JP7467065B2 - Oral Composition - Google Patents

Description

The present disclosure relates to oral compositions and the like, and more specifically to oral compositions and the like that contain aluminum lactate and silica.

Aluminum lactate is an active ingredient in preventing dentin hypersensitivity, and is therefore incorporated into oral compositions in the hope of achieving this effect. Silica is also incorporated into oral compositions as a dental abrasive, etc.

Japanese Patent Application Laid-Open No. 5-155745

The present inventors have found that when an oral composition containing a thickener, aluminum lactate, and silica is stored (particularly when stored at relatively high temperatures, for example, about 40 to 60°C), the viscosity increases significantly. This level of temperature is quite acceptable during the distribution of oral composition products (particularly during distribution in summer), and from the viewpoint of maintaining a constant product quality, such an increase in viscosity over time during transportation or storage is undesirable.

The inventors therefore investigated a method for suppressing the increase in viscosity over time of an oral composition containing a thickener, aluminum lactate, and silica. As a result, they found that it may be possible to efficiently suppress the increase in viscosity of the oral composition (particularly the increase in viscosity over time) by further blending hydroxyapatite particles into the oral composition. Based on this finding, they then conducted further investigations.

The present disclosure includes, for example, the subject matter described in the following sections:
Item 1.
An oral composition comprising a thickener, aluminum lactate, silica, and hydroxyapatite particles.
Item 2.
Item 2. The oral composition according to item 1, wherein the thickener is at least one selected from the group consisting of alginic acid or a salt thereof, hydroxyalkyl cellulose, carboxyalkyl cellulose or a salt thereof, xanthan gum, and carrageenan.
Item 3.
Item 2. The oral composition according to item 1, wherein the thickener is carboxymethylcellulose or a salt thereof.
Item 4.
Item 4. The oral composition according to any one of Items 1 to 3, having a viscosity of 400 Pa·s or less at 30° C.
Section A.
A method for suppressing an increase in viscosity over time of an oral composition containing a thickener, aluminum lactate, and silica, the method comprising further blending hydroxyapatite particles in the preparation of the oral composition.

An oral composition is provided that contains a thickener, aluminum lactate, and silica, and that is inhibited from increasing in viscosity during storage.

This is a graph showing the values calculated by subtracting the viscosity value immediately after preparation from the viscosity value measured after storing each oral composition at 55° C. for 6 days.

Each embodiment included in the present disclosure will be described in more detail below. The present disclosure preferably includes oral compositions, particularly oral compositions containing a thickener, aluminum lactate, and silica, but is not limited thereto, and the present disclosure includes all that is disclosed in this specification and that can be recognized by a person skilled in the art.

The oral composition encompassed by the present disclosure contains hydroxyapatite particles in addition to a thickener, aluminum lactate, and silica. In this specification, the oral composition may be referred to as the "oral composition of the present disclosure."

Hydroxyapatite particles that are known in the field of oral compositions can be used. Hydroxyapatite particles prepared by a known method or a method that can be easily derived from a known method can also be used. Furthermore, commercially available hydroxyapatite products can also be purchased and used. For example, they can be purchased and used from Tomita Pharmaceutical Co., Ltd.

The median diameter (d50) of the hydroxyapatite particles is not particularly limited, but 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 examples include 1 μm or more, 2 μm or more, or 3 μm or more. More specifically, examples include 1 to 5 μm. The median diameter is a value measured by a laser diffraction/scattering method. More specifically, it is a value measured by dry particle size distribution measurement using a laser diffraction particle size distribution measurement device.

Hydroxyapatite particles can be prepared, for example, by a method for producing hydroxyapatite particles, which includes a step of mixing an aqueous solution of an alkali phosphate salt having a pH of 4 or more and less than 7 with a calcium hydroxide slurry and reacting them at 35 to 85°C.

The alkali phosphate salt is not particularly limited and includes hydrates and anhydrates. 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, etc., and preferably sodium phosphate salts such as sodium dihydrogen phosphate, disodium hydrogen phosphate, and trisodium phosphate, and more preferably sodium dihydrogen phosphate.

The concentration of the alkali phosphate 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 mass, more preferably 5 to 20% by mass, and even more preferably 7 to 15% by mass.

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

The calcium hydroxide slurry has oxalic acid reactivity, and it is preferable that the calcium hydroxide slurry is a slurry of calcium hydroxide that has a specific reactivity with oxalic acid.

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

Calcium hydroxide slurry having high oxalic acid reactivity (e.g., reactivity to the specific oxalic acid described above) can typically be obtained by grinding calcium hydroxide slurry. The grinding process can further increase the oxalic acid reactivity (shorten the time defined above). The grinding process is performed, for example, using a bead mill. There are no particular limitations on the conditions for the grinding process, and for example, the conditions according to the method described in JP 2017-036176 A can be adopted.

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

The solids 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 amount of the alkali phosphate aqueous solution to the amount of the calcium hydroxide slurry is not particularly limited as long as it is a ratio that allows the production of hydroxyapatite particles. It is desirable to adjust the ratio 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.

The manner in which the aqueous alkali phosphate solution and the calcium hydroxide slurry are mixed is not particularly limited. For example, the aqueous alkali phosphate solution may be added to a reaction vessel containing the aqueous alkali phosphate solution (mode 1), the aqueous alkali phosphate solution may be added to a reaction vessel containing the calcium hydroxide slurry (mode 2), or the aqueous alkali phosphate solution and the calcium hydroxide slurry may be added to the reaction vessel simultaneously (mode 3). Among these, mode 1 is preferred. During the above-mentioned addition to the reaction vessel, the liquid in the reaction vessel is usually stirred.

It is desirable to carry out the above-mentioned addition to the reaction vessel 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 to 85°C. The reaction temperature is preferably 40 to 75°C, more preferably 45 to 70°C, even more preferably 50 to 70°C, and even more preferably 55 to 65°C. When the pH of the aqueous alkali phosphate solution is relatively low (for example, when the pH is 4 or more and less than 5), the reaction temperature is relatively high, for example, 65 to 85°C, preferably 70 to 85°C, and more preferably 75 to 85°C. The reaction time (the time starting from when the aqueous alkali phosphate solution and the calcium hydroxide slurry are completely mixed, and in the above embodiments 1 to 3, the time starting from the time when the addition of the aqueous alkali phosphate solution and the calcium hydroxide slurry is completed) is, for example, 10 to 180 minutes, preferably 20 to 120 minutes, more preferably 40 to 90 minutes, and even more preferably 50 to 70 minutes.

The hydroxyapatite particles produced by the above process may be subjected to a purification process, if necessary. Examples of purification processes include filtration and water washing. If necessary, the particles may also be subjected to a drying process.

Hydroxyapatite particles can be contained in the oral composition in an amount of, for example, about 1 to 10% by mass. The upper or lower limit of the content range may be, for example, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, or 9.5% by mass. For example, the range is more preferably 2 to 8% by mass or 3 to 7% by mass.

In addition, aluminum lactate is preferably contained in the oral composition of the present disclosure in an amount of 0.05 to 3% by mass. The upper or lower limit of the range may be, for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, or 2.9% by mass. For example, the range may be 0.1 to 2.7% by mass or 0.2 to 2.5% by mass.

Although not particularly limited, the mass ratio of hydroxyapatite particles and aluminum lactate contained in the oral composition is preferably about 0.2 to 0.6 parts aluminum lactate to 1 part hydroxyapatite particle. The upper or lower limit of this range may be 0.25, 0.3, 0.35, 4, 0.45, 0.5, or 0.55, and is preferably about 0.25 to 0.55 or 0.3 to 0.5.

Thickeners contained in the oral composition of the present disclosure may be any known thickeners used in the field of oral compositions. Examples of such thickeners include alginic acid or its salts, hydroxyalkyl cellulose, carboxyalkyl cellulose or its salts, xanthan gum, gellan gum, tragacanth gum, karaya gum, arabic gum, carrageenan, dextrin, polyvinyl alcohol, polyvinylpyrrolidone, thickening silica, veegum, O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethyl cellulose chloride, polyacrylic acid or its salts, agar, etc.

Among these, alginic acid or its salts, hydroxyalkyl cellulose, carboxyalkyl cellulose or its salts, xanthan gum, and carrageenan are preferred.

As the salt of alginic acid, an alkali metal salt of alginic acid is preferred, more specifically, the potassium salt and the sodium salt are preferred. Sodium alginate is particularly preferred.

The alkyl of the hydroxyalkyl cellulose is preferably an alkyl having 1 to 4 carbon atoms (1, 2, 3, or 4). Specific examples of preferred hydroxyalkyl cellulose include hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.

The alkyl of the carboxyalkyl cellulose is preferably an alkyl having 1 to 4 carbon atoms (1, 2, 3, or 4). Specific examples of hydroxyalkyl cellulose include carboxymethyl cellulose and carboxymethyl ethyl cellulose. In addition, the salt of the carboxyalkyl cellulose is preferably an alkali metal salt, more specifically, a potassium salt or a sodium salt.

Preferred examples of salts of polyacrylic acid include sodium salts and potassium salts.

The thickener may be used alone or in combination of two or more. The thickener may be contained in the oral composition in an amount of, for example, about 0.5 to 5% by mass, and the upper or lower limit of the range may be, for example, 1, 1.5, 2, 2.5, 3, 3.5, 4, or 4.5% by mass. For example, the range may be 1 to 3% by mass or 1 to 2.5% by mass.

As the silica contained in the oral composition of the present disclosure, a known silica used in the field of oral compositions can be used. For example, precipitated silica can be used. Also, polishing silica can be used. Although not particularly limited, the silica is preferably silica having an average particle size of 2 to 20 μm. The average particle size is a value measured by a laser diffraction/scattering method. The silica also preferably has a pH (5 aq. Sol.) of, for example, about 5.5 to 7.5 or about 6 to 7. The pH (5 aq. Sol.) refers to the pH when 5 g of silica is dispersed in 95 mL of purified water. The silica also preferably has an oil absorption (cc/100 g) of, for example, about 10 to 500 or about 20 to 400. The silica can be contained in the oral composition in an amount of, for example, about 1 to 30% by mass. The upper or lower limit of the content range may be, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29% by mass. For example, the range is more preferably 2 to 25% by mass or 3 to 20% by mass.

The oral composition of the present disclosure does not undergo a significant increase in viscosity even when stored at relatively high temperatures (e.g., about 40 to 60°C). In particular, when stored at 55°C for 6 days, the difference in viscosity (Pa·s) between before and after storage is preferably 300 or less in absolute value, and more preferably 250 or less, 200 or less, 150 or less, or 100 or less in absolute value.

In this specification, the viscosity of the composition is a value measured using a Brookfield viscometer (Brookfield, spindle T-F, rotation speed: 10 rpm/min) after the composition is kept at 30°C for 30 minutes in a thermostatic bath to bring the composition to 30°C.

The oral composition of the present disclosure preferably has a viscosity of 400 Pa·s or less at 30°C, regardless of the time since preparation or storage conditions (particularly storage temperature). In other words, the oral composition of the present disclosure preferably has a viscosity of 400 Pa·s or less at 30°C, whether immediately after preparation or after storage at a relatively high temperature. The viscosity may be, for example, 390, 380, 370, 360, 350, 340, 330, 320, 310, 300, 290, 280, 270, 260, or 250 Pa·s or less. There is no particular lower limit to the viscosity, but examples include about 10, 20, 30, 40, 50, or 60 Pa·s.

The oral composition of the present disclosure may further contain other ingredients than those mentioned above, either alone or in combination of two or more, that can be incorporated into the oral composition, to the extent that the effect is not impaired.

For example, the surfactant may be a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant. Specifically, examples of 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; polyoxyethylene alkyl ethers with a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group with 13 to 15 carbon atoms; polyoxyethylene alkylphenyl ethers with a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group with 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan; and the like. Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and polyoxyethylene lauryl ether sodium sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and polyoxyethylene lauryl ether sodium sulfosuccinate; acylamino acid salts such as sodium cocoyl sarcosine and sodium lauroyl methyl alanine; and sodium cocoyl methyl taurine. Examples of amphoteric surfactants include acetate betaine type surfactants such as lauryl dimethylamino acetate betaine and coconut oil fatty acid amidopropyl dimethylamino acetate betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; and amino acid type surfactants such as N-lauryl diaminoethyl glycine. 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.

Sweetening agents such as saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, and p-methoxycinnamic aldehyde may also be added. These may be used alone or in combination of two or more. These may be added in an amount of 0.01 to 1% by mass based on the total amount of the composition.

In addition, sorbitol, glycerin, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, etc. can be used alone or in combination of two or more types as humectants.

Preservatives that can be used include parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride, either alone or in combination of two or more.

Coloring agents may include legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral pigments such as ultramarine, enhanced ultramarine, and Prussian blue, and titanium oxide, either alone or in combination of two or more kinds.

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 may be blended alone or in combination of two or more kinds so that the pH of the composition is in the range of 4 to 8, preferably 5 to 7. The amount of pH adjuster blended is, for example, 0.01 to 2% by weight.

As a medicinal ingredient, a bactericide may be added. Examples of the bactericide include cationic bactericides such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate, amphoteric bactericides such as dodecyldiaminoethylglycine, nonionic bactericides such as triclosan and isopropylmethylphenol, and hinokitiol. In addition, medicinal ingredients other than bactericides may be added. For example, potassium nitrate, vitamin E such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, sodium fluoride, etc. may be added. The medicinal ingredients may be added alone or in combination of two or more kinds. Note that potassium nitrate is a medicinal ingredient for preventing dentin hypersensitivity, and is therefore particularly preferable for further addition to the oral composition of the present disclosure. In particular, when potassium nitrate is added, it may be contained in the oral composition in an amount of, for example, about 1 to 10% by mass. The upper or lower limit of the content range may be, for example, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, or 9.5% by mass. For example, the range is more preferably 2 to 8% by mass or 3 to 7% by mass.

As bases, 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 optional ingredients are merely examples and do not limit the optional ingredients that may be used.

In this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present disclosure includes any combination of the constituent elements described in this specification.

Furthermore, the various characteristics (properties, structures, functions, etc.) described for each embodiment of the present disclosure above may be combined in any way to identify the subject matter encompassed by the present disclosure. In other words, the present disclosure encompasses all subject matter consisting of any combination of the combinable characteristics described in this specification.

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

Production Example 1: Preparation of Hydroxyapatite Particles A 10.7% by mass aqueous solution of sodium dihydrogen phosphate dihydrate and a 8.6% by mass solids grinding-treated calcium hydroxide slurry (BET specific surface area: 6.7 m ² /g, oxalic acid reactivity: 15 minutes 30 seconds, JP 2017-036176 A) were prepared so that the Ca/P molar ratio was 0.5. The aqueous solution of sodium dihydrogen phosphate dihydrate was placed in a stainless steel beaker, heated to 60°C while stirring, and maintained until the stirring was stopped. A 10% aqueous solution of NaOH was added to adjust the pH to 5.5. The calcium hydroxide slurry was added thereto over 30 minutes. After the addition was completed, the mixture was stirred for another hour, filtered, washed with water, and dried at 80°C to obtain hydroxyapatite particles (powder).

Study example: Study of viscosity change of oral composition by aluminum lactate Each oral composition was prepared by mixing each component shown in Table 1. Caustic soda was also added to the composition containing aluminum lactate to adjust the pH to about 7. The numerical values of each component shown in Table 1 indicate mass %. In addition, in Table 1, "Production Example 1 HAp" indicates hydroxyapatite particles obtained in the same manner as in Production Example 1, and "Commercially available HAp" indicates commercially available hydroxyapatite particles (manufactured by Tomita Pharmaceutical Co., Ltd.). In addition, as "silica" in Table 1, one of five commercially available types of silica (referred to as silica a, b, c, d, and e) was used, and as "hydroxyapatite particles", Production Example 1 HAp or commercially available HAp was used, or no HAp was used. Each of these "silica" and each of the "hydroxyapatite particles" was combined to prepare each oral composition (see Tables 2a, 2b, and 2c). In addition, the characteristics of the five types of silica used are summarized in Table 3.

The viscosity of each oral composition was measured immediately after preparation. In addition, 60 mL or more was filled into a colorless, transparent glass container (manufactured by Kashiwa Glass) with a full capacity of 83.5 mL and a body diameter of 45.5 mm, and the viscosity was measured immediately after filling and after storage at 55°C in a dark place for 6 days. The viscosity was measured using a B-type viscometer (manufactured by Brookfield, spindle T-F, rotation speed: 10 rpm/1 minute) after keeping each oral composition warm for 30 minutes in a thermostatic bath at 30°C. The viscosity immediately after preparation is shown in Table 2a, and the viscosity after storage at 55°C for 6 days is shown in Table 2b. Furthermore, the viscosity value immediately after preparation is subtracted from the viscosity value after storage, and the calculated value is shown in Table 2c. The results of Table 2c are shown in a graph in Figure 1.

In addition, oral compositions were prepared and stored in the same manner as above, except that commercially available HAp was used as the hydroxyapatite particles, silica c, silica d, or silica e was used as the commercially available silica, the amount of aluminum lactate was 0.2 mass%, the amount of 48% caustic soda was 0.1 mass%, and the storage conditions were storage at room temperature for 6 days, and the viscosity was examined. The viscosity immediately after preparation is shown in Table 4a, and the viscosity after storage at room temperature for 6 days is shown in Table 4b. Furthermore, the value calculated by subtracting the viscosity value immediately after preparation from the viscosity value after storage is shown in Table 4c.

Claims (4)

A composition for an oral cavity comprising carboxymethylcellulose or a salt thereof , aluminum lactate, silica, and hydroxyapatite particles,
0.5 to 5% by mass of carboxymethylcellulose or a salt thereof,
0.05 to 3 mass% aluminum lactate,
Silica: 1 to 30% by mass;
1 to 10% by mass of hydroxyapatite particles,
Contains
The silica has an average particle size of 6 to 20 μm and an oil absorption (cc/100 g) of 90 to 400.
Oral compositions. 2. The oral composition according to claim 1 , which has a viscosity at 30°C of 400 Pa·s or less. When stored at 55°C for 6 days, the difference in viscosity (Pa·s) before and after storage is 150 or less in absolute value.
The oral composition according to claim 1 or 2 . 1 to 3% by mass of carboxymethylcellulose or a salt thereof,
0.1 to 2.7% by mass of aluminum lactate,
2 to 25% by mass of silica,
2 to 8% by mass of hydroxyapatite particles,
contains,
The oral composition according to any one of claims 1 to 3.