KR101477336B1 - Liquid oral composition - Google Patents

Abstract

(A) a quaternary ammonium salt type bactericide, (B) 0.001 mass% to 0.5 mass% of a total amount of acetic acid esters and lactones, and (C) at least one selected from polyhydric alcohols and sugar alcohols in an amount of 40 mass% % By mass of the composition.

Description

[0001] LIQUID ORAL COMPOSITION [0002]

The present invention relates to a composition for a liquid oral cavity such as a water solution and a mouthwash solution in which the bitter taste derived from a quaternary ammonium salt type bactericide is reduced or suppressed and storage stability is improved.

In general, the solution of the third solution or the aqueous solution is a preparation containing a bactericide for the purpose of sterilization of the mouth or neck, disinfection, treatment of inflammation, prevention of infectious diseases such as cold and the like. And the like.

Quaternary ammonium salt type fungicides such as cetylpyridinium chloride have been widely used as disinfecting agents for disinfecting effects on mouth and neck. However, when a quaternary ammonium salt type fungicide is blended, a bitter taste and a bitter taste are produced and adults can continue to use it, but it is difficult to use the product continuously because of bitter taste or bitter taste. As a technique for suppressing such bitter taste and bitter taste, for example, in Patent Documents 1 to 6, a sweetener or the like has been studied but not sufficient.

It is also proposed that a solution of a refreshing agent or an ordinary perfume (for example, I-menthol, peppermint oil, eucalyptus oil, chrysanthemum oil, etc.) is solubilized by combining ethanol and a surfactant to improve storage stability (See Patent Document 7). However, in this proposal, the bitterness and feeling of use of the ethanol or the surfactant blended were not particularly preferable for children.

Further, as a use form, there is an advantage that it can be used directly at the time of use in a chemical liquid type which is used directly without dilution. However, when the product is transported to a store, transportation costs are required, and a large storage space is required. Further, even if the user brings it back to his / her home after purchase, the volume becomes large or a storage place becomes necessary.

On the other hand, in the case of the diluted type in which the content component is concentrated, a surfactant, ethanol or the like is added in order to improve the stability in terms of stability, such as precipitation and cloudiness, because the component is enriched (see Patent Document 7) . When the above-mentioned surfactant is compounded, there is a case where the bitter taste is increased and the mucous membrane stimulation in the mouth occurs. Such ethanol often causes mucous membrane detachment in the oral cavity and irritation in the oral cavity. In particular, deterioration of the feeling of use occurs in children, which makes it difficult to continue use.

Therefore, in a composition for liquid oral cavity (liquid for oral solution or aqueous solution) in which a quaternary ammonium salt type fungicide such as cetylpyridinium chloride is blended, bitterness and irritation are greatly suppressed to enhance taste palatability and convenience A composition having a high storage stability and a high storage stability is desired.

Patent Document 1: Japanese Patent Application Laid-Open No. 2005-247713

Patent Document 2: Japanese Patent Application Laid-Open No. 2007-15995

Patent Document 3: Japanese Patent Application Laid-Open No. 2006-306768

Patent Document 4: JP-A-2001-72562

Patent Document 5: Japanese Patent Application Laid-Open No. 2000-26260

Patent Document 6: Japanese Patent Application Laid-Open No. 8-268855

Patent Document 7: JP-A-7-25735

It is an object of the present invention to provide a composition for liquid oral cavity which is highly convenient and has excellent storage stability while significantly suppressing the bitter taste and irritation even when a quaternary ammonium salt type bactericide is blended, .

As a result of intensive study by the present inventors to solve the above problems, the present inventors have found that the total content of (A) a quaternary ammonium salt type bactericide, (B) acetic acid esters and lactones is 0.001 mass% to 0.5 mass% and (C) Containing at least one selected from polyhydric alcohol and sugar alcohol in an amount of 40% by mass to 80% by mass, it is possible to greatly suppress the bitter taste and irritation of the quaternary ammonium salt type bactericide, And a liquid oral composition excellent in storage stability at the time of carrying can be obtained.

The present invention is based on the above knowledge by the present inventors, and means for solving the above problems are as follows. In other words,

<1> (A) A quaternary ammonium salt type fungicide,

(B) acetic acid esters and lactones in an amount of 0.001 mass% to 0.5 mass% and

(C) 40% by mass to 80% by mass of at least one selected from polyhydric alcohols and sugar alcohols.

<2> The process according to <1>, wherein the acetic acid ester is any one of ethyl acetate, butyl acetate, propyl acetate, isopropyl acetate, amyl acetate and isoamyl acetate,

The lactones are any of gamma-nonalactone, gamma-decaractone, delta-decaractone, gamma-undecalactone and delta-undecalactone,
Acetic acid esters include at least one of ethyl acetate, butyl acetate, propyl acetate, isopropyl acetate, amyl acetate and isoamyl acetate,
Wherein the lactones are at least one of gamma-nonalactone, gamma-decaractone, delta-decaractone, gamma-undecalactone and delta-undecalactone.

<3> The liquid oral composition according to any one of <1> to <2>, wherein the mass ratio (B ₁ / B ₂ ) of the acetic acid esters (B ₁ ) to the lactones (B ₂ ) to be.

<4> The pharmaceutical composition according to any one of <1> to <3>, wherein the mass ratio (B / A) of the acetic acid esters and lactones of component (B) to the quaternary ammonium salt type bactericide of component (A) is 0.04 to 2.00 Liquid oral composition according to any one of &lt; 1 &gt;

According to the present invention, it is possible to solve various problems in the prior art, and even if a quaternary ammonium salt type bactericide is blended, bitter taste and irritation are greatly suppressed to enhance taste palatability, It is possible to provide a liquid oral composition excellent in stability.

1 is a photograph showing the presence or absence of turbidity in evaluation of sterilizing power as an example.

The liquid oral composition of the present invention is a liquid oral composition comprising (A) a quaternary ammonium salt type bactericide, (B) at least one selected from acetic acid esters and lactones, (C) polyhydric alcohols and sugar alcohols, It also contains other ingredients as required.

- (A) Quaternary ammonium salt type fungicide -

The quaternary ammonium salt type fungicide of the component (A) is not particularly limited and can be appropriately selected in accordance with the purpose. It is preferable that the compound represented by any one of the following general formula (A1) and the following general formula (A2) .

In the formulas (A1) and (A2), R ² and R ³ each represent a hydrocarbon group having 8 to 18 carbon atoms or a hydrocarbon group having an ether bond.

Z ¹ and Z ² each represent a halogen atom, an amino acid, or an aliphatic fatty acid.

Examples of the quaternary ammonium salt-type fungicide of component (A) include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and the like. These may be used alone, or two or more kinds may be used in combination. Among these, cetylpyridinium chloride and benzethonium chloride are preferable, and cetylpyridinium chloride is particularly preferable.

The content of the quaternary ammonium salt type bactericide (preferably, the total amount when two or more of them are used together) is preferably 0.05 to 1% by mass, more preferably 0.1 to 0.5% by mass.

If the content is less than 0.05% by mass, the sterilizing performance may be insufficient. If the content is more than 1% by mass, the bitter taste may become strong and it may become difficult to use.

- (B) Acetic acid esters and lactones -

As the (B) acetic acid esters and lactones, acetic acid esters and lactones are used in combination.

The acetic acid esters preferably have a total carbon number of 4 to 8, and the lactones preferably have a total carbon number of 9 to 11.

The above-mentioned acetic acid esters having a total carbon number of 4 to 8 have a crisp, sweet smell and taste, but when the compounding amount is large, there is a sense of irritation due to smell and taste. The lactones having the total number of carbon atoms of 9 to 11 are likewise sweet and smell good, but when the amount is large, an oil smell may occur. By combining the above-mentioned acetic acid esters and lactones in an optimum amount and ratio, the bitter taste can be masked and a flavor with high palatability can be imparted.

Examples of the acetic acid esters include ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, amyl acetate, isoamyl acetate, and hexyl acetate. Among these, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate having a total carbon number of 4 to 6 are particularly preferable.

Examples of the lactones include gamma-nonaractone, gamma-decaractone, delta-decaractone, gamma-undecalactone, and delta-undecalactone. Of these, gamma-decalactone, delta-decalactone, gamma-undecalactone and delta-undecalactone having a total carbon number of 10 to 11 are particularly preferable.

Examples of the combination of the acetic acid esters and the lactones include (1) at least one of ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate, (2) gamma-decarboxyl, The combination of at least one of carotone and delta-undecalactone is particularly preferable in view of masking a bitter taste, imparting a highly palatable flavor, and lacking a bitter taste at the time of mouth rinsing (mouth rinse).

The mass ratio (B ₁ / B ₂ ) of the acetic acid esters (B ₁ ) and the lactones (B ₂ ) is preferably 0.1 to 5.0, more preferably 0.2 to 2.0 in view of no bitter taste desirable. When the mass ratio (B ₁ / B ₂ ) is less than 0.1, the oil smell of lactones may be larger than the fresh, sweet taste and smell of the acetic acid ester. When the mass ratio is more than 5.0, It may become difficult to mask the bitter taste due to the taste and smell.

The component (B) may be in the form of a natural perfume containing them or a combination perfume combined with a plurality of perfumes.

The total content of the acetic acid esters and lactones as the component (B) is 0.001 mass% to 0.5 mass%, and preferably 0.01 mass% to 0.3 mass%, depending on the content of the quaternary ammonium salt type bactericide used as the component (A) % By mass is preferable. If the total content is less than 0.001% by mass, the bitter taste masking effect is insufficient. If the total content exceeds 0.5% by mass, the storage stability of the preparation system may deteriorate.

The mass ratio (B / A) of the acetic acid esters and lactones of the component (B) to the quaternary ammonium salt type bactericide of the component (A) is preferably 0.04 to 2.00, From the viewpoint of stability, it is more preferably 0.20 to 1.20. When the mass ratio (B / A) is less than 0.04, the effect of suppressing the bitter taste may be insufficient. When the mass ratio is more than 2.00, it is preferable from the viewpoint of storage stability such as cloudiness, precipitation and separation in the preparation not.

- (C) a polyhydric alcohol or sugar alcohol-

The polyhydric alcohol or sugar alcohol as the component (C) is not particularly limited and may be appropriately selected in accordance with the purpose. Examples thereof include ethylene glycol, diethylene glycol, hexylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, Glycerin, glycerin, hexaglycerin, decaglycerin, 1,3-butylene glycol, trimethylpropane, erythritol, pentaerythritol, dipentaerythritol, glucose, mannose, galactose, Sucrose, fructose, mannose, maltitol, xylitol, inositol, sorbitan, sorbitol, or their EO adducts. These may be used alone, or two or more kinds may be used in combination. Of these, propylene glycol, glycerin, 1,3-butylene glycol and sorbitol are preferable in view of flavor and storage stability, and propylene glycol is particularly preferable.

The content of the polyhydric alcohol or sugar alcohol is 40% by mass to 80% by mass, preferably 50% by mass to 70% by mass. If the content is less than 40% by mass, turbidity may appear on the appearance, and if it exceeds 80% by mass, there is a possibility that an abnormality such as a bitter taste may occur.

- Other ingredients -

Examples of the other components include a fungicide other than the component (A), a perfume composition other than the component (B), a solvent other than the component (C), a water-soluble dye, an anti-inflammatory agent, a refreshing agent, Essential oils), pH adjusting agents, and the like, and they can be appropriately compounded in such a range that the effect of the present invention is not impaired.

Examples of the germicide other than the above-mentioned component (A) include isopropylmethylphenol, trichloro black line, trichlorocarbonylide, chlorhexidine hydrochloride, alkyldiaminoethylglycine, and occiprofilox.

A perfume composition excluding the component (B) is a perfume composition, a perfume solvent, and a perfume stabilizer.

As a list of ingredients of fragrance to be used as the fragrance ingredient, various literatures can be referred to. Such literature includes, for example, &quot; Perfume and Flavor Chemicals &quot;, Vol. I and II, Steffen Arctander, Allured Pub. Co. (1994); "Synthetic Perfume Chemistry and Commodity Knowledge," Uchimoto Ichi, Japan Chemical Industry Daily (1996); &Quot; Perfume and Flavor Materials of Natural Origin &quot;, Steffen Arctander, Allured Pub. Co. (1994); "Encyclopedia of Fragrance", Association of Japan Spice Association, Asakura Bookstore (1989); "Perfumery Material Performance V. 3.3", Boelens Aroma Chemical Information Service (1996); F &quot; lower oils and Floral Compounds In Perfumery &quot;, Danute Lajaujis Anonis, Allured Pub. Co. (1993). The fragrance ingredient may be appropriately selected from among the fragrance ingredients described in these literatures and may be selected from the group consisting of eucalyptus, camphor, borneol, lemon oil, orange oil, lime oil, grapefruit extract, lavender oil, lavender extract, Oil, rosemary extract, and the like.

Examples of the above-mentioned solvent for the flavorings include, but are not limited to, ethanol, benzyl benzoate, acetine (triacetin), MMB acetate (3-methoxy-3-methylbutyl acetate), ethylene glycol (Isopropyl myristate), methyl carbitol (diethylene glycol monomethyl ether), carbitol (diethylene glycol monoethyl ether), benzyl benzoate, diethyl phthalate, azole (Dimethyl phthalate), delethyl prime (isopropyl palmitate), parnesene, dioctyl adipate, tributyrin (glyceryl tributanoate), propylene glycol diacetate, cetyl acetate (hexadecyl acetate) (Acetyltriethyl citrate), Cytoroflex A-4 (tributyl acetyl citrate), Cytoroplex No. 2 (triethyl citrate) MITD (isotridecyl myristate), polyol limonene (limonene polymer), and the like can be given as examples of the polyurethane resin (trade name: TRITO), Citroflex No. 4 (tributyl citrate), Dora fix (methyl dihydroabietate) . These may be used alone, or two or more kinds may be used in combination.

The content of the perfume composition is preferably 0.005 mass% to 5 mass%, more preferably 0.01 mass% to 1 mass%, in the liquid oral composition.

Examples of the solvent other than the component (C) include ethanol, propanol, isopropanol, ester oil, triacetin, and heavy chain fatty acid triglyceride (MCT), which are alcohols having 2 to 5 carbon atoms.

Examples of the anti-inflammatory agent include dipotassium glycyrrhizinate, sodium azulene sulfonate, and the like.

The water-soluble coloring matter is a coloring matter soluble in water at substantially room temperature, and can be optionally selected from those having high safety. For example, blue 1, blue 2, blue 201, blue 403, green 3, yellow 4, yellow 5, yellow 103, red 2, red 3, red 104, red 106 Synthetic colors such as; Natural coloring matter such as gardenia pigment, carotene pigment, safflower pigment, anthocyanin pigment, red spot coloring pigment and the like. These may be used alone, or two or more kinds may be used in combination. Of these, synthetic dyes are usually suitable because of the uniformity of quality.

The content of the water-soluble dye is not particularly limited and can be appropriately selected in accordance with the purpose, and it can be determined usually within a range of 0.00005 mass% to 0.01 mass%.

By adding the water-soluble coloring matter, it is useful from the viewpoint of improving the usability such that the solution in the product is diluted by dividing the solution into containers, which improves the discrimination and is easy to be metered and prevents erroneous drinking.

Examples of the refreshing agent include menthol, peppermint oil, spearmint oil, peppermint oil, N-ethyl-p-menthane-3-carboxamide (WS3, manufactured by Ziboda), menthyl glyceryl ether Ltd.) and the like.

Examples of essential oils containing anethole as the main component include fennel oil, star anise oil, and penne oil.

Examples of the pH adjuster include citric acid, sodium citrate and the like.

The method for producing the liquid oral composition of the present invention is not particularly limited and may be appropriately selected in accordance with the purpose, and each component may be used singly or in combination of plural kinds, and may be prepared by a usual manufacturing method . &Lt; / RTI &gt;

The liquid oral composition is not particularly limited and may be appropriately selected in accordance with the purpose. For example, a plurality of stirring blades (for example, propeller, turbine, dipera, etc.) A stirring device equipped with a stirrer, and the like.

The liquid oral composition of the present invention is characterized by having a pH at 25 占 폚 measured using a pH meter (HM-30G manufactured by Toa Denshi Kogyo Co., Ltd.) and a pH electrode (GST-5721C, More preferably 5 to 6, and particularly preferably 5.2. If the pH is less than 4.5, stability of the system (system) may be deteriorated due to precipitation of cetylpyridinium chloride or the like. If the pH is more than 7.5, the pH adjuster must be used excessively, Lt; / RTI &gt;

- Use -

The liquid oral composition of the present invention is in a transparent aqueous liquid phase and can be used as a water solution, an aqueous solution, a saline solution, and a saline solution when the solution is diluted uniformly in water.

As the container for housing the liquid oral composition of the present invention, PET (polyethylene terephthalate), glass, polypropylene and polyethylene can be used, but the use of PET or glass in terms of inhibition of adsorption of quaternary ammonium salt- .

Example

Hereinafter, the embodiments of the present invention will be described, but the present invention is not limited to these embodiments at all. In the following examples, &quot;% &quot; represents &quot; mass% &quot;, and the amounts of the components described in Examples and Comparative Examples are all converted to net fractions.

(Examples 1 to 31 and Comparative Examples 1 to 10)

- Preparation of liquid oral composition -

The composition for oral cavity according to the examples and the comparative examples was prepared in accordance with the routine method, and the compositions (mass%) shown in Tables 1 to 7 were prepared. The pH of each liquid oral composition obtained was all 5.2.

Next, with respect to each liquid oral composition obtained, the sterilizing power, no bitterness at the time of gargling, and storage stability were evaluated as follows. The results are shown in Tables 1 to 7.

&Lt; Evaluation of sterilizing power &

(50-fold dilution as tap water with respect to 1 ml of each liquid oral composition) was prepared. Each solution was diluted 2-fold in a liquid medium (medium) (soybean / casein digest medium "DAIKO", manufactured by Nippon Pharmaceutical Co., Ltd., one station (test for live bacteria / specific microorganism) (0.02 ml) was inoculated to the cells and incubated at 32 DEG C for 72 hours. The presence or absence of turbidity was visually determined based on the following criteria. The test tube on the right side of Fig. 1 is &quot; no turbidity; State of O, &quot; the test tube on the left side of Fig. 1 is &quot; in the presence of turbidity; X &quot;. In addition, Stapylococcus aureus ATCC 6538 solution was used with an inoculation amount of 1.4 x 10 ⁸ cells / ml.

[Evaluation standard]

○: No turbidity (effective as sterilizing power)

X: There is turbidity (invalid as sterilizing power)

Evaluation of no bitterness at the time of mouth rinse (mouth rinse)

Each liquid oral composition was diluted 50 times with water to make a 10 ml volume of the solution, which was then held for 30 seconds and evaluated for the absence of bitter taste remaining in the mouth. The sensory evaluation was performed by 10 professional panelists, the average value of the results was calculated, and evaluated by the following criteria.

[Evaluation standard]

5 points: There is no bitter taste at all

4 points: Almost no bitter (within acceptable range)

3 points: There is a slight bitter taste (within acceptable range)

2 points: Bitter taste (out of acceptable range)

1 point: It is quite bitter (out of acceptable range)

[Criteria for the Average of Ratings]

◎: not less than 4.0

○: 3.0 or more, less than 4.0

?: 2.0 or more, less than 3.0

×: less than 2.0

<Evaluation of Storage Stability>

Each liquid oral composition was filled in a 50 ml hard glass bottle and observed for appearance at 0 占 폚 for one month and evaluated according to the following criteria.

[Evaluation standard]

◎: Transparent appearance (no change)

O: slightly dark (transparent appearance when returned to room temperature)

×: Appearance or separation of opacity

(* 1) to (* 9) in Tables 1 to 7 indicate the following meanings.

* 1: manufactured by Wako Pure Chemical Industries, Ltd. In the above general formula (A2), the alkyl chain length of R ³ is C ₁₆ H ₃₃ , Z ² is Cl-: cetylpyridinium chloride

* 2: manufactured by YOYU KK: In the above general formula (A1), the alkyl chain length of R ² is C ₁₂ H ₂₅ / C ₁₄ H ₂₉ = 63/37 (mass ratio), Z ¹ is Cl-: 50E

* 3: manufactured by Matsumoto Yushi Pharmaceutical Co., Ltd. In the above general formula (A1), R ² is C ₁₈ H ₂₉ O ₂ , Z ¹ is Cl -: benzethonium chloride

* 4: SOHWA ELECTRIC CO., LTD.: PG-P (Japanese Pharmacopoeia)

* 5: manufactured by Shin Nihon Ehwa Co., Ltd.: glycerin (Japanese Pharmacopoeia)

* 6: Asahi Telephone Industry Co., Ltd.: Sorbitol (Japanese Pharmacopoeia)

* 7: manufactured by Maruzen Pharmaceutical Co., Ltd.: di-potassium diglycolic acid

* 8: Takasago Flavor Industry Co., Ltd.: l-menthol (Japanese pharmacy)

* 9: Made by Terpen Chemical Japan Co., Ltd.: Eucalyptus oil (15 Japanese pharmacopoeia)

(Example 32)

- Three benefits -

A liquid oral composition having the composition shown in Table 8 was prepared by a routine method and evaluated in the same manner as described above. The results are shown in Table 8.

In Table 8, (* 1), (* 4), (* 7), (* 8) and (* 9) show the same contents as above.

(Industrial availability)

INDUSTRIAL APPLICABILITY The composition for liquid oral cavity of the present invention can remarkably suppress bitter taste and irritation even when a quaternary ammonium salt type fungicide such as cetylpyridinium chloride is compounded to enhance taste palatability, And therefore, it is suitably used as, for example, a water solution, a citric acid solution, a saline solution or the like.

Claims (4)

(A) a quaternary ammonium salt type fungicide,
(B) acetic acid esters and lactones,
(C) polyhydric alcohols and sugar alcohols,
The acetic acid esters of component (B) are at least one of (B ₁ ) ethyl acetate, butyl acetate, propyl acetate, isopropyl acetate, amyl acetate and isoamyl acetate,
The lactones of component (B) may be at least one of (B ₂ ) gamma-nonalactone, gamma-decaractone, delta-decaractone, gamma- undecalactone and delta- undecalactone,
, The content of the component (B ₁ ) is 0.0005 mass% to 0.25 mass%
Wherein the content of the component (B ₂ ) is 0.0005 mass% to 0.25 mass%
, The total content of (B ₁ ) and (B ₂ ) is from 0.001 mass% to 0.5 mass%
And 40% by mass to 80% by mass of at least one component selected from the above component (C)
Acetic acid esters (B ₁₎ and the lactones (B ₂₎ a mass ratio (B ₁ / B ₂₎ a composition for oral liquid, characterized in that 0.1 to 5.0. The method according to claim 1,
Wherein the mass ratio (B / A) of the acetic acid esters and lactones of the component (B) to the quaternary ammonium salt type bactericide of the component (A) is 0.04 to 2.00. 3. The method according to claim 1 or 2,
Wherein the content of the component (A) is 0.05% by mass to 1% by mass. The method according to claim 1,
Wherein the component (C) is any one selected from propylene glycol, glycerin, 1,3-butylene glycol and sorbitol.

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