JP7704543B2 - Method for inhibiting precipitation of insoluble substances in liquid oral compositions, and liquid oral compositions - Google Patents

Description

The present invention relates to a method for inhibiting the precipitation of insoluble substances in a liquid oral composition, and to a liquid oral composition.

Oral compositions such as toothpastes and mouthwashes have been used to keep teeth clean and the oral cavity healthy. Oral compositions contain a wide variety of ingredients to impart functions according to various applications.

One of the problems in the oral cavity is dentin hypersensitivity, which occurs when the enamel of the tooth disappears and the dentin is exposed, and pain occurs when this dentin is subjected to external stimuli such as temperature, chemical, and mechanical. It is thought that this is caused by nerve stimulation through the dentin tubules that run from the outermost layer of the dentin to the dental pulp, and as a countermeasure for dentin hypersensitivity, methods such as blocking the dentin tubules with aluminum lactate and desensitizing the nerves with potassium nitrate have been used.
For example, Patent Document 1 proposes an oral composition that contains aluminum and a carboxylate group in a dissolved state, and is formulated with an active ingredient for occluding dentinal tubules, in which the molar ratio of the carboxylate group to 1 mole of aluminum is 6 or less, and that also contains a phosphate compound and has a pH of 5 or more.

Furthermore, for the purpose of achieving an anti-inflammatory effect in the oral cavity, an anti-inflammatory agent such as glycyrrhizinate has been blended into oral compositions.
For example, Patent Document 2 proposes a dentifrice composition containing (A) dipotassium glycyrrhizinate, (B) sodium chloride, and (C) trimethylglycine, in which the blending amount of component (B) is 1 to 15 mass% of the total composition, and the mass ratio of component (A) to component (C) [(C)/(A)] is 50 to 500.

Japanese Patent Application Publication No. 07-165550 JP 2009-107988 A

The inventors' research has revealed that when aluminum lactate and glycyrrhizinate are mixed together in a liquid oral composition such as a mouthwash or liquid toothpaste, insoluble substances precipitate and deposit over time. Insoluble deposits in liquid oral compositions are a major problem in terms of the product's appearance.

The present invention aims to provide a method for suppressing the precipitation of insoluble substances when aluminum lactate and glycyrrhizinate are blended into a liquid oral composition, and a liquid oral composition containing aluminum lactate and glycyrrhizinate in which the precipitation of insoluble substances is suppressed.

As a result of extensive research, the inventors discovered that adding potassium nitrate to a liquid oral composition containing aluminum lactate and glycyrrhizinate can suppress the precipitation of insoluble substances, which led to the completion of the present invention.

That is, the present invention is achieved by the following (1) to (4).
(1) A method for inhibiting precipitation of insoluble substances in a liquid oral composition, characterized by including (C) potassium nitrate in a liquid oral composition containing (A) aluminum lactate and (B) glycyrrhizinate.
(2) A method for inhibiting precipitation of insoluble substances in the liquid oral composition described in (1), characterized in that (C) potassium nitrate is contained in the liquid oral composition in a range of 1 to 15 w/v %.
(3) A liquid oral composition comprising (A) aluminum lactate and (B) glycyrrhizinate, and further containing (C) potassium nitrate.
(4) A liquid oral composition described in (3) characterized in that the light transmittance at a wavelength of 660 nm is 95% or more when left at 50°C for four weeks.

The method of the present invention can suppress the precipitation of insoluble substances caused by the incorporation of aluminum lactate and glycyrrhizinate into the liquid oral composition. This can suppress the occurrence of insoluble precipitates in the liquid oral composition, and maintain the stability of the product over time.

Hereinafter, the embodiments of the present invention will be described in more detail.
In addition, in the present invention, the unit of formulation amount "w/v %" refers to mass to volume percentage (ingredients content (g) in liquid oral composition (100 mL)).

(Method for inhibiting precipitation of insoluble substances in liquid oral compositions)
The method for inhibiting the precipitation of insoluble substances in the liquid oral composition of the present invention includes adding (C) potassium nitrate to a liquid oral composition containing (A) aluminum lactate and (B) glycyrrhizinate.

(A) Aluminum lactate blocks the dentinal tubules in the dentin of teeth, which are the pathways through which pain is transmitted, so in oral compositions it is effective in suppressing dentin hypersensitivity.

(A) Aluminum lactate is preferably contained in the liquid oral composition in the range of 1 to 10 w/v%. If the content of (A) aluminum lactate is 1 w/v% or more, a dentinal tubule sealing effect is obtained and the stability of aluminum lactate in the composition decreases, so it is preferable to contain it at 10 w/v% or less. The content of (A) aluminum lactate is more preferably 1 to 7 w/v%, even more preferably 1 to 5 w/v%, and particularly preferably 1 to 3 w/v%.

(B) Glycyrrhizinate has an anti-inflammatory effect in the oral composition.
Examples of glycyrrhizinate include potassium salts such as monopotassium glycyrrhizinate and dipotassium glycyrrhizinate, sodium salts such as monosodium glycyrrhizinate and disodium glycyrrhizinate, and ammonium salts such as monoammonium glycyrrhizinate and diammonium glycyrrhizinate. Among these, from the viewpoint of the stability of the liquid oral composition, potassium salts and ammonium salts of glycyrrhizinate are preferred, and dipotassium glycyrrhizinate and monoammonium glycyrrhizinate are more preferred.

The amount of (B) glycyrrhizinate salt in the liquid oral composition is preferably 0.001 to 3 w/v% in terms of glycyrrhizinic acid. If the amount of (B) glycyrrhizinate salt is 0.001 w/v% or more in terms of glycyrrhizinic acid, an effective anti-inflammatory effect can be obtained, and it is preferable to include it at 3 w/v% or less in consideration of flavor, which is lower than the range permitted for incorporation into cosmetics, medicines, or quasi-drugs for external use. The amount of (B) glycyrrhizinate salt is more preferably 0.001 to 2 w/v% in terms of glycyrrhizinic acid, and even more preferably 0.01 to 1 w/v%.

The content of glycyrrhizinic acid can be measured by standard high-performance liquid chromatography.

The liquid oral composition of the present invention preferably contains (D) water in the range of 40 to 99 w/v%. If the (D) water content is less than 40 w/v%, it becomes difficult to keep the oral composition liquid, and if it is 99 w/v% or less, an effective amount of the active ingredient can be contained. The (D) water content is more preferably 40 to 90 w/v%, and even more preferably 50 to 80 w/v%.

Examples of water include purified water, ionized water, distilled water, etc.

In this specification, the term "liquid" refers to a material that has fluidity and has a viscosity of 20 mPa·s or less, preferably 10 mPa·s or less, at 20°C. Here, the viscosity can be measured using a commercially available rotational viscometer (for example, an R-type viscometer manufactured by Toki Sangyo Co., Ltd.).

When (A) aluminum lactate and (B) glycyrrhizinate are present together in a liquid oral composition, an insoluble substance may precipitate over time, resulting in a precipitate. This is presumed to be because (A) aluminum lactate reacts with (B) glycyrrhizinate to precipitate aluminum glycyrrhizinate, which is insoluble in water and thus exists in the liquid oral composition as a precipitate. The inventor's research has revealed that when (C) potassium nitrate is added to a liquid oral composition containing (A) aluminum lactate and (B) glycyrrhizinate, the precipitation of such an insoluble substance is suppressed, although its effect is unclear.
(C) Potassium nitrate is used in the oral composition as an active ingredient for suppressing dentin hypersensitivity, similar to (A) aluminum lactate, but in the present invention, it is used as an agent for inhibiting the precipitation of insoluble substances.

(C) Potassium nitrate is preferably contained in the liquid oral composition in the range of 1 to 15 w/v%. When potassium nitrate (C) is contained in an amount of 1 w/v% or more, the effects of the present invention can be obtained, and when the content is 15 w/v% or less, the flavor of the liquid oral composition is not impaired. (C) Potassium nitrate is more preferably contained in the range of 1 to 12 w/v%, and even more preferably 1 to 5 w/v%.

In addition, from the viewpoint of obtaining an appropriate effect of inhibiting the precipitation of insoluble substances in the liquid oral composition, it is preferable to contain (C) potassium nitrate in a mass ratio of 0.5 to 5 parts of potassium (C) nitrate per 1 part of aluminum (A) lactate. When the content of potassium (C) nitrate is 0.5 or more times the mass ratio of 1 part of aluminum (A) lactate, the effect of the present invention can be obtained, and even if an amount exceeding 5 times is contained, no significant difference in effect is observed. It is more preferable to contain (C) potassium nitrate in a mass ratio of 1 to 5 parts of potassium (C) nitrate per 1 part of aluminum (A) lactate.

(Liquid oral composition)
The liquid oral composition of the present invention contains (A) aluminum lactate and (B) glycyrrhizinate, and further contains (C) potassium nitrate.

(A) The aluminum lactate content is as described above, and the preferred range of content is the same.

(B) Glycyrrhizinate is as described above, and the same applies to the preferred glycyrrhizinate and the preferred range of content.

(C) The potassium nitrate content is as described above, and the preferred range of content is the same.

The liquid oral composition preferably contains 40 to 99 w/v% water (D). The details of water (D) are as described above, and the preferred range of the content is the same.

The liquid oral composition of the present invention may contain various components that can be applied to the oral cavity, as long as they do not impair the effects of the present invention. Examples of such components include solvents, humectants, flavoring agents, bactericides, anti-inflammatory agents, surfactants (solubilizers), pH adjusters, enzymes, ion sources, preservatives (preservatives), fragrances, herbal medicines, and colorants.

Solvents include, for example, water and lower alcohols such as ethanol.

Examples of humectants include glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, and polypropylene glycol.

Examples of flavoring agents include sweeteners such as stevia, xylitol, erythritol, maltitol, sorbitol, sodium saccharin, sucralose, reduced palatinose, and aspartame.

Examples of disinfectants include cationic disinfectants such as benzethonium chloride, cetylpyridinium chloride, benzalkonium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate, triclosan, isopropylmethylphenol, hinokitiol, thymol, and alkyldiaminoethylglycine hydrochloride solution.

Anti-inflammatory agents include, in addition to glycyrrhizinate, tranexamic acid, epsilon aminocaproic acid, allantoin, aluminum chlorohydrate allantoin, dihydrocholesterol, and glycyrrhetinic acid.

Examples of surfactants include nonionic surfactants, cationic surfactants, anionic surfactants, and amphoteric surfactants. Specifically, examples of nonionic surfactants include glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, fatty acid diethanolamides, fatty acid monoglycerides, polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oil, alkyl glucosides, and polyoxyethylene polyoxypropylene block copolymers. Examples of cationic surfactants include alkyl trimethyl ammonium chloride and dialkyl dimethyl ammonium chloride. Examples of anionic surfactants include sulfate ester salts, α-olefin sulfonate salts, sulfosuccinate salts, N-acyl amino acid salts, and acylated methyl taurine salts. Examples of amphoteric surfactants include betaine acetate type surfactants and imidazoline type surfactants.

Examples of pH adjusters include monosodium phosphate, disodium phosphate, sodium citrate, citric acid, glucono-δ-lactone, sodium gluconate, sodium acetate, sodium hydroxide, and hydrates thereof.

Examples of enzymes include protease, dextranase, amylase, mutanase, lysozyme, etc.

Ion sources include, for example, fluoride ion sources such as sodium fluoride, monofluorophosphate, and stannous fluoride, and phosphate ion sources such as calcium phosphate and hydroxyapatite.

Examples of preservatives include parahydroxybenzoic acid esters such as methyl parahydroxybenzoate and propyl parahydroxybenzoate, sodium benzoate, and phenoxyethanol.

Fragrances include, for example, natural essential oils such as peppermint oil, spearmint oil, menthol oil, eucalyptus oil, clove oil, thyme oil, and rosemary oil, and fragrance components such as l-menthol, l-carvone, carvacrol, eugenol, anethole, 1,8-cineole, hinokitiol, and thymol.

Examples of herbal medicines include Phellodendron bark extract and Angelica acutiloba extract.

Examples of pigments include Blue No. 1, Yellow No. 4, Red No. 102, and Green No. 3.

(Production of liquid oral composition)
The liquid oral composition of the present invention can be used in the form of a mouthwash, liquid toothpaste, mouth freshener, mouthwash (gargle), etc. These can be prepared into preparations by known means.

For example, to prepare a mouthwash, (D) water and an alcoholic solvent such as ethanol may be used as the solvent, and (A) aluminum lactate, (B) glycyrrhizinate, (C) potassium nitrate, and other various components as desired may be added and prepared in a conventional manner. For example, the mouthwash may be prepared by adding a surfactant and an oily component (such as a fragrance or preservative) to an alcoholic solvent, adding water to solubilize the mixture, and then adding aluminum lactate, glycyrrhizinate, potassium nitrate, and water-soluble components.

It is preferable to include an alcohol-based solvent in an amount of 25 w/v% or less of the total amount of the mouthwash, as this can reduce irritation in the oral cavity. It is more preferable that the content of the alcohol-based solvent is 10 w/v% or less.

(Physical properties of liquid oral composition)
When the liquid oral composition of the present invention is left at rest for 4 weeks at 50° C., if no insoluble substances are precipitated in the liquid oral composition, the light transmittance at a wavelength of 660 nm is 95% or more, and it can be confirmed that the liquid oral composition is stable over time. The light transmittance is more preferably 97% or more, and even more preferably 99% or more.

The light transmittance can be measured in accordance with the transmitted light measurement method in the turbidity test method of the Japanese Pharmacopoeia (16th Amendment, Second Supplement). Specifically, it is determined by measuring the transmittance of the liquid oral composition at a wavelength of 660 nm using a spectrophotometer or photoelectric photometer by the ultraviolet-visible light measurement method.

In addition, the liquid oral composition of the present invention preferably has a pH of 5 to 10, since this provides a better feel when used in the oral cavity.

(Method of using the liquid oral composition)
The method of using the liquid oral composition of the present invention is, when it is applied to the oral cavity as a mouthwash, to hold 5 to 25 mL of the liquid oral composition in the mouth and rinse the oral cavity for 15 to 60 seconds, thereby allowing the liquid oral composition of the present invention to be sufficiently distributed in the oral cavity.

The present invention will be further explained below with reference to examples and comparative examples, but the present invention is not limited to the following examples.

<Test Example 1>
(Examples 1 to 10, Comparative Examples 1 to 3, Reference Examples 1 and 2)
1. Preparation of liquid oral composition According to the formulation shown in Table 1, the components were mixed under stirring to prepare a liquid oral composition. Since the pH of the composition changes depending on the amount of aluminum lactate, making it impossible to solubilize the composition, sodium hydroxide "0.33" was added to aluminum lactate mass "1" to keep the pH almost constant. However, in Example 5, aluminum lactate mass "3" was solubilized with "0.72".

2. Confirmation of Precipitation of Insoluble Substances 80 g of the liquid oral composition was filled into a transparent plastic bottle (volume 87 mL) to obtain a test sample.
The test specimens were stored at 50° C. for 4 weeks, and after 4 weeks, the appearance was visually inspected to evaluate the presence or absence of insoluble substances. Those in which no insoluble substances were observed were evaluated as “◯”, and those in which insoluble substances were observed were evaluated as “×”. The results are shown in Table 1.

3. Measurement of light transmittance The liquid oral composition after 4 weeks of static storage at 50°C, evaluated in "2. Confirmation of precipitation of insoluble substances", was measured for light transmittance (%) at a wavelength of 660 nm using a spectrophotometer by ultraviolet-visible light measurement method in accordance with the transmitted light measurement method in the turbidity test method of the Japanese Pharmacopoeia (16th Amendment, Second Supplement). The results are shown in Table 1.

Comparing Reference Examples 1 and 2 with Comparison Examples 1 to 3, it was found that the coexistence of aluminum lactate and glycyrrhizinate caused insoluble substances to precipitate in the liquid oral composition.
It was also found from Examples 1 to 10 that the inclusion of potassium nitrate in a liquid oral composition containing aluminum lactate and glycyrrhizinate can suppress the precipitation of insoluble substances. In Examples 1 to 10, no precipitation of insoluble substances was observed even after storage at 50°C for 4 weeks, and the light transmittance was all 99% or more, demonstrating excellent transparency.
Storage at 50°C for four weeks is equivalent to approximately 12 months when stored at room temperature (15 to 25°C, according to the Japanese Pharmacopoeia), demonstrating that the liquid oral composition of the present invention has excellent long-term storage stability.

<Test Example 2>
(Examples 11 to 12, Comparative Example 4)
1. Preparation of liquid oral composition In Test Example 1, dipotassium glycyrrhizinate was used as the glycyrrhizinate salt, while in Test Example 2, monoammonium glycyrrhizinate was used as the glycyrrhizinate salt.
According to the formulation shown in Table 2, each component was mixed under stirring to prepare a liquid oral composition.

2. Confirmation of precipitation of insoluble substances and measurement of light transmittance For the liquid oral compositions of Examples 11 to 12 and Comparative Example 4, the presence or absence of precipitation of insoluble substances was confirmed in the same manner as in Test Example 1, and the light transmittance was measured.
The results are shown in Table 2.

The results in Table 2 show that even when ammonium glycyrrhizinate is used as the glycyrrhizinate salt, the inclusion of potassium nitrate in a liquid oral composition containing aluminum lactate and ammonium glycyrrhizinate can suppress the precipitation of insoluble substances. In addition, Examples 11 and 12 had a light transmittance of 99% or more, and were found to have excellent transparency.

Claims (4)

A method for inhibiting precipitation of insoluble substances in a liquid oral composition , comprising: (A) aluminum lactate and (B) glycyrrhizinate, the amount of (B) glycyrrhizinate being 0.0047 to 0.014 mass of the glycyrrhizinate per mass of the (A) aluminum lactate; and further comprising (C) potassium nitrate. The method for inhibiting precipitation of insoluble substances in a liquid oral composition according to claim 1, characterized in that the liquid oral composition contains potassium nitrate (C) in an amount ranging from 1 to 15 w/v %. A liquid oral composition (except when a straight-chain aliphatic aldehyde having 8 to 11 carbon atoms and a lactone having 6 to 12 carbon atoms are simultaneously contained), characterized in that it contains (A) aluminum lactate and (B) glycyrrhizinate, wherein the content of the (B) glycyrrhizinate is 0.0047 to 0.014 in terms of glycyrrhizinic acid per 1 mass of the (A) aluminum lactate, and further contains (C) potassium nitrate . The liquid oral composition according to claim 3, characterized in that the light transmittance at a wavelength of 660 nm is 95% or more when left standing at 50°C for 4 weeks.