JP2021008417A - Composition for oral cavity - Google Patents

Abstract

To provide a composition for an oral cavity, the composition containing particles that have dentinal tubule-sealing properties and excellent fixation inside the dentinal tubules.SOLUTION: The present invention provides a hydroxyapatite particle-containing composition for an oral cavity, where the ratio of the diffraction peak intensity around 2θ=32° to the diffraction peak intensity around 2θ=26° of the hydroxyapatite particles is 0.8-1.5 in an x-ray powder diffraction pattern measured using Cu-Kα characteristic x-rays.SELECTED DRAWING: None

Description

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

Hypersensitivity in teeth is caused by exposure of the dentin of teeth due to physical wear such as brushing, chemical wear due to acid, and the like. When the dentin is exposed, external stimuli stimulate nerves in the dentin tubules in the dentin, making pain more likely.

For hypersensitivity, for example, by blocking the dentin tubules with particles such as fluoride and aluminum salt (for example, Patent Document 1), the arrival of external stimuli to nerves is suppressed. .. However, most of the conventional methods have insufficient sticking after sealing, and there is a problem in sustainability of the effect.

JP-A-2010-222325 Japanese Patent Application Laid-Open No. 2017-036176 Public Relations

An object of the present invention is to provide particles having a sealing property of an ivory canaliculus and having excellent adhesiveness in the ivory canaliculus.

As a result of diligent research in view of the above problems, the present inventors have found that the ratio of the diffraction peak intensity near 2θ = 32 ° to the diffraction peak intensity near 2θ = 26 ° in the specific hydroxyapatite particles (X-ray diffraction pattern). It has been found that hydroxyapatite particles (0.8 to 1.5) can solve the above-mentioned problems. Then, based on this finding, we proceeded with further studies.

The present disclosure includes, for example, the subjects described in the following sections.
Item 1.
An oral composition containing hydroxyapatite particles and a fluorine compound.
The ratio of the diffraction peak intensity near 2θ = 32 ° to the diffraction peak intensity near 2θ = 26 ° in the powder X-ray diffraction pattern measured by the CuKα characteristic X-ray of the hydroxyapatite particles is 0.8 to 1.5. is there,
Oral composition.
Item 2.
Item 2. The oral composition according to Item 1, wherein the Ca / P molar ratio of the hydroxyapatite particles is less than 1.67 (preferably 1.60 or less).
Item 3.
Item 2. 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 ^2. 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 in which the hydroxyapatite particles have a ratio of the diffraction peak intensity near 2θ = 34 ° to the diffraction peak intensity near 2θ = 32 ° in the powder X-ray diffraction pattern measured by CuKα characteristic X-ray. The oral composition according to any one of 4.
Item 6.
The hydroxyapatite particles are aggregates of hydroxyapatite plate-like crystals.
Item 8. The oral composition according to any one of Items 1 to 5.
Item 7.
Item 2. The oral composition according to any one of Items 1 to 6, further 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 used for preventing or improving hypersensitivity.
Item 9.
The hydroxyapatite particles were produced by a method for producing hydroxyapatite particles, which comprises a step of mixing an aqueous solution of an alkali phosphate salt having a pH of 4 or more and less than 7 and a calcium hydroxide slurry and reacting them at 35 to 85 ° C. Item 2. The oral composition according to any one of Items 1 to 8.
Item 10.
Item 9. The oral 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 at a concentration of 5% by mass and maintained at 25 ± 1 ° C., 0.5 mol / liter maintained at 25 ± 1 ° C. Item 9. The oral composition according to Item 9 or 10, wherein 40 g of a concentrated oxalic acid aqueous solution is added all at once, and the time (minutes) until the pH reaches 7.0 after the addition is 40 minutes or less.
Item 12.
Item 2. 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.
Item 13.
The oral composition according to any one of claims 1 to 12, wherein the fluorine compound is at least one compound selected from the group consisting of sodium monofluorophosphate, sodium fluoride, and tin fluoride.
Item 14.
The oral composition according to any one of claims 1 to 13, wherein the fluorine compound is contained in an amount of 2000 ppm or less in terms of fluoride ion concentration.

Provided is an oral composition having a sealing property of an ivory canaliculus and having excellent adhesion in the dentin canaliculus.

The X-ray diffraction peak of the hydroxyapatite particle of Example 1 is shown. The X-ray diffraction peak of the commercially available reagent product hydroxyapatite particles is shown. The SEM photograph of the hydroxyapatite particle of Example 1 is shown. The X-ray diffraction peak of the hydroxyapatite particle of Example 2 is shown. The SEM photograph of the hydroxyapatite particles of Example 2 is shown. The X-ray diffraction peak of the hydroxyapatite particles of Example 3 is shown. The SEM photograph of the hydroxyapatite particle of Example 3 is shown. The X-ray diffraction peak of the hydroxyapatite particle of Example 4 is shown. The SEM photograph of the hydroxyapatite particle of Example 4 is shown. The X-ray diffraction peak of the hydroxyapatite fine particles of Example 5 is shown. The SEM photograph of the hydroxyapatite fine particles of Example 5 is shown. The X-ray diffraction peak of the hydroxyapatite particles of Comparative Example 1 is shown. The SEM photograph of the 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 the black circle is the diffraction peak of monetite. The SEM photograph of the sample of Comparative Example 2 is shown. The X-ray diffraction peak of the sample of Comparative Example 3 is shown. The SEM photograph of the sample of Comparative Example 3 is shown. The X-ray diffraction peak of the hydroxyapatite particles of Comparative Example 4 is shown. The SEM photograph of the 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 the black circle is the diffraction peak of monetite. The SEM photograph of the sample of Comparative Example 5 is shown. The X-ray diffraction peak (Test Example 1) before and after the immersion of the hydroxyapatite particles in artificial saliva is shown. An SEM photograph (Test Example 2) of the ivory canaliculus before and after brushing is shown. The SEM photograph (Test Example 3) of the ivory tubule before and after the water pressure treatment is shown. The SEM photograph (Test Example 4) of the ivory tubule before and after brushing with the dentifrice solution containing hydroxyapatite particles is shown. The SEM photograph (Test Example 5) of the dentin tubule before and after applying the gel preparation containing hydroxyapatite particles to dentin by soft pick is shown. The flow of the clinical trial using the gel preparation containing hydroxyapatite particles is shown. The results of evaluating the degree of scratch pain on the VAS scale in a clinical trial using a gel preparation containing hydroxyapatite particles are shown. From left to right, the b * values of the oral compositions of Comparative Example 1a, Example 1a, Comparative Example 2a, Comparative Example 1b, Example 1b, Comparative Example 2b, Comparative Example 1c, Example 1c, and Comparative Example 2c are shown. Shown.

Hereinafter, each embodiment included in the present disclosure will be described in more detail. It should be noted that the present disclosure preferably includes, but is not limited to, an oral composition, particularly an oral composition containing specific hydroxyapatite particles, and the present disclosure is disclosed herein and those skilled in the art. Includes everything that can be recognized.

The oral compositions included in the present disclosure contain specific hydroxyapatite particles. In addition, in this specification, the said oral composition may be referred to as "the oral composition of this disclosure".

The specific hydroxyapatite particles are hydroxyapatite particles in which the ratio of the diffraction peak intensity near 2θ = 32 ° to the diffraction peak intensity near 2θ = 26 ° in the X-ray diffraction pattern is 0.8 to 1.5. .. In the present specification, the hydroxyapatite particles may be referred to as "particles of the present disclosure".

The diffraction peak near 2θ = 26 ° is a peak of hydroxyapatite, specifically, a diffraction peak of 2θ = 25.5 to 26.5 °, preferably 2θ = 25.8 to 26.2 °. Diffraction peak of. When a plurality of diffraction peaks exist in the vicinity of 2θ = 26 °, it means the diffraction peak having the highest intensity.

The diffraction peak near 2θ = 32 ° is the peak of hydroxyapatite, specifically, the diffraction peak of 2θ = 31.5 to 32.5 °, preferably 2θ = 31.8 to 32.2 °. Diffraction peak of. When a plurality of diffraction peaks exist in the vicinity of 2θ = 32 °, it means the diffraction peak having 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 the 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 disclosure have a ratio (32 ° / 26 °) of the diffraction peak intensity near 2θ = 32 ° to the diffraction peak intensity near 2θ = 26 ° of 0.8 to 1.5. 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.

As for the particles of the present disclosure, it is preferable that each particle itself is an agglomerate of hydroxyapatite plate-like crystals. The shape of the plate-like crystal constituting the particles of the present disclosure is not particularly limited, and examples thereof include a circular shape, a polygonal shape (particularly a hexagonal shape), a shape close to a rod shape, and a shape obtained by combining these. Further, the plate-shaped crystal may be in either a state in which the surface is bent or a state in which the surface is not bent and the planar structure is maintained. Normally, a plate-shaped hydroxyapatite crystal 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. When a particle is formed of a plurality of crystals, the crystal is called a crystallite.

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

Although not a limited interpretation, the particles of the present disclosure are partly due to the fact that they have a shape and structure represented by a specific X-ray diffraction pattern and that the plate-like particles are composed of aggregates. In combination with these, it is considered that the dentinal tubules exhibit excellent sealing properties and excellent adhesion in the dentinal tubules.

The particles of the present disclosure preferably have a ratio (34 ° / 32 °) of the diffraction peak intensity near 2θ = 34 ° to the diffraction peak intensity near 2θ = 32 ° in the X-ray diffraction pattern of 1 or less. Specifically, the diffraction peak near 2θ = 34 ° is a diffraction peak of 2θ = 33.5 to 34.5 °, preferably a diffraction peak of 2θ = 33.8 to 34.2 °. When a plurality of diffraction peaks exist in the vicinity of 2θ = 34 °, it means the diffraction peak having the highest intensity. The peak intensity ratio is preferably 0.1 to 1, more preferably 0.2 to 0.9, still more preferably 0.3 to 0.8, still more preferably 0.4 to 0.7, and particularly preferably. Is 0.4 to 0.6.

The particles of the present disclosure are preferably all within the range of 25.5 ° ≤ 2θ ≤ 26.5 ° with respect to 100% of the total area of all diffraction peaks within the range of 25 ° ≤ 2θ ≤ 35 °. The sum of the area of the diffraction peaks and the areas of all the diffraction peaks in the range of 31.5 ° ≤ 2θ ≤ 32.5 ° is 30 to 45%. The value is preferably 33 to 42%, more preferably 35 to 40%. Further, the particles of the present disclosure have a crystallite size of preferably 4 to 12 nm, more preferably 5 to 10 nm, calculated from the diffraction peak on the (130) plane near 2θ = 40 °. Although we do not want a limited interpretation, it is thought that the relatively low crystallinity will increase the crystal growth in the tubules after the ivory tubules are closed, which will further improve the stickiness in 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 it is not desired to have a limited interpretation, it is considered that a part of calcium is replaced with another element (sodium, etc.) in the particles of the present disclosure, and therefore the Ca / P molar ratio is relatively high. 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, still more preferably 1.55 or less or 1.50 or less. 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. The Ca / P molar ratio is a value calculated from the measured values obtained by measuring the Ca and P contents of the particles of the present disclosure by inductively coupled plasma emission spectroscopy.

The median diameter (d50) of the particles of the present disclosure is not particularly limited, but is preferably 5 μm or less, more preferably 4.5 μm or less, from the viewpoint of ivory capillary sealing property, adhesiveness, and the like. The lower limit of the median diameter is not particularly limited, and examples thereof include 1 μm or more, 2 μm or more, or 3 μm or more. More specifically, for example, 1 to 5 μm can be mentioned. The median diameter is a value measured by a laser diffraction / scattering method. More specifically, it is a value measured by a dry particle size distribution measurement using a laser diffraction type 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 ivory capillary sealing property, adhesiveness, etc., for example, 30 m ² / g or more, preferably 40 m ² / g or more, more preferably 50 m ² / G or more, 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, and 90 m ² / g. The specific surface area is a value measured by the nitrogen gas adsorption method.

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

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

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

The concentration of the alkali phosphate salt in the aqueous solution of the alkali phosphate salt 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 even more preferably 7 to 15% by mass.

The pH of the aqueous phosphate alkali salt 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 aqueous solution of the alkali phosphate is relatively low (for example, when the pH is 4 or more and less than 5), an anhydride is used as the alkali phosphate and the reaction temperature is relatively high. For example, it is desirable to set it at 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 calcium hydroxide slurry 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 maintained at 25 ± 1 ° C., and 40 g of an aqueous oxalic acid solution having a concentration of 0.5 mol / liter maintained at 25 ± 1 ° C. Is added all at once, and the time (minutes) until the pH reaches 7.0 after the addition.

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

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, and 10 m ² / g.

A calcium hydroxide slurry having high oxalic acid reactivity (for example, having reactivity with the above-mentioned specific oxalic acid) can be typically obtained by grinding the calcium hydroxide slurry. By the grinding treatment, the oxalic acid reactivity can be further enhanced (the time defined above can be 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-A-2017-036176 can be adopted.

The 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 in a kiln at about 1000 ° C. to produce quicklime, adding about 10 times the amount of hot water to the quicklime 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 aqueous solution of the alkali salt phosphate to the calcium hydroxide slurry is not particularly limited as long as the ratio can produce hydroxyapatite particles. The amount 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. Is desirable.

The mode in which the aqueous solution of the alkali salt phosphate and the 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 aqueous alkali salt phosphate solution (Aspect 1), an embodiment in which an aqueous alkali salt phosphate solution is added to a reaction vessel containing a calcium hydroxide slurry (Aspect 2), and phosphoric acid. An embodiment (aspect 3) in which an aqueous alkaline salt solution and a calcium hydroxide slurry are added to the reaction vessel at the same time can be mentioned. Among these, aspect 1 is preferable. At the time of 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, and 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., still more preferably 50 to 70 ° C., still more preferably 55 to 65 ° C. The reaction temperature is relatively high when the pH of the aqueous solution of the alkali phosphate solution is relatively low (for example, when the pH is 4 or more and less than 5), for example, 65 to 85 ° C, preferably 70 to 85 ° C, more preferably 75. ~ 85 ° C. Reaction time (time to start after all the aqueous alkali salt solution and calcium hydroxide slurry are mixed, time to start from the time when the addition of the aqueous alkali phosphate solution and calcium hydroxide slurry is completed in the above embodiments 1 to 3). ) Is, for example, 10 to 180 minutes, preferably 20 to 120 minutes, more preferably 40 to 90 minutes, still more preferably 50 to 70 minutes.

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

The particles of the present disclosure have the sealing property of the dentinal tubules and are excellent in the adhesiveness in the ivory tubules. Therefore, the oral composition containing the particles of the present disclosure (that is, the oral composition of the present disclosure) can be preferably used particularly for the prevention or improvement of hyperesthesia.

The particles of the present disclosure can be contained in the oral composition, for example, in an amount of about 1 to 10% by mass. The upper 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 mass. For example, the range is more preferably 2 to 8% by mass or 3 to 7% by mass.

The oral composition of the present disclosure can be produced by a conventional method, and can also be used as, for example, pharmaceuticals, quasi-drugs, and cosmetics. The form of the oral composition of the present disclosure is not particularly limited, but according to a conventional method, for example, an ointment, a paste, a pasta, a gel, a liquid, a spray, a mouthwash, a liquid dentifrice, and the like. It can be in the form (dosage form) of a dentifrice, a coating agent, or the like. Of these, mouthwashes, liquid dentifrices, dentifrices, pastes, liquids, sprays, gels and coatings are preferable, and dentifrices, pastes and gels are more preferable. Further, it is preferable to perform brushing after placing the oral composition on a toothbrush or applying the oral composition into the oral cavity, and therefore, it is preferable that the form is suitable for brushing. By brushing, the particles of the present disclosure can be pushed into the cavity of the tooth dentin, and the effect can be more preferably obtained.

In the oral composition of the present disclosure, in addition to the particles of the present disclosure, any component that can be blended in the oral composition is further blended alone or in combination of two or more as long as the effect is not impaired. May be good.

Fluorine compounds are preferably mentioned as such components. In other words, the oral composition of the present disclosure preferably contains the particles of the present disclosure and a fluorine compound.

Unlike conventional hydroxyapatite particles, the particles of the present disclosure are contained in an oral composition in combination with a fluorine compound, so that the color of the oral composition becomes yellow (that is, yellowing occurs). The effect of remarkably suppressing can be achieved. It is preferable that yellowing is suppressed because it can be one of the causes that consumers avoid when choosing an oral composition.

As the fluorine compound, for example, a fluorine compound known in the field of oral composition can be preferably used. More specifically, for example, sodium monofluorophosphate, sodium fluoride, tin fluoride and the like can be mentioned, and among them, sodium monofluorophosphate and sodium fluoride are more preferable.

Further, the fluorine compound is preferably contained in the oral composition in an amount of, for example, 2000 ppm or less in terms of fluoride ion concentration, and more preferably 50 to 2000 ppm. The upper or lower limit of the range is, for example, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1050, 1100. It may be 1,150, 1200, 1250, 1300, 1350, 1400, 1450, 1500, 1550, 1600, 1650, 1700, 1750, 1800, 1850, 1900, or 1950 ppm. For example, the range is more preferably 100 to 1800 ppm or 200 to 1600 ppm.

As other optional components, for example, as a surfactant, a nonionic surfactant, an anionic surfactant or an amphoteric surfactant can be blended. Specifically, as nonionic surfactants, 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 , Polyoxyethylene alkyl ether having an alkyl group having 13 to 15 carbon atoms; polyoxyethylene alkylphenyl ether having a polyoxyethylene addition coefficient of 10 to 18 and having an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxy Ethylene-hardened castor oil; fatty acid polyoxyethylene sorbitan and the like are exemplified. As anionic surfactants, sulfate 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 sarcosin and lauroylmethylalanine. Acrylic amino acid salts such as sodium; cocoyl methyl taurine sodium and the like are exemplified. Examples of amphoteric ion surfactants include betaine acetate-type activators such as lauryldimethylaminoacetate betaine and coconut oil fatty acid amide propyldimethylaminoacetic acid betaine; Activator; Amino acid type activator such as N-lauryldiaminoethylglycine and the like are exemplified. These surfactants can be blended alone or in combination of two or more. The blending amount is usually 0.1 to 5% by mass based on the total amount of the composition.

In addition, sweeteners such as sodium saccharin, acesulfame potassium, stebioside, neohesperidyl dihydrochalcone, perillartine, taumatin, asparatylphenylalanyl methyl ester, and p-methoxycinnamic aldehyde 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.

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

Further, as the wetting agent, sorbitol, glycerin, polypropylene glycol, xylit, martit, lactite, polyoxyethylene glycol and the like can be blended alone or in combination of two or more.

As the preservative, 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 a colorant, legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral pigments such as ultramarine, reinforced ultramarine, and navy blue, titanium oxide, etc. are blended alone or in combination of two or more. May be good.

As the pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphate, acetic acid, nitric acid, chemically possible salts thereof, sodium hydroxide and the like may be blended. These can be blended alone or in combination of two or more so that the pH of the composition is in the range of 4 to 8, preferably 5 to 7. For example, the blending amount of the pH adjuster is 0.01 to 2% by weight.

A bactericidal agent may be blended as a medicinal ingredient. For example, cationic bactericides such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, amphoteric bactericides such as dodecyldiaminoethylglycine, nonionic bactericides such as triclosan and isopropylmethylphenol. Examples include hinokithiol. Furthermore, a medicinal ingredient other than the bactericidal agent can be blended. For example, vitamin Es such as aluminum lactate, potassium nitrate, dl-α-tocopherol acetate, tocopherol succinate, tocopherol nicotinate, sodium fluoride and the like may be blended. The medicinal ingredient can be blended alone or in combination of two or more. Among them, aluminum lactate and potassium nitrate are particularly preferable to be blended in the oral composition of the present disclosure because they are medicinal ingredients for preventing hypersensitivity.

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.

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

In addition, in this specification, "including" also includes "consisting essentially" and "consisting of" (The term "comprising" includes "consisting essentially of" and "consisting of."). The present disclosure also includes all combinations of the constituent requirements described herein.

In addition, the various properties (property, structure, function, etc.) described for each embodiment of the present disclosure described above may be combined in any way in specifying the subject matter included in the present disclosure. That is, the present disclosure includes all subjects consisting of any combination of each combinable property described herein.

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

Example 1
10.7 mass% sodium dihydrogen phosphate / dihydrate aqueous solution and 8.6 mass% solid content ground 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 30 seconds Japanese Patent Application Laid-Open No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate / dihydrate was placed in a stainless steel beaker and heated to 60 ° C. with stirring and maintained until stirring was stopped. A 10% aqueous NaOH solution was added to adjust the pH to 5.5. Calcium hydroxide slurry was added thereto over 30 minutes. After completion of the addition, 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 carried out in the range of 2θ = 25 to 45 ° by an X-ray diffractometer MultiFlex (manufactured by Rigaku Co., Ltd.). 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 FIG. Further, FIG. 2 shows an X-ray diffraction pattern of hydroxyapatite (reagent HAp), which is a commercially available reagent product. The ratio of the diffraction peak intensity by the (221) plane near 2θ = 26 ° to the diffraction peak intensity ratio by the (211) plane near 2θ = 32 ° 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 the c-plane was exposed in a relatively large amount. Further, with respect to 100% of the total area of all diffraction peaks in the range of 25 ° ≤ 2θ ≤ 35 °, the area of all diffraction peaks in 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 37.2%. This is clearly lower than the 52.1% indicated by the reagent HAp, and the relatively broad X-ray diffraction pattern also indicates low crystallinity. Further, the crystallite size calculated from the diffraction peak on the (130) plane near 2θ = 40 ° is 7 nm, which is clearly smaller than the 52 nm indicated 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 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 hydroxyapatite particles was calculated from the measured values obtained by measuring the Ca and P contents by inductively coupled plasma emission spectroscopy using iCAP 6000 ICP-OES (manufactured by Thermo Fisher). 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 SEM). The results are shown in FIG. From this result, it was shown that the hydroxyapatite particles obtained were aggregates of plate-like crystals.

Example 2
10.7 mass% sodium dihydrogen phosphate / dihydrate aqueous solution and 8.6 mass% solid content ground 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 Japanese Patent Application Laid-Open No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate / dihydrate was placed in a stainless steel beaker and heated to 60 ° C. with stirring and maintained until stirring was stopped. A 10% aqueous NaOH solution was added to adjust the pH to 6.0. Calcium hydroxide slurry was added thereto over 30 minutes. After completion of the addition, 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 result of X-ray crystal diffraction is shown in FIG. The ratio of the diffraction peak intensity by the (221) plane near 2θ = 26 ° to the diffraction peak intensity ratio by the (211) plane near 2θ = 32 ° was 1.1, which was the same value as in Example 1. .. Further, with respect to 100% of the total area of all diffraction peaks in the range of 25 ° ≤ 2θ ≤ 35 °, the area of all diffraction peaks in 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 38.6%. The crystallite size calculated from the diffraction peak on 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. It was confirmed that it was an aggregate of plate-like crystals as in Example 1.

Example 3
10.7 mass% sodium dihydrogen phosphate / dihydrate aqueous solution and 8.6 mass% solid content ground 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 Japanese Patent Application Laid-Open No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate / dihydrate was placed in a stainless steel beaker and heated to 40 ° C. with stirring and maintained until stirring was stopped. A 10% aqueous NaOH solution was added to adjust the pH to 5.5. Calcium hydroxide slurry was added thereto over 50 minutes. After completion of the addition, 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 result of X-ray crystal diffraction is shown in FIG. The ratio of the diffraction peak intensity by the (221) plane near 2θ = 26 ° to the diffraction peak intensity ratio by the (211) plane near 2θ = 32 ° was 1.2, which was the same value as in Example 1. .. Further, with respect to 100% of the total area of all diffraction peaks in the range of 25 ° ≤ 2θ ≤ 35 °, the area of all diffraction peaks in 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%. The crystallite size calculated from the diffraction peak on 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 aggregates of plate-like crystals.

Example 4
10.7 mass% sodium dihydrogen phosphate anhydrous aqueous solution and 8.6 mass% solid content ground calcium hydroxide slurry (BET specific surface area 7.) so that the Ca / P molar ratio becomes 0.5. 9 m ² / g Calcium reactivity: 12 minutes 30 seconds (Japanese Patent Laid-Open No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate anhydride was placed in a stainless 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 completion of the addition, 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 result of X-ray crystal diffraction is shown in FIG. The ratio of the diffraction peak intensity by the (221) plane near 2θ = 26 ° to the diffraction peak intensity ratio by the (211) plane near 2θ = 32 ° was 1.4, which was the same value as in Example 1. .. Further, with respect to 100% of the total area of all diffraction peaks in the range of 25 ° ≤ 2θ ≤ 35 °, the area of all diffraction peaks in 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 37.8%. The crystallite size calculated from the diffraction peak on 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 aggregates of plate-like crystals.

Example 5
10.7 mass% sodium dihydrogen phosphate anhydrous aqueous solution and 8.6 mass% solid content ground calcium hydroxide slurry (BET specific surface area 7.) so that the Ca / P molar ratio becomes 0.5. 9 m ² / g Calcium reactivity: 12 minutes 30 seconds (Japanese Patent Laid-Open No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate anhydride was placed in a stainless 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 completion of the addition, 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 result of X-ray crystal diffraction is shown in FIG. The ratio of the diffraction peak intensity by the (221) plane near 2θ = 26 ° to the diffraction peak intensity ratio by the (211) plane near 2θ = 32 ° was 1.1, which was the same value as in Example 1. .. Further, with respect to 100% of the total area of all diffraction peaks in the range of 25 ° ≤ 2θ ≤ 35 °, the area of all diffraction peaks in 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 31.6%. The crystallite size calculated from the diffraction peak on 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 that it was an agglomerate of plate-like fine particles as in Example 1.

Comparative Example 1
10.7 mass% sodium dihydrogen phosphate anhydrous aqueous solution and 8.6 mass% solid content ground calcium hydroxide slurry (BET specific surface area 7.) so that the Ca / P molar ratio becomes 0.5. 9 m ² / g Calcium reactivity: 12 minutes 30 seconds (Japanese Patent Laid-Open No. 2017-036176) was prepared. The calcium hydroxide slurry was placed in a stainless steel beaker and heated to 40 ° C. with stirring. An aqueous solution of sodium dihydrogen phosphate anhydride (pH: 4.2) was added thereto over 30 minutes. After completion of the addition, the mixture was further stirred for 1 hour, filtered, washed with water, and dried at 80 ° C. to obtain hydroxyapatite particles (powder) obtained.

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 result of X-ray crystal diffraction is shown in FIG. The ratio of the diffraction peak intensity of the (002) plane near 2θ = 26 ° to the diffraction peak intensity ratio of the (211) plane near 2θ = 32 ° is 1.7, which is clearly higher than that of Example 1. The value is shown. In addition, the diffraction peaks 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 agglomerating spindle-shaped crystals.

Comparative Example 2
10.7 mass% sodium dihydrogen phosphate / dihydrate aqueous solution and 8.6 mass% solid content ground calcium hydroxide slurry so that the Ca / P molar ratio becomes 0.5 (Japanese Patent Laid-Open No. No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate / dihydrate was placed in a stainless steel beaker and heated to 60 ° C. with stirring and maintained until stirring was stopped. The pH remained at 4.2 and was not adjusted. Calcium hydroxide slurry was added thereto over 45 minutes. After completion of the addition, 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 result of X-ray crystal diffraction is shown in FIG. In addition to the diffraction peak of hydroxyapatite, the diffraction peak of other substances was confirmed. The peak indicated by a black circle in the figure is a diffraction peak of monetite, which is calcium phosphate that is easily formed in an acidic state.

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

Comparative Example 3
10.7 mass% sodium dihydrogen phosphate aqueous solution and 8.6 mass% solid content high-purity calcium hydroxide slurry (BET specific surface area) so that the Ca / P molar ratio becomes 0.5. : 2.4 m ² / g, calcium reactivity: 25 seconds (Japanese Patent Laid-Open No. 2011-126772) was prepared. An aqueous solution of sodium dihydrogen phosphate / dihydrate was placed in a stainless steel beaker and heated to 60 ° C. with stirring and maintained until stirring was stopped. A 10% aqueous NaOH solution was added to adjust the pH to 5.5. Calcium hydroxide slurry was added thereto over 30 minutes. After completion of the addition, 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 result of X-ray crystal diffraction is shown in FIG. In addition to the diffraction peak of hydroxyapatite, the diffraction peak of calcium hydroxide was confirmed around 2θ = 28 ° and around 34 °.

The shape observation result is shown in FIG. Large plate-shaped particles of calcium hydroxide were confirmed. It was considered that the physical characteristics of the raw material calcium hydroxide had an effect on the difference from Example 1.

Comparative Example 4
10.7 mass% sodium dihydrogen phosphate / dihydrate aqueous solution and 8.6 mass% solid content ground 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 Japanese Patent Application Laid-Open No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate / dihydrate was placed in a stainless steel beaker, and a 10% aqueous solution of NaOH was added to adjust the pH to 5.5. Calcium hydroxide slurry was added thereto over 50 minutes. After completion of the addition, the mixture was further stirred for 1 hour, then the stirring was stopped, and 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 result of X-ray crystal diffraction is shown in FIG. The ratio of the diffraction peak intensity of the (002) plane near 2θ = 26 ° to the diffraction peak intensity ratio of the (211) plane near 2θ = 32 ° was 1.3.

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

Comparative Example 5
10.7 mass% sodium dihydrogen phosphate / dihydrate aqueous solution and 8.6 mass% solid content ground calcium hydroxide slurry so that the Ca / P molar ratio becomes 0.5 (Japanese Patent Laid-Open No. No. 2017-036176) was prepared. An aqueous solution of sodium dihydrogen phosphate / dihydrate was placed in a stainless steel beaker and heated to 80 ° C. with 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 completion of the addition, 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 result of X-ray crystal diffraction is shown in FIG. In addition to the diffraction peak of hydroxyapatite, the diffraction peak of other substances was confirmed. The peak indicated by a black circle in the figure is a diffraction peak of monetite, which is calcium phosphate that is easily formed in an acidic state.

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

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

[Test method]
0.5 g of hydroxyapatite particles obtained in the same manner as in Example 1 were added to artificial saliva (CaCl ₂ : 1.5 mM, KH ₂ PO ₄ : 0.9 mM, KCl: 130 mM, HEPES: 20 mM, pH 7.0 (KOH)). ) Soaked in 200 mL for 7 days. The powder filtered by suction filtration was measured by 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: 8.0 mm
-Light receiving slit: 0.3 mm.

The results are shown in FIG. Improvement of crystallinity (increased sharpness of peaks, appearance of peaks hidden by broad) was confirmed by artificial saliva immersion. From this, it was confirmed that the hydroxyapatite particles are particles that change (have reactivity) in the oral cavity.

When the same 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, and the crystals were crystalline. Did not change.

Test example 2. Ivory tube sealing test of hydroxyapatite particles [Test purpose]
In order to evaluate the ability of hydroxyapatite particles to block the dentin tubules, the bovine dentin surface was brushed with a hydroxyapatite particle solution, and the degree of blockage of the dentin tubules was examined by electron microscopy (SEM) observation.

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

Preparation of hydroxyapatite particle solution 5. 0.3 g of hydroxyapatite particles obtained in the same manner as in Example 1 was suspended in 39.7 g of a viscous diluent to obtain hydroxyapatite particles. 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 hydroxyapatite particle solution (40 g) (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 measurement conditions]
{Thin-film deposition}
-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 blocked by brushing in the hydroxyapatite particle solution. From this, it was confirmed that the hydroxyapatite particles are particles that block the dentin tubules existing on the surface of the dentin.

Test example 3. Sessility test [Test purpose]
In order to evaluate the ability of hydroxyapatite particles to adhere in the dentin canaliculus, the surface of bovine dentin was brushed with a solution of hydroxyapatite particles, and then water pressure was applied from the back surface of the dentin, and whether the water pressure was tolerated by the blockage of the hydroxyapatite particles. Was examined by electron microscope (SEM) observation.

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

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

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

Hydraulic treatment 10. The dentin disc after the brushing treatment was reported by pashley et al. (Pashley DH, Galloway SE. The effects of oxalate treatment on the smear layer of ground surface 198; ground surface Surfaces Pressurization was performed at 0.1 MPa for 30 minutes using the same apparatus.

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

[Observation measurement conditions]
{Thin-film deposition}
-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 ivory tubules were blocked even after the hydraulic treatment. From this, it was confirmed that the hydroxyapatite particles are particles that adhere in the dentinal tubules and maintain a closed state.

Test example 4. Ivory tubule sealability test for dentifrice [test purpose]
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 with an electron microscope (SEM).

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

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. Hereinafter, the unit "%" of the blending 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. The dentin block was brushed with a toothbrush (GUM # 211) for 30 seconds in the dentifrice solution (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 measurement conditions]
{Thin-film deposition}
-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: 25000 times

The results are shown in FIG. 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 has a high effect of sealing the dentinal tubules.

Test example 5. Ivory tubule sealability test when gel preparation is applied with a soft pick [Test purpose]
In order to confirm the ability of the gel preparation containing hydroxyapatite particles to seal the dentin 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 the dentin tubules was electron microscopically. It was examined with a microscope (SEM).

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

Coating process 6. A gel preparation containing (or not containing) hydroxyapatite particles obtained in the same manner as in Example 1 was placed on the brush portion of the 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 measurement conditions]
{Thin-film deposition}
-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: 25000 times

The results are shown in FIG. It was confirmed that the dentinal tubules were blocked by applying a gel preparation containing hydroxyapatite particles by soft picking.

Test example 6. Gel preparation clinical trial [Purpose of study]
The clinical effect of the gel preparation containing hydroxyapatite particles on antihyperesthesia was investigated. In this study, hydroxyapatite particles obtained in the same manner as in Example 1 were used as the hydroxyapatite particles.

[Test design]
(I) Gel preparation containing hydroxyapatite particles, aluminum lactate, and potassium nitrate (HAp + Al + K), (ii) Gel preparation containing aluminum lactate and potassium nitrate (Al + K), and (iii) Gel preparation containing potassium nitrate (K). Comparison was made with the three preparations of. The composition of these gel preparations is shown in Table 3 below.

Each gel preparation was used by 20 people, and the degree of scratch pain (applying a probe to the exposed root surface and rubbing horizontally) at 1, 2, or 4 weeks after use was measured on the VAS scale. I had you describe it in. In addition, the VAS scale shows the patient 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 indicate how much the current pain is. It is a visual scale. The flow of the test is shown in FIG. 27. In FIG. 27, the “hyperesthesia care set (gel preparation (test product))” indicates the gel preparations (i) to (iii) above, and the “hypersensitivity care set (gel preparation (placebo product))” is described above. The gel preparation obtained by removing potassium nitrate from the gel preparation of (iii) is shown.

[How to use the test product]
The subjects were allowed to use the gel preparation (test product) twice a day (morning and evening) (after waking up, after eating, before going to bed, etc., and according to their own oral cleaning habits). Specifically, first, after brushing with a designated toothbrush (Gum Pros Dental Brush # 3C: Sunstar Co., Ltd.) and a toothpaste (Corp Non-foam Toothpaste N), wash the mouth with about 10 ml of water for 20 seconds ( Brushing time is not specified), after which the gel preparation was used. To use the gel preparation, specifically, apply about 0.04 g (about the size of a rice grain) of the gel preparation (test product) to one test tooth with a tuft brush (Butler Single Tuft Brush # 01F: Sunstar Co., Ltd.). It was applied to the test site, and the test site and its 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 used between the test site and both adjacent teeth. It was inserted from the buccal side into the interdental part of the tooth and reciprocated 5 times. After using the gel preparation (test product), the mouth was washed with about 10 ml of water for 20 seconds.

The result of evaluating the degree of scratch pain on the VAS scale is shown in FIG. In the group using the hydroxyapatite combination preparation, the scratch pain was significantly improved 1 week after use as compared with the group using no combination. From this, it was found that the hydroxyapatite combination preparation has an effect of suppressing hypersensitivity symptoms at an early stage when used in combination with known medicinal ingredients for preventing hypersensitivity, such as aluminum lactate and potassium nitrate.

Test example 7. Examination of the effect of hydroxyapatite particles and fluorine compound-containing oral composition Hydroxyapatite particles obtained in the same manner as in Example 1 (Example 1 procedure-produced HAp) or commercially available hydroxyapatite particles (commercially available HAp (Tomita Pharmaceutical Co., Ltd.) (Manufactured); Commercially available hydroxyapatite different from the above reagent HAp), and sodium monofluorophosphate or sodium fluoride were used to prepare an oral composition. Specifically, each component shown in Table 4 was mixed to prepare each oral composition. The numerical value of each component shown in Table 4 indicates mass%. Further, when X-ray crystal diffraction was performed on the manufacturing HAp produced in the procedure of Example 1 and the commercially available HAp in the same manner as in Example 1, 2θ = 32 with respect to the diffraction peak intensity ratio by the (002) plane near 2θ = 26 °. The ratio of the diffraction peak intensities due to the (211) plane near ° was 1.44 for the HAp produced in the procedure of Example 1 and 2.72 for the commercially available HAp.

25 g of each of the obtained oral compositions was filled in a laminated tube having a diameter of 8 mm, stored at 55 ° C. in a dark place for 6 months and returned to room temperature, and then the color difference was measured as follows. The oral composition after storage was filled in a polystyrene container to a height of 2 cm, and an image was taken with an FD-5 (fluorescence spectrophotometer manufactured by Konica Minolta) on a white plate. The shooting conditions were constant lighting, shutter speed, squeezing, and focal length. B * in the L * a * b * color system of the 6 measured parts was measured, and the average value was calculated and used as an index for evaluating yellowing (yellowing). The result (b * value of each oral composition) is shown in FIG. The 9-bar graph of FIG. 29 shows Comparative Example 1a, Example 1a, Comparative Example 2a, Comparative Example 1b, Example 1b, Comparative Example 2b, Comparative Example 1c, Example 1c, and Comparative Example, respectively, in order from the left. The b * value of 2c, is shown.

From the results, it was confirmed that yellowing was synergistically suppressed in the oral composition containing hydroxyapatite particles and a fluorine compound.

Prescription examples (prescription examples 1 to 3) are shown below. The numerical value of the prescription example represents a mass part. In addition, Formulation Example 1 contains 1100 ppm of a fluorine compound in terms of fluoride ion concentration, Formulation Example 2 contains 1450 ppm of a fluorine compound in terms of fluoride ion concentration, and Formulation Example 3 contains a fluorine compound. It contains 1450 ppm in terms of fluoride ion concentration.

Claims (10)

An oral composition containing hydroxyapatite particles and a fluorine compound.
The ratio of the diffraction peak intensity near 2θ = 32 ° to the diffraction peak intensity near 2θ = 26 ° in the powder X-ray diffraction pattern measured by the CuKα characteristic X-ray of the hydroxyapatite particles is 0.8 to 1.5. is there,
Oral composition. The oral composition according to claim 1, wherein the Ca / P molar ratio of the hydroxyapatite particles is less than 1.67. The oral composition according to claim 1 or 2, wherein the hydroxyapatite particles have a median diameter of 5 μm or less. The oral composition according to any one of claims 1 to 3, wherein the hydroxyapatite particles have a specific surface area of 55 to 200 m ² / g. The ratio of the diffraction peak intensity near 2θ = 34 ° to the diffraction peak intensity near 2θ = 32 ° in the powder X-ray diffraction pattern measured by CuKα characteristic X-ray of the hydroxyapatite particles is 1 or less, claim 1. The oral composition according to any one of 4 to 4. The hydroxyapatite particles are aggregates of hydroxyapatite plate-like crystals.
The oral composition according to any one of claims 1 to 5. The oral composition according to any one of claims 1 to 6, further comprising potassium nitrate and / or aluminum lactate. The oral composition according to any one of claims 1 to 7, which is for preventing or improving hypersensitivity. The oral composition according to any one of claims 1 to 8, wherein the fluorine compound is at least one compound selected from the group consisting of sodium monofluorophosphate, sodium fluoride, and tin fluoride. The oral composition according to any one of claims 1 to 9, wherein the fluorine compound is contained in an amount of 2000 ppm or less in terms of fluoride ion concentration.