HK1171942B - Isopropyl methyl phenol-containing liquid composition for oral cavity - Google Patents

Description

Liquid oral composition containing isopropyl methyl phenol

Technical Field

The present invention relates to a liquid oral composition containing isopropyl methylphenol, which exhibits a high permeation bactericidal effect on periodontal pathogenic biofilms, is free from an unpleasant odor derived from isopropyl methylphenol, has a good refreshing feeling, is less irritating, has no sticky feeling in the oral cavity, has a good feeling of use, and is free from clouding or crystal precipitation with time during storage at low temperatures, and is excellent in stability with time.

Background

Isopropyl methylphenol is a non-ionic bactericide which has attracted attention as a bactericidal agent having a high permeation bactericidal effect on periodontal pathogenic biofilms. Heretofore, various oral compositions using isopropylmethylphenol have been proposed (see patent document 1: Japanese patent laid-open No. 62-24010, patent document 2: Japanese patent laid-open No. 1-305021, patent document 3: Japanese patent laid-open No. 7-48237, patent document 4: Japanese patent laid-open No. 10-330230).

However, since the isopropyl methylphenol-containing composition has a peculiar odor and significantly impairs the feeling of use, improvement is required for the disadvantage.

To solve this problem, for example, a technique of mixing a specific acylmethylglycine at a specific mixing ratio with phenoxyethanol to reduce the odor of an antibacterial component (patent document 5: Japanese patent laid-open No. 2007-143613) and a technique of mixing 1-menthol and sodium chloride at a specific mass ratio with isopropyl methylphenol to reduce the odor and odor (patent document 6: Japanese patent laid-open No. 2008-143825) have been proposed. However, when a large amount of acyl methylglycinate is mixed, oral mucosa irritation which is considered to be derived from acyl methylglycinate occurs, and when sodium chloride is mixed, flavor types are limited due to salty taste, and the like, and the appearance of these new problems makes it difficult to say that the feeling of use is satisfactory.

In addition, there is a method of masking or reducing an off-flavor by a sweetener such as saccharin, and in this case, even if the sweet taste of the sweetener is emphasized too much, it is not always possible to suppress an off-flavor. Therefore, new techniques are needed to reduce the off-flavor derived from isopropyl methylphenol.

In general, 1-menthol is contained as a main component of a flavor in an oral composition for the purpose of providing a refreshing feeling, and such a composition is not sufficient for eliminating an odor derived from isopropyl methylphenol.

Further, if the content of the surfactant is reduced in order to secure the bactericidal activity of isopropyl methylphenol and the content of ethanol is reduced in order to reduce the irritation of ethanol, crystals of 1-menthol are precipitated during storage at low temperatures, which causes a problem that the stability of the appearance of the composition is significantly impaired. Further, patent document 7 (Japanese patent laid-open No. 2007-31394) proposes a composition containing a cationic bactericide and 1-menthol and having a small ethanol content, in which the precipitation of crystals of 1-menthol can be prevented by mixing methyl paraben and ethyl paraben together.

On the other hand, isopropyl methylphenol is an oil-soluble compound and is hardly soluble in water without any treatment, and therefore can be made soluble by mixing various surfactants and a solvent such as ethanol. Among them, since a surfactant inactivates an active site of a bactericide, if the amount of the surfactant to be mixed is increased, the bactericidal activity cannot be sufficiently exhibited, and if the amount of the surfactant to be mixed is decreased in order to improve the bactericidal activity, white turbidity appears in a solution with time at low temperature and high temperature, and there is a problem that the stability of the appearance of the composition is impaired.

In addition, since the mixing of ethanol used as a solvent for making an oil-soluble compound soluble causes a pungent and hot feeling when an oral composition is used, in recent years, an ethanol-free mouth rinse containing no ethanol has been widely used. However, since a liquid oral composition in which a nonionic bactericide is mixed without mixing ethanol has a lower solubilizing ability than that in the case of mixing ethanol, it is difficult to ensure the appearance stability with time during storage at low temperatures.

The mixing wetting agent has an effect of solubilizing the oil-soluble compound by dissolving isopropyl methylphenol while compensating for the lowering of the solubilizing ability caused by not mixing the surfactant or ethanol at a low concentration. However, when a humectant is blended at a high concentration, there is a problem that the bitter taste of the humectant itself and the sticky feeling after use deteriorate the feeling in use.

Further, it has been proposed that the water content in the preparation is 40% or less to have an effect on the stability of the phenol-based bactericide (see patent document 8: Japanese patent laid-open No. 11-322554), and that the water content in the mixture is adjusted to be not more than half of the amount of the polyhydric alcohol to be mixed to have an effect on preventing the decrease of the retention of the water-insoluble active ingredient with time (see patent document 9: Japanese patent laid-open No. 2001-199854), but these techniques are not sufficient.

In order to solve this problem and to make isopropyl methylphenol soluble, a technique has been proposed in which a wetting agent, a low-concentration nonionic surfactant and an anionic surfactant are combined, whereby the amount of the wetting agent causing thickening is reduced and the stability and bactericidal activity of isopropyl methylphenol are ensured even in a system not containing ethanol. (see patent document 10: International publication No. 2007/148551). However, the above-mentioned techniques still do not solve the problem derived from the odor of isopropyl methylphenol.

Thus, there is a need for an isopropyl methylphenol-containing liquid oral composition which exhibits a high permeation bactericidal effect on periodontal pathogenic biofilms by isopropyl methylphenol, suppresses an odor derived from isopropyl methylphenol, and has good appearance stability over time, but conventional techniques cannot satisfy all of these characteristics.

Therefore, in order to solve the above-mentioned various problems, there has been a demand for the development of a liquid oral composition containing isopropylmethylphenol, which exhibits a high permeation bactericidal effect on periodontal pathogenic biofilms and which has both good feeling of use without unpleasant odor and high storage stability over time.

In addition, in example 17 of patent document 11 (japanese patent laid-open No. 2007-106728), it is described that when ethanol is not mixed, a combination of isopropyl methylphenol, polyoxyethylene hardened castor oil as a nonionic surfactant, glycerin, propylene glycol, menthol, and methyl paraben; in example 22 of patent document 10, a combination of isopropyl methylphenol, polyoxyethylene hardened castor oil as a nonionic surfactant, glycerin, propylene glycol, polyethylene glycol, menthol, and methyl paraben is described in the case where ethanol is not mixed. However, the problem of off-flavors derived from isopropyl methylphenol has not been solved in these techniques.

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open No. 62-24010

Patent document 2: japanese patent laid-open No. Hei 1-305021

Patent document 3: japanese patent laid-open No. Hei 7-48237

Patent document 4: japanese patent laid-open No. Hei 10-330230

Patent document 5: japanese patent laid-open No. 2007-161613

Patent document 6: japanese patent laid-open No. 2008-143825

Patent document 7: japanese patent laid-open No. 2007-31394

Patent document 8: japanese laid-open patent publication No. 11-322554

Patent document 9: japanese patent laid-open No. 2001-199854

Patent document 10: international publication No. 2007/148551 handbook

Patent document 11: japanese patent laid-open No. 2007-106728

Disclosure of Invention

Problems to be solved by the invention

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an ethanol-free liquid oral composition containing isopropylmethylphenol, which exhibits a high permeation bactericidal effect on periodontal pathogenic biofilms, is free from an odor derived from isopropylmethylphenol, is excellent in feeling of use, and has good appearance stability at low temperatures.

Means for solving the problems

The present inventors have made extensive studies to achieve the above object and as a result, have found that a liquid oral composition containing isopropylmethylphenol as a bactericidal component contains a nonionic surfactant, 1 or 2 or more humectants selected from glycerin, propylene glycol, polyethylene glycol and sorbitol, 1-menthol and p-hydroxybenzoate in a total amount of 5 to 20% by mass of the total composition, and further contains 1 or 2 or more perfume components selected from 3-octanol, 3-octyl acetate, 3-octanone and fenchytone, and that the composition containing substantially no ethanol exhibits a high penetration bactericidal effect on pathogenic biofilms, reduces the odor derived from isopropylmethylphenol, has an excellent feeling in use, and has excellent appearance stability during low-temperature storage.

According to the present invention, various problems described above are solved in a liquid oral composition containing isopropylmethylphenol by mixing the above specific components in a predetermined ratio, and the liquid oral composition is prepared by mixing ethanol, not only exerts excellent bactericidal activity against intraoral bacteria including periodontal disease germs in periodontal pathogenic biofilms, but also suppresses an odor derived from isopropyl methylphenol, moreover, the refreshing feeling in use is good, the stimulation caused by ethanol and the like and the sticky feeling in the oral cavity are not generated, the use feeling is excellent, and turbidity over time and crystal precipitation of 1-menthol due to insolubilization of isopropylmethylphenol during low-temperature storage can be prevented, and dregs or white turbidity and crystal precipitation over time are not generated, so that excellent appearance stability is obtained, and all the characteristics are achieved.

The flavor component (E) has a characteristic flavor, and is used in a small amount in a compound flavor such as cheese, but is limited in use as a flavor for a liquid oral composition because of its unpleasant flavor. The present inventors have surprisingly found that when a specific flavor of the component (E) is mixed with isopropyl methylphenol in a liquid oral composition, the odor derived from isopropyl methylphenol can be sufficiently suppressed.

Further, in the present invention, by mixing (F) anisaldehyde in the liquid oral composition in which the components (a) to (E) are mixed, the peculiar smell derived from isopropyl methylphenol can be further reduced, and the feeling in use can be further improved.

Accordingly, the present invention provides the following liquid oral compositions.

1: a liquid oral composition comprising isopropyl methylphenol, characterized in that,

mixing with liquid oral composition containing isopropyl methyl phenol

(A) A non-ionic surfactant,

(B) More than 1 humectant selected from glycerol, propylene glycol, polyethylene glycol, and sorbitol,

(C) 1-menthol,

(D) P-hydroxybenzoic esters,

(E) 1 or more perfume components selected from 3-octanol, 3-octyl acetate, 3-octanone, and fenchone

And the total content of the component (B) is 5-20% by mass of the total composition, and the total content is substantially free of ethanol.

2: the liquid oral composition according to claim 1, wherein the nonionic surfactant (A) is at least 1 selected from the group consisting of a polyoxyethylene hardened castor oil having an average molar number of addition of ethylene oxide of 40 to 100 moles and a polyoxyethylene alkyl ether having an alkyl group of 16 to 18 carbon atoms and an average molar number of addition of ethylene oxide of 10 to 40 moles.

3: the liquid oral composition according to claim 1 or 2, wherein the component (B) is a combination of glycerin and propylene glycol, glycerin and polyethylene glycol, or glycerin, propylene glycol and polyethylene glycol.

4: the liquid oral composition according to 1, 2 or 3, wherein the content of ethanol in the composition is 100ppm or less.

5: the liquid oral composition according to any one of claims 1 to 4, which comprises 0.1 to 1.0% by mass of the component (A), 0.01 to 0.3% by mass of the component (C), 0.01 to 0.3% by mass of the component (D), and 0.001 to 0.1% by mass of the component (E).

6: the liquid oral composition according to any one of claims 1 to 5, wherein the water content in the composition is 70% by mass or more.

7: the liquid oral composition according to any one of claims 1 to 6, further comprising (F) anisaldehyde.

8: the liquid oral composition according to claim 5, wherein the component (F) is contained in an amount of 0.0001 to 0.1% by mass.

ADVANTAGEOUS EFFECTS OF INVENTION

The liquid oral composition of the present invention exhibits a high permeation bactericidal effect on periodontal pathogenic biofilms, reduces an odor derived from isopropyl methylphenol, has a good refreshing feeling when used, has no sticky feeling or irritation in the oral cavity, has an excellent feeling when used, has excellent appearance stability when stored at low temperatures, and is effective for preventing or inhibiting oral diseases such as periodontal disease.

Detailed Description

The liquid oral composition of the present invention comprises isopropyl methylphenol as an antibacterial component, contains (A) a nonionic surfactant, (B) a humectant selected from glycerin, propylene glycol, polyethylene glycol and sorbitol, and (C) 1-menthol, (D) a paraben, and (E) a flavor component selected from 3-octanol, 3-octyl acetate, 3-octanone and fenchytone in a total amount of 5 to 20% by mass of the total composition, and is substantially free of ethanol.

The isopropylmethylphenol used in the present invention is 4-isopropyl-3-methylphenol, and commercially available products such as those sold by Osaka Kasei Corp.

In view of the effect of sterilizing the periodontal pathogenic biofilm by permeation, isopropyl methylphenol itself has a strong odor, and the amount of isopropyl methylphenol to be mixed is 0.01 to 0.2% by mass, preferably 0.02 to 0.1% by mass, based on the total composition, and if the amount of isopropyl methylphenol to be mixed is less than 0.01% by mass, the capability of sterilizing the biofilm may not be exhibited, and if the amount of isopropyl methylphenol to be mixed exceeds 0.2% by mass, white turbidity may occur, the appearance stability may be impaired, and the odor may not be resolved.

The nonionic surfactant as the component (a) used in the present invention is preferably 1 or 2 or more selected from polyoxyethylene hardened castor oil having an average molar number of addition of ethylene oxide of 40 to 100 mol, particularly 60 to 100 mol, and polyoxyethylene alkyl ether having 16 to 18 carbon atoms in the alkyl group and an average molar number of addition of ethylene oxide of 10 to 40 mol, particularly 20 to 40 mol, from the viewpoints of the solubilizing ability of isopropylmethylphenol, the penetration bactericidal power against periodontal pathogenic biofilm, and the taste. Among them, polyoxyethylene hardened castor oil having an average number of moles of ethylene oxide added thereto of 60 to 100 moles, and polyoxyethylene alkyl ether having an alkyl group having 16 to 18 carbon atoms and an average number of moles of ethylene oxide added thereto of 20 to 40 moles are preferably used in view of penetration sterilization capability to periodontal pathogenic biofilm and solubilization of isopropyl methylphenol.

When the average number of moles of ethylene oxide added to the polyoxyethylene hardened castor oil is less than 40 moles, precipitation may occur during storage at low temperatures, and generally, no polyoxyethylene hardened castor oil is commercially available in an amount exceeding 100 moles.

When the average number of moles of ethylene oxide added to the polyoxyethylene alkyl ether is less than 10 moles, precipitation may occur when the mixture is kept at a low temperature as described above, and a product having an average number of moles of ethylene oxide added to the polyoxyethylene alkyl ether of more than 40 moles is not generally commercially available. In the polyoxyethylene alkyl ether, when the number of carbon atoms in the alkyl group is less than 16, bitterness and irritation are strong, and when the number exceeds 18, appearance stability at low temperature or high temperature may be poor.

The total amount of the component (a) to be mixed is preferably 0.1 to 1.0% by mass, more preferably 0.3 to 0.7% by mass of the total composition, from the viewpoint of the ability to sterilize the periodontal pathogenic biofilm by penetration and the solubility of isopropyl methylphenol. If the amount is less than 0.1% by mass, clouding may occur at low temperatures and it may be difficult to maintain the stability of appearance, and if it exceeds 1.0% by mass, the sterilizing ability may be deteriorated.

The humectant of component (B) may be at least 1 selected from glycerin, propylene glycol, polyethylene glycol, and sorbitol.

Here, the polyethylene glycol preferably has an average molecular weight of 190 to 630. The average molecular weight is an average molecular weight described in reference to cosmetic raw materials (note 2 nd edition), and is an average molecular weight measured by titration with sodium hydroxide when phthalic anhydride is reacted with pyridine to form a phthalate.

As polyethylene glycol having an average molecular weight of 190 to 630, polyethylene glycol 200 (average molecular weight of 190 to 210), polyethylene glycol 300 (average molecular weight of 280 to 320), polyethylene glycol 400 (average molecular weight of 380 to 420), and polyethylene glycol 600 (average molecular weight of 570 to 630) can be suitably used. Some commercial products will have a # between polyethylene glycol and the number, such as polyethylene glycol # 200.

Further, 1 kind of the component (B) may be used alone or 2 or more kinds may be used in combination, and from the viewpoint of taste at the time of use, 2 or more kinds are preferably used, and from the viewpoint of external stability such as clouding at low temperature, 3 or more kinds are more preferably used. The combination of 2 species is preferably a combination of glycerin and propylene glycol, and glycerin and polyethylene glycol #400, and the combination of 3 species is preferably a combination of glycerin, propylene glycol and polyethylene glycol # 400.

The total amount of the component (B) is 5 to 20% by mass of the total composition, and is preferably 8 to 15% by mass from the viewpoint of appearance stability at low and high temperatures and usability of the composition. If the amount is less than 5% by mass, the appearance stability at low temperature is difficult to maintain, and white turbidity occurs, while if it exceeds 20% by mass, sticky feeling after use or the like occurs, and the refreshing feeling due to menthol and perfume components is impaired, and the usability and the feeling in use are impaired.

As the 1-menthol as the component (C), 1-menthol may be used as it is, or an essential oil or plant extract such as 1-menthol-containing peppermint oil or Japanese peppermint oil may be used, or these may be used in combination.

The amount of 1-menthol to be mixed is 0.01 to 0.3% by mass, and particularly preferably 0.05 to 0.2% by mass, from the viewpoint of ensuring a cool feeling. When the amount is less than 0.01% by mass, it may be difficult to secure a satisfactory refreshing feeling and to satisfactorily improve the odor, and when it exceeds 0.3% by mass, it may be impossible to prevent the precipitation of 1-menthol at low temperatures or the appearance stability may be impaired by the occurrence of white turbidity at low temperatures.

As the paraben (D), those generally mixed in oral compositions can be used. Specifically, alkyl esters having 1 to 4 carbon atoms in the alkyl group such as methyl ester, ethyl ester, propyl ester, and butyl ester of p-hydroxybenzoic acid can be used.

The amount of the paraben to be mixed is 0.01 to 0.3% by mass, particularly preferably 0.05 to 0.2% by mass of the total composition, from the viewpoint of preventing the precipitation of 1-menthol during low-temperature storage. If the amount to be mixed is less than 0.01% by mass, precipitation of 1-menthol during low-temperature storage may not be prevented, resulting in white turbidity, while if it exceeds 0.3% by mass, bitterness may not be suppressed, or bitterness derived from paraben may be increased, resulting in poor feeling upon use.

The component (E) is a perfume component effective for masking the odor originating from isopropylmethylphenol, and is 1 or 2 or more kinds of perfume components selected from 3-octanol, 3-octyl acetate, 3-octanone and fenchone.

When 2 or more of the above-mentioned perfume ingredients are used in combination, a combination of 3-octanol and 3-octyl acetate and/or fenchone is preferable.

In addition, 1-octanol is generally used as a flavor for liquid oral compositions, although octanol is also used, but it is not suitable for use as a flavor ingredient in the present invention because the purpose of masking the odor originating from isopropylmethylphenol is not satisfactorily achieved.

As the component (E), commercially available products such as those manufactured under the salt form of tamarind (R) 3-octanol, those manufactured under the salt form of tamarind (R) 3-octyl acetate and 3-octanone (R), and those manufactured under the salt form of fenchong (R) fenchone (R) can be used.

The total amount of the component (E) to be mixed is not particularly limited, but is 0.0001 to 0.1% by mass, particularly preferably 0.0005 to 0.05% by mass, and particularly preferably 0.001 to 0.02% by mass, based on the total composition. When the amount is less than 0.0001% by mass, the odor derived from isopropyl methylphenol may not be masked, and the feeling of use may be poor, while when it exceeds 0.1% by mass, the odor may be generated due to excessively strong fragrance of the perfume component itself.

Further, in the present invention, it is preferable to mix anisaldehyde as the component (F), and by adding anisaldehyde in addition to the perfume component of the component (E), the masking effect against the odor derived from isopropyl methylphenol can be further improved, and a more favorable flavor can be obtained.

As the anisaldehyde, commercially available products such as those of the anise spice (ltd.) can be used. The amount to be mixed is preferably 0.0001 to 0.1% by mass, particularly preferably 0.001 to 0.02% by mass, based on the whole composition. When the amount is less than 0.0001% by mass, the masking effect on the odor derived from isopropylmethylphenol may not be sufficiently improved, and when it exceeds 0.1% by mass, the odor of anisaldehyde itself may be too strong and the odor may appear as in the case of the component (B).

When anisaldehyde (F) is blended, the total amount of the component (E) and the component (F) is preferably 0.0002 to 0.15% by mass, and particularly preferably 0.002 to 0.03% by mass, from the viewpoint of further enhancing the masking effect on the odor derived from isopropyl methylphenol and further improving the flavor. If the total amount is less than 0.0002% by mass, the masking effect on the odor may not be sufficiently improved, and if it exceeds 0.15% by mass, the odor may be generated due to excessively strong odor of the components (E) and (F).

In addition, as the combination of the component (E) and the component (F), a combination of 3-octanol and anisaldehyde is particularly preferable, and thus, an excellent masking effect is exerted particularly against an odor derived from isopropylmethylphenol.

The composition of the present invention is mixed with a solvent such as pure water, but the water content is 70% by mass or more of the total composition from the viewpoint of usability and taste of the liquid oral composition, and more preferably 75% by mass or more based on the feeling of use. The upper limit of the moisture content may be 94.8698 mass% where the total of the moisture content and the lower limit of the amounts of the components (a) to (F) and isopropylmethylphenol is 100 mass%.

The liquid oral composition of the present invention does not substantially contain ethanol, and if ethanol is mixed, irritation occurs, and an unpleasant odor cannot be satisfactorily suppressed, and the feeling of use cannot be improved. Here, "substantially no ethanol" means that the amount of ethanol in the composition is preferably 100ppm or less, more preferably 50ppm or less, particularly preferably 10ppm or less, with the lower limit of 0ppm, relative to the entire composition. In addition, although the liquid oral composition of the present invention does not contain ethanol, the flavor to be mixed in the composition contains a small amount of ethanol derived from the raw material, and for these reasons, the flavor and the like do not contain ethanol in addition to the small amount of ethanol contained therein.

The liquid oral composition of the present invention can be suitably used for preparing a mouthwash, a liquid toothpaste, etc., and as an application method, a method of brushing the teeth with a toothbrush, etc., can be adopted as needed after gargling.

In the liquid oral composition of the present invention, other than the above-mentioned components, any component may be mixed as needed in accordance with the dosage form within the range not to impair the effect of the present invention. For example, a thickener, a binder, a pH adjuster, a preservative, a sweetener, a flavor, a surfactant, an active ingredient, a coloring agent, and the like other than the above-mentioned components may be contained.

As the thickener, sugar alcohols and polyols such as butanediol, ethylene glycol, xylitol, maltitol (maltol) and lactitol (lactitol) other than the above-mentioned component (B) can be used within a range not to impair the effects of the present invention, and the range of 0.1 to 10% is preferable in the case of mixing.

Examples of the binder include: cellulose binders such as sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylethylcellulose, and methylcellulose, xanthan gum, carrageenan, guar gum, sodium alginate, cationized cellulose, montmorillonite, animal gum, and sodium polyacrylate, and 1 or 2 or more of these may be mixed. The amount of the binder is usually 0.001 to 0.5% by mass based on the whole composition.

As the pH adjuster, 1 or 2 or more kinds of substances such as phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid, carbonic acid, and potassium salts, sodium salts, and ammonium salts thereof, ribonucleic acid and salts thereof, and sodium hydroxide can be used, and a combination of phosphoric acid, citric acid, and sodium salts thereof is particularly preferable.

It is particularly preferable to adjust the pH of the liquid oral composition of the present invention to 5.5 to 7.5 at 25 ℃, and as the pH adjuster adjacent thereto, it is preferable to use sodium dihydrogen phosphate and disodium hydrogen phosphate, or a combination of citric acid and sodium citrate.

The preservative may include a benzoate such as sodium benzoate, alkyldiaminoethylglycine hydrochloride, potassium sorbate, and the like.

Examples of the sweetener include saccharin sodium, aspartame, stevia extract, p-methoxycinnamaldehyde, neohesperidin dihydrochalcone, perillatin (perillarin), and the like.

As other perfumes, in addition to the component (E) and the component (F), there can be used, for example, a combination of: natural flavors such as eucalyptus oil, wintergreen oil, cinnamon oil, clove oil, thyme oil, sage oil, basil oil, cardamom oil, coriander oil, spearmint, orange oil, lemon oil, orange oil, lime oil, grapefruit oil, sweet pomelo (sweet) oil, lavender oil, rosemary oil, bay oil, chamomile oil, caraway oil, marjoram oil, celery oil, bay leaf oil, oregano oil, pine needle oil, orange flower oil, lemongrass oil, rose oil, jasmine oil, patchouli oil, iris extract, rose essential oil, orange flower essential oil, vanilla essential oil, mango essential oil, patchouli essential oil, ginger resin oil, pepper resin oil, persimmon pepper resin oil, capsicum extract, etc.; and processed (fore-run, after-run, fractional distillation, liquid-liquid extraction, refining, powdered flavoring) these flavors; and limonene, terpenes, butanol, isoamyl alcohol, n-hexenol, cis-3-hexenol, cis-6-nonenal, linalool, alpha-terpineol, benzyl alcohol, phenethyl alcohol, anethole, thymol, methyl piperitol, eugenol, carvone, menthone, pulegone, 1, 8-eucalyptol, ionone, watermelonketone, n-hexanal, trans-2-ethenal, citral, cinnamaldehyde, benzaldehyde, ethyl acetate, ethyl butyrate ester salt, isoamyl acetate, hexyl acetate, ethyl 2-methyl butyrate, allyl hexyl propionate, allyl cyclohexyl propionate, linalyl acetate, menthyl lactate, carvoyl acetate, phenoxyethyl isobutyrate, methyl jasmonate, methyl salicylate, ethyl salicylate, methyl cinnamate, methyl anthranilate, methyl nicotinate, ethyl nicotinate, Simple flavors such as phenylethyl glycidate, ethyl lactate, vanillin, maltol, gamma and lactone having 4 to 12 carbon atoms, pelargonide, dimethyl sulfide, trimethylpyrazine, ethyl beta-methylthiopropionate, furanone, ethyl cyclopentenolone, methyl cyclopentenolone, 2-methylbutyric acid, propionic acid, p-methoxycinnamaldehyde, 3-1-menthoxypropane-1, 2-diol, menthone glycerol ketal, chrysanthenol, monomenthyl succinate, linalool oxide, vanillyl alcohol butyl ether, and isopulegol; and blending flavors such as strawberry flavor, apple flavor, melon flavor, banana flavor, peach flavor, raspberry flavor, pineapple flavor, grape flavor, tropical fruit flavor, mango flavor, dark plum flavor, orange flavor, lemon flavor, grapefruit flavor, tea flavor, butter flavor, milk flavor, etc.; and known flavor materials used in oral compositions such as flavor solvents such as ethyl alcohols, propylene glycol, glycerin acetate, glycerin fatty acid esters, and the like. The amount of these perfume materials is not particularly limited, and is preferably 0.000001 to 1% by mass in the composition. In addition, as the perfume for giving fragrance using the perfume raw material, 0.1 to 2.0 mass% is preferably used in the composition.

As the surfactant, other surfactants commonly used in oral compositions may be mixed in addition to the nonionic surfactant of the component (a). Examples thereof include: examples of the anionic surfactant include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate; sodium acyl sarcosinates such as sodium lauroyl sarcosinate and sodium myristoyl sarcosinate; n-acyl glutamates such as sodium dodecylbenzenesulfonate, sodium hydrogenated coconut fatty acid monoglyceride monosulfate, sodium lauryl sulfoacetate, and sodium N-palmitoyl glutamate; sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acyl alanine, sodium alpha-olefin sulfonate, and the like. As the amphoteric surfactant, lauryl dimethyl amino acetic acid betaine, N-coconut oil fatty acid acyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine, etc. can be used, but not limited thereto.

When a surfactant other than the above-mentioned component (a) is mixed, the amount to be mixed is preferably 0.01 to 5% by mass of the total composition, and the surfactant can be used within a range not impairing the effects of the present invention.

As the various active ingredients, in addition to isopropyl methylphenol, other active ingredients such as: fluorine compounds such as sodium fluoride, sodium monofluorophosphate and tin fluoride; enzymes such as glucanase and mutanase; water-soluble phosphoric acid compounds such as potassium salts and sodium salts of orthophosphoric acid; chelating phosphoric acid compounds such as tranexamic acid, -aminocaproic acid, allantoin chlorohydroxyaluminum, thujanol, sodium lauroyl sarcosine, ascorbic acid, dl-tocopherol acetate, dihydrocholesterol, α -bisabolol, chlorohexidine salts, azulene, glycitein, glycitinic acid, sodium copper chlorophyllin, chlorophyll, and glycerophosphate; copper compounds such as copper gluconate, aluminum lactate, strontium chloride, potassium nitrate, berberine, hydroxamic acid and derivatives thereof; sodium tripolyphosphate, zeolite, vinyl methyl ether, maleic anhydride copolymer, polyvinylpyrrolidone, epidihydrocholesterol, cetylpyridinium chloride, benzethonium chloride, dihydrocholesterol, trichlorodiphenylurea, zinc citrate, soft extract of radix Angelicae sinensis, cortex Phellodendri extract, flos Chrysanthemi, flos Caryophylli, herba Rosmarini officinalis, Scutellariae radix, Carthami flos, etc. In addition, the amount of other effective components may be mixed in an effective amount within a range not to impair the effects of the present invention.

As the coloring material, water-soluble coloring matters such as blue No. 1, green No. 3, yellow No. 4 (FD & C, yellow No.5(19140)), red No. 105, red No. 106, and the like can be added.

As a container for containing the liquid oral composition of the present invention, PET (polyethylene terephthalate), glass, polypropylene, polyethylene can be used, and PET and glass are preferably used in view of suppression of adsorption of nonionic bactericidal agent and flavor.

Examples

The present invention will be described in more detail below based on experimental examples, examples and comparative examples, but the present invention is not limited to these examples. In addition, the% described below means mass% when not particularly specified in advance.

These liquid oral compositions were prepared using isopropylmethylphenol (manufactured by Osaka chemical Co., Ltd.), polyoxyethylene (60) hardened castor oil (manufactured by Sun-light ケミカルズ Co., Ltd.), polyoxyethylene (30) hexadecyl ether (manufactured by Japan エマルジヨン Co., Ltd.), glycerin (85 mass%, manufactured by Saka chemical Co., Ltd.), propylene glycol (manufactured by Asahi Niger Co., Ltd.), polyethylene glycol #400 (manufactured by ライオン chemical Co., Ltd.), sorbitol (manufactured by Toho chemical Co., Ltd.), 1-menthol (manufactured by Gaosha spice Co., Ltd.), methyl hydroxybenzoate (methyl p-hydroxybenzoate, manufactured by Shang pharmaceutical Co., Ltd.), 3-octyl acetate and 3-octanone (manufactured by Kogyo perfumery), fenchone (manufactured by Shangrong, Ltd.), anisaldehyde (manufactured by Atlantic perfumery), 1-octanol (manufactured by Gaosha perfumery Co., Ltd.) Citric acid (produced by Hibiscus chemical Co., Ltd.), sodium citrate (produced by Hibiscus chemical Co., Ltd.), and saccharin sodium (produced by Aisanchi chemical Co., Ltd.). In addition, ethanol (product of japan アルコ - ル vending machine) was used in the comparative example. Note that POE in the table indicates polyoxyethylene, PEG indicates polyethylene glycol, and any of the following% means mass% unless otherwise specified. The components in the form of an aqueous solution are also included in the table, and are all mixed amounts in terms of purity.

Fragrance compositions a to I having the compositions shown in tables 8 and 9 were mixed as fragrances.

[ example 1]

Liquid oral compositions having compositions shown in tables 1 to 7 were prepared by a conventional method, and the permeation bactericidal effect on a model biofilm was evaluated by the following method. The results are shown in tables 1 to 7.

In examples 1 to 41 in tables 1 to 3 and examples 42 to 84 in tables 5 to 7, the same results were obtained by replacing the fragrance composition A with any one of the fragrance compositions B to I.

The evaluation method of the sterilization effect of the model biological membrane comprises the following steps:

hydroxyapatite (HA) plates 7mm in diameter were treated with human non-irritating saliva filtered through a 0.45 μm filter for 4 hours, and cultured continuously for 2 weeks in tryptone soy broth supplemented with hemin and vitamin K3 in 5 mixed strains of Streptococcus mutans (Streptococcus mutans), actinomyces naeslundii (actinomyces natlundii), Veillonella parvula (Veillonella parvula), clostridium nucleatum (fusobacterium nuciferum), and Porphyromonas gingivalis (Porphyromonas gingivalis) to form model biofilms on the HA plates. After 2 weeks of incubation, 1 time a day 1 was added 2 times by mass of human oral saliva (50mmol/LKCl +1mmol/L KH) to the liquid oral composition shown in the following Table₂P0₄+1mmol/L CaCl₂+0.1mmol/L MgCl₂(pH7.0)), dispersing the mixture, centrifuging the dispersion, using the supernatant as a test agent, immersing the model biofilm in the dispersion for 3 minutes, and then culturing the model biofilm for 3 days. After the completion of the culture, the model biofilm was taken out and dispersed, and the viable cell count of each strain in the model biofilm was determined by culturing on an agar plate. The number of viable bacteria varied somewhat depending on the culture conditions, and it was judged that the bactericidal activity against a biofilm was high when the human saliva was used in place of the test drug at about 8.5log cfu (colony forming units/HA plate) and less than 6.0log cfu/HA plate.

Model biological film sterilization effect evaluation benchmark

Very good: less than 5.0log cfu/HA plate

O: more than 5.0log cfu/HA plate to less than 6.0log cfu/HA plate

And (delta): more than 6.0log cfu/HA plate and less than 7.0log cfu/HA plate

X: 7.0log cfu/HA plate or more

[ example 2]

The liquid oral compositions having the compositions shown in tables 1 to 7 were evaluated for appearance stability and crystal deposition by the following methods. The results are shown in tables 1 to 7.

Appearance stability, crystal precipitation:

a450 mL PET container was filled with 450mL samples shown in tables 1 to 7, and the appearance stability and crystal precipitation after 3 months of storage in a-5 ℃ incubator were determined visually according to the following criteria.

Evaluation criteria for appearance stability

Very good: no change was observed compared to the initial product.

O: although very little dross was found, there were no problems.

And (delta): slight cloudiness was found.

X: considerable white turbidity or precipitation was found.

Evaluation criteria for Crystal precipitation

Very good: no difference was observed from the initial product, and no crystal deposition was observed.

O: an extremely small amount of precipitates was found.

And (delta): trace needle crystals were found.

X: precipitation of needle-like crystals was found.

[ example 3]

The liquid oral compositions having the compositions shown in tables 1 to 7 were evaluated for their feeling of use and the presence or absence of an offensive odor by the following methods. The results are shown in tables 1 to 7.

(1) Feeling of use

20mL of the samples shown in tables 1 to 7 were put into the mouth, and after rinsing for 30 seconds, the degree of coolness, the degree of irritation, and the degree of stickiness immediately after rinsing were evaluated in the following 4 stages, and for each evaluation, the average scores of 10 persons were expressed in terms of "X", "O", "Delta", and "Xx" on the following criteria.

Cool feeling after gargling

4: it is considered to have a cool feeling.

3: it is considered to have a slight cooling feeling.

2: it is considered to have a very weak cooling sensation.

1: no cooling sensation was considered.

Presence or absence ofStimulation after rinsing

4: no irritation was felt.

3: little irritation was felt.

2: the stimulus was slightly felt.

1: no irritation was felt.

Presence or absence ofSticky feeling after gargling

4: no sticky feeling was felt.

3: almost no sticky feeling was felt.

2: a sticky feeling was slightly felt.

1: the feeling of stickiness was felt.

Evaluation criterion of feeling of use

Very good: average score of 4.0

O: an average score of 3.0 points or more and less than 4.0 points

And (delta): an average score of 2.0 points or more and less than 3.0 points

X: an average score of 1.0 or more and less than 2.0

(2) Whether or not there is peculiar smell

Sensory tests were performed using a panel of 10 experts. 20mL of the samples shown in tables 1 to 7 were placed in the mouth, rinsed for 30 seconds, and the degree of unpleasant odor felt during use was evaluated according to the following scale. The average of the average results of 10 persons was obtained, and the liquid oral composition was judged to have no unpleasant odor by the evaluation results of "x" and "o" as follows.

(rating)

And 4, dividing: completely free of peculiar smell

And 3, dividing: almost no peculiar smell

And 2, dividing: slightly peculiar smell

1 minute: has peculiar smell

(evaluation criteria)

Very good: 3.7 to 4.0 minutes inclusive

Excellent to o: more than 3.3 minutes to less than 3.7 minutes

O: more than 3.0 minutes to less than 3.3 minutes

And (delta): more than 2.0 minutes to less than 3.0 minutes

X: less than 2.0 minutes

[ Table 1]

[ Table 2]

[ Table 3]

[ Table 4]

[ Table 5]

[ Table 6]

[ Table 7]

The perfume compositions are shown in tables 8 and 9. The following flavor compositions contained no 3-octanol, no 3-octyl acetate, no 3-octanone, no fenchytone, no anisaldehyde, and no 1-menthol. In addition, it does not contain parabens.

[ Table 8]

[ Table 9-1]

< composition of perfume 1 >

[ tables 9-2]

< composition of perfume 2 >

[ tables 9 to 3]

< composition of perfume 3 >

[ tables 9 to 4]

< composition of perfume 4 >

[ tables 9 to 5]

< composition of perfume 5 >

[ tables 9 to 6]

< composition of perfume 6 >

Claims (7)

1. A liquid oral composition comprising isopropyl methylphenol, characterized in that,

mixing with a liquid oral composition containing 0.01 to 0.1 mass% of isopropyl methylphenol

(A) 0.1 to 1.0% by mass of 1 or more nonionic surfactants selected from polyoxyethylene hardened castor oils having an average molar number of addition of ethylene oxide of 40 to 100 mol and polyoxyethylene alkyl ethers having an alkyl group of 16 to 18 carbon atoms and an average molar number of addition of ethylene oxide of 10 to 40 mol,

(B) 5 to 20 mass% of at least one humectant selected from glycerin, propylene glycol, polyethylene glycol having an average molecular weight of 190 to 630, and sorbitol,

(C) 0.01-0.3 mass% of l-menthol,

(D) 0.01 to 0.3 mass% of a paraben,

(E) 0.001-0.02 mass% of at least one fragrance component selected from 3-octanol, 3-octyl acetate, 3-octanone and fenchone, wherein the ethanol content in the composition is 100ppm or less.

2. The liquid oral composition according to claim 1, wherein the component (B) is a combination of glycerin and propylene glycol, glycerin and polyethylene glycol, or glycerin, propylene glycol and polyethylene glycol.

3. The liquid oral composition according to claim 1 or 2, wherein the water content in the composition is 70% by mass or more.

4. The liquid oral composition according to claim 1 or 2, further comprising (F) anisaldehyde.

5. The liquid oral composition according to claim 3, further comprising (F) anisaldehyde.

6. The liquid oral composition according to claim 4, which contains 0.0001 to 0.1% by mass of the component (F).

7. The liquid oral composition according to claim 5, which contains 0.0001 to 0.1% by mass of component (F).