JP7346102B2 - Oral composition - Google Patents

Description

The present disclosure relates to oral compositions and the like, and more particularly to oral compositions containing hydroxyapatite particles. Note that the contents of all documents described in this specification (particularly Japanese Patent Application Laid-open No. 2017-036176) are incorporated into this specification by reference.

Hypersensitivity in teeth occurs when the dentin of the tooth is exposed due to physical abrasion such as brushing, chemical abrasion due to acid, etc. When dentin is exposed, external stimuli stimulate the nerves within the dentinal tubules in the dentin, making it easier to experience pain.

For hypersensitivity, attempts have been made to block the dentinal tubules with particles such as fluoride and aluminum salt (see, for example, Patent Document 1) to prevent external stimuli from reaching the nerves. . However, most of the conventional methods have insufficient adhesion after sealing and have problems with sustainability of effects.

Japanese Patent Application Publication No. 2010-222325 Publication of Unexamined Patent Publication No. 2017-036176

It is an object of the present invention to provide particles that have the ability to seal dentinal tubules and have excellent adhesion within the dentinal tubules.

The present inventors conducted intensive research in view of the above problems and found that the ratio of the diffraction peak intensity around 2θ = 32° to the diffraction peak intensity around 2θ = 26° in the X-ray diffraction pattern of a specific hydroxyapatite particle (X-ray diffraction pattern) It has been found that hydroxyapatite particles having a particle diameter of 0.8 to 1.5) can solve the above problems. Based on this knowledge, further investigation was conducted.

The present disclosure includes, for example, the embodiments described in the following sections.
Item 1.
An oral composition containing hydroxyapatite particles, the composition comprising:
The hydroxyapatite particles have a powder X-ray diffraction pattern measured by CuKα characteristic X-rays, in which the ratio of the diffraction peak intensity around 2θ = 32° to the diffraction peak intensity around 2θ = 26° is 0.8 to 1.5. be,
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.
Items 1 to 1, wherein 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-rays of 1 or less. 4. The oral composition according to any one of 4.
Item 6.
the hydroxyapatite particles are aggregates of hydroxyapatite plate crystals;
Item 5. The oral composition according to any one of Items 1 to 5.
Section 7.
Item 7. The oral composition according to any one of Items 1 to 6, further containing potassium nitrate and/or aluminum lactate.
Section 8.
Item 8. The oral composition according to any one of Items 1 to 7, which is used to prevent or improve hypersensitivity.
Item 9.
The hydroxyapatite particles were produced by a method for producing hydroxyapatite particles, which includes a step of mixing an aqueous alkali phosphate salt solution with a pH of 4 or more and less than 7 and a calcium hydroxide slurry and reacting the mixture at 35 to 85°C. Item 9. The oral composition according to any one of Items 1 to 8.
Item 10.
10. The oral cavity composition according to item 9, wherein the calcium hydroxide slurry is a ground calcium hydroxide slurry.
Item 11.
Oxalic acid reactivity of the calcium hydroxide slurry (50 g of calcium hydroxide slurry prepared to a concentration of 5% by mass and kept at 25 ± 1°C was added with 0.5 mol/liter of calcium hydroxide slurry kept at 25 ± 1°C) Item 11. The oral composition according to Item 9 or 10, wherein 40 g of a concentrated oxalic acid aqueous solution is added at once and the time (minutes) until the pH reaches 7.0 after 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.
However, further studies revealed that when cetylpyridinium chloride (CPC), which is a component frequently used as a bactericidal agent in the field of oral compositions, is added to the oral composition containing the hydroxyapatite particles, It was found that apatite strongly adsorbs CPC and inhibits CPC from achieving its original effects. From this, it was thought that in the oral composition containing the above hydroxyapatite and CPC, it would be preferable to take measures to suppress the adsorption of CPC by the above hydroxyapatite, and further studies focused on this point. As a result, they found that in an oral composition containing magnesium chloride or γ-cyclodextrin in addition to the hydroxyapatite and CPC, the adsorption of the hydroxyapatite to CPC was suppressed.
Therefore, the present invention also includes, for example, the embodiments described in the following sections.
Section 1a.
hydroxyapatite particles,
cetylpyridinium chloride, and
An oral composition containing at least one member selected from the group consisting of magnesium chloride and γ-cyclodextrin,
The hydroxyapatite particles have a powder X-ray diffraction pattern measured by CuKα characteristic X-rays, in which the ratio of the diffraction peak intensity around 2θ = 32° to the diffraction peak intensity around 2θ = 26° is 0.8 to 1.5. be,
Oral composition.
Section 2a.
Item 1a. The oral composition according to Item 1a, wherein the hydroxyapatite particles have a Ca/P molar ratio of less than 1.67 (preferably 1.60 or less).
Section 3a.
Item 1a or 2a, wherein the hydroxyapatite particles have a median diameter of 5 μm or less.
Section 4a.
The oral composition according to any one of Items 1a to 3a, wherein the hydroxyapatite particles have a specific surface area of 55 to 200 m ² /g.
Section 5a.
Items 1a to 3, wherein the hydroxyapatite particles have a ratio of the diffraction peak intensity around 2θ = 34° to the diffraction peak intensity around 2θ = 32° in a powder X-ray diffraction pattern measured by CuKα characteristic X-rays of 1 or less. 4a. The oral composition according to any one of 4a.
Section 6a.
the hydroxyapatite particles are aggregates of hydroxyapatite plate crystals;
The oral composition according to any one of Items 1a to 5a.
Section 7a.
The oral composition according to any one of Items 1a to 6a, further comprising potassium nitrate and/or aluminum lactate.
Section 8a.
The oral composition according to any one of Items 1a to 7a, which is for preventing or improving hypersensitivity.
Section 9a.
The hydroxyapatite particles were produced by a method for producing hydroxyapatite particles, which includes a step of mixing an aqueous alkali phosphate salt solution with 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 oral composition according to any one of Items 1a to 8a, which is
Section 10a.
The oral composition according to item 9a, wherein the calcium hydroxide slurry is a ground calcium hydroxide slurry.
Section 11a.
Oxalic acid reactivity of the calcium hydroxide slurry (50 g of calcium hydroxide slurry prepared to a concentration of 5% by mass and kept at 25 ± 1°C was added with 0.5 mol/liter of calcium hydroxide slurry kept at 25 ± 1°C) Item 9a or 10a, wherein 40 g of a concentrated oxalic acid aqueous solution is added at once, and the time (minutes) until the pH reaches 7.0 after addition is 40 minutes or less.
Section 12a.
Item 9. The oral composition according to any one of items 9a to 11a, wherein the calcium hydroxide slurry has a BET specific surface area of 5 m ² /g or more.

Provided is an oral cavity composition that has the ability to seal dentinal tubules and has excellent adhesion within the dentinal tubules. In addition, the oral composition can achieve this effect by containing a specific hydroxyapatite, but the hydroxyapatite adsorbs CPC, but magnesium chloride or γ-cyclodextrin prevents this adsorption. Can be suppressed.

1 shows X-ray diffraction peaks of hydroxyapatite particles of Example 1. 1 shows the X-ray diffraction peaks of commercially available reagent hydroxyapatite particles. A SEM photograph of hydroxyapatite particles of Example 1 is shown. 3 shows X-ray diffraction peaks of hydroxyapatite particles of Example 2. A SEM photograph of hydroxyapatite particles of Example 2 is shown. 3 shows X-ray diffraction peaks of hydroxyapatite particles of Example 3. A SEM photograph of hydroxyapatite particles of Example 3 is shown. 3 shows X-ray diffraction peaks of hydroxyapatite particles of Example 4. A SEM photograph of hydroxyapatite particles of Example 4 is shown. 3 shows the X-ray diffraction peaks of the hydroxyapatite fine particles of Example 5. A SEM photograph of hydroxyapatite fine particles of Example 5 is shown. 1 shows the X-ray diffraction peaks of hydroxyapatite particles of Comparative Example 1. A SEM photograph of hydroxyapatite particles of Comparative Example 1 is shown. The X-ray diffraction peak of the sample of Comparative Example 2 is shown. The peak indicated by a black circle is the diffraction peak of monetite. A SEM photograph of a sample of Comparative Example 2 is shown. The X-ray diffraction peak of the sample of Comparative Example 3 is shown. A SEM photograph of a sample of Comparative Example 3 is shown. The X-ray diffraction peak of the hydroxyapatite particles of Comparative Example 4 is shown. A SEM photograph of hydroxyapatite particles of Comparative Example 4 is shown. The X-ray diffraction peak of the sample of Comparative Example 5 is shown. The peak indicated by a black circle is the diffraction peak of monetite. A SEM photograph of a sample of Comparative Example 5 is shown. The X-ray diffraction peaks of hydroxyapatite particles before and after immersion in artificial saliva (Test Example 1) are shown. SEM photographs (Test Example 2) of dentinal tubules before and after brushing are shown. SEM photographs (Test Example 3) of dentinal tubules before and after water pressure treatment are shown. SEM photographs (Test Example 4) of dentinal tubules before and after brushing with a dentifrice solution containing hydroxyapatite particles are shown. SEM photographs (Test Example 5) of dentinal tubules before and after applying a gel preparation containing hydroxyapatite particles to dentin using a soft pick are shown. The flow of a clinical trial using a gel formulation containing hydroxyapatite particles is shown. The results are shown in which the degree of pain from rubbing was evaluated using a VAS scale in a clinical trial using a gel preparation containing hydroxyapatite particles. In an oral composition containing hydroxyapatite particles and cetylpyridinium chloride, it is a graph showing how much water solubility of cetylpyridinium chloride is maintained without being adsorbed to the particles. In an oral composition containing cetylpyridinium chloride, it is a graph showing to what extent the water solubility of cetylpyridinium chloride is maintained without being adsorbed to the particles.

Each embodiment included in the present disclosure will be described in further detail below. Note that the present disclosure preferably includes oral compositions, particularly oral compositions containing specific hydroxyapatite particles, but is not limited thereto; includes everything that can be recognized.

Oral compositions encompassed by this disclosure contain certain hydroxyapatite particles. Note that in this specification, the oral composition may be referred to as "the oral composition of the present disclosure."

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. . Note that in this specification, the hydroxyapatite particles may be referred to as "particles of the present disclosure."

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°. This is the diffraction peak of When multiple diffraction peaks exist 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°. This is the diffraction peak of When there are multiple diffraction peaks around 2θ=32°, it means the diffraction peak with the highest intensity.

In this specification, an X-ray diffraction pattern is a powder X-ray diffraction pattern measured by CuKα characteristic X-rays. Examples of measurement conditions include the following conditions. Target: Cu, tube voltage 40kV, tube current: 30mA, sampling width: 0.02°, scan speed: 2.00°/min, divergence slit: 1.0°, scattering slit: 1.0°, light receiving slit: 0.3mm.

In the particles of the present disclosure, the ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° (32°/26°) is 0.8 to 1.5. The peak intensity ratio is preferably 0.9 to 1.3, more preferably 1.0 to 1.25, even more preferably 1.05 to 1.2, even more preferably 1.05 to 1.15. be.

In the particles of the present disclosure, each particle itself is preferably an aggregate of hydroxyapatite plate crystals. The shape of the plate crystals constituting the particles of the present disclosure is not particularly limited, and examples thereof include a circle, a polygon (particularly a hexagon), a shape close to a rod shape, or a combination thereof. Further, the plate crystal may be in either a state in which the planes are bent or in a state in which the plane structure is maintained without bending the planes. Note that plate-shaped hydroxyapatite crystals usually 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. Further, when a particle is formed of a plurality of crystals, the crystals are called crystallites.

The particles of the present disclosure are particles containing hydroxyapatite as a main component, preferably particles consisting essentially of hydroxyapatite. In the X-ray diffraction pattern of the particles of the present disclosure, even when other substances (eg, monetite, etc.) are included, 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.

Although not intended to be interpreted as limiting, the particles of the present disclosure have a shape and structure expressed by a specific X-ray diffraction pattern, and are composed of agglomerated plate-like particles. It is thought that these factors combine to exhibit excellent sealing properties of dentinal tubules and excellent adhesion within dentinal tubules.

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

The particles of the present disclosure preferably have all diffraction peaks within the range of 25.5°≦2θ≦26.5° for 100% of the total area of all diffraction peaks within the range of 25°≦2θ≦35°. The sum of the area of the diffraction peak 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 33-42%, more preferably 35-40%. Further, in the particles of the present disclosure, the crystallite size 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 we do not wish to give a restrictive interpretation, it is thought that the relatively low crystallinity increases the ability of crystals to grow within the tubules after sealing the dentinal tubules, and that this further improves the adhesion within the tubules. Conceivable.

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 we do not wish to give a restrictive interpretation, it is believed that in the particles of the present disclosure, some of the calcium is substituted with other elements (sodium, etc.), and therefore the Ca/P molar ratio is relatively low. It can be a low value. From this point of view, 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, even more preferably 1.55 or less, or more 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 disclosure is not particularly limited and may be, for example, 1.0, 1.1, or 1.2. Note that 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 measured by inductively coupled plasma emission spectrometry.

The median diameter (d50) of the particles of the present disclosure is not particularly limited, but from the viewpoint of dentinal tubule sealing properties, adhesion properties, 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, but may be, for example, 1 μm or more, 2 μm or more, or 3 μm or more. More specifically, the thickness is, for example, 1 to 5 μm. Note that the median diameter is a value measured by a laser diffraction/scattering method. More specifically, it is a value measured by dry particle size distribution measurement using a laser diffraction particle size distribution measuring device.

The specific surface area of the particles of the present disclosure is not particularly limited, but from the viewpoint of dentinal tubule sealing properties, adhesion properties, etc., it is, 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, or 90 m ² /g. Note that the specific surface area is a value measured by a nitrogen gas adsorption method.

The particles of the present disclosure preferably react with saliva to improve crystallinity. Here, the term "improved crystallinity" means that in the powder X-ray diffraction pattern measured by CuKα characteristic X-rays, there is at least one (preferably 1, 2, 3, 4, or more) after the saliva reaction than before the saliva reaction. (more specifically, the diffraction intensity is improved). As saliva, artificial saliva ( _CaCl2 : 1.5mM, _KH2PO4 : _0.9mM , KCl: 130mM, HEPES: 20mM, pH 7.0 (KOH)) is used. The reaction is also carried out by immersing the particles in saliva for 7 days.

The particles of the present disclosure can be produced by a method for producing hydroxyapatite particles, which includes, for example, mixing an aqueous alkali phosphate salt solution with a pH of 4 or more and less than 7 and a calcium hydroxide slurry and reacting the mixture at 35 to 85°C. It can be prepared.

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

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

The pH of the aqueous alkali phosphate solution is preferably 4 or more and less than 7. The pH is more preferably 5 to 6.5. As described below, when the pH of the aqueous alkali phosphate solution is relatively low (for example, pH 4 or more and less than 5), an anhydride is used as the alkali phosphate 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, more preferably 75 to 85°C.

The calcium hydroxide slurry has oxalic acid reactivity, and the calcium hydroxide slurry is preferably a calcium hydroxide slurry that has a specific reactivity to oxalic acid.

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

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

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, or 10 m ² /g.

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

Calcium hydroxide slurry can be prepared, for example, by reacting quicklime (calcium oxide) obtained by calcining limestone with water. For example, calcium hydroxide slurry can be prepared by calcining limestone at about 1000°C in a kiln to produce quicklime, then adding about 10 times the amount of hot water to the quicklime and stirring for 30 minutes. 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 even more preferably 6 to 12% by mass.

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

The manner in which the aqueous alkali phosphate solution and calcium hydroxide slurry are mixed is not particularly limited. For example, an embodiment in which a calcium hydroxide slurry is added to a reaction vessel containing an alkali phosphate salt aqueous solution (aspect 1), an embodiment in which an alkali phosphate salt aqueous solution is added to a reaction vessel containing a calcium hydroxide slurry (aspect 2), a phosphoric acid Examples include an embodiment (Embodiment 3) in which the aqueous alkali salt solution and calcium hydroxide slurry are added to the reaction vessel at the same time. Among these, aspect 1 is preferred. 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 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, more preferably 20 to 40 minutes.

The reaction is usually carried out under stirring. The reaction temperature is 35-85°C. The reaction temperature is preferably 40 to 75°C, more preferably 45 to 70°C, even more preferably 50 to 70°C, even more preferably 55 to 65°C. When the pH of the aqueous alkali phosphate solution is relatively low (for example, pH 4 or more and less than 5), the reaction temperature is relatively high, for example 65 to 85°C, preferably 70 to 85°C, more preferably 75°C. ~85°C. Reaction time (time starting after the aqueous alkali phosphate solution and calcium hydroxide slurry are all mixed; in embodiments 1 to 3 above, time starting from the time when addition of the aqueous alkali phosphate 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, even more preferably 50 to 70 minutes.

The particles of the present disclosure produced through the above steps are subjected to purification treatment, if necessary. Examples of the purification treatment include filtration treatment, water washing treatment, and the like. Moreover, it can also be subjected to drying treatment, if necessary.

The particles of the present disclosure have the ability to seal dentinal tubules and have excellent adhesion within the dentinal tubules. Therefore, an oral composition containing the particles of the present disclosure (ie, an oral composition of the present disclosure) can be particularly preferably used for preventing or improving hypersensitivity.
The particles of the present disclosure can be contained in an oral composition, for example, about 1 to 10% by mass. The upper limit or lower limit of the content ratio range is, 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 weight. For example, the range is more preferably 2 to 8% by weight or 3 to 7% by weight.

The oral composition of the present disclosure can be manufactured by a conventional method, and can be used, for example, as a pharmaceutical, a quasi-drug, or a cosmetic. In addition, the oral composition of the present disclosure may be in any form according to conventional methods, such as ointments, pastes, pastes, gels, liquids, sprays, mouth washes, liquid dentifrices, etc., although the form thereof is not particularly limited. It can be in the form of toothpaste, liniment, etc. (dosage form). Among these, mouth rinses, liquid dentifrices, toothpastes, pastes, liquids, sprays, gels, and liniments are preferred, and toothpastes, 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 to the oral cavity, and therefore, it is preferable that the composition is in a form suitable for brushing. 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.

The oral composition of the present disclosure may further contain optional components that can be added to the oral composition, either singly or in combination of two or more, to the extent that the effects are not impaired.

For example, a bactericide may be added as a medicinal ingredient. For example, cationic fungicides such as cetylpyridinium chloride (CPC), benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate, amphoteric fungicides such as dodecyldiaminoethylglycine, and nonionic fungicides such as triclosan and isopropylmethylphenol. Examples include bactericides, hinokitiol, and the like. Furthermore, medicinal ingredients other than bactericides can also be blended. For example, vitamin E such as aluminum lactate, potassium nitrate, dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, sodium fluoride, and the like may be added. The medicinal ingredients may be used alone or in combination of two or more. Among these, aluminum lactate and potassium nitrate are particularly preferable for inclusion in the oral composition of the present disclosure, since they are medicinal ingredients for preventing hypersensitivity.

Note that when cetylpyridinium chloride (CPC) is blended into the oral composition of the present disclosure, it is preferable to further blend magnesium chloride and/or γ-dextrin. In other words, as a preferred form of the oral composition of the present disclosure, an oral composition containing the particles of the present disclosure, cetylpyridinium chloride, and at least one member selected from the group consisting of magnesium chloride and γ-dextrin. can be mentioned.

The content of CPC is, for example, about 0.01 to 1% by mass. The upper limit or lower limit of the range is, for example, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0. .2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8 , 0.85, 0.9, or 0.95% by mass. For example, the range may be about 0.05 to 0.75% by weight or about 0.1 to 0.5% by weight.

The content of magnesium chloride is, for example, about 0.1 to 10% by mass. The upper or lower limit of the range is, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2 .5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, or 9.5% by mass Good too. For example, the range may be about 0.1 to 8% by weight or about 0.2 to 6% by weight. Further, the content of magnesium chloride is preferably about 1 to 10 parts by mass, for example, based on 10 parts by mass of the particles of the present disclosure. The upper or lower limit of the range is, 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 parts by mass. For example, the range may be 2 to 9 parts by weight or 3 to 8 parts by weight.

The content of γ-cyclodextrin is, for example, about 0.05 to 10% by mass. The upper or lower limit of the range is, for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5. , 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, or 9.5 mass It may be %. For example, the range may be about 0.1 to 8% by weight or about 0.2 to 5% by weight. Further, the content of γ-cyclodextrin is preferably about 0.1 to 10 parts by mass, for example, based on 10 parts by mass of the particles of the present disclosure. The upper or lower limit of the range is, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2 .5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, or 9.5 parts by mass, Good too. For example, the range may be 0.5 to 5 parts by weight or 1 to 3 parts by weight.

As other optional components, for example, a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant can be blended as a surfactant. Specifically, nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; sorbitan fatty acid esters; fatty acid monoglycerides; and polyoxyethylene addition coefficients of 8 to 10. , polyoxyethylene alkyl ether in which the alkyl group has 13 to 15 carbon atoms; polyoxyethylene alkylphenyl ether in which the polyoxyethylene addition coefficient is 10 to 18 and the alkyl group has 9 carbon atoms; diethyl sebacate; polyoxy Examples include ethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan. Examples of anionic surfactants include sulfuric ester salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; sodium cocoyl sarcosine and lauroyl methylalanine. Acyl amino acid salts such as sodium; sodium cocoyl methyl taurate, etc. are exemplified. Examples of zwitterionic surfactants include betaine acetate type surfactants such as betaine lauryldimethylaminoacetate and betaine coconut oil fatty acid amidopropyldimethylaminoacetate; imidazoline type surfactants such as sodium N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine; Active agent: Amino acid type active agents such as N-lauryldiaminoethylglycine are exemplified. These surfactants may be used alone or in combination of two or more. The amount incorporated is usually 0.1 to 5% by mass based on the total amount of the composition.

In addition, sweeteners such as saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, asparatylphenylalanyl methyl ester, p-methoxycinnamic aldehyde, etc. may be blended. 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.

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

Further, as a wetting agent, sorbitol, glycerin, polypropylene glycol, xylit, maltit, lactit, polyoxyethylene glycol, etc. may be blended alone or in combination of two or more.

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

As a coloring agent, legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, Green No. 3, mineral pigments such as ultramarine, reinforced ultramarine, and navy blue, titanium oxide, etc. may be used alone or in combination of two or more. Good too.

As a pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically possible salts thereof, sodium hydroxide, etc. may be blended. These can be used 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, for example, 0.01 to 2% by weight.

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

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

Note that in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." Further, the present disclosure includes all arbitrary combinations of the constituent elements described in this specification.

Further, the various characteristics (properties, structures, functions, etc.) described for each embodiment of the present disclosure described above may be combined in any manner in order to specify the subject matter covered by the present disclosure. That is, the present disclosure encompasses all subject matter consisting of any and all combinations of the combinable features described herein.

In the following, the subject matter of the present disclosure will be explained in more detail based on examples, but the subject matter of the present disclosure is not limited to these examples.

Example 1
A 10.7 mass % sodium dihydrogen phosphate dihydrate aqueous solution and a ground calcium hydroxide slurry with a solid content concentration of 8.6 mass % (BET ratio Surface area: 6.7 m ² /g Oxalic acid reactivity: 15 minutes 30 seconds JP 2017-036176A) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60° C. while stirring, and maintained until stirring was stopped. The pH was adjusted to 5.5 by adding 10% NaOH aqueous solution. 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.

Measurement was performed in the range of 2θ=25 to 45° using an X-ray diffraction device MultiFlex (manufactured by Rigaku Co., Ltd.). The measurement conditions are as follows. Target: Cu, tube voltage 40kV, tube current: 30mA, sampling width: 0.02°, scan speed: 2.00°/min, divergence slit: 1.0°, scattering slit: 1.0°, light receiving slit: 0.3mm. The results are shown in Figure 1. Furthermore, the X-ray diffraction pattern of hydroxyapatite (reagent HAp), which is a commercially available reagent, is shown in FIG. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity ratio due to the (002) plane near 2θ = 26° is 1.1, and the same peak intensity ratio of the reagent HAp is 2.7. The result was clearly lower than that of . From this, it was found that the obtained hydroxyapatite particles were aggregates of plate-like crystals in which a relatively large amount of the c-plane was exposed. In addition, the area of all diffraction peaks within the range of 25.5°≦2θ≦26.5° and 31 The sum total of the area of all the diffraction peaks within the range of .5°≦2θ≦32.5° was 37.2%. This value is clearly lower than the 52.1% shown by the reagent HAp, and the relatively broad X-ray diffraction pattern also indicates that the crystallinity is low. In addition, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ = 40° is 7 nm, which is clearly smaller than the 52 nm shown by the reagent HAp, which also indicates that the crystallinity is low. .

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 Mountec 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 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 of Ca and P contents measured by inductively coupled plasma 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 using a scanning electron microscope (manufactured by JEOL Ltd., hereinafter referred to as SEM). The results are shown in Figure 3. The results showed that the obtained hydroxyapatite particles were aggregates of plate-like crystals.

Example 2
A 10.7 mass % sodium dihydrogen phosphate dihydrate aqueous solution and a ground calcium hydroxide slurry with a solid content concentration of 8.6 mass % (BET ratio Surface area: 7.9 m ² /g Oxalic acid reactivity: 12 minutes 30 seconds JP 2017-036176A) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60° C. while stirring, and maintained until stirring was stopped. The pH was adjusted to 6.0 by adding 10% NaOH aqueous solution. 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 results are shown in FIG. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity ratio due to the (002) plane near 2θ = 26° was 1.1, which was the same value as in Example 1. . In addition, the area of all diffraction peaks within the range of 25.5°≦2θ≦26.5° and 31 The sum total of the area of all the diffraction peaks within the range of .5°≦2θ≦32.5° was 38.6%. Further, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 7 nm.

The specific surface area was 75.4 m ² /g.

Figure 5 shows the shape observation results. As in Example 1, it was confirmed that it was an aggregate of plate-like crystals.

Example 3
A 10.7 mass % sodium dihydrogen phosphate dihydrate aqueous solution and a ground calcium hydroxide slurry with a solid content concentration of 8.6 mass % (BET ratio Surface area 7.9 m ² /g Oxalic acid reactivity: 12 minutes 30 seconds JP 2017-036176A) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 40° C. while stirring, and maintained until stirring was stopped. The pH was adjusted to 5.5 by adding 10% NaOH aqueous solution. 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 results are shown in FIG. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity ratio due to the (002) plane near 2θ = 26° was 1.2, which was the same value as in Example 1. . In addition, the area of all diffraction peaks within the range of 25.5°≦2θ≦26.5° and 31 The sum of the areas of all diffraction peaks within the range of .5°≦2θ≦32.5° was 36.0%. Further, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 6 nm.

The specific surface area was 81.5 m ² /g.

Figure 7 shows the shape observation results. It was confirmed that the hydroxyapatite particles obtained in the same manner as in Example 1 were aggregates of plate-like crystals.

Example 4
A 10.7 mass % sodium dihydrogen phosphate anhydrous aqueous solution and a milled 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 2017-036176A) was prepared. An aqueous sodium dihydrogen phosphate anhydride solution was placed in a stainless steel beaker and heated to 80° C. with stirring. The pH remained at 4.2 and was not adjusted. 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 results are shown in FIG. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity ratio due to the (002) plane near 2θ = 26° was 1.4, which was the same value as in Example 1. . In addition, the area of all diffraction peaks within the range of 25.5°≦2θ≦26.5° and 31 The sum total of the area of all the diffraction peaks within the range of .5°≦2θ≦32.5° was 37.8%. Further, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 9 nm.

The specific surface area was 163.4 m ² /g.

Figure 9 shows the shape observation results. It was confirmed that the hydroxyapatite particles obtained in the same manner as in Example 1 were aggregates of plate-like crystals.

Example 5
A 10.7 mass % sodium dihydrogen phosphate anhydrous aqueous solution and a milled 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 2017-036176A) was prepared. An anhydrous sodium dihydrogen phosphate aqueous solution was placed in a stainless steel beaker and heated to 60° C. with stirring. The pH remained at 4.2 and was not adjusted. 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 results are shown in FIG. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity ratio due to the (002) plane near 2θ = 26° was 1.1, which was the same value as in Example 1. . In addition, the area of all diffraction peaks within the range of 25.5°≦2θ≦26.5° and 31 The sum total of the area of all the diffraction peaks within the range of .5°≦2θ≦32.5° was 31.6%. Further, the crystallite size calculated from the diffraction peak due to the (130) plane near 2θ=40° was 7 nm.

The specific surface area was 94.7 m ² /g.

Figure 11 shows the shape observation results. As in Example 1, it was confirmed that the particles were aggregates of plate-like fine particles.

Comparative example 1
A 10.7 mass % sodium dihydrogen phosphate anhydrous aqueous solution and a milled 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 2017-036176A) was prepared. The calcium hydroxide slurry was placed in a stainless steel beaker and heated to 40°C while stirring. An anhydrous sodium dihydrogen phosphate aqueous solution (pH: 4.2) 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 results are shown in FIG. The ratio of the diffraction peak intensity due to the (211) plane near 2θ = 32° to the diffraction peak intensity ratio due to the (002) plane near 2θ = 26° is 1.7, which is clearly higher than in Example 1. The value was shown. Furthermore, a diffraction peak due to the (300) plane near 2θ=33° appeared separately.

The specific surface area was 50.9 m ² /g.

Figure 13 shows the shape observation results. It was confirmed that the obtained hydroxyapatite particles were formed by agglomeration of spindle-shaped crystals.

Comparative example 2
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a milled calcium hydroxide slurry with a solid content concentration of 8.6 mass% were prepared so that the Ca/P molar ratio was 0.5. No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60° C. while stirring, and maintained until stirring was stopped. The pH remained at 4.2 and was not adjusted. A 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 results are 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 the diffraction peaks of monetite, which is calcium phosphate that is easily produced in acidic conditions.

The shape observation results are 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 high purity calcium hydroxide slurry with a solid content concentration of 8.6 mass% (BET specific surface area : 2.4 m ² /g, oxalic acid reactivity: 25 seconds (Japanese Unexamined Patent Publication No. 2011-126772) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60° C. while stirring, and maintained until stirring was stopped. The pH was adjusted to 5.5 by adding 10% NaOH aqueous solution. 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 results are shown in FIG. In addition to the diffraction peaks of hydroxyapatite, diffraction peaks of calcium hydroxide were confirmed around 2θ=28° and around 34°.

Further, the shape observation results are shown in FIG. 17. Large plate-shaped particles of calcium hydroxide were confirmed. The difference from Example 1 was thought to be due to the physical properties of the raw material calcium hydroxide.

Comparative example 4
A 10.7 mass % sodium dihydrogen phosphate dihydrate aqueous solution and a ground calcium hydroxide slurry with a solid content concentration of 8.6 mass % (BET ratio Surface area 7.9 m ² /g Oxalic acid reactivity: 12 minutes 30 seconds JP 2017-036176A) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, and a 10% aqueous NaOH solution was added to adjust the pH to 5.5. Calcium hydroxide slurry was added thereto over 50 minutes. After the addition was completed, stirring was further continued for 1 hour, then stirring was stopped, and after being allowed to stand at room temperature for 9 days, the mixture was 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 results are shown in FIG. The ratio of the diffraction peak intensity due to the (211) plane near 2θ=32° to the diffraction peak intensity ratio due to the (002) plane near 2θ=26° was 1.3.

Figure 19 shows the shape observation results. The shape of the particles was confirmed to be an aggregate of minute spindle-shaped particles.

Comparative example 5
A 10.7 mass% sodium dihydrogen phosphate dihydrate aqueous solution and a milled calcium hydroxide slurry with a solid content concentration of 8.6 mass% were prepared so that the Ca/P molar ratio was 0.5. No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 80° C. while stirring, and maintained until stirring was stopped. The pH remained at 4.2 and was not adjusted. 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 results are 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 the diffraction peaks of monetite, which is calcium phosphate that is easily produced in acidic conditions.

Figure 21 shows the shape observation results. Large plate-shaped particles of monetite were confirmed.

Test example 1. Crystallinity change confirmation test [Test purpose]
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 using a powder X-ray diffraction device.

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

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

The results are shown in FIG. 22. Improved crystallinity (increased peak sharpness, appearance of broad peaks) was confirmed by immersion in artificial saliva. From this, it was confirmed that the hydroxyapatite particles were particles that changed (had reactivity) in the oral cavity.

In addition, when a similar study was conducted using known hydroxyapatite particles instead of the hydroxyapatite particles obtained in the same manner as in Example 1, the peak did not change at all before and after immersion in artificial saliva, indicating that the crystallinity did not change.

Test example 2. Dentinal tubule sealing test of hydroxyapatite particles [Test purpose]
In order to evaluate the ability of hydroxyapatite particles to seal dentinal tubules, the surface of bovine dentin was brushed with a hydroxyapatite particle solution, and the degree of sealing of dentinal tubules was examined using an electron microscope (SEM).

[Test method]
Preparation of dentin block (sample)
1. The dentin of the root surface of an extracted bovine tooth was cut into a size of 5 x 5 mm.
2. The cut out tooth pieces were embedded in resin (polymethyl methacrylate) to create a block, which was polished using waterproof 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. Ultrasonication was performed in distilled water for 5 minutes.

Preparation of hydroxyapatite particle liquid5 . 0.3 g of hydroxyapatite particles obtained in the same manner as in Example 1 were suspended in 39.7 g of a viscous diluent to obtain hydroxyapatite particles. Note that the viscous diluent is an aqueous solution containing 0.5 w/w% carboxymethyl cellulose sodium and 10 w/w% glycerin.

Brushing process 6. The dentin block was brushed in the hydroxyapatite particle solution (40 g) for 30 seconds with a toothbrush (GUM #211) (stroke: 150 rpm, load: 160 g).
7. After washing the dentin block with water, it was immersed in artificial saliva (CaCl ₂ : 1.5mM, KH ₂ PO ₄ : 0.9mM, KCl: 130mM, HEPES: 20mM, pH 7.0 (KOH)) for 5 minutes.
8. The above operations 1 and 2 were repeated 6 times.

SEM observation9 . After the surface was subjected to vapor deposition treatment, it was observed using an electron microscope.

[Observation measurement conditions]
{Vapor deposition treatment}
・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. It was confirmed that the dentinal tubules were sealed by brushing in the hydroxyapatite particle solution. 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 [Test purpose]
In order to evaluate the ability of hydroxyapatite particles to adhere within 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 whether the sealing of hydroxyapatite particles withstood the water pressure. was investigated by electron microscopy (SEM) observation.

[Test method]
Preparation of dentin disk (sample)
1. The dentin of the root surface of an extracted bovine tooth was cut into a size of 5 x 5 mm.
2. The cut tooth pieces were polished with waterproof abrasive paper.
3. The resulting dentin discs were immersed in a 5% w/w EDTA aqueous solution (pH 7.0) for 2 minutes.
4. Ultrasonication was performed in distilled water for 5 minutes.

Preparation of hydroxyapatite particle liquid5 . 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. Note that the viscous diluent is an aqueous solution containing 0.5 w/w% carboxymethyl cellulose sodium and 10 w/w% glycerin.

Brushing process 6. The dentin disc was brushed in the hydroxyapatite particle solution (40 g) for 30 seconds with a toothbrush (GUM #211) (stroke: 150 rpm, load: 160 g).
7. After washing the disk with water, it was immersed in artificial saliva ( _CaCl2 : 1.5mM, _KH2PO4 : _0.9mM , KCl: 130mM, HEPES: 20mM, 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 treatment10 . The dentin disc after the brushing treatment was treated as described by Pashley et al. (Pashley DH, Galloway SE. The effects of oxalate treatment on the smear layer of ground surfaces of h Uman dentin. Arch Oral Biol 1983; 30: 731-737.) Pressure was applied at 0.1 MPa for 30 minutes using a device equipped with the following methods.

SEM observation 11. After the surface was subjected to vapor deposition treatment, it was observed using an electron microscope.

[Observation measurement conditions]
{Vapor deposition treatment}
・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. It was confirmed that the dentinal tubules were sealed even after the water pressure treatment. From this, it was confirmed that the hydroxyapatite particles were particles that adhered within the dentinal tubules and maintained a sealed state.

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

[Test method]
Preparation of dentin block (sample)
1. The dentin of the root surface of an extracted bovine tooth was cut into a size of 5 x 5 mm.
2. The cut out tooth pieces were embedded in resin (polymethyl methacrylate) to create a block, which was polished using waterproof 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. Ultrasonication was performed in distilled water for 5 minutes.

Preparation of dentifrice solution5 . 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 addition, below, the unit "%" of compounding amount in a table|surface shows mass %.

Brushing process 6. 10 g of the dentifrice was diluted 4 times with distilled water to obtain a dentifrice solution. The dentin block was brushed in the dentifrice solution (40 g) for 30 seconds with a toothbrush (GUM #211) (stroke: 150 rpm, load: 160 g).
7. After washing the dentin block with water, it was immersed in artificial saliva ( _CaCl2 : 1.5mM, _KH2PO4 : _0.9mM , KCl: 130mM, HEPES: 20mM, pH 7.0 (KOH)) for 5 minutes.
8. The above operations 1 and 2 were repeated 6 times.

SEM observation9 . After the surface was subjected to vapor deposition treatment, it was observed using an electron microscope.

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

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

Test example 5. Dentinal tubule sealing test when gel preparation is applied with soft pick [Test purpose]
In order to confirm the ability of a gel preparation containing hydroxyapatite particles to seal dentinal tubules, the gel preparation was applied to the surface of bovine dentin using a soft pick (rubber interdental brush), and the degree of sealing of dentinal tubules was measured electronically. Examined using a microscope (SEM).

[Test method]
Preparation of dentin block (sample)
1. The dentin of the root surface of an extracted bovine tooth was cut into a size of 5 x 5 mm.
2. The cut out tooth pieces were embedded in resin (polymethyl methacrylate) to create a block, which was polished using waterproof 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. Ultrasonication was performed in distilled water for 5 minutes.
5. The two dentin blocks were fixed with tape so that the dentin surfaces faced each other with an interval of 1.1 mm to form a pseudo interdental space.

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

SEM observation8 . After the surface was subjected to vapor deposition treatment, it was observed using an electron microscope.

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

The results are shown in FIG. It was confirmed that the dentinal tubules were sealed by applying a gel formulation containing hydroxyapatite particles using a soft pick.

Test example 6. Gel formulation clinical trial [Test purpose]
The clinical effects of a gel formulation containing hydroxyapatite particles on anti-hypersensitivity were investigated. In this study, hydroxyapatite particles obtained in the same manner as in Example 1 were used as hydroxyapatite particles.

[Test design]
(i) Gel formulation containing hydroxyapatite particles, aluminum lactate, and potassium nitrate (HAp+Al+K), (ii) Gel formulation containing aluminum lactate and potassium nitrate (Al+K), and (iii) Gel formulation containing potassium nitrate (K) A comparison was made between three formulations. The compositions of these gel formulations are shown in Table 3 below.

Each gel formulation was used by 20 people, and the degree of abrasion pain (applying a probe to the exposed root surface and rubbing horizontally) at 1, 2, or 4 weeks after use was measured on a VAS scale. I had it written down. The VAS scale shows the patient a 10cm long black line (the left end indicates "no pain at all" and the right end indicates "the most painful/severe pain") and indicates the current level of pain. It is a visual scale. Further, the flow of the test is shown in FIG. 27. In FIG. 27, "hypersensitivity care set (gel formulation (test product))" indicates the gel formulations (i) to (iii) above, and "hypersensitivity care set (gel formulation (placebo product))" indicates the gel formulations (i) to (iii) above. A gel formulation obtained by removing potassium nitrate from the gel formulation (iii) is shown.

[How to use test product]
Subjects were asked to use the gel formulation (test product) twice a day (morning and evening) (there were no restrictions on when to clean the gel after waking up, after meals, before going to bed, etc., and the time was to be adjusted to suit each individual's oral cleaning habits). Specifically, first, after brushing with a designated toothbrush (Gum Pros Dental Brush #3C: Sunstar Co., Ltd.) and toothpaste (Coop Non-Foam Toothpaste N), rinse your mouth with approximately 10 ml of water for 20 seconds ( (The brushing time was not specified.) After that, a gel preparation was used. To use the gel preparation, specifically, apply approximately 0.04 g (about the size of a grain of rice) of the gel preparation (test product) to one test tooth using a tufted brush (Butler Single Tufted Brush #01F: Sunstar Co., Ltd.). It was applied to the test site, and the test site and both adjacent teeth were brushed for at least 5 seconds per tooth. If it is possible to insert the specified interdental cleaning tool (gum soft pick curved type: Sunstar Co., Ltd.) between the test site and both adjacent teeth, insert the interdental cleaning tool between the test site and both adjacent teeth. It was inserted into the interdental area from the buccal side and reciprocated 5 times. After using the gel formulation (test product), the mouth was rinsed with approximately 10 ml of water for 20 seconds.

FIG. 28 shows the results of evaluating the degree of abrasion pain using the VAS scale. In the group using the hydroxyapatite-containing preparation, the pain from rubbing improved significantly in the first week after use, compared to the group using the non-preparation preparation. From this, it has been found that the hydroxyapatite-containing preparation is effective in suppressing hypersensitivity symptoms at an early stage when used in combination with aluminum lactate and potassium nitrate, which are known medicinal ingredients for preventing hypersensitivity.

Test example 7. Study of oral composition containing hydroxyapatite particles and cetylpyridinium chloride An oral composition was prepared using hydroxyapatite particles (HAp manufactured by the procedure of Example 1) obtained in the same manner as in Example 1 and cetylpyridinium chloride (CPC). Prepared. Specifically, an oral composition was prepared by mixing the hydroxyapatite particles with distilled water in which CPC was dissolved (0.05% by mass CPC aqueous solution) to a final concentration of 5% by mass. The oral composition was shaken and stirred for 20 seconds using a vortex mixer, and water-insoluble components were precipitated by centrifugation to obtain a water-soluble supernatant. Add the extract (10mM sodium lauryl sulfate-40mM citrate buffer (pH 3.0)/acetonitrile = 25/75 (volume ratio)) to 2mL of the supernatant or 0.05% CPC aqueous solution to make the total volume 20mL, and HPLC ( The amount (μg) of CPC in each composition was determined using an ultra-high performance liquid chromatograph (Nexera system, manufactured by Shimadzu Corporation). As a result, 984.3 μg of CPC was detected from the 0.05% CPC aqueous solution, whereas only 51.4 μg of CPC was detected from the prepared oral composition. This was thought to be because the hydroxyapatite particles strongly adsorbed CPC.

Therefore, we searched for a component that can suppress the CPC adsorption of the hydroxyapatite. Specifically, the components listed in Tables 4 and 5 below are mixed (more specifically, the test substance listed in Table 5 is added to distilled water (0.05% CPC aqueous solution) in which CPC is dissolved). After mixing and stirring, each oral composition (Compositions 1 to 21) prepared by mixing the hydroxyapatite particles was analyzed by HPLC in the same manner as above, and the amount of CPC in each composition ( μg) was determined. The results are shown in FIG. In addition, the numerical value of each component shown in Table 4 and Table 5 shows mass %. In addition, FIG. 29 shows the results of the 0.05 mass % CPC aqueous solution (CPC 0.05%) and the 0.05 mass % CPC aqueous solution (HAp 5%) containing 5 mass % HAp produced by the procedure of Example 1, which were analyzed above. Also shown.

Note that for the alkyl glycoside No. 17 in Table 5, lauryl glucoside was specifically used. These results strongly suggested that the CPC adsorption of the hydroxyapatite could be suppressed by further blending magnesium chloride or γ-cyclodextrin.

Therefore, we further investigated the following. Example 1 Procedure Preparation Oral compositions were prepared using HAp, cetylpyridinium chloride (CPC), and magnesium chloride or γ-cyclodextrin. Specifically, each component shown in Table 6 is mixed (more specifically, magnesium chloride or γ-cyclodextrin is mixed with distilled water in which CPC is dissolved and stirred, and then the hydroxyapatite particles are mixed. ), each oral composition was prepared. Then, the amount (μg) of CPC in each composition was determined in the same manner as above. The results are shown in FIG. From the results, it was confirmed that magnesium chloride or γ-cyclodextrin can suppress CPC adsorption of the hydroxyapatite.

Claims (9)

hydroxyapatite particles,
cetylpyridinium chloride, and
An oral composition containing γ - cyclodextrin , the composition comprising:
Contains 1 to 10% by mass of hydroxyapatite particles and 0.01 to 1% by mass of cetylpyridinium chloride,
Contains 0.05 to 10% by mass of γ -cyclodextrin,
The hydroxyapatite particles have a powder X-ray diffraction pattern measured by CuKα characteristic X-rays, in which the ratio of the diffraction peak intensity around 2θ = 32° to the diffraction peak intensity around 2θ = 26° is 0.8 to 1.5. be,
Oral compositions (excluding oral compositions containing 0.5 parts by mass or more of sodium chloride per 100 parts by mass of hydroxyapatite) . The oral composition according to claim 1, further containing 0.1 to 10% by mass of magnesium chloride. The oral composition according to claim 1 or 2 , wherein the Ca/P molar ratio of the hydroxyapatite particles is less than 1.67. The oral composition according to any one of claims 1 to 3 , wherein the hydroxyapatite particles have a median diameter of 5 μm or less. The oral composition according to any one of claims 1 to 4 , wherein the hydroxyapatite particles have a specific surface area of 55 to 200 m ² /g. 1 . The ratio of the diffraction peak intensity around 2θ = 34° to the diffraction peak intensity around 2θ = 32° in a powder X-ray diffraction pattern measured by CuKα characteristic X-rays of the hydroxyapatite particles is 1 or less. - 5. The oral composition according to any one of 5 . the hydroxyapatite particles are aggregates of hydroxyapatite plate crystals;
The oral composition according to any one of claims 1 to 6 . The oral composition according to any one of claims 1 to 7 , further comprising potassium nitrate and/or aluminum lactate. The oral composition according to any one of claims 1 to 8 , which is used to prevent or improve hypersensitivity.

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