably 1.55 or less or 1.50 or less, and even more preferably 1.45 or less or 1.40 or less. The lower limit of the Ca / P molar ratio of the particles of the present disclosure is not particularly limited and can 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 disclosure by inductively coupled plasma optical emission spectrometry.

[0024] The median diameter (d50) of the particles of the present disclosure is not particularly limited, but from the viewpoints of dentinal tubule sealing property, adhesiveness, etc., it is preferably 5 μm or less, more preferably 4.5 μm or less. The lower limit of the median diameter is not particularly limited, and examples include 1 μm or more, 2 μm or more, or 3 μm or more. More specifically, for example, 1 to 5 μm can be mentioned. The median diameter is a value measured by the laser diffraction / scattering method. More specifically, it is a value measured by dry particle size distribution measurement using a laser diffraction type particle size distribution measuring device.

[0025] The specific surface area of the particles of the present disclosure is not particularly limited, but from the viewpoints of dentinal tubule sealing property, adhesiveness, etc., for example, 30 m 2 / g or more, preferably 40 m 2 / g or more, more preferably 50 m 2 / g or more, still more preferably 55 m 2 / g or more. The upper limit of the specific surface area is not particularly limited, and examples include 200 m 2 / g, 170 m 2 / g, 150 m 2 / g, 120 m 2 / g, 100 m 2 / g, or 90 m 2It is / g. The specific surface area is a value measured by the nitrogen gas adsorption method.

[0026] The particles of the present disclosure preferably react with saliva to improve crystallinity. The improvement in crystallinity here means that in the powder X-ray diffraction pattern measured by CuKα characteristic X-rays, the sharpness of at least one (preferably 1, 2, 3, 4, or more) peak is improved (more specifically, the diffraction intensity is improved) after the reaction with saliva compared to before. 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 carried out by immersing the particles in saliva for 7 days.

[0027] The particles of the present disclosure can be prepared, for example, by a method for producing hydroxyapatite particles including a step of mixing an aqueous solution of an alkali phosphate having a pH of 4 or more and less than 7 and a calcium hydroxide slurry and reacting them at 35 to 85°C.

[0028] The alkali phosphate is not particularly limited and includes hydrates and anhydrides. Examples of the alkali phosphate include sodium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, tetrasodium pyrophosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, tripotassium phosphate, etc. Preferred are sodium phosphate salts such as sodium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, etc., and more preferred is sodium dihydrogen phosphate.

[0029] The concentration of the alkali phosphate in the aqueous solution of the alkali phosphate is not particularly limited and is, for example, 3 to 50% by mass. The concentration is preferably 3 to 30% by mass, more preferably 5 to 20% by mass, and still more preferably 7 to 15% by mass.

[0030] The pH of the aqueous alkali phosphate solution is preferably 4 or more and less than 7, more preferably 5 to 6.5. As described below, when the pH of the aqueous alkali phosphate solution is relatively low (for example, when it is 4 or more and less than 5), it is desirable to use the 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.

[0031] Since the calcium hydroxide slurry has oxalic acid reactivity, it is preferable that the calcium hydroxide slurry is a slurry of calcium hydroxide having a specific reactivity with respect to oxalic acid.

[0032] The reactivity with respect to oxalic acid can be represented, for example, by the following definition: Oxalic acid reactivity: The time (minutes) until the pH reaches 7.0 after adding 40 g of an aqueous oxalic acid solution having a concentration of 0.5 mol / liter maintained at 25 ± 1 ° C all at once to 50 g of a calcium hydroxide slurry prepared at a concentration of 5% by mass and maintained at 25 ± 1 ° C.

[0033] As the specific reactivity with respect to oxalic acid, when represented by the above definition, it is preferably 1 to 40 minutes, more preferably 5 to 30 minutes, and even more preferably 10 to 20 minutes.

[0034] The BET specific surface area of the calcium hydroxide slurry is preferably 5 m 2 / g or more, more preferably 6 m 2 / g or more. The upper limit of the BET specific surface area is not particularly limited, but for example, 20 m 2 / g, 15 m 2 / g, 10 m 2 / g.

[0035] Calcium hydroxide slurry with high oxalic acid reactivity (for example, having reactivity with the specific oxalic acid described above) can typically be obtained by grinding the calcium hydroxide slurry. By the grinding treatment, the oxalic acid reactivity can be further enhanced (the time defined above can be made shorter). The grinding treatment is performed, for example, using a bead mill. The conditions of the grinding treatment are not particularly limited, and for example, the conditions according to the method described in JP-A-2017-036176 can be adopted.

[0036] The calcium hydroxide slurry can be prepared, for example, by reacting quicklime (calcium oxide) obtained by firing limestone with water. For example, limestone is fired in a kiln at about 1000 °C to produce quicklime, and about 10 times the amount of hot water is added to this quicklime and stirred for 30 minutes, whereby a calcium hydroxide slurry can be prepared.

[0037] The solid content concentration of the calcium hydroxide slurry is not particularly limited, but is, for example, 1 to 30% by mass, preferably 3 to 20% by mass, more preferably 5 to 15% by mass, and still more preferably 6 to 12% by mass.

[0038] The quantitative ratio of the aqueous alkali phosphate solution and the calcium hydroxide slurry is not particularly limited as long as it is a ratio capable of producing hydroxyapatite particles. It is desirable that the quantitative ratio be adjusted so that the Ca / P molar ratio is preferably 0.3 to 0.7, more preferably 0.4 to 0.6, and still more preferably 0.45 to 0.55.

[0039] The mode of mixing the aqueous alkali phosphate solution and the calcium hydroxide slurry is not particularly limited. For example, a mode of adding the calcium hydroxide slurry to a reaction vessel containing the aqueous alkali phosphate solution (Mode 1), a mode of adding the aqueous alkali phosphate solution to a reaction vessel containing the calcium hydroxide slurry (Mode 2), a mode of simultaneously adding the aqueous alkali phosphate solution and the calcium hydroxide slurry to the reaction vessel (Mode 3), etc. can be mentioned. Among these, Mode 1 is preferred. When adding the above to the reaction vessel, usually, the liquid in the reaction vessel is being stirred.

[0040] It is desirable to carry out the above addition to the reaction vessel over a certain period of time. The time from the start of the addition to the end of the addition is, for example, 10 to 90 minutes, preferably 20 to 60 minutes, more preferably 20 to 40 minutes.

[0041] The reaction is usually carried out with stirring. The reaction temperature is 35 to 85°C. The reaction temperature is preferably 40 to 75°C, more preferably 45 to 70°C, still more preferably 50 to 70°C, and even more preferably 55 to 65°C. When the pH of the aqueous alkali phosphate solution is relatively low (for example, when the pH is 4 or more and less than 5), the reaction temperature is a relatively high temperature, for example, 65 to 85°C, preferably 70 to 85°C, more preferably 75 to 85°C. The reaction time (the time starting from when the aqueous alkali phosphate solution and the calcium hydroxide slurry are completely mixed, in the above Modes 1 to 3, the time starting from when the addition of the aqueous alkali phosphate solution 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 still more preferably 50 to 70 minutes.

[0042] Although not particularly limited, when producing the particles of the present disclosure, it is preferable to pay attention to the pH of the aqueous solution of the alkali phosphate before mixing with the calcium hydroxide slurry, and whether the alkali phosphate is a hydrate or an anhydrate. For example, when the alkali phosphate used is an anhydride, the pH of the aqueous solution of the alkali phosphate used is preferably set relatively low (for example, pH 4 or more and less than 5, preferably 4 or more and 4.5 or less). Further, for example, when the alkali phosphate used is a hydrate, the pH of the aqueous solution of the alkali phosphate used is preferably set relatively high (for example, pH 5 or more and 6.5 or less). Furthermore, it is preferable to add and mix the calcium hydroxide slurry to the aqueous solution of the alkali phosphate, rather than adding and mixing the aqueous solution of the alkali phosphate to the calcium hydroxide slurry. Furthermore, the calcium hydroxide slurry used preferably has an oxalic acid reactivity of about 5 to 30 minutes. By performing the production while paying attention to these conditions, the particles of the present disclosure having the above-described characteristics can be preferably obtained.

[0043] The particles of the present disclosure produced by the above process are, if necessary, subjected to a purification treatment. Examples of the purification treatment include a filtration treatment, a water washing treatment, and the like. Further, if necessary, it can also be subjected to a drying treatment.

[0044] The particles of the present disclosure have a sealing property of the dentinal tubules and are excellent in adhesiveness within the dentinal tubules. Therefore, the oral composition containing the particles of the present disclosure (that is, the oral composition of the present disclosure) can be preferably used particularly for the prevention or improvement of tooth hypersensitivity.

[0045] The particles of the present disclosure can be contained in the oral composition in an amount of, for example, about 0.1 to 10% by mass. The upper or lower limit of the content ratio range may be, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, or 9.5% by mass. For example, the range may be 0.2 to 9.5% by mass, 0.5 to 9% by mass, or 1 to 8% by mass.

[0046] The oral composition of the present disclosure can be produced by conventional methods and can also be used, for example, as pharmaceuticals, quasi-drugs, and cosmetics. Further, the form of the oral composition of the present disclosure is not particularly limited, but according to conventional methods, for example, it can be made into forms (dosage forms) such as ointments, pastes, pastas, gels, liquids, sprays, mouthwashes, liquid dentifrices, toothpastes, and coating agents. Among them, mouthwashes, liquid dentifrices, toothpastes, pastes, liquids, sprays, gels, and coating agents are preferred, and toothpastes, pastes, and gels are more preferred. Further, it is preferable to place the oral composition on a toothbrush or apply the oral composition into the oral cavity and then perform brushing. For this reason, it is preferably in a form suitable for brushing. By brushing, the particles of the present disclosure can be pushed into the cavities of the dental dentin, and the effect can be obtained more suitably.

[0047] In addition to the particles of the present disclosure, the oral composition of the present disclosure may further contain optional components that can be formulated in the oral composition, alone or in combination of two or more, as long as the effects are not impaired. Examples of such components include surfactants, sweeteners, wetting agents, preservatives, colorants, pH adjusters, medicinal components, cleaning agents (abrasives), bases, and the like.

[0048] The inventors further studied to obtain an oral composition containing hydroxyapatite particles and potassium nitrate and excellent in all of drawability, foaming property, and dispersibility. As a result, they found that an oral composition containing potassium nitrate, a specific surfactant, a specific binder, and specific hydroxyapatite particles is excellent in all of these effects. Among the oral compositions of the present disclosure, the oral composition containing potassium nitrate, a specific surfactant, a specific binder, and specific hydroxyapatite particles may be hereinafter referred to as a potassium nitrate-containing oral composition. The potassium nitrate-containing oral composition is not particularly limited as long as the above effects are not impaired, but potassium nitrate can be contained, for example, in an amount of about 1 to 10% by mass, 2 to 8% by mass, 3 to 7% by mass, or 4 to 6% by mass.

[0049] The specific surfactant is polyoxyethylene hydrogenated castor oil. The polyoxyethylene hydrogenated castor oil used is not particularly limited as long as the above effects are not impaired. For example, the average number of moles of ethylene oxide added to the polyoxyethylene hydrogenated castor oil is 40 to 95 (40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, or 95). For example, about 45 to 90, about 50 to 80, about 55 to 70, or about 55 to 65 is preferable. The polyoxyethylene hydrogenated castor oil can be used alone or in combination of two or more.

[0050] The polyoxyethylene hydrogenated castor oil is not particularly limited as long as the above effects are not impaired, but can be contained in the potassium nitrate-containing oral composition, for example, in an amount of about 0.1 to 5% by mass, or about 0.5 to 2% by mass.

[0051] In addition, as long as the above effects are not impaired, other surfactants may be used. For example, nonionic surfactants, anionic surfactants, amphoteric surfactants, etc. may be mentioned. Specifically, examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester, lactose fatty acid ester; fatty acid alkanolamides; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers with a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group carbon number of 13 to 15; polyoxyethylene alkyl phenyl ethers with a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group carbon number of 9; diethyl sebacate; fatty acid polyoxyethylene sorbitan, etc. Examples of anionic surfactants include sulfate esters such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; acyl amino acid salts such as sodium cocoyl sarcosinate and sodium lauroyl methyl alaninate; sodium cocoyl methyl taurine, etc. Examples of amphoteric ion surfactants include betaine type activators such as lauryldimethylaminoacetic acid betaine and coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine; imidazoline type activators such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; N - amino acid type activators such as lauryldiaminoethyl glycine, etc. These surfactants can be blended alone or in combination of two or more.

[0052] The specific binder is xanthan gum and alginic acid or its salts. Examples of salts of alginic acid include sodium salt or potassium salt. These can be used alone or in combination of two or more.

[0053] The specific binder is not particularly limited as long as the above effects are not impaired. For example, it can be incorporated into a potassium nitrate-containing oral composition at about 0.1 to 5% by mass, or about 0.5 to 3% by mass.

[0054] In addition, as long as the above effects are not impaired, other binders may be used. For example, carboxymethyl cellulose salts (such as sodium or potassium), carboxymethyl ethyl cellulose salts (such as sodium or potassium), cellulose derivatives such as hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, microbial polysaccharides such as xanthan gum and gellan gum, natural polymers or natural rubbers such as tragacanth gum, karaya gum, gum arabic, carrageenan, dextrin, synthetic polymers such as polyvinyl alcohol and polyvinyl pyrrolidone, inorganic binders such as Veegum and thickening silica, and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl] hydroxyethyl cellulose chloride are exemplified. These can be used alone or in combination of two or more. However, sodium carboxymethyl cellulose should be used with caution as it may impair the above effects.

[0055] The specific hydroxyapatite particles are the above-mentioned hydroxyapatite particles. The specific hydroxyapatite particles are not particularly limited as long as the above effects are not impaired, but can be contained in, for example, a potassium nitrate-containing oral composition at about 0.1 to 5% by mass, or about 0.5 to 3% by mass.

[0056] In addition, when other components are described in more detail, for example, as sweeteners, saccharin sodium, acesulfame potassium, stevioside, neohesperidin dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanine methyl ester, p-methoxycinnamic aldehyde, etc. can be blended. These can be used alone or in combination of two or more. Also, these can be blended in an amount of 0.01 to 1% by mass based on the total amount of the composition. can be.

[0057] In addition, 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.

[0058] In addition, as a preservative, parabens such as methylparaben, ethylparaben, propylparaben, butylparaben, etc., sodium benzoate, phenoxyethanol, alkyldiaminoethyl glycine hydrochloride, etc. can be blended alone or in combination of two or more kinds.

[0059] In addition, as a coloring agent, legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, Green No. 3, etc., mineral dyes such as ultramarine, reinforced ultramarine, dark blue, etc., titanium oxide, etc. can be blended alone or in combination of two or more kinds.

[0060] In addition, 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 can 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 exemplified by, for example, 0.01 to 2% by weight.

[0061] In addition, as a medicinal ingredient, a bactericide may be blended. For example, cationic bactericides such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, etc., amphoteric bactericides such as dodecyldiaminoethyl glycine, nonionic bactericides such as triclosan, isopropylmethylphenol, etc., hinokitiol, etc. can be mentioned. Furthermore, medicinal ingredients other than bactericides can also be blended. For example, vitamin E compounds such as aluminum lactate, dl-α-tocopherol acetate, succinic acid tocopherol, or tocopherol nicotinate, sodium fluoride, etc. may be blended. The medicinal ingredients can be blended alone or in combination of two or more kinds.

[0062] In addition, as a base, for example, alcohols, silicones, apatites, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastic base, etc. can be added alone or in combination of two or more kinds.

[0063] Note that the description of the above optional components is illustrative and does not limit the optional components that can be used.

[0064] By the way, although not particularly limited, one or more of the following oral compositions may be excluded from the oral composition containing potassium nitrate. · Dentifrices described in Table 1 below (the unit of the blending amount in the table, “%”, indicates mass%; also, hydroxyapatite in the table indicates the particles of the present disclosure).

[0065]

Table 1

[0066] · Gel agents described as “HAp5%” in Table 2 below (the unit of the blending amount in the table, “%”, indicates mass%; also, hydroxyapatite in the table indicates the particles of the present disclosure).

[0067]

Table 2

[0068] · Gel agents described as “HAp + Al + K” in Table 3 below (the unit of the blending amount in the table, “%”, indicates mass%; also, hydroxyapatite in the table indicates the particles of the present disclosure).

[0069]

Table 3

[0070] · An oral composition containing 1% by mass of sodium carboxymethylcellulose.

[0071] In addition, as used herein, the term "comprising" includes "consisting essentially of” and "consisting of." Further, the present disclosure encompasses any combination of the constituent elements described herein.

[0072] Moreover, the various characteristics (properties, structures, functions, etc.) described for each of the embodiments of the present disclosure above may be combined in any manner when identifying the subject matter encompassed by the present disclosure. That is, the present disclosure encompasses all subject matters consisting of any combination of the combinable characteristics described herein.

Example

[0073] Hereinafter, the subject matter of the present disclosure will be described in more detail based on examples, but the subject matter of the present disclosure is not limited to these examples.

[0074] Example 1 An aqueous solution of sodium dihydrogen phosphate dihydrate with a mass percentage of 10.7% and a ground calcium hydroxide slurry with a solid content concentration of 8.6% (BET specific surface area: 6.7 m 2 / g, oxalic acid reactivity: 15 minutes and 30 seconds, JP-A No. 2017-036176) were prepared so that the Ca / P molar ratio would be 0.5. The aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker and heated to 60°C with stirring and maintained until stirring stopped. A 10% NaOH aqueous solution was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over 30 minutes. After completion of the addition, stirring was continued for another 1 hour, followed by filtration, washing with water, and drying at 80°C to obtain hydroxyapatite particles (powder).

[0075] X-ray crystallography, specific surface area measurement, particle size distribution measurement, Ca / P molar ratio measurement, and shape observation were performed on the obtained hydroxyapatite particles.

[0076] Measurements were carried out in the range of 2θ = 25 to 45° using an X-ray diffractometer MultiFlex (manufactured by Rigaku Corporation). The measurement conditions are as follows. Target: Cu, tube voltage 40 kV, tube current: 30 mA, sampling width: 0.02°, sc anning speed: 2.00° / min, divergence slit: 1.0°, scattering slit: 1.0°, receiving slit: 0.3 mm. The results are shown in Figure 1. Also, the X-ray diffraction pattern of commercially available reagent hydroxyapatite (reagent HAp) is shown in Figure 2. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° is 1.1, which is clearly lower than the same peak intensity ratio of 2.7 for reagent HAp. From this, it was found that the obtained hydroxyapatite particles are aggregates of plate-like crystals with a relatively large exposure of the c-plane. Also, with respect to 100% of the total area of all diffraction peaks in the range of 25° ≤ 2θ ≤ 35°, 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 37.2%. This shows a value clearly lower than 52.1% shown by reagent HAp, and also indicates low crystallinity from the fact that the X-ray diffraction pattern is relatively broad. Also, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° is 7 nm, which is clearly smaller than 52 nm shown by reagent HAp, and this also indicates low crystallinity from this point.

[0077] The specific surface area of the hydroxyapatite particles was measured by the nitrogen gas adsorption method using a fully automatic specific surface area measuring device Macsorb HM model-1208 (manufactured by Mountech Co., Ltd.). As a result, the specific surface area was 61.9 m 2 / g.

[0078] 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.

[0079] The Ca / P molar ratio of the hydroxyapatite particles was calculated from the measured Ca and P contents determined by inductively coupled plasma optical emission spectrometry using an iCAP 6000 ICP-OES (manufactured by Thermo Fisher). As a result, the Ca / P molar ratio was 1.33.

[0080] 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 Fig. 3. From these results, it was shown that the obtained hydroxyapatite particles were aggregates of plate-like crystals.

[0081] Example 2 An aqueous solution of sodium dihydrogen phosphate dihydrate with a mass fraction of 10.7% and a ground calcium hydroxide slurry with a solid content concentration of 8.6% (BET specific surface area: 7.9 m 2 / g, oxalic acid reactivity: 12 minutes and 30 seconds, JP-A No. 2017-036176) were prepared. The aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60 °C with stirring and maintained until stirring stopped. A 10% NaOH aqueous solution was added to adjust the pH to 6.0. The calcium hydroxide slurry was added thereto over 30 minutes . After completion of the addition, stirring was continued for another 1 hour, followed by filtration, washing with water, and drying at 80 °C to obtain hydroxyapatite particles (powder).

[0082] For the obtained hydroxyapatite particles, X-ray crystallography, specific surface area measurement, and shape observation were performed in the same manner as in Example 1.

[0083] The X-ray crystal diffraction results are shown in Fig. 4. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.1, which was the same value as in Example 1. Also, with respect to 100% of the total area of all diffraction peaks within the range of 25° ≤ 2θ ≤ 35°, the sum of the areas of all diffraction peaks within the range of 25.5° ≤ 2θ ≤ 26.5° and the sum of the areas of all diffraction peaks within the range of 31.5° ≤ 2θ ≤ 32.5° was 38.6%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 7 nm.

[0084] The specific surface area was 75.4 m 2 / g.

[0085] The shape observation results are shown in Fig. 5. It was confirmed that it was an aggregate of plate-like crystals as in Example 1.

[0086] Example 3 An aqueous solution of sodium dihydrogen phosphate dihydrate with a concentration of 10.7% by mass and a slurry of ground calcium hydroxide with a solid content concentration of 8.6% by mass (BET specific surface area 7.9 m 2 / g, oxalic acid reactivity: 12 minutes 30 seconds, JP-A No. 2017-036176) was prepared. The aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 40°C while stirring, and maintained until stirring stopped. 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, it was further stirred for 1 hour, then filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

[0087] For the obtained hydroxyapatite particles, X-ray crystal diffraction, specific surface area measurement, and shape observation were performed in the same manner as in Example 1.

[0088] The X-ray diffraction results are shown in Fig. 6. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.2, which was the same value as in Example 1. Also, with respect to 100% of the total area of all diffraction peaks in the range of 25° ≤ 2θ ≤ 35°, 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%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 6 nm.

[0089] The specific surface area was 81.5 m 2 / g.

[0090] The shape observation results are shown in Fig. 7. It was confirmed that the hydroxyapatite particles obtained in the same manner as in Example 1 were aggregates of plate-like crystals.

[0091] Example 4 An aqueous solution of sodium dihydrogen phosphate anhydride with a concentration of 10.7% by mass and a slurry of ground calcium hydroxide with a solid content concentration of 8.6% by mass (BET specific surface area 7.9 m 2 / g, oxalic acid reactivity: 12 minutes 30 seconds, Japanese Patent Application Laid-Open No. 2017-036176) was prepared. The aqueous solution of sodium dihydrogen phosphate anhydride was placed in a stainless steel beaker and heated to 80°C while stirring. The pH was not adjusted and remained at 4.2. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, stirring was continued for another 1 hour, followed by filtration, washing with water, and drying at 80°C to obtain hydroxyapatite particles (powder). For the obtained hydroxyapatite particles, X-ray diffraction, specific surface area measurement, and shape observation were performed in the same manner as in Example 1.

[0092]

[0093] ​The X-ray crystal diffraction results are shown in Fig. 8. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.4, which was the same value as in Example 1. Also, with respect to the total area of 100% of all diffraction peaks in the range of 25° ≤ 2θ ≤ 35°, the sum of the areas of all diffraction peaks in the range of 25.5° ≤ 2θ ≤ 26.5° and the areas of all diffraction peaks in the range of 31.5° ≤ 2θ ≤ 32.5° was 37.8%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 9 nm.

[0094] The specific surface area was 163.4 m 2 / g.

[0095] The shape observation results are shown in Fig. 9. It was confirmed that the hydroxyapatite particles obtained in the same manner as in Example 1 were aggregates of plate-like crystals.

[0096] Example 5 An aqueous solution of sodium dihydrogen phosphate anhydride with a concentration of 10.7% by mass and a slurry of ground calcium hydroxide with a solid content concentration of 8.6% by mass (BET specific surface area 7.9 m 2 / g, oxalic acid reactivity: 12 minutes and 30 seconds, Japanese Patent Laid-Open No. 2017-036176) was prepared. The aqueous solution of sodium dihydrogen phosphate anhydride was placed in a stainless steel beaker and heated to 60°C while stirring. The pH was not adjusted and remained at 4.2. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, stirring was continued for another 1 hour, followed by filtration, washing with water, and drying at 80°C to obtain hydroxyapatite fine particles (powder).

[0097] For the obtained hydroxyapatite fine particles, X-ray crystal diffraction, specific surface area measurement, and shape observation were performed in the same manner as in Example 1.

[0098] The X-ray diffraction results are shown in Fig. 10a. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.1, which was the same value as in Example 1. Also, with respect to the total area of 100% of all diffraction peaks in the range of 25° ≤ 2θ ≤ 35°, the total of the areas of all diffraction peaks in the range of 25.5° ≤ 2θ ≤ 26.5° and the areas of all diffraction peaks in the range of 31.5° ≤ 2θ ≤ 32.5° was 31.6%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 7 nm.

[0099] The specific surface area was 94.7 m 2 / g.

[0100] The shape observation results are shown in Fig. 10b. It was confirmed that it was an aggregate of plate-like fine particles as in Example 1.

[0101] Example 6 An aqueous solution of sodium dihydrogen phosphate anhydrous with a concentration of 10.7 mass% and a slurry of ground calcium hydroxide with a solid content concentration of 8.6 mass% (BET specific surface area: 7.9 m2 / g, oxalic acid reactivity: 12 minutes 30 seconds, Japanese Patent Laid-Open No. 2017-036176) were prepared so that the Ca / P molar ratio became 0.5. The aqueous solution of sodium dihydrogen phosphate anhydrous was put into a stainless steel beaker and heated to 80°C while stirring. The pH was not adjusted and remained at 4.2. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, it was further stirred for 1 hour, then filtered, washed with water, and dried at 80°C to obtain hydroxyapatite fine particles (powder). After the addition was completed, it was further stirred for 1 hour, then filtered, washed with water, and dried at 80°C to obtain hydroxyapatite fine particles (powder).

[0102] For the obtained hydroxyapatite fine particles, X-ray diffraction, specific surface area measurement, and shape observation were carried out in the same manner as in Example 1.

[0103] The X-ray diffraction results are shown in Fig. 11a. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.58. Also, with respect to 100% of the total area of all diffraction peaks within the range of 25° ≤ 2θ ≤ 35°, the sum of the areas of all diffraction peaks within the range of 25.5° ≤ 2θ ≤ 26.5° and the sum of the areas of all diffraction peaks within the range of 31.5° ≤ 2θ ≤ 32.5° was 40.9%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 7 nm.

[0104] The specific surface area was 105.0 m 2 / g.

[0105] The shape observation results are shown in Fig. 11b. It was confirmed that it was an aggregate of plate-like fine particles as in Example 1.

[0106] Example 7 An aqueous solution of sodium dihydrogen phosphate dihydrate at 10.7 mass% and a ground calcium hydroxide slurry with a solid content concentration of 8.6 mass% (BET specific surface area: 6.7 m2 / g, oxalic acid reactivity: 15 minutes 30 seconds, JP-A No. 2017-036176) were prepared so that the Ca / P molar ratio became 0.5. The aqueous solution of sodium dihydrogen phosphate dihydrate was put into a stainless steel beaker, heated to 60° C. with stirring and maintained until the stirring stopped. A 10% NaOH aqueous solution was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, it was further stirred for 1 hour, then filtered, washed with water, dried at 80° C., and then left standing for 6 months under the conditions of 40° C. and 75% RH to obtain hydroxyapatite fine particles (powder).

[0107] For the obtained hydroxyapatite fine particles, X-ray diffraction, specific surface area measurement, and shape observation were performed in the same manner as in Example 1.

[0108] The X-ray diffraction results are shown in Fig. 11c. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.21. Also, with respect to 100% of the total area of all diffraction peaks within the range of 25° ≤ 2θ ≤ 35°, the sum of the areas of all diffraction peaks within the range of 25.5° ≤ 2θ ≤ 26.5° and the sum of the areas of all diffraction peaks within the range of 31.5° ≤ 2θ ≤ 32.5° was 39.4%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 8 nm.

[0109] The specific surface area was 34.8 m 2 / g.

[0110] Comparative Example 1 An aqueous solution of sodium dihydrogen phosphate anhydride with a concentration of 10.7% by mass and a slurry of ground calcium hydroxide with a solid content concentration of 8.6% by mass (BET specific surface area 7.9 m 2 / g, oxalic acid reactivity: 12 minutes 30 seconds, Japanese Patent Application Laid-Open No. 2017-036176) were prepared. The calcium hydroxide slurry was placed in a stainless steel beaker and heated to 40°C while stirring. An aqueous solution of sodium dihydrogen phosphate anhydride (pH: 4.2) was added in portions over 30 minutes. After the addition was completed, stirring was continued for another hour, followed by filtration, washing with water, and drying at 80°C to obtain hydroxyapatite. Hydroxyapatite particles (powder) were obtained.

[0111] For the obtained hydroxyapatite particles, X-ray diffraction, specific surface area measurement, and shape observation were carried out in the same manner as in Example 1.

[0112] The X-ray diffraction results are shown in Fig. 12. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.7, showing a clearly higher value compared to Example 1. Also, a diffraction peak by the (300) plane near 2θ = 33° was separated and appeared.

[0113] The specific surface area was 50.9 m 2 / g.

[0114] The shape observation results are shown in Fig. 13. It was confirmed that the obtained hydroxyapatite particles were formed by aggregation of spindle-shaped crystals.

[0115] Comparative Example 2 An aqueous solution of 10.7 mass% sodium dihydrogen phosphate dihydrate and a slurry of ground calcium hydroxide with a solid content concentration of 8.6 mass% (Japanese Patent Laid-Open No. 2017-036176) were prepared so that the Ca / P molar ratio would be 0.5. The aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60°C while stirring, and maintained until stirring stopped. The pH was not adjusted and remained at 4.2. The calcium hydroxide slurry was added thereto over 45 minutes. After the addition was completed, stirring was continued for another 1 hour, followed by filtration, washing with water, and drying at 80°C to obtain a sample.

[0116] For the obtained sample, X-ray crystallographic diffraction and shape observation were performed in the same manner as in Example 1.

[0117] The X-ray crystallographic diffraction results are shown in Fig. 14. In addition to the diffraction peaks of hydroxyapatite, diffraction peaks of other substances were confirmed. The peak indicated by a black circle in the figure is the diffraction peak of monetite, which is a calcium phosphate that is likely to be formed in an acidic state.

[0118] The shape observation results are shown in Fig. 15. Plate-like large particles of monetite were confirmed.

[0119] Comparative Example 3 An aqueous solution of 10.7 mass% sodium dihydrogen phosphate dihydrate and a slurry of high-purity calcium hydroxide with a solid content concentration of 8.6 mass% (BET specific surface area: 2.4 m 2 / g, Oxalic acid reactivity: 25 seconds (Japanese Patent Application Laid-Open No. 2011-126772) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60°C with stirring, and maintained until stirring stopped. A 10% NaOH aqueous solution was added to adjust the pH to 5.5. A calcium hydroxide slurry was added thereto over 30 minutes. After completion of the addition, stirring was continued for another 1 hour, followed by filtration, washing with water, and drying at 80°C to obtain a sample.

[0120] X-ray crystallographic analysis was performed on the obtained sample in the same manner as in Example 1.

[0121] The X-ray crystallographic analysis results are shown in Fig. 16. In addition to the diffraction peaks of hydroxyapatite, diffraction peaks of calcium hydroxide were confirmed at around 2θ = 28° and around 34°.

[0122] Also, the shape observation results are shown in Fig. 17. Large plate-like particles of calcium hydroxide were confirmed. Regarding the difference from Example 1, it was considered that the physical properties of the raw material calcium hydroxide had an influence. It was considered that.

[0123] Example 8 An aqueous solution of 10.7 mass% sodium dihydrogen phosphate dihydrate and a ground calcium hydroxide slurry with a solid content concentration of 8.6 mass% (BET specific surface area 7.9 m 2 / g, Oxalic acid reactivity: 12 minutes 30 seconds (Japanese Patent Application Laid-Open No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, and a 10% NaOH aqueous solution was added to adjust the pH to 5.5. A calcium hydroxide slurry was added thereto over 50 minutes. After completion of the addition, stirring was continued for another 1 hour, then stirring was stopped, and the mixture was allowed to stand at room temperature for 9 days, followed by filtration, washing with water, and drying at 80°C to obtain hydroxyapatite particles (powder).

[0124] X-ray crystallographic analysis and shape observation were performed on the obtained hydroxyapatite particles in the same manner as in Example 1.

[0125] The X-ray crystallographic diffraction results are shown in Fig. 18. The ratio of the diffraction peak intensity by the (211) plane near 2θ = 32° to the diffraction peak intensity ratio by the (002) plane near 2θ = 26° was 1.3.

[0126] The shape observation results are shown in Fig. 19. It was confirmed that the shape of the particles is an aggregate of minute spindle-shaped particles.

[0127] Comparative Example 4 An aqueous solution of sodium dihydrogen phosphate dihydrate with a concentration of 10.7 mass% and a slurry of ground calcium hydroxide with a solid content concentration of 8.6 mass% (Japanese Patent Laid-Open No. 2017-036176) were prepared so that the Ca / P molar ratio became 0.5. The aqueous solution of sodium dihydrogen phosphate dihydrate was put into a stainless steel beaker, heated to 80°C with stirring and maintained until the stirring stopped. The pH was not adjusted and remained at 4.2. The calcium hydroxide slurry was added thereto over 50 minutes. After the addition was completed, the mixture was further stirred for 1 hour, then filtered, washed with water, and dried at 80°C to obtain a sample.

[0128] For the obtained sample, X-ray crystallographic diffraction and shape observation were carried out in the same manner as in Example 1.

[0129] The X-ray crystallographic diffraction results are shown in Fig. 20. In addition to the diffraction peaks of hydroxyapatite, diffraction peaks of other substances were confirmed. The peak indicated by a black circle in the figure is the diffraction peak of monetite, which is calcium phosphate that is likely to be formed in an acidic state.

[0130] The shape observation results are shown in Fig. 21. Plate-like large particles of monetite were confirmed.

[0131] Test Example 1. Crystallinity Change Confirmation Test [Test Purpose] In order to evaluate the reactivity of hydroxyapatite particles in the oral cavity, the change in crystallinity before and after immersion in artificial saliva was measured with a powder X-ray diffractometer.

[0132] [Test Method] 0.5 g of hydroxyapatite particles obtained in the same manner as in Example 1 were 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 filtered by suction filtration was measured with a powder X-ray diffractometer, and the change in crystallinity before and after immersion in artificial saliva was observed.

[0133] [Measurement conditions] · Model used: Miniflex II (Rigaku Corporation) · Start angle: 20° · End angle: 40° · Sampling width: 0.02° · Scan speed: 4.0° / min · Target: Cu · Tube voltage: 30 kV · Tube current: 15 mA · Divergence slit: 1.25° · Scattering slit: 8.0 mm · Receiving slit: 0.3 mm.

[0134] The results are shown in Fig. 22. Improvement in crystallinity (increase in peak sharpness, appearance of peaks that were broad and hidden) was confirmed due to immersion in artificial saliva. From this, it was confirmed that the hydroxyapatite particles are particles that change (have reactivity) in the oral cavity.

[0135] In addition, when the same examination was conducted using known hydroxyapatite particles instead of the hydroxyapatite particles obtained in the same manner as in Example 1, the peaks did not change at all before and after immersion in artificial saliva, and the crystallinity did not change.

[0136] Test Example 2. Hydroxyapatite Particle Dentinal Tubule Occlusion Test [Test purpose] In order to evaluate the ability of hydroxyapatite particles to seal dentinal tubules, the surface of bovine dentin was brushed with a hydroxyapatite particle solution, and the degree of dentinal tubule occlusion was examined by observation with an electron microscope (SEM).

[0137] [Test Method] Preparation of Dentin Block (Sample) 1. The dentin of the bovine extracted root surface was cut into a size of 5×5 mm. 2. The cut tooth pieces were embedded in a resin (polymethyl methacrylate) to create blocks, polished using waterproof abrasive paper, and surface finishing was performed. 3. The dentin blocks were immersed in a 5% w / w EDTA aqueous solution (pH 7.0) for 2 minutes. 4. Ultrasonic treatment was performed in distilled water for 5 minutes.

[0138] Preparation of Hydroxyapatite Particle Solution 5. 0.3 g of hydroxyapatite particles obtained in the same manner as in Example 1 was suspended in 39.7 g of a viscous diluent to obtain a hydroxyapatite particle solution. The viscous diluent is an aqueous solution containing 0.5 w / w% sodium carboxymethyl cellulose and 10 w / w% glycerin.

[0139] Brushing Treatment 6. In the hydroxyapatite particle solution (40 g), the dentin blocks were brushed with a toothbrush (GUM #211) for 30 seconds (stroke: 150 rpm, load: 160 g). 7. After washing the dentin blocks with water, they were 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 operations 1 and 2 were repeated 6 times.

[0140] SEM Observation 9. After surface vapor deposition treatment, observation was carried out with an electron microscope.

[0141] [Observation and Measurement Conditions] {Vapor Deposition Treatment} · Model used: MCI1000 (Hitachi High-Technologies Corporation) · Current: 20 mA · Treatment time: 120 seconds {SEM Observation} · Model in use: S-3400N (Hitachi High-Technologies Corporation) · Detector: SE (secondary electron image) · Applied voltage: 5 kV · Probe current: 50 mA · Magnification: 25,000 times.

[0142] The results are shown in Fig. 23. It was confirmed that the dentinal tubules were blocked by brushing in the hydroxyapatite particle solution. From this, it was confirmed that the hydroxyapatite particles are particles that block the dentinal tubules present on the dentin surface.

[0143] Test Example 3. Adhesion Test [Test objective] In order to evaluate the ability of hydroxyapatite particles to adhere inside the dentinal tubules, after brushing the surface of bovine dentin with a hydroxyapatite particle solution, water pressure was applied from the back of the dentin, and whether the hydroxyapatite particle blockage could withstand the water pressure was examined by electron microscope (SEM) observation.

[0144] [Test method] Preparation of Dentin Disk (Sample) 1. Dentin from the root facial part of bovine extracted teeth was cut out into a size of 5 × 5 mm. 2. The cut tooth pieces were polished with waterproof abrasive paper. 3. The obtained dentin disks were immersed in a 5% w / w EDTA aqueous solution (pH 7.0) for 2 minutes. 4. Ultrasonic treatment was performed in distilled water for 5 minutes.

[0145] Preparation of Hydroxyapatite Particle Solution 5. 1 g of hydroxyapatite particles obtained in the same manner as in Example 1 was suspended in 39 g of a viscous diluent to obtain a hydroxyapatite particle solution. The viscous diluent is an aqueous solution containing 0.5 w / w% sodium carboxymethylcellulose and 10 w / w% glycerin.

[0146] Brushing Treatment 6. In hydroxyapatite particle solution (40 g), the dentin disk was brushed with a toothbrush (GUM #211) for 30 seconds (stroke: 150 rpm, load: 160 g). 7. After washing 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 operations 1 and 2 were repeated 6 times. 9. It was immersed in artificial saliva for 7 days.

[0147] Hydrostatic Pressure Treatment 10. After the brushing treatment, the dentin disk was pressurized at 0.1 MPa for 30 minutes using a device referring to 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.).

[0148] SEM Observation 11. After vapor deposition treatment on the surface, it was observed with an electron microscope.

[0149] [Observation and measurement conditions] {Vapor deposition treatment} · Model used: MCI1000 (Hitachi High - Technologies Corporation) · Current: 20 mA · Treatment time: 120 seconds {SEM observation} · Model used: S - 3400N (Hitachi High - Technologies Corporation) · Detector: SE (secondary electron image) · Applied voltage: 5 kV · Probe current: 50 mA · Magnification: 25000 times.

[0150] The results are shown in Fig. 24. It was confirmed that the dentinal tubules were blocked even after the hydrostatic pressure treatment. From this, it was confirmed that the hydroxyapatite particles are particles that adhere within the dentinal tubules and maintain the blocked state.

[0151] Test Example 4. Toothpaste Dentinal Tubule Occlusion Test [Test objective] To confirm the ability of the dentifrice preparation with the material formulation to block the dentinal tubules, the surface of bovine dentin was brushed with the material solution, and the degree of blockage of the dentinal tubules was examined by an electron microscope (SEM). [Test method] Preparation of Dentin Block (Sample) 1. The dentin of the bovine extracted root surface was cut out into a size of 5×5 mm. 2. The cut tooth piece was embedded in a resin (polymethyl methacrylate) to prepare a block, which was polished using waterproof abrasive paper for surface finishing. 3. The dentin block was immersed in a 5 w / w% EDTA aqueous solution (pH 7.0) for 2 minutes. 4. Ultrasonic treatment was performed in distilled water for 5 minutes.

[0152] Preparation of Toothpaste Solution 5. 10 g of a dentifrice containing 3 w / w% of 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 the following table. Hereinafter, the unit “%” of the blending amount in the table indicates mass%.

[0153]

Table 4

[0154] Brushing Treatment 6. 10 g of the dentifrice was diluted 4-fold 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. After washing the dentin block 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. Operations 1 and 2 above were repeated 6 times.

[0155] SEM Observation 9. After surface vapor deposition treatment, it was observed with an electron microscope. [Observation and measurement conditions] {Vapor deposition treatment} · Model used: MCI1000 (Hitachi High-Technologies Corporation) · Current: 20 mA · Treatment time: 120 seconds {SEM observation} · Model used: S-3400N (Hitachi High-Technologies Corporation) · Detector: SE (secondary electron image) · Applied voltage: 5 kV · Probe current: 50 mA · Magnification: 25,000 times

[0156] The results are shown in Figure 25. It was confirmed that the dentinal tubules were blocked by brushing in the dentifrice solution containing hydroxyapatite particles. From this, it was confirmed that the dentifrice containing the hydroxyapatite particles has a high effect of blocking the dentinal tubules.

[0157] Test Example 5. Dentinal Tubule Occlusion Test When Gel Preparation is Applied with a Soft Pick [Test purpose] To confirm the ability of the gel preparation containing hydroxyapatite particles to block dentinal tubules, the gel preparation was applied to the surface of bovine dentin using a soft pick (rubber interdental brush), and the degree of blockage of the dentinal tubules was examined with an electron microscope (SEM). [Test method] Preparation of Dentin Block (Sample) 1. The dentin on the root surface of bovine extracted teeth was cut out to a size of 5 × 5 mm. 2. The cut tooth pieces were embedded in a resin (polymethyl methacrylate) to create blocks, polished using waterproof abrasive paper, and surface-finished. 3. The dentin blocks were immersed in a 5 w / w% EDTA aqueous solution (pH 7.0) for 2 minutes. 4. Ultrasonic treatment was performed in distilled water for 5 minutes. 5. Two of the dentin blocks were fixed with tape so that the dentin surfaces faced each other at an interval of 1.1 mm, creating a pseudo-interproximal space.

[0158] Coating Treatment 6. A 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 curve type: Sunstar Inc.), inserted into the space, and reciprocated 5 times. The composition of the gel preparation is shown in the following table. 7. The dentin blocks were washed with water.

[0159]

Table 5

[0160] SEM Observation 8. After vapor deposition treatment on the surface, observation was carried out with an electron microscope. [Observation and measurement conditions] {Vapor deposition treatment} · Equipment used: MCI1000 (Hitachi High-Technologies Corporation) · Current: 20 mA · Treatment time: 120 seconds {SEM observation} · Equipment used: S-3400N (Hitachi High-Technologies Corporation) · Detector: SE (secondary electron image) · Applied voltage: 5 kV · Probe current: 50 mA · Magnification: 25,000 times

[0161] The results are shown in Fig. 26. It was confirmed that the dental tubules were blocked by applying a gel preparation containing hydroxyapatite particles by soft packing.

[0162] Test Example 6. Gel Preparation Clinical Test [Test objective] The clinical effect of a gel preparation containing hydroxyapatite particles on anti-hypersensitivity was examined. In this examination, the hydroxyapatite particles obtained in the same manner as in Example 1 were used as the hydroxyapatite particles. [Test design] (i) A gel preparation containing hydroxyapatite particles, aluminum lactate, and potassium nitrate (HAp+Al+K), (ii) a gel preparation containing aluminum lactate and potassium nitrate (Al+K), and (iii) a gel preparation containing potassium nitrate (K) were compared. The compositions of these gel preparations are shown in the following table.

[0163]

Table 6

[0164] Each gel preparation was used by 20 people each, and the degree of brushing pain (applying a probe to the exposed root surface site and brushing horizontally) at 1, 2, or 4 weeks after use was described on a VAS scale. The VAS scale is a visual scale that shows a 10-cm long black line (the left end is "no pain at all" and the right end is "the most stinging / strongest pain") to the patient to indicate the degree of current pain. The flow of the test is shown in Fig. 27. In Fig. 27, "hypersensitivity care set (gel preparation (test article))" indicates the gel preparations of (i) to (iii) above, and "hypersensitivity care set (gel preparation (placebo article))" indicates a gel preparation obtained by removing potassium nitrate from the gel preparation of (iii) above.

[0165] [Method of using test article] The subject was made to use a gel preparation (test article) twice a day (in the morning and evening) (without stipulating after getting up, after meals, before going to bed, etc., and adjusting according to each person's oral hygiene habits). Specifically, first, after brushing with a designated hub brush (gum, Proz dental brush #3C: Sunstar Inc.) and toothpaste (Cope non-foam toothpaste N), rinse the mouth with about 10 ml of water for 20 seconds (without stipulating the brushing time), and then use the gel preparation. Specifically, for each test tooth, apply about 0.04 g (about the size of a grain of rice) of the gel preparation (test article) to the test site with a tuft brush (Battler single tuft brush #01F: Sunstar Inc.), and brush the test site and its two adjacent teeth for 5 seconds or more per tooth. If a designated interdental cleaning tool (gum, soft pick Curve type: Sunstar Inc.) can be inserted, insert the interdental cleaning tool into the interdental area between the test site and its two adjacent teeth from the buccal side and reciprocate 5 times. After using the gel preparation (test article), Rinse the mouth with about 10 ml of water for 20 seconds.

[0166] Figure 28 shows the results of evaluating the degree of abrasion pain on the VAS scale. In the group using the hydroxyapatite-containing preparation, the abrasion pain was significantly improved at the first week after use compared with the non-containing group. From this, it was found that the hydroxyapatite-containing preparation has the effect of suppressing hypersensitivity symptoms early by combining with aluminum lactate and potassium nitrate, which are known medicinal ingredients for preventing hypersensitivity.

[0167] Test Example 7. Examination of Potassium Nitrate-Containing Oral Compositions Hydroxyapatite particles obtained in the same manner as in Example 1 (HAp manufactured by the procedure of Example 1) or commercially available hydroxyapatite particles (commercially available HAp (manufactured by Tomita Pharmaceutical Co., Ltd.); commercially available hydroxyapatite different from the above reagent HAp), and various surfactants and various binders were used to prepare an oral composition. Specifically, each component shown in Table 7 was mixed to prepare each oral composition. The numerical values of each component shown in Table 7 represent mass%. Further, when X-ray crystallography was performed on HAp manufactured by the procedure of Example 1 and commercially available HAp in the same manner as in Example 1, the ratio of the diffraction peak intensity of the (211) plane near 2θ = 32° to the diffraction peak intensity ratio of the (002) plane near 2θ = 26° was 1.44 for HAp manufactured by the procedure of Example 1 and 2.72 for commercially available HAp. The average number of added moles of ethylene oxide of the polyoxyethylene hydrogenated castor oil used was 60.

[0168] And for each oral composition, drawability, foaming property, and dispersibility were evaluated by the following methods. This evaluation is also shown in accordance with Table 7.

[0169] <Drawability> Each obtained oral composition was filled into a colorless and transparent glass container (manufactured by Kashiwa Yoko Glass Co., Ltd.) with a filling volume of 83.5 mL and a body diameter of 45.5 mm to a level of 60 mL or more, and the paste surface was leveled. After the plunger contacted the paste surface and was pushed down by 8 mm, the height (mm) of the drawn thread when it was pulled up at a speed of 1000 mm / min was evaluated as the drawability evaluation according to the following criteria. Note that if the drawability is too high, the composition will have poor cutting during use, which is not preferable. 〇: <10 mm, △: 10 - 20 mm, ×: ≧20 mm

[0170] <Foaming property> For each obtained oral composition, 3 times the mass of water was added to prepare a 4-fold diluted water slurry, and 5 mL was measured into a plastic round-bottom tube with a total length of 9.5 cm and a diameter of 1.5 cm. After covering the tube with a lid, it was reciprocated up and down 10 times, and after standing at room temperature for 3 minutes, the height of the foam was measured and evaluated according to the following criteria. 〇: ≧5 mm, △: 2 mm - 5 mm, ×: <2 mm

[0171] <Dispersibility> 5 g of each obtained oral composition and 15 g of distilled water were weighed into a glass beaker with a diameter of 4.5 cm, and stirred at a speed of 500 rpm using a stir bar with a diameter of 0.6 cm and a length of 3.0 cm. After stirring for 5 minutes, the presence or absence of precipitation of the undispersed oral composition was visually confirmed. 〇: No precipitation can be confirmed. ×: Precipitation can be confirmed.

[0172]

Table 7

Claims

1. Hydroxyapatite particles, Potassium nitrate, Polyoxyethylene hydrogenated castor oil, and Xanthan gum, contained, wherein the ratio of the diffraction peak intensity near 2θ = 32° to the diffraction peak intensity near 2θ = 26° in the powder X-ray diffraction pattern measured by CuKα characteristic X-rays of the hydroxyapatite particles is 0.8 to 1.6, The Ca / P molar ratio of the hydroxyapatite particles is less than 1.67, the median diameter is 5 μm or less, and the specific surface area is 30 to 200 m ２ / g, and the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° of the hydroxyapatite particles is 5 to 10 nm, the hydroxyapatite particles are aggregates of hydroxyapatite plate-like crystals, an oral composition (however, an oral composition containing sodium carboxymethyl cellulose is excluded).

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

3. The oral composition according to claim 1 or 2, further containing aluminum lactate.

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

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