JP7236623B2 - oral composition - Google Patents

Description

TECHNICAL FIELD The present invention relates to an oral composition containing tranexamic acid or ε-aminocaproic acid, which is an anti-inflammatory component, in a stable manner and providing excellent halitosis control effects.

Periodontal disease often accompanies bad breath, and adding the anti-inflammatory ingredient and a medicinal ingredient effective in suppressing bad breath to an oral composition intended for gum care to provide the effects of both is effective against periodontal disease. It is effective and preferable for the prevention or suppression of
Tranexamic acid and ε-aminocaproic acid, which have anti-inflammatory effects, are anti-inflammatory ingredients used in oral compositions such as dentifrices for preventive measures against periodontal disease, which is an inflammatory disease. Depending on the compounded ingredients, the stability may deteriorate, causing discoloration of the formulation over time, and other ingredients cannot be easily added, making it difficult to use other halitosis suppressing ingredients in combination.
In Patent Document 1 (Japanese Patent No. 5842565), tranexamic acid or ε-aminocaproic acid is blended with cinnamic aldehyde and an alkyl sulfate to suppress discoloration of a liquid oral composition.

By the way, copper and zinc have the effect of suppressing volatile sulfur compounds (VSC) generated by periodontal disease-causing bacteria, and water-soluble copper or zinc compounds that supply copper or zinc ions have the effect of suppressing bad breath. However, the long-lasting effect of suppressing halitosis is not sufficient.
In Patent Documents 2 and 3 (Japanese Patent No. 2580657, Japanese Patent No. 2738021), a water-soluble copper compound such as copper gluconate or copper citrate is used in combination with polybasic acid or modified aluminum hydroxide to prevent bad breath. It is proposed that the preventive 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 that stably contains tranexamic acid or ε-aminocaproic acid, which is an anti-inflammatory component, and that provides an excellent long-lasting effect of suppressing bad breath. do.

As a result of intensive studies to achieve the above object, the present inventors found that (A) tranexamic acid or ε-aminocaproic acid as an anti-inflammatory component and (B) copper ion or zinc ion as an anti-halitosis component, preferably is combined with a water-soluble copper compound or zinc compound as a source of the ion, and (C) sodium monofluorophosphate is combined in a specific amount and blended into an oral composition, resulting in a formulation derived from component (A) Discoloration is suppressed even after storage, and the bad breath suppressing effect is maintained even after several hours from immediately after use, and the component (A) can be stably blended and an excellent bad breath suppressing effect can be imparted. reached.

In more detail, even if the component (A) having an anti-inflammatory action is combined with the component (B) having an anti-halitosis effect and blended into an oral composition, the anti-halitosis effect does not persist, and it is not used. After a few hours, it is almost not observed (see Comparative Example 6 below), and when the amount of component (B) is increased in order to improve the sustained effect of suppressing bad breath, discoloration of the formulation derived from component (A) is caused. However, there was a problem in terms of performance (see Comparative Example 5 described later). Therefore, in order to solve the above-mentioned problems related to bad breath suppression and discoloration of the preparation, the present inventors conducted further studies and found that the addition of a specific amount of component (C) solved the above problems and discoloration of the preparation. It was suppressed even after storage, and the halitosis suppressing effect could be maintained without blending the component (B) 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 bad breath suppressing effect that persists for several hours after use. In this case, even if component (C) was used in combination with components (A) and (B), discoloration of the formulation was observed when the amount of component (C) was relatively small and inappropriate (Comparative Example 1, which will be described later, 2), but when the amount of component (C) added is at least a specific value, component (C) unexpectedly suppresses the discoloration of the formulation, and almost no discoloration of the formulation was observed even after long-term storage. (See Examples below). Therefore, according to the present invention, component (A) and component (B) can be blended at the same time to impart the above-described special effects.
The effect of the present invention is that, for example, as shown in Comparative Example 4 described later, when disodium hydrogen phosphate is used instead of component (C), the effect of suppressing bad breath is inferior, and other than component (C) is used. In the case of using the fluorine-containing compound of (B) or in the case of using copper citrate, which is sparingly soluble in water, in place of the component (B), the effect of the present invention was inferior. On the other hand, the oral composition containing the components (A), (B) and (C) of the present invention shown in the examples, and the content of the component (C) is within a specific range, does not cause discoloration of the formulation. It was suppressed even after storage, had excellent absence of discoloration, and had excellent halitosis suppressing effect (immediately after) and its persistence (after 3 hours).

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

Accordingly, the present invention provides the following oral compositions.
[1]
(A) tranexamic acid or ε-aminocaproic acid,
An oral composition containing (B) copper ions or zinc ions and (C) sodium monofluorophosphate, wherein the content of component (C) is 0.8 to 3% by mass.
[2]
(B) The oral composition according to [1], wherein the source of copper ions or zinc ions is a water-soluble copper compound or zinc compound having a water solubility of 5 g/100 mL or more at 25°C.
[3]
(B) The source of copper ions or zinc ions 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 composition for oral cavity 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. thing.
[5]
The oral composition according to any one of [1] to [4], containing 0.006 to 0.5% by mass of component (A) and 0.001 to 0.1% by mass of component (B).
[6]
The oral cavity composition according to any one of [1] to [5], wherein (C)/(B) is 10 to 1,500 as a mass ratio.
[7]
The oral composition according to any one of [1] to [6], which is a dentifrice composition.

According to the present invention, there is provided an oral composition that stably contains tranexamic acid or ε-aminocaproic acid, which is an anti-inflammatory component, and that provides an excellent halitosis-suppressing effect that lasts for several hours from immediately after use. can provide. The oral cavity composition can be effectively used for prevention or suppression of periodontal disease.

The present invention will be described in further detail below. 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 above-mentioned "copper ion or zinc ion" means a copper ion or zinc ion of a copper compound or a zinc compound dissolved in a liquid medium (such as water) of the composition, and an insoluble copper ion existing in a solid state in the composition. copper compounds, not zinc compounds.

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

The blending amount of component (A) is preferably 0.006 to 0.5% (% by mass, the same shall apply hereinafter), more preferably 0.03 to 0.2%, based on the total composition. The larger the compounding amount, the higher the anti-inflammatory effect, and when it is 0.006% or more, a sufficient anti-inflammatory effect can be obtained. When the content is 0.5% or less, discoloration of the preparation is sufficiently suppressed, and development of irritation due to the component (A) itself can be sufficiently prevented.

(B) Component is a copper ion or a zinc ion.
Copper ions or zinc ions dissolved in the composition for oral use of the present invention are components having an effect of suppressing halitosis. 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 can be blended using a water-soluble copper compound or zinc compound as the source of the ions. The water-soluble compound here is a compound having a water solubility of 5 g/100 mL or more at 25°C. Examples of such water-soluble copper compounds include copper gluconate, copper sulfate, copper chloride, sodium copper chlorophyllin, and copper acetate. Water-soluble zinc compounds include zinc chloride, zinc sulfate, zinc nitrate, and zinc gluconate. These can be used alone or in combination of two or more. Among them, copper gluconate, sodium copper chlorophyllin, zinc chloride, and zinc gluconate are preferable, and more preferably copper gluconate and copper gluconate, which are water-soluble copper compounds. Chlorophyllin sodium.
Component (B), in another embodiment, may be a poorly water-soluble or insoluble copper compound or a copper ion or zinc ion derived from a solution of a zinc compound dissolved in another solvent. It can also be used as and blended. For example, copper ions and zinc ions obtained by dissolving water-insoluble copper oxide or 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, "sparingly water-soluble or insoluble" means that the water solubility at 25°C is less than 5 g/100 mL.

The amount of component (B) to be added is preferably 0.001 to 0.1%, more preferably 0.005 to 0.05%, based on the total amount of copper ions and zinc ions. When the amount is 0.001% or more, the effect of suppressing halitosis and its persistence is sufficiently obtained, and when the amount is 0.1% or less, discoloration of the formulation is sufficiently suppressed.
As the component (B), it is preferable to blend the above copper compound and zinc compound in an amount that satisfies the blending amount range of the above component (B). 0.01 to 0.5%, particularly 0.05 to 0.3% of the total product is preferred.

(C) Sodium monofluorophosphate is known as an active ingredient for dental caries prevention. It also has the effect of improving the durability of the bad breath suppressing effect. If a fluorine-containing compound other than the component (C), such as sodium fluoride, is used, discoloration of the formulation is not suppressed, and the effects of the present invention are inferior.

The amount of component (C) is 0.8 to 3%, preferably 1 to 2%, particularly 1 to 1.5%, of the total composition. If the blending amount is less than 0.8%, the effect of suppressing discoloration of the preparation is inferior. The higher the content, the more the discoloration of the preparation is suppressed and the longer the bad breath suppressing effect lasts.

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

The oral composition of the present invention can be prepared in various dosage forms such as dentifrices such as toothpaste and liquid dentifrice, mouthwashes, coatings, sprays, patches, chewing gums, and gummies, but dentifrices are preferred. agents, mouthwashes, coatings, especially dentifrices, especially toothpastes, and more preferably dentifrice compositions. Moreover, the oral cavity composition can be prepared by adopting a conventional method depending on the dosage form. In this case, in addition to the above components, other known components can be arbitrarily blended depending on the purpose of the composition, dosage form, and the like. For example, in the case of toothpaste, abrasives, thickeners, binders, surfactants, and if necessary, sweeteners, preservatives, coloring agents, flavoring agents, (A), (B) and (C) ) can be mixed with active ingredients other than the component, and can be produced by mixing these ingredients with water.

Abrasives include silica-based abrasives such as precipitated silica, aluminosilicate, and zirconosilicate; calcium phosphate-based abrasives such as dicalcium phosphate dihydrate or anhydrate, monocalcium phosphate, and tribasic calcium phosphate; and calcium carbonate. , aluminum hydroxide. The compounding amount of the abrasive is preferably 0 to 50%, particularly 5 to 30% of the total composition.

Examples of thickening agents include sugar alcohols such as sorbitol, xylitol and erythritol, and polyhydric alcohols such as glycerin and propylene glycol. The content of the thickening agent is preferably 5-60%, more preferably 20-50%, of the total composition.

The binder can be an organic or inorganic binder. Specifically, organic binders include cellulose derivatives such as sodium carboxymethylcellulose and methylcellulose, gums such as xanthan gum and gum arabic, alginic acid derivatives, and carrageenan, and inorganic binders include gelling silica, gelling aluminum silica, Veegum, Laponite. The amount of the binding agent can be adjusted depending on the dosage form. In the case of toothpaste, the organic binding agent is preferably 0.1 to 5%, particularly 0.5 to 3% of the total composition, and the inorganic binding agent is 1 to 10%, particularly 2 to 8% of the total composition is preferred. In a liquid formulation mouthwash, 0 to 5% of each of the organic and inorganic binders in the total composition is preferred.

As surfactants, anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants can be blended.
Anionic surfactants include alkyl sulfates such as sodium lauryl sulfate, acyl amino acid salts, acyl taurine salts, and the like.
Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, sugar alcohol fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, etc. polyoxyethylene fatty acid esters and polyoxyethylene higher alcohol ethers.
Cationic surfactants include alkylammonium salts, and amphoteric surfactants include alkylbetaines, fatty acid amidoalkylbetaines, and fatty acid amidopropyldimethylaminoacetate betaines.
The content of the surfactant is preferably 0-10%, particularly 0.1-5%, of the total composition.

Sweetening agents include saccharin sodium, and preservatives include paraoxybenzoic acid esters, benzoic acid or salts thereof.
Colorants include Blue No. 1, Yellow No. 4, and titanium dioxide.

Peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime. Oil, Lavender Oil, Rosemary Oil, Laurel Oil, Chamomile Oil, Caraway Oil, Marjoram 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, etc., and processing of these natural flavors (pre-reservoir cut, post-reservoir cut, fractional distillation, liquid-liquid extraction, essence formation, powder perfume ), and menthol, carvone, anethole, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, Menthyl acetate, N-substituted-paramenthane-3-carboxamide, pinene, octylaldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl Glycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate, ethylthioacetate, etc., strawberry flavor, apple flavor, banana flavor, pineapple flavor , grape flavor, mango flavor, butter flavor, milk flavor, mixed fruit flavor, and tropical fruit flavor. It is not limited to the fragrances mentioned in the examples. In addition, although the blending amount is not particularly limited, the above-mentioned perfume material is preferably used in an amount of 0.000001 to 1% in the composition, and the perfume for perfuming using the perfume material is used in a formulation composition of 0.1 to 1%. It is preferred to use 2%.

The active ingredient is a medicinal ingredient related to periodontal disease, such as isopropylmethylphenol, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, antibacterial agents such as lauroyl sarcosinate sodium, vitamins such as vitamin E, allantoin, hinokitiol, glycyrrhetinic acid. , dipotassium glycyrrhizinate, sodium chloride, potassium nitrate, and psyllium. These optional active ingredients can be blended in an effective amount within a range that does not impair the effects of the present invention.

EXAMPLES Hereinafter, the present invention will be specifically described by showing examples and comparative examples, but the present invention is not limited to the following examples. In the following examples, % indicates % by mass unless otherwise specified.

[Examples, Comparative Examples]
Dentifrice compositions (toothpaste) having compositions shown in Tables 1 to 3 were prepared by a conventional method and evaluated by the following methods. The results are also shown in Tables 1-3. 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.

<Method for evaluating formulation discoloration (absence of discoloration)>
100 g of the dentifrice composition was filled in a laminate tube container with a diameter of 8 mm for filling and stored at 60° C. for 1 month. A similar container was filled with the same dentifrice composition and stored at −5° C. for 1 month to obtain a standard product for comparison. Each sample was observed for discoloration when extruded from the tube container after storage, and compared with a standard product, and evaluated according to the following evaluation criteria.
Evaluation criteria ◎: No discoloration observed compared to -5°C stored product (standard product) ○: Almost no discoloration observed compared to -5°C stored product (standard product) ×: -5°C stored product Discoloration is observed compared to (standard product)

<Method for evaluating bad breath inhibitory effect and its sustainability>
A test subject consisting of five expert panelists evaluated the usability. 1 g of the dentifrice composition was placed on a toothbrush (clinica advantage toothbrush, 4-row compact regular type) and brushed for 3 minutes. Gargling the mouth with water, conducting a questionnaire about the bad breath sensation immediately after rinsing and 3 hours after rinsing, and based on the following rating criteria: halitosis control effect (immediately) and durability of halitosis control effect (after 3 hours) were determined respectively. The average score of 5 people was obtained and evaluated according to the following evaluation criteria. Eating and drinking was prohibited during the evaluation of the bad breath suppressing effect.
Rating criteria 5: I do not feel bad breath 4: I hardly feel bad breath 3: I feel bad breath a little, but there is no problem level 2: I feel bad breath considerably 1: I feel bad breath very much Evaluation criteria ◎: The average score of 5 people is 4 points ○: 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) 0.006 to 0.5% by mass of tranexamic acid or ε-aminocaproic acid,
(B) 0.005 to 0.1% by mass of copper ions or zinc ions
and (C) sodium monofluorophosphate, wherein the content of component (C) is 1 to 3% by mass. 2. The oral composition according to claim 1, wherein (B) the source of copper ions or zinc ions is a water-soluble copper compound or zinc compound having a water solubility of 5 g/100 mL or more at 25[deg.]C. (B) The source of copper ions or zinc ions 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 cavity composition according to any one of claims 1 to 4, containing 0.03 to 0.2 % by mass of component (A) and 0.0088 to 0.05 % by mass of component (B). The oral composition according to any one of claims 1 to 4 , wherein (C)/(B) is 10 to 214.3 as a mass ratio. The oral composition according to any one of claims 1 to 6, which is a dentifrice composition.