Oral composition

Abstract

To provide a composition for an oral cavity, the composition containing particles that have dentinal tubule-sealing properties and excellent fixation inside the dentinal tubules.SOLUTION: The present invention provides a hydroxyapatite particle-containing composition for an oral cavity, where the ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° of the hydroxyapatite particles is 0.8-1.5 in an x-ray powder diffraction pattern measured using Cu-Kα characteristic x-rays.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 the 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 by particles such as fluoride and aluminum salts (as an example, Patent Document 1) to suppress the reach of external stimuli to the nerves. However, many of the conventional methods have insufficient adhesion after blocking and problems with the persistence 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 present inventors 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 1.5) can solve the above problems. And based on this finding, further studies were conducted.

[0007] This disclosure includes, for example, the subject matter described in the following items. Item 1. An oral composition containing hydroxyapatite particles, 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 1.5, 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 (preferably 1.60 or less). 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 55 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 oral composition according to any one of Items 1 to 5, wherein the hydroxyapatite particles are aggregates of hydroxyapatite plate-like crystals. 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 potassium nitrate and / or aluminum lactate. Item 8. The oral composition according to any one of items 1 to 7, which is for preventing or improving hypersensitivity. 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 including a step of mixing an aqueous alkali phosphate solution having a pH of 4 or more and less than 7 and a calcium hydroxide slurry and reacting them at 35 to 85°C. Item 10. The oral composition according to item 9, wherein the calcium hydroxide slurry is a ground calcium hydroxide slurry. Item 11. The oral composition according to item 9 or 10, wherein the oxalic acid reactivity of the calcium hydroxide slurry (the time (minutes) until the pH becomes 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 maintained at 25 ± 1°C and adjusted to a concentration of 5 mass%) is 40 minutes or less. Item 12. The oral composition according to any one of items 9 to 11, wherein the BET specific surface area of the calcium hydroxide slurry is 5 m 2 / g or more. Item 1a. An oral composition containing hydroxyapatite particles and potassium nitrate, 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 1.5. Oral composition. Item 2a. The oral composition according to item 1a, wherein the Ca / P molar ratio of the hydroxyapatite particles is less than 1.67 (preferably 1.60 or less). Item 3a. The oral composition according to item 1a or 2a, wherein the median diameter of the hydroxyapatite particles is 5 μm or less. Item 4a. The specific surface area of the hydroxyapatite particles is 55 to 200 m 2The oral composition according to any one of items 1a to 3a, which is / g. Item 5a. The oral composition according to any one of items 1a to 4a, 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 6a. The hydroxyapatite particles are aggregates of hydroxyapatite plate-like crystals. The oral composition according to any one of items 1a to 5a. Item 7a. Furthermore, the oral composition according to any one of items 1a to 6a, which contains aluminum lactate. Item 8a. The oral composition according to any one of items 1a to 7a, which is for preventing or improving tooth hypersensitivity. Item 9a. The hydroxyapatite particles are produced by a method for producing hydroxyapatite particles, which includes a step of mixing an aqueous alkali phosphate solution having a pH of 4 or more and less than 7 and a calcium hydroxide slurry and reacting them at 35 to 85°C. The oral composition according to any one of items 1a to 8a. Item 10a. The oral composition according to item 9a, wherein the calcium hydroxide slurry is a ground calcium hydroxide slurry. Item 11a. The oxalic acid reactivity of the calcium hydroxide slurry (40 g of an oxalic acid aqueous solution having a concentration of 0.5 mol / liter maintained at 25 ± 1°C is added all at once to 50 g of a calcium hydroxide slurry maintained at 25 ± 1°C and adjusted to a concentration of 5 mass%, and the time (minutes) until the pH becomes 7.0 after the addition) is 40 minutes or less. The oral composition according to item 9a or 10a. Item 12a. The BET specific surface area of the calcium hydroxide slurry is 5 m 2 / g or more. The oral composition according to any one of items 9a to 11a. Item 13a. An oral composition according to any one of items 1a to 12a, containing 0.1 to 15% by mass of potassium nitrate. Item 13b. An oral composition according to any one of items 1a to 12a, containing 0.1 to 15% by mass of potassium nitrate (however, an oral composition containing 5% by mass of potassium nitrate is excluded). Item 13c. An oral composition containing hydroxyapatite particles and potassium nitrate, wherein the ratio of the diffraction peak intensity at around 2θ = 32° to the diffraction peak intensity at around 2θ = 26° in the powder X-ray diffraction pattern measured by CuKα characteristic X-rays of the hydroxyapatite particles is 0.8 to 1.5, and it is an oral composition according to any one of items 1a to 12a (however, an oral composition containing 5% by mass of potassium nitrate is excluded). Note that, although not particularly limited, the oral compositions described in Tables 1 to 3 of the following examples may be excluded from the subject matter of the present disclosure.

Advantages of the Invention

[0008] An oral composition is provided which has the property of sealing dentinal tubules and is excellent in adhesiveness within the dentinal tubules.

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 an oral composition, particularly an oral composition containing specific hydroxyapatite particles, but is not limited thereto, and the present disclosure includes all that is 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 1.5. 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 the peak of hydroxyapatite. Specifically, it is a diffraction peak with 2θ = 25.5 - 26.5°, preferably a diffraction peak with 2θ = 25.8 - 26.2°. When there are multiple 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, it is a diffraction peak with 2θ = 31.5 - 32.5°, preferably a diffraction peak with 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. As an example of the measurement conditions, the following conditions can be mentioned. 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] For the particles of the present disclosure, the ratio (32° / 26°) of the diffraction peak intensity near 2θ = 32° to the diffraction peak intensity near 2θ = 26° is 0.8 - 1.5. The peak intensity ratio is preferably 0.9 - 1.3, more preferably 1.0 - 1.25, still more preferably 1.05 - 1.2, and even more preferably 1.05 - 1.15.

[0017] The particles of the present disclosure preferably have each particle itself being 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), rod-like shapes, or combinations thereof. 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 being the c-plane and the side surface being the a-plane. When the particles are formed by a plurality of crystals, the crystals are called crystallites.

[0018] The particles of the present disclosure are particles containing hydroxyapatite as a main component, and 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. Therefore, the particles of the present disclosure are distinguished from particles with high peak intensities of these peaks.

[0019] Although not wishing to be bound by a limiting interpretation, it is considered that the particles of the present disclosure exhibit excellent sealing properties of the dental canal and excellent adhesion within the dental canal due to having a shape and structure represented by a specific X-ray diffraction pattern and being composed of aggregated plate-like particles.

[0020] 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 a plurality of 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.

[0021] The particles of the present disclosure preferably have a total area of all diffraction peaks in the range of 25.5° ≤ 2θ ≤ 26.5° and a total area of all diffraction peaks in the range of 31.5° ≤ 2θ ≤ 32.5° that is 30 to 45% with respect to the total area of all diffraction peaks in 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 due to 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 limited interpretation, it is considered that due to relatively low crystallinity, the crystal growth property in the capillary is further enhanced after the capillary is sealed, and thereby the adhesion property in the capillary is further improved.

[0022] 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 limited 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 thus 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.

[0023] The median diameter (d50) of the particles of the present disclosure is not particularly limited, but from the viewpoints of root canal 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 thereof 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.

[0024] The specific surface area of the particles of the present disclosure is not particularly limited, but from the viewpoints of root canal 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 thereof include 150 m 2 / g, 120 m 2 / g, 100 m 2 / g, 90 m 2 / g. The specific surface area is a value measured by the nitrogen gas adsorption method.

[0025] The particles of the present disclosure preferably react with saliva to improve crystallinity. The improvement of 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 (CaCl 2 : 1.5 mM, KH 2 PO 4 : 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.

[0026] The particles of the present disclosure can be prepared by a method for producing hydroxyapatite particles, which includes, for example, a step of mixing an aqueous solution of an alkali metal 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.

[0027] The alkali metal phosphate is not particularly limited and includes hydrates and anhydrides. Examples of the alkali metal 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.

[0028] The concentration of the alkali metal phosphate in the aqueous solution of the alkali metal 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.

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

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

[0031] The reactivity with respect to oxalic acid can be represented, for example, by the following definition: Oxalic acid reactivity: The time (in minutes) until the pH reaches 7.0 after adding 40 g of an oxalic acid aqueous solution with a concentration of 0.5 mol / L 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.

[0032] As the specific reactivity with respect to oxalic acid, when expressed 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.

[0033] 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, it is 20 m 2 / g, 15 m 2 / g, 10 m 2 / g.

[0034] A calcium hydroxide slurry with high oxalic acid reactivity (for example, having the reactivity with respect to 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 for 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.

[0035] 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 to prepare a calcium hydroxide slurry.

[0036] The solid content concentration of the calcium hydroxide slurry is not particularly limited, but for example, it is 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.

[0037] 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.

[0038] 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 making the above addition to the reaction vessel, usually, the liquid in the reaction vessel is being stirred.

[0039] It is desirable that the above addition to the reaction vessel be carried out over a certain period of time. The time from the start of addition to the end of addition is, 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 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 solution of the alkali phosphate 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 solution of the alkali phosphate and the calcium hydroxide slurry are completely mixed, in the above aspects 1 to 3, the time starting from when the addition of the aqueous solution of the 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 still more preferably 50 to 70 minutes.

[0041] 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 filtration treatment, washing treatment with water, etc. Further, if necessary, it can also be subjected to a drying treatment.

[0042] The particles of the present disclosure have the property of sealing dentinal tubules and are excellent in the adhesiveness within 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.

[0043] The particles of the present disclosure can be contained in the oral composition in an amount of, for example, about 1 to 10% by mass. The upper or lower limit of the content ratio range may be, for example, 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 is more preferably 2 to 8% by mass or 3 to 7% by mass.

[0044] 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 can be made into forms (dosage forms) such as ointments, pastes, pastilles, gels, liquids, sprays, mouthwashes, liquid dentifrices, dentifrices, and coatings according to conventional methods. Among them, mouthwashes, liquid dentifrices, dentifrices, pastes, liquids, sprays, gels, and coatings are preferred, and dentifrices, pastes, and gels are more preferred. Further, it is preferable to perform brushing after placing the oral composition on a toothbrush or applying the oral composition into the oral cavity. Therefore, a form suitable for brushing is preferable. By brushing, the particles of the present disclosure can be pushed into the cavities of the tooth dentin, and the effect can be obtained more preferably.

[0045] In addition to the particles of the present disclosure, the oral composition of the present disclosure may further contain optional components that can be incorporated into the oral composition, alone or in combination of two or more, within a range that does not impair the effects.

[0046] Potassium nitrate is preferably mentioned as such a component. In other words, the oral composition of the present disclosure preferably includes a form containing the particles of the present disclosure and potassium nitrate. This is because the oral composition containing potassium nitrate in addition to the particles of the present disclosure can suppress yellowing that occurs over time.

[0047] More specifically, unlike conventional hydroxyapatite particles, when the particles of the present disclosure are contained in an oral composition, the inventors have found that there is a problem that when the oral composition is stored at a relatively high temperature (for example, about 40 to 60 ° C), the oral composition turns yellow (over time). Such a temperature is sufficiently achievable during the distribution of oral composition products (especially during summer distribution), and yellowing can be one of the reasons for consumers to avoid when selecting an oral composition, so it is preferably suppressed. Here, as described above, in an oral composition containing potassium nitrate in addition to the particles of the present disclosure, the yellowing that may occur over time is suppressed, which is particularly preferable.

[0048] Potassium nitrate can be contained in the oral composition, for example, in an amount of about 0.1 to 15% by mass. The upper or lower limit of the 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, 9.5, 10, 11, 12, 13, or 14% by mass. For example, the range may be about 0.5 to 10% by mass, or about 1 to 8% by mass.

[0049] As other optional components, for example, as surfactants, nonionic surfactants, anionic surfactants or amphoteric surfactants can be blended. 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 having 13 to 15 carbon atoms; polyoxyethylene alkyl phenyl ethers with 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 anionic surfactants include sulfate esters such as sodium lauryl sulfate, sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate, sodium polyoxyethylene lauryl ether sulfosuccinate; acyl amino acid salts such as sodium cocoyl sarcosinate, sodium lauroyl methylalaninate; sodium cocoyl methyl taurine and the like. Examples of amphoteric ion surfactants include betaine type activators such as lauryldimethylaminoacetic acid betaine, coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine; imidazoline type activators such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; amino acid type activators such as N-lauryl diaminoethyl glycine and the like. 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.

[0050] In addition, sweeteners such as sodium saccharin, acesulfame potassium, stevioside, neohesperidin dihydrochalcone, perillartine, thaumatin, aspartylphenylalanyl methyl ester, p-methoxycinnamic aldehyde 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.

[0051] Also, as the binder, for example, cellulose derivatives such as sodium carboxymethyl cellulose, carboxymethyl ethyl cellulose salt, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, microbial-produced polymers 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 beegum and thickening silica, and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl] hydroxyethyl cellulose chloride can be used alone or in combination of two or more.

[0052] Furthermore, as the wetting agent, sorbitol, glycerin, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, etc. can be blended alone or in combination of two or more.

[0053] As the preservative, parabens such as methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate, phenoxyethanol, alkyl diaminoethyl glycine hydrochloride, etc. can be blended alone or in combination of two or more.

[0054] As the colorant, legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, Green No. 3, mineral-based dyes such as ultramarine, reinforced ultramarine, dark blue, titanium oxide, etc. can be blended alone or in combination of two or more.

[0055] As the pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or their chemically possible salts and sodium hydroxide, etc. can be blended. These can be blended alone or in combination of two or more 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 0.01 to 2% by weight, for example.

[0056] 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, hinokitiol, etc. may 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. Among them, aluminum lactate is particularly preferable for blending in the oral composition of the present disclosure because it is a medicinal ingredient for preventing hypersensitivity.

[0057] Also, as a base, for example, alcohols, silicon, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastic base, etc. can be added alone or in combination of two or more.

[0058] Note that the description of the above optional components is illustrative and does not limit the optional components that can be used.

[0059] In this specification, "comprising" includes "consisting essentially of" and "consisting of". Also, the present disclosure includes all combinations of the constituent elements described in this specification.

[0060] Also, regarding the various characteristics (properties, structures, functions, etc.) described for each of the above-described embodiments of the present disclosure, they may be combined in any way in identifying the subject matter encompassed by the present disclosure. That is, the present disclosure includes all subject matters consisting of any combination of the various characteristics that can be combined as described in this specification.

Examples

[0061] The subject matter of the present disclosure will be described in more detail below based on examples, but the subject matter of the present disclosure is not limited to these examples.

[0062] Example 1 An aqueous solution of sodium dihydrogen phosphate dihydrate with a mass fraction of 10.7% and a slurry of ground calcium hydroxide with a solid content concentration of 8.6% (BET specific surface area: 6.7 m 2 / g, oxalic acid reactivity: 15 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 60°C with stirring, and maintained until stirring stopped. A 10% aqueous NaOH 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).

[0063] X-ray crystallographic diffraction, specific surface area measurement, particle size distribution measurement, Ca / P molar ratio measurement, and shape observation were performed on the obtained hydroxyapatite particles.

[0064] The measurement was 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°, 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. 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° was 1.1, which was clearly lower than the same peak intensity ratio of 2.7 of 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 value is 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° was 7 nm, which was clearly smaller than 52 nm shown by reagent HAp, and this also indicates low crystallinity from this point.

[0065] 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 Mount Tech Co., Ltd.). As a result, the specific surface area was 61.9 m 2 / g.

[0066] 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.

[0067] The Ca / P molar ratio of the hydroxyapatite particles was calculated from the measured values of the Ca and P contents 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 1.33.

[0068] 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. It was shown that the hydroxyapatite particles obtained from these results were aggregates of plate-like crystals.

[0069] Example 2 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, JP-A No. 2017-036176) was prepared. 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. 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).

[0070] For the obtained hydroxyapatite particles, X-ray crystal diffraction, specific surface area measurement, and shape observation were carried out in the same manner as in Example 1.

[0071] The X-ray 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 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 38.6%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 7 nm.

[0072] The specific surface area was 75.4 m 2 / g.

[0073] 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.

[0074] Example 3 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 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).

[0075] 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.

[0076] The X-ray crystallographic 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.

[0077] The specific surface area was 81.5 m 2 / g.

[0078] 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.

[0079] 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, JP-A 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, the mixture was further stirred for 1 hour, then filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

[0080] For the obtained hydroxyapatite particles, X-ray crystallographic diffraction, specific surface area measurement, and shape observation were performed in the same manner as in Example 1.

[0081] The X-ray 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 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 37.8%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 9 nm.

[0082] The specific surface area was 163.4 m 2 / g.

[0083] 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.

[0084] Example 5 An aqueous solution of sodium dihydrogen phosphate anhydride 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 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).

[0085] 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.

[0086] The X-ray crystallographic diffraction results are shown in Fig. 10. 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 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%. Further, the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° was 7 nm.

[0087] The specific surface area was 94.7 m 2 / g.

[0088] The shape observation results are shown in Fig. 11. It was confirmed that it was an aggregate of plate-like fine particles as in Example 1.

[0089] Comparative Example 1 An aqueous solution of sodium dihydrogen phosphate anhydride with a mass fraction of 10.7% and a slurry of ground calcium hydroxide 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) was 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 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).

[0090] For the obtained hydroxyapatite particles, X-ray crystallographic diffraction, specific surface area measurement, and shape observation were performed in the same manner as in Example 1.

[0091] The X-ray diffraction results are shown in Fig. 12. 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 1.7, showing a clearly higher value compared with Example 1. Further, the diffraction peak of the (300) plane near 2θ = 33° appeared separately.

[0092] The specific surface area was 50.9 m 2 / g.

[0093] 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.

[0094] Comparative Example 2 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 Application 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 60°C while 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 45 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.

[0095] For the obtained sample, X-ray diffraction and shape observation were carried out in the same manner as in Example 1.

[0096] The X-ray 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 calcium phosphate that is likely to be formed in an acidic state.

[0097] The shape observation results are shown in Fig. 15. Plate-like large particles of monetite were confirmed.

[0098] Comparative Example 3 An aqueous solution of sodium dihydrogen phosphate dihydrate with a concentration of 10.7% by mass and a slurry of high-purity calcium hydroxide with a solid content concentration of 8.6% by mass (BET specific surface area: 2.4 m 2 / g, oxalic acid reactivity: 25 seconds; Japanese Patent Application Laid-Open No. 2011-126772) 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 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 a sample.

[0099] The obtained sample was subjected to X-ray diffraction in the same manner as in Example 1.

[0100] The X-ray diffraction 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°.

[0101] Also, the shape observation results are shown in Fig. 17. Large plate-like particles of calcium hydroxide were confirmed. It was considered that the physical properties of the raw material calcium hydroxide affected the difference from Example 1.

[0102] Comparative Example 4 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 and 30 seconds; Japanese Patent Application Laid-Open No. 2017-036176) were prepared. The 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. The 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).

[0103] With respect to the obtained hydroxyapatite particles, X-ray crystallographic diffraction and shape observation were performed in the same manner as in Example 1.

[0104] 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.

[0105] The shape observation results are shown in FIG. 19. It was confirmed that the shape of the particles was an aggregate of minute spindle-shaped particles.

[0106] Comparative Example 5 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 (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 placed in a stainless steel beaker, heated to 80° C. with stirring, and maintained until the stirring was 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, stirring was continued for another 1 hour, followed by filtration, washing with water, and drying at 80° C. to obtain a sample.

[0107] With respect to the obtained sample, X-ray crystallographic diffraction and shape observation were performed in the same manner as in Example 1.

[0108] 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 the 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.

[0109] The shape observation results are shown in FIG. 21. Plate-like large particles of monetite were confirmed.

[0110] Test Example 1. Crystallinity Change Confirmation Test [Test Purpose] To evaluate the reactivity of hydroxyapatite particles in the oral cavity, changes in crystallinity before and after immersion in artificial saliva were measured using a powder X-ray diffractometer.

[0111] [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 (CaCl 2 : 1.5 mM, KH 2 PO 4 : 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH)) for 7 days. The powder filtered by suction filtration was measured using a powder X-ray diffractometer, and changes in crystallinity before and after immersion in artificial saliva were observed.

[0112] [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.

[0113] The results are shown in Figure 22. An improvement in crystallinity (increase in peak sharpness and 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.

[0114] In addition, when the same examination was carried out 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.

[0115] Test Example 2. Hydroxyapatite Particle Dentinal Tubule Occlusion Test [Purpose of the test] To evaluate the ability of hydroxyapatite particles to block the dentinal tubules, the surface of bovine dentin was brushed with a hydroxyapatite particle solution, and the degree of dentinal tubule occlusion was examined by electron microscopy (SEM).

[0116] [Test method] Preparation of Dentin Block (Sample) 1. Dentin from the root surface of bovine extracted teeth was cut into pieces of 5×5 mm size. 2. The cut tooth pieces were embedded in a resin (polymethyl methacrylate) to make blocks, which were polished using waterproof abrasive paper for surface finishing. 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.

[0117] 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.

[0118] 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 (CaCl 2 : 1.5 mM, KH 2 PO 4 : 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.

[0119] SEM Observation 9. After the surface was subjected to vapor deposition treatment, it was observed with an electron microscope.

[0120] [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.

[0121] 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.

[0122] Test Example 3. Adhesion Test [Test purpose] 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 surface of the dentin, and it was examined by electron microscope (SEM) observation whether the hydroxyapatite particle blockage could withstand the water pressure.

[0123] [Test method] Preparation of Dentin Disk (Sample) 1. The dentin of 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.

[0124] 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 carboxymethyl cellulose and 10 w / w% glycerin.

[0125] Brushing Treatment 6. In the hydroxyapatite particle solution (40 g), a 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 (CaCl 2 : 1.5 mM, KH 2 PO 4 : 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.

[0126] Hydrostatic Pressure Treatment 10. After the dentin disk after the brushing treatment 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.).

[0127] SEM Observation 11. After vapor deposition treatment on the surface, it was observed with an electron microscope.

[0128] [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.

[0129] The results are shown in Figure 24. It was confirmed that the ivory tubules were blocked even after the hydrostatic pressure treatment. From this, it was confirmed that the hydroxyapatite particles are particles that adhere within the ivory tubules and maintain a blocked state.

[0130] Test Example 4. Toothpaste Dentinal Tubule Occlusion Test [Test Purpose] To confirm the ability of the scraping preparation with the material composition to block the ivory tubules, the surface of bovine dentin was brushed with the material solution, and the degree of blockage of the ivory tubules was examined with an electron microscope (SEM).

[0131] [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 create a block, polished using waterproof abrasive paper, and surface finishing was performed. 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.

[0132] Preparation of Toothpaste Solution 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. Hereinafter, the unit “%” of the blending amount in the table indicates mass%.

[0133]

Table 1

[0134] Brushing Treatment 6. The 10 g of the dentifrice was diluted 4-fold with distilled water to obtain a dentifrice solution. In the dentifrice solution (40 g), a 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 (CaCl 2 : 1.5 mM, KH 2 PO 4 : 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.

[0135] SEM Observation 9. After the surface was subjected to vapor deposition treatment, it was observed with an electron microscope.

[0136] [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

[0137] The results are shown in Fig. 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.

[0138] 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 seal the dentinal tubules, the gel preparation was applied to the bovine dentin surface using a soft pick (rubber interdental brush), and the degree of dentinal tubule occlusion was examined by scanning electron microscopy (SEM).

[0139] [Test method] Preparation of Dentin Block (Sample) 1. Dentin from the root surface of bovine extracted teeth was cut into pieces of 5×5 mm size. 2. The cut tooth pieces were embedded in a resin (polymethyl methacrylate) to make blocks, which were polished using water-resistant abrasive paper for surface finishing. 3. The dentin blocks were immersed in a 5 w / w% aqueous EDTA 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 with a 1.1 mm interval to create a pseudo-interdental space.

[0140] 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 Table 2 below. 7. The dentin blocks were washed with water.

[0141] [Table 2]

[0142] SEM Observation 8. After vapor deposition treatment on the surface, observation was carried out with an electron microscope.

[0143] [Observation and measurement conditions] [Vapor deposition treatment] · Equipment used: MCI1000 (Hitachi High-Technologies Corporation) · Current: 20 mA · 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: 50 mA · Magnification: 25,000 times

[0144] The results are shown in Fig. 26. By applying a gel preparation containing hydroxyapatite particles by soft pick, it was confirmed that the dental tubules were sealed.

[0145] 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, hydroxyapatite particles obtained in the same manner as in Example 1 were used as the hydroxyapatite particles.

[0146] [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 among three preparations. The compositions of these gel preparations are shown in Table 3 below.

[0147]

Table 3

[0148] Each gel preparation was used by 20 people each, and the degree of abrasion pain (applying a probe to the exposed root surface area and rubbing horizontally) at 1, 2, or 4 weeks after use was recorded 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 patients to indicate the degree of current pain. Also, the flow of the said test is shown in Figure 27. In Figure 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 the gel preparation obtained by removing potassium nitrate from the gel preparation of (iii) above.

[0149] [Method of using test article] The subjects were made to use the gel preparation (test article) twice a day (morning and evening) (without stipulating after getting up, after meals, before going to bed, etc., and adjusting according to their respective oral cleaning habits). Specifically, first, after brushing with a designated toothbrush (Gum·Proz Dental Brush #3C: Sunstar Inc.) and toothpaste (Cope Non-foam Toothpaste N), they were rinsed with about 10 ml of water for 20 seconds (without stipulating the brushing time), and then the gel preparation was used. The use of the gel preparation was specifically as follows: for each test tooth, about 0.04 g (about the size of a grain of rice) of the gel preparation (test article) was applied to the test site with a tufted brush (Battler Single Tuft Brush #01F: Sunstar Inc.), and the test site and its two adjacent teeth were brushed for 5 seconds or more per tooth. When a designated interdental cleaning tool (Gum·Soft Pick Curve Type: Sunstar Inc.) could be inserted between the test site and the two adjacent teeth, the said interdental cleaning tool was inserted into the interdental area between the test site and the two adjacent teeth from the buccal side and reciprocated 5 times. After using the gel preparation (test article), they were rinsed with about 10 ml of water for 20 seconds.

[0150] The results of evaluating the degree of friction pain using the VAS scale are shown in Fig. 28. In the group using the hydroxyapatite-containing preparation, the friction pain was significantly improved at the first week after use compared to the non-containing group. From this, it was found that the hydroxyapatite-containing preparation has the effect of suppressing hypersensitivity symptoms early by being used in combination with aluminum lactate and potassium nitrate, which are known active ingredients for preventing hypersensitivity.

[0151] Test Example 7. Examination of the Effects of Hydroxyapatite Particles and Oral Compositions Containing Potassium Nitrate Using 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.); a commercially available hydroxyapatite different from the above reagent HAp), and potassium nitrate, an oral composition was prepared. Specifically, each component shown in Table 4 was mixed to prepare each oral composition. The numerical values of each component shown in Table 4 indicate mass%. Also, for HAp manufactured by the procedure of Example 1 and commercially available HAp, when X-ray crystal diffraction was performed in the same manner as in Example 1 above, 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 1.44 for HAp manufactured by the procedure of Example 1 and 2.72 for commercially available HAp.

[0152]

Table 4

[0153] Each obtained oral composition was filled into a laminated tube with a diameter of 8 mm at 25 g, stored in the dark at 55°C for 6 months, and then returned to room temperature. After that, the color difference was measured as follows. The oral composition after storage was filled into a polystyrene container to a height of 2 cm, and photographed with an FD-5 (fluorescence spectroscopic densitometer manufactured by Konica Minolta) on a white plate. The photographing conditions were constant illumination, shutter speed, aperture, and focal length. b* in the L*a*b* color system of 6 measurement sites was measured, and the average value was calculated and used as an index for evaluating yellowing (browning). The results (b* values of each oral composition) are shown in Fig. 29. In the 9-bar graph of Fig. 29, the b* values of Reference Example 1a, Reference Example 2a, Reference Example 3a, Comparative Example 1a, Example 1a, and Comparative Example 2a are shown in order from the left, respectively.

[0154] From the results, it was confirmed that the hydroxyapatite particles obtained in the examples, unlike the conventional hydroxyapatite particles, when contained in an oral composition, when the oral composition was stored at a relatively high temperature (for example, about 40 to 60°C), the oral composition became yellowish (over time) (Reference Example 2a and Reference Example 3a), and that in addition to the hydroxyapatite particles obtained in the examples, an oral composition containing potassium nitrate had the yellowing significantly suppressed (Example 1a).

Claims

1. An oral composition containing 1 to 10% by mass of hydroxyapatite particles and 0.1 to 15% by mass of potassium nitrate, 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 1.0 to 1.2, the Ca / P molar ratio of the hydroxyapatite particles is 1.2 to 1.4, the median diameter of the hydroxyapatite particles is 3 to 4.5 μm, The specific surface area of the hydroxyapatite particles is 55 to 90 m ２ / g, and and the crystallite size calculated from the diffraction peak by the (130) plane near 2θ = 40° of the hydroxyapatite particles is 4 to 12 nm, an oral composition.

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

3. The oral composition according to claim 1 or 2, which is for preventing or improving tooth sensitivity.

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