JPWO2019216108A1 - Oral composition - Google Patents

Abstract

Provided is an oral composition which stably blends the anti-inflammatory component tranexamic acid or ε-aminocaproic acid and gives an excellent halitosis suppressing effect. It contains (A) tranexamic acid or ε-aminocaproic acid, (B) copper ion or zinc ion, and (C) sodium monofluorophosphate, and the content of (C) component is 0.8 to 3% by mass. Oral composition.

Description

The present invention relates to an oral composition in which the anti-inflammatory component tranexamic acid or ε-aminocaproic acid is stably blended and has an excellent halitosis suppressing effect.

Periodontal disease is often accompanied by halitosis, and it is possible to combine the above-mentioned anti-inflammatory component with a medicinal component effective for suppressing halitosis in an oral composition for gum care to give the effects of both. It is effective and preferable for prevention or suppression of.
Tranexamic acid and ε-aminocaproic acid, which have anti-inflammatory effects, are anti-inflammatory components used in oral compositions such as toothpaste for preventive measures against periodontal disease, which is an inflammatory disease. Depending on the ingredients, the stability may be deteriorated, the preparation may be discolored over time, other ingredients cannot be easily added, and it is difficult to use other halitosis-suppressing ingredients together.
In Patent Document 1 (Patent No. 5842565), tranexamic acid or ε-aminocaproic acid is blended with a synamic aldehyde and an alkyl sulfate to suppress discoloration of the liquid oral composition.

By the way, copper and zinc have an effect of suppressing volatile sulfur compounds (VSC) generated from periodontal disease-causing bacteria, and water-soluble copper or zinc compounds that supply copper or zinc ions have an effect of suppressing bad breath. Although it is known as a component having, these effects of suppressing bad breath were not sufficient.
In Patent Documents 2 and 3 (Japanese Patent No. 2580657 and Japanese Patent No. 2738021), a water-soluble copper compound such as copper gluconate and copper citrate is combined with a polybasic acid or modified aluminum hydroxide to cause a bad odor. It has been proposed that the prevention effect can be improved.

Japanese Patent No. 5842565 Japanese Patent No. 2580657 Japanese Patent No. 2738021 Japanese Patent No. 3922329

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an oral composition in which tranexamic acid or ε-aminocaproic acid, which are anti-inflammatory components, is stably blended and which has an excellent halitosis-suppressing and lasting effect. To do.

As a result of diligent studies to achieve the above object, the present inventors preferably use (A) tranexamic acid or ε-aminocaproic acid as an anti-inflammatory component and (B) copper ion or zinc ion as a halitosis-suppressing component. Is a preparation derived from the component (A) when a water-soluble copper compound or zinc compound is used in combination as the source of the ions and (C) sodium monofluorophosphate is combined in a specific amount and blended into the oral composition. It has been found that discoloration is suppressed even after storage, and the halitosis suppressing effect is maintained even after several hours have passed immediately after use, and the component (A) can be stably blended and an excellent halitosis suppressing effect can be imparted. It came to.

More specifically, even if the component (A) having an anti-inflammatory effect and the component (B) having an anti-halitosis effect are blended in combination with the oral composition, the halitosis-suppressing effect is not sustained, and it is used. After a few hours, it is hardly observed (see Comparative Example 6 described later), and when the amount of component (B) is increased in order to improve the long-lasting effect of suppressing halitosis, discoloration of the preparation derived from component (A) is caused. A sexual problem occurred (see Comparative Example 5 below). Therefore, in order to solve the above-mentioned problems related to halitosis suppression and discoloration of the preparation, the present inventors further studied, and when the component (C) was further added in a specific amount, the above-mentioned problem was solved and the discoloration of the preparation was caused. It was possible to suppress the effect even after storage and to maintain the halitosis suppressing effect even if the component (B) was not added in a relatively large amount. As a result, in addition to the anti-inflammatory effect of the component (A), it has become possible to provide an excellent halitosis suppressing effect that lasts for several hours even after use. In this case, even if the component (C) was used in combination with the components (A) and (B), discoloration of the preparation was observed when the amount of the component (C) was relatively small and inappropriate (Comparative Example 1 described later, Comparative Example 1). (See 2) However, when the amount of the component (C) added was more than a specific value, surprisingly, the discoloration of the preparation was suppressed by the component (C), and the discoloration of the preparation was hardly observed even after long-term storage. (See Examples below). Therefore, according to the present invention, the component (A) and the component (B) can be blended at the same time to impart the above-mentioned special action and effect.
As for the action and effect of the present invention, for example, when disodium hydrogen phosphate is used instead of the component (C) as shown in Comparative Example 4 described later, the effect of sustaining halitosis suppression is inferior, and other than the component (C). The effect of the present invention was also inferior when the fluorine-containing compound of No. 1 was used, or when poorly soluble copper citrate was used in water instead of the component (B). On the other hand, the oral composition containing the components (A), (B) and (C) of the present invention shown in Examples and the content of the component (C) within a specific range causes discoloration of the preparation. It was suppressed even after storage and was excellent in no discoloration, and had an excellent halitosis suppressing effect (immediately after) and its durability (after 3 hours had passed).

Patent Document 4 (Patent No. 3922329) is an invention in which the astringency and metallic taste of a dentifrice composition containing a condensed phosphate or the like and a water-soluble transition metal compound are improved while preventing discoloration due to amino acids. Therefore, no attention is paid to the effect of suppressing bad breath and no mention is made.

Therefore, the present invention provides the following oral compositions.
[1]
(A) Tranexamic acid or ε-aminocaproic acid,
An oral composition containing (B) copper ion or zinc ion, and (C) sodium monofluorophosphate, and the content of the component (C) is 0.8 to 3% by mass.
[2]
(B) The oral composition according to [1], wherein the source of the copper ion or zinc ion is a water-soluble copper compound or zinc compound having a water solubility at 25 ° C. of 5 g / 100 mL or more.
[3]
(B) The source of copper ion or zinc ion is one or more water-soluble copper compounds or zinc compounds selected from copper gluconate, sodium copper chlorophyllin, zinc chloride and zinc gluconate [1]. Or the oral composition according to [2].
[4]
(B) The oral composition according to [1], wherein the source of copper ions or zinc ions is an acidic aqueous solution of a poorly water-soluble or water-insoluble copper compound or zinc compound having a water solubility of less than 5 g / 100 mL at 25 ° C. Stuff.
[5]
The oral composition according to any one of [1] to [4], which contains 0.006 to 0.5% by mass of the component (A) and 0.001 to 0.1% by mass of the component (B).
[6]
The oral composition according to any one of [1] to [5], wherein (C) / (B) has a mass ratio of 10 to 1,500.
[7]
The oral composition according to any one of [1] to [6], which is a dentifrice composition.

According to the present invention, an oral composition which stably blends the anti-inflammatory component tranexamic acid or ε-aminocaproic acid and gives an excellent halitosis-suppressing effect in which the halitosis-suppressing effect lasts for several hours immediately after use. Can be provided. The oral composition can be effectively used for prevention or suppression of periodontal disease.

Hereinafter, the present invention will be described in more detail. The oral composition of the present invention contains (A) tranexamic acid or ε-aminocaproic acid, (B) copper ion or zinc ion, and (C) sodium monofluorophosphate. The "copper ion or zinc ion" means a copper compound or zinc ion of a copper compound or zinc compound dissolved in a liquid medium (water or the like) of the composition, and is insoluble in the composition in a solid state. It is not a copper compound or zinc compound.

(A) Tranexamic acid or ε-aminocaproic acid is an active ingredient having an anti-inflammatory effect. As the component (A), tranexamic acid and ε-aminocaproic acid can be used, but tranexamic acid and ε-aminocaproic acid can also be used in combination.

The blending amount of the component (A) is preferably 0.006 to 0.5% (mass%, the same applies hereinafter) of the entire composition, and more preferably 0.03 to 0.2%. The larger the amount, the higher the anti-inflammatory effect, and if it is 0.006% or more, a sufficient anti-inflammatory effect can be obtained. When it is 0.5% or less, discoloration of the preparation can be sufficiently suppressed, and the onset of irritation caused by the component (A) itself can be sufficiently prevented.

The component (B) is a copper ion or a zinc ion.
The copper ion or zinc ion dissolved in the oral composition of the present invention is a component having a halitosis-suppressing effect. As the component (B), the copper ion or zinc ion can be used alone, or both ions can be used in combination.
The component (B) can be derived from a water-soluble compound, and a water-soluble copper compound or zinc compound can be used as a source of the ions and blended. The water-soluble compound here is a compound having a water solubility at 25 ° C. of 5 g / 100 mL or more. Examples of such a water-soluble copper compound include copper gluconate, copper sulfate, copper chloride, sodium copper chlorophyllin, and copper acetate. Examples of the water-soluble zinc compound include zinc chloride, zinc sulfate, zinc nitrate, and zinc gluconate. These can be used alone or in combination of two or more, but among them, copper gluconate, sodium copper chlorophyllin, zinc chloride, and zinc gluconate are preferable, and more preferably, water-soluble copper compounds such as copper gluconate and copper. Chlorophyllin sodium.
As another embodiment, the component (B) may use a poorly water-soluble or insoluble copper compound, a copper ion derived from a solution of a zinc compound in another solvent, or a zinc ion, and the above solution may be used as an ion source. It can also be used as a compound. For example, copper ions and zinc ions obtained by dissolving water-insoluble copper oxide and zinc oxide in an acidic aqueous solution such as dilute hydrochloric acid can also be used. Alternatively, a metal complex may be formed and dissolved in the system. Here, "water-soluble or insoluble" means that the water solubility at 25 ° C. is less than 5 g / 100 mL.

The blending amount of the component (B) is preferably 0.001 to 0.1%, more preferably 0.005 to 0.05% of the entire composition as the amount of copper ions and zinc ions. When the blending amount is 0.001% or more, the halitosis suppressing effect and its sustainability are sufficiently obtained, and when it is 0.1% or less, the discoloration of the preparation is sufficiently suppressed.
As the component (B), it is preferable to blend the copper compound and the zinc compound in an amount that satisfies the range of the blending amount of the component (B). In this case, the blending amount of the copper compound and the zinc compound is the composition. 0.01 to 0.5% of the whole product, particularly 0.05 to 0.3% is preferable.

(C) Sodium monofluorophosphate is known as an active ingredient for preventing caries, but in the present invention, by blending at a predetermined concentration or more, discoloration of the preparation due to the combined system of the components (A) and (B) is suppressed. It also has the effect of improving the sustainability of the halitosis suppressing effect. When a fluorine-containing compound other than the component (C), for example, sodium fluoride is used, discoloration of the preparation is not suppressed and the action and effect of the present invention are inferior.

The blending amount of the component (C) is 0.8 to 3%, preferably 1 to 2%, and particularly 1 to 1.5% of the entire composition. If the blending amount is less than 0.8%, the effect of suppressing discoloration of the preparation is inferior. The larger the blending amount, the more the discoloration of the preparation is suppressed, and the sustainability of the halitosis suppressing effect is enhanced. However, if it exceeds 3%, the astringency and bitterness of the component (C) itself develop and it becomes unsuitable for use.

In the present invention, (C) / (B) indicating the ratio of the (B) component amount (copper ion, zinc ion amount) and the (C) component amount is not particularly limited, but the mass ratio is 10 to 1,500. It is preferable, more preferably 35 to 1,100, still more preferably 35 to 150. Within the above range, the effect of suppressing discoloration of the preparation is more excellent, and the effect of suppressing halitosis and its sustainability are also excellent. If the mass ratio of (C) / (B) is less than 10, the effect of suppressing discoloration of the preparation may not be sufficiently obtained, and if it exceeds 1,500, the effect of suppressing bad breath can be sufficiently sustained. It may not be.

The oral composition of the present invention can be prepared in various dosage forms such as dentifrices such as dentifrices and liquid dentifrices, mouthwashes, coating agents, sprays, patches, chewing gums, and gummy, but it is preferable to use dentifrices. It is more preferably prepared as an agent, a mouthwash, a coating agent, particularly a dentifrice, particularly a dentifrice, and a dentifrice composition. In addition, the oral composition can be prepared by adopting a conventional method according to the dosage form. In this case, other known components may be optionally added in addition to the above components depending on the purpose of the composition, the dosage form, and the like. For example, in the case of dentifrices, abrasives, thickeners, binders, surfactants and, if necessary, sweeteners, preservatives, colorants, fragrances, (A), (B) and (C). ) Active ingredients other than the ingredients can be blended, and these ingredients and water can be mixed and manufactured.

Abrasives include silica-based abrasives such as precipitated silica, aluminosilicate and zirconosilicate, calcium dibasic phosphate dihydrate or anhydride, calcium phosphate-based abrasives such as calcium primary phosphate and calcium tertiary phosphate, and calcium carbonate. , Aluminum hydroxide. The blending amount of the abrasive is preferably 0 to 50%, particularly 5 to 30% of the entire composition.

Examples of the viscous agent include sugar alcohols such as sorbitol, xylitol and erythritol, and polyhydric alcohols such as glycerin and propylene glycol. The blending amount of the thickener is preferably 5 to 60%, particularly 20 to 50% of the total composition.

As the binder, an organic or inorganic binder can be blended. Specifically, the organic binders are cellulose derivatives such as sodium carboxymethyl cellulose and methyl cellulose, gums such as xanthan gum and Arabic gum, alginic acid derivatives and carrageenan, and the inorganic binders are gelling silica and gelling aluminum silica. Examples include bee gum and raponite. The blending amount of the binder can be adjusted according to the dosage form. In the case of toothpaste, the organic binder should be 0.1 to 5% of the total composition, especially 0.5 to 3%, and the inorganic binder should be. 1-10% of the total composition, especially 2-8%, is preferable. In the liquid mouthwash, both the organic binder and the inorganic binder are preferably 0 to 5% of the total composition.

As the surfactant, an anionic surfactant, a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant can be blended.
Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate, acyl amino acid salts, and acyl taurine salts.
Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid ester, sugar alcohol fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil and the like. Polyoxyethylene fatty acid ester and polyoxyethylene higher alcohol ether can be mentioned.
Examples of the cationic surfactant include an alkylammonium salt, and examples of the amphoteric surfactant include alkyl betaine, fatty acid amide alkyl betaine, and fatty acid amide propyl dimethylamino acetate betaine.
The blending amount of the surfactant is preferably 0 to 10%, particularly 0.1 to 5% of the total composition.

Examples of the sweetener include sodium saccharin, and examples of the preservative include paraoxybenzoic acid ester, benzoic acid or a salt thereof.
Examples of the colorant include Blue No. 1, Yellow No. 4, and Titanium Dioxide.

Fragrances are peppermint oil, sparemint oil, anis oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamon oil, coriander oil, mandarin oil, lime. Oil, lavender oil, rosemary oil, laurel oil, camomill oil, caraway oil, majorum oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie oil , Yuzu oil, iris concrete, absolute peppermint, absolute rose, orange flower and other natural fragrances, and processing of these natural fragrances (pre-reservoir cut, rear-reservoir cut, distilling, liquid extraction, essence, powder fragrance Perfume, menthol, carboxylic, anator, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-mentoxypropane-1,2-diol, timole, linalol, linalyl acetate, limonene, menton, Menthylacetate, N-substituted-paramentan-3-carboxamide, pinen, octylaldehyde, citral, pregon, calvier acetate, anisaldehyde, ethylacetate, ethylbutyrate, allylcyclohexanepropionate, methylanthranilate, ethylmethylphenyl Single flavors such as glycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethylsulfide, cycloten, furfural, trimethylpyrazine, ethyllactate, ethylthioacetate, strawberry flavor, apple flavor, banana flavor, pineapple flavor , Grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor and other blended flavors, and known flavoring materials used in oral compositions can be used in combination. It is not limited to the fragrances described in the examples. The blending amount is not particularly limited, but the above-mentioned fragrance material is preferably 0.000001 to 1% in the composition, and the fragrance for fragrance using the fragrance material is 0.1 to 0.1 in the composition. It is preferable to use 2%.

The active ingredient is a medicinal ingredient related to periodontal disease, for example, a bactericide such as isopropylmethylphenol, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, sodium lauroylsarcosin, vitamins such as vitamin E, allantin, hinokithiol, glycyrrhetinic acid , Dipotassium glycyrrhizinate, sodium chloride, potassium nitrate, and crude drugs such as Oobaku. These arbitrary active ingredients can be blended in an effective amount within a range that does not interfere with the effects of the present invention.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples,% indicates mass% unless otherwise specified.

[Examples, comparative examples]
Toothpaste compositions (dentifrices) having the compositions shown in Tables 1 to 3 were prepared by a conventional method and evaluated by the following method. The results are also shown in Tables 1 to 3. The numerical value indicating the amount of component (B) in the table is the amount of copper or zinc ions derived from the compound used.
All of the dentifrice compositions of Examples had an anti-inflammatory effect.

<Evaluation method of formulation discoloration (no discoloration)>
The dentifrice composition was filled in a laminated tube container having a diameter of 8 mm for filling 100 g, and stored at 60 ° C. for 1 month. Further, the dentifrice composition having the same composition was filled in the same container and stored at −5 ° C. for 1 month to prepare a standard product for comparison. After each was stored, the discoloration state when extruded from the tube container was observed, and the evaluation was made according to the following evaluation criteria by comparing with the standard product.
Evaluation Criteria ◎: No discoloration compared to -5 ° C storage product (standard product) ○: Almost no discoloration compared to -5 ° C storage product (standard product) ×: -5 ° C storage product Discoloration is observed compared to (standard product)

<Evaluation method of halitosis suppression effect and its sustainability>
The usability was evaluated by a subject consisting of five specialized panelists. 1 g of the dentifrice composition was placed on a toothbrush (Clinica Advantage toothbrush, 4-row compact normal type), and the toothpaste was brushed for 3 minutes. Rinse the mouth with water, conduct a questionnaire about the actual feeling of halitosis immediately after rinsing and after 3 hours of rinsing, and based on the following score criteria, the halitosis suppressing effect (immediately after) and the sustainability of the halitosis suppressing effect (after 3 hours) Was judged respectively. The average score of 5 people was calculated and evaluated according to the following evaluation criteria. Eating and drinking was prohibited during the evaluation of the halitosis suppressing effect.
Rating criteria 5: No bad breath 4: Almost no bad breath 3: Slightly felt bad breath but no problem Level 2: Very bad breath 1: Very bad breath Evaluation criteria ◎: Average score of 5 people is 4 points Above ○: Average score of 5 people is 3 points or more and less than 4 points ×: Average score of 5 people is less than 3 points

Mass number Copper gluconate: 453.84
Zinc chloride: 136.29
Zinc oxide: 81.408
Copper ion: 63.546
Zinc ion: 65.38

Claims (7)

(A) Tranexamic acid or ε-aminocaproic acid,
An oral composition containing (B) copper ion or zinc ion, and (C) sodium monofluorophosphate, and the content of the component (C) is 0.8 to 3% by mass. (B) The oral composition according to claim 1, wherein the source of the copper ion or zinc ion is a water-soluble copper compound or zinc compound having a water solubility at 25 ° C. of 5 g / 100 mL or more. (B) Claim 1 that the source of copper ion or zinc ion is one or more water-soluble copper compounds or zinc compounds selected from copper gluconate, sodium copper chlorophyllin, zinc chloride and zinc gluconate. Or the oral composition according to 2. (B) The oral composition according to claim 1, wherein the source of copper ions or zinc ions is an acidic aqueous solution of a poorly water-soluble or water-insoluble copper compound or zinc compound having a water solubility of less than 5 g / 100 mL at 25 ° C. .. The oral composition according to any one of claims 1 to 4, which contains 0.006 to 0.5% by mass of the component (A) and 0.001 to 0.1% by mass of the component (B). The oral composition according to any one of claims 1 to 5, wherein (C) / (B) has a mass ratio of 10 to 1,500. The oral composition according to any one of claims 1 to 6, which is a dentifrice composition.