JP2020105106A - Oral composition - Google Patents

Abstract

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

Description

The present invention relates to an oral composition and the like, and more particularly to an oral composition and the like containing hydroxyapatite particles. In addition, the contents of all the documents described in this specification (especially Japanese Patent Laid-Open No. 2017-036176) are incorporated herein by reference.

Hypersensitivity in teeth is caused by exposure of dentin of teeth due to physical abrasion such as brushing and chemical abrasion due to acid. When the dentin is exposed, the external stimulus stimulates the nerve in the dentinal tubule in the dentin, and the pain easily occurs.

Regarding hypersensitivity, for example, particles of fluoride, aluminum salt (as an example, Patent Document 1) or the like block the dentinal tubules to suppress the external stimulation from reaching the nerve. .. However, many of the conventional methods have insufficient fixability after blocking, and thus have a problem in sustaining the effect.

JP, 2010-222325, A Japanese Patent Laid-Open No. 2017-036176

It is an object of the present invention to provide particles which have the sealing property of dentinal tubules and which are excellent in stickiness in the dentinal tubules.

The inventors of the present invention have conducted extensive studies in view of the above problems, and as a result, specific hydroxyapatite particles (the ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° in the X-ray diffraction pattern was found to be It was found that hydroxyapatite particles having a particle size of 0.8 to 1.5) can solve the above problems. Then, further investigation was carried out based on this finding.

The present invention includes the embodiments described in the following sections, for example.
Item 1.
An oral composition containing hydroxyapatite particles,
The hydroxyapatite particles have a ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° in the powder X-ray diffraction pattern measured by CuKα characteristic X-ray of 0.8 to 1.5. is there,
Oral composition.
Item 2.
Item 2. The oral composition according to Item 1, wherein the hydroxyapatite particles have a Ca/P molar ratio of less than 1.67 (preferably 1.60 or less).
Item 3.
Item 3. The oral composition according to Item 1 or 2, wherein the hydroxyapatite particles have a median diameter of 5 µm or less.
Item 4.
Item 4. The oral composition according to any one of Items 1 to 3, wherein the hydroxyapatite particles have a specific surface area of 55 to 200 m ² /g.
Item 5.
Item 1 wherein the hydroxyapatite particles have a ratio of the diffraction peak intensity around 2θ=34° to the diffraction peak intensity around 2θ=32° in the powder X-ray diffraction pattern measured by CuKα characteristic X-ray of 1 or less. The composition for oral cavity according to any one of 4 above.
Item 6.
The hydroxyapatite particles are aggregates of hydroxyapatite plate crystals,
Item 6. The oral composition according to any one of Items 1 to 5.
Item 7.
Furthermore, the composition for oral cavity in any one of claim|item 1-6 containing potassium nitrate and/or aluminum lactate.
Item 8.
Item 8. The oral composition according to any one of Items 1 to 7, which is for preventing or improving hyperesthesia.
Item 9.
The hydroxyapatite particles are produced by a method for producing hydroxyapatite particles, which comprises a step of mixing an aqueous solution of an alkaline phosphate having a pH of 4 or more and less than 7 and a calcium hydroxide slurry and reacting the mixture at 35 to 85°C. The composition for oral cavity according to any one of Items 1 to 8, which is a substance.
Item 10.
Item 10. The oral composition according to Item 9, wherein the calcium hydroxide slurry is a milled calcium hydroxide slurry.
Item 11.
Oxalic acid reactivity of the calcium hydroxide slurry (50 g of calcium hydroxide slurry prepared at a concentration of 5% by mass and kept at 25±1° C., 0.5 mol/liter of 0.5 mol/liter kept at 25±1° C. Item 10. The oral composition according to Item 9 or 10, wherein 40 g of an aqueous oxalic acid solution having a concentration is added all at once, and the time (minutes) until the pH becomes 7.0 after the addition is 40 minutes or less.
Item 12.
Item 12. The oral composition according to any one of Items 9 to 11, wherein the calcium hydroxide slurry has a BET specific surface area of 5 m ² /g or more.

Provided is a composition for oral cavity, which has a sealing property for dentinal tubules and is excellent in adhesion in dentinal tubules.

2 shows the X-ray diffraction peak of the hydroxyapatite particles of Example 1. The X-ray-diffraction peak of a commercially available reagent hydroxyapatite particle is shown. 3 shows an SEM photograph of the hydroxyapatite particles of Example 1. 4 shows the X-ray diffraction peak of the hydroxyapatite particles of Example 2. 5 shows an SEM photograph of hydroxyapatite particles of Example 2. 4 shows the X-ray diffraction peak of the hydroxyapatite particles of Example 3. 5 shows an SEM photograph of hydroxyapatite particles of Example 3. 4 shows the X-ray diffraction peak of the hydroxyapatite particles of Example 4. 5 shows an SEM photograph of the hydroxyapatite particles of Example 4. 5 shows the X-ray diffraction peak of the hydroxyapatite fine particles of Example 5. 5 shows an SEM photograph of hydroxyapatite fine particles of Example 5. The X-ray diffraction peak of the hydroxyapatite particle of Comparative Example 1 is shown. The SEM photograph of the hydroxyapatite particle of Comparative Example 1 is shown. The X-ray-diffraction peak of the sample of the comparative example 2 is shown. Peaks indicated by black circles are diffraction peaks of monetite. The SEM photograph of the sample of the comparative example 2 is shown. The X-ray-diffraction peak of the sample of the comparative example 3 is shown. The SEM photograph of the sample of the comparative example 3 is shown. The X-ray-diffraction peak of the hydroxyapatite particle of Comparative Example 4 is shown. The SEM photograph of the hydroxyapatite particle of Comparative Example 4 is shown. The X-ray-diffraction peak of the sample of the comparative example 5 is shown. Peaks indicated by black circles are diffraction peaks of monetite. The SEM photograph of the sample of the comparative example 5 is shown. The X-ray-diffraction peak (Test Example 1) before and after immersion of artificial hydroxyapatite particles in artificial saliva is shown. The SEM photograph (Test Example 2) of the dentin tubule before and after brushing is shown. The SEM photograph (Test Example 3) of the ivory tubule before and after a hydraulic treatment is shown. The SEM photograph (Test Example 4) of the dentinal tubule before and after brushing using the dentifrice solution containing a hydroxyapatite particle is shown. The SEM photograph (Test Example 5) of the dentinal tubule before and after applying the gel formulation containing a hydroxyapatite particle to dentin by a soft pick is shown. 1 shows a flow of a clinical test using a gel preparation containing hydroxyapatite particles. The result of having evaluated the degree of abrasion pain by the VAS scale in a clinical test using a gel preparation containing hydroxyapatite particles is shown.

Hereinafter, each embodiment included in the present invention will be described in more detail. The present invention preferably includes oral compositions, particularly oral compositions containing specific hydroxyapatite particles, but the present invention is not limited thereto, and the present invention is disclosed in this specification. Includes all that can be recognized.

The oral composition included in the present invention contains specific hydroxyapatite particles. In addition, in this specification, the said oral cavity composition may be called "the oral cavity composition of this invention."

The specific hydroxyapatite particles are hydroxyapatite particles in which the ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° in the X-ray diffraction pattern is 0.8 to 1.5. .. In addition, in this specification, the said hydroxyapatite particle may be called "the particle|grain of this invention."

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

The diffraction peak near 2θ=32° is a peak of hydroxyapatite, specifically, the diffraction peak at 2θ=31.5 to 32.5°, preferably 2θ=31.8 to 32.2°. Is a diffraction peak of. When there are a plurality of diffraction peaks near 2θ=32°, it means the diffraction peak with the highest intensity.

In the present specification, the X-ray diffraction pattern is a powder X-ray diffraction pattern measured by CuKα characteristic X-ray. The following conditions can be mentioned as an example of measurement conditions. 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°, light receiving slit: 0.3 mm.

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

It is preferable that each particle of the present invention itself is an aggregate of hydroxyapatite plate crystals. The shape of the plate-like crystal that constitutes the particles of the present invention is not particularly limited, and examples thereof include a circle, a polygon (particularly a hexagon), a shape close to a bar, and a shape obtained by combining these. Further, the plate crystal may be in a state in which the plane is bent or in a state in which the plane is not folded and the planar structure is maintained. The plate-shaped hydroxyapatite crystal usually has a structure called a hexagonal crystal in which the top surface of the plate is the c-plane and the side surface is the a-plane. Further, when a particle is formed by a plurality of crystals, the crystal is called a crystallite.

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

Although not intended to be limited, the particles of the present invention have a shape and structure represented by a specific X-ray diffraction pattern, and partly because the plate-like particles are agglomerated. It is considered that, in combination with these, they exhibit an excellent sealing property of the dentinal tubule and an excellent fixing property in the dentinal tubule.

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

The particles of the present invention are preferably all in the range of 25.5°≦2θ≦26.5° with respect to 100% of the total area of all diffraction peaks in the range of 25°≦2θ≦35°. The total of the area of the diffraction peaks and the area of all the diffraction peaks within the range of 31.5°≦2θ≦32.5° is 30 to 45%. The value is preferably 33 to 42%, more preferably 35 to 40%. The crystallite size of the particles of the present invention calculated from the diffraction peak of the (130) plane near 2θ=40° is preferably 4 to 12 nm, more preferably 5 to 10 nm. Although it is not intended to limit the interpretation, it is considered that the relatively low crystallinity further enhances the crystal growth in the tubule after the dentinal tubule is sealed, and thus the adherence in the tubule is further improved. Conceivable.

The Ca/P molar ratio of the particles of the present invention is not particularly limited as long as it is a value that hydroxyapatite can have. Although not intended to be limited, it is considered that a part of calcium is replaced with another element (such as sodium) in the particles of the present invention. Therefore, the Ca/P molar ratio is relatively high. It can be low. From this viewpoint, the Ca/P molar ratio of the particles of the present invention is preferably less than 1.67, more preferably 1.65 or less or 1.60 or less, still more preferably 1.55 or less or 1.50 or less, and More preferably, it is 1.45 or less or 1.40 or less. The lower limit of the Ca/P molar ratio of the particles of the present invention is not particularly limited and can be 1.0, 1.1, or 1.2, for example. The Ca/P molar ratio is a value calculated from the measured values of the Ca and P contents of the particles of the present invention measured by inductively coupled plasma emission spectroscopy.

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

The specific surface area of the particles of the present invention, but are not particularly limited, dentinal tubule occlusion, from the viewpoint of stickiness, for example 30 m 2 / ^g or more, preferably 40 m 2 / ^g or more, more preferably 50 m ² /G or more, more preferably 55 m ² /g or more. The upper limit of the specific surface area is not particularly limited, but is, for example, 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.

The particles of the present invention preferably react with saliva to improve crystallinity. In the powder X-ray diffraction pattern measured by CuKα characteristic X-ray, the improvement in the crystallinity means that at least one (preferably 1, 2, 3, 4, or it) is before the saliva reaction. The above means that the sharpness of the peak is improved (more specifically, the diffraction intensity is improved). As 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 performed by immersing the particles in saliva for 7 days.

The particles of the present invention can be produced, for example, by a method of producing hydroxyapatite particles, which comprises 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. It can be prepared.

The phosphoric acid alkali salt is not particularly limited and includes hydrates and anhydrides. Examples of the phosphoric acid alkali salt include sodium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, tetrasodium pyrophosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, tripotassium phosphate and the like. Of these, sodium phosphate such as sodium dihydrogen phosphate, disodium hydrogen phosphate and trisodium phosphate are preferable, and sodium dihydrogen phosphate is more preferable.

The concentration of the alkaline phosphate salt in the aqueous alkaline phosphate solution 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 further preferably 7 to 15% by mass.

The pH of the alkaline phosphate aqueous solution 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 alkaline phosphate aqueous solution is relatively low (for example, when the pH is 4 or more and less than 5), an anhydride is used as the alkaline phosphate salt and the reaction temperature is set to a relatively high temperature. For example, it is desirable to set the temperature to 65 to 85°C, preferably 70 to 85°C, and more preferably 75 to 85°C.

Where the calcium hydroxide slurry has oxalic acid reactivity, the calcium hydroxide slurry is preferably a slurry of calcium hydroxide having a specific reactivity with oxalic acid.

Reactivity to oxalic acid can be expressed, for example, by the following definition:
Oxalic acid reactivity: 50 g of calcium hydroxide slurry prepared at a concentration of 5% by mass and kept at 25±1° C., 40 g of an aqueous solution of oxalic acid having a concentration of 0.5 mol/liter kept at 25±1° C. Was added all at once, and the time (minutes) until the pH reached 7.0 after the addition.

The specific reactivity with respect to the oxalic acid is preferably 1 to 40 minutes, more preferably 5 to 30 minutes, still more preferably 10 to 20 minutes when expressed by the above definition.

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 is, for example, 20 m ² /g, 15 m ² /g, 10 m ² /g.

A calcium hydroxide slurry having high oxalic acid reactivity (for example, having reactivity with the specific oxalic acid described above) can be typically obtained by milling a calcium hydroxide slurry. The milling process allows for greater oxalic acid reactivity (less time defined above). The grinding treatment is performed using, for example, 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.

The calcium hydroxide slurry can be prepared, for example, by reacting quick lime (calcium oxide) obtained by firing limestone with water. For example, a calcium hydroxide slurry can be prepared by calcining limestone in a kiln at about 1000° C. to produce quick lime, adding about 10 times the amount of hot water to this quick lime, and stirring for 30 minutes. it can.

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 further preferably 6 to 12% by mass.

The amount ratio of the alkaline phosphate aqueous solution and the calcium hydroxide slurry is not particularly limited as long as it is a ratio that can produce hydroxyapatite particles. The amount ratio is adjusted such that the Ca/P molar ratio is preferably 0.3 to 0.7, more preferably 0.4 to 0.6, and further preferably 0.45 to 0.55. Is desirable.

The mode of mixing the alkaline phosphate aqueous solution and the calcium hydroxide slurry is not particularly limited. For example, a mode (aspect 1) in which a calcium hydroxide slurry is added to a reaction vessel containing an alkali phosphate aqueous solution, a mode (aspect 2) in which an alkali phosphate aqueous solution is added to a reaction vessel containing a calcium hydroxide slurry, and phosphoric acid A mode (mode 3) in which the alkaline salt aqueous solution and the calcium hydroxide slurry are simultaneously added to the reaction vessel is exemplified. Among these, aspect 1 is preferable. During the above addition to the reaction vessel, the liquid in the reaction vessel is usually stirred.

It is desirable that the above addition to the reaction container takes a certain amount 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.

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, still more preferably 55 to 65°C. The reaction temperature is a relatively high temperature, for example, 65 to 85° C., preferably 70 to 85° C., and more preferably 75, when the pH of the alkaline phosphate aqueous solution is relatively low (eg, pH 4 or more and less than 5). ~85°C. Reaction time (time starting after all the alkaline phosphate aqueous solution and calcium hydroxide slurry are mixed, in the above-mentioned aspects 1 to 3, time starting from the time when the addition of the alkaline phosphate aqueous solution and calcium hydroxide slurry is completed ) Is, for example, 10 to 180 minutes, preferably 20 to 120 minutes, more preferably 40 to 90 minutes, and further preferably 50 to 70 minutes.

The particles of the present invention produced by the above steps are subjected to a purification treatment, if necessary. Examples of the purification treatment include filtration treatment and water washing treatment. Further, if necessary, it can be subjected to a drying treatment.

The particles of the present invention have a sealing property for dentinal tubules and are excellent in adhesion in dentinal tubules. Therefore, the oral composition containing the particles of the present invention (that is, the oral composition of the present invention) can be preferably used particularly for preventing or improving hyperesthesia.

The oral composition of the present invention can be produced by a conventional method, and can be used, for example, as a drug, a quasi drug, or a cosmetic. Further, the form of the composition for oral cavity of the present invention is not particularly limited, for example, ointment, paste, pasta, gel, liquid, spray, mouthwash, liquid dentifrice, according to a conventional method, It may be in the form (form) of a toothpaste or a coating agent. Of these, mouthwashes, liquid dentifrices, toothpastes, pastes, liquids, sprays, gels and coatings are preferable, and toothpastes, pastes and gels are more preferable. In addition, brushing is preferably performed after the oral composition is placed on a toothbrush or after the oral composition is applied to the oral cavity. Therefore, a form suitable for brushing is preferable. By brushing, the particles of the present invention can be pushed into the cavity of the tooth dentin, and the effects of the present invention can be obtained more preferably.

In the oral composition of the present invention, in addition to the particles of the present invention, optional components that can be blended in the oral composition, alone or in combination of two or more, in addition to the particles of the present invention, You may mix.

For example, as the surfactant, a nonionic surfactant, an anionic surfactant or an amphoteric surfactant can be blended. Specifically, as the nonionic surfactant, sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester and lactose fatty acid ester; fatty acid alkanolamides; sorbitan fatty acid ester; fatty acid monoglyceride; polyoxyethylene addition coefficient of 8 to 10 A polyoxyethylene alkyl ether having an alkyl group having 13 to 15 carbon atoms; a polyoxyethylene addition coefficient of 10 to 18 and a polyoxyethylene alkylphenyl ether having an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxy Ethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan, etc. are exemplified. As anionic surfactants, sulfate ester salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate; sulfosuccinate salts such as sodium lauryl sulfosulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; cocoyl sarcosine sodium, lauroyl methylalanine Acyl amino acid salts such as sodium; cocoyl methyl taurine sodium and the like are exemplified. As the zwitterionic surfactant, betaine acetate-type surfactants such as lauryldimethylaminoacetic acid betaine and coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine; imidazoline-type such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium Activator; amino acid type activators such as N-lauryldiaminoethylglycine are exemplified. These surfactants may be blended alone or in combination of two or more. The blending amount is usually 0.1 to 5 mass% with respect to the total amount of the composition.

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

Further, as a binder, for example, sodium carboxymethyl cellulose, carboxymethyl ethyl cellulose salt, hydroxyethyl cellulose, hydroxypropyl cellulose, cellulose derivatives such as hydroxypropyl methyl cellulose, xanthan gum, microbial-produced polymers such as gellan gum, tragacanth gum, karaya gum, arabia gum, carrageenan. , Natural polymers or natural rubbers such as dextrin, synthetic polymers such as polyvinyl alcohol and polyvinylpyrrolidone, thickening silica, inorganic binders such as bee gum, O-[2-hydroxy-3-(trimethylammonio) chloride] One or a combination of two or more cationic binders such as propyl]hydroxyethyl cellulose can be used.

Further, as a wetting agent, sorbit, glycerin, polypropylene glycol, xylit, maltite, lactit, polyoxyethylene glycol, etc. can be blended alone or in combination of two or more kinds.

As preservatives, parabens such as methylparaben, ethylparaben, propylparaben and butylparaben, sodium benzoate, phenoxyethanol, alkyldiaminoethylglycine hydrochloride and the like can be blended alone or in combination of two or more.

As colorants, legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral-based pigments such as ultramarine blue, reinforced ultramarine blue, and dark blue, titanium oxide, etc. may be used alone or in combination of two or more. Good.

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 or sodium hydroxide may be added. 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 compounding amount of the pH adjuster is, for example, 0.01 to 2% by weight.

A bactericide may be added as a medicinal component. For example, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, cationic fungicides such as chlorhexidine gluconate, amphoteric fungicides such as dodecyldiaminoethylglycine, triclosan, nonionic fungicides such as isopropylmethylphenol, Hinokitiol and the like can be mentioned. Further, medicinal components other than the bactericide can be blended. For example, aluminum lactate, potassium nitrate, dl-α-tocopherol acetate, tocopherol succinate, or vitamin Es such as tocopherol nicotinate, sodium fluoride or the like may be added. The medicinal components can be blended alone or in combination of two or more. Among them, aluminum lactate and potassium nitrate are particularly preferable for compounding in the oral composition of the present invention, because they are medicinal components for preventing hyperesthesia.

Further, as a base, for example, alcohols, silicon, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase and the like can be added alone or in combination of two or more kinds.

The above description of the optional components is an example, and does not limit the optional components that can be used.

In addition, in this specification, "comprising" includes "consisting essentially of" and "consisting of." is also included including "consisting essentially of" and "consisting of". Further, the invention includes all combinations of the constituent elements described in this specification.

Further, various characteristics (properties, structures, functions, etc.) described in the above-described embodiments of the present invention may be combined in any manner to specify the subject matter included in the present invention. That is, the invention includes all subject matter that is made up of any combination of the combinable properties described herein.

Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to these examples.

Example 1
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry (BET ratio) so that the Ca/P molar ratio becomes 0.5. Surface area: 6.7 m ² /g Oxalic acid reactivity: 15 minutes and 30 seconds JP, 2017-036176, A) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless beaker, heated to 60° C. with stirring, and maintained until the stirring was stopped. The pH was adjusted to 5.5 by adding 10% aqueous NaOH solution. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain hydroxyapatite particles (powder).

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

The measurement was performed in the range of 2θ=25 to 45° by 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°, light receiving slit: 0.3 mm. The results are shown in Figure 1. Moreover, the X-ray diffraction pattern of hydroxyapatite (reagent HAp) which is a commercially available reagent product is shown in FIG. 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, and the peak intensity ratio of the reagent HAp was 2.7. The result was clearly lower than that of. From this, it was found that the obtained hydroxyapatite particles were plate-shaped crystal aggregates in which the c-plane was exposed in a relatively large amount. In addition, the total area of all the diffraction peaks within the range of 25°≦2θ≦35° is 100%, and the area of all the diffraction peaks within the range of 25.5°≦2θ≦26.5° is 31%. The total area of all diffraction peaks within the range of 0.5°≦2θ≦32.5° was 37.2%. This value is clearly lower than 52.1% shown by the reagent HAp, and the crystallinity is low because the X-ray diffraction pattern is relatively broad. Further, 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 the reagent HAp, which also indicates low crystallinity. ..

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

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

The Ca/P molar ratio of the hydroxyapatite particles was calculated from the measured values by measuring the Ca and P contents by inductively coupled plasma optical emission spectroscopy using iCAP 6000 ICP-OES (manufactured by ThermoFisher). As a result, the Ca/P molar ratio was 1.33.

The shape of the hydroxyapatite particles was observed by using a scanning electron microscope (manufactured by JEOL Ltd.: hereinafter SEM). Results are shown in FIG. From this result, it was shown that the hydroxyapatite particles obtained were aggregates of plate crystals.

Example 2
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry (BET ratio) so that the Ca/P molar ratio becomes 0.5. Surface area: 7.9 m ² /g Oxalic acid reactivity: 12 minutes 30 seconds JP 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless beaker, heated to 60° C. with stirring, and maintained until the stirring was stopped. The pH was adjusted to 6.0 by adding 10% NaOH aqueous solution. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain hydroxyapatite particles (powder).

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

The X-ray crystal diffraction result is shown in FIG. 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. .. In addition, the total area of all the diffraction peaks within the range of 25°≦2θ≦35° is 100%, and the area of all the diffraction peaks within the range of 25.5°≦2θ≦26.5° is 31%. The total area of all diffraction peaks within the range of 0.5°≦2θ≦32.5° was 38.6%. The crystallite size calculated from the diffraction peak of the (130) plane near 2θ=40° was 7 nm.

The specific surface area was 75.4 m ² /g.

The shape observation result is shown in FIG. As in Example 1, it was confirmed to be an aggregate of plate crystals.

Example 3
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry (BET ratio) so that the Ca/P molar ratio becomes 0.5. Surface area: 7.9 m ² /g Oxalic acid reactivity: 12 minutes 30 seconds JP-A-2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless beaker, heated to 40° C. with stirring, and maintained until the stirring was stopped. The pH was adjusted to 5.5 by adding 10% aqueous NaOH solution. The calcium hydroxide slurry was added thereto over 50 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain hydroxyapatite particles (powder).

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

The X-ray crystal diffraction result is shown in FIG. The ratio of the diffraction peak intensity by the (211) plane near 2θ=32° to the ratio of the diffraction peak intensity by the (002) plane near 2θ=26° was 1.2, which was the same value as in Example 1. .. In addition, the total area of all the diffraction peaks within the range of 25°≦2θ≦35° is 100%, and the area of all the diffraction peaks within the range of 25.5°≦2θ≦26.5° is 31%. The total area of all diffraction peaks within the range of 0.5°≦2θ≦32.5° was 36.0%. The crystallite size calculated from the diffraction peak of the (130) plane near 2θ=40° was 6 nm.

The specific surface area was 81.5 m ² /g.

The shape observation result is shown in FIG. It was confirmed that the hydroxyapatite particles obtained in the same manner as in Example 1 were plate-shaped crystal aggregates.

Example 4
A 10.7 mass% sodium dihydrogen phosphate anhydrous aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry (BET specific surface area 7. 9 m ² /g oxalic acid reactivity: 12 minutes and 30 seconds (JP-A-2017-036176). An anhydrous sodium dihydrogen phosphate aqueous solution was placed in a stainless beaker and heated to 80° C. with stirring. The pH remained at 4.2 and was not adjusted. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain hydroxyapatite particles (powder).

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

The X-ray crystal diffraction result is shown in FIG. The ratio of the diffraction peak intensity by the (211) plane near 2θ=32° to the ratio of the diffraction peak intensity by the (002) plane near 2θ=26° was 1.4, which was the same value as in Example 1. .. In addition, the total area of all the diffraction peaks within the range of 25°≦2θ≦35° is 100%, and the area of all the diffraction peaks within the range of 25.5°≦2θ≦26.5° is 31%. The total area of all diffraction peaks within the range of 0.5°≦2θ≦32.5° was 37.8%. The crystallite size calculated from the diffraction peak of the (130) plane near 2θ=40° was 9 nm.

The specific surface area was 163.4 m ² /g.

The shape observation result is shown in FIG. It was confirmed that the hydroxyapatite particles obtained in the same manner as in Example 1 were plate-shaped crystal aggregates.

Example 5
A 10.7 mass% sodium dihydrogen phosphate anhydrous aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry (BET specific surface area 7. 9 m ² /g oxalic acid reactivity: 12 minutes and 30 seconds (JP-A-2017-036176). The anhydrous sodium dihydrogen phosphate aqueous solution was placed in a stainless beaker and heated to 60° C. with stirring. The pH remained at 4.2 and was not adjusted. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain hydroxyapatite fine particles (powder).

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

The X-ray crystal diffraction result is shown in FIG. 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. .. In addition, the total area of all the diffraction peaks within the range of 25°≦2θ≦35° is 100%, and the area of all the diffraction peaks within the range of 25.5°≦2θ≦26.5° is 31%. The sum total with the area of all diffraction peaks within the range of 0.5°≦2θ≦32.5° was 31.6%. The crystallite size calculated from the diffraction peak of the (130) plane near 2θ=40° was 7 nm.

The specific surface area was 94.7 m ² /g.

The shape observation result is shown in FIG. It was confirmed to be an aggregate of plate-like fine particles as in Example 1.

Comparative Example 1
A 10.7 mass% sodium dihydrogen phosphate anhydrous aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry (BET specific surface area 7. 9 m ² /g oxalic acid reactivity: 12 minutes and 30 seconds (JP-A-2017-036176). The calcium hydroxide slurry was placed in a stainless beaker and heated to 40°C with stirring. An anhydrous sodium dihydrogen phosphate aqueous solution (pH: 4.2) was added thereto over 30 minutes. After completion of the addition, the mixture was further stirred for 1 hour, then filtered, washed with water, and dried at 80° C. to obtain hydroxyapatite particles (powder).

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

The X-ray crystal diffraction result is shown in FIG. The ratio of the diffraction peak intensity by the (211) plane near 2θ=32° to the ratio of the diffraction peak intensity by the (002) plane near 2θ=26° is 1.7, which is clearly higher than that in Example 1. Showed the value. Further, a diffraction peak due to the (300) plane near 2θ=33° appeared separately.

The specific surface area was 50.9 m ² /g.

The shape observation result is shown in FIG. It was confirmed that the obtained hydroxyapatite particles were formed by aggregation of spindle-shaped crystals.

Comparative example 2
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry so that the Ca/P molar ratio becomes 0.5 (Patent Document 1) No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless beaker, heated to 60° C. with stirring, and maintained until the stirring was stopped. The pH remained at 4.2 and was not adjusted. The calcium hydroxide slurry was added thereto over 45 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain a sample.

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

The X-ray crystal diffraction result is shown in FIG. In addition to the diffraction peak of hydroxyapatite, diffraction peaks of other substances were confirmed. The peaks indicated by black circles in the figure are diffraction peaks of monetite, which is calcium phosphate that is easily generated in an acidic state.

The shape observation result is shown in FIG. Large plate-shaped particles of monetite were confirmed.

Comparative Example 3
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a solid content concentration of 8.6 mass% high-purity calcium hydroxide slurry (BET specific surface area) so that the Ca/P molar ratio becomes 0.5. : 2.4 m ² /g, oxalic acid reactivity: 25 seconds JP 2011-126772 A) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless beaker, heated to 60° C. with stirring, and maintained until the stirring was stopped. The pH was adjusted to 5.5 by adding 10% aqueous NaOH solution. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain a sample.

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

The X-ray crystal diffraction result is shown in FIG. In addition to the diffraction peak of hydroxyapatite, the diffraction peaks of calcium hydroxide were confirmed near 2θ=28° and around 34°.

Further, the result of shape observation is shown in FIG. 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.

Comparative Example 4
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry (BET ratio) so that the Ca/P molar ratio becomes 0.5. Surface area: 7.9 m ² /g Oxalic acid reactivity: 12 minutes 30 seconds JP-A-2017-036176) was prepared. The sodium dihydrogen phosphate dihydrate aqueous solution was placed in a stainless beaker, and 10% NaOH aqueous solution was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over 50 minutes. After the addition was completed, the mixture was further stirred for 1 hour, then the stirring was stopped, the mixture was allowed to stand at room temperature for 9 days, filtered, washed with water, and dried at 80° C. to obtain hydroxyapatite particles (powder).

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

The X-ray crystal diffraction result is shown in FIG. 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.

The shape observation result is shown in FIG. It was confirmed that the particle shape was an aggregate of fine spindle-shaped particles.

Comparative Example 5
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a solid content concentration of 8.6 mass% milled calcium hydroxide slurry so that the Ca/P molar ratio becomes 0.5 (Patent Document 1) No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless beaker, heated to 80° C. with stirring, and maintained until the stirring was stopped. The pH remained at 4.2 and was not adjusted. The calcium hydroxide slurry was added thereto over 50 minutes. After the addition was completed, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80° C. to obtain a sample.

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

The X-ray crystal diffraction result is shown in FIG. In addition to the diffraction peak of hydroxyapatite, diffraction peaks of other substances were confirmed. The peaks indicated by black circles in the figure are diffraction peaks of monetite, which is calcium phosphate that is easily generated in an acidic state.

The result of shape observation is shown in FIG. Large plate-shaped particles of monetite were confirmed.

Test Example 1. Crystallinity change confirmation test [Purpose of test]
In order to evaluate the reactivity of hydroxyapatite particles in the oral cavity, changes in crystallinity before and after immersion in artificial saliva were measured by a powder X-ray diffractometer.

[Test method]
0.5 g of hydroxyapatite particles obtained in the same manner as in Example 1 was mixed with artificial saliva (CaCl ₂ : 1.5 mM, KH ₂ PO ₄ : 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH). ) Immersed in 200 mL for 7 days. The powder separated by suction filtration was measured by a powder X-ray diffractometer to observe the change in crystallinity before and after the immersion in artificial saliva.

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

The results are shown in Fig. 22. Immersion in artificial saliva confirmed that the crystallinity was improved (peak sharpness increased, and peaks hidden by broad appearance appeared). From this, it was confirmed that the hydroxyapatite particles of the present invention are particles that change (have reactivity) in the oral cavity.

A similar study was conducted using known hydroxyapatite particles instead of the hydroxyapatite particles obtained in the same manner as in Example 1, and the peak did not change at all before and after the artificial saliva immersion, and the crystallinity was improved. Did not change.

Test example 2. Test for blocking dentin tubules of hydroxyapatite particles [Purpose of test]
In order to evaluate the ability of hydroxyapatite particles to block dentinal tubules, the surface of bovine dentin was brushed with a hydroxyapatite particle liquid, and the degree of dentinal tubule blockage was examined by electron microscope (SEM) observation.

[Test method]
Creation of dentin block (sample) 1. The dentin of the root surface of the extracted bovine tooth was cut into a size of 5×5 mm.
2. The cut out tooth pieces were embedded in a resin resin (polymethylmethacrylate) to form a block, which was polished with a water-resistant abrasive paper to expose the surface.
3. The dentin block was immersed in a 5% w/w EDTA aqueous solution (pH 7.0) for 2 minutes.
4. Sonication was performed for 5 minutes in distilled water.

Preparation of hydroxyapatite particle liquid 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 hydroxyapatite particles as a liquid. The viscous diluent is an aqueous solution containing 0.5 w/w% sodium carboxymethyl cellulose and 10 w/w% glycerin.

Brushing process 6. The dentin block was brushed with a toothbrush (GUM #211) for 30 seconds in a hydroxyapatite particle liquid (40 g) (stroke: 150 rpm, load: 160 g).
7. The dentin block was washed with water and then 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.

SEM observation 9. After the surface was vapor-deposited, it was observed with an electron microscope.

[Observation and measurement conditions]
{Deposition process}
・Model used: MCI1000 (Hitachi High-Technologies Corporation)
・Current: 20mA
・Processing time: 120 seconds {SEM observation}
・Model used: S-3400N (Hitachi High-Technologies Corporation)
・Detector: SE (secondary electron image)
・Applied voltage: 5kV
・Probe current: 50mA
-Magnification: 25,000 times.

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

Test example 3. Adhesion test [Purpose of test ]
In order to evaluate the ability of hydroxyapatite particles to stick in dentinal tubules, after brushing the bovine dentin surface with a hydroxyapatite particle solution, water pressure was applied from the back surface of the dentin, and whether the water pressure was blocked by the hydroxyapatite particles. Was examined by electron microscope (SEM) observation.

[Test method]
Making a dentin disc (sample) 1. The dentin of the root surface of the extracted bovine tooth was cut into a size of 5×5 mm.
2. The cut-out tooth pieces were polished with water-resistant abrasive paper.
3. The obtained dentin disk was immersed in a 5% w/w EDTA aqueous solution (pH 7.0) for 2 minutes.
4. Sonication was performed for 5 minutes in distilled water.

Preparation of hydroxyapatite particle liquid 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 liquid. The viscous diluent is an aqueous solution containing 0.5 w/w% sodium carboxymethyl cellulose and 10 w/w% glycerin.

Brushing process 6. The dentin disk was brushed with a toothbrush (GUM #211) for 30 seconds in a hydroxyapatite particle liquid (40 g) (stroke: 150 rpm, load: 160 g).
7. The disc was washed with water and then 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.

Water pressure treatment 10. The dentin discs after the brushing treatment are referred to by Pashley, et al. The pressure was applied at 0.1 MPa for 30 minutes using the apparatus described above.

SEM observation 11. After the surface was vapor-deposited, it was observed with an electron microscope.

[Observation and measurement conditions]
{Deposition process}
・Model used: MCI1000 (Hitachi High-Technologies Corporation)
・Current: 20mA
・Processing time: 120 seconds {SEM observation}
・Model used: S-3400N (Hitachi High-Technologies Corporation)
・Detector: SE (secondary electron image)
・Applied voltage: 5kV
・Probe current: 50mA
-Magnification: 25,000 times.

The results are shown in Fig. 24. It was confirmed that the dentinal tubules were blocked even after the hydraulic treatment. From this, it was confirmed that the hydroxyapatite particles were particles that were fixed in the dentinal tubules and maintained the blocked state.

Test example 4. Dentifrice dentinal tubule sealing test [purpose of test]
In order to confirm the ability of the toothpaste preparation containing the material to seal the dentin tubules, the bovine dentin surface was brushed with the material solution, and the degree of sealing of the dentin tubules was examined by an electron microscope (SEM).

[Test method]
Creation of dentin block (sample) 1. The dentin of the root surface of the extracted bovine tooth was cut into a size of 5×5 mm.
2. The cut out tooth pieces were embedded in a resin resin (polymethylmethacrylate) to form a block, which was polished with a water-resistant abrasive paper to expose the surface.
3. The dentin block was immersed in a 5 w/w% EDTA aqueous solution (pH 7.0) for 2 minutes.
4. Sonication was performed for 5 minutes in distilled water.

Preparation of dentifrice 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 Table 1 below. In the following, the unit "%" of the compounding amount in the table indicates mass%.

Brushing process 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 (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.

SEM observation 9. After the surface was vapor-deposited, it was observed with an electron microscope.

[Observation and measurement conditions]
{Deposition process}
・Model used: MCI1000 (Hitachi High-Technologies Corporation)
・Current: 20mA
・Processing time: 120 seconds {SEM observation}
・Model used: S-3400N (Hitachi High-Technologies Corporation)
・Detector: SE (secondary electron image)
・Applied voltage: 5 kV
・Probe current 50mA
・Magnification: 25,000 times

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

Test example 5. Test for sealing dentinal tubules when applying a gel formulation with a soft pick [Test purpose]
In order to confirm the ability of the gel formulation containing hydroxyapatite particles to seal the dentinal tubules, the gel formulation was applied to the bovine dentin surface using a soft pick (rubber interdental brush) to determine the degree of dentinal tubule sealing. It was examined under a microscope (SEM).

[Test method]
Creation of dentin block (sample) 1. The dentin of the root surface of the extracted bovine tooth was cut into a size of 5×5 mm.
2. The cut out tooth pieces were embedded in a resin resin (polymethylmethacrylate) to form a block, which was polished with a water-resistant abrasive paper to expose the surface.
3. The dentin block was immersed in a 5 w/w% EDTA aqueous solution (pH 7.0) for 2 minutes.
4. Sonication was performed for 5 minutes in distilled water.
5. The two dentin blocks were fixed with a tape so that the dentin surfaces face each other with a gap of 1.1 mm, to form a pseudo interdental space.

Coating process 6. The gel preparation containing (or not containing) hydroxyapatite particles obtained in the same manner as in Example 1 was placed on the brush portion of a soft pick (gum/soft pick curve type: Sunstar Co., Ltd.) and inserted into the void. I made 5 round trips. The composition of the gel preparation is shown in Table 2 below.
7. The dentin block was washed with water.

SEM observation 8. After the surface was vapor-deposited, it was observed with an electron microscope.

[Observation and measurement conditions]
{Deposition process}
・Model used: MCI1000 (Hitachi High-Technologies Corporation)
・Current: 20mA
・Processing time: 120 seconds {SEM observation}
・Model used: S-3400N (Hitachi High-Technologies Corporation)
・Detector: SE (secondary electron image)
・Applied voltage: 5 kV
・Probe current 50mA
・Magnification: 25,000 times

Results are shown in FIG. It was confirmed that the dentinal tubules were blocked by applying the gel formulation containing hydroxyapatite particles by soft pick.

Test example 6. Clinical trial of gel formulation [Purpose of study]
The clinical effect of a gel formulation containing hydroxyapatite particles on antihypersensitivity was examined. In the examination, hydroxyapatite particles obtained in the same manner as in Example 1 were used as the hydroxyapatite particles.

[Trial design]
(I) Gel preparation (HAp+Al+K) containing hydroxyapatite particles, aluminum lactate and potassium nitrate, (ii) Gel preparation (Al+K) containing aluminum lactate and potassium nitrate, and (iii) Gel preparation (K) containing potassium nitrate. The three formulations were compared. The composition of these gel formulations is shown in Table 3 below.

Each of the gel preparations was used by 20 people, and the degree of abrasion pain (horizontal abrasion by applying a probe to the exposed root surface part) at 1, 2 or 4 weeks after use was measured by VAS scale. It was described in. In addition, the VAS scale shows a black line with a length of 10 cm (the left end is “no pain at all” and the right end is “most painful/strong pain”) to the patient, and indicates how much the current pain is. It is a visual scale. Further, the flow of the test is shown in FIG. In FIG. 27, the “hypersensitivity care set (gel preparation (test product))” indicates the gel preparation of (i) to (iii) above, and the “hypersensitivity care set (gel preparation (placebo product))” indicates the above. The gel formulation which removed potassium nitrate from the gel formulation of (iii) is shown.

[How to use test products]
The test subjects were allowed to use the gel preparation (test product) twice a day (morning/evening) (after wake-up, after meals, before bedtime, etc., and not according to their own oral cleaning habits). Specifically, first, after brushing with a specified toothbrush (Gum Pros Dental Brush #3C: Sunstar Co., Ltd.) and a dentifrice (COPE non-foam toothpaste N), rinse with mouth with about 10 ml of water for 20 seconds ( The brushing time is not specified.), and then the gel preparation was used. To use the gel preparation, specifically, use a tuft brush (Butler Single Tuft Brush #01F: Sunstar Co., Ltd.) with about 0.04 g (about a rice grain size) of gel preparation (test product) for one test tooth. It was applied to the test site, and the test site and both adjacent teeth were brushed for 5 seconds or more per tooth. If a designated interdental cleaning tool (gum/soft pick curve type: Sunstar Co., Ltd.) can be inserted between the test site and both adjacent teeth, the interdental cleaning tool should be inserted between the test site and both adjacent teeth. It was inserted into the interdental part from the buccal side and reciprocated 5 times. After using the gel preparation (test product), the mouth was rinsed with about 10 ml of water for 20 seconds.

FIG. 28 shows the result of evaluation of the degree of scratches on the VAS scale. In the hydroxyapatite-containing preparation use group, abrasion pain was significantly improved one week after use, as compared with the non-use combination use group. From this, it was found that the hydroxyapatite-containing preparation has an effect of suppressing the hypersensitivity symptom at an early stage by using it in combination with the known drug components for preventing hypersensitivity such as aluminum lactate and potassium nitrate.

Claims (8)

An oral composition containing hydroxyapatite particles,
The hydroxyapatite particles have a ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° in the powder X-ray diffraction pattern measured by CuKα characteristic X-ray of 0.8 to 1.5. is there,
Oral composition. The oral composition according to claim 1, wherein the hydroxyapatite particles have a Ca/P molar ratio of less than 1.67. The oral composition according to claim 1, wherein the hydroxyapatite particles have a median diameter of 5 μm or less. The oral composition according to claim 1, wherein the hydroxyapatite particles have a specific surface area of 55 to 200 m ² /g. The hydroxyapatite particles have a ratio of a diffraction peak intensity around 2θ=34° to a diffraction peak intensity around 2θ=32° in a powder X-ray diffraction pattern measured by CuKα characteristic X-ray of 1 or less. The composition for oral cavity according to any one of to 4. The hydroxyapatite particles are aggregates of hydroxyapatite plate crystals,
The composition for oral cavity according to any one of claims 1 to 5. Furthermore, the composition for oral cavity in any one of Claims 1-6 containing potassium nitrate and/or aluminum lactate. The composition for oral cavity according to any one of claims 1 to 7, which is for preventing or improving hyperesthesia.